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Colorectal cancer (CRC) is the third most prevalent cancer. Ongoing research aims to uncover the causes of CRC, with a growing focus on the role of gut microbiota (GM) in carcinogenesis. The GM influences CRC development, progression, treatment efficacy, and therapeutic toxicities. For example, Fusobacterium nucleatum and Escherichia coli can regulate microbial gene expression through the incorporation of human small noncode RNA and potentially contribute to cancer progression. Metallic nanoparticles (MNPs) have both negative and positive impacts on GM, depending on their type. Several studies state that titanium dioxide may increase the diversity, richness, and abundance of probiotics bacteria, whereas other studies demonstrate dose‐dependent GM dysbiosis. The MNPs offer cytotoxicity through the modulation of MAPK signaling pathways, NF‐kB signaling pathways, PI3K/Akt signaling pathways, extrinsic signaling pathways, intrinsic apoptosis, and cell cycle arrest at G1, G2, or M phase. MNPs enhance drug delivery, enable targeted therapy, and may restore GM. However, there is a need to conduct well‐designed clinical trials to assess the toxicity, safety, and effectiveness of MNPs‐based CRC therapies. [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum, a gram‐negative anaerobic bacterium abundantly found in the human oral cavity, is widely recognized as a key pathobiont responsible for the initiation and progression of periodontal diseases due to its remarkable aggregative capabilities. Numerous clinical studies have linked F. nucleatum with unfavorable prognostic outcomes in various malignancies. In further research, scholars have partially elucidated the mechanisms underlying F. nucleatum's impact on various types of cancer, thus gaining a certain comprehension of the role played by F. nucleatum in cancer. In this comprehensive review, we present an in‐depth synthesis of the interplay between F. nucleatum and different cancers, focusing on aspects such as tumor initiation, metastasis, chemoresistance, and modulation of the tumor immune microenvironment and immunotherapy. The implications for cancer diagnosis and treatment are also summarized. The objective of this review is to enhance our comprehension of the intricate relationship between F. nucleatum and oncogenic pathogenesis, while emphasizing potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: Mast cells, their serine proteinase tryptase, and immunoglobulin E (IgE) can be involved in cutaneous carcinogenesis. Materials and methods: To study the association of tryptase+ and IgE+ cells with photodamage and skin cancers 385 adult patients (201 males, 184 females, 75 with immunosuppression) at risk of any type of skin cancer were examined. Skin biopsies were taken from the sun-protected medial arm and from the photodamaged dorsal forearm skin followed by immunohistochemical staining for tryptase and IgE. Results: The results show that tryptase+ and IgE+ cells are significantly higher in number in the photodamaged than sun-protected skin, both in immunocompetent and -compromised subjects, and there is a strong correlation between tryptase+ and IgE+ cells. The numbers of forearm tryptase+and especially IgE+cells associated significantly with the forearm photodamage severity. In the logistic regression analysis, the forearm to upper arm ratio of IgE+ cells produced a univariate odds ratio of 1.521 (p=.010) and a multivariate one of 3.875 (p=.047) for the history of squamous cell carcinoma. The serum level of total IgE correlated significantly to the IgE to tryptase ratio in both skin sites. Conclusions: Therefore, IgE+ mast cells participate in photodamage and carcinogenesis, though it is unclear whether they are tumor-protective or -causative. [ABSTRACT FROM AUTHOR]

Conventional therapies for metastatic cancers have limited efficacy. Recently, cancer therapies targeting noncancerous cells in tumor microenvironments have shown improved clinical outcomes in patients. However, further advances in our understanding of the metastatic tumor microenvironment are required to improve treatment outcomes. Adipocytes are distributed throughout the body, and as a part of the metastatic tumor microenvironment, they interact with cancer cells in almost all organs. Adipocytes secrete various factors that are reported to exert clinical effects on cancer progression, including engraftment, survival, and expansion at the metastatic sites. However, only a few studies have comprehensively examined their impact on cancer cells. In this review, we examined the impact of adipocytes on cancer by describing the adipocyte-secreted factors that are involved in controlling metastatic cancer, focusing on adipokines, such as adiponectin, leptin, visfatin, chemerin, resistin, apelin, and omentin. Adipocyte-secreted factors promote cancer metastasis and contribute to various biological functions of cancer cells, including migration, invasion, proliferation, immune evasion, and drug resistance at the metastatic sites. We propose the establishment and expansion of "adipo-oncology" as a research field to enhance the comprehensive understanding of the role of adipocytes in metastatic cancers and the development of more robust metastatic cancer treatments. [ABSTRACT FROM AUTHOR]

The revised Kyoto guidelines have a new catalog of high-risk stigmata and worrisome features for the risk stratification of intraductal papillary mucinous neoplasms (IPMNs). We aimed to validate the stratification system in terms of short- and long-term risks of pancreatic carcinoma. We included 3336 patients diagnosed with IPMNs in 2000–2021 and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma diagnosis. We used the multivariable competing-risks proportional hazards regression model to calculate subdistribution hazard ratios for long-term incidence of pancreatic carcinoma with adjustment for potential confounders. In short-term analyses, pancreatic carcinomas were prevalent predominantly in IPMNs with high-risk stigmata (49% vs 1.3% and 0.05% in IPMNs with worrisome features and no risk factors, respectively). In long-term analyses of worrisome features, the main pancreatic duct diameter of 5–9.9 mm, acute pancreatitis, and IPMN growth rate of 2.5 mm/y were associated with a high incidence with multivariable subdistribution hazard ratios of 3.46 (95% confidence interval [CI], 2.04–5.89), 5.65 (95% CI, 1.86–17.2), and 3.83 (95% CI, 2.14–6.86), respectively. An increasing number of worrisome features at baseline was associated with a higher prevalence and incidence of pancreatic carcinoma (P trend <.001). Patients with 1, 2, and 3–4 worrisome features had multivariable subdistribution hazard ratios for pancreatic cancer incidence of 1.43 (95% CI, 0.93–2.19), 2.17 (95% CI, 1.17–4.05), and 10.1 (95% CI, 4.20–24.5), respectively (vs no positive feature). The revised Kyoto criteria stratify IPMN patients well in terms of the short- and long-term risks of pancreatic carcinoma diagnosis, potentially informing personalized patient management. [ABSTRACT FROM AUTHOR]

