Molecular classifications of colorectal cancer (CRC) are benefitting cancer research by providing insights into subtype-specific disease prognosis and better therapeutic intervention. So far different conventional DNA markers such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), chromosomal instability (CIN), and BRAF and KRAS mutations have been used to classify CRC patients but have not shown promising prognostic values. Here, for the first time, we show classification of CRC tumors from Saudi Arabian patients based on gene expression profile (GEP). An existing method of CRC subtyping has been applied to the GEP of tumors from Saudi CRC patients. Survival analysis was carried out on predicted CRC subtypes. In-silico functional analyses were conducted on the gene signature used for subtype prediction. The predicted subtypes showed distinct but statistically insignificant overall survival distribution (log-rank test, p = 0.069). Comparison of predicted subtypes in Saudi CRC patients with that of the French one showed significant dissimilarity in the two populations (Chi-square test, p = 0.0091). Functional analyses of the gene signature used for subtyping suggest their association with “cancer” and “gastrointestinal diseases”. Most of the signature genes were found differentially expressed in CRC tumors compared to adjacent normal tissues. Such a classification framework might help improve the treatment of colorectal cancer patients.

Angiogenesis is a hallmark of ovarian cancer (OC) it promotes rapid cell growth and the associated metastasis. Identifying new bioactive compounds to target angiogenesis may provide valuable paradigms as therapeutic strategies. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received i.p. injections of melatonin (200 µg/100 g body weight/day) for 60 days. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1R was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFB1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC of an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.

MicroRNAs (miRNAs) are a kind of conserved small non-coding RNAs that participate in regulating gene expression by targeting multiple molecules. Early studies have shown that the expression of miRNAs changes significantly in different tumor tissues and cancer cell lines. It is well acknowledged that such variation is involved in almost all biological processes, including cell proliferation, mobility, survival and differentiation. Increasing experimental data indicate that miRNA dysregulation is a biomarker of several pathological conditions including cancer, and that miRNA can exert a causal role, as oncogenes or tumor suppressor genes, in different steps of the tumorigenic process. Anticancer therapies based on miRNAs are currently being developed with a goal to improve outcomes of cancer treatment. In our present study, we review the function of miRNAs in tumorigenesis and development, and discuss the latest clinical applications and strategies of therapy targeting miRNAs in cancer.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

The development of multiple drug resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrated that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient derived xenograft (PDX) model of human breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemosensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, Doxorubicin (DOX). Using cell cycle arrest/release experiments we show that chemo-sensitive and -resistant MCF7 cells progress through the cell cycle at similar rates, but mitosis is delayed in MDR cells with elevated substrate levels. When treated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically-MDR human breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.

Geijera Schott is a plant genus of the Rutaceae Juss. (rue and citrus) family, comprising six species which are all native to Oceania. Of the plants belonging to this genus, the most significant species that has a customary use is Geijera parviflora, which was used by Indigenous Australians, primarily as a pain reliever. Herein, a comprehensive review of the literature published on the genus Geijera from 1930-2023 was conducted. This is the first review for this plant genus and it highlights the chemical constituents reported to date, together with the range of pharmacological properties described from the various species and different parts of the plant. These properties include anti-inflammatory, anti-microbial, anti-parasitic, insect repellent, analgesic, neuroactive, and anti-cancer activities. Finally, a reflection on some of the important areas for future focused studies of this plant genus is provided.

Background: PD1 and its ligand PD-L1 are related to the prognosis in many solid tumors, whether its role in oral squamous cell carcinoma (OSCC) remains unclear. Methods: Retrospective monocentric study including all patients with OSCC diagnosed and treated between 01/2020 and 05/2022. PD-L1 expression was assessed by combined positive score (CPS), considering CPS > or equal to 1 as positive (1-20 “low expression”, and ≥20 “high”). Descriptive analysis of patient cohort and tumors was performed, including tumor size, stage, lymph node involvement, recur-rence and survival. Results: 65 patients (65 tumors) were analyzed. 66.15% of tumors were ad-vanced stages (III-IV), of them, 97.67% PD-L1+ versus 71.42% within early stages (I-II). T4 tumors expressed PD-L1 in 100% of cases, compared with 54’54% in T1 tumors. 50.79 % of tumors showed lymph node involvement (pN+), 100% of them showing PD-L1+. Prevalence of pN+ was 59.38% for PD-L1 high expression versus 40.63% for low expression. Patients' follow-up ranged from 2 to 34.5 months. No significant difference was seen between overall survival (OS) and PD-L1 +/- (CPS ≥1 vs CPS <1) neither PD-L1 high (CPS ≥20) vs low CPS <20) (p 0.97 and 0.64, re-spectively). Conclusions: The method used to measure (laboratory test with Dako 22C3 an-ti-PD-L1 primary antibody) PD-L1 was reliable and accurate, with a correlation coefficient be-tween the PD-L1 expression in the biopsy and surgical piece of 0.83 (p 0.0001). CPS≥1 was ob-served in large tumors (p<0.001), and was correlated with of lymph node metastases (p<0.004). Further analysis of PD-L1 expression and its relevance in tumor biology and prognosis is needed.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants for mutual benefits. The interactions with a host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. Ethyl acetate extract from isolated A. flavus showed significant cytostatic effects (IC50: 16.25 μg mL−1) against breast cancer cells (MCF-7). Morphology of cells and DAPI stained nuclei along with the results of flow cytometry annexin V/PI assay suggested apoptosis to be the main process leading to cells’ death. While investigating the mechanism that triggers apoptosis, we found that the extract of A. flavus increased ROS generation and caused loss of mitochondrial membrane potential of MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was examined using gas chromatography-mass spectrometry (GC-MS). Interestingly, nine phytochemicals were found to have potential inhibitory effects of anti-apoptotic protein (Bcl-2) in the breast cancer cells. In the in silico molecular docking and molecular dynamics simulation studies revealed that two compounds: 2,4,7-Trinitrofluorenone and 3alpha, 5alpha-Cyclo-ergosta-7,9(11),22t-triene-6beta-ol exhibited significant binding affinities (-9.20, and -9.50 Kcal mol-1, respectively) against Bcl-2 along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer.

Instead of tissue-based detection, blood-based tumor mutation burden (bTMB) is becoming an alternative promising alternate to predict the response of immune checkpoint inhibitor in cancers, especially non-small-cell lung cancer. Although bTMB is more convenient and less invasive, many evidences identified its limited predictive ability and less accurate discrimination of candidates to receive immunotherapy. Several ways of adjustments have been applied to improve the clinical usefulness of bTMB, such as setting restriction for threshold of allele frequency to exclude some unwanted mutations. But many questions remained to be explored such as the number and the type of mutations that should be incorporated into the bTMB estimation. This viewpoint summarized the current attempts to modify bTMB and provided granular aspects that have implications for further enhancement of bTMB’s predictive capability.

(1) Background: Breast cancer is the leading malignancy worldwide and in Ghana it has a poor overall survival. However, approximately 50% of cases are early stage disease and with advances in breast cancer treatment and improvement in survival, quality of life (QOL) becomes as im-portant as treatment of the disease. (2) Methodology: This was a cross-sectional study of survivors who had breast conserving surgery (BCS), mastectomy only (M) and mastectomy with breast re-construction (BRS) from 2016 to 2020 at a tertiary hospital in Ghana, comparatively assessing their QOL using EORTC QLQ C-30 and EORTC QLQ BR-23. (3) Results: The study participants had an overall Global Health Status (GHS) median score of 83.3 [IQR: 66.7-91.7] with no significant differences between the surgery types. The BRS group had a statistically significant lower median scores for the Functional scale (82.8 and 51.0) and the highest scores for the Symptomatic scale (15.7 and 16.5). Body image was significantly lowest for the BRS group 83.3 [68.8-91.7] and highest 100 [91.7-100] for the BCS group (p < 0.001). (4) Conclusion: There is a need to develop support systems tailored at improving the QOL of breast cancer survivors taking into consideration the type of surgery performed.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common cancer types with a high mortality rate. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, that have been related to treatment. Several studies have shown that after-treatment, HL patients and survivors present persistent chromosomal instability, including non-clonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting non-clonal chromosomal aberrations and genomic chaos in a fraction of non-cancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer.

The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility and differentiation. Dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the “rotation model”). This model is also able to explain how oncogenic mutations activate the receptor in the absence of ligand without assuming that the mutations induce receptor dimerization. In this review, we discuss mechanisms underlying ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.

Background and Objectives: Previous studies revealed anti-angiogenic, antiproliferative and anti-inflammatory effects of Vitamin D on cancer cells. Although this body of evidence supported the correlation of high Vitamin D levels with reduced incidence rates for various malignancies, contradictory results were reported regarding non-melanoma skin cancer (NMSC). Aim of this overview was to summarize the available evidence from the existing pool of systematic reviews and meta-analyses, focusing on Vitamin D serum status, dietary intake, and Vitamin D receptor (VDR) polymorphisms in correlation to NMSC incidence. Materials and Methods: A literature search in electronic databases was conducted from inception to January 2023. Inclusion criteria were systematic reviews and meta-analyses published in peer-reviewed journals, evaluating Vitamin D serum levels, dietary and/or supplementary intake, or VDR gene polymorphisms, and reporting data on NMSC. Results: A total of 10 studies were included in the data analysis models. A positive association between Vitamin D serum levels and NMSC is highlighted. However, dietary/supplementation of Vitamin D doesn’t exhibit a likewise strong linkage to NMSC. Despite the contradictory findings, VDR polymorphisms may play a crucial role in the intricate NMSC pathogenesis. Conclusions: This umbrella review showed that high Vitamin D levels are associated with increased NMSC incidence, potentially due to its direct correlation with increased sun exposure. Further research on VDR polymorphisms is suggested to explore their true effect size on NMSC risk.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

Breast cancer (BC) is among the leading causes of mortality from cancer in women. Many of the available anticancer drugs have various side effects. Therefore, researchers are seeking novel anticancer agents particularly from natural compounds and in this regard, snake venom is still one of the main sources of drug discovery. Previous studies showed potential anticancer effects of Cytotoxin II (CTII) from Naja naja oxiana against the different types of cancers. In this study, a pET-SUMO-CTII vector was transformed into SHuffle® T7 Express, an Escherichia coli strain, for recombinant protein expression (rCTII) and the cytotoxic effects of this protein was assessed in MCF-7 cells. The flow cytometry assay was applied to measure the apoptosis and cell cycle. Also, mRNA levels of the Bax, Bcl2, P53, caspase-3, caspase-8, caspase-9, caspase-10, matrix metalloproteinases (MMP)-3, and MMP-9 were analyzed by quantitative real-time PCR to determine the underlying cellular pathways affected by rCTII. The results of this study showed that treatment with 4 µg mL-1 of rCTII enhanced apoptosis through the intrinsic and extrinsic pathways. Also, the increase of the cells' proportion in the sub-G1 phase as well as a reduction in S phase was observed. In addition, the expression of MMP-3 and MMP-9 was decreased in the treated group in comparison to the control group that may contribute to the reduced migratory ability of tumor cells. These experimental results indicate that rCTII has anti-proliferative potential, and so this protein could be a potential drug for BC therapy in combination with other drugs.

