Muscle-enriched A-type lamin-interacting protein (MLIP) is an emerging protein involved in cellular homeostasis and stress adaptation. Eukaryotic cells regulate various cellular processes, including metabolism, DNA repair, and cell cycle progression, to maintain cellular homeostasis. Disruptions in this homeostasis can lead to diseases such as cancer, characterized by uncontrolled cell growth and division. This review aims to explore for the first time the unique role MLIP may play in cancer development and progression, given its interactions with the PI3K/Akt/mTOR pathway, p53, and FOXO transcription factors, all critical regulators of cellular homeostasis and tumor suppression. We discuss the current understanding of MLIP's involvement in pro-survival pathways and its potential implications in cancer cells' metabolic remodeling and dysregulated homeostasis. Additionally, we examine the potential of MLIP as a novel therapeutic target for cancer treatment. This review aims to shed light on MLIP's potential impact on cancer biology and contribute to developing innovative therapeutic strategies.

Polydatin, a polyphenolic compound sourced from various natural origins, has garnered attention due to its potential anti-tumor properties and low toxicity. This research utilized Molecular Docking methods to investigate the molecular interactions between Polydatin and the Crystal Structure of Human UDP-glucuronic acid decarboxylase (UXS1), aiming to uncover the mechanisms contributing to its anti-tumor effects. The study revealed a substantial binding energy value of approximately -10 kcal/mol for the Polydatin-UXS1 interaction, indicating a robust and favorable binding. This suggests that Polydatin holds significant promise in cancer research, offering insights into its ability to interact with and potentially modulate the activity of UXS1. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of polydatin ( or piceid). From these results, the parameters for polydatin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile.These findings position Polydatin as a compelling candidate for further exploration in cancer research, highlighting both its efficacy and safety considerations.

Abstract The relationship between cancer and neurodegeneration has spurred extensive scientific discourse, challenging their historical classification as distinct disorders. While cancer signifies uncontrolled cellular proliferation and neurodegeneration marks progressive neuronal loss, recent insights highlight intriguing interconnections between these seemingly disparate conditions. Cancer entails perpetual signaling for growth, evasion of growth inhibitors, resistance to cell death, acquisition of replicative immortality, stimulation of blood vessel growth (angiogenesis), and initiation of invasion and metastasis. Conversely, investigations emphasize disrupted cellular energy regulation and evasion of immune surveillance as key traits arising from genome instability, mutations, and inflammation driving tumorigenesis. Neurodegeneration involves neuronal malfunction and depletion, synaptic impairment, and protein abnormalities aggregations contributing to muscle atrophy and cognitive deficits. Varied clinical studies underscore contrasting correlations between cancer and neurodegeneration, hinting at mirrored molecular pathways that foster cell resilience or vulnerability. Research explores cellular signaling in tumorigenesis, shared with neurodegenerative disorders. Aberrant expression or mutations in crucial genes implicated in neurodegeneration also surface in cancer contexts. Debates persist on the nature of the relationship between cancer and neurodegeneration, contemplating inverse associations or shared pathways. Understanding their complex interplay, encompassing genetics, cellular mechanisms, and environmental influences, remains pivotal in unraveling their connections. This review explores the intriguing perspective that neurodegeneration and cancer might share fundamental genetic links, delving into potential implications for their onset and progression.

The Fas associated Death Domain (FADD) is an adaptor protein that predominantly transduces apoptosis signal from death receptor (DR) to activate caspases, leading to the initiation of apoptotic signaling and the coordinated removal of damaged, infected, or unwanted cells. In addition to its apoptotic functions, FADD is involved in signaling pathways related to autophagy, cell proliferation, necroptosis, and cellular senescence, indicating its versatile role in cell survival and proliferation. The subcellular localization and intracellular expression of FADD play a crucial role in determining its functional outcomes, thereby highlighting the importance of spatiotemporal mechanisms and regulation. Furthermore, FADD has emerged as a key regulator in inflammatory signaling, contributing to immune responses and cellular homeostasis. This review provides a comprehensive summary and analysis of cellular dynamics of FADD in regulating of programmed cell death and inflammation through distinct molecular mechanisms associated with various signaling pathways.

Background: The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. We hence aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Methods: Among 2,152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery, and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated focusing on their post-recurrence therapies and prognoses. Results: The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701–2.912; log-rank, p = 0.324), and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459–1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Conclusions: Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as it can cure the recurrence and can delay the start of administration of molecular-targeted therapies.

Cancer have been known as a most important global mortality reason, which in spite of novel therapeutic ways, the leading death is still considerable. Molecular targeted diagnosis and therapy using aptamers with high affinity have converted to a popular technique for pathological angiogenesis and cancer therapy scientists. In this paper several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently) and biosensors, which successfully designed for biomarkers, are critically reviewed. The results obviously demonstrated that aptamer have potentially incorporated with targeted delivery systems and biosensors for detection of biomarkers which expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, as the main field of medical sciences, possess high potential in cancer therapy, pathological angiogenesis and increase of community health. The clinical use of aptamer is so limited due to unreliability resulted from targets impurities, inaccuracy in SELEX stages process, and in vitro synthesis which led to the lower selectivity for in vivo targets. Moreover, size behavior, probable toxicity, low-distribution and unpredictable behavior of nanomaterials in in vivo media make critical their usage in clinical assays. This review can be helpful for implementation and designing the future studies which are effective and applicable for clinical use.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

Ceramide is a lipid that regulates cell death including apoptosis and necroptosis and acts as a powerful tumor suppressor. These characteristics have supported the development of ceramide-based cancer therapeutics. In the present study, ceramide mimetics (RT-25, RT-71 and YM-07) were designed and chemically synthesized, and their potential as necroptosis-inducing chemotherapeutic reagents was examined. RT-71 and YM-07, but not RT-25, potently decreased cell viability in multiple cancer cell lines. The ranges of IC50 values for RT-71 and YM-07 were 8.4–40.8 µM and 4.4–23.7 µM, respectively. Cleavage of PARP, an apoptosis marker, was not observed in MCF-7 cells treated with the mimetics. To determine the effects on necroptotic cell death, we used siRNAs specific to mixed lineage kinase domain-like protein (MLKL). MLKL knockdown significantly suppressed the cell death induced by YM-07 but not RT-71. These results suggest that YM-07 exhibits pro-necroptotic activity. Taken together, these findings indicate ceramide mimetic YM-07 as a lead compound for developing MLKL-activating necroptotic reagents. Our results help establish a foundation for pro-necroptotic therapy for cancer.

PIM1is involved in critical cellular processes, playing a key role in the regulation of the cell cycle, apoptosis, transcriptional activation, and broader signal transduction pathways . The exploration of PIM1inhibitors, such as small molecules or antibodies, represents a promising avenue in cancer research for developing novel treatment strategiess. Its significance in oncogenic signaling has led to extensive research on PIM1 as a target in cancer studies. Docking studies have revealed a robust interaction between hypericin and PIM1, suggesting a strong binding affinity (-12.5 kcal/mol). This research aims to explore the molecular dynamics of the hypericin-PIM1 interaction, identifying potential binding sites and elucidating the impact on PIM1-mediated cellular processes, such as cell cycle regulation and apoptosis. The findings may contribute valuable insights into developing hypericin-based therapies targeting PIM1, paving the way for novel and effective strategies in cancer research.

Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs have been developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.

(1) Background: Triple negative breast cancer (TNBC) is a distinct subgroup of breast cancer presenting high level of recurrence and neo-adjuvant chemotherapy is beneficial in its therapy management. Anti-PD-L1 immunotherapy improves effect of neo-adjuvant therapy in TNBC. (2) Methods: Immune-modulation and ferroptosis related R-packages were developed for integrative transcriptome to analyze transcriptome datasets: TNBC cells stimulated with ferroptosis inducers (GSE173905, GSE154425), breast tumors with clinical data (TCGA and METABRIC cohorts). Protein level validation was investigated through protein atlas proteome experiments. (3) Results: Erastin/RSL3 ferroptosis inducers up-regulate CD274 in TNBC cells (MDA-MB-231 and HCC38). In breast cancer, CD274 expression is associated to overall survival. Breast tumors presenting high expression of CD274 up-regulated some ferroptosis drivers associated to prognosis: IDO1, IFNG and TNFAIP3. CD274-ferroptosis-driver score computed on breast tumor transcriptome stratified patients on their prognosis: low score was observed in basal subgroup with higher level of recurrent risk scores: oncotypeDx, ggi and gene70 scores. In METABRIC cohort, CD274, IDO1, IFNG and TNFAIP3 were found overexpressed in TNBC subgroup. CD274-ferroptosis-driver score was found associated to overall survival independently of TNM classification and age diagnosis. Tumor expression of CD274, TNFAIP3, IFNG and IDO1 in biopsy of breast ductal carcinoma was confirmed at protein level (4) Conclusion: Ferroptosis inducers up-regulate PD-L1 in TNBC cells, known as effective target of immunotherapy in high risk early TNBC which received neo-adjuvant therapy. Basal and TNBC tumors highly expressed CD274 and ferroptosis drivers: IFNG, TNFAIP3 and IDO1. CD274-ferroptosis driver score is associated to prognosis and to the risk of recurrence in breast cancer. A potential synergy of ferroptosis inducers with anti-PD-L1 immunotherapy is suggested in recurrent TNBC.

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of estrogen signaling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear estrogen signaling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of estrogen in CRC through various genomic and non-genomic signaling pathways involving membrane and nuclear estrogen receptors. Furthermore, we examine the interplay between estrogen receptors and other signaling pathways, in particular the Wnt/-catenin proliferative pathway and hypoxia in shaping biological sex differences and estrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting estrogen signaling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon.

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now known also as a modulator of gene expression. What is important for cancer, is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts the enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NFκB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which have a significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. In general, the capacity of cancer cells to adapt to oxidative stress depends on molecular systems such as the interface of OGG1 with NFκB, which bestows a cancer cell with the molecular mechanism of transformation of its microenvironment to enable adaptation and survival of malignant clones.