The immune system serves as a fundamental defender against the initiation and progression of cancer. Failure of the immune system augments immunosuppressive action that leading to cancer manifestation. This immunosuppressive effect causes from significant alterations in immune checkpoint expression associated with tumoral progression. The tumor microenvironment promotes immune escape mechanisms that further amplifying immunosuppressive actions. Notably, substantial targeting of immune checkpoints has been pragmatic in the advancement of cancer research. This study highlights a comprehensive review of emerging druggable targets aimed at modulating immune checkpoint co-inhibitory as well as co-stimulatory molecules in response to immune system activation. This modulation has prompted to the development of newer therapeutic insights, eventually inducing immunogenic cell death through immunomodulatory actions. The study emphasizes the role of immune checkpoints in immunogenic regulation of cancer pathogenesis and explores potential therapeutic avenues in cancer immunotherapy. Modulation of Immunosuppressive and Immunostimulatory pathways of immune checkpoints in cancer immunotherapy [ABSTRACT FROM AUTHOR]

The intestinal microbiota, having enormous metabolic potential, makes a significant contribution to the physiological and pathological processes of humans and animals and is currently considered as an important factor in the pathogenesis of cancer. The aim of this study is to determine changes in the quantitative and qualitative composition of the intestinal microbiota in Wistar rats during chemical induction of breast cancer (BC). Material and methods. The work was performed on female Wistar rats (n = 40) aged 3 months, weighing 200–210 g, using cultural methods for studying fecal microbiota in intact rats (1 group) on the 1st, 14th, 35th days and in rats with induction of breast cancer and and in rats, whereby N-methyl-N-nitrosourea was administered to induce breast cancer (2 group) on the 1st (before injection of N-methyl-N-nitrosourea), 14th, 35th days after injection of N-methyl-N-nitrosourea. Results and discussion. In all experimental animals, representatives characteristic of the intestinal normobiota of warm-blooded animals predominated, namely: Bifidobacterium spp., Lactobacillus spp., Escherichia coli with pronounced enzymatic properties, Enterococcus spp., Clostridium spp. In addition, Staphylococcus spp., yeast-like fungi of the genus Candida and mold. Escherichia coli with reduced enzymatic activity was also detected. It was established that the isolated bacteria belonged to 3 types, 4 classes, 5 orders, 6 families, 6 genera of the bacterial domain. Also, 2 genera of fungi belonging to the order Saccharomycetales were isolated. The most significant changes in the composition of the intestinal microbiota were noted in rats with chemically induced breast cancer on the 35th day tumor induction: the appearance of pathogenic microflora in the intestine was revealed.

Objective To investigate the expression level of long non-coding RNA (lncRNA) AL365181.2 in cholangiocarcinoma (CHOL) and its effect on the functional characteristics of CHOL cells. Methods The Cancer Genome Atlas (TCGA) database was used to compare the expression level of lncRNA AL365181.2 between cancerous tissue and paracancerous tissue in CHOL patients, and the association between the expression level of lncRNA AL365181.2 and immune cell infiltration in CHOL tissue was analyzed. The Gene Set Enrichment Analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for lncRNA AL365181.2. EdU assay, wound healing assay, Transwell assay, and xenograft tumor formation experiment were used to investigate the impact of lncRNA AL365181.2 on the proliferation, migration, invasion, and tumorigenic abilities of CHOL cells. Results The analysis of TCGA data showed that the expression level of lncRNA AL365181.2 in CHOL tissue was significantly higher than that in paracancerous tissue (Z=4.00,P

Abstract Rational Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial “field” of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases). Methods Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot. Results (a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs. Conclusions These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis.

Carbon nanotubes (CNTs), members of the nanomaterial family, are increasingly being used in consumer products and extensively studied for various biomedical applications. Due to their benign elemental composition, large surface area, and chemical and biological activities, CNTs demonstrate great potential in cancer therapy, including drug delivery, imaging analysis, photothermal therapy, photodynamic therapy, and radiotherapy. However, there is still a major knowledge gap when it comes to transitioning from research to clinical applications. One of the important issues is that the biological toxicity of CNTs, especially in terms of carcinogenesis, and the underlying mechanisms are not fully understood. Therefore, a thorough evaluation of toxicity and the underlying mechanisms of carcinogenesis is essential to enable the wide application of CNTs. In this review, we summarize the recent progress of CNTs as multifunctional therapeutics in cancer therapy. Furthermore, a detailed discussion is provided on the carcinogenesis and potential mechanisms of CNTs. Finally, the review ends with further challenges and prospects for CNTs with the expectation of facilitating their broader utilization.