Cold plasma (CP) is an ionised gas containing excited molecules and ions, radicals, free electrons, and emits electric fields and UV radiation. CP is potently antimicrobial and can be applied safely to biological tissue, birthing the field of plasma medicine. Reactive oxygen and nitrogen species (RONS) produced by CP affect biological processes directly or indirectly via the modification of cellular lipids, proteins, DNA, and intracellular signalling pathways. CP can be applied at lower levels for oxidative eustress to activate cell proliferation, motility, migration, and antioxidant production in normal cells, mainly potentiated by the unfolded protein response, Nrf2-activated antioxidant response element and PI3K/Akt pathway, which also activates NFκB. At higher CP exposures, inactivation, apoptosis and autophagy of malignant cells can occur via degradation of PI3K/Akt and MAPK-dependent and -independent activation of the master tumour suppressor p53, leading to caspase-mediated cell death. These opposing responses validate a hormesis approach to plasma medicine. Clinical applications of CP are becoming increasingly realised in wound healing, while clinical effectiveness in tumours is currently coming to light. This review will outline advances in plasma medicine and compare the main redox and intracellular signalling responses to CP in wound healing and cancer.

Colorectal liver metastases (CRLM) patients combined with hepatic lymph node metastases was a negative prognostic factor associated with outcomes. Up to now, there was still lack of a reliable method to identify the status of hepatic lymph nodes. The aim of this study was to investigate the predictive ability of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) models to distinguish between benign and malignant hepatic lymph nodes in CRLM patients who underwent neoadjuvant chemotherapy prior to surgery. In total, 97 CRLM patients with pathologically proved hepatic lymph node status were included. Various quantitative parameters, including the apparent diffusion coefficient (ADC) from mono-exponential model, D, D*, and f derived from intravoxel incoherent motion (IVIM) model, as well as DDC and α from stretched-exponential model (SEM), were measured. Multivariate analysis revealed that the pre- treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes. A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients, with an area under the curve (AUC) of 0.873. Therefore, the nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.

Lifetime cancer risk characterization of ambient PM-bound carcinogenic metals and polycyclic aromatic hydrocarbons (PAHs) were examined in the cities of Los Angeles (USA), Thessaloniki (Greece) and Milan (Italy), which share similar Mediterranean climates but are different in their urban emission sources and governing air quality regulations. The samples in Milan and Thessaloniki were mostly dominated by biomass burning activities whereas the particles collected in Los Angeles were primary impacted by traffic emissions. We analyzed the ambient PM2.5 mass concentration of Cadmium (Cd), Hexavalent Chromium (Cr(VI)), Nickel (Ni), Lead (Pb), as well as 13 PAH compounds in the PM samples, collected during both cold and warm periods at each location. The Pb exhibited the highest annual-average concentration in all 3 cities, followed by Ni, As, Cr(VI), Cd and PAHs, respectively. The cancer risk assessment based on outdoor pollutants was performed based on three different scenarios, with each scenario corresponding to a different level of infiltration of outdoor pollutants into the indoor environment. Thessaloniki exhibited rather high risk value associated with lifetime inhalation of As, Cr(VI) and PAHs. The highest cancer risk values were calculated in Milan where the lifetime risk of exposure to As, Cr(VI) and PAHs exceeded the US EPA standard across all scenarios by a considerable margin. The risk associated with Cr(VI) in Milan, which was the most significant among the investigated elements, ranged from (6.08±0.36)×10-6 to (9.82±0.58) ×10-6. In contrast, the estimated risks associated with metal and PAHs in Los Angeles were mostly comparable to the guideline value, even when the infiltration factor was assumed to be at peak. This observation highlights the impact of local air quality measures in improving the air quality and lowering the cancer risks in Los Angeles compared to the other two cities.

HCC is a highly aggressive malignancy with limited treatment options. In this study, novel conjugates, of NSAIDs - Ibuprofen and Ketoprofen with oleanolic acid oximes derivatives (OAO) were synthesized and their activity as modulators of signaling pathways involved in HCC pathogenesis was evaluated in normal THLE-2 liver cells and HCC derived HepG2 cells. The results demonstrated that conjugation with OAO derivatives reduces the cytotoxicity of parent compounds in both cell lines. In THLE-2 cells treatment with conjugates resulted in increased activation of the Nrf2-ARE pathway. An opposite effect was observed in HepG2 cells. In the later reduction of NF-κB was observed along with modulation of MAPK signaling pathways (AKT, ERK, p38, p70S6K, and JNK). Moreover, STAT3, STAT5, and CREB transcription factors on protein levels were significantly reduced as a result of treatment with IBU- and KET-OAO derivatives conjugates. The most active were conjugates with OAO-morpholide. Overall, the findings of this study demonstrate that IBU-OAO and KET-OAO derivatives conjugates modulate the key signaling pathways involved in hepatic cancer development. Their effect on specific signaling pathways varied depending on the structure of the conjugate. Since the conjugation of IBU and KET with OAO derivatives reduced their cytotoxicity, the conjugates may be considered good candidates for the prevention of liver cancer.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

(1) Context: Cancer triggers significant changes in family dynamics. It is noteworthy that coping and problem-solving skills, particularly in situations involving cancer in children and adolescents, have not been adequately explored in the context of family adaptation. This study aims to analyze the effectiveness of family interventions in coping to improve problem-solving skills in parents and/or caregivers of children and adolescents during and after oncological treatment. (2) Methods: This is a scoping review following the recommendations of the Joanna Briggs Institute and the Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR), from 2014 to 2024, in the databases LILACS, CINAHL, SCOPUS, Web of Science, and PUBMED. (3) Results: Forty-five studies were eligible. Coping strategies were categorized as follows: (1) positive attitudes (including a sense of courage and hope, family support to enhance resilience, and future planning), (2) caregiver empowerment (involving acceptance of diagnosis, emotional distancing, and coping through religiosity), and (3) communication skills (encompassing professional communication, horizontal dialogue with healthcare teams, and sincere communication with friends and family). (4) Conclusions: Over time, families develop coping and problem-solving strategies that influence changes in family functioning patterns, aiding them in accepting, reinterpreting, and reframing ideas and feelings associated with neoplasia.

Background: In the present study, cisplatin, artemisinin and oleanolic acid were evaluated alone and in combination, on human ovarian A2780, A2780ZD0473R and A2780cisR cancer cell lines with aim of overcoming cisplatin resistance and side effects. Methods: Cytotoxicity was assessed by MTT reduction assay. CI values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Results: Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism and biosynthetic processes and drug resistance and detoxification. Conclusion: Results indicate that appropriately sequenced combinations of cisplatin with ART and OA may provide a means to reduce side effects and circumvent platinum resistance.

Diffuse intrinsic pontine glioma (DIPG) is recognized as a pediatric brainstem cancer with a 0% survival rate. On a molecular basis, DIPG commonly results from mutations in histone H3, specifically a mutation in the H3K27M gene, that promotes tumorigenesis and results in presentation of this fatal brainstem tumor. DIPG is challenging to treat, as surgical intervention is inefficacious due to the location where the glioma resides. To date, traditional treatments such as radiation, chemotherapy, and immunotherapy have not increased survival rates and have only been successful at relieving symptoms. Future therapeutic approaches such as proton beam radiation, Chimeric Antigen Receptor T Cell (CAR-T) immunotherapy, and alternative epigenetic pharmaceuticals are under investigation for potential benefits. Various clinical trials have also explored these treatment procedures to discover potential increases in survival rates in both animal and human studies. In this review, we will evaluate the pathology and molecular characteristics of DIPG, the current and future approaches to DIPG treatment; and, lastly, we will discuss clinical trials that have been completed to develop successful treatment options.

Tumor-associated macrophages are a key component in the tumor microenvironment, secreting extracellular vesicles (EVs) such as exosomes and other various factors for intercellular communication. However, macrophage-derived EVs heterogeneity and their cytotoxicity to cancer cells has not been well understood. Here, we aimed to separately isolate various types of macro-phage-EVs by size exclusion chromatography (SEC) method and investigate EV transmission and cytotoxicity to oral cancer cells. For fluorescence-labeling of cellular and EV membranes, palmitoylation signal-fused GFP and tdTomato were expressed in THP-1 monocytic cells and HSC-3 oral cancer cells, respectively. We found that fluorescence-labeled EVs secreted by macrophages were highly transmissive to oral cancer cells than those from parental monocytic cells. In a co-culture system and conditioned medium (CM), a macrophage-secreted unidentified factor was cytotoxic to oral cancer cells. We fractionated macrophage-derived EVs by the SEC method and performed western blotting to characterize various EV types. Three fractions were characterized: small exosomes (EXO-S: < 50 nm) fraction containing HSP90α, HSP90β, CD63 (EV marker) and β-actin; large exosomes (EXO-L: 50-200 nm) fraction containing CD9 (EV marker) and HSP90β; large EVs (100-500 nm) fraction. Notably, the macrophage-derived small exosomes fraction was cytotoxic to oral cancer cells, while large exosomes and large EVs were not. There-fore, it was implicated that macrophage-derived small exosomes are cytotoxic with high trans-mission potential to cancer cells.