Lung cancer remains the leading cause of cancer-related mortality worldwide. The main issue is the absence of a screening test available in clinical practice; the identification of non-invasive biomarkers is thus an urgent clinical necessity. Currently, low-dose computed tomography (LD-CT) demonstrates a 20% reduction of lung cancer mortality. However, it is not particularly suitable for clinical practice because of the costs, radiation, and the false positive rate. Several studies have therefore focused on research into biomarkers in body fluids. Despite the power of certain molecules to distinguish lung cancer patients from healthy subjects, no biomarker has yet been shown to significantly and reliably influence clinical decisions or to be translated from the laboratory to clinical practice. We performed an overview of the peer-reviewed biomedical literature published in the last 10 years on the research regarding biomarkers for the early diagnosis of lung cancer via a comprehensive analysis of the reviews published this past year. Our main aim was to bring to light the limitations and strengths of the research already conducted. Furthermore, future prospectives have been explored, bearing in mind the management of clinical trials and their integration into clinical practice.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

Next-generation cancer and oncology research needs to take full advantage of the multi-modal structured, or graph, information, with the graph datatypes ranging from molecular structures to spatially resolved imaging and digital pathology to biological networks to knowledge graphs. Graph Neural Networks (GNNs) efficiently combine the graph structure representations with the high predictive performance of deep learning, especially on the large multi-modal datasets. In this review article, we survey the landscape of recent (2020-present) GNN applications in the context of cancer and oncology research, and delineate six currently predominant research areas. Subsequently, we identify the most promising directions for future research. We compare GNNs with graphical models and "non-structured" deep learning, and devise the guidelines for cancer and oncology researchers or physician-scientists asking the question of whether they should adopt the GNN methodology in their research pipelines.

Heat shock factor 1 (HSF1) is a transcription factor crucial for regulating heat shock response (HSR), one of the significant cellular protective mechanisms. When cells are exposed to proteotoxic stress, HSF1 induces the expression of heat shock proteins (HSPs) to act as chaperones, correcting the protein-folding process and maintaining proteostasis. In addition to its role in HSR, HSF1 is overexpressed in multiple cancer cells, where its activation promotes malignancy and leads to poor prognosis. The mechanisms of HSF1-induced tumorigenesis are complex and involve diverse signaling pathways, dependent on cancer type. With its important roles in tumorigenesis and tumor progression, targeting HSF1 offers a novel cancer treatment strategy. In this article, we examine the basic function of HSF1 and its regulatory mechanisms, focus on the mechanisms involved in HSF1’s roles in different cancer types, and examine current HSF1 inhibitors as novel therapeutics to treat cancers.

Introduction and objectives Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that a significant role in its onset is played by the reduced activity of the upper airway muscles. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. The purpose of this review is to examine and demonstrate the prevalence of OSA in patients with associated pathologies, especially in patients with head and neck tumors, as well as the role of surgical and non-surgical therapeutic methods in improving the quality of life. Material and methods Taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing PubMed, Medline and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Results Our results demonstrate the involvement of OSA in the presence of comorbidities and also, an increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions The clinician must recognize the increased prevalence of OSA in patients with head and neck cancer, as well as the coexistence of OSA with certain comorbidities. They should actively engage in early diagnosis and establish optimal treatment methods to improve the quality of life for patients with associated conditions such as head and neck tumors or cardiovascular pathology.

Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, Sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.

Purpose: Therapeutic targeting of RAF1 is promising, but it requires further investigation for the relation between clinical features and RAF1 aberrations regarding the MAPK signaling pathway in various solid tumors to realize the precision medicine. Methods: Between October 2019 and June 2023, Samsung Medical Center, 3,895 patients with metastatic cancer patients received a next-generation sequencing (NGS) using TruSight Oncology 500 (TSO500) assay as a routine clinical practice. We surveyed the incidence of RAF1 aberration including mutation (single-nucleotide variant [SNV]), amplification (copy-number variation), and fusion. Results: In 3,895 metastatic cancer patients, 77 (2.0%) had RAF1 aberrations in their tumor specimen. Of 77 patients, 44 (1.1%) had RAF1 mutations (SNV), 25 (0.6%) had RAF1 amplification and 10 (0.3%) had RAF1 fusions. Among 10 patients with RAF1 fusion, concurrent RAF1 amplification and RAF1 mutation were detected in one patient each. The most common tumor types were bladder cancer (11.5%), followed by ampulla of Vater (AoV) cancer (5.3%), melanoma (3.0%), gallbladder (GB) cancer (2.6%), and gastric cancer (2.3%). Microsatellite instability high (MSI-H) tumors were found in 5 out of 76 patients (6.6%) with RAF1 aberration, while MSI-H tumors were found only in 2.1% of patients with wild-type RAF1 cancer (p < 0.0001). Conclusion: We showed that when patients with metastatic solid cancer receive NGS test, approximately 2.0% have RAF1 aberrations in their tumor specimen.

Background: Colorectal cancer (CRC) is one of the major causes of cancer-related death worldwide. Aerobic glycolysis precedes obtainment of oncogenic mutations and loss of tumor suppressors, promoting the progress of CRC. Although numerous biomarkers have been identified to be associated with prognosis and survival, a glycolysis-related gene signature in CRC has not been explored. Methods: mRNA expression profiling data in a group of CRC patients (n = 540) was extracted from the Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GESA) was performed to identify gene sets that were significantly different between CRC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan–Meier survival estimates and the log-rank test were used to validate the significance of risk parameters for prognosis prediction. Results: Five glycolysis-related genes (ENO3, GPC1, P4HA1, IDUA, ANKZF1) were identified to be significantly associated with overall survival (AUC=0.754). Based on the five‑gene signature, patients with CRC were divided into high and low‑risk subgroups. CRC patients with a low-risk score had better survival benefits than those with a high one (P &lt; 0.001). Conclusions: A five-gene signature associated with glycolysis for predicting the outcome of CRC patients was generated, serving as a valuable prognosis model with high efficiency and potential targeted therapy of CRC patients.

Cancer is a complex and heterogeneous disease, influenced by various factors that affect its progression and response to treatment. Although histopathological diagnosis is crucial for identifying and classifying cancer, it may not accurately predict the disease's development and evolution in all cases. To address this limitation, liquid biopsy has emerged as a valuable tool, enabling a more precise and non-invasive analysis of cancer. Liquid biopsy offers the ability to detect tumor DNA fragments, circulating tumor cells, and exosomes released by cancer cells into the bloodstream. Exosomes, in particular, have attracted significant attention in cancer research due to their specific protein composition, which can provide valuable insights into the disease. The protein profile of exosomes often differs from that of normal cells, reflecting the unique molecular characteristics of cancer. Analyzing these proteins can help identify cancer-associated markers that play critical roles in tumor progression, invasion, and metastasis. Ongoing research and clinical validation are essential to advance and effectively utilize protein biomarkers in cancer. Nevertheless, their potential to improve diagnosis and treatment is highly promising. This review discuss several exosome proteins of interest in breast cancer, particularly focusing on studies conducted in mammary tissue and cell lines in humans and experimental animals. Unfortunately, the studies conducted in the canine species are scarce. This emphasis sheds light on the limited research available in this field. Additionally, we present a curated selection of studies that have explored exosomal proteins as potential biomarkers, aiming to achieve the aforementioned benefits in breast cancer diagnosis, prognosis, monitoring, and treatment.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with can-cer. Indeed, cancer patients have a significantly higher incidence of AF than that ob-served in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screen-ing, especially in older adults. The pathophysiological mechanisms are many and var-ied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general popula-tion; however, the numerous interactions with chemotherapeutics, which lead to a sig-nificant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities in de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have changed the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road towards a personalized treatment for de novo mHSPC is still long considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as predictive biomarker requires further validation, as well as it remains to ascertain how the genomic alterations detected in mHSPC, that are considered predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Skin cancer is a disease that reflects most malignant neoplasms worldwide, whose rate of involvement has increased significantly in recent decades. Treatments that offer efficient results with attenuation of adverse reactions and greater patient compliance have been the subject of many systematic investigations. This review aims to qualitatively present published works that showed new strategies to increase the penetration power of natural substances through the skin in the topical treatment against skin cancer. In this sense, nanoengineering mechanisms, the iontophoresis technique, and photodynamic therapy using natural products (NP) contribute to new knowledge about substance carrier strategies in topical treatments against skin cancer.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine the impact on survival of adjuvant RT according to the Sedlis criteria. Patients with early-stage cervical cancer who underwent radical hysterectomy between 2005 and 2022 at a single tertiary institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analyzed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. In this retrospective study 121 patients were included of whom 48(39.7%) received adjuvant RT due to the presence of unfavorable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p=0.584) or disease-free survival (DFS) (p=0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate-risk factors.

In order to provide a new direction for the diagnosis and treatment of gastric cancer, the differentially expressed blood-based miRNAs in gastric carcinoma were obtained and analyzed from the datasets GSE113486, GSE112264 and GSE113740 by the SangerBox, the miRNA - target genes prediction, GO and KEGG functional enrichment analyses with DAVID 6.8, and the STRING database with Cytoscape, respectively. The correlation between the key miRNAs expression and the prognosis and diagnostic value of gastric cancer patients were detected by survival prognosis and ROC curve. QRT-PCR was used to detect the possible key miRNAs expression in human blood species. The dataset GSE108307 which shows the miRNAs affected by H. pylori infection was analyzed by GEO2R. The expression level of CagA and the clinically used gastric cancer markers were detected in human blood species for contrast. Five key blood-based miRNAs were determined, including hsa-miR-124-3p, hsa-miR-125a-3p, hsa-miR-29b-3p, hsa-miR-4276, and hsa-miR-575.The detection in human blood species as well as the cross analysis with H. pylori infection and clinically used markers expression suggested the importance and efficacy of the specific miRNAs in the early diagnosis and monitoring of gastric carcinoma. The study identified potential novel blood miRNA biomarkers of gastric cancer by bioinformatics and human blood species detection, which may give a new possibility of the important biomarkers for the diagnosis and prognosis of gastric cancer.

Regulatory T cell master transcription factor, Forkhead box P3 (Foxp3) has been detected in cancer cells, but its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumor administration of Ad.P60 in breast tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells, and that gene therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.