Abstract High Mobility Group A2 (HMGA2) oncofetal proteins are a distinct category of Transcription Factors (TFs) known as “architectural factors” due to their lack of direct transcriptional activity. Instead, they modulate the three-dimensional structure of chromatin by binding to AT-rich regions in the minor grooves of DNA through their AT-hooks. This binding allows HMGA2 to interact with other proteins and different regions of DNA, thereby regulating the expression of numerous genes involved in carcinogenesis. Consequently, multiple mechanisms exist to finely control HMGA2 protein expression at various transcriptional levels, ensuring precise concentration adjustments to maintain cellular homeostasis. During embryonic development, HMGA2 protein is highly expressed but becomes absent in adult tissues. However, recent studies have revealed its re-elevation in various cancer types. Extensive research has demonstrated the involvement of HMGA2 protein in carcinogenesis at multiple levels. It intervenes in crucial processes such as cell cycle regulation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, cancer cell stemness, and DNA damage repair mechanisms, ultimately promoting cancer cell survival. This comprehensive review provides insights into the HMGA2 protein, spanning from the genetic regulation to functional protein behavior. It highlights the significant mechanisms governing HMGA2 gene expression and elucidates the molecular roles of HMGA2 in the carcinogenesis process. Graphical Abstract

Abstract Hepatocellular carcinoma (HCC) remains a major global health concern with limited therapeutic options and poor prognosis. Chemokines have emerged as critical regulators in the progression and metastasis of HCC. This study aims to investigate the mechanisms involved in CCL28-promoted progression of HCC and provide novel therapeutic targets for HCC treatment. Relationship between CCL28 expression and HCC progression were investigated by bioinformatic analysis and immunohistochemical staining assays. CCK-8, Transwell, and colony formation assay were conducted to explore the impact of CCL28 on the growth, migration and invasion of HCC cells. Quantitative real-time PCR and western blotting assays were performed to learn potential molecular mechanisms underlying the transformation of HCC driven by CCL28. The results showed that there was a direct link between increased CCL28 levels and the advancement of HCC, leading to a worse outcome. CCL28 significantly augmented malignant transformation of HCC cells, containing proliferation, migration, invasion, and clonogenicity, via activation of PDGFD-regulated MMP9 and VEGFA pathways. CCL28 emerges as a pivotal contributor to HCC tumorigenesis, propelling HCC development through the PDGFD signaling pathway. Our findings unveil potential therapeutic targets for HCC treatment.

It is known that chronic social stress leads to immunity disorders in humans and experimental animals. It has been shown that the effect of stress is also manifested in changes in the level of expression of genes involved in the functioning of various physiological systems in the brain of mice, in particular, in the hypothalamus. It was noted that in stressed animals, genes involved in the processes of carcinogenesis and apoptosis change their expression, and in animals without signs of developing a malignant process, but under conditions conducive to tumor growth. In this regard, we used the RNA-seq method to study the expression of cytokine response genes in the hypothalamus of male mice under the influence of chronic social stress caused by repeated experience of defeats in intermale confrontations, compared with control individuals. Multidirectional changes in the expression of cytokine genes, their receptors and genes performing a regulatory function were detected (IL17d, IL18, IL33, Csf1r, Csf2ra, IL11ra1, IL13ra1, IL2ra, IL3ra, IL5ra, Lifr, Cish, IL4i1, Irf1, Irf5, Irf9, Jak2, Socs3, Stat3, Tgfb1, Tlr3). Thus, it has been shown that changes in the cytokine response in the brain under the influence of stress occur at the level of changes in gene expression. In this case, we should not talk about the activation of the system or a decrease in its activity, but about the disruption of its functioning. Next, we analyzed the correlations between the level of expression of genes of the cytokine system and the main genes of carcinogenesis and apoptosis that we studied earlier (Akt1, Bag6, Foxp4, Mapk3, Mapk8, Nol3, Pdcd10, Xiap). The Akt1, Jak2, Stat3 genes were identified, for which the maximum number of correlations was found, moreover, negative correlations were most characteristic of Jak2, and positive correlations were most characteristic of Stat3 and Akt1. In addition, protein-protein interactions between genes of carcinogenesis and apoptosis and genes of the cytokine system were analyzed using the String database in mice under chronic social stress. It was confirmed the key role of these genes in the development of dysfunction of cytokines in the brain.

Background. In oncology, of particular interest is the study of the T-cell receptor excision circles (TREC) and the κ-deletion B-cell receptor excision circles (KREC), which are extrachromosomal DNA structures. In many malignancies, the effectiveness of immune checkpoint inhibitors depends on the mutational load of the tumor, which correlates with the formation of specific antitumor immunity. Quantitative indicators of recombination excision circles reflect the occurrence of a different repertoire of T-cell receptors, an integral component in the formation of specific immunity. Understanding the change in quantitative values of TREC and KREC in cancer patients can improve the selection of patients for immunotherapy. Aim. To determine quantitative indicators of TREC and KREC for immunological evaluation of patients with malignancies. Materials and methods. The study included 55 healthy individuals and 180 patients with malignancies. Among healthy individuals, 49.1% (27/55) were males and 50.9% (28/55) females. Among patients with malignancies, 20.5% (37/180) were males and 79.5% (143/180) females. The median age in healthy individuals was 36 years [Q1–Q3: 26–58]. The median age in the group of patients with malignancies was 57 years [Q1–Q3: 47.5–67]. Results. In the general population of healthy individuals, the median TREC level was 60.1 [Q1-Q3: 31.3-188.9] and the median KREC level was 256 [Q1-Q3: 149.8-353]. In the general population of patients with malignancies, the median TREC rate was 4.6 [Q1-Q3: 0.9-17.3] and the median KREC was 111.9 [Q1-Q3: 29.3-339.28]. According to the results of the study, we noted statistically significant differences in TREC and KREC indices between all patients with malignancies and healthy individuals (p0.001, p=0.001). Analysis of TREC and KREC indices in patients with malignancies of various localizations (breast cancer, ovarian cancer, lung cancer, colorectal cancer, skin melanoma, lymphomas) in comparison with healthy individuals statistically significant differences in TREC level were noted (p=0.001, p0.001). When analyzing the KREC level in the studied groups, statistically significant differences in patients with ovarian malignancies (p0.001), lymphoma (p0.001), colorectal cancer (p=0.001) and melanoma (p=0.039) in comparison with healthy individuals were obtained. When comparing groups pairwise, it was found that TREC level in patients with malignancies in the age group of 25–44 years was significantly higher than in the age group of 45–60 years (p=0.03); TREC level in the age group of 25–44 years was significantly higher than in the age group of persons over 60 years (p0.001); TREC level in the age group of 45–60 years was significantly higher than in the age group over 60 years (p0.001). Statistically significant differences of KREC level in the studied patients with malignancies depending on the age group were not established (p=0.16), there were no age differences of groups by KREC level. Conclusion. The results demonstrate a significant decrease in TREC and KREC levels in patients with malignancies compared to healthy individuals. The study of TREC and KREC excision circles in peripheral blood is one of the promising approaches for the immunological evaluation of cancer patients.

