This study aims to evaluate the patient’s dose exposure from Computed Tomography Pulmonary Angiography (CTPA) examination and to estimates the cancer risk induced from the examinations based on the patient’s size. One hundred patients were recruited, and data information was collected retrospectively. A multi-detector (MDCT) (Philips Brilliance 128, USA) scanner were utilized for the CTPA examination, and dose data were obtained from the system. The effective diameter of each subjects’ image was measured for the Size-specific dose estimates (SSDEs). All subjects divided into Group 1 (19 – 25 cm), Group 2 (25-28 cm) and Group 3 (28-38 cm), where the association between gender were analysed. Effective dose (E), SSDE, organ dose and cancer risk of each group were evaluated and compared statistically using independent t-test and one-way ANOVA. The range of mean CTDI_vol, DLP and E values were (6.44 – 17.42 mGy), (239 – 631 mGy), (5.19 – 13.90 mSv), respectively. In respective with the patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89 mGy, 13.70 ± 9.04 mGy and 22.29 ± 7.35 mGy. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. Lung and breast with more massive patient’s effective diameter received the highest dose exposure which increases the probability of the cancer risk. CTDI_vol was found to be underestimated, and SSDE provides more accurate in describing the radiation dose and cancer risk. Body effective diameter found to be significant on the estimation except for gender. Therefore, it is essential to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

Very hot (> 65 °C) beverages such as espresso were evaluated by the International Agency for Research on Cancer (IARC) as probably carcinogenic to humans. For this reason, research into lowering beverage temperature without compromising its quality or taste is important. For espresso, one obvious possibility consists in lowering the brewing temperature. In two sensory trials using ISO 4120:2004 triangle test methodology, brewing temperatures of 80°C vs. 128°C and 80° vs. 93°C were compared. From the tested levels, espresso brewed at the lowest temperature had the highest acceptance. However, most tasters were unable to distinguish between 80°C and 93°C. The results of these pilot experiments proof the possibility to decrease the health hazard of very hot beverages by lower brewing temperatures.

Background: Feasibility trials are preliminary trials that assess the viability and acceptability of intervention studies and the effects of the intervention on intermediate endpoints. Due to their short duration, they are unable to establish the effects of the intervention on long-term clinical outcomes. We propose a novel method that could transform the interpretation of feasibility trials using modified two-stage randomisation analyses. Methods In this two-stage process, we explored the effects of a 6-month feasibility factorial randomised controlled trial (RCT) of lycopene and green tea dietary interventions (ProDiet) on 159 serum metabolic traits in 133 men with raised PSA levels but prostate cancer (PCA) free. In the first stage, we conducted an intention-to-treat analysis, using linear regression to examine the effects of the interventions on metabolic traits, compared to the placebo group and instrumental variable analysis to assess the causal effect of the intervention on the outcomes. In the second stage, we used a two-sample Mendelian Randomization (MR) approach to assess the causal effect of metabolic traits altered by the interventions, on PCA risk, using summary statistics data from an international PCA consortium of 44,825 cancer cases and 27,904 controls. ResultsThe systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2= 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate (standard deviation difference versus placebo (β)): 0.69; 95% CI= 0.24, 1.15; p=0.003), valine (β: -0.62; -1.03, -0.02; p=0.004), pyruvate (β: -0.56; -0.95, -0.16; p=0.006), and docosahexaenoic acid (β: -0.50; -085, -0.14; p=0.006). The instrumental variable analysis showed there was no evidence that green tea altered the metabolome, but lycopene was associated with an increase in acetate (β=2.13; p=0.006) and decreases in pyruvate (β=-1.90; p=0.009), valine (β=-1.79; p=0.023), diacylglycerol (β=-1.81; p=0.026), alanine (β=-1.55; p=0.015) and DHA (p=0.097), where the regression coefficient represents the standard deviation (SD) difference in metabolite measures per unit change in lycopene (µmol/L) or EGCG (nM).Using MR, a genetically instrumented SD increase in pyruvate increased the odds of PCA by 1.29 (1.03, 1.62; p=0.027). Conclusion Using a two-stage randomization analysis in a feasibility RCT, we found that lycopene lowered levels of pyruvate, which our Mendelian randomization analysis suggests may be causally related to reduced PCA risk.

Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection with adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs that can be identified by embryonic stem cell markers express components of the renin-angiotensin system and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB rarely develops distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in relation to CSCs, circulating CSCs, the RAS and the novel therapeutic approach by repurposing drugs that target the renin-angiotensin system to improve overall symptom-free survival and maintain quality of life.

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. Studies have unveiled that miR-139-5p expression is significantly downregulated in other types of cancers. However, the functions and mechanisms of miR-139-5p in PANC remain unclear. Methods: Bioinformatic analysis was performed to analyze the differentially expressed genes in the TCGA database. PANC cell line with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and has been used to detect cell proliferation, migration, invasion and colony formation in PANC. Subsequently, bioinformatic analysis and luciferase assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mouse model was used to investigate the role of miR-139-5p in PANC tumorigenicity. Results: Through bioinformatic analysis, miR-139-5p was predicted to regulate phosphatidylinositol signaling pathway by targeting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, migration, and invasion could be inhibited by miR-139-5p overexpression and could be promoted by SLC7A11 overexpression. MiR-139-5p could regulate the protein expression level of PI3K and Akt associated with phosphatidylinositol signaling pathway could be by inhibiting the expression of SLC7A11. MiR-139-5p overexpression could suppress PANC tumor growth and the expression of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibiting effect of miR-139-5p to PANC cell proliferation, invasion and migration, at least, was partly due to its inhibiting effect on SLC7A11 expression. Conclusion: These results demonstrated a novel role of miR-139-5p/SLC7A11 in PANC and provided potential prognostic predictors for PANC patients.

There are many species of endemic plants from Mexico, without food or commercial use, but with different applications in traditional medicine and valuable for their content of secondary metabolites. In this sense, we found two species of Cucurbitacea family plants natives of southeast and gulf of México, with traditionally use how soap and laundry agent, control of some pests, and it has also been used how infusion for the treatment of different types of dermatitis and stomachache. In the present work, we evaluate the antiproliferative activity in vitro, of six crude organic extracts, tested against six human tumor cell lines, A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast) and WiDr (colon), the results indicated that at least three extracts from both species presents an interesting antiproliferative activity on five tumor cell lines.

Iodide is an essential micronutrient present in very small quantities in the human body, with a fundamental action for the adequate synthesis of thyroid hormones, which are critical for cell differentiation, growth and metabolism. In the form of iodide, iodine is widely distributed in the environment, although in an irregular manner, occurring in abundant amounts in the oceans and in coastal areas and scarcely found on islands and mountains. The diet is the main source of iodine, whose intake varies according to the amount present in soil and water and according to eating habits. Governmental policies have been adopted to satisfy and guarantee the necessary daily supply of iodine, such as fortification of industrialized salt for domestic iodine consumption or addition to the bread commonly consumed in a given region, or the offer of iodized oil to the population, or even iodine supplementation through medications. Iodide deficiency is the main avoidable cause of brain damage to fetuses and children, as well as retardation of psychomotor development. Thyroid hormones are almost universally involved in the development and proliferation of fetal neural tissue. Permanent lesions of the cerebral cortex, hippocampus and cerebellum may occur, with loss of, or damage to the brainstem or spinal cord, affecting cortical areas that integrate highly specialized stimuli, which become poorly defined on an anatomical basis, including silent areas of the associative cortex. One of the more significant metabolic problems due to dietary iodine deficiency is the presence of goiter (increased volume of the thyroid gland). Thyroid carcinoma is the most frequent endocrine neoplasia affecting the human species and plasma iodine concentration is related to the development of specific subtypes of this neoplasia. An increased prevalence of follicular carcinoma, a more aggressive tumor, has been observed in areas of iodine deficiency, while the correction of this deficiency is associated with a higher prevalence of papilliferous carcinoma, a less aggressive form. CONCLUSION: An ideal plasma iodide concentration is necessary to insure the proper mental development of fetuses and young children and to minimize the aggressiveness of thyroid cancer from follicular cells in humans.

This study analyzes oral supplement of molecular iodine (I2) alone and in combination with the neoadjuvant therapy 5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin (FEC/TE) in women with Early (stage II) and Advanced (stage III) breast cancer. In the Early group, 30 women were treated with I2 (5 mg/day) or placebo (colored water) for 7–35 days before surgery. For the Advanced group, 30 patients received I2 or placebo along with FEC/TE treatment. After surgery, all patients received FEC/TE + I2 for 170 days. I2 supplementation showed a significant attenuation of the side effects and absence of tumor chemoresistance. Control, I2, FEC/TE, and FEC/TE+I2 groups exhibit response rate of 0, 33%, 73%, and 100%, respectively, and a pathologic complete response of 18%, and 36% in the last two groups. Five-year disease-free survival rate was significantly higher in patients with I2 supplement before and after surgery compared to those receiving the supplement only after surgery (82% vs. 46%). I2-treated tumors exhibit less invasive potential, and significant increases in apoptosis, estrogen receptor expression, and immune cell infiltration. Transcriptomic analysis indicated activation of the antitumoral immune response. The results led us to register a phase III clinical trial analyzing chemotherapy + I2 treatment for advanced breast cancer.

Although there is a several array of diagnostic and therapeutic choices for pancreatic cancer in recent years, a crucial medical approach for the refractory disease is still needed. Oligonucleotide therapeutics, such as those based on antisense RNAs, RNA interference, aptamers and decoys, are promising agents against pancreatic cancer because they identify a specific nucleotide sequence or protein and interfere with gene expression as molecular-targeted agents. Within just the past quarter-century, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Actually, there have been several clinical and preclinical studies of oligonucleotides for patients with pancreatic cancer so far. To support the discovery of effective diagnostic or therapeutic options by using oligonucleotide-based strategies in the absence of satisfactory therapies for long-term survival and the rising trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients with underlying preclinical or scientific data and focus on the possibility of oligonucleotides to target pancreatic cancer in clinical implications.

Owing to fascinating applications of ZnO in modern devices, it is interesting to explore its more features for future devices. Hence, herein, we have synthesized the high quality ZnO spherical nanoparticles (SNPs) through a facile green synthesis route and robust structural and biomedical studies are carried out. Hexagonal phase with 93.2% crystallinity was confirmed through XRD analysis. ZnO nanoparticles were tested for their bioactivities both in vivo (acute cytotoxicity test) and in vitro (Anti-cancer activities on liver (HepG2) and cervical (Hela) cancer cell lines, stimulatory/inhibitory effects on normal rat splenic cells and hemolytic effects on red blood cells). Results showed that ZnO SNPs has no cytotoxic effects on vital organ like liver and has no hemolytic action on red blood cells. ZnO SNPs showed inhibitory consequence on normal rat splenic cells growth at all tested concentrations. ZnO nanoparticles showed an inhibitory effect on HepG2 cell line. While showed stimulatory effect on Hela cell line. Current study presents the synthesized ZnO SNPs as highly applicable in bio-optoelectronics.