The gut microbiota's part in colon cancer has become an exciting and hopeful area of study because it shows complex links that affect how cancer starts, spreads, and responds to treatments. Dysbiosis, which is an imbalance in the community of germs in the gut, has been linked to a higher risk of colon cancer by causing inflammation and making a place where tumours can grow. Researchers have found that some kinds of bugs can either help colon cancer grow or stop it from doing so. This shows how important it is to maintain a healthy gut bacteria. In both preclinical and clinical research, therapeutic treatments that target the microbiome in the gut have shown promise. Probiotics and prebiotics can change the environment around a tumour, change the balance of microorganisms in the gut, and boost immune responses that fight the cancer. Faecal microbiota transfer (FMT) is being looked at as a new way to change the bacteria in the guts of people with colon cancer. By adding microbiota-targeted drugs to standard cancer treatments, it may be possible to make the treatment more effective and lessen side effects. Microbiota-focused treatments for colon cancer are still in their early stages, but they show promise. More research needs to be done to find out how they work and show that they work in the clinic. The link between the bacteria in the gut and colon cancer opens up new ways to help patients and give them better results. This might make a difference in how colon cancer is handled in the future.

The study of notable people as agents for increasing cancer awareness started just in the last decades of the 20th century. This study aimed to identify Pan-American notable people with head and neck cancer (HNC) and to assess HNC’s professional perspective on communicating stories of notable patients with HNC to promote prevention. Methods: This cross-sectional study was conducted by applying a RedCap questionnaire to oral medicinists, oral pathologists, head and neck surgeons, and clinical oncologists with experience in HNC research, education, or treatment in Pan-American countries. Additionally, a structured search was performed on PubMed, Scopus, EMBASE, Web of Science, LILACS, and gray literature Results: We identified 42 notable people from the United States, Brazil, Argentina, Mexico, El Salvador, Chile, Colombia, and Peru who were mainly actors, athletes, and musicians. Participants agreed that stories of notable patients with HNC can positively impact the population and promote prevention if communicated by the internet, social media, and television. Conclusion: In the Pan-American region, notable individuals who have suffered from HNC may be powerful advocates for increasing cancer awareness and promoting prevention strategies. The professionals involved in the study expressed a positive inclination towards using the stories of these notable HNC survivors as an effective prevention strategy.

Background: Music therapy (MT) is a non-pharmacological treatment increasingly used to reduce stress and anxiety in hospitalized children affected by cancers. The aim of this study was to eval-uate the impact of MT on quality of life of children with cancer. Methods: We have conducted a quasi-experimental study between April 1 and August 31, 2021 at Bechir Hamza children's Hos-pital in Tunis, including children treated for cancer. The child or the parent completed PedsQL Module Cancer french version 3.0 questionnaires before and after four weekly music therapy ses-sions. Child's respiratory and heart rate were measured before and after each session. Results: We included 20 children whose mean age was 7 ± 4.5 years [2-14]. The median value of the total questionnaire score increased from 57 [46; 70] to 72 [67; 85] (p < 10-3) with a significant reduction in pain (p = 0.02), nausea (p = 0.009), anxiety related to medical procedures (p = 0.009) and worry about the future (p = 0.005). We highlighted a significant decrease in respiratory and heart rate after MT (p<0,05). Conclusions: MT has positive impact of on quality of life of children with cancer.

Cancer patients may experience significant distress. The “Emotion Thermometers” (ETs) are a short visual analogue scale used to screen patients for psychosocial risk. This study aimed to assess emotional distress in a large sample of cancer patients attending psychological services at an NGO, and to explore factors that may contribute to it. The ETs were answered by 899 cancer patients. They were, on average, 59.9 years old, the majority were female, had breast cancer, were under treatment or were disease-free survivors, and reported high levels of emotional distress, above the cut-off (≥5). A Generalized Linear Model was used to measure the association between the level of Distress and 33 items of the problem list. Four items - sadness, depression, sleep and breathing - were found to be significantly related to a higher level of Distress. Additionally, women and those who were in the palliative phase also had significantly higher levels of Distress. Conclusions: The results confirm the need for early emotional screening in cancer patients, as well as the relevance of attending to the characteristics of each patient. Additionally, they highlight the utility of the ETs for the clinical practice, allowing to optimize the referral to specialized psy-chosocial services.

Colon cancer (CC) is one of the leading causes of cancer-related death worldwide. Gene hypermethylation is a well-known alteration that contributes to tumour progression in CC. It is essential to analyse new molecular markers that can delineate more aggressive CC cases. The detection of new epigenetic alterations such as hypermethylation and hypomethylation of regulatory gene regions that participate in crucial mechanisms of cancer progression, such as epithelial mesenchymal transition (EMT), could be useful for identifying cases that might benefit from a closer follow-up by clinicians. In the present report we describe, for the first time, the hypermethylation of the ZEB1 gene, which is more frequent in cases without expression of hMLH1. More importantly, this epigenetic alteration is a good prognostic factor related to disease-free and overall survival in all cases and Consensus Molecular Subtypes (CMS2/3) independently of other clinical parameters such as patient age, stage, lymph node involvement, and blood vessel and perineural invasion.

Oncological changes in the prostate are a common cause of death among elderly men. Malignant cells are difficult to identify at early stages, which are asymptomatic. The patient often seeks medical assistance when the disease has already progressed, and the treatment is less effective. Early diagnosis of prostate cancer (PC) is thus one of the priority tasks of modern urology and healthcare in general. The aim of this study is the detection of microRNAs (miRNAs), which are known to be associated with PC. The detection of the target miRNAs in human plasma samples has been performed with a nanoribbon biosensor system, which was based on "silicon-on-insulator" structures (SOI-NR biosensor). In order to provide biospecific detection of the target miRNAs, the surface of individual nanoribbons has been modified with DNA oligonucleotide probes (oDNA probes), whose nucleotide sequences were complementary to those of the target miRNAs. The high detection sensitivity has been demonstrated with the use of model oDNAs, which are complementary to nanoribbon-immobilized oDNA probes, in buffer solutions. The sensitivity threshold was 1.1 × 10^-17 M. The successful detection of target miRNAs, isolated from real plasma samples of PC patients, has also been demonstrated. We believe that the development of highly sensitive nanotechnology-based biosensors for PC markers is a step towards personalized medicine.

Breast cancer is the foremost common in women, and its early diagnosis will help treat and increase patients' survival. This review article aims to studies on recent findings of standard imaging techniques and their characteristics for breast cancer diagnosis and recent nanoparticles (NPs) which are used for breast cancer detection. Herein, The search was performed in the literature through scientific citation websites, including Google Scholar, PubMed, Scopus, and Web of Science until May 2023. A comprehensive study on different imaging modalities and NPs for breast cancer diagnosis is reviewed, and their successes, challenges, and limitations are discussed.

Abstract: A recent approach to radiotherapy for prostate cancer is the administration of high doses of radiation to the prostate while minimizing the risk of side effects. Thus, image-guided radiotherapy utilizes advanced imaging techniques and is a feasible strategy for increasing the radiation dose. New radioactive particles are another approach to achieving high doses and safe procedures. Prostate brachytherapy is currently considered as a combination therapy. Spacers are useful to protect adjacent organs, specifically the rectum, from excessive radiation exposure.

The stability of the gut barrier is very important for keeping the gut healthy and stopping dangerous substances from getting into the bloodstream. Several diseases, including cancer, have been linked to the gut barrier being broken. Live bacteria called probiotics that are good for the host have been shown to have the ability to improve the gut barrier and lower the risk of cancer in the gastrointestinal system. This review looks at how probiotics affect the health of the gut barrier and what that might mean for preventing cancer. Researchers have found that probiotics strengthen the connections between intestine cells, encourage the production of protective mucins, and change the make-up and balance of the gut bacteria. These processes help keep the gut barrier strong and stop harmful chemicals from getting into the bloodstream. Probiotics may help lower the chance of cancer by reducing inflammation throughout the body and protecting the GI tract from harmful substances. But more study is needed to fully understand the benefits of different probiotic strains, the best amounts to take, and how they affect the health of the gut barrier. Understanding how probiotics, the health of the gut barrier, and the risk of cancer all work together can help us come up with new ways to avoid and treat cancer.

(1) Background: This case report focuses on a 46-year-old female patient diagnosed with a rare and aggressive form of breast cancer known as rapidly growing, ulcerated breast cancer. The patient exhibited rapid progression of the disease, experiencing discomfort and noticeable changes in the size and texture of the affected breast over a short period of time; (2) Methods: An intensive neoadjuvant chemotherapy regimen was employed as the primary treatment approach. The patient's response to this treatment was closely monitored and assessed. Various diagnostic tests and imaging techniques were utilized to evaluate the extent of the disease and track its response to the chemotherapy; (3) Results: The patient's response to the neoadjuvant chemotherapy regimen was remarkable, resulting in a complete pathologic response. This outcome, although unusual in rapidly growing, ulcerated breast cancers, highlights the effectiveness of neoadjuvant chemotherapy in managing large, locally advanced breast cancers; (4) Conclusions: The multidisciplinary approach employed in managing this complex breast cancer case proved to be crucial to the patient's favorable outcome. Despite the aggressive nature of the disease and the challenges posed by the rapid growth and ulceration, the patient achieved a positive result. This case contributes to the limited clinical literature on such unusual and aggressive breast cancer cases, providing valuable insights for future clinical practice.8

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

The incidence of gastrointestinal cancers has seen a significant increase in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, among others. These issues have necessitated the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable interest due to their ability to generate heat in tumor regions upon the application of an external alternating magnetic field, a process known as hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating gastrointestinal cancers. After applying various inclusion and exclusion criteria, a total of 40 articles were analyzed. The results revealed that iron oxide is the preferred material for magnetism generation in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly, novel therapies employing nanoparticles loaded with chemotherapeutic drugs demonstrated an excellent antitumor effect. In conclusion, hyperthermia treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment of gastrointestinal cancers, offering advantages over traditional therapies.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions, and ultimately, patient outcomes. However, heterogeneity of therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness, and highlight how epigenetic activity may inform therapeutic response. We conclude by providing perspectives on the future of therapeutic targeting of epigenetic enzymes, an approach which holds untapped potential to improve breast cancer patient outcomes.