Background/Aims Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the microbiome during gastric carcinogenesis in structural and functional aspects, with a specific focus on the association between oral and gastric microbiomes. Methods We collected saliva, gastric juice, and gastric tissue samples from 141 patients at different stages of gastric carcinogenesis and processed them for microbiome analysis using 16S rRNA gene profiling. The alpha and beta diversities were analyzed, and the differences in microbiome composition and function profiles were analyzed among the groups, as well as the correlation between changes in the oral and gastric microbiomes during carcinogenesis. Results We observed significant differences in microbial diversity and composition between the disease and control groups, primarily in the gastric juice. Specific bacterial strains, including Schaalia odontolytica, Streptococcus cristatus, and Peptostreptococcus stomatis, showed a significant increase in abundance in the gastric juice in the low-grade dysplasia and gastric cancer groups. Notably, the correlation between the oral and gastric microbiota compositions, increased as the disease progressed. Predictive analysis of the metagenomic functional profiles revealed changes in functional pathways that may be associated with carcinogenesis (ABC transport and two-component systems). Conclusions During gastric carcinogenesis, the abundance of oral commensals associated with cancer increased in the stomach. The similarity in microbial composition between the stomach and oral cavity also increased, implying a potential role of oral-gastric bacterial interactions in gastric cancer development.

INTRODUCTION. The development of malignant neoplasms is associated with changes in the expression of small non-coding RNAs (miRNAs). This emphasises the need for research into the development of miRNA-targeted inhibitors as a promising approach to cancer treatment.AIM. This study aimed to compare current strategies for suppressing the functional activity of tumour-associated miRNAs based on the use of therapeutic nucleic acids and to determine the application potential of these strategies.DISCUSSION. This study analysed known oligonucleotide-based miRNA inhibitors with different mechanisms of action. Based on their mechanism of action, miRNA-targeted inhibitors can be classified into two groups. The first group of miRNA-targeted inhibitors exhibits an indirect inhibitory effect, either by blocking functional connections between miRNAs and specific mRNA targets through the use of miRNA-masking oligonucleotides or by introducing mutations into miRNA genes and disrupting gene biosynthesis processes through the use of the CRISPR/Cas system. Despite their relatively high biological potential, these strategies are mostly used as search tools to study miRNA functional roles and molecular interactions in carcinogenesis. The second group of oligonucleotide constructs interacts with miRNA targets directly, which leads to steric blocking or degradation of oncogenic microRNAs. These miRNA-binding oligonucleotide constructs come in a variety of structural variants, including miRNA sponges, RNA zippers, antisense oligonucleotides, and miRNases, which demonstrate high therapeutic potential in vitro and in vivo.CONCLUSION. The described analysis of the biological properties, therapeutic potential, and key advantages of the developed miRNA-targeted oligonucleotide constructs helps outline the areas for their potential practical application in cancer treatment.

The authors have studied, analyzed, and summarized the data from publications of recent decades regarding the effect of vitamin D on the outcomes of breast cancer treatment, the place and role of its active form and metabolites at the stages of carcinogenesis, in vivo and in vitro manifestations of its “non-classical” effects, prediction of the possible practical application of the results obtained at the molecular-cellular level. Studying the potential influence of vitamin D on the effectiveness of systemic therapy for breast cancer occupies an impor­tant place in modern research. The connection between vitamin D deficiency and breast cancer is a field of extensive debate that continues on many aspects (risk factors, predictors, treatment effectiveness, survival). In this literature review, which included studies different in design and sampling, we attempted to systematize the results obtained in recent years on this topic and to evaluate their potential implementation in clinical practice. Particularly noteworthy are scientific works of various designs devoted to identifying the potential predictive influence of initial and final vitamin D levels on the success of neoadjuvant treatment and enhancement of tumor response in patients with locally advanced breast cancer. The systematized data obtained serve as a vector for further scientific research among patients with breast cancer in Ukraine.

Humans have generally evolved some adaptations to protect against UV and different levels of background ionizing radiation. Similarly, elephants and whales have evolved adaptations to protect against cancer, such as multiple copies of the tumor suppressor gene p53, due to their large size and long lifespan. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Humans living in regions with high levels of background radiation, e.g. in Ramsar, Iran where exposure rates exceed those on the surface of Mars, seem to have developed some kind of protection against the ionizing radiation. However, humans in general have not developed cancer-fighting adaptations, so they instead rely on medical technologies and interventions. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Studying elephant adaptations may provide insights into new cancer prevention and treatment strategies for humans, but further research is required to fully understand the evolutionary disparities.

Hepatitis B virus (HBV) infection is a significant health problem that can result in progression to liver cirrhosis, decompensation, and the development of hepatocellular carcinoma (HCC). On a country level, the prevalence of chronic HBV infection varies between 0.1% and 35.0%, depending on the locality and the population being investigated. One-third of all liver cancer fatalities worldwide are attributable to HBV. The adoption of standard birth-dose immunization exerted the most significant impact on the decline of HBV prevalence. HCC incidence ranges from 0.01% to 1.40% in noncirrhotic patients and from 0.9% to 5.4% annually, in the settings of liver cirrhosis. Although antiviral therapy significantly reduces the risk of developing HBV-related HCC, studies have demonstrated that the risk persists, and that HCC screening is still essential. This review discusses the complex relationship between HBV infection and HCC, recent epidemiological data, different aspects of clinical disease characteristics, and the impact of antiviral therapy in this context.