Direct intercellular communication, mediated by gap junctions formed by the connexin transmembrane protein family, is frequently dysregulated in cancer. Connexins have been described as tumour suppressors, but emerging evidence suggests that they can also act as tumour promoters. This feature is connexin- and tissue-specific and may be mediated by complex signalling pathways through gap junctions or hemichannels or by completely junction-independent events. Lung cancer is the number one cancer in terms of mortality worldwide, and novel biomarkers and therapeutic targets are urgently needed. Our objective was to gain a better understanding of connexins in this setting. We used several in silico tools to analyse TCGA data in order to compare connexin mRNA expression between healthy lung tissue and lung tumours and correlated these results with gene methylation patterns. Using Kaplan-Meier plotter tools, we analysed a microarray dataset and an RNA-seq dataset of non-small cell lung tumours in order to correlate connexin expression with patient prognosis. We found that connexin mRNA expression is frequently either upregulated or downregulated in lung tumours. This correlated with both good and poor prognosis (overall survival) in a clear connexin isoform-dependent manner. These associations were strongly influenced by the histological subtype (adenocarcinoma versus squamous cell carcinoma). We present an overview of all connexins but particularly focus on four isoforms implicated in lung cancer: Cx26, Cx30.3, Cx32 and Cx43. We further analysed the protein expression and localization of Cx43 in a series of 72 human lung tumours. We identified a subset of tumours that exhibited a unique strong nuclear Cx43 expression pattern that predicted worse overall survival (p=0.014). Upon sub-stratification, the prognostic value remained highly significant in the adenocarcinoma subtype (p=0.002) but not in the squamous carcinoma subtype (p=0.578). This finding highlights the importance of analysis of connexin expression at the protein level, particularly the subcellular localization. Elucidation of the underlying pathways regulating Cx43 localization may provide for novel therapeutic opportunities.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

Development of novel anti-cancer peptides requires a rapid screening process which can be accelerated by using appropriate in vitro tumor models. Breast carcinoma tissue is a three dimensional (3D) microenvironment, which contains a hypoxic center surrounded by dense proliferative tissue. Biochemical clues provided by such 3D cell mass cannot be recapitulated in conventional 2D culture systems. In this experiment, we evaluate the efficacy of the sandalwood peptide, cyclosaplin on established in vitro 3D silk breast cancer model using invasive MDA-MB-231 cell line. The anti-proliferative effect of the peptide on 3D silk tumor model is monitored by alamar blue assay, with conventional 2D culture as control. The proliferation rate, glucose consumed, LDH, and MMP-9 activity of Human breast cancer cells are higher in 3D constructs compared to 2D. A higher concentration of drug is required to achieve 50% cell death in 3D culture than 2D cultures. The cyclosaplin treated MDA-MB-231 cells showed significant decrease in MMP-9 activity in 3D constructs. Microscopic analysis revealed the formation of cell clusters evenly distributed in the scaffolds. The drug treated cells were less in number, smaller and showed unusual morphology. Overall, these findings indicate the role of cyclosaplin as a promising anti-cancer therapeutics.

Introduction: Novel robotic surgery systems (da Vinci Xi) are superior to classical open and laparoscopic techniques with its clear and three-dimensional view. We aimed to present the first case low anterior resection of rectal cancer and vaginal specimen extraction with Da Vinci Xi.Case: A 75-year-old female patient with rectum adenocarcinoma was undergone robotic-assisted low anterior resection (LAR) of the rectum, vaginal removal of the specimen, colorectal anastomosis and loop ileostomy. The operation time was 190 minutes. There were no postoperative complications. Pathological tumor stage was stage pT1N0 with negative proximal, distal and radial resection margins. The patient was discharged on the third postoperative day.Conclusion: Robot-assisted LAR, total mesorectal excision, vaginal removal of the specimen, colorectal anastomosis, and loop ileostomy can be performed easily and safely with Da Vinci Xi at early stage rectal cancer. And the vaginal extraction of the specimen avoids us from a traditional abdominal incision.

As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl- 2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silybin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40–3.06 µM, a 17- to 52-fold improvement in potency as compared with silybin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G0/G1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.

Background: Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. beta-lapachone (bL) has been widely used to treat cancer development, but its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast cancer stem cell (BCSC) marker positive cells, MDA-MB-231. Methods: MDA-MB-231 Cells, which is negative for NQO1 expression, was constructed to stably express NQO1(NQO1 stable cells) to see the effect of bL. The effect of bL on cells were evaluated by wound healing and Transwell cell culture chambers, and ALDEFLUOR assay. Results: Here, we show that bL inhibited the proliferative ability of mammosphere derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. bL treatment efficiently downregulated expression level of BCSC markers CD44, ALDH1A1, and DLGAP5 that recently identified as a stem cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulates cell proliferation and migration activities. Conclusions: These results strongly suggest that bL could be a therapeutic agent targeting breast cancer stem cells with proper NQO1 expression.

Convenient labeling of proteins is important for observing its function under physiological conditions. In tissues particularly, heptamethine cyanine dyes (Cy-7) are valuable because they absorb in near infrared (NIR) region (750 – 900 nm) where light penetration is maximal. In this work, we found Cy-7 dyes with a meso-Cl functionality covalently binding to proteins with free Cys residues under physiological conditions (aqueous environments, at near neutral pH, and 37 °C). It transpired that the meso-Cl of the dye was displaced by free thiols in protein, while nucleophilic side-chains from amino acids like Tyr, Lys, and Ser did not react. This finding shows a new possibility for convenient and selective labeling of proteins with near-IR fluorescent probes.

Cancer is a leading cause of morbidity and mortality worldwide, yet much is still unknown about its mechanism of establishment and destruction. Recently, studies had shown that tumor cells cannot survive under the high temperature conditions. This treatment technique is called Hyperthermia. This report presents the case of radiative microwave heating of hyperthermia therapy on breast cancer in a porous medium. In this study, the steady state is solved analytically while unsteady state is solved using semi-implicit finite difference to get a more accurate prediction of blood temperature distributions within the breast tissues. A moderate temperature hyperthermia treatment is apply which results into cell death due to an increase in the level of cell sensitivity to radiation therapy and blood flow in tumor and oxygen. The results show that by applying metabolic heat generation rate of $3.97 X 10^{5}Wm^{-3}$, it takes upto 2 minutes for the tumor cells to get the require therapeutic temperature point.

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of a timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including an angiogenic switch, immune escape, cancer stem cells, extra cellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced-p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer, and discuss the implications of such approaches in cancer treatment.

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of a timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including an angiogenic switch, immune escape, cancer stem cells, extra cellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced-p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer, and discuss the implications of such approaches in cancer treatment.

Peripheral tissue metabolism of steroids (intracrinology) is now accepted as a key way in which tissues, such as the endometrium, can utilize inactive steroids present in the blood to respond to local physiological demands and ‘fine-tune’ the activation or inhibition of steroid hormone receptor-dependent processes. Expression of enzymes that play a critical role in activation and inactivation of bioactive oestrogens (E1, E2) and androgens (A4, T, DHT), as well as expression of steroid hormone receptors, has been detected in endometrial tissues and cells recovered during the menstrual cycle. There is robust evidence that increased expression of aromatase is important for creating a local microenvironment that can support a pregnancy. Measurement of intra-tissue concentrations of steroids using liquid chromatography–tandem mass spectrometry has been important in advancing our understanding of a role for androgens in the endometrium acting both as active ligands for the androgen receptor and as substrates for oestrogen biosynthesis. The emergence of intracrinology, associated with disordered expression of key enzymes such as aromatase, in the aetiology of common women’s health disorders such as endometriosis and endometrial cancer has prompted renewed interest in development of drugs targeting these pathways opening up new opportunities for targeted therapies and precision medicine.

Cyclin E2, a member of the cyclin family, is a key cell cycle-related protein. This protein plays essential roles in cancer progression, and as such, an inhibitor of cyclin E2 has been approved to treat several types of cancers. Even so, mechanisms underlying how to regulate cyclin E2 expression in cancer remain largely unknown. The current study found that miR-3687 is up-regulated in clinical bladder cancer (BC) tumor tissues, TCGA database and human BC cell lines. Inhibition of miR-3687 expression significantly reduces human BC cell proliferation in vitro and tumor growth in vivo, which are concurrently with the induction of G0/G1 cell cycle arrest and downregulation of cyclin E2 protein expression. Interestingly, overexpression of cyclin E2 reversed the inhibition of BC proliferation induced by miR-3687. Mechanistic studies suggest that miR-3687 could bind to the 3'-UTR of foxp1 mRNA, downregulates FOXP1 protein expression, and in turn promotes the transcription of cyclin E2, thereby promoting the growth of BC cells. Collectively, the current study not only establishes a novel regulatory axis of miR-3687/FOXP1 in regard to regulation of cyclin E2 expression in BC cells, but also provides strong suggestive evidence that miR-3687 and FOXP1 may be potentially promising targets in therapeutic strategies of human BC.

Owing to their unique physicochemical properties, nanoparticles are used in a variety of ways in the field of cancer treatment, including imaging, drug delivery, and photothermal and photodynamic therapies. The fascinating properties of nanoparticles are determined by their size, morphology, and constituent elements, and various synthetic methods and post-synthetic techniques have been applied to control these factors. Herein, we present examples of shape and composition control through galvanic replacement, a technique that exploits redox potential differences between elements to induce spontaneous ion-exchange and highlight its specific contributions to cancer treatment applications. The present article identifies the recent advances in nanoparticle formation techniques and discusses the future outlook of the field.

The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability. As well characterised clinical and experimental agents, we have detailed knowledge of adenoviruses’ mechanisms of pathogenicity, supported by detailed virological studies and in vivo interactions. In this review we highlight the strides made in the engineering of bespoke adenoviral vectors to specifically infect, replicate within, and destroy tumour cells. We discuss how mutations in genes regulating adenoviral replication after cell entry can be used to restrict replication to the tumour, and summarise how detailed knowledge of viral capsid interactions enable rational modification to eliminate native tropisms, and simultaneously promote active uptake by cancerous tissues. We argue that these designer-viruses, exploiting the viruses natural mechanisms and regulated at every level of replication, represent the ideal platforms for local overexpression of therapeutic transgenes such as immunomodulatory agents. Where T-Vec has paved the way, Ad-based vectors now follow. The era of designer oncolytic virotherapies looks decidedly as though it will soon become a reality.

Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are over-expressed in different kinds of cancer, including breast, prostate and bladder carcinoma, with positive effects on cancer proliferation and chemo-resistance. For these reasons, these enzymes are potential therapeutic cancer targets. Methods: In the present study, we analyzed the effects of three different inhibitors of KDM5 enzymes in MCF-7 breast cancer cells over-expressing JARID1B. In particular we tested H3K4 demethylation (western blot); target gene transcription (RNAseq and real time PCR); radio-sensitivity (citoxicity and clonogenic assays) and damage accumulation (kinetics of H2AX phosphorylation). Results: we show that two compounds with completely different chemical structure can selectively inhibit KDM5 enzymes and that both compounds are capable of increasing sensitivity of breast cancer cells to ionizing radiation and H2AX phosphorylation. Conclusions: These findings confirm the involvement of H3K4 specific demethylases in DNA damage signaling and repair and suggest new strategies for the therapeutic use of their inhibitors.

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and FACS analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and H&E and TUNEL staining analyses were performed and compared between small (tumor volume of <50 mm³) and large (tumor volume of >50 mm³) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.

The International Agency for Research on Cancer (IARC) evaluates “very hot (>65 °C) beverages” as probably carcinogenic to humans. However, there is a lack of research regarding what temperatures consumers actually perceive as “very hot” or as “too hot”. A methodology for organoleptical assessment of such threshold temperatures was developed. The participants were asked to mix a very hot coffee step by step into a cooler coffee. Because of that, the coffee to be tasted was incrementally getting hotter during the test. The participants took a sip at every addition, until they perceive the beverage as too hot for consumption. The protocol was evaluated using 87 participants. Interestingly, the average pain threshold of the test group (67 °C) and the preferred drinking temperature (63 °C) iterated around the IARC threshold for carcinogenicity. The developed methodology was found as fit for the purpose and may be applied in larger studies.

Pancreatic ductal adenocarcinoma (PDA), the most frequent type of pancreatic cancer, is one of the main unfinished businesses in the biomedical and clinical fields, with still discouraging 5 year survival rates and poor therapy efficiency. PDA abundant desmoplasia has for long played the lead in the mechanisms involved in poor drug performance, being the main source of cytokines and chemokines orchestrating rapid and silent tumor progression and guilty of isolating tumor cells into a extense fibrotic reaction resulting in inefficient drug delivery. However, since immunotherapy was proclaimed the breakthrough of the year back to 2013, the focus in the stroma of pancreatic cancer has interestingly moved from activated fibroblasts to the immune compartment, trying to understand the immunosuppressive factors that play part in the strong immune evasion that characterizes PDA. PDA microenvironment is highly immune-suppressive, being basically composed of T regulatory cells (Tregs), tumor-associated macrophages (TAMs) and myeloid-derived suppressive cells (MDSCs), which boycott CD8⁺ T-cell duties in tumor recognition and clearance. Interestingly, preclinical data have highlighted the importance of this immune evasion as the source of resistance to single checkpoint immunotherapies and cancer vaccines and point at pathways inhibiting the immune attack as the key to solve the therapy puzzle. Here, we will discuss the molecular mechanisms involved in PDA immune escape as well as the state of the art of the PDA immunotherapy.

Abstract On the background of new research results in screening of breast cancer, together with the expectation of the participants in a screening for breast cancer, the conventional mammography requires supplementation by means of tomosynthesis or additive ultrasound. Alternatively, ultrasound now seems to be an independent method of early detection of breast cancer because of its superior sensitivity, especially in the case of aggressive mammary carcinoma types. The MRI remains at present still a preferred method in high-risk cases and as an additive examination in case of insufficient presentation of the glandular tissue by conventional methods. MRI is also preoperatively valuable for more accurately measuring the extent of multifocal carcinomas.

Zucchini (Cucurbita pepo subsp. pepo) is a seasonal vegetable with high nutritional and medical value. Many useful properties of this fruit are attributed to its bioactive compounds. Zucchini fruits (“Yellow” and “Light Green” varieties) and four distinctive components (lutein, β-carotene, zeaxanthin and dehydroascorbic acid)were selected. Firstly it was determinated the lutein, β-carotene, zeaxanthin and dehydroascorbic acid content in these fruits and then, in order to measure the safety and suitability of their use different assays were carried out: (i) Genotoxicity and antigenotoxicity tests to determine the safety and DNA-protection against hydrogen peroxide; (ii) cytotoxicity and (iii) DNA fragmentation assay to evaluate the proapoptotic effect. Results showed that: (i) all the substances were non-genotoxic, (ii) all the substances were antigenotoxic except the highest concentration of lutein, (iii) “Yellow” Zucchini epicarp and mesocarp exhibited the highest cytotoxic activity (IC₅₀ > 0.1 mg/mL and 0.2 mg/mL, respectively) and iv) “Light Green” Zucchini skin and pulp induced internucleosomal DNA fragmentation . To sump up, Zucchini fruit could play a positive role in human health and nutrition due to this fruit and its components were safe, able to inhibit significantly the H₂O₂-induced damage and exhibit antiproliferative and pro-apoptotic properties toward HL60 tumour cells. The information generated from this research should take into account to select potential accessions for breeding programs purposes.

The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC₅₀) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of kappa-light-chain-enhancer of activated B cells (NF-кB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-кB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-кB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-кB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-кB crosstalk.

Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3 percent of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls. Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day). Our study showed dietary folate intake was modestly but significantly inversely associated with pancreatic cancer (OR=0.99, P <.0001). The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.

Although mammography has been the gold standard for early detection of breast cancer, if a woman has dense breast tissue, a false negative diagnosis may occur. Breast ultrasound, whether hand-held or automated, is a useful adjunct to mammography but adds extra time and cost. The primary aim was to demonstrate that our second-generation Aceso system, which combines full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in a single platform, is able to produce improved quality images that provide clinically meaningful results. Aceso was first tested using two industry standards: a CDMAM phantom to assess the FFDM images; and the CIRS 054GS phantom to evaluate the ABUS images. In addition, 25 women participated in a clinical trial: 14 were healthy volunteers while 11 were patients referred by the breast clinic at Groote Schuur Hospital. The CDMAM phantom results showed the FFDM results were better than EUREF’s standard of “acceptable” and were approaching “achievable”. The ABUS results showed lateral and axial spatial resolution of 0.5 mm and adequate depth penetration of 80 mm. Our second-generation Aceso system, with its improved quality of clinical FFDM and ABUS images, has demonstrated its potential for early detection of breast cancer in a busy clinic.

Tumor microenvironment including cancer-associated fibroblasts (CAF) has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell – tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles. There is evidence that miRs have very similar roles in activating hepatic (HSC) and pancreatic stellate cells (PSC) as part of precancerous fibrotic diseases. In summary, deregulated miRs affect various intracellular functional complexes, such as transcriptional factors, extracellular matrix, cytoskeleton, EMT/MET regulation, soluble factors, tyrosine kinase and G-protein signaling, apoptosis and cell cycle & differentiation, but also formation and composition of the extracellular microenvironment. These processes result in the clinical appearance of desmoplasia involving CAFs and fibrosis characterized by deregulated stellate cells. In addition, modulated release of soluble factors can act as (auto)activating feedback loop for transition of NFs into their pathological counterparts. Furthermore, epigenetic communication between CAFs and cancer cells may confer to cancer specific functional readouts and transition of NF into their pathological counterparts. MiR related epigenetic regulation with many similarities should be considered as key factor in development of cancer and fibrosis specific environment.

Cervical Cancer affects a large part of female population that makes the prediction of this disease based on Machine Learning (ML) by outmost importance. ML algorithms can be integrated in complex intelligent agent-based systems that can offer decision support to the resident medical doctors or even to experienced medical doctors. For instance can be mentioned the situation when an experienced medical doctor diagnose a case but he/she needs expertise support that is related to another medical specialty. Data imbalance is frequent in healthcare data and has a negative influencing effect in making predictions using ML algorithms. Cancer data generally and cervical cancer data particularly are frequently imbalanced. Based on this fact the study of data imbalance impact on diverse state-of-the-art ML prediction algorithms is important. This research subject is also motivated by the fact that in many research are presented experimental evaluations of algorithms without characterization of the data on that they have been applied. Such characterizations could give clear indication to other researchers regarding the applicability of the algorithms on their specific data. Specifically, if the data have the respective characteristics than are expectable the same performance evaluation results like those in the reported research. For the study we chosed a messy real-life Cervical Cancer dataset available in a recognized data repository included a large amount of missing and noisy values. To identify the best imbalanced technique for this medical dataset, it is compared the performance of eleven important resampling methods combined with the following state-of-the-art ML models: K-Nearest Neighbours (with k values of 2 and 3), binary Logistic Regression, and Random Forest, that are frequently applied in prediction types of researches in healthcare. The studied resampling methods includes seven undersampling methods namely Condensed Nearest Neighbour, Tomek Links, Edited Nearest Neighbours, Repeated Edited Nearest Neighbours, All K-Nearest Neighbours, NearMiss, Neighbourhood Cleaning Rule, and Instance Hardness Threshold, and four oversampling methods namely Synthetic Minority Oversampling Technique (SMOTE), Adaptive Synthetic Sampling Approach for Imbalanced Learning SMOTE, Support Vector Machine SMOTE and Borderline SMOTE. In the case of the dataset for the confidence interval with 95% confidence level was between 9.23 and 16.22, while the imbalance ratio is 12.73. The obtained results show that resampling methods help the learning models to improve the classification ability of cervical cancer. The applied oversampling techniques generally showed better results than undersampling methods. In the case of Logistic Regression classifier had the highest impact on balanced techniques, while Random Forest had promising performance, even before balancing techniques and KNN2 was generally better than KNN3.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we will discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of proliferation and carcinogenesis evolution. FZD proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in carcinogenesis of gastroenteric tract. Here, a still unrecognized role of Frizzled 10 (FZD10) protein was identified. In particular, the presence of FZD10 and FZD10-mRNA in exosomes extracted from culture medium of the untreated colorectal, gastric, hepatic and cholangio cancer cell lines, was detected. A substantial reduction in the FZD10 and FZD10-mRNA level was achieved in FZD10-mRNA silenced cells and in their corresponding exosomes and, concomitantly a significant decrease in viability of the silenced cells compared to their respective controls was observed. Interestingly, the incubation of silenced cells with exosomes extracted from culture medium of the same untreated cells promoted a remarkable restoration of the cell viability and, also, of the FZD10 and FZD10-mRNA level, thus indicating that the FZD10 and FZD10-mRNA delivering exosomes may be potential messengers of cancer reactivation and play an active role in long-distance metastatization

The shift towards Personalized Cancer Medicine (PCM) represents a significant transformation in cancer care, emphasizing tailored treatments based on genetic understanding of cancer at the cellular level. This review draws on recent literature to explore key factors influencing PCM implementation, highlighting the role of innovative leadership, interdisciplinary collaboration, and coordinated funding and regulatory strategies. Success in PCM relies on overcoming challenges such as integrating diverse medical disciplines, securing sustainable investment for shared infrastructures, and navigating complex regulatory landscapes. Effective leadership is crucial for fostering a culture of innovation and teamwork, essential for translating complex biological insights into personalized treatment strategies. The transition to PCM necessitates not only organizational adaptation but also the development of new professional roles and training programs, underscoring the need for a multidisciplinary approach and the importance of team science in overcoming the limitations of traditional medical paradigms. The conclusion underscores that PCM's success hinges on creating collaborative environments that support innovation, adaptability, and shared vision among all stakeholders involved in cancer care.