Abstract: This study aimed at investigating the effects of Valencia KK4-type peanut skin ethanolic extract (KK4-PSE) in combination with cisplatin or 5-fluorouracil (5-FU) against HeLa cells in vitro and in xenograft models. MTT assay showed that KK4-PSE, cisplatin, and 5-FU suppressed proliferation of HeLa cells in a dose and time dependent manner. Drug interactions by Chou-Talalay method demonstrated that KK4-PSE enhanced antiproliferative activity of 5-FU against HeLa cells with combination index (CI) values of 0.49 (48 h) and 0.60 (72 h), indicating a synergistic effect, while KK4-PSE combined with cisplatin exhibited an additive effect (CI = 1.02) (72 h) and antagonistic effect at 24 and 48 h exposures (CI = 1.12 and 1.18, respectively). In nude mouse xenograft models, the combination of 5-FU and KK4-PSE markedly reduced HeLa tumor weights compared with control and single agent treatments. The combination of KK4-PSE and 5-FU achieved greater tumor growth inhibition than that of the KK4-PSE-cisplatin combination. KK4-PSE mitigated hepatotoxicity induced by both cisplatin and 5-FU in nude mice. The spleen hyaloserositis was significantly reduced in the combination treatment of 5-FU and KK4-PSE. These findings suggest a potential of KK4-PSE to inhibit cervical cancer cell growth while alleviating the toxicities of cisplatin and 5-FU.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachythera-py has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision-making regarding radiological parameters by radiation oncologists. Combined use of LDR brachytherapy with other therapeutical modalities, such as external beam radiation and androgen deprivation therapy, for clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology depart-ments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Assessment of stigma among cancer patients is of utmost importance as stigma may lead to various psychological sequelae and lower quality of life. This study aimed to translate the English version of the Shame and Stigma Scale (SSS) into Malay and validate the Malay version of the SSS (SSS-M) among cancer patients in Malaysia. Initially, concurrent translation and back translation of the SSS-M was performed, and face and content validity were assessed. Then, the SSS-M was administered to a total of 234 patients of mixed types of cancer to assess its reliability (internal consistency and test-retest reliability), construct validity (convergent and discriminant validity), exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The SSS-M total score registered good internal consistency (Cronbach’s α of 0.886) and test-retest reliability (intraclass correlation coefficient of 0.846, p < 0.001). EFA and CFA confirmed that the SSS-M consisted of 20 items in 5 domains. Its convergent and discriminant validity were achieved. Hence, the SSS-M demonstrated good psychometric properties and is available for use to assess stigma among cancer patients in Malaysia.

Both soybean variety and processing affect product characteristics. This study’s objective was to characterize the effect of four extraction methods (variations of soaking and grinding) combined with cooking on the content and composition of phenolic substances, antioxidant and anti-DU145 prostate cancer cell proliferative properties of soymilk prepared from a yellow soybean of the ProSoy variety, which is a high protein variety. Results showed soymilk processing yield was the greatest by Method 4, but Method 2 gave the highest solids and protein yields by about 14 and 12%, respectively. Method 4, a two-step grinding also increased yields (8 and 7%, for solids and protein, respectively), and in all but one instance produced higher total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC) and total isoflavone content in both raw and cooked soymilk as compared to Method 1. Cooking soymilk reduced 14-17% of total phenolic substances. Cooking reduced anticancer capacity of Method-4-prepared soymilk phenolic extract by increasing IC50 value from about 4.9 mg/mL to 6.8 mg/mL. The increases in phenolic compounds and antioxidants produced in Prosoy soymilk by Methods 2 and 4 with simultaneous increases in product solids yield are significant to benefit the soymilk industry and consumer health. Keywords: ProSoy yellow soybean, soymilk processing, phenolics, isoflavones, antioxidant capacity, anti-DU145 prostate cancer proliferation

Abstract: Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA and their segregation during cell division are the origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

The heat and matter transfer during glucose catabolism in living systems and their relation with entropy production are a challenging subject of the classical thermodynamics applied to biology. In this respect, an analogy between mechanics and thermodynamics has been performed via the definition of the entropy density acceleration expressed by the time derivative of the rate of entropy density and related to heat and matter transfer in minimum living systems. Cells are regarded as open thermodynamic systems that exchange heat and matter resulting from irreversible processes with the intercellular environment. Prigogine’s minimum energy dissipation principle is reformulated using the notion of entropy density acceleration applied to glucose catabolism. It is shown that, for out-of-equilibrium states, the calculated entropy density acceleration is finite and negative and approaches as a function of time a zero value at global thermodynamic equilibrium for heat and matter transfer independently of the cell type and the metabolic pathway. These results could be important for a deeper understanding of entropy generation and its correlation with heat transfer in cell biology with special regard to glucose catabolism representing the prototype of irreversible reactions and a crucial metabolic pathway in stem cells and cancer stem cells.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, Middle East and USA areas. While in the ancient time pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, up to consider pomegranate as a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs) and its consumption appears to exert numerous healthy beneficial effects, in particular, in several pathological conditions, namely in patients affected by metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and in dentistry represents a promising field, as it could permit the development of innovative natural adjuvant therapies, able to empower the standard pharmaceutical therapies.

The recurrent coronavirus outbreaks in China (SARS-CoV and its relative, SARS-CoV-2) have raised speculations that perhaps Asians are somehow more susceptible to these coronaviruses. Here, we test this possibility based on an analysis of the lung-specific expression of ACE2, which encodes the known cell-entry receptor of both SARS-CoV and SARS-CoV-2. We show that ACE2 expression is not affected during tumorigenesis, supporting that the abundant transcriptomes in cancer genomic studies can be informatively used to study ACE2 expression among diverse individuals without cancer. We find that ACE2 expression in the lung increases with age, but is not associated with sex. Further, Asians do not differ from other populations for ACE2 expression and do not harbor unique genetic polymorphisms in the ACE2 locus. Thus, beyond illustrating an innovative method for assessing the potential impacts of demographic factors for non-cancer diseases from large-scale cancer sample datasets, our statistically robust findings emphasize that individuals of all races require the same level of personal protection against SARS-CoV-2.

Abstract: Breast cancer is one of the leading causes of death in the female population due to the re-sistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubil-ity and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxy curcumin magnesium complex with cyclodex-trin (DiMeOC-Mg-BCD, 5) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media (PBS) was improved by a factor of 6x over the free metal complex (DiMeOC-Mg). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the MMP-2 and MMP-9, IL-6, and STAT3 expression levels on MDA MB 231 cell lines. Results of an antitumor assay in an in-ovo model showed up to 30% inhi-bition of tumour growth for breast cancer (MDA-MB-231) when using 5 (0.650 mg/Kg dose), and 17.29 % inhibition with the free homoleptic metal complex (1.5 mg/Kg dose, DiMeOC-Mg). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new DiMeOC-Mg-BCD exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

Prototype of a family of at least nine members, c-src tyrosine kinase is a therapeutically interesting target, because its inhibition might be of interest not only in a number of malignancies, but also in a diverse array of conditions, from neurodegenerative pathologies to certain viral infections. Computational methods in drug discovery are considerably cheaper than conventional methods and offer opportunities of screening very large numbers of compounds in conditions that would be simply impossible within the wet lab experimental settings. We have explored the use of global QSAR models and molecular ligand docking in the discovery of new c-src tyrosine kinase inhibitors. Using a data set of 1038 compounds from ChEMBL and 19 blocks of molecular descriptors, we have developed over 200 QSAR classification models, based on six machine learning algorithms and 17 feature selection methods. We have selected 49 with reasonably good performance (positive predictive value and balanced accuracy higher than 70% in nested cross validation) and the models were assembled by stacking with a simple majority vote and used for the virtual screening of over the “named” ZINC data set (over 100,000 compounds). 744 compounds were predicted by at least 50% of the QSAR models as active, 147 compounds were within the applicability domain and predicted by at least 75% of the models to be active. The latter 147 compounds were submitted to molecular ligand docking using Vina and Ledock, and a number of 90 were predicted to be active based on the binding energy. External data from CHEMBL and PUBCHEM confirmed that at least 7.83% (in the case of QSAR) or 6.67% (in the case of integrated QSAR and molecular docking) of the compounds are active on the c-src target.

Abstract Traditional plants are known to contain a wide array of secondary metabolites with important biological activity, including anticancer activity. One of such metabolites is saponin; a steroidal or triterpenoid glycoside that is distinguished by its soap forming nature. Different saponins have been characterized and purified so far, and are gaining attention in cancer chemotherapy. Saponins possess incredible structural diversity which has been linked to their activity. They have been implicated in cancer chemoprevention and chemotherapy. Several studies have reported the role of saponins in cancer and their mechanism of actions including cell cycle arrest, antioxidant, cellular invasion inhibition, induction of apoptosis and autophagy. Despite the extensive research and significant anticancer effect of saponins there are no known FDA approved saponin based anticancer drugs due to a number of limitations including toxicities and drug likeness properties. Recent studies have explored options such as structural optimization, combination therapy and drug delivery systems to design saponins with increased efficacy and decreased toxicities. This review discussed the current knowledge on different saponins, their anticancer activity, mechanism of action as well as the current promising research on saponins within the last two decades and recommendations for future studies.

Next-generation sequencing (NGS) has actualized human papillomavirus (HPV) virome profiling for in-depth investigation of viral evolution and pathogenesis. However, viral computational analysis remains a bottleneck due to semantic discrepancies between computational tools and curated reference genomes. To address this, we developed and tested automated workflows for HPV taxonomic profiling and visualization using a customized Papillomavirus database in CLC Microbial Genomics Module. HPV genomes from Papilloma Virus Episteme were customized and incorporated into CLC “ready-to-use” workflows for stepwise data processing to include: 1) Taxonomic Analysis, 2) Estimate Alpha/Beta Diversities, and 3) Map Reads to Reference. Low-grade (n = 95) and high-grade (n = 60) Pap smears were tested with ensuing collective runtimes: Taxonomic Analysis (36 min); Alpha/Beta Diversities (5 sec); Map Reads (45 min). Tabular output conversion to visualizations entailed 1-2 keystrokes. Biodiversity analysis between low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) revealed loss of species richness and gain of dominance by HPV-16 in HSIL. Integrating clinically relevant, taxonomized HPV reference genomes within automated workflows proved to be an ultra-fast method of virome profiling. The entire process named “HPV DeepSeq” provides a simple, accurate and practical means of NGS data analysis for a broad range of applications in viral research.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

An emerging picture in cancer biology is that, paradoxically, chemotherapy can actively induce changes that favor cancer progression. These pro-cancer changes can be either inside (intrinsic) or outside (extrinsic) the cancer cells. In this review, we will discuss the extrinsic pro-cancer effect of chemotherapy; that is, the effect of chemotherapy on the non-cancer host cells to promote cancer progression. We will focus on metastasis, and will first discuss recent data from mouse models of breast cancer. Intriguingly, despite reducing the size of primary tumors, chemotherapy changes the tumor microenvironment, resulting in an increased escape of cancer cells into the blood stream. Furthermore, chemotherapry changes the tissue microenvironment at the distant sites, making it more hospitable to cancer cells upon their arrival. We will then discuss the idea and evidence that these devastating pro-metastatic effects of chemotherapy can be explained in the context of stress response. At the end, we will discuss the potential relevance of these mouse data to human breast cancer and their implication on chemotherapy in the clinic.