(1) Background: Breast cancer is a frequent heterogeneous disorder diagnosed in woman and is a high cause of mortality of them in reason to rapid metastasis and disease recurrence. Ferroptosis can inhibit breast cancer cell growth, improve the sensitivity of chemotherapy and radiotherapy and inhibit distant metastases so potentially acts on tumor micro-environment; (2) Methods: Ferroptosis/Extracellular matrix remodeling literature text-mining results were integrated in breast cancer transcriptome cohort according their distant relapse free survival (DRFS) under adjuvant therapy (anthracyclin+taxanes) and also in MDA-MB-231 transcriptome functional experiments with ferroptosis activations (GSE173905); (3) Results: Ferroptosis/Extracellular matrix remodeling text-mining identified 910 associated genes in at list 10 articles. Univariate Cox analyses censored on breast cancer (GSE25066) selected 252 individual significant genes and 171 of them found with an adverse expression. Functional enrichment of these 171 adverse genes predicted basal breast cancer signatures. By text-mining some ferroptosis significant adverse selected genes shared citations in domain of ECM remodeling such as: TNF, IL6, SET, CDKN2A, EGFR, HMGB1, KRAS, MET, LCN2, HIF1A, TLR4. A molecular score based on expression the eleven genes was found predictive of worst prognosis breast cancer at univariate level: basal subtype, short DRFS, high grade values 3 and 4, estrogen and progesterone receptors negative and nodal stages 2 and 3. This eleven gene signature was validated as regulated by ferroptosis inductors (erastin and RSL3) in triple negative breast cancer cellular model MDA-MB-231.; (4) Conclusions: Crosstalk between ECM remodeling-Ferroptosis functionalities allowed to define a molecular score which have been characterized as an independent adverse parameter in prognosis of breast cancer patients. Gene signature of this molecular score have been validated to be regulated by erastin/RSL3 ferroptosis activators. This molecular score could be promising to evaluate ECM impact of ferroptosis target therapies in breast cancer.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in differential growth inhibition across the 60-cell line panel of the NCI Developmental Therapeutic Program (DTP). Many natural products and synthetic analogues are revealed, as potential NAD(P)H:quinone oxidoreductase 1 (NQO1) substrates through correlations to dipyridoimidazo[5,4-f]benzimidazoleiminoquinone (DPIQ), and as potential thioredoxin reductase (TrxR) inhibitors, through correlations to benzo[1,2,4]triazin-7-ones and pleurotin. The strong correlation to NQO1 infers the enzyme has a major influence on the amount of active compound with benzo[e]perimidines, phenoxazinones, benz[f]pyrido[1,2-a]indole-6,11-quinones, seriniquinones, kalasinamide, indolequinones, and furano[2,3-b]naphthoquinones, hypothesized as prodrugs. Compounds with very strong correlations to known TrxR inhibitors had inverse correlations to the expression of both reductase enzymes, NQO1 and TrxR, including naphtho[2,3-b][1,4]oxazepane-6,11-diones, benzo[a]carbazole-1,4-diones, pyranonaphthoquinones (including kalafungin, nanomycin A, and analogues of griseusin A), and discorhabdin C. Quinoline-5,8-dione scaffolds based on streptonigrin and lavendamycin can correlate to either reductase. Inhibitors of TrxR are not necessarily (imino)quinones, e.g., parthenolides, while oxidizing moieties are essential for correlations to NQO1, as with the mitosenes. Herein, an overview of synthetic methods and biological activity of each family of heterocyclic imino(quinone) is provided.

Blood-based circulating cell free DNA(cfDNA) detection offers a non-invasive and easily accessible way for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to develop the clinical biomarkers. For example, cfDNA with genetic alterations often compose a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from health population will be important for the cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in small amount of cfDNA-based cancer test. We hypothesize that, the combination of diverse types of cancer studies on cfDNA can provide us a new insight to identify low-frequency genetic variant across cancer types for early clinical detection of cancers. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritize 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting to membrane, some of which are tumor suppressor, oncogene and related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as the common biomarkers in early cancer diagnosis.

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second most common cause of death due to cancer. About 30% of patients with PCa who have been castrated develop a castration-resistant form of the disease (CRPC), which is incurable. In the last decade, new treatments that control the disease have emerged, slowing progression and spread, and prolonging survival while maintaining the quality of life. These include immunotherapies; however, we do not yet know the optimal combination and sequence of these therapies with the standard ones. All therapies are not always suitable for every patient due to co-morbidities or adverse effects of therapies or both, so there is an urgent need for further work on new therapeutic options. Advances in cancer immunotherapy with an immune checkpoint inhibition mechanism (e.g., ipilimumab, an anti-CTLA-4 inhibitor) have not shown a survival benefit in patients with CRPC. Other immunological approaches have also not given clear results, which has indirectly prevented breakthrough for this type of therapeutic strategy into clinical use. Currently, the only approved form of immunotherapy for patients with CRPC is a cell-based medicine, but it is only available to patients in some parts of the world. Based on the experience gained from recently completed clinical research on immunotherapy with dendritic cell-based immunohybridomas, the aHyC dendritic cell vaccine, for patients with CRPC, we highlight the current status, and possible alternatives that should be considered in the future.

Abstract: Cancer patients are explored by CT-scans more than others. The study reports the local prevalence of these embolisms, the oncological profile of the cases as well as the therapeutic management. Patients and methods: The work was based on the Analysis of the CT-examinations performed on patients of the Radiology department, for reasons other than the search for pulmonary embolism. The examinations are interpreted by 2 radiologist doctors. Results: In 389 patients, 12 cases of asymptomatic pulmonary embolism were detected, representing a prevalence of the order of 3%. The mean age of onset is 67 years. 11 patients had metastatic cancer at the time of diagnosis of pulmonary embolism. 4 PE patients are proximal, while 8 others had segmental and / or sub-segmental PE. 10 patients are treated for carcinomas, the rest for melanoma and splenic lymphoma. After analysis of clinical records, 3 of the 4 proximal pulmonary embolisms were manifested by a discrete clinical symptom attributed to diagnoses other than pulmonary embolism. 10 patients are undergoing chemotherapy alone or combined with radiotherapy, surgery or hormone therapy. At the time of the diagnosis of pulmonary embolism, 3 patients were hospitalized, while 9 were followed up on an outpatient basis. Conclusion: Asymptomatic pulmonary embolism in cancer patients is becoming more frequent. Asymptomatic pulmonary embolisms are mainly peripheral, segmental or sub-segmental. As for symptomatic VTE, asymptomatic pulmonary embolism is diagnosed in patients with metastatic cancer, especially carcinoma type, and treated with chemotherapy.

Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.

Marine seaweeds are nature’s largesse resource in human well-being. Seaweed’s contribution to the food industry is being widened for its rich source of essential vitamins, minerals, and PUFA. ‘Nori’ is a dried sheet of red seaweed Porphyra sp. used to make ‘sushi’ a renowned cuisine in Japan, and other Southeast Asian countries. In this present study, commercial-grade ‘Nori’ was extracted and fractionated with different solvents, and subjected to evaluate the cytotoxic activity on human ovarian tetracarcinoma cells (PA1). As a result, the ethyl acetate fraction was found effective in inhibiting the proliferation of human ovarian cancer cells with an IC50 value of 41.1 µg/mL. The main component responsible for anticancer activity was determined as a sesquiterpene lactone Tatridin B (3h-cyclodeca[b]furan-2-one, 4,9-dihydroxy-6-methyl-3,10-dimethylene-). Moreover, it was found effective in inhibiting NSD2, an important and recently proposed biomarker for several types of cancer. This is a hitherto report on the presence of this compound in ‘Nori’ showing potent anticancer activity on human ovarian tetracarcinoma (PA1).

Background of the Study: We investigated the link between hypertension and cancer since it has been suggested that hypertension may raise the long-term risk of cancer. Previous large observational cohort studies found that greater blood pressure (BP) was related to a higher risk of cancer. Mendelian randomization (MR) was utilized to produce less confounded blood pressure estimates (BP) on overall and site-specific malignancies. The study aims to draw conclusions on the relationship between high blood pressure and cancer. Methods: Studies on high blood pressure and various malignancies are inconclusive, except for renal cell carcinoma. However, given that most meta-analyses only contained a limited number of trials, some relative risks had small to moderate magnitudes, and several may have been impacted by residual confounding, careful interpretation is necessary. The study was conducted using the meta-analysis technique. Cochran's Q test and I2 test were used to assess statistical heterogeneity between studies in the current investigation for research involving two or more cause and outcome combinations. Results: Positive correlations were also reported between high blood pressure and esophageal adenocarcinoma, squamous cell carcinoma, liver, and squamous cell carcinoma. However, most studies lacked multivariable adjustments. Physical and numerical risk of cardiovascular disease is linked to bowel cancer but no other cancers. According to a meta-analysis, hypertensive persons could also be at increased danger of gastrointestinal and breast cancer. Most meta-analyses comprised several trials with moderate or mild hazard ratios.ConclusionDifferent types of cancers have been noted to be directly caused by hypertension. In addition, some treatments have also been associated with the side effects of cancer treatments to cause hypertension. Women facing hypertension have an increased risk of getting breast cancer. Although some cancers showed a real relationship with hypertension, others had no connection at all.

Introduction: The aim of our study was to evaluate the efficacy and toxicity of a daily-adaptive MR-guided SBRT on 1.5 T MR-linac in patients affected by lymphnode oligometastases from PCa. Materials and Methods: The present study is a prospective observational study conducted in a single institution (protocol n°: MRI / LINAC n. 23748). Patients with oligometastatic lymphnodes from PCa treated with daily-adaptive MR-guided SBRT on 1.5T MR-linac were included in the study. Minimum required follow-up of 3 months after SBRT. Primary end-point was local progression-free survival (LPFS). Secondary end-points were: nodal progression-free survival (NPFS), and progression-free survival (PFS), and toxicity. Results: 118 lymphnode oligometastases from PCa were treated with daily-adaptive 1.5T MR-guided SBRT in 63 oligometastatic patients. 63.5% patients were oligoprogressive and 36.5% oligoprogressive. Two-year LPFS was 94.5%. Median NPFS was 22.3 months, and the 2-year NPFS was 46.5%. Having received hormone therapy before SBRT was correlated with lower NPFS at the multivariate analysis (1-y NPFS 87.1% versus 42.8%; p= 0.002 - HR 0.199, 95% CI 0.073-0.549). Furthermore, the oligorecurrent state during ADT was correlated with a lower NPFS than the oligoprogressive state. Median PFS was 10.3 months, the 2-year PFS was 32.4%. Patients treated with hormone therapy before SBRT had a significantly lower 1-year PFS the others (28% versus 70.4%; p= 0.01 - HR 0.259, 95% CI 0.117-0.574). No acute and late toxicities occurred during treatment. Conclusion: the present is the largest prospective study of 1.5T lymphnode SBRT on MR-linac in patients with PCa. Lymphnode SBRT by 1.5T MR-linac provides high local control rates with an excellent toxicity profile.