Background: Although endoscopic submucosal dissection (ESD) can provide a high rate of curative resection, remaining gastric mucosa after ESD is at risk of metachronous recurrence. We investigated risk factors for metachronous superficial gastric epithelial neoplasms (MSGENs) following ESD. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. The primary endpoint was to identify clinicopathological risk factors for the occurrence of MSGENs. The secondary endpoint was to evaluate the association of Helicobacter pylori (Hp) eradication with the MSGENs. Results: Twenty-seven MSGENs were occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in upper or middle part (INUM) in the MSGEN group. The HIM group and INUM group had significantly higher cumulative incidence of MSGENs. We compared the 27 patients of MSGEN group and 27 patients of matched not-MSGEN (Mnot-MSGEN) group that was matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of Hp spontaneous eradication in the MSGEN group. Conclusion: HIM, INUM and Hp spontaneous eradication may be clinicopathological risk factors for developing MSGENs after ESD.

The study of the optical properties of biological tissues for a wide spectral range is necessary for the development and planning of noninvasive optical methods to be used in clinical practice. In this study, we propose a new method to calculate almost all optical properties of tissues as a function of wavelength directly from spectral measurements. Using this method and with the exception of the reduced scattering coefficient, which was obtained by traditional simulation methods, all the other optical properties were calculated in a simple and fast manner for human and pathological colorectal tissues. The obtained results are in good agreement with previous published data, both in magnitude and in wavelength dependence. Since this method is based on spectral measurements and not on discrete-wavelength experimental data, the calculated optical properties contain spectral signatures that correspond to major tissue chromophores such as DNA and hemoglobin. Analysis of the absorption bands of hemoglobin in the wavelength dependence of the absorption spectra of normal and pathological colorectal mucosa allowed to identify differentiated accumulation of a pigment in these tissues. The increased content of this pigment in the pathological mucosa may be used for the future development of noninvasive diagnostic methods for colorectal cancer detection.

Breast cancer is the most common cause of death for women worldwide. Thus, the ability of artificial intelligence systems to predict and classify breast cancer is very important. In this paper, a hybrid ensemble method classification mechanism is proposed based on a majority voting mechanism. First, the performance of different state-of-the-art machine learning classification algorithms for the Wisconsin Breast Cancer Dataset (WBCD) were evaluated. The three best classifiers were then selected based on their F3 score. F3 score is used to emphasize the importance of false negatives (recall) in breast cancer classification. Then, these three classifiers, simple logistic Regression learning, stochastic gradient descent learning and multilayer perceptron network, are used for ensemble classification using a voting mechanism. We also evaluated the performance of hard and soft voting mechanism. For hard voting, majority-based voting mechanism was used and for soft voting we used average of probabilities, product of probabilities, maximum of probabilities and minimum of probabilities-based voting methods. The hard voting (majority-based voting) mechanism shows better performance with 99.42% as compared to the state-of-the-art algorithm for WBCD.

Background: During normal development, epithelial cells can experience alterations at transcriptional and morphological levels, which can trigger a process named the epithelial-mesenchymal transition (EMT). The EMT underpins changes in cytoskeleton dynamics that are characteristic of neoplastic transformation. Described in many tumors, including colorectal cancer (CRC), over the past ten years, although it is an essential process in cancer development it is still poorly understood. Once initiated, the EMT regulates metastasis, the microenvironment and immune system resistance in CRC. Overexpression of the pro-inflammatory molecule inorganic polyphosphate (iPolyP) has been shown to play important role in CRC progression, alongside its binding receptor called transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8). In this study we tested whether iPolyP/TRPM8 axis regulates EMT changes as well as NLRP3 inflammasome activation within the tumor microenvironment (TME) of CRC. Methods: To investigate these issues, western blotting, fixed and live cells immunofluorescence, 2D and 3D cell culture on CRC-patient derived biopsies, ELISA and wound healing assays were performed. Results: iPolyP triggers the expression of several EMT markers in CRC cell lines compared to control. Pharmacological inhibition of TRPM8 receptor restricts the migratory effects of cancer cells due to the presence of iPolyP. Moreover, the iPolyP/TRPM8 axis also displays an indirect pro-tumorigenic performance through shaping the immune microenvironment. By triggering NLRP3 inflammasome activation, iPolyP ensures high levels of the pro-inflammatory cytokine IL-1, which foster CRC carcinogenesis. Conclusion: This study suggests that the iPolyP/TRPM8 signaling axis is a promising target for impeding CRC progression and spread.

Background: The early identification of patients at risk of peri-procedural complications and poor prognosis is very important. We conducted our study to determine if there are associations between serum orexigenic neuropeptide Y (NPY) concentration and nutritional status, and prognosis among patients undergoing surgery for colorectal cancer (CRC). Materials and Methods: A cohort study with a 3-month follow-up was conducted with 84 consecutive inpatients who underwent elective surgery in one center between 2016 and 2019 for primary CRC. In all patients, clinical characteristics and nutritional status were assessed. In a long-term follow-up (median; IQR: 1322; 930-1788 days; average 3.6 years), the patients’ survival status was checked during a telephone visit. Results: Before CRC surgery, patients with serum NPY concentration equal to or higher than the median value (661.70 pg/ml) had, in comparison to individuals with lower blood NPY concentration, higher scores in Mini Nutritional Assessment, Barthel, and Instrumental Activities of Daily Living (IADL) questionnaires, greater handgrip strength, a lower score in the Patient-Generated Subjective Global Assessment, almost a three times lower risk of perioperative complications, as well as, at the 3-month follow-up visit, higher Barthel and IADL scores and larger calf circumference. Higher blood NPY concentration was predictive of a low Nutritional Risk Screening 2002 score at the 3-month visit, and significantly influenced patients’ survival during the 1200 days after CRC surgery. Conclusions: Higher blood NPY concentration was associated with lower nutritional risk, more favorable patient nutritional and functional status, and better survival during the 1200 days after CRC surgery.

Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves extracts contain high amounts of flavonoids and terpenoids, endowed with potential antioxidant, anti-inflammatory, anticancer, antidiabetic and antimicrobial effects. Re-cently, many in vitro and in vivo studies have assessed different potential health benefits of per-simmon leaves; however, its anticancer activity towards colorectal cancer (CRC), the second deadliest cancer in Western countries, has not been investigated in depth. Since CRC current therapies are associated with serious side effects and show no efficacy towards patients carrying RAS/BRAF mutations, the search for new and more effective therapies has turned to plant extracts, which could help reduce conventional drugs dosages and toxicity. The effect of Diospyros kaki al-coholic extract has been investigated on E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS activating mutation. This extract is effective in reducing tumor cells viability, without affecting the healthy mucosa cell line CCD 841, and it triggers apoptosis in CRC cells, by disrupting mitochondrial functionality and increasing oxidative stress.

Fusobacterium nucleatum (F. nucleatum, Fn), an oral commensal that can become pathogenic, is associated with periodontitis (PD), adverse pregnancy outcomes, and colorectal cancer (CRC). MicroRNAs (miRNAs) are conserved, non-coding RNAs that play a regulatory role in gene expression and are detected in microbial infections. The aim of this study was to characterize the global microRNA expression kinetics in the mandibles of C57BL/6J mice infected with F. nucleatum for 8 and 16 weeks, and to identify miRNAs as biomarkers of the PD process using high-throughput NanoString nCounter® miRNA panels. Mice were divided into four groups: 8 weeks of Fn infection, 16 weeks of Fn infection, and their respective sham infection. Fn-infected mice at both 8- and 16 weeks showed 100% bacterial colonization on the gingival surface, along with a significant increase in alveolar bone resorption (p<0.0001) and intravascular dissemination to heart, indicating its invasive potential. Out of 577 miRNAs analyzed, seven miRNAs (miR-361-5p, miR-99b-5p) were upregulated, and two miRNAs (miR-362-3p and miR-720) were downregulated in the 8-week Fn infection group. In the 16-week Fn infection group, seven miRNAs (miR-361-5p, miR-99b-5p) were upregulated miRNAs and 13 miRNAs (miR-323-3p, miR-488) were downregulated. Notably, miRNAs such as miR-205, miR-210, miR-199a-3p which were differentially expressed (DE) in the Fn-infected mice at 8 weeks and miR-28 at 16 weeks, have been previously reported in human periodontitis. The 13 miRNAs induced by F. nucleatum (miR-361-5p) are linked to multiple malignancies, including esophageal, gastric, pancreatic, and colorectal cancers. Additionally, the DE miR-126-5p in the 8-week infection group has been identified as a potential biomarker for patients with PD and cardiovascular disease. The results indicate that F. nucleatum acts as a potent oncomicrobe, inducing several miRNAs associated with PD and linking it to systemic comorbidities. Furthermore, the study revealed similar expressions between PD-associated miRNAs and nine CRC tumor-expressed miRNAs.

Mismatch repair (MMR) deficiency can be indicative of Lynch syndrome (LS) and guide treatment with immune checkpoint inhibitors. Colorectal cancers (CRCs) and endometrial cancers (ECs) are routinely screened to identify LS, primarily using immunohistochemistry (IHC) or Microsatellite Instability (MSI) testing, but concordance between methods is variable in ECs. Here, we investigate this variability by using the amplicon sequencing based Newcastle MSI assay (NCL_MSI) to re-analyse 361 ECs from the Ohio OCCPI/OPTEC (n=196) and Manchester PETALS (n=165) trials. NCL_MSI was consistent with Ohio results (94% and 97% concordance with IHC and original MSI assays respectively), and increased concordance in the Manchester cohort from 78% to 86% (MSI) and 84% (IHC). Among discordant Manchester samples, NCL_MSI was significantly associated with MLH1 promoter methylation status (p=0.0028), and had the highest concordance with methylation, 62/69 samples (90%), indicating utility as a screening tool in this tumour type. However, tumours with germline MSH6 defects were only detected efficiently with IHC; 7/8 LS tumours classified as MSS by either MSI assay had isolated MSH6 loss, compared to 4/12 classified as MSI-H by both (p=0.028). Furthermore, reduced MSI signal was observed in tumours with isolated MSH6 loss (p=0.009 Ohio, p=6.2x10-5 Manchester), and in both ECs and CRCs with germline defects although this only reached significance in CRCs (p=0.002). These results provide further evidence that ECs with MSH6 loss in particular, and LS tumours in general, have an attenuated MSI signal, and supports current guidelines specifically recommending IHC for LS detection and immune checkpoint therapy assessment in EC.