The number of individuals meeting criteria for genetic counseling and testing for hereditary cancer syndromes (HCS) is far less than the number that actually receive it. To facilitate identification of patients at risk for HCS, Counsyl developed a digital identification tool (digital ID tool) to match personal and family cancer history to National Comprehensive Cancer Network (NCCN) BRCA-related Hereditary Breast and Ovarian Cancer (HBOC), Lynch syndrome, and polyposis testing criteria in one-to-one, automated fashion. The purpose of this study was to validate the ability of the digital ID tool to accurately identify histories that do and do not meet NCCN testing criteria. Methods: Third-party recorded three-generation pedigrees were retrospectively reviewed by a certified genetic counselor (CGC) to determine if independent events included in pedigree histories met NCCN guidelines, and were then sorted into groups: high risk events (meets criteria) and low risk events (does not meet criteria). Events were entered into the digital ID tool to determine the extent of its concordance with events sorted by CGC review. Statistical tests of accuracy were calculated at a 95% confidence interval (CI). Results: 197 pedigrees were reviewed consecutively representing 765 independent events for analysis across groups. 382/382 (100%) high risk events identified by the digital ID tool and 381/383 (99.47%) low risk events identified by the digital ID tool were concordant with CGC sorting. The digital ID tool had a sensitivity of 100% (99.04-100% CI) and specificity of 99.48% (98.13-99.94% CI). The overall accuracy of the digital ID tool was estimated to be 99.74% (99.06-99.97% CI), reflecting the rate at which the digital ID tool reached the same conclusion as that of CGC review of pedigree events for the recommendation of genetic testing for individuals at risk for HCS. Conclusions: The digital ID tool accurately matches NCCN criteria in one-to-one fashion to identify at-risk individuals for HCS and may be useful in clinical practice, specifically for BRCA-related HBOC and Lynch Syndrome.

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

Arsenic trioxide (ATO) has been shown to inhibit pancreatic cell growth in vitro and to promote the inhibitory effects of gemcitabine on pancreatic cancer in vivo. However, the high toxicity of ATO associated with the required high doses and indiscriminate targeting has limited its clinical application. This study aimed to determine whether coupling arsenic to a tumor homing peptide would increase the inhibitory potency against pancreatic cancer cells. The effects of this peptide-linked arsenic compound and ATO on pancreatic cancer growth were tested in vitro and in a mouse model. The data demonstrated that the peptide-linked arsenic compound inhibited pancreatic cancer cell growth more potently with IC50 values 10 times lower than ATO. Like ATO, the peptide-linked compound induced cell death and cell cycle arrest. More importantly, the peptide-linked arsenic compound inhibited pancreatic cancer growth in mice and enhanced the inhibitory effect of gemcitabine on pancreatic cancer growth at 2 times lower molar concentration than ATO. These results indicate that the peptide-linked arsenic compound inhibited pancreatic cancer more potently than ATO and suggest a potential clinical use for the combination of gemcitabine with the peptide-linked arsenic compound for the treatment of pancreatic cancer.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

Objectives: To evaluate the relationship between the type of conization, the volume and dimensions of the cone, with the persistence/recurrence of CIN 2-3, presence of affected margins and post-cone HR-HPV positivity. Methods: 227 women treated with LLETZ and histologically confirmed CIN2-3 were evaluated between 1996 and 2006 and followed up until June 2016. Age, type of resection according to IFCPC 2011, volume, cone dimensions, margins were studied. of resection, post-cone high-risk human papillomavirus (HR-HPV) status and viral load. Determinants of HR-HPV positivity were estimated using unconditional logistic regression and time to recurrence was assessed using Kaplan-Meier curves. Results: Persistent/recurrent CIN2-3 was found in 12 cases (5.2%), type 1 conization was performed in 81 patients, with 5 recurrences (6.1%), type 2 in 101 patients, with 6 recurrences (5 .9%) and type 3 resection in 45 women, with 1 recurrence (2.2%). Volume and dimensions were not associated with recurrence. The Log-Rank Test did not show a significant difference between the 3 treatments (p= 0.18). The free margins in type 1 were 37%, in type 2 resection 61% and in type 3 71% (p=0.001). Resection type 1 had 15% HR-HPV post positive cone, type 2 reached 16% and type 3 had 9%, this difference being non-significant (p=0.58). The incidence of recurrence at 36 months in type 1 resection was 0.08%, in type 2 treatment it was 0.04% and in type 3 resection it was 0.0%. Conclusions : Type 3 resection had a higher proportion of free margins and lower post-cone HR-HPV positivity, with a lower incidence of persistence/recurrence.

In this paper we report on the use of an in-house developed solid-state hybrid microwave and radiofrequency generator operating at frequencies of 2.45 GHz and/or 480 kHz for cancer ablation in various tissues. The generator has demonstrated increased accuracy due to its custom-designed hardware, which incorporates the latest technologies and algorithms to control the emitted power versus temperature profile of the treated sample. In particular, the hybrid generator incorporates control systems based on impedance or reflected power measurements that allow controlled ablation without causing unwanted carbonisation and without including areas where tissue damage is not desired. Tests performed ex-vivo on chicken breast and bovine liver show that radiofrequency ablation (RFA) is very effective for performing controlled ablations with minimally invasive probes, such as cardiac pathologies, small lesions, tissues with particular composition, while microwave ablation (MWA) is optimal for performing large ablations in highly vascularised tissues, such as liver cancer, where it is necessary to achieve higher temperatures.

Early detection of cancer increases the probability of recovery. This paper presents an intelligent decision support system (IDSS) for the early diagnosis of cancer based on gene expression profiles collected using DNA microarrays. Such datasets pose a challenge because of the small number of samples (no more than a few hundred) relative to the large number of genes (on the order of thousands). Therefore, a method of reducing the number of features (genes) that are not relevant to the disease of interest is necessary to avoid overfitting. The proposed methodology uses the information gain (IG) to select the most important features from the input patterns. Then, the selected features (genes) are reduced by applying the grey wolf optimization (GWO) algorithm. Finally, the methodology employs a support vector machine (SVM) classifier for cancer type classification. The proposed methodology was applied to two datasets (Breast and Colon) and was evaluated based on its classification accuracy, which is the most important performance measure in disease diagnosis. The experimental results indicate that the proposed methodology is able to enhance the stability of the classification accuracy as well as the feature selection

Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. Here, we comprehensively summarize and systematically review the current experimental evidence on this topic.

Background: PRAME, NY-ESO-1 and SSX2 are cancer testis antigens (CTAs), which in normal tissues are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterized cohort soft tissue sarcomas (STS). Methods: On protein level, we examined PRAME, NY-ESO-1 and SSX2 expression in tumour tissues of 249 STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including Tumour-infiltrating lymphocyte (TIL) counts, grading and long- term survival. Results: Expression of PRAME, NY-ESO-1 and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo subtypes. Expression of PRAME was associated with shorter patient survival (p=0.005) and higher grade (G2 vs G3, p=0.001) while NY-ESO-1 expression was correlated with more favourable survival (p=0.037) and low grade (G2 vs G3, p=0.029). Both PRAME and NY-ESO-1 expression was more frequent in STS with low TILs counts. Conclusions: CTAs PRAME, NY-ESO-1 and SSX2 show distinct expression patterns in different STS subtypes. These results may guide future immunotherapeutic approaches in STS.

Testicular granulosa cell tumors (TGCTs) are rare tumors of sex cord stromal origin. TGCTs can be classified into the adult type and the juvenile type. The adult type is extremely rare with only 93 known cases reported in the literature. We, herein, present a report of a case of a 30 year old male patient who presented with a testicular mass, underwent radical inguinal orchiectomy and the pathology examination revealed an adult type granulosa tumor. We additionally review the literature to summarize the scientific knowledge of an entity barely described worldwide.

Background: Cancer patients may fail to distinguish COVID-19 symptoms such as anosmia, dysgeusia/ageusia, anorexia, headache, and fatigue, which are frequent after cancer treatments. We aimed to identify symptoms associated with COVID-19 and to assess the strength of their association in cancer and cancer-free populations. Methods: The prospective multicenter cohort study PAPESCO-19 included 878 cancer patients and 940 healthcare workers (HCWs) systematically tested for SARS-CoV-2-specific antibodies. Participants reported the results of routine screening RT-PCR and thirteen COVID-19 symptoms. Backward logistic regression identified the symptom combinations significantly associated with COVID-19. Results: COVID+ proportions were similar in patients (8%) and HCWs (9.5%, p=0.26), whereas symptomatic proportions were lower in patients (32%) than HCWs (52%, p&lt;0.001). Anosmia, anorexia, fever, headache, and rhinorrhea together accurately discriminated (c-statistic=0.7027) COVID-19 cases in patients. Anosmia, dysgeusia/ageusia, muscle pain, intense fatigue, headache, and chest pain better discriminated (c-statistic=0.8830) COVID-19 cases in HCWs. Anosmia had the strongest association in patients (OR=7.48, 95% CI: 2.96–18.89) and HCWs (OR=5.71, 95% CI: 2.21–14.75). Conclusions: COVID-19 symptoms and their diagnostic performance differ in cancer patients and HCWs. Anosmia is associated with COVID-19 for patients, while dysgeusia/ageusia are not. Cancer patients deserve tailored preventive measures due to their particular COVID-19 symptom pattern.