Alkylating agents such as N-Ethyl-N-Nitrosourea (ENU) are ubiquitous within living cells and in the environment. This study designed to evaluate the chemopreventive activity of vanillic acid on ENU-induced toxicity and carcinogenesis in mice as an animal model of chronic lymphocytic leukemia (CLL). The female, Swiss albino mice were divided into three groups each with 7 mice, group I received normal saline, group II, mice received ENU at a dose of 80 mg/kg body weight i.p. to induce CLL on the 31th day of the study, and group III, the mice pretreated with vanillic acid at a dose of 20 mg/kg body weight/day, i.p. up to 30 days and received ENU. The animals were monitored for weight changes and mortality during 120 days, and then were sacrificed for isolation of lymphocytes, as target cells in CLL. Cellular parameters like reactive oxygen species (ROS) formation, malondialdehyde (MDA) production, depletion of glutathione (GSH), mitochondrial membrane potential (MMP) and lysosomal membrane integrity were studied. We found that pretreatment with vanillic acid significantly increased the survival of mice up to 57%, delay in death time (30%) and prevented weight changes after exposure to ENU. In addition, it was found that vanillic acid protected ROS formation, lipid peroxidation mitochondrial dysfunction, and lysosomal membrane destabilization in isolated lymphocytes. These data suggest that vanillic acid exhibited significant protection against ENU-induced toxicity and carcinogenicity, which might be related to the protection of the mitochondria and lysosomes and the reduction of ROS formation and oxidative stress.

Hepatitis C virus (HCV) chronically infects approximately 170 million people worldwide and is a known etiological agent of hepatocellular carcinoma (HCC). The molecular mechanisms of HCV-mediated carcinogenesis are not fully understood. This review article focuses on the oncogenic potential of NS3, a viral protein with transformative effects on cells, although the precise mechanisms remain elusive. Unlike the more extensively studied Core and NS5A proteins, NS3's roles in cancer development are less defined but critical. Research indicates that NS3 is implicated in several carcinogenic processes such as proliferative signaling, cell death resistance, genomic instability and mutations, invasion and metastasis, tumor-related inflammation, immune evasion, and replicative immortality. Understanding the direct impact of viral proteins such as NS3 on cellular transformation is crucial for elucidating HCV's role in HCC development. Overall, this review sheds light on the molecular mechanisms used by NS3 to contribute to hepatocarcinogenesis, and highlights its significance in the context of HCV-associated HCC, underscoring the need for further investigation into its specific molecular and cellular actions. [ABSTRACT FROM AUTHOR]

Background: Patients' expectations regarding medical information in advanced stages of cancer are still poorly understood. Tailoring information to advanced cancer patients is a subtle task. We developed a question prompt list (QPL) that serves as a patient-oncologist communication aid in France. Methods: A four-step sequential mixed method involving patients with luminal B/triple-negative metastatic breast cancer or metastatic uveal melanoma (N = 110) and patients' partners, oncologists, and researchers (N = 18) was used. In-depth interviews and questionnaires focused on the information needed at the disclosure of metastasis or resistance to treatment (step 1), the formulation of questions and procedures for use in oncology visits (steps 2 and 3), and the acceptability of the final tool (stage 4). Results: The initial version of the QPL consists of 17 questions covering 5 themes (disease, current treatment, other options, living with cancer, prognosis). In step 2, 13 questions were added, 2 were merged, and 5 were deleted; a short form (4 questions) and recommendations for clinical use were proposed. In step 3, 2 questions were merged, and 6 were deleted. Four oncologists (27% of the target population) took part in step 4, and the QPL was discussed with 20 patients, revealing a positive appraisal. Conclusion: We provide a rigorously developed, relevant, concise, and acceptable question prompt list for clinical application in the advanced cancer care setting in France. Further research needs to assess whether this tool actually facilitates oncologist–patient communication and improves satisfaction with care and health outcomes. Trial registration: The study is listed on ClinicalTrials.gov (NCT04118062) and registered under identification n° IRRID "International Registered Report Identifier": DERR1-10.2196/26414. [ABSTRACT FROM AUTHOR]

Pregnancy‐associated breast cancer has been increasing. In this study, we analyzed patients with breast cancer that occurred during pregnancy (PrBC) and compared their genetic profiles with those of patients with breast cancer that did not occur during pregnancy, within 1 year after childbirth nor during lactation (non‐PrBC). We performed gene expression analyses of patients with PrBC and non‐PrBC using microarrays and qRT‐PCR. Microarray analysis showed that 355 genes were upregulated in the luminal‐type PrBC group compared to those in the non‐PrBC group. The C‐X‐C motif chemokine ligand 13 (CXCL13) gene was the most upregulated in the PrBC group compared to that in the non‐PrBC group, especially in the luminal A‐type (p = 0.016). This result was corroborated by the qRT‐PCR analysis of microdissected cancer cells (p < 0.001). A negative correlation was observed between CXCL13 and estrogen receptor 1 (ESR1) mRNA expression levels in luminal A‐type breast carcinoma (p < 0.001). Our results provide clues for a better understanding of breast cancer pathogenesis during pregnancy. [ABSTRACT FROM AUTHOR]