The incidence of non-palpable breast cancer is increasing due to widespread screening and neoadjuvant therapies. Among the available tumor localization techniques, radio-guided occult lesion localization (ROLL) has largely replaced wire-guided localization (WGL). This study aimed to compare ROLL and WGL techniques in terms of the effectiveness of isotopic marking of axillary sentinel lymph nodes and to assess patient perspectives along with surgeon and radiologist preferences. A single-center, prospective randomized study enrolled 110 patients with non-palpable breast lesions (56 ROLL, 54 WGL). Breast type, tumor volume, location, histological and radiological features, and localization/surgical duration were evaluated in the context of sentinel lymph node marking using isotope (Technetium-99m labelled human serum albumin) and blue dye. Statistical analysis was performed with significance set at p&lt;0.05 and strong significance at p&lt;0.01. Both techniques were successful in localizing non-palpable lesions (100%). However, patients reported WGL as more painful. A notable difference was observed in axillary lymph node marking, with subareolar isotope injection (used in WGL) showing better results compared to ROLL. While ROLL provided advantages in terms of patient comfort, and logistical simplicity, WGL was superior for axillary sentinel lymph node marking, particularly in inner quadrant tumors, suggesting WGL may be preferred for these cases.

Hyperhomocysteinemia (HHcy) is a medical condition characterized by an abnormally high level of homocysteine (Hcy) in the blood. Homocysteine is a toxic sulfur-containing amino acid that is produced during the metabolism of methionine. Under normal circumstances, Hcy is recycled back to methionine via the remethylation pathway, through the action of various enzymes and vitamins, particularly folic acid (vitamin B9) and B12 used when intracellular methionine levels are low, thus restoring the necessary levels to correctly maintain active protein synthesis. A second pathway, used in cases of intracellular methionine excess, (the trans-sulfuration pathway) is the one that recicles Hcy into cysteine (a precursor of glutathione), first passing through cystathionine (via the enzyme cystathionine beta-synthase), a reaction that requires vitamin B6 in its active form. HHcy has been identified as a risk factor for a variety of disorders, including cardiovascular diseases, multiple sclerosis, diabetes, Alzheimer's and Parkinson's diseases, osteoporosis and cancer. However, it remains unclear whether the slightly elevated concentration of Hcy (Hcy 7-10 μmol/L) is a causative factor or simply a marker of these pathologies. In human plasma, the concentration of Hcy ([Hcy]) is classified in mild (15 to 30 μmol/L), moderate (30 to 100 μmol/L), and severe (greater than 100 μmol/L). Interestingly, many laboratories continue to consider 25 μmol/L as normal. This review seeks to examine the controversial literature regarding the normal range of HHcy and emphasizes that even a [Hcy] level of 10 μmol/L may contribute to the development of several diseases, aiming to discuss whether it would be appropriate to lower the threshold of HHcy normal values.

Objectives: To assess the role of soluble PD-L1 and PD-1 in combination with mRNA transcripts of PCA3, PSMA, AR genes in diagnostics of clinically significant prostate cancer (PCa). Methods: For 68 PCa patients, plasma sPD-L1 and sPD-1 were measured by ELISA method and the urinary PSMA, PCA3 and AR were tested using RT-qPCR. Results: PSMA and AR were iden-tified as the most reliable biomarkers for predicting clinically significant prostate cancer, with AUCs of 0.81 and 0.78, respectively. Additionally, the expression levels of PSMA and PCA3 were associated with the pT3 stage. Despite the diagnostic potential of mRNA transcripts alone, the ad-dition of sPD-L1 and sPD-1 significantly enhanced diagnostic accuracy. Combination doubled the specificity of PCA3 from 44.1% to 88.0%, compared to PCA3 alone. sPD-L1, sPD-1 and AR resulted in the best distinction between clinically significant and insignificant prostate cancer, achieving an AUC of 0.97, an accuracy of 0.95, a sensitivity of 100%, a specificity of 95%, revealing the potential of AR in distinguishing clinically significant PCa, more effectively than PSMA and PCA3. Our find-ings highlight the significant potential of sPD-1 in enhancing diagnostic accuracy when added to a triple gene panel, achieving an AUC of 0.90 compared to an AUC of 0.78 without sPD-1. This un-derscores the value of sPD-1, which has been less explored than sPD-L1 in cancer diagnostics. Con-clusions: sPD-L1 and sPD-1 has a potential to significantly enhance the accuracy of PCa diagnostics when added to the diagnostic panel, alongside PSMA, PCA3, and AR mRNA transcripts.

Aim: The aim in this study was to conduct a prospective survey regarding the socio-demographics and lifestyle risk factors for cancer of a population of Caribbean immigrants living in the U.S. Materials and Methods: The data were processed and analysed using SPSS software 27 and Excel. Crosstabulations were performed. The chi-square test was used to evaluate differ-ent hypotheses. Statistical significance was defined as p < 0.05. Results: Statistically significant differences in the country of birth of the Caribbean immigrants were found for sex (p = 0.038) and the cleanness of their neighbourhoods (p = 0.045). We found differences in occupations between men and women (p = 0.001). Men were less unemployed than women (p = 0.011). Sex also showed statistically significant differences in how easily the immigrants balanced their work and per-sonal life (p = 0.044). Age groups depicted differences in the physical health of the immigrants (p = 0.001). The use of alcohol and tobacco was not an important risk factor among participants (p = 0.529). Conclusions: These findings suggest that the sociodemographics risk factors for cancer among a population of Caribbean immigrants were significantly different between the sexes. However, the use of tobacco and alcohol showed insignificant differences among the immigrants.

Despite the role of metabolism in breast cancer metastasis, we still cannot predict which breast tumors will progress to distal metastatic lesions or remain dormant. This work uses metabolic imaging to study breast cancer cell lines (4T1, 4T07, and 67NR) with differing metastatic potential in a 3D collagen gel bioreactor system. Within the bioreactor, hyperpolarized magnetic resonance spectroscopy (HP-MRS) is used to image lactate/pyruvate ratios, while fluorescence lifetime imaging microscopy (FLIM) of endogenous metabolites measures metabolism at the cellular scale. HP-MRS results showed no lactate peak for 67NR and a comparatively large lactate/pyruvate ratio for both 4T1 and 4T07 cell lines, suggestive of greater pyruvate utilization with greater metastatic potential. Similar patterns were observed using FLIM with significant increases in FAD intensity, redox ratio, and NAD(P)H lifetime. The lactate/pyruvate ratio was strongly correlated to NAD(P)H lifetime, consistent with the role of NADH as an electron donor for the glycolytic pathway, suggestive of an overall upregulation of metabolism (both glycolytic and oxidative), for the 4T07 and 4T1 cell lines compared to the non-metastatic 67NR cell line. These findings support a complementary role for HP-MRS and FLIM enabled by a novel collagen gel bioreactor system to investigate metastatic potential and cancer metabolism.

Polymeric nanoparticles (NPs) have garnered significant interest due to their potential in drug delivery. Specifically, nanopolymers functionalized with molecules such as proteins or peptides serve as versatile vehicles for this purpose. Curcumin (Cur) is a widely studied anticancer compound known for its positive effects on human health. Nevertheless, its insolubility and low bio-distribution hinder the exploitation of its beneficial traits. In this study, our team developed a nanodelivery system using a nanopolymer called poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG), functionalized with A6 peptide to enable targeted delivery of Cur. The designed system exhibited favorable characteristics, including a stable zeta potential of -13.8 mV, a small size of 76.4 nm, uniform surface morphology, and high hydrophilicity with a contact angle of 31.53°. Additionally, the targeted delivery system demonstrated high encapsulation efficiency (EE%) (93 ± 0.89%), drug loading (DL%) (16.7 ± 0.9%), and a slow and gradual release profile with a release of approximately 83.1 ± 0.12%. The MTT assay results showed significant cell death in MDA-MB-231 cancer cells (IC₅₀ = 21.3 ± 1.57 µM) when treated with the Cur-NPs-A6 formulation, while the toxicity of the designed NPs was reduced on non-cancerous MCF-10A cells. Moreover, both the RT-qPCR and invasion assays demonstrated the system's effectiveness in activating apoptosis pathways and inhibiting cell invasion. These findings suggest that the engineered intelligent delivery system, equipped with the A6 peptide, which has a strong affinity for CD44 (a protein with increased expression in malignancy), could be an exceptionally effective strategy for cancer treatment.

Radiotherapy remains a cornerstone in cancer treatment, leveraging ionizing radiation to eradicate malignant cells. Its efficacy, however, is frequently challenged by the heterogeneous sensitivity of tumors and surrounding tissues to radiation. Therefore, understanding the molecular mechanisms underlying radiosensitivity is crucial for improving treatment outcomes. Among the myriad of molecular players involved, the tumor suppressor protein p53 stands out as a central regulator with significant implications for radiosensitivity. Known as the “guardian of the genome,” p53 plays a pivotal role in maintaining genomic stability and orchestrating cellular responses such as cell cycle arrest, DNA repair, apoptosis, and senescence in response to various stress signals, including radiation-induced DNA damage. Activation of p53 triggers the transcription of target genes involved in DNA repair pathways, such as p21, MDM2, and GADD45, facilitating the repair of radiation-induced DNA damage or the elimination of irreparably damaged cells. This, in turn, influences the overall radiosensitivity of tissues. Mutations in the TP53 gene, which encodes p53, are among the most frequent genetic alterations in human cancers. Loss or dysfunction of p53 can compromise the cellular response to radiation, leading to increased resistance to therapy and poorer clinical outcomes. Conversely, intact p53 function is associated with enhanced radiosensitivity due to its ability to promote cell cycle arrest and apoptosis in response to radiation-induced DNA damage. In conclusion, elucidating the molecular mechanisms by which p53 influences radiosensitivity is essential for advancing our understanding of radiation response in cancer cells and developing more effective therapeutic approaches in cancer treatment. This review provides a comprehensive overview of the multifaceted role of p53 in modulating cellular responses to radiation, emphasizing its influence on radiosensitivity.

Objective: To investigate the causal relationships between intestinal microbiome biomarkers and colorectal cancer (CRC) and its subtypes. Method: The meta-analysis method was used to integrate the largest genome-wide association study data from the MiBioGen consortium (n=18,340). Single nucleotide polymorphisms (SNPs) significantly associated with intestinal microbial relative abundance were extracted as instrumental variables (IVs). Based on the Finnish database (R9 version) with 326,322 participants, the two-sample Mendelian randomization (MR) analysis was adopted to explore the causal relationships between intestinal microbes and CRC and its specific subtypes, such as colon cancer and rectal cancer. Result: A total of 3,310 SNPs were screened as IVs. The MR analysis revealed significant associations between various microbial traits and CRC, including its subtypes. Specific microbes, such as Erysipelotrichaceae, exhibited protective effects, while others, like Orato, were demonstrated as risk factors. Notably, specific biomarkers (e.g., Streptococcus thermophilus) for CRC were determined. This study provides new insights and potential targets for the pathogenesis, diagnosis, and treatment of CRC. Conclusion: Significant causal relationships exist between intestinal microbes and CRC and its pathological types. Specific microbes, such as Erysipelotrichaceae, play a protective role, whereas others, like Orato, serve as risk factors. These findings offer new insights into the pathogenesis of CRC and provide a foundation for future prevention and treatment strategies.