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

Cervical cancer is preventable through vaccination, early detection, and treatment of precancerous lesions. However, global inequalities mean that the disease remains a leading cause of cancer death around the world, with over 80% of new cases and 90% of deaths occurring in low and middle-income countries (LMICs). In El Salvador, joint efforts between the Ministry of Health (MoH) and the non-profit organization Basic Health International (BHI) have been in place since 2008 with the goal of reducing the country’s disease burden. While the World Health Organization’s (WHO) call to action to eliminate cervical cancer provided worldwide momentum to implement new public health initiatives, the COVID-19 pandemic disrupted ongoing programs and jeopardized plans for the future. The purpose of this manuscript is to describe the progress that El Salvador has achieved in improving cervical cancer prevention, the impact of the pandemic on current strategies, and potential solutions that can help the country meet the WHO’s strategic targets by 2030 to accelerate the elimination of cervical cancer.

Almost 6% of cancers worldwide are attributable to alcohol consumption. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear why alcohol consumption preferentially causes a local carcinogenic effect. We recently hypothesized that the cytotoxic activity of ethanol could explain the high risk of these cancers in alcohol users. Here we report that short-term exposures (2-3 seconds) to ethanol concentrations between 10% and 15% start to cause a marked cytotoxic effect on human epithelial keratinocytes in a concentration-dependent manner. After discussing new evidence that cancer is the end-result of the accumulation of cell divisions in stem cells, we explain why regular alcohol consumption imposes a high risk of cancer on these tissues. Briefly, the cytotoxicity of ethanol reduces the lifespan of the cells lining these tissues. The stem cells located in deeper layers need to divide more often than usual to renew the damaged epithelia. The accumulation of cell divisions in stem cells leads to the accumulation of cancer-promoting errors (e.g., mutations arising during DNA replication) that increase their risk of malignant transformation. Cell division also exposes the DNA of the stem cells to the genotoxic activity of acetaldehyde and tobacco carcinogens. We propose that choosing alcoholic beverages containing non-cytotoxic concentrations of ethanol, or diluting ethanol to non-cytotoxic concentrations, is a simple way to reduce the risk of cancer of the oral cavity, pharynx, larynx and esophagus in alcohol users. This preventive strategy may also abolish the known synergistic effect of alcohol drinking and tobacco smoking on the risk of these cancers.

Animal-assisted interventions (AAI) use human-animal interactions to positive effect in various contexts including cancer care. This systematic literature review is the first part of a two-part paper series focusing on the research methods and quantitative results of AAI studies in oncology. We find methodological consistency in the use of canines as therapy animals, in the types of high-risk patients excluded from studies, and in the infection precautions taken with therapy animals throughout cancer wards. The investigated patient endpoints are not significantly affected by AAI, with the exceptions of improvements in oxygen consumption, quality of life, depression, mood, and satisfaction with therapy. The AAI field in oncology has progressed significantly since its inception and has great potential to positively impact future patient outcomes. To advance the field, AAI research in oncology should consistently improve the methodological design of studies, report data more completely, and focus on the therapy animal’s well-being.

Radiation therapy is employed in treating various cancer types. However, depending on the type and stage of cancer, its benefits can be limited, and it may cause serious side effects that detrimentally affect the quality of life (QOL) for the patient. Preventing the side effects of radiation therapy can enhance the response to cancer treatment and improve the patient’s QOL. Independently, vitamin C and hydrogen have demonstrated potential in reducing the side effects of anticancer drugs and radiation therapy. Furthermore, both have been postulated to possess direct anticancer properties. However, the effects of their combined therapy remain underexplored. This study investigates the hypothesis that combining vitamin C and hydrogen efficiently prevents radiation-induced injuries. Survival rates were investigated in cancer cell lines (MDA-MB231 and GL261) and normal cells (HUVEC) treated with hydrogen, vitamin C and irradiation. Apoptosis was assessed using the FLICA test, and EMT gene expression was elucidated via the qPCR technique. In the normal cell line, the introduction of vitamin C and hydrogen to the culture medium boosted survival rates, exhibiting a radioprotective effect upon irradiation. In contrast, cancer cells showed a decreased survival rate with the introduction of vitamin C and hydrogen, which was further diminished with irradiation. Treated cancer cells showed signs of apoptosis. Caspase activity in viable cells was reduced by the combination treatment with vitamin C and hydrogen. Additionally, glioblastoma cells treated with this combination showed reduced EMT gene expression. This study reveals that a combined therapy of hydrogen and vitamin C offers radioprotective effects on normal cells and exerts direct anticancer effects on cancer cells, while also amplifying the anticancer effects of radiation. Importantly, this combined therapy attenuated the radiation-induced EMT signature in the GL261 murine glioma cell line, suggesting potential in diminishing treatment resistance and tumor invasion.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

According to the ECCB, cancer represents the transition of a genomically damaged multicellular cell to a lower level of cell organization, controlled by the ancestral gene regulatory network (GRN) from the ancestral compartment of human and metazoan genomes. Cancer adopts ancient mechanisms and rules of the common ancestor, similar to those observed in parasitic amoebae. In cancer, the productive cell line generating CSCs is a non-gametogenic cancer germline. This germline proliferates through asymmetric cell division (ACD phenotype). CSCs lack proliferative capacity; they persist in hypoxic niches in a quiescent cell state or transition to an amplifying cell state that performs cyst-like polyploidization cycles, giving rise to precursors and CSCs capable of differentiation. Malignization arises from genomically dysfunctional tetraploid germline cells (DSCD phenotype) that proliferate in a precancerous stage through symmetric cell cycles. DSCD progeny undergo homotypic fusion, forming multinucleated genome repair syncytia (MGRS pathway) driving carcinogenesis. During tumorigenesis, metastasis, and recurrence, subsequent germline clones initiate a cascade of increasingly pathogenic CSCs through mechanisms such as heterotypic cell fusion, soma-to-germ transition, and polyploid giant cell structures (PGCCs). Irradiation and chemotherapies drive some of the very few surviving but dysfunctional CSCs through a PGCC repair pathway homologous to the MGRS pathway of carcinogenesis. The large number of PGCCs during metastasis and recurrence results from the perpetual germline cell damage and CSC poverty induced by oxygen levels above 6.0% O2 (germline hyperoxia).

Breast and prostate cancer lead incidence rankings in Chile, with obesity and overweight as important risk factors involved in prognosis. Nutritional interventions have shown to be beneficial therapies in patients with cancer, improving anthropometric and biochemical measurements. This study investigates the feasibility and effectiveness of Calorie Restriction and Time-Restricted Feeding in overweight or obese patients undergoing curative radiotherapy for breast and prostate cancer. The research was conducted as a prospective, interventional, non-randomized clinical trial, involving 27 participants, of whom 23 completed the study. Findings indicate that both interventions are feasible and effective. Notably, Time-Restricted Feeding demonstrated superior adherence and more significant improvements in weight loss and metabolic parameters. A mean weight reduction of 3.6 kg and waist circumference decrease of 4.9 cm was observed across participants. Serum levels of glucose, insulin, LDL, HDL and TG showed an average reduction, indicating positive metabolic changes. Results suggest that Time-Restricted Feeding could be a superior beneficial dietary intervention for cancer patients undergoing radiotherapy, due to its ease of adherence and positive impact on metabolic health. This research contributes to the growing evidence on the role of nutritional interventions in cancer treatment and underscores the need for more extensive studies to validate these findings.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide as peptide fragment of the linker, including two phenylalanine residues in the L-configuration, and 3- or 4-(tributylstannyl)benzoic acid as prosthetic group in their structures for radiolabeling. The standard compounds ([127I]PSMA-m-IB and [127I]PSMA-p-IB) for comparative and characterization studies were firstly synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence, followed by replacement of the Sn(Bu)3 group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [123I]PSMA-p-IB was higher than those of [123I]PSMA-m-IB, which were 74.9± 1.0% and 49.4 ± 1.2%, respectively. The radiochemical purity of [123I]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [123I]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [123I]PSMA-p-IB showed less accumulation than [177Lu]Lu-PSMA-617 in several normal organs (liver, kidney and bone). These results warrants further preclinical development including toxicology evaluation and experiments in tumor-bearing mice.

The frequent incidents of oil spills and other forms of pollution arising from crude oil exploration and exploitation (OEE) in the Niger Delta have caused several investigations on Polycyclic Aromatic Hydrocarbons (PAHs) pollution. This study aimed at developing a comprehensive report on PAH pollution and its human health risks recorded in the Niger Delta. Studies were extracted from Google Scholar, PubMed, and ResearchGate using a defined selection criterion. The quality of each study was assessed using the Newcastle – Ottawa Scale. Thirty-eight studies were selected with the majority reporting on PAH pollution in aquatic environments. Across all the selected studies, the total number of PAHs recorded ranged from 7 to 28 PAH congeners. Also, PAH potential sources reported in the studies were of pyrogenic and petrogenic sources. PAH concentrations recorded in water, sediment, aquatic organisms (fish and shrimp), soil, dust, and crop samples ranged from below detection limit (BDL) to 450 ± 117.9 mg/L, BDL to 1821.5 mg/kg, 0.005 to 1.098 mg/kg, ND to 4154 ± 3461 mg/kg, 165.1 to 1012 mg/kg, and 0.020 to 3.37 mg/kg, respectively. Majority of the selected studies reported PAH levels which were higher than the permissible limits. Incremental Lifetime Cancer Risk (ILCR) assessment of PAHs in samples ranged from low to high via ingestion and dermal routes of exposure to humans. It is recommended that the Federal Government of Nigeria promotes environmentally friendly operations of OEE. Future studies should focus on PAH pollution in farmlands, ambient air and the associated human and ecological health risks.

Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and miti-gating the burden of this life-threatening disease. This review aims to provide an overview of our current under-standing of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.

Simple summary This reassessment of the findings from our Phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate-high risk prostate cancer in the absence of androgen-deprivation therapy due to patient’s refusal, with a median follow-up of 6.5 years. Our primary focus is on analysing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade 2 or higher, both genitourinary and gastrointestinal. Abstract Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intraprostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intraprostatic recurrences occurred in 7 patients (21%), with ≥ 75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patient. Notably, 5 patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intraprostatic recurrences. Extended follow-up revealed grade 2 or higher late GU and GI toxicity in 18% (n=6) and 6% (n=2) of the patients. Conclusions: Among patients with intermediate-high risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: focal dose escalated prostate SBRT prevented recurrences in the dominant nodule, however extra-prostatic recurrence sites were frequent.