Skin cancer is an uncommon but serious malignancy. Dermoscopic images examination and biopsy are required for cancer detection. Deep learning (DL) is extremely effective in learning characteristics and predicting malignancies. However, DL requires a large number of images to train. Image augmentation and transferring learning were employed to overcome the lack of images issue. In this study we divided images into two categories: benign and malignant. To train and test our models, we used the public ISIC 2020 database. Melanoma is classified as malignant in the ISIC 2020 dataset. Along with categorization, the dataset was studied to demonstrate variation. The performance of three top pretrained models was then benchmarked in terms of training and validation accuracy. Three optimizers were employed to optimize the loss: RMSProp, SGD, and ADAM. Using ResNet, VGG16, and MobileNetV2, we obtained training accuracy of 98.73%, 99.12%, and 99.76%, respectively. Using these three pretrained models, we attained a validation accuracy of 98.39%.

The G protein-coupled receptor (GPCR) Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations of Smo have been identified in various other tumours, although their oncogenic effect remains unknown in these tissues. Drug resistance is a common challenge in cancer therapies targeting Smo, and data analysis shows that healthy individuals also harbour resistance mutations. Based on the importance of Smo in cancer progression and the high incidence of resistance towards Smo inhibitors, this review suggests that detection of Smo variants through tumour profiling could lead to increased precision and improved outcomes of anti-cancer treatments.

Seemingly normal tissues progressively become populated by mutant clones over time. Most of these clones bear mutations in well-known cancer genes but only rarely do they transform into cancer. This poses questions on what triggers cancer initiation and what implications somatic variation has for cancer early detection. We analysed recent mutational screens of healthy and cancer-free diseased tissues to compare somatic drivers and the causes of somatic variation across tissues. We then reviewed the mechanisms of clonal expansion and their relationships with age and diseases other than cancer. We finally discussed the relevance of somatic variation for cancer initiation and how it can help or hinder cancer detection and prevention. The extent of somatic variation is highly variable across tissues and depends on intrinsic features, such as tissue architecture and turnover, as well as the exposure to endogenous and exogenous insults. Most somatic mutations driving clone expansion are tissue-specific and inactivate tumour suppressor genes involved in chromatin modification and cell growth signalling. Some of these genes are more frequently mutated in normal tissues than cancer, indicating a context-dependent cancer promoting or protective role. Mutant clones can persist over a long time or disappear rapidly, suggesting that their fitness depends on the dynamic equilibrium with the environment. The disruption of this equilibrium is likely responsible for their transformation into malignant clones and knowing what triggers this process is key for cancer prevention and early detection. Somatic variation should be considered in liquid biopsy, where it may contribute cancer-independent mutations, and in the identification of cancer drivers, since not all mutated genes favouring clonal expansion also drive tumourigenesis. Somatic variation and the factors governing homeostasis of normal tissues should be taken into account when devising strategies for cancer prevention and early detection.

Cigarette smoking and air pollution (particulate matter) are recognized as two major etiological factors for lung cancer. Of all the risk factors, cigarette smoking is significantly associated with lung carcinogenesis. The main mechanism lies in the metabolically activated carcinogens (majorly polycyclic aromatic hydrocarbons and nitrosamines), which could covalently bind with DNA molecules and lead to irreversible mutations in pivotal cancer genes, such as TP53 and KRAS. Another major etiological factor for lung cancer is air pollution, which is with complex compositions and ubiquitous in daily life, especially in developing countries as China and India. The latest literatures on lung cancer epidemiology and etiology have been briefly summarized and reviewed in this work.

Introduction The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 Gy is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the presented study to assess the safety of dose escalation up to 84 Gy. Patients and methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients had received 84 Gy (35 without pelvis- and 27 with pelvis-radiotherapy). Regarding acute toxicities, no adverse events > grade 2 occurred. 12.5% of patients treated with 80Gy, in 25.7% of patients treated with 84 Gy excluding pelvis, and in 51.9% of patients treated with 84Gy including pelvis suffered from Grade 2 GU acute toxicity (80 Gy versus 84 Gy: p=0.186; with pelvis versus without pelvis: p=0.032). Grade 2 GI toxicity occurred in 12.5% of patients irradiated with 80Gy, in 14.3% of patients treated with 84 Gy excluding pelvis, and in 12.9% of patients treated with 84Gy including pelvis (80 Gy versus 84 Gy: p=0.582; with pelvis versus without pelvis: p=0.510).GU late toxicity of grade ≥ 2 occurred in 4.2% of patients treated with 80 Gy, in 7.1% of patients treated with 84 Gy excluding pelvic RT, and in 18.2% of patients treated with 84 Gy including pelvic RT (logrank-test p=0.237). 8.3% of patients treated with 80 Gy, in 3.6% of patients treated with Gy excluding pelvic RT, and in 0% of patients treated with 84 Gy including pelvic RT suffered from GI late toxicity of grade ≥ 2(logrank-test p=0.358). Conclusion We were able to show that dose-escalated RT in PCA up to 84 Gy is feasible and safe without asubstantial increase in toxicity. Further follow up is needed to assess survival.

Skin cancer is an exquisite disease globally nowadays. Because of the poor contrast and apparent resemblance between skin and lesions, automatic identification of skin cancer is complicated. The rate of human death can be massively reduced if melanoma skin cancer can be detected quickly using dermoscopy images. In this research, an anisotropic diffusion filtering method is used on dermoscopy images to remove multiplicative speckle noise and the fast-bounding box (FBB) method is applied to segment the skin cancer region. Furthermore, the paper consists of two feature extractor parts. One of the two features extractor parts is the hybrid feature extractor (HFE) part and another is the convolutional neural network VGG19 based CNN feature extractor part. The HFE portion combines three feature extraction approaches into a single fused feature vector: Histogram-Oriented Gradient (HOG), Local Binary Pattern (LBP), and Speed Up Robust Feature (SURF). The CNN method also is used to extract additional features from test and training datasets. This two-feature vector is fused to design the classification model. This classifier performs the classification of dermoscopy images whether it is melanoma or non-melanoma skin cancer. The proposed methodology is performed on two ordinary datasets and achieved the accuracy 99.85%, sensitivity 91.65%, and specificity 95.70%, which makes it more successful than previous machine learning algorithms.

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

Abstract – Objective: Ovarian cancer, although not possessing a high incidence, is still the most common cancer-related deaths among women diagnosed with a gynecologic malignancy. The present study aims to highlight the epidemiology, risk factors of this disease and the significance of development of improved early detection strategies. Materials and Methods: This study was conducted using current published English studies by searching PubMed and Google Scholar. The search strategy included the keywords “ovarian cancer”, “diagnosis”, “risk factors”, “screening”, “epidemiology”. Studies on incidence and mortality were also considered. Case reports were excluded.Results: The highest incidence and mortality rates are observed in Central and Eastern Europe, while rates are relatively low in Asia and Africa. These rates are highest among the white population (14.3 per 100,000) and lowest among blacks (10 per 100,000) and Asians (9.7 per 100,000). The risk factors for this disease includes a family history, hormonal factors, nutrition and diet and physical activity, with some of them playing protective roles in reducing risk of ovarian cancers. There are no reliable screening methods for ovarian cancers. The most common diagnosis methods include a transvaginal ultrasound and a blood test to detect CA125 markers.Conclusions: The mortality rate of ovarian cancer is gradually increasing; thus, preventative measures are required to reduce lifetime risk of ovarian cancers and improve mortality rate.

Findings of new targeted treatments with adequate safety evaluations is essential for better cancer cures and mortality rates. Immunotherapy holds promise for patients with relapsed disease, with the ability to elicit long-term remissions. Emerging promising clinical results in B-cell malignancy using gene-altered T-lymphocytes uttering chimeric antigen receptors have sparked a lot of interest. This treatment could open the path for a major difference in the way we treat tumors that are resistant or recurring. Genetically altered T cells used to produce tumor-specific chimeric antigen receptors are resurrected field of adoptive cell therapy by demonstrating remarkable success in the treatment of malignant tumors. Because of the molecular complexity of chimeric antigen receptors -T cells, a variety of engineering approaches to improve safety and effectiveness are necessary to realize larger therapeutic uses. In this study, we investigate at new strategies for enhancing chimeric antigen receptors-T cell therapy by altering chimeric antigen receptors proteins, T lymphocytes, and their relations with other solid tumor microenvironment (TME) aspects.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responds to immunotherapy. The relationships between tumor DNA damage response, the immune system and immunotherapy have recently attracted attention. Accumulating evidence indicate that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsible to immunotherapy, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of gastric adenocarcinoma. The results showed that DRGS high score patients showed significantly better therapeutic outcomes compared to DRGS low score patients (P < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocytes infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival and may benefit more from ICB therapy, as compared to the low-score patients. Therefore, the DRGS and its scoring system may have implications in tailoring immunotherapy in gastric cancers.