It is known that Radon gas within the air could reach lung cells and cause cancer. We suggest a technique to absorb alpha particles radiated by Radon decay near DNAs within human cells. In this technique, we create some non-paired negative electrons on graphene sheets and build some negative graphene tubes. Alpha particles are attracted and negative beta particles are repelled by the graphene tubes.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research highlights the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between microbiome and esophageal carcinogenesis, focusing on eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.

Men of African ancestry suffer disproportionately from prostate cancer (PCa) than other racial groups in South Africa. Equally concerning is that black South African men generally present later with higher stage and grade of the disease than their non-black counterparts. Despite this, South African black men continue to have little uptake in PCa screening behaviors. The objective of the study was to explore knowledge and beliefs of PCa among black South African survivors. A sample of 20 prostate cancer survivors, with ages ranging from 67 to 85 years (meanage = 76yrs; SD = 5.3) were selected through purposive sampling and requested to participate in the study. Data were collected through in-depth, semi-structured individual interviews, and analysed using interpretative phenomenological analysis (IPA). The findings demonstrated that black South African men had poor knowledge of PCa and that this may create an unfortunate system that preclude this population group from taking part in life-saving PCa screening services. The results highlight a need to elevate knowledge and awareness of PCa among black South African men and ultimately enhance screening practices.

Recent advances in organoid technology have revolutionized cancer biology and thera-peutic interventions, offering personalized immunotherapy treatment. Organoids, three-dimensional cell cultures derived from patient tumors, accurately replicate the tumor microenvi-ronment, providing unprecedented insights into tumor-immune interactions and therapeutic re-sponses. In this literature-based study, we discuss various culture methods for the diverse appli-cations of organoids in cancer immunotherapy, including drug screening, personalized treatment strategies, and mechanistic studies. Additionally, we address the technological challenges asso-ciated with these methods and propose potential future solutions to accelerate the development of novel immunotherapeutic approaches. This review highlights the transformative potential of or-ganoid models in advancing preclinical cancer immunotherapy modeling, screening, and evalua-tion, paving the way for more effective and personalized cancer treatments.

Timely screening for breast cancer plays a pivotal role in early detection and treatment; however, Afghan refugee females face significant barriers that hinder their access to these life-saving screening services. Cultural norms, socioeconomic factors, proficiency with the English language, and the challenges of navigating foreign healthcare systems contribute to low screening rates within this population. The current review article seeks to identify barriers to breast cancer screening in the Afghan refugee population in the United States (US) and address possible measures to overcome these challenges.

The interplay between the human gut microbiota and the peripheral immune system significantly affects the efficacy of immune checkpoint inhibitors (ICIs) in cancer therapy. Despite this profound connection, the practical implications of microbiota dysbiosis in cancer immunotherapy ICIs & and CAR-T remain intricate and poorly understood in practical terms. This paper offers a comprehensive review of current literature on the role of gut microbiota dysbiosis in tumor development, and emerging microbiota modulation interventions, with a focus on fecal microbiota transplantation (FMT). FMT is a cost-effective therapeutic avenue, particularly in addressing diseases rooted in antibiotic-resistant bacteria, such as Clostridium difficile. Here we provided insights into the applications of FMT and other gut microbiota therapies in the landscape of cancer treatment, emphasizing their influence on the tumor microenvironment and the efficacy of ICIs with suggestions for future research directions and their implications for clinical practice.

Epigenetic changes regulate gene expression through histone modifications, chromatin remod-eling and proteins interpreter of these modifications. The PRC1 and PRC2 complexes shape gene repression via histone modifications. Specifically, the CBX protein family aids PRC1 recruitment to chromatin, impacting the progressive multistep process driving chromatin silencing. Among family members, CBX3 is a complex protein involved in aberrant epigenetic mechanisms that drive lung cancer progression. CBX3 promotes lung tumorigenesis by interacting with key pathways such as PI3K/AKT, Ras/KRAS, Wnt/β-catenin, MAPK, Notch, and p53, leading to in-creased proliferation, inhibition of apoptosis, and enhanced resistance to therapy. Given our current lack of knowledge, additional research is required to uncover the intricate mechanisms underlying CBX3 activity, as well as its involvement in molecular pathways and its potential biomarker evaluation. Specifically, the dissimilar roles of CBX3 could be reexamined in order to gain a greater insight into lung cancer pathogenesis. This review aims to provide a clear overview of the context-related molecular profile of CBX3, which could be useful for addressing clinical challenges and developing novel targeted therapies based on personalized medicine.

In genomics analysis, with the development of sequencing technology and the rapid growth of data volume, how to effectively identify and analyze important information in genomic data from massive data has become an important challenge. Identify key patterns and features in genomic data through advanced community testing methods. First, genomic data often contains a lot of noise and redundant information that needs to be processed through steps such as normalization, filtering, and dimensionality reduction. Normalization makes data at different scales comparable, filtering out data points with low quality or missing values, and dimensionality reduction reduces data dimensions through principal component analysis (PCA) and retains the main information. The gene co-expression network establishes the connection relationship between genes by calculating the expression similarity matrix between genes, and applies the Louvain algorithm to maximize the modularity of the network, aggregate nodes layer by layer, form a community structure, and identify the complex relationship and potential structure between genes. Finally, we utilize the cancer dataset to evaluate the proposed model. From our extensive experimental results, we can observe that Louvain's algorithm indicates outperformances and accuracy in the recognition and analysis of genomic data.

Background: Colorectal cancer (CRC) can significantly impact mental health, increasing suicide risk. Variables such as pain and threat perception may be crucial. This study aims to identify predictors of suicide risk in individuals with CRC. Methods: A total of 71 participants (76.06% men) aged 27 to 88 years (M = 65.18, SD = 12.02) were assessed using the SF-36 for pain, the Brief Illness Perception Questionnaire (B-IPQ) for threat perception, the Hospital Anxiety and Depression Scale (HADS) for emotional distress, and the Plutchik suicide risk scale for suicide risk. Descriptive, comparative, and correlational analyses were performed, followed by a linear regression analysis. Results: Nearly 20% of participants exhibited high suicide risk. There was a moderate to high association between suicide risk and the perception of threat, pain, and emotional distress. The linear regression model explained 39% of the variance in suicide risk, with threat perception, pain, and emotional distress as significant predictors. Conclusions: These results indicate the need for multidisciplinary care for individuals with CRC, including emotional support from health psychologists, and holistic, human-centered care from nursing and medical professionals. Future research is necessary to further explore these relationships and improve patient care strategies.

Genome-wide association studies (GWAS) have accelerated the exploration of genotype-phenotype associations, facilitating the discovery of replicable genetic markers associated with specific traits or complex diseases. This narrative review explores the statistical methodologies developed using GWAS data to investigate relationships between various phenotypes, focusing on endometrial cancer, the most prevalent gynecological malignancy in developed nations. Advancements in analytical techniques such as genetic correlation, colocalization, cross-trait locus identification, and causal inference analyses have enabled deeper exploration of associations between different phenotypes, enhancing statistical power to uncover novel genetic risk regions. These analyses have unveiled shared genetic associations between endometrial cancer and many phenotypes, enabling identification of novel endometrial cancer risk loci and furthering our understanding of risk factors and biological processes underlying this disease. The current status of research in endometrial cancer is robust; however, this review demonstrates that further opportunities exist in statistical genetic that hold promise for advancing the understanding of endometrial cancer and other complex diseases.

ABSTRACT: Background: Virtual Reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR's effectiveness on cancer-related symptoms, vital signs, and patients' perception of the chemotherapy in lung cancer patients. Methods: A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results: VR had a significant impact on reducing the perception of the chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity and vital signs. The only exceptions were oxygen saturation, where a significant difference (p = 0.02) was reported, and perception of chemotherapy duration. Conclusions: As a non-pharmacological intervention, VR proves beneficial in minimizing the perceived length of chemotherapy session for lung cancer patients, enhancing their overall treatment experience. The intervention showed to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR's potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes.

Abstract Introduction PCa is one of the cancers that exhibits the widest disparity gaps. Geographical place of residence has been shown to be associated with healthcare access/utilization and PCa outcomes. Geographical Information Systems (GIS) are widely being utilized for PCa disparities research, however, inconsistencies in their application exist. This systematic review will summarize GIS application within PCa disparities research, highlight gaps in the literature and propose alternative approaches. Methods This paper followed the methods of the Cochrane Collaboration and the criteria set of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles published in peer-reviewed journals were searched through the PubMed, Embase, and Web of Science databases till December 2022. The main inclusion criteria were employing a GIS approach and examining a relationship between geographical components and PCa disparities. The main exclusion criteria were studies conducted outside the US and those that were not published in English. Results A total of 25 articles were included, 23 focused on PCa measures as outcomes: incidence, survival, and mortality while only two examined PCa management. GIS application in PCa disparities research was grouped into three main categories: mapping, processing, and analysis. GIS mapping allowed for the visualization of quantitative, qualitative, and temporal trends of PCa factors. GIS processing was mainly used for geocoding and smoothing of PCa rates. GIS analysis mainly served to evaluate global spatial autocorrelation and distribution of PCa cases, while local cluster identification techniques were mainly employed to identify locations with poorer PCa outcomes, soliciting public health interventions. Discussion Varied GIS applications and methodologies have been used in researching PCa disparities. Multiple geographical scales were adopted leading to variation in associations and outcomes. Geocoding quality varied considerably leading to less robust findings. Limitations in cluster-detection approaches were identified especially when variations were captured using the Spatial Scan Statistic. GIS approaches utilized in other diseases might be applied within PCa disparities research for more accurate inferences. A novel approach for GIS research in PCa disparities could be focusing more on geospatial disparities in procedure utilization especially when it comes to PCa screening techniques. Conclusion This systematic review summarized and described the current state and trend of GIS application in PCa disparities research. Although GIS is of crucial importance when it comes to PCa disparities research, future studies should rely on more robust GIS techniques, carefully select the geographical scale studied, and partner with GIS scientists for more accurate inferences. Such interdisciplinary approaches have the potential to bridge the gaps between GIS and cancer prevention and control to further advance cancer equity.