Activated Wnt/β-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of β-catenin in liver cancer. SLC13A3 expression is elevated in human liver cancer samples with gain of function (GOF) mutant CTNNB1, the gene encoding β-catenin. Activation of β-catenin up-regulates SLC13A3, leading to intracellular accumulation of endogenous SLC13A3 substrates. SLC13A3 is identified as a low-affinity transporter for glutathione (GSH). Silencing of SLC13A3 downregulates the leucine transporter SLC7A5 via c-MYC signaling, leading to leucine depletion and mTOR inactivation. Furthermore, silencing of SLC13A3 depletes GSH and induces autophagic ferroptosis in β-catenin-activated liver cancer cells. Importantly, both genetic inhibition of SLC13A3 and a small molecule SLC13A3 inhibitor suppress β-catenin-driven hepatocarcinogenesis in mice. Altogether, our study suggests that SLC13A3 could be a promising therapeutic target for treating human liver cancers with GOF CTNNB1 mutations. The therapeutic approaches directly targeting activated β-catenin in liver cancers are restricted by toxicities. Here the authors identify that the solute carrier transporter SLC13A3 is upregulated by activation of β-catenin and silencing of SLC13A3 induces ferroptosis, which could be exploited as a therapeutic opportunity in β-catenin-driven liver cancers. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression. [ABSTRACT FROM AUTHOR]

The placenta, a pivotal organ in mammalian reproduction, allows nutrient exchange and hormonal signaling between the mother and the developing fetus. Understanding its molecular intricacies is essential for deciphering normal embryonic development and pathological conditions such as tumorigenesis. Here, we explore the multifaceted role of the tumor suppressor BRCA1-associated protein 1 (BAP1) in cancer and placentation. Initially recognized for its tumor-suppressive properties, BAP1 has emerged as a key regulator at the intersection of tumorigenesis and placental development. BAP1 influences crucial cellular processes such as cell death, proliferation, metabolism, and response to hypoxic conditions. By integrating insights from tumor and developmental biology, we illuminate the complex molecular pathways orchestrated by BAP1. This perspective highlights BAP1's significant impact on both cancer and placental development, and suggests novel therapeutic strategies that could improve outcomes for pregnancy disorders and cancer. This perspective explores the dual role of the tumor suppressor BAP1 in placental development and cancer. By integrating insights from tumor and developmental biology, the study offers new therapeutic targets for pregnancy disorders and cancer. [ABSTRACT FROM AUTHOR]

Quinazolinone derivatives have garnered attention for their diverse biological activities, including anticancer properties. This review combines findings from 2018 to 2024, focusing on the impact of quinazolinones on cancer cells, tubulin formation, and EGFR/PI3 K pathways. By unraveling the intricacies of structure‐activity relationships, this review endeavors to provide guidance for researchers in identifying promising avenues for the development of cancer treatments. Although in vitro studies underscore significant potential, it is imperative that future research prioritizes pre‐clinical investigations to seamlessly traverse the transitional phase towards clinical applications, thereby propelling the advancement of quinazolinone‐based cancer therapy. [ABSTRACT FROM AUTHOR]

Introduction: The thyroid cancer has the ninth larger incidence of cancer in the world. Investigations related to the exposure to metals have become important due to the sensibility of the thyroid gland to them. Studies reveal that carcinogenic progressions are associated to the deficiency of the essential trace elements. In this context, the zinc is highlighted, essential for the metabolism of the thyroidal hormone and has a potential relation with the pathogenesis of the thyroid cancer. The objective of this systematic review and meta-analysis is to evaluate the low serum zinc as a risk factor for thyroid cancer in adults. Methods and analysis: PubMed/MEDLINE, Scopus, Embase and LILACS databases will be searched for observational studies investigating the low serum zinc as a risk factor for thyroid cancer in adults. No language or publication period restrictions will be imposed. The primary outcome will be that the low serum zinc is a risk factor for thyroid cancer. Three independent reviewers will select the studies and extract data from the original publications. The risk-of-bias will be assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data synthesis will be performed using the R software (V.4.3.1) and to assess heterogeneity, we will compute the I2 statistic and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence. Prospero registration number: International Prospective Register of Systematic Reviews (PROSPERO) CRD42023463747. [ABSTRACT FROM AUTHOR]