Background: HMGA2 encodes a small non histone chromatin-associated protein that has no intrinsic transcriptional activity, but can modulate transcription by altering the chromatin architecture. HMGA2 was found overexpressed in a variety of epithelial and mesenchymal tumors and promoted invasion and metastasis in most malignant epithelial tumors. A recent study showed that P53 inhibited CRC progression by targeting HMGA2. However, the mechanism by which HMGA2 affect angiogenesis in CRC has not been clarified. Methods: The expression of HMGA2 was analyzed by IHC, WB and bio infomatic analysis. Cbioportal and mexpress online tools were applied to explore the CNV and methylation of HMGA2 in CRC patients. Single cell data from GEO was used to examine the specific cell type that contribute to the high HMGA2 expression in CRC. Lentivirus was used to knock down HMGA2 in CRC cells and HUVECs was used to study angiogenesis. Results: In the current study, we first detected the expression pattern of HMGA2 in CRC patients and evaluated its clinical values and CNV amplification could possibly contribute to the up regulation of HMGA2 in CRC patients. By analyzing CRC single cell data we found that HMGA2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of HMGA2 suppresses angiogenesis via dual regulation of VEGF-A and SEMA3A in CRC through inactivating VEGRR2 pathway in HUVECs. Conclusions: HMGA2 might be a promising prognostic marker and target for treating advanced CRC patients.

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote bladder cancer development directly by stimulating bladder urothelium and indirectly by suppressing immunity. We are particularly interested in natural killer (NK) cells because they are important, but often overlooked anti-cancer lymphocytes.

Background: Esophageal cancer was hardly diagnosed in early stage, and more potential biomarkers should be found. Methods: 252 patients and normal controls which recruited in Renmin Hospital of Wuhan University, were divided into esophageal carcinoma group (105 cases), disease control group (75 cases) and the control group of healthy people (72 cases). Moreover, TISIDB and GEPIA databases were used to investigate the different expression of EC and normal tissues, and explore the roles of C1q in tumor-immune system interactions in EC. Results: The concentration of serum C1q in EC group is 196.8(180~219.4) mg/L, which is higher than the level of DC [178.10(153.70~200.85) mg/L]and HC [183.00(167.75~201.00) mg/L] (P<0.05). A higher expression level of C1q was observed in Ⅲ and Ⅳ grades [214(192~237.3) mg/ml] than grades Ⅰ and Ⅱ [180.95(172.03~193.85) mg/L] (P<0.05). C1q was positively correlated with eosinophils, active CD8 T cells, myeloid derived suppressor cells, natural killer cells, monocytes and macrophages (r = 0.373; r = 0.659; r = 0.846; r = 0.760; r = 0.499; r = 0.757; P<0.05). Conclusion: The concentrations of C1q increased in EC and related to the severity of EC, which had potential value of diagnosis of EC. There were correlations in C1q and tumor-infiltrating lymphocytes.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC) may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

Ongoing concerns regarding the morbidity and mortality from cancer-associated thrombosis led the European Cancer Patient Coalition (ECPC), the voice of cancer patients across Europe, to create a pan-European cancer-associated awareness patient survey to assess CAT knowledge among a large population of patients with cancer. The ECPC survey represents the largest of its kind amongst patients/caregivers with CAT and identified significant gaps in patient awareness and knowledge of CAT. It also identified a need for educational CAT-related discussions and interventions between healthcare professionals and patients with cancer and their caregivers. The aim of this paper is to highlight these gaps and to provide healthcare professionals with awareness of what information should be shared with patients/caregivers as well as how and when that information should be provided. Notably, the importance of providing information on CAT risk and risk factors, how to reduce their risk of CAT, the role of anticoagulant prophylaxis and treatment (short- and long-term) including possible side-effects, and finally how to early identify CAT symptoms. Here we outline what type of information should be provided, as well as when and how to best discuss CAT with our oncology patients and their caregivers along the cancer care continuum, to reduce the risk of CAT and associated complications with a goal of improving patient outcomes.

Biologists seek to identify a small number of significant features that are important, non-redundant, and relevant from diverse omics data. For example, statistical methods like LIMMA and DEseq distinguish differentially expressed genes between a case and control group from the transcript profile. Researchers also apply various column subset selection algorithms on genomics datasets for a similar purpose. Unfortunately, genes selected by such statistical or machine learning methods are often highly co-regulated, making their performance inconsistent. Here, we introduce a novel feature selection algorithm that selects highly disease-related and non-redundant features from a diverse set of omics datasets. We successfully applied this algorithm to three different biological problems: a) disease to normal sample classification, b) multiclass classification of different disease samples, and c) disease subtypes detection. Considering classification ROC-AUC, False-positive, and False-negative rates, our algorithm outperformed other gene selection and differential expression (DE) methods for all six types of cancer datasets from TCGA considered here for binary and multiclass classification problems. Moreover, genes picked by our algorithm improved the disease subtyping accuracy for four different cancer types over the state-of-the-art methods. Hence, we posit that our proposed feature reduction method can support the community to solve various problems, including the selection of disease-specific biomarkers, precision medicine design, and disease sub-type detection.

Breast cancer is the most widespread malignancy in women from corner to corner of the world. Nanostructured lipid carrier (NLC) proved its efficacy in the treatment of cancer. NLC loaded with Imatinib (IMA) (NANIMA) was prepared and evaluated for in vitro efficacy in MCF-7 breast cancer cells. Hot homogenization method was used for the preparation of NANIMAs. Aqueous solution of surfactants (hot) was mixed with molten mixture of stearic acid and sesame oil (hot) under homogenization. The prepared NANIMAs were characterized and evaluated for size, polydispersity index, zeta potential, encapsulation efficiency, release studies, stability studies and MTT assay (cytotoxicity studies). The optimized NANIMA revealed particle size of 104.63 ± 9.55 d.nm, PdI of 0.227 ± 0.06 and EE of 99.79 ± 0.03. All NANIMAs revealed slow and sustained release behaviour. The surfactants used in the preparation of NANIMAs exhibited their effects on particle size, zeta potential, encapsulation efficiency, stability studies and release studies. The cytotoxicity studies unveiled 8.75 times increase in cytotoxicity for optimized NANIMA (IC50 = 6 µM) when compared with IMA alone (IC50 = 52.5 µM) on MCF-7 breast cancer cells. After this, NLC containing IMA possibly will be employed for the cure of breast cancer. A lesser amount of IMA loaded NLC will be sufficient than IMA alone for the treatment of breast cancer. Moreover, the patient will exhibit not as much of adverse effects as in case of IMA alone. Consequently, NANIMA could prove to be useful for effective therapeutic outcome in breast cancer treatment.

Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

Cancer is one of the health concerns in modern societies. The application of nanotechnology in medical sciences has created new possibilities for the diagnosis, imaging and the treatment of tumors in humans. The present article reviews the application of marine-based gold nanoparticles in diagnosing and treating cancer. The main data were collected from research article on the application of different marine-based gold nanoparticles in detecting and imaging cancer cells as well as in drug delivery system in treatment of cancer. Chitosan is the most used marine natural compound used to fabricate gold nanocomposites and the most reported application of this type of nano-composites is related to drug delivery system. Despite the excellent anticancer potential of different marine natural products, less studies have been conducted on the use of their compositions with gold nanoparticles in cancer therapy than other materials. Moreover, most reports available in this filed are related to their application as a drug delivery system not anticancer drug. In general, there are still challenges and limitations to the use of nanoparticles in medicine, it is hoped that in the near future nanoparticles will create a dramatic revolution not only in oncology but also in medicine.

The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.

Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. We analyzed recurrence and mortality dynamics in randomized clinical trials (RCTs) from Australia and Canada. The combined Australian RCTs evaluated, at median follow-up of 8.3 years, an 8-month pragmatic exercise intervention in 337 women with newly diagnosed breast cancer, while the Canadian RCT evaluated, at median follow-up of 7.4 years, supervised aerobic or resistance exercise during chemotherapy in 242 patients. For each RCT, the control arm consisted of patients undergoing usual care. We estimated the event dynamics by the discrete hazard function, through flexible regression of yearly conditional event probabilities with generalized additive models. In the considered RCTs, the recurrence and mortality risk of patients enrolled in the physical activity arm was stably reduced at medium/long term after five year of follow-up. In the Australian RCTs where patients were recruited by urban versus rural area, the latter group did not display benefit from physical activity. Estimated Odds Ratios (95% Confidence Intervals) for Disease Free Survival (DFS) in urban women were 0.63 (0.22-1.85); 0.27 (0.079-0.90); 0.11 (0.013-0.96) at the 3rd, 5th and 7th year of follow-up, respectively. For rural women, DFS patterns were overlapping with ORs approximating 1 at the different years of follow-up. Although not reaching statistical evidence, the estimates in the Canadian trial were in line with the results from the Australian urban women with ORs (95% CI) forDFS of 0.70 (0.33-1.50); 0.47 (0.19-1.18); 0.32 (0.077-1.29) at 3rd, 5th, 7th follow-up year, respectively. While we acknowledge that the analyzed RCTs were not designed for investigating disease recurrence over time, these results support the evidence that physical activity reduces the risk of developing medium/long-term metastases. Additional translational research is needed to clarify the mechanisms underlying these observations.

Dehydrodiisoeugenol (DEH), a novel lignan component extracted from the Nutmeg seeds, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anti-cancer activity in gastrointestinal cancer is still to be investigated. Here, the anti-cancer effect of DEH to human colorectal cancer and its underlying mechanism were evaluated. The DEH treatment arrests the cell cycle of colorectal cancer cells at G1/S phase, which leading to a significant cell growth inhibition. Moreover, it can induce strong cellular autophagy and the autophagy would be inhibited through autophagic inhibitors with reducing EDH-induced inhibition of cell growth in colorectal cancer cells. Further studies indicated that DEH can also induce endoplasmic reticulum (ER) stress, and could subsequently stimulating autophagy through activating PERK/eIF2α and IRE1α/XBP-1s/CHOP pathways. Knockdown of PERK or IRE1α can significantly decrease the DEH-induced autophagy and retrieve cell viability in cells treated with DEH. What’s more, DEH exhibits significant anti-cancer activities through CDX- and PDX-model as well. Taken together, our studies strongly suggest that DEH might be a potential anti-cancer agent against colorectal cancer via activating ER stress-induced autophagy inhibition.