Background. Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. Case presentation. We identified across different Cancer Centers six cases of both BRCA wild-type and BRCA-mutated EOC spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as by clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Conclusion. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for optimal disease control of this unfortunate patient’s subset. Albeit not being directly investigated in BM patients, the PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

The prospect of drinking water serving as a conduit for gut bacteria, artificially selected by disinfection strategies and lack of monitoring at the point of use, is concerning. Certain opportunistic pathogens, notably some nontuberculous mycobacteria (NTM), often exceed coliform bacteria levels in drinking water, posing safety risks. NTM and other microbiota resist chlorination and thrive in plumbing systems. When inhaled, opportunistic NTM can infect the lungs of immunocompromised or chronically ill patients, and the elderly, primarily postmenopausal women. When ingested with drinking water, NTM often survive stomach acidity, reach the intestines, migrate to other organs using immune cells as vehicles, potentially colonizing tumor tissue, including in breast cancer. The link between the microbiome and cancer is not new, yet the recognition of intratumoral microbiomes is a recent development. Breast cancer risk rises with age, and NTM infections emerged as a concern among breast cancer patients. In addition to studies hinting at a potential association between chronic NTM infections and lung cancer, NTM have also been detected in breast tumors at levels higher than normal adjacent tissue. Evaluating the risks of continued ingestion of contaminated drinking water is paramount, especially given the ability of various bacteria to migrate from the gut to breast tissue via entero-mammary pathways. This underscores a pressing need to revise water safety monitoring guidelines and delve into hormonal factors, which includes addressing the disproportionate impact of NTM infections and breast cancer on women and examining the potential health risks posed by the cryptic and unchecked microbiota from drinking water.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Tertiary lymphoid structures (TLSs) have become the focus of antitumor immunity. However, the prognostic significance of TLSs in epithelial ovarian cancer (EOC) treated with primary debulking surgery (PDS) or interval debulking surgery (IDS) remains unelucidated. This retrospective study examined the prognostic value of TLSs in tumor tissues obtained during PDS and IDS. Pathological specimens were collected from patients with EOC who underwent PDS or IDS between 2017 and 2020 at the National Cancer Center Hospital East. The correlation of tumor-infiltrating lymphocyte frequency, TLS presence, and PD-L1 expression with progression-free survival (PFS) and overall survival (OS) and the correlation between TLS and PD-L1 expression were analyzed. Overall, 25 specimens (15 from PDS and 10 from IDS) were analyzed. The presence of TLS was associated with a significantly longer OS in patients who underwent PDS but not in patients who underwent IDS. No correlation was identified between TLS and PFS in patients with PDS or with IDS. However, TLS was positively correlated with PD-L1 positivity. The prognostic impact of TLS, specifically in pre-chemotherapy specimens, and a positive correlation between TLS and PD-L1 indicate the potential of TLS as a meaningful biomarker for understanding antitumor immunity and developing immunotherapy for EOC.

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring.

Background: Methotrexate (MTX) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible anti-tumoral potential of them in breast cancer (BC) cells. We aimed to determine the effects of MTX, which is widely used in clinical practice, on cell viability, Hypoxia-inducible factor (HIF) -1α, HIF-2α and prolyl 4-hydroxylase-transmembrane (P4H-TM) in BC cells (MCF-7) and health breast cell (HTERT-HME1) treated with MTX. Methods: Human healthy breast cells (HTERT-HME1) and BC cells (MCF-7) treated with MTX for 24 h, 48h, and 72 h, the effects of MTX on cell viability. Results: The cell viability and with half-maximal inhibitory concentration (IC50) values of of MTX treatment in healthy breast cells were determined to be higher than in MCF-7 cells. MTX showed higher cytotoxicity against MCF-7 cells. MTX significantly reduced cell viability values in HTERT-HME1 and MCF-7 cells. HIF-1α, HIF-2α, and P4H-TM levels was significantly higher in the MCF-7 group than the other groups. Morever, there was a moderate significant correlation between HIF-1α and HIF-2α levels and between HIF-1α and P4H-TM. Conclusions: MTX will show a further decrease in cell viability in long-term treatments of 48 and 72 hours, it is predicted that short-term use may be more appropriate. P4H-TM may be a novel regulator of hypoxia in BC cells. HIF-1α, a key protein responsible for the molecular mechanism of hypoxia in cells, is a key mediator between P4H-TM and hypoxia in MTX-treated cells. HIF-1α, HIF-2α, and P4H-TM values may be markers that can be used as a panel to differentiate BC from healthy women.

Globally, Type 2 diabetes (T2D) and Cancer are the major cause of morbidity and mortality worldwide and is considered to be one of the most significant public health concerns of the 21st century. Over the next two decades, the global burden is expected to increase by approximately 60%. Several observational studies as well as clinical trials have demonstrated the health benefits of consuming whole grains and lower the risk of several chronic non communicable diseases including T2D and cancer. Cereals grains are the primary source of energy in the human diet. The most widely consumed pseudo cereals include (quinoa, amaranth and buckwheat) and cereals (wheat, rice and corn). From a nutritional perspective, both pseudo cereals and cereals are recognized for their complete protein, essential amino acids, dietary fibres and phenolic acids. The bran layer of the seed contains the majority of these components. Greater intake of whole grains than refined grains has been consistently linked to a lower risk of T2D and cancer. Due to their superior nutritional compositions, whole grains make them a preferred choice over refined grains. The modulatory effects of whole grains on T2D and cancer are also likely to be influenced by several mechanisms, some of these effects may be direct; while others involve altering the composition of gut microbiota, increasing the abundance of beneficial bacteria, and lowering harmful bacteria, increasing insulin sensitivity, lowering solubility of free bile acids, protein broken down into peptides and amino acids, producing short-chain fatty acids (SCFAs) and other beneficial metabolites that promote the proliferation in the colon which modulate the anti-diabetic and anti-cancer pathway. Thus the present review are two folded; first summarizes the recent knowledge about the nutritional composition and bioactive acids in pseudo cereals (quinoa, amaranth and buckwheat) and cereals (wheat, rice and corn); the second section summarizes and discusses the progress in recent human studies, such as observational (cross-sectional studies, case-control studies and cohort studies) and intervention studies in understanding their role in T2D and cancer including the potential mechanism. Overall according to the scientific data, whole grain consumption may reduce the incidence of T2D and cancer. Future studies should carry out randomized controlled trials to validate observational results and establish causality; in addition the current manuscript encourages to investigate the specific mechanisms by which whole grains exert their beneficial effects on health by examining the effects of different types of specific protein, dietary fibres and phenolic acids that might help to prevent or treat T2D and cancer.

The role of the microbiome in cancer and its crosstalk with the tumor microenvironment (TME) has been extensively studied and characterized. An emerging field in the cancer microbiome research is the concept of the intratumoral microbiome, which refers to the microbiome residing within the tumor. This microbiome primarily originates from the local microbiome of the tu-mor-bearing tissue or from translocating microbiome from distant sites, such as the gut. Despite the increasing number of studies on intratumoral microbiome, it remains unclear whether it is a driver or a bystander of oncogenesis and tumor progression. This review aims to elucidate the intricate role of the intratumoral microbiome in tumor development by exploring its effects on reshaping the multi-leveled ecosystem in which tumors thrive, the TME. To dissect the complexity and the multitude of layers within the TME, we distinguish six specialized tumor microenvironments, namely the immune, metabolic, hypoxic, acidic, mechanical and innervated microenvironments. Accordingly, we attempt to decipher the effects of the intratumoral microbiome on each specialized microenvironment and ultimately decode its tumor-promoting or tumor-suppressive impact. Additionally, we portray the intratumoral microbiome as an orchestrator in the tumor milieu, fine-tuning the responses in distinct, specialized microenvironments and remodeling the TME in a multi-leveled and multi-faceted manner.

Indocyanine Green (ICG) has significantly advanced minimally invasive surgery. It is widely recognized for its ability to visualize blood vessel patency in real-time across various surgical specialties. While its primary use in colorectal surgery is to evaluate anastomoses for leaks, nu-merous other applications have been documented in the literature. In this review, we aim to explore both established and emerging applications of ICG fluorescence in colorectal surgery, with the goal of improving patient outcomes. This includes preoperative tumor marking and the detection of metastatic disease. Some applications, such as lymphatic mapping, require further research to determine their impact on clinical practices. Conversely, oth-ers, like the intraoperative localizations of ureters, necessitate additional procedures and are not yet widely accepted by the surgical community. However, the development of alternative com-pounds could offer better solutions. Future research should focus on areas like quantitative ICG and protocol standardization in prospective multicenter studies.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

A pathway frequently altered in cancer is glutaminolysis where glutaminase (GA) catalyses the main step: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 may function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We have reviewed the literature to highlight the critical roles of GLS and GLS2 to restrain ROS and regulate both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes and also by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy to dual activate ferroptosis and inhibit cancer cell growth in a ROS-mediated mechanism.

In this multicenter, retrospective study we evaluated the added value of magnetic resonance dispersion imaging (MRDI) to standard multiparametric MRI (mpMRI) for PCa detection. The study included 76 patients - 51 with clinically significant prostate cancer (csPCa), who underwent radical prostatectomy and had an mpMRI including dynamic contrast enhanced-MRI. Two radiologists performed three separate randomized scorings based on mpMRI, MRDI and mpMRI+MRDI. Radical prostatectomy histopathology was used as the reference standard. Imaging and histopathology were both scored according to the Prostate Imaging-Reporting and Data System V2.0 sector map. Sensitivity and specificity for PCa detection were evaluated for mpMRI, MRDI and mpMRI+MRDI. Inter- and intra-observer variability for both radiologists were evaluated using Cohen’s Kappa. On a per patient level, sensitivity for csPCa for radiologist 1 (R1) for mpMRI, MRDI and mpMRI+MRDI were 0.94, 0.82 and 0.94, respectively. For the second radiologist (R2) these were 0.78, 0.94 and 0.96. R1 detected 4% additional csPCa cases using MRDI compared to mpMRI and R2 detected 20% extra csPCa cases using MRDI. Inter-observer agreement was significant only for MRDI (Cohen’s kappa = 0.4250, p=0.004). The results of this study show the potential of MRDI to improve interobserver variability and the detection of csPCa.

Background: The aim of this study was to investigate a series of complete blood cell count – based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78–10.82 vs. 3.31; IQR: 2.15–4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82–21.20 vs. 9.20; IQR: 7.45–11.20, p = 0.013), and systemic inflammation index (SII, median: 1,395; IQR: 929–3,334 vs. 945; IQR: 552–1,373, p = 0.025), but only NLR and NMR remained independently related with clinical response in multivariate logistic regression. In univariate analysis white blood cells (OR:1.2202; 95% CI: 1.0339 - 1.4400, p=0.019), neutrophils (OR:1.2916; 95% CI: 1.0692 - 1.5604, p=0.008), NLR (OR:1.3601: 95% CI: 1.0949 - 1.6896, p=0.005) and NMR (OR:1.2159; 95% CI: 1.00396 - 1.4221, p=0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR and MLR were independently associated with survival; NLR at a cut-off value of 4.0 showed the better AUC (0.749) in predicting survival. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

Colorectal cancer is the third most common malignancy and the second most lethal malignancy of the general population. Right sided colon cancer is less common than left sided, occurring more frequently in females, and associated with an older age and poor prognosis. Intraabdominal abscess formation is a rare complication from colorectal cancer. Thus, we present a case of a 66-year-old male who presented to the emergency department with 4 days of sudden onset, intractable right lower quadrant abdominal pain associated with nausea and vomiting. After further evaluation, he was diagnosed with right sided colon adenocarcinoma complicated by peri-colonic abscess formation. He was treated with hemicolectomy without immunotherapy. Considering the scarcity of data concerning colonic abscess formation and colorectal adenocarcinoma, more research is needed on this dual presentation. These authors reinforce that in older patients presenting with acute abdomen, colorectal cancer should be noted as a differential

Skeletal muscle (SKM), despite comprising ~40% of body mass, is rare. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer.