Background: Chromosome stability is crucial for homeostasis of pluripotent stem cells (PSCs) and early-stage embryonic development. Chromosomal defects may raise carcinogenic risks in regenerative medicine when using PSCs as original materials. However, the detailed mechanism regarding PSCs chromosome stability maintenance is not fully understood. Methods: Mouse embryonic stem cells (line D3) and human embryonic stem cells (line H9) were cultured under standard conditions. To confirm the loading of RetSat protein on mitotic chromosomes of PSCs, immunostaining was performed in PSCs spontaneous differentiation assay and iPSC reprogramming assay from mouse embryonic fibroblasts (MEFs), respectively. In addition, qPCR, immunoprecipitation, LC-MS/MS and immunoblotting were used to study the expression of RetSat, and interactions of RetSat with cohesin/condensin components. RNA sequencing and teratoma formation assay was conducted to evaluate the carcinogenic risk of mouse embryonic stem cells with RetSat deletion. Results: We reported a PSC high-expressing gene, RetSat, plays key roles in chromosome stabilization. We identified RetSat protein localizing onto mitotic chromosomes specifically in stemness positive cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We found dramatic chromosome instability, e.g. chromosome bridging, lagging and interphase micronuclei in mouse and human ESCs when down regulating RetSat. RetSat knock-out mouse ESCs upregulated cancer associated gene pathways, and displayed higher tumorigenic capacities in teratoma formation assay. Mechanistically, we confirmed that RetSat interacts with cohesin/condensin components Smc1a and Nudcd2. RetSat deletion impaired the chromosome loading dosage of Smc1a, Smc3 and Nudcd2. Conclusions: In summary, we reported RetSat to be a key stabilizer of chromosome condensation in pluripotent stem cells. This highlights the crucial roles of RetSat in early-stage embryonic development, and potential value of RetSat as an effective biomarker for assessing the quality of pluripotent stem cells. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is one of the most common gynecologic cancers. In recent years, research has focused on the genetic characteristics of the tumors to detail their prognosis and tailor therapy. In the case of EC, genetic mutations have been shown to underlie their formation. It is very important to know the mechanisms of EC formation related to mutations induced by estrogen, among other things. Noncoding RNAs (ncRNAs), composed of nucleotide transcripts with very low protein-coding capacity, are proving to be important. Their expression patterns in many malignancies can inhibit tumor formation and progression. They also regulate protein coding at the epigenetic, transcriptional, and posttranscriptional levels. MicroRNAs (miRNAs), several varieties of which are associated with normal endometrium as well as its tumor, also play a particularly important role in gene expression. MiRNAs and long noncoding RNAs (lncRNAs) affect many pathways in EC tissues and play important roles in cancer development, invasion, and metastasis, as well as resistance to anticancer drugs through mechanisms such as suppression of apoptosis and progression of cancer stem cells. It is also worth noting that miRNAs are highly precise, sensitive, and robust, making them potential markers for diagnosing gynecologic cancers and their progression. Unfortunately, as the incidence of EC increases, treatment becomes challenging and is limited to invasive tools. The prospect of using microRNAs as potential candidates for diagnostic and therapeutic use in EC seems promising. Exosomes are extracellular vesicles that are released from many types of cells, including cancer cells. They contain proteins, DNA, and various types of RNA, such as miRNAs. The noncoding RNA components of exosomes vary widely, depending on the physiology of the tumor tissue and the cells from which they originate. Exosomes contain both DNA and RNA and have communication functions between cells. Exosomal miRNAs mediate communication between EC cells, tumor-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and play a key role in tumor cell proliferation and tumor microenvironment formation. Oncogenes carried by tumor exosomes induce malignant transformation of target cells. During the synthesis of exosomes, various factors, such as genetic and proteomic data are upregulated. Thus, they are considered an interesting therapeutic target for the diagnosis and prognosis of endometrial cancer by analyzing biomarkers contained in exosomes. Expression of miRNAs, particularly miR-15a-5p, was elevated in exosomes derived from the plasma of EC patients. This may suggest the important utility of this biomarker in the diagnosis of EC. In recent years, researchers have become interested in the topic of prognostic markers for EC, as there are still too few identified markers to support the limited treatment of endometrial cancer. Further research into the effects of ncRNAs and exosomes on EC may allow for cancer treatment breakthroughs. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among the highest in the world. Cancer development is associated with aberrant signaling pathways. Autophagy is a process of cell self-digestion that maintains the intracellular environment and has a bidirectional regulatory role in cancer. Apoptosis is one of the important death programs in cancer cells and is able to inhibit cancer development. Studies have shown that a variety of substances can regulate autophagy and apoptosis in colorectal cancer cells through signaling pathways, and participate in the regulation of autophagy on apoptosis. In this paper, we focus on the relevant research on autophagy in colorectal cancer cells based on the involvement of related signaling pathways in the regulation of apoptosis in order to provide new research ideas and therapeutic directions for the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Recent advances in genomic research have increasingly focused on the fat massand obesity-associated (FTO) gene due to its notable correlation with obesity. Initially explored for its contribution to increased body weight, FTO was later discovered to function as an m6A demethylase. This pivotal role enhances our understanding of its broader implications across various pathologies. Epigenetic modifications, such as m6A, have been implicated in gynecological cancers, including ovarian, endometrial, and cervical malignancies. However, the precise mechanisms by which FTO influences the development of gynecological cancers remain largely unknown. This analysis underscores the growing relevance of investigations into the FTO gene in elucidating the mechanisms underlying gynecological cancers and exploring potential therapeutic avenues. [ABSTRACT FROM AUTHOR]

Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers' understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most common brain tumor with the worst prognosis. Temozolomide is the only first-line drug for GBM. Unfortunately, the resistance issue is a classic problem. Therefore, it is essential to develop new drugs to treat GBM. As an oncogene, Skp2 is involved in the pathogenesis of various cancers including GBM. In this study, we investigated the anticancer effect of AAA237 on human glioblastoma cells and its underlying mechanism. Methods: CCK-8 assay was conducted to evaluate IC50 values of AAA237 at 48, and 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) was employed to ascertain the status of Skp2 as an intrinsic target of AAA237 inside the cellular milieu. The EdU-DNA synthesis test, Soft-Agar assay and Matrigel assay were performed to check the suppressive effects of AAA237 on cell growth. To identify the migration and invasion ability of GBM cells, transwell assay was conducted. RT-qPCR and Western Blot were employed to verify the level of BNIP3. The mRFP-GFP-LC3 indicator system was utilized to assess alterations in autophagy flux and investigate the impact of AAA237 on the dynamic fusion process between autophagosomes and lysosomes. To investigate the effect of compound AAA237 on tumor growth in vivo, LN229 cells were injected into the brains of mice in an orthotopic model. Results: AAA237 could inhibit the growth of GBM cells in vitro. AAA237 could bind to Skp2 and inhibit Skp2 expression and the degradation of p21 and p27. In a dose-dependent manner, AAA237 demonstrated the ability to inhibit colony formation, migration, and invasion of GBM cells. AAA237 treatment could upregulate BNIP3 as the hub gene and therefore induce BNIP3-dependent autophagy through the mTOR pathway whereas 3-MA can somewhat reverse this process. In vivo, the administration of AAA237 effectively suppressed the development of glioma tumors with no side effects. Conclusion: Compound AAA237, a novel Skp2 inhibitor, inhibited colony formation, migration and invasion of GBM cells in a dose-dependent manner and time-dependent manner through upregulating BNIP3 as the hub gene and induced BNIP3-dependent autophagy through the mTOR pathway therefore it might be a viable therapeutic drug for the management of GBM. [ABSTRACT FROM AUTHOR]