This review provides an overview of eXplainable AI (XAI) methods for oncological ultrasound image analysis and compares their performance evaluations. A systematic search of Medline Embase and Scopus between March 25 and April 14 2024 identified 17 studies describing 14 XAI methods, including visualization, semantics, example-based, and hybrid functions. These methods primarily provided specific, local, and post-hoc explanations. Performance evaluations focused on AI model performance, with limited assessment of explainability impact. Standardized evaluations incorporating clinical end-users are generally lacking. Enhanced XAI transparency may facilitate AI integration into clinical workflows. Future research should develop real-time methodologies and standardized quantitative evaluative metrics.

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine therapy is a cornerstone in DTC management, but sometimes it became useless when cancer cells develop refractoriness. Radioactive Iodine Refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used, it has a demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. FA-Pi, PSMA, SSTR tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed to re-induce RAI accumulation in DTC cells. Results appeared promising, despite not excellent. Conclusions: RAIR-DTC yet represent a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation with post-therapy whole body scan (PT-WBS) is the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents oblige physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

Lung cancer remains a pervasive global health challenge, necessitating precise and efficient classification methods to inform optimal treatment strategies. In this study, we investigate the potential of machine learning algorithms in developing a computer-aided diagnostic tool for early and accurate lung cancer classification, leveraging essential protein biomarkers as predictive features. Our investigation reveals the superiority of Deep Neural Networks (DNNs) in lung cancer classification, achieving an impressive accuracy of 96.91%. This highlights the transformative potential of DNNs in facilitating real-world clinical applications, offering clinicians a powerful tool for accurate diagnosis and prognosis. Additionally, we analyze the performance of Ensemble Methods, including Voting (91.75%) and Bagging (93.81%), as viable alternatives to DNNs. These ensemble techniques demonstrate robust performance, further underlining their utility in lung cancer classification tasks. Furthermore, our study underscores the critical role of hyperparameter tuning, particularly in adjusting parameters such as min child weights and learning rates, in mitigating overfitting and enhancing the generalizability of diverse machine learning models. For instance, Support Vector Machines (SVM) exhibit varying accuracies ranging from 74.23% to 95.88% across different hyperparameter configurations, emphasizing the importance of hyperparameter optimization in maximizing model performance. In summary, our comprehensive comparative analysis sheds light on the efficacy of different machine learning approaches in lung cancer classification. By leveraging advanced algorithms and optimizing model parameters, researchers and clinicians can harness the power of machine learning to advance early detection and personalized treatment strategies for lung cancer patients.

Abstract This study delved into the application of various machine learning (ML) models for the classification of lung cancer levels. Through meticulous monitoring of parameters such as minimum child weight and learning rate, efforts were made to mitigate overfitting while optimizing model performance. The Deep Neural Network (DNN) emerged as a standout performer, showcasing robust performance across training, validation, and testing stages. Ensemble methods like voting and bagging also demonstrated promising results. However, Support Vector Machine (SVM) models with the Sigmoid kernel faced challenges in achieving satisfactory performance. Overall, the investigation sheds light on the efficacy of different ML models in lung cancer level classification and underscores the importance of parameter tuning to address overfitting concerns.

Cancers, a large and heterogeneous group of malignancies, are becoming an increasingly important cause of premature mortality worldwide. 2% of these are primary CNS tumors, of which 24% are gliomas. These tumors are diverse, but what they have in common is one of the most unfavorable prognoses among all cancers. A patient's future varies depending on the grade of the diagnosed glioma. To date, however, no standard treatment for grade IV has been established. All glioblastomas eventually undergo progression or recurrence. The current standard of treatment, which includes surgical intervention, radiation therapy and chemotherapy, is therefore far from sufficient. Work is constantly underway to discover a new, effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound - a photosensitizer (PS), which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating activation processes leading to the formation of reactive oxygen species and selective destruction of inappropriate cells. Currently, this method has been approved for the treatment of several cancers. Research focusing on the effective use of PDT in glioma therapy is already underway, with promising results. In our work, we present molecular insights into PDT of glioma. Based on the available literature, we analyze and systematize the impact of various molecules, proteins, transporters and transmitters on the efficacy of PDT and the effect of PDT on their expression. In addition, we highlight gaps in current knowledge and point out directions for future research that may contribute to the efficacy of PDT glioma.

In the digital age, Artificial Intelligence (AI) is emerging as a transformative force in various sectors, in-cluding medicine. This article explores the potential of AI, akin to the magical genie of Aladdin's lamp, particularly within thoracic surgery and lung cancer management. It examines AI applications like ma-chine learning and deep learning in achieving more precise diagnoses, preoperative risk assessment, and improved surgical outcomes. The challenges and advancements in AI integration, especially in computer vision and multi-modal models, are discussed alongside their impact on robotic surgery and operating room management. Despite its transformative potential, implementing AI in medicine faces challenges regarding data scarcity, interpretability issues, and ethical concerns. Collaboration between AI and medi-cal communities is essential to address these challenges and unlock the full potential of AI in revolution-izing clinical practice. This article underscores the importance of further research and interdisciplinary collaboration to ensure the safe and effective deployment of AI in real-world clinical settings.

Prostate Cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. Accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep-learning techniques with comprehensive datasets, our approach presents a step forward in the pursuit of personalized and targeted cancer care.

Introduction: Cervical cancer is the fourth most common cancer in women globally and the most common cancer in Tanzania, resulting in about 9772 new cases and 6695 deaths each year. Research has shown an association between low levels of risk perception and knowledge of the prevention, risks, signs, etiology, and treatment of cervical cancer and low screening uptake, as contributing to high rates of cervical cancer-related mortality. However, there is scant literature on the perspectives of a wider group of stakeholders (e.g., policymakers, healthcare providers (HCPs), and women at risk), especially those living in rural and semi-rural settings. Methods: We adapted Risso-Gill and colleagues’ framework for a Health Systems Appraisal (HSA), to identify HCPs' perspective of the extent to which health system requirements for effective cervical cancer screening, prevention, and control are in place in Tanzania. We adapted interview topic guides for cervical cancer screening using the HSA framework approach. Study participants (69 in total) were interviewed between 2014-2018 –participants included key stakeholders, HCPs, and women at risk for cervical cancer. The data was analyzed using reflexive thematic analysis methodology. Results: Seven themes emerged from our analysis of semi-structured interviews and focus groups: 1) knowledge of cervical cancer risk and the role of screening and preventive care/services (e.g., prevention, risks, signs, etiology, and treatment), 2) training and knowledge of HCPs, 3) knowledge of cervical cancer screening among women at risk, 4) beliefs about cervical cancer screening, 5) role of traditional medicine, 6) risk factors, and 7) symptoms and signs. Conclusion: It is evident that there is a low level of knowledge of cervical cancer risk and the role of screening and preventive services among stakeholders, HCPs, and women living in rural and semi-rural locations in Tanzania. There is a critical need to implement more initiatives and programs to increase the uptake of screening and related services and allow women to make more informed decisions on their health.

The magnesium ion is an essential cation in the human body and participates in numerous physiological activities. A deficiency in magnesium ions is closely associated with tumor development, and supplementation with magnesium ions has been shown to partially inhibit tumor growth. However, the specific mechanisms by which magnesium ions suppress tumor proliferation remain unclear. Currently, studies have revealed that mitochondria may serve as a crucial intermediate link in the regulation of tumors by magnesium ions. Mitochondria might intervene in the proliferation and invasion of tumor cells by modulating energy metabolism and oxidative stress levels. Therefore, this article provides a comprehensive review of the relationship between magnesium ions and tumors, the mechanisms by which magnesium ions regulate mitochondrial function, and the theoretical basis and prospects of magnesium ion regulation of mitochondrial function for tumor treatment. This review aims to offer insights for clinical tumor treatment strategies involving magnesium ion intervention.

As times goes, the survival was improved attributed to target therapy and chemotherapy. Metastasis to skeletal muscle tissue is rare. Herein, we reported a case presenting with deep venous thrombosis but skeletal muscle metastasis. Though it was rare, oncologist shoud be keep in mind due to worse prognosis .

Uterine pathologies pose a challenge to women’s health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the Microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

Colorectal cancer (CRC) with KRAS mutation is prone to develop metachronous metastasis. However, effective measures for prediction and prevention of such clinical issue are currently unavailable. In this study, we confirmed that KRAS mutation is a risk factor for CRC metachronous metastasis through meta-analysis and public database analysis. Based on the ICGC-AGRO database, we have constructed a risk scoring model for predicting metachronous metastasis in KRAS-mutant CRC using machine learning, which was validated in public datasets. Furthermore, we discovered that KRAS inhibitors can effectively suppress the migration and invasion capabilities of high risk CRC cells by wound healing assay and transwell experiment, which was validated ex vivo and in vivo using organoids and splenic liver metastatic mouse model. Finally, RNA sequencing, RT-qPCR, and western blots have proven that KRAS inhibitors can suppress the epithelial-mesenchymal transition (EMT) and transforming growth factor beta (TGF-beta) signaling pathway in CRC. Collectively, our study suggests that KRAS inhibitors may inhibit the metastatic ability of CRC by suppressing EMT and the TGF-beta pathway, suggesting their potential for the prevention of metachronous metastasis in CRC with KRAS mutation.

Pancreatic cancer is an intractable disease with the worst prognosis of all cancers. The currently used treatment regimens do not significantly impact patient survival, and therefore, effective treatment strategies are urgently needed. Drug repurposing, which identifies new indications for existing and approved drugs, has proven to be a promising approach to anti-cancer drug discovery. Indeed the antihelmintic drug, pyrvinium pamoate has shown promise as an anti-pancreatic cancer drug, but to date, the inhibition of mitochondrial function is the only mechanism of action described in pancreatic cancer. This study showed, using pancreatic cancer 2D cell cultures and 3D spheroids, that pyrvinium pamoate exhibited short- and long-term cytotoxicity, inhibited epithelial-to-mesenchymal transition and cell invasion and migration. Mechanistically, pyrvinium pamoate induced DNA damage, inhibited the PI3K/AKT cell survival pathway, and triggered cell cycle arrests, as well as apoptotic and autophagic cell death. Importantly, pyrvinium pamoate acted synergistically with the first-line drug, gemcitabine in 2D and 3D pancreatic cancer cell culture models. This study provided evidence that pyrvinium pamoate is effective as a single agent and in combination with gemcitabine for the treatment of pancreatic cancer.