The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the improvements in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa in latest years. The USA SEER Research Data (2000-2017) were analyzed using the SEER*Stat software. The Kaplan-Meier method and Cox regression were used. Patients with de novo mPCa were allocated to 3 cohorts based on year of diagnosis: A (2000-2003), B (2004-2010), C (2011-2014). Maximum follow-up was fixed to 5 years. Overall, 26434 patients were included. Age, race and metastatic stage significantly affected OS and CSS. After adjustment for age and race, patients in cohort C showed 9% reduced risk of death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) and 8% reduced risk of cancer-specific death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) compared to those in cohort A. After adjustment for age, race and metastatic stage, patients in cohort C showed an improvement in OS and CSS compared to cohort B (HR:0.94 [95% CI, 0.91-0.97], p=0.001 and HR:0.89 [95% CI, 0.85-0.92], p&lt;0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between cohort B and C. In conclusion, the prognosis of de novo mPCa remains poor with a median OS of 30 months and a median CSS of 35 months. Limited OS and CSS improvements were observed in latest years.

Endometrial Cancer (EC) is the sixth most commonly occurring cancer in women with 380 000 cases in 2018. Sadly, EC morbidity and mortality are continuously increasing, therefore the medical society have a substantial need for an accurate and inexpensive diagnostic test for EC early detection and a prognostic tool for treatment planning and evaluation. Considering experience with different types of cancers C-reactive protein (CRP) appears to be a promising diagnostic and prognostic factor. Aiming to investigate its potential and in view of EC authors, this paper reviewed the following databases for metanalysis, randomized controlled trials and review articles published up to June 2020: Pubmed, Scopus, Google scholar and ClinicalKey. Studies indicate CRP >3.33 mg/l correlate with EC incidence with HR = 2.29 (p<0.05). Moreover, High-sensitivity CRP assay allows to detect CRP in very low concentrations and distinguish patients with endometriosis, soft tissue sarcomas and possibly EC. Preoperational and postoperational CRP, as well as its dynamic change are independent prognostic factors for EC and are more reliable if analyzed together. However, CRP-to-albumin ratio as well as Glasgow Prognostic Scale have greater prognostic value that CRP alone. Additionally, CRP is possibly a mediator of carcinogenesis and cancer progression through activation of inter alia FcgRs/MAPK/ERK, FcgRs/IL-6/AKT/STAT3 and FcgRs/NF-κB/NLRP3 pathways.

Background: Lung cancer is one of the common causes of death worldwide. Although the incidence rate of lung cancer in Western countries is decreasing, it presents a growing trend in developed countries. Since there is no accurate enough information about the epidemiological and Histopathologic features of lung cancer in central Iran, Isfahan, we were motivated to conduct this research. Materials and Methods: This was a descriptive, cross-sectional study carried out in central Iran, Isfahan. All demographic, histopathological and clinical data of the lung cancer patients registered in MACSA, a referral charity-based cancer center in central Iran, was analyzed within 2012-2018 using SPSS v.22 software. Results: Altogether 260 patients with lung cancer were included in this study from 6127 cancer patients registered within 2012-2018 (4.2%). Out of them, 66.2% were men, and 18.8 % of the patients were alive at the time of the study. The mean age of the patients at diagnosis was 61.56 (SD=14.11, range: 9-93). Altogether, 63.1% of patients had metastasis of whom 57.6% were in stage IV at diagnosis. The Frequency of different types of lung cancer was 36.9% adenocarcinomas, 14.2% squamous cell carcinoma, 9.6% bronchogenic carcinoma and 8.1% small cell lung cancer, respectively. Altogether, 128 cases were smokers with an average 35.45 ± 14 pack- years. Only in 36.2% of the patients, the diagnostic and therapeutic biomarkers had been checked, and CK7 was positive in 88.9% of the cases in which the biomarker had been checked. Conclusion: Despite to similar Iranian studies, the most common histopathologic type of lung cancer among the patients was adenocarcinoma that it may be attributed to the lower consumption of smoking in our population and their different genetic context. Molecular biomarkers had been checked in a small portion of the patients. More education of the clinicians along with the development of cancer molecular testing may lead to promote the personalized-based approach.

To systematically investigate the epidemiology of breast cancer risk factors in Iran, we performed a systematic search via PubMed, Scopus, Web of Science and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models.Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47-2.12), HRT (OR: 5.48, 95%CI 0.84-1.74), ER positive (OR: 1.87, 95%CI 1.41-2.33), PR positive (OR: 1.84, 95%CI 1.38-2.29), stress condition (OR: 2.67, 95%CI 1.84-3.50), passive smokers (OR: 1.68, 95%CI 1.34-2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19-5.63), abortion (OR: 1.84, 95%CI 1.35-2.33), sweets consumption (OR: 1.71, 95%CI 1.32-2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07-2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32-0.83), nulliparity (OR: 0.68, 95%CI 0.39-0.96), 13 to 24 months of breastfeeding (OR: 0.68, 95%CI 0.46-0.90), daily exercise (OR: 0.59, 95%CI 0.44-0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10-0.46).This study suggest that factors such as family history, HRT, ER and PR positive status, stress condition, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13-24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.

HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that HIF-1α interaction with NQO1 inhibits its proteasomal degradation, thus suggesting that targeting the stability of NQO1 could led to destabilization of HIF-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, we review here our current knowledge on the intracellular functions and stability of NQO1, its pharmacological modulation by small ligands, and the molecular determinants of its roles as a chaperone of many different proteins including cancer-associated factors such as p53 and p73α. This knowledge is then discussed in the context of potentially targeting the intracellular stability of HIF-1α by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies.

Breast cancer (BC) is the most frequent form of malignancy and the second only to lung cancer as common cause of cancer-causing deaths in women. Notwithstanding many progresses in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet patients‘ needs, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level expressed in cancer cells of patients or as antigens on the surface of cell membranes. Fibroblast growth factor receptor (FGFR) is a druggable target -which is activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation. Herein we provide an update on the knowledge on genetic alterations of the receptors in breast cancer, their role in tumorigenesis and the most recent drugs against this particular receptor to treat the disease.

Epithelial-mesenchymal transition (EMT) has been well recognized for its essential role in cancer progression as well as normal tissue development. In cancer cells, activation of EMT permits the cells to acquire migratory and invasive abilities and stem-like properties. However, simple categorization of cancer cells into epithelial and mesenchymal phenotypes misleads the understanding of the complicated metastatic process, and contradictory results from different studies also indicate the limitation of application of EMT theory in cancer metastasis. Nowadays, growing evidence suggests the existence of an intermediate status between epithelial and mesenchymal phenotypes, i.e., the “hybrid epithelial-mesenchymal (hybrid E/M)”state, provides a possible explanation for those conflicting results. Appearance of hybrid E/M phenotype offers a more plastic status for cancer cells to adapt the stressful environment for proceeding metastasis. In this article, we review the biological importance of the dynamic changes between the epithelial and the mesenchymal states. The regulatory mechanisms encompassing the translational, post-translational, and epigenetic control for this complex and plastic status are also discussed .

Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoral breast cell lines. We identified putative regulatory elements, containing CCVs, that loop to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumor suppressor gene. Furthermore, the risk allele of CCV rs12155535, located in another DUSP4 enhancer element, was negatively correlated with looping of this element to the DUSP4 promoter region, suggesting that this allele would be associated with reduced expression. These findings provide the first evidence that CCV risk alleles downregulate DUSP4 expression, suggesting that this gene is a regulatory target of the 8p12 breast cancer risk locus.

After reviewing cancer theories, cancer treatment development histories, randomized clinical trial's performance, cancer treatment strategy, trial follow-up times, and conducting numerous simulations using existing data, the authors found: (1) medical treatments come with three to four lethal factors: treatment side-effects, emotional distress and chronic dress, lack of exercises or physical inactivity, and excessive nutrition in some cases; (2) clinical trial exaggerates the benefits of fast-acting treatments and underestimates the slow-delivering adverse side effects as a result of statistical averaging, interfering effects of personal lifestyle factors, and insufficient follow-up times; (3) the benefits of medical treatments are limited by chain comparison, where surgery sets up a negative standard relative to the best way for resolving cancer; (4) the strategy of destroying the tumor is unworkable; (5) medical treatments can turn natural cancer growth curve into approximately doubly exponential curve; (6) multiple factor non-medical measures are much more powerful than medical treatments in controlling cancer growth and metastasis rates; and (7) cancer early diagnosis and over treatments are bad strategies that have great adverse impacts on cancer patients. Based on huge increases in cancer growth rate constants, substantial of loss of organ functional capacity, and severe systemic aging-like cellular damages, the authors concluded that medical treatments promote cancer growth and metastasis rates and shorten patient lives in most cases, and the claimed benefits are caused by triple biases of clinical trials. The authors believe that the better strategy for ending the global cancer epidemic is abandoning clinical trails as the research model, changing caner treatment strategy from killing cancer cells to slowing down cancer growth rates by using multiple factors optimization approach in personalized medicine.

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis, published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial-mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

CCCTC-binding factor (CTCF) is a conserved transcription factor that performs diverse roles in transcriptional regulation and chromatin architecture. Cancer genome sequencing reveals diverse acquired mutations in CTCF, which we have shown, functions as a tumour suppressor gene. While CTCF is essential for embryonic development, little is known of its absolute requirement in somatic cells and the consequences of CTCF haploinsufficiency. We examined the consequences of CTCF depletion in immortalised human and mouse cells using shRNA knockdown and CRISPR/Cas9 genome editing and examined the growth and development of heterozygous Ctcf (Ctcf^+/-) mice. We also analysed the impact of CTCF haploinsufficiency by examining gene expression changes in CTCF-altered endometrial carcinoma. Knockdown and CRISPR/Cas9-mediated editing of CTCF reduced the cellular growth and colony-forming ability of K562 cells. CTCF knockdown also induced cell cycle arrest and a pro-survival response to apoptotic insult. However, in p53 shRNA-immortalised Ctcf^+/- MEFs we observed the opposite: increased cellular proliferation, colony formation, cell cycle progression and decreased survival after apoptotic insult compared to wild type MEFs. CRISPR/Cas9-mediated targeting in Ctcf^+/- MEFs revealed a predominance of in-frame microdeletions in Ctcf in surviving clones, however protein expression could not be ablated. Examination of CTCF mutations in endometrial cancers showed locus-specific alterations in gene expression due to CTCF haploinsufficiency, in concert with downregulation of tumour suppressor genes and upregulation of estrogen-responsive genes. Depletion of CTCF expression imparts a dramatic negative effect on normal cell function. However, CTCF haploinsufficiency can have growth-promoting effects consistent with known cancer hallmarks in the presence of additional genetic hits. Our results confirm the absolute requirement for CTCF expression in somatic cells and provide definitive evidence of CTCF’s role as a haploinsufficient tumour suppressor gene. CTCF genetic alterations in endometrial cancer indicate that gene dysregulation is a likely consequence of CTCF loss, contributing to, but not solely driving cancer growth.