Breast cancer is the second most common cancer worldwide, primarily affecting women, while histopathological image analysis is one of the possibilities used to determine tumor malignancy. Regarding image analysis, the application of deep learning has become increasingly prevalent in recent years. However, a significant issue is the unbalanced nature of available datasets, with some classes having more images than others, which may impact the performance of the models due to poorer generalisability. A possible strategy to avoid this problem is downsampling the class with the most images to create a balanced dataset. Nevertheless, this approach is not recommended for small datasets as it can lead to poor model performance. Instead, techniques such as data augmentation are traditionally used to address this issue. These techniques apply simple transformations, such as translation or rotation, to the images to increase variability in the dataset. Recently, Generative Adversarial Networks (GANs) have emerged, which can generate images from a relatively small training set. This work aims to enhance the model’s performance in classifying histopathological images by applying data augmentation using GANs instead of traditional techniques.

Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15- 20 % of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is by analysis of tumor biopsies for HER2 expression and amplification. Previously patients were either defined as HER2-positive or negative, however, with approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 and lacking HER2 amplification have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is mo-lecular imaging with radiotracers. In case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Affibody-based radiotracers are clinically validated molecules with favorable characteristics for imaging. In this article we summarize the HER2-targeted therapeutic landscape, describe the experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as novel diagnostic tool in breast cancer and beyond.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

.Background: Clostridioides difficile infections (CDI) vary in severity from mild diarrhea to life-threatening conditions like pseudomembranous colitis or toxic megacolon, often leading to sepsis and death. The COVID-19 pandemic prompted changes in healthcare practices, potentially affecting CDI incidence, though reported data are inconclusive. We studied factors influencing CDI incidence and outcomes at a university hospital throughout the COVID-19 pandemic years. Methods: We conducted a retrospective study on all adult hospitalized CDI cases from January 1, 2020, to December 31, 2022. We collected demographic information, comorbid conditions, and concurrent infections. Results: While overall CDI and COVID-19 rates decreased in 2022, a nota-ble increase in CDI infections was observed among oncological patients and those undergoing some aggressive treatments, such as colon or gastroscopies. The prevalence of comorbidities remained unmodified, and there were declines in prior gastrointestinal surgeries and proton pump inhibitor prescriptions. Factors associated with patient fatality or prolonged hospitaliza-tion included older age, cancer, chronic kidney disease, higher Charlson and McCabe indices, elevated C-reactive protein, and low albumin concentrations. Conclusion: Our study shows the evolving landscape of CDI during the COVID-19 pandemic and emphasizes the impact of de-layed diagnoses and treatments exacerbated by telemedicine adoption. Identified risk factors for CDI-related mortality or prolonged hospital stays underscore the importance of targeted inter-ventions in high-risk populations.

Histone demethylases, enzymes responsible for removing methyl groups from histone proteins, have emerged as critical players in regulating gene expression and chromatin dynamics, thereby influencing various cellular processes. LSD2 and LSD1 have attracted considerable interest among these demethylases because of their associations with cancer. However, while LSD1 has received significant attention, LSD2 has not been recognized to the same extent. In this study, we conduct a comprehensive comparison between LSD2 and LSD1, with a focus on exploring LSD2's implications. While both share structural similarities, LSD2 possesses unique features. Functionally, LSD2 shows diverse roles, particularly in cancer, with tissue-dependent roles. Additionally, LSD2 extends beyond histone demethylation, impacting DNA methylation and DNA damage repair pathways. This study underscores the distinct roles of LSD2, providing insights into their contributions to cancer and other cellular processes.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Metabolomics profiling for accurate and reliable quantification of organic acids that carry a carboxylic acid functional group in complex biological samples, remains a major analytical challenge in clinical chemistry research. Several procedural barriers associated with quantification of clinically important carboxylic containing metabolites (CCMs) including spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column, limit the sensitivity, specificity, and reproducibility of multiple-reaction monitoring (MRM) based LC-MS assay development. We report a targeted metabolomics-based analytical method for the quantification of CCMs using phenylenediamine derivatization. Accurate and sensitive quantification of CCMs is successfully demonstrated in an array of biological matrices. Recovery of metabolites from different matrices (plasma, serum, urine, saliva, tissues, and cell extracts), ranged from 90% to 105%, with all the CVs ≤ 10%. The method showed linearity over a broad dynamic range from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 for most of the metabolites tested herein, that covers broad-based applicability with the analysis of biological samples. In most cases the LODs were as low as 0.01 ng/mL. The phenylenediamine-based derivatization of carboxyl acid library consisting of more than 70 endogenous metabolites was constructed for metabolite identification, which spanned more than 40 biological pathways. The library included a wide-variety of structurally variant CCMs such as amino acids/conjugates, short to medium chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids and some ring-containing CCMs. We compared the CCMs profiles of pancreatic cancer cells with normal pancreatic epithelial cells to test and validate the biological utility of this method. The comparative profiling between cancerous and normal cells resulted in the identification of potential biomarkers in pancreatic cancer, and their correlation with several key metabolic pathways such as central carbon energy metabolism, protein metabolism, including TCA cycle, glycolysis, Gln-Glu pathway, and biosynthesis of amino acids and unsaturated fatty acids was established. The method, described herein, for the first time enables the sensitive and highly specific quantification of CCMs on small sample size with high reproducibility in a high throughput manner. Given the biological and functional significance of this class of metabolites, this mass spectrometry based targeted quantitative assay, fills an important gap and is likely to support a wide range of applications for basic, clinical, and translational research.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

Abstract: Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded daily, or nearly daily exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, tumor distant recurrence remains a concern, prompting exploration of Total Neoadjuvant Therapy (TNT) as a comprehensive treatment strat-egy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Non-operative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving clinical complete response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for treatment response assessment. This review synthesizes current evidence on TNT, ICIs, NOM and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

This study was to identify clinical cancer biomarkers for recurrent gastric cancer survivors using artificial intel-ligence. From a hospital-based cancer registry database in Taiwan, the datasets of the incidence of recurrence and clinical risk features were included in 2476 gastric cancer survivors. We benchmarked Random forest with MLP, C4.5, AdaBoost, and Bagging algorithms on metrics and leveraged synthetic minority oversampling technique (SMOTE) for imbalanced dataset issues, cost-sensitive learning for risk assessment, and SHapley Additive ex-Planations (SHAP) for feature importance analysis in this study. Our proposed Random forest outperformed the other models with an accuracy of 87.9%, a recall rate of 90.5%, an accuracy rate of 86% and F1 of 88.2% on re-current category by a 10-fold cross-validation in a balanced dataset. We identified clinical features of recurrent gastric cancer, which are the top five features, stage, number of regional lymph node involvement, Helicobacter pylori, BMI(body mass index), and gender, which significantly affect the prediction model's output, are worth paying attention to in the following causal effect analysis. Using an artificial intelligence model, the risk factors for recurrent gastric cancer could be identified and cost-effectively ranked according to their feature importance. In addition, they should be crucial clinical features to provide physicians with the knowledge to screen high-risk patients in gastric cancer survivors as well.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR&gt;MTYR&gt;&gt;TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. Summarizing, incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. The incident T2DM and diabetes free Hungarian population were included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p&lt;0.0001. The risk of having cancer was age-dependent, having the highest odd in the age group 18-39. The incidence of cancer was declining in the non-diabetic but was unchanged in T2DM population. The average lag time of diagnosing a cancer after the detection of T2DM was 3.86 months.; (4) Conclusions: Iincident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Black spot disease is associated with the breakdown of chitin by chitinolytic bacteria resulting in extensive black lesions across the body of crustaceans. Black spot is prevalent across most fished crustaceans worldwide. Severely infected individuals are rejected from the fishery resulting in financial loss to both fisher’s and seafood export and processing companies. Ecologically, populations with high infection rates may have increased mortalities resulting in fewer individuals surviving the population. The prevalence and severity of shell disease in the edible crab, Cancer pagurus, of various size classes, was assessed via scaled images taken from crabs sampled within the Berwickshire Marine Reserve, UK. A total of 22.4% of individuals across all size groups were found to contain black spot lesions. Male crabs were more commonly affected (26.21%), with more body parts showing lesions and a greater overall blackspot coverage (1.75%) than females (16.43% and 1% respectively). Crabs under the MLS (140mm) showed a significantly higher black spot coverage, but size did not significantly affect infection rates. Carapace and chelae were the most commonly affected areas. Compared to previous studies the Berwickshire Marine Reserve has a relatively low prevalence of black spot disease in Cancer pagurus.

Background This study aimed to determine the association between immune checkpoint inhibitors (ICIs) and the risk of herpes zoster (HZ) incidence in patients with lung cancer. Method We obtained national claims data of 51,021 patients from South Korea with lung cancer between August 2017 and December 2021. The study population was classified into ICIs and non-ICIs groups based on prescription of ICIs at least once during the study period. To estimate the effects of ICIs treatment compared with those without ICIs treatment on HZ incidence, we used the Cox proportional hazards model adjusted for sex, age, comorbidities, and concomitant use of immunosuppressive drugs. Stratified analyses based on sex, age, and comorbidities were conducted to identify corresponding risk factors. Results Of the 51,021 study participants, 897 (1.8%) were prescribed ICIs, and 2,262 (4.4%) were diagnosed with HZ. Approximately 75.6% of the patients were male, and the prevalence of diabetes, cardiovascular disease, and chronic lung disease in the ICIs group was significantly lower than that in the non-ICIs group. The Kaplan–Meier plot showed that the probability of incidence of HZ in the ICIs group was lower than that in the non-ICIs group. Additionally, treatment with ICIs was associated with a 31% lower risk of developing HZ when compared to that seen without ICIs treatment (95% confidence interval [CI], 0.48–1.00). This association was stronger in females (hazard ratio [HR], 0.42; 95% CI, 0.19–0.94) and those less than 68 years of age (HR, 0.58; 95% CI, 0.34–0.99). Conclusion In these real-world data from an Asian population with lung cancer, ICIs treatment might be associated with a reduced risk of HZ compared to that without ICIs treatment.

Recently, I described a novel approach for cancer therapy in an article entitled “Promoting Oncolytic Vector Replication with Switches that Detect Ubiquitous Mutations”. However, there are a few more design details that should potentially be taken into consideration. Also, multiregion, multisample tumor sequencing may be simplified by analyzing cell-free DNA in the blood of patients.