Colorectal cancer (CRC) is the second cause of cancer-related death where the CpG-island methylation pathways (CIMP) is associated to KRAS/BRAF mutations, two oncogenes rewiring cell metabolism, worst prognosis and resistance to classical chemotherapies. Despite this, the question of a possible metabolic rewiring in CIMPs has never been asked. Here we asked if metabolic dysregulations were associated to the methylation status of tumours by evaluating the transcriptome of CRC tumours. CIMP-high patients were found to present a hyper-metabolism activating mainly carbohydrates, folates, sphingolipids and arachidonic acid metabolic pathways. A third of these genes had epigenetic targets of Myc in their proximal promoter, activating carboxylic acid, tetrahydrofolate interconversion, nucleobase, and oxoacid metabolisms. Amongst the Myc signature, the expression of GAPDH, TYMS, DHFR, TK1 was enough to predict methylation levels, microsatellite instability (MSI) and mutations in the mismatch repair (MMR) machinery, which are strong indicators of responsiveness to immunotherapies. Finally, we discovered that CIMP patients harboured an increase in genes involved in the one-carbon metabolism, a pathway critical to provide nucleotides for cancer growth and methyl donors for DNA methylation which was associated to worse prognosis. Transcriptomics could hence become a tool to help clinicians stratify their patients better.

Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

Lung cancer remains a formidable global health challenge that necessitates inventive strategies to improve therapeutic outcomes. Conventional treatments, including surgery, chemotherapy, and radiation, have demonstrated limitations in achieving sustained responses. Therefore, the explora-tion of novel approaches encompasses a range of interventions that show promise in enhancing outcomes for patients with lung cancer, particularly those facing advanced or refractory cases. These groundbreaking interventions hold the potential to overcome cancer resistance and offer personalized solutions. Despite the rapid evolution of emerging lung cancer therapies, persistent challenges such as resistance, toxicity, and patient selection underscore the need for continued development. Consequently, the landscape of lung cancer therapy is transforming with the in-troduction of precision medicine, immunotherapy, and innovative therapeutic modalities. Addi-tionally, a multifaceted approach involving combination therapies through the integration of tar-geted agents, immunotherapies, or traditional cytotoxic treatments addresses the heterogeneity of lung cancer while minimizing adverse effects. This review provides a brief overview of the latest emerging therapies that are reshaping the landscape of lung cancer treatment. As these novel treatments progress through clinical trials and integrate into standard care, the potential for more effective, targeted, and personalized lung cancer therapies comes into focus, instilling renewed hope for patients facing challenging diagnoses.

Sleep is a fundamental human need: sleep disruption, in fact, causes an increase in the activity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms and pro-inflammatory responses. Sci-entific literature is finally starting to pay attention to the central role of sleep-wake rhythm alterations for patients health. Oxaliplatin is used extensively for the treatment of gastrointestinal cancer and other malignancies, with increased frequency of use in recent years. This study aims to understand the effects of sleep-wake rhythm alterations on health and quality of life on cancer patients treated with oxaliplatin. Study has been conducted through the creation and distribution of questionnaires to patients to inves-tigate the potential alteration of the sleep-wake quality. Evaluating the influence of the collected variables on sleep quality, only liver and biliary tract and pancreas tumor lo-calization, in males, and previous difficulty sleeping, and anxiety, worries and stress, in females, resulted statistically significant. The results obtained may serve as foundation for designing awareness campaigns and updating of patients, healthcare personnel and caregivers, to improve health and quality of patients life.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 antibody, named H₂Mab-250/H₂CasMab-2 (IgG₁, kappa). H₂Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H₂Mab-250 did not react with non-transformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs including H₂Mab-119 (IgG₁, kappa) reacted with both cancer and normal epithelial cells. Furthermore, a core-fucose deleted IgG_2a-type H₂Mab-250 (H₂Mab-250-mG_2a-f) could trigger the antibody-dependent cellular cytotoxicity activity to BT-474, but not to HaCaT cells. Furthermore, H₂Mab-250-mG_2a-f exhibited an in vivo antitumor effect against BT-474 xenograft. Immunohistochemical analysis demonstrated that H₂Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared to H₂Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H₂Mab-250. H₂Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.

Rectal cancer presents significant diagnostic and therapeutic challenges, with neoadjuvant therapy playing a pivotal role in improving resectability and patient outcomes. MRI serves as a critical tool in assessing treatment response. However, differentiating viable tumor tissue from therapy-induced changes on MRI remains a complex task. In this comprehensive review, we explore treatment options for rectal cancer based on resectability status, focusing on the role of MRI in guiding therapeutic decisions. We delve into the nuances of MRI-based evaluation of treatment response following neoadjuvant therapy, with particular attention to emerging techniques like radiomics. Drawing from current literature and insights, we provide essential recommendations for post-neoadjuvant therapy management in rectal cancer, all within the context of MRI-based findings.

Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared to normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate utilizing several cell lines from the breast and lung. Initial screening was done in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of growth media used. Given the paradigm-shifting nature of our discovery, we pursued possible mechanisms responsible. Neither mass, cell doubling, nor volume, accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased ATP at premigratory-wound induction – but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.

The aim of this prospective study was to examine the issues of these items to evaluate the possibility of their application to clinical practice. This prospective survey was performed on pharmacists of 14 hospitals. The number of confirmation items was 345 and 375 items in the control group and recommended item group, respectively. The mean time required for completing a regimen check (±standard deviation) was 4 minutes and 14 seconds (±1 minute and 50 seconds) and 6 minutes and 18 seconds (±1 minute and 7 seconds) in the control group and recommended item group, respectively. Among the recommended items, the mean number of items that pharmacists confirmed was 12.4 and 18.6 in the control and recommended items, respectively. The number of doubt inquiries was higher in the recommended item group than in the control group (41 vs. 27 cases). The number of doubt inquiries related to dosage, premedication, urinalysis, and a history of hepatitis B virus was higher in the recommended item group than in the control group. In the present study, we created 19 items that should be confirmed in regimen checks and examined the possibility of their application to clinical practice.

Objective: To compare the overall survival (OS) and surgical outcomes between open and minimally invasive surgery (MIS) in a large cohort of women with Type II endometrial cancer. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, carcinosarcoma) between January 2010 and December 2014. Primary outcome was the comparison of OS between MIS and the open approach. Secondary outcomes included the length of hospital stay, readmission rate, 30- and 90-day mortality. Multivariable logistic regression and inverse propensity weighting analyses were performed. Results: A total of 12,905 patients with Type II, Stage I-III endometrial cancer who underwent hysterectomy were identified. Among these patients, 7,123 (55.2%) underwent MIS. The utilization of MIS increased from 39% to 64% over the four-year period. In propensity-score-weighted analysis, MIS was associated with superior OS (101.7 vs. 86.7 months, p=0.0003 by the log-rank test), with a hazard ratio of 0.9 (CI 0.857-0.954, p=0.0002). MIS was also associated with improved perioperative outcomes, including a shorter length of stay (1 vs. 4 days, p<0.001), lower 30-day readmission rate (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p<0.001). The time interval between surgery and initiation of chemotherapy was shorter in the MIS group (38 vs. 41 days, p<0.001).The increase in MIS adoption correlated with a decrease in 90-day postoperative mortality (2.8% to 2.2%, r=-0.89; p=0.003) and 12-month overall mortality (51% to 38%, r=-0.95, p=0.006). Conclusions: In an epidemiologic study, MIS is associated with improved overall survival and superior perioperative outcomes compared to open surgery in women with Type II endometrial cancer.

Background: Lung cancer is still the most lethal malignancy in the world from the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate always affected by the adverse reaction and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms which can affect the response to chemotherapy and clinical outcome in lung cancer patients. Objective: The objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis in platinum-based chemotherapy in lung cancer patients. Patients and Methods: We performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients by Sequenom MassARRAY. We used Cox proportional hazard models, state and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. Results: We found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treat by platinum-based chemotherapy (p=0.031*). We also discovered that the polymorphisms in rs873601 was significantly associated with the prognosis in age more than 55 years, Small Cell Lung Cancer (SCLC) and smoking patients, Long Intergenic Non-protein Coding RNA (PNKY) rs2444933 in age less than 55 years, SCLC, metastasis and stage III/IV/ED patients, Short Tau Inversion Recovery (STIR1) rs3740051 in SCLC and metastasis patients, PNKY rs1869641 in SCLC patients, XRCC5 rs1051685 in non-metastasis patients, respectively. Conclusion: The ERCC5 rs873601(G>A) maybe a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy. Statements and Declarations: The authors declare that they have no conflict of interest.

Chrysin, a flavonoid compound, has attracted interest as a therapeutic agent due to its anti-inflammatory, antidiabetic, antidepressant, and particularly its anticancer properties. Although studies have presented findings regarding the anticancer properties of chrysin, research on its molecular mechanisms of action remains largely insufficient. This research aimed to deeply investigate chrysin's effects on the breast cancer cell line, MDA-MB-231, in terms of proliferation, invasion, colony formation, and apoptosis. The XTT test results confirmed chrysin's cytotoxic effect on MDA-MB-231 cells, indicating a 48-hour IC50 value of 115.77 µM. Chrysin induced apoptosis in cells, as evidenced by Annexin V assay, and also reduced their colony-forming and invasion. Gene expression analyses showed elevated levels of APC, AXIN1, AXIN2, GSK3A, GSK3B, CK1α, CTNNB1, as well as apoptosis-related genes CASP3, -7, -9, and BAX. This increase was corroborated by the observed rise in protein levels of caspase 3/7 and GSK3B. Moreover, molecular docking results showed that chrysin interacted with genes in the WNT/β-catenin pathway and exhibited drug-like ADME properties. In conclusion, chrysin exhibits potential anticancer effects against MDA-MB-231 cells. It is hoped that these findings will advance preclinical and clinical studies on chrysin's potential in breast cancer treatment.