Rational: Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial "field" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases). Methods: Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot. Results: (a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs. Conclusions: These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Cell‐free DNA (cfDNA) fragmentation patterns have immense potential for early cancer detection. However, the definition of fragmentation varies, ranging from the entire genome to specific genomic regions. These patterns have not been systematically compared, impeding broader research and practical implementation. Here, 1382 plasma cfDNA sequencing samples from 8 cancer types are collected. Considering that cfDNA within open chromatin regions is more susceptible to fragmentation, 10 fragmentation patterns within open chromatin regions as features and employed machine learning techniques to evaluate their performance are examined. All fragmentation patterns demonstrated discernible classification capabilities, with the end motif showing the highest diagnostic value for cross‐validation. Combining cross and independent validation results revealed that fragmentation patterns that incorporated both fragment length and coverage information exhibited robust predictive capacities. Despite their diagnostic potential, the predictive power of these fragmentation patterns is unstable. To address this limitation, an ensemble classifier via integrating all fragmentation patterns is developed, which demonstrated notable improvements in cancer detection and tissue‐of‐origin determination. Further functional bioinformatics investigations on significant feature intervals in the model revealed its impressive ability to identify critical regulatory regions involved in cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that physiologically normal skin harbors pervasive mutant clones with cancer drivers. Normal skin has the highest burden of somatic mutations due to persistent ultraviolet exposure throughout life. The mutation burden exponentially increases with age and is further modified by skin site, sun-damage history, and skin phototype. Driver gene profiles in normal skin are similar to those in cutaneous squamous cell carcinoma where NOTCH family, FAT family, and TP53 are consistently reported, while other reported profiles include PPM1D, KMT2D, ASXL1, and RBM10. Normal skin seldom harbors canonical hotspot mutations with therapeutic relevance. The pathologic role of mutant clones with cancer drivers in normal skin is classically considered precursors for skin cancer; however, recent evidence also suggests their putative cancer-protective role. Copy number alterations and other structural variants are rare in normal skin with loss in 9q region encompassing NOTCH1 being the most common. Study methodologies should be carefully designed to obtain an adequate number of cells for sequencing, and a comparable number of cells and read depth across samples. In conclusion, this review provides mutational landscapes of normal skin and discusses their potential implications in the development of skin cancer, highlighting the role of driver genes in early malignant progression. [ABSTRACT FROM AUTHOR]

Lin28A and Lin28B are paralogous RNA‐binding proteins that play fundamental roles in development and cancer by regulating the microRNA family of tumor suppressor Let‐7. Although Lin28A and Lin28B share some functional similarities with Let‐7 inhibitors, they also have distinct expression patterns and biological functions. Increasing evidence indicates that Lin28A and Lin28B differentially impact cancer stem cell properties, epithelial‐mesenchymal transition, metabolic reprogramming, and other hallmarks of cancer. Therefore, it is important to understand the overexpression of Lin28A and Lin28B paralogs in specific cancer contexts. In this review, we summarize the main similarities and differences between Lin28A and Lin28B, their implications in different cellular processes, and their role in different types of cancer. In addition, we provide evidence of other specific targets of each lin28 paralog, as well as the lncRNAs and miRNAs that promote or inhibit its expression, and how this impacts cancer development and progression. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective observational study recruited 380 patients, 115 with lung cancer and 265 in the control group. Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) were significantly higher in cancer patients than in the control group. The correlation of PLR with the probability of lung cancer differs between men and women. CRP values did not differ according to histological types of lung cancer (p = 0.242) and were not associated with the presence of mutations in EGFR (p = 0.679). CRP values were significantly lower in NSCLC patients with PD-L1 mutations than in those without PD-L1 mutations (22.7 [IQR: 10.4;40.3] vs. 76.7 [IQR: 32.6;140] mg/L, p = 0). Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș involving patients with lung cancer. The parameters analyzed included histopathological type (NSCLC: squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters, and associated comorbidities. Results: A total of 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5.30 versus 2.60, p < 0.001; 217 versus 136, p < 0.001, respectively). NLR and PLR differ between men and women (p = 0.005 and p = 0.056, respectively). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusions: The NLR and PLR values may serve as new predictive biomarkers for the diagnosis of disease in patients with lung cancer, especially those with NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is a complex disease arising from an interplay of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. While most cSCC cases can be treated with surgery, metastatic and locally advanced forms have a significantly worse prognosis and limited treatment options. The high mutational burden in cSCC makes it challenging to identify true driver alterations. Beyond genetics, the tumor microenvironment and its interaction with the immune system play a critical role in cSCC progression, evidenced by differences observed between immunocompromised and immunocompetent patients. In recent years, new therapeutic approaches have emerged, including immunotherapy and EGFR inhibitors, which have shown efficacy in treating advanced cSCC. Understanding the underlying mechanisms driving cSCC is crucial for developing novel and more effective therapies. This review aims to provide a comprehensive overview of the mutational landscape and microenvironmental factors in cSCC. Cutaneous squamous cell carcinoma (cSCC) manifests through the complex interactions of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. A high mutational burden is present in cSCC, as well as both cSCC precursors and normal skin, making driver genes difficult to differentiate. Despite this, several key driver genes have been identified, including TP53, the NOTCH family, CDKN2A, PIK3CA, and EGFR. In addition to mutations, the tumor microenvironment and the manipulation and evasion of the immune system play a critical role in cSCC progression. Novel therapeutic approaches, such as immunotherapy and EGFR inhibitors, have been used to target these dysregulations, and have shown promise in treating advanced cSCC cases, emphasizing the need for targeted interventions considering both genetic and microenvironmental factors for improved patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Resistance to standard therapies represents a major challenge in melanoma treatment. This is mainly related to the high heterogeneity of this malignancy due to the presence of different types of cells in the tumor mass. Cancer stem cells (CSCs) are a small subset of cells endowed with self-renewal and tumorigenic capacity and the ability to escape anticancer therapies. Melanoma CSCs can be identified by the expression of biomarkers and intracellular pathways deeply involved in their malignant phenotype. Dissecting the molecular mechanisms underlying CSC biological functions might pave the way for novel therapeutic approaches. Herein, we highlight the intricate bidirectional communication between melanoma CSCs and their surrounding cells in the tumor microenvironment