Ovarian Cancer (OC) is a type of cancer that affects ovaries in women, and is difficult to detect at initial stage due to which it remains as one of the leading causes of cancer death. The ovarian cancer data generated from the Internet of Medical Things (IoMT) was used and a novel approach was proposed for distinguishing the ovarian cancer by utilizing Self Organizing Maps (SOM) and Optimal Recurrent Neural Networks (ORNN). SOM algorithm was utilized for better feature subset selection and was also utilized for separating profitable, understood and intriguing data from huge measures of medical data. In supervised learning techniques, the SOM-based feature selection seems to be a tougher challenge because of the absence of class labels that would guide the search for relevant information to the classifier model. The classification approach can identify ovarian cancer data as benign/malignant. The ovarian cancer detection process can be improved by optimizing the weights of RNN structure using Adaptive Harmony Search Optimization (AHSO). The proposed model in this study can be used to detect cancer at early stages with high accuracy and low Root Mean Square Error (RMSE).

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, the metastatic breast cancer leaves a poor prognosis. In an era of personalized medicine, there is an urgent need for a better knowledge of the biology leading to the disease, which can lead to the design of always more accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the Fibroblast Growth Factor Receptor (FGFR) pathway, triggered by specific ligands. The FGFRs/FGFs axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of the FGFRs mutations leading to tumour formation and summarizes the state-of-the-art of therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.

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

The epidermis is the outermost layer of skin and provides a protective barrier against environmental insults. It is a rapidly renewing tissue undergoing constant regeneration, maintained by several types of stem cells. Hedgehog (HH) ligands activate one of the fundamental signaling pathways that contribute to epidermal development, homeostasis and repair. The HH pathway interacts with other signal transduction pathways such as those activated by Wnt and bone morphogenetic protein. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important to elucidate fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in skin development, homeostasis and basal cell carcinoma formation, providing an update of current knowledge in this field.

Green Tea Catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human Prostate Cancer (PCa) chemoprevention.In the last decades many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown that GTCs specifically interact with cellular targets including, cell surface receptors, lipid rafts and endoplasmic reticulum, modulate gene expression through direct effect on transcription factors or indirect epigenetic mechanisms, interfere with intracellular proteostasis at various levels. Many of the effects observed in vitro are dose and cell context dependent and take place at concentration that cannot be achieved in vivo.Poor intestinal absorption together with an extensive systemic and enteric metabolism influence GTCs bioavailability through still poor understood mechanisms. Recent efforts to develop delivery systems that increase GTCs overall bioavailability, by mean of biopolymeric nanoparticles, represent the main way to translate preclinical results in a real clinical scenario for PCa chemoprevention.

Neuroblastoma (NB) is a solid tumor occurring in infancy and childhood, whose high-risk form has currently a survival rate &lt; 50 %, despite aggressive treatments. Additionally, drugs-induced secondary tumorigenesis and the emergency of drug resistance worsen the already worrying scenario, calling for an urgent development of new extra-genomic treatments. Quaternary phosphonium salts (QPSs) possess both antimicrobial and anticancer effects. Triphenyl phosphonium salts (TPPs) are mitochondria-targeting compounds, exerting anticancer effects, impairing mitochondria functions and damaging DNA, at the same time. TPP-based bola-amphiphiles, previously proven to self-assemble nanoparticles (NPs) in water and successfully assayed as possible antibacterials, were never tested as suitable antitumor agents. Here, aiming at the development of new antitumor devices to counteract resistant forms of NB, the anticancer effects of a TPP-based amphiphile molecule have been investigated for the first time. To this end, we considered the water-soluble sterically hindered quaternary phosphonium salt (BPPB) encompassing two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying both the characteristics of mitochondria-targeting compounds and those of bola-amphiphiles. The anticancer effects of BPPB were assessed against HTLA-230 human stage-IV NB cells and their counterpart resistant to etoposide (ETO), doxorubicin (DOX) and to many other therapeutics (HTLA-ER). Determined IC50 values were very low on both cell populations, already after 24 hours of treatment, when cells viability did not significantly differ from that observed for the longest exposure timing. Moreover, to investigate a putative future inclusion of BPPB in a chemotherapeutic cocktail for NB, its cytotoxic effects were assessed against mammalian cell lines. These included monkey kidney cells (Cos-7), human hepatic cells (HepG2), a lung-derived fibroblast cell line (MRC-5) and red blood cells. From appreciable to very high selectivity indices have been determined after 24 hours treatments, an exposure time after which both NB cell populations tested appeared already fully exterminated.

Aim: In our study, the chemotherapeutic drug doxorubicin (Dox) and the natural anticancer property thymoquinone (TQ) were applied to OVCAR3 human ovarian adenocarcinoma cells and human skin keratinocyte cell line HaCat cells, and their cytotoxic effects were investigated through the EGFR/FOXP3 signaling pathway. Materials and Methods: In our study, different doses of thymoquinone and doxorubicin were applied to the cells for 24, 48 and 72 hours and the cytotoxicity level was determined by the MTT method. With Western blot and qRT-PCR analysis, metastasis markers Epidermal growth factor receptor (EGFR) and forkhead box p3 (FOXP3) and apoptosis marker apoptosis inbibitory 5 (API5) genes and their expression levels were examined. Colony counting was performed after DAPI staining and its effect on cell proliferation was determined. An in vitro wound model for metastasis was created and cell migration was evaluated morphologically. All results were analyzed statistically. Results: By the cell viavility test, it was found that cytotoxicity was at the highest level in the TQ and Dox applied group, metastasis was prevented especially in the TQ and Dox combined treatment group, and by qRT-PCR analysis, the activity in the EGFR and FOXP3 pathway decreased the most with TQ and the amount of protein decreased with TQ and Dox. Conclusion: As a result of the study, it was seen that the highest cytotoxic effect and the highest apoptosis induction occurred with TQ treatment. Additionally, it was determined that a significant decrease in EGFR and FOXP3 levels occurred in TQ and Dox applications.

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

Acute myeloid leukemias are characterized by genetic alterations that lead to a complete or partial block at various stages of myeloid differentiation, leading to continual proliferation of myeloid progenitor cells. These alterations can include a well-documented chromosomal translocation that leads to the synthesis of the PML-retinoic acid receptor fusion protein that leads to a block in differentiation and the ability to induce differentiation with all-trans retinoic acid and other small molecules. In essence, in large part, the disease is due to stem cell-like cells that are blocked in their ability to undergo terminal differentiation to more mature, non-proliferative cell types. We discovered a long non-coding RNA (lncRNA), lncRNAp53int1, encoded from the first intron of the p53 tumor suppressor gene. Interestingly, lncRNAp53int1 appears to play an important regulatory role in maintaining the undifferentiated and proliferative state in a manner independent from p53 gene expression. lncRNAp53int1 is expressed at high levels in proliferating, undifferentiated promyelocytes and its levels fall significantly during their terminal differentiation to non-proliferating granulocytes or macrophages. Furthermore, forced overexpression of lncRNAp53int1 blocks terminal differentiation. The observation that the expression of this lncRNA is repressed during terminal differentiation of human leukemic cells and its expression blocks differentiation of leukemic myeloid progenitor cells, is likely to have clinical implications with regards to differentiation therapy for myeloid leukemia. Ongoing research aims to identify the molecular partners that it associates with and the signaling pathways that this lncRNA participates in with the long-term goal of identifying molecules that inhibit lncRNAp53int1 activity and serve as potential therapeutic drugs. The goal of this mini-review is to disseminate these novel and interesting findings to readers and to describe where we think this research is headed and the impact it can have on myeloid leukemias.

Delta 9 tetrahydrocannabinol (Δ-9-THC or THC), the primary psychoactive constituent of marijuana, has been found to affect the human body in a variety of ways. According to the Substance Abuse and Mental Health Services Administration (SAMHSA) of the U.S. Department of Health and Human Services, the amount of THC in marijuana has steadily climbed over the past few decades, with today's marijuana having three times the concentration of THC compared to 25 years ago. Inhalation is a major route of exposure, allowing substances to enter the body via the respiratory tract. Therefore, it is imperative to understand the molecular underpinning of THC exposure in the lung epithelium, as lung cells receive significant amounts of THC during marijuana smoking. In this study, the transcriptional alterations caused by various concentrations of THC in non-cancerous human bronchial epithelial cell line (BEAS-2B) were studied. THC exposure (0, 800, 1000, 1200, and 1500 ng/mL) caused a significant dose-dependent decrease in cell viability after 24-hour exposure. Transcriptome analysis showed a distinct dose-dependent response. HIF-1 signaling, ferroptosis, AMPK signaling, and immunogenic pathways were activated by upregulated genes associated with dosing concentration of THC. Glutathione and fatty acid metabolic pathways were significantly altered by THC-dependent downregulated genes. and downregulated genes and their associated pathways in BEAS-2B cells. Ingenuity Pathway Analysis revealed several top canonical pathways altered by THC exposure, among which ferroptosis, NRF-2 mediated oxidative stress response, caveolar mediated endocytosis (loss of cell adhesion to the substrate), tumor microenvironment, HIF1alpha signaling, and the unfolded protein response pathways were the major pathways affected. The top genes that were significantly altered as a result of THC exposure were HMOX1, CDK7, HLA-C, and SLC39A4. Present results suggested that THC exposure can induce a variety of effects, including cell death, which may involve ferroptosis and the NRF-2 signaling pathway. Moreover, the Δ-9-THC-induced cell death was ameliorated by inhibiting the ferroptosis pathway. In contrast, the ferroptosis agonist exacerbated the cell death process, suggesting that Δ-9-THC utilizes the ferroptosis pathway to induce cell death in bronchial epithelial cells.