Cathepsins (Caths) are lysosomal proteases that participate in various physiological and pathological processes. Accumulating evidence suggests that cathepsins play a multifaceted role in radiotherapy response. Firstly, cathepsins contribute to the remodelling of the tumor microenvironment by degrading extracellular matrix components, promoting angiogenesis, and facilitating tumor invasion and metastasis. Their proteolytic activity influences the tumor's response to radiation by affecting oxygenation, nutrient availability, and immune cell infiltration within the tumor microenvironment. Furthermore, cathepsins have been implicated in DNA damage repair processes, including non-homologous end joining and homologous recombination. Cathepsin-mediated DNA repair mechanisms can promote radioresistance in cancer cells, limiting the efficacy of radiotherapy. Additionally, cathepsins have been associated with the activation of prosurvival signalling pathways, such as PI3K/Akt and NF-κB, which can confer resistance to radiation-induced cell death. Radiotherapy plays a crucial role in the treatment of various malignancies. However, the effectiveness of radiotherapy can be limited by intrinsic or acquired resistance mechanisms in cancer cells. In recent years, there has been growing interest in understanding the role of cathepsins, a family of proteases, in modulating the response of tumor cells to radiotherapy. In this study, we shed light on the regulation and expression of cathepsin B in colon carcinoma cell line (Caco-2) before and after exposure to radiation were investigated. Radiation-induced upregulation of cathepsin B in dose-independent manner. Proteolytic inhibition of cathepsin B by cathepsin B specific inhibitor CA074 has increased the cytotoxic effect of ionizing irradiation in caco-2 cells. Similar results were also obtained after cathepsin B knockout by CRISPR CAS9. These results showed that cathepsin B could contribute to ionizing radiation resistance and abolishing of cathepsin B either by inhibition its proteolytic activity or expression has increased in caco-2 cells susceptibility to ionizing irradiation.

Thyroid surgery has been for years one of the most common elective procedures performed in general surgery. In the last 25 years, there have been significant advances in the diagnosis and treatment of thyroid disorders, and new technologies are being implemented. The aim of this study was to ana-lyze 25 years of experience in thyroid surgery in the Department of General, Minimally Invasive and Endocrine Surgery at the Medical University of Wroclaw in terms of demographic changes, indica-tions for surgical treatment, the type of thyroid surgery performed and complications. The impact of recent advances on changes in endocrine surgery was evaluated. For this purpose, clinical material from the years 1996-2020 was analyzed, with a total of 3748 patients (7285 RLN at risk of injury). Period I included the years: 1996-2003, period II: 2011-2015 and 2018-2020. Results: In the last 25 years, the percentage of patients operated on for thyroid cancer has increased threefold (p <0.00001); the extent of thyroid surgery has changed: in 1996-2003, subtotal thyroid operation was performed in more than 90% of patients vs. 1.7% of total thyroid gland surgery; 2011-2015 and 2018-2020 were more than 94% of total thyroid surgery vs. 4% of subtotal surgery (p<0.00001). The increase in the extent of surgery did not affect the percentage of total amount recurrent laryngeal nerve palsy (RLN palsy) (5.17% vs. 4.38% p = 0.1785), it did affect the percentage of transient RLN palsy in group II vs. group I (0.41% vs. 1.34%, p<0.00001), while the percentage of permanent RLN palsy in group I was statistically significantly higher than in group II (4.77% vs. 3.05%, p=0.0016). An increase in the percentage of postoperative clinical hypoparathyroidism in group II was observed: 4.84% vs. 8.93% (p<0.00001). Conclusions: Over 25 years, there has been a significant increase in the number of sur-geries performed for thyroid cancer, the range of surgeries from partial resections to total excision of the thyroid gland has changed, and the increased range of surgeries did not have a statistically signifi-cant effect on the number of vocal fold paralysis, but increased the percentage of postoperative hypo-parathyroidism. Intraoperative neuromonitoring had a significant impact on changing the scope of surgery and preventing complications.

Oral Squamous Cell Carcinoma is one among the most common cancer and early detection is the main key to avoid deaths. Automated diagnostic tools that process the histopathological images of a patient to detect abnormal oral lesions will be very much useful for the clinicians. A deep learning framework have been designed with an intermediate layer between feature extraction layers and classification layers for classifying the histopathological images into two categories, namely normal and oral squamous cell carcinoma. The intermediate layer is constructed using the proposed Swarm Intelligence technique called Modified Gorilla Troops Optimizer. Various optimization algorithms are implemented in literature for optimal parameter identification, weights updating and feature selection in deep learning models, but this work focuses on usage of optimization algorithm as intermediate layer that transforms the extracted features into the features that are more suitable for classification. Three datasets totally comprising 2784 normal and 3632 oral squamous cell carcinoma subjects are considered in this work. Three popular CNN architectures namely InceptionV2, MobileNetV3, and EfficientNetB3 are investigated as feature extraction layers. Two fully connected Neural Network layers along with batch normalization and dropout are used as classification layers. Among the investigated feature extraction models, MobileNetV3 performs well in all the three datasets with the highest accuracy of 0.89. Usage of the proposed Modified Gorilla Troops Optimizer as an intermediate layer boosts this accuracy to 0.95.

Apigenin (API) possesses excellent antitumor properties, but its limited water solubility and low bioavailability restrict its therapeutic impact. Thus, a suitable delivery systems is needed to overcome these limitations and improve the therapeutic efficiency. Poly (lactic-co-glycolic acid) (PLGA) is a copolymer extensively utilized in drug delivery. Hyaluronic acid (HA) is a major extracellular matrix and can specifically bind with CD44 on colon cancer cells. Chitosan (CS) can serve as an intermediate binding with HA and PLGA. Herein, we aimed to perpare receptor-selective HA-coated PLGA nanoparticles (NPs) for colon cancer with high expression of CD44. Firstly, API was encapsulated in PLGA to obtain PLGA-API-NPs, which were then sequentially combined with CS and HA to form HA-coated PLGA NPs. HA coated PLGA NPs had a stronger sustained-release capability. Cellular uptake of HA coated PLGA NPs was enhanced in HT-29 cells with high expression of CD44. HA-PLGA-DiR-NPs can target specificity towards the HT-29 ectopic tumor model. Overall, HA coated PLGA NPs was an effectively drug deliver platform for API in treatment of colon cancer with high expression of CD44.

Aims: This systematic review aims to evaluate the influence of Environmental Enrichment (EE) on oncological factors in experimental studies involving various types of cancer models. Methods: A comprehensive search was conducted in three databases: PubMed (161 articles), Embase (335 articles), and Scopus (274 articles). Eligibility criteria were applied based on the PICOS strategy to minimize bias. Two independent researchers performed the searches, with a third participant resolving any discrepancies. The selected articles were analyzed, and data regarding sample characteristics and EE protocols were extracted. The outcomes focused solely on cancer and tumor-related parameters, including cancer type, description of the cancer model, angiogenesis, tumor occurrence, volume, weight, mice with tumors, and tumor inhibition rate. Key-findings: A total of 770 articles were identified across the three databases, with 12 studies meeting the inclusion criteria for this systematic review. The findings demonstrated that different EE protocols were effective in significantly reducing various aspects of tumor growth and development, such as angiogenesis, volume, weight, and the number of mice with tumors. Furthermore, EE enhanced the rate of tumor inhibition in mouse cancer models. Findings: This systematic review highlights the significant impact of EE protocols on multiple parameters associated with tumor growth and development, including angiogenesis, occurrence, volume, weight, and tumor incidence. Moreover, EE demonstrated the potential to increase the rate of tumor inhibition. These findings underscore the importance of EE as a valuable tool in the management of cancer.

The scalp is a unique anatomical region with distinct challenges for reconstruction, especially in cases of melanoma excision. This study explores the utilization of the O-Z flap technique as an alternative approach for patients with melanoma, where traditional free flap reconstruction may not be feasible due to age or underlying health conditions. However, in this case, the patient had a history of angina and was unwilling to undergo a long operation due to his advanced age. This study highlights the importance of following NCCN guidelines for melanoma resection margins based on tumor thickness and underscores the value of staged resection planning to minimize deficits. This requires an individualized approach as each patient may have different circumstances (general health condition, age, compliance, etc.). So we planned a staged excision first. In the first surgery, we would resect the tumor minimally and then determine the exact size of the tumor. Then, in the second surgery, we resected it with a safety margin according to the guidelines. The O-Z flap, a local flap with an "O"-shaped defect and "Z"-shaped incision line, is introduced as a reconstructive option. The surgical procedure, advantages, and limitations of this approach are discussed. This study provides valuable insights into achieving successful scalp reconstruction while considering aesthetic outcomes and patient-specific factors.

Breast cancer and cardiovascular diseases (CVD) represent significant global health challenges, with CVD being the leading cause of mortality and breast cancer showing a complex pattern of incidence and mortality. We explore the intricate interplay between these two seemingly distinct medical conditions, shedding light on their shared risk factors and potential pathophysiological connections. A specific connection between hypertension (HTN), atrial fibrillation (AF), myocardial infarction (MI), and breast cancer was evaluated. HTN is explored in detail, emphasizing the role of aging, menopause, insulin resistance, and obesity as common factors linking HTN and breast cancer. Moreover, an attempt is made to identify the potential impact of antihypertensive medications and highlight the increased risk of breast cancer among those women, with a focus on potential mechanisms. A summary of key findings underscores the need for a multisystemic approach to understanding the relationship between CVD and breast cancer is also explored with a highlight for all the gaps in current research, such as the lack of clinical observational data on MI and breast cancer in humans and the need for studies specifically designed for breast cancer. This paper concludes that there should be a focus on potential clinical applications of further investigation in this field, including personalized prevention and screening strategies for women at risk. Overall, the authors attempt to provide a comprehensive overview of the intricate connections between breast cancer and cardiovascular diseases, emphasizing the importance of further research in this evolving field of cardio-oncology.

Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.

Since there are no morphological clues capable of making a pathologist suspect a possible mammary origin of a metastatic lesion without adequate clinical information, the histologic diagnosis of brain metastasis from BC is still based on the immunohistochemical expression of mammary gland markers such as GATA-3, ERs, PgRs and HER-2. The present retrospective study aimed to select purely morphological features capable to suggest the mammary origin of a metastatic carcinoma to the brain. The following histological features were collected on a series of 30 cases of brain metastases from breast cancer:(i) solid growth pattern; (ii) presence of comedonecrosis; (iii) glandular differentiation. Our results showed that most cases histologically exhibited solid growth pattern with at least focal comedonecrosis, producing an overall morphology closely reminiscent of mammary high-grade ductal carcinoma in situ. Although the above-mentioned morphological parameters are not strictly specific to a mammary origin, they may have an important diagnostic utility in leading pathologists to suspect a possible breast primary tumor and to include GATA-3, ERs, PgRs and HER-2 to the immunohistochemical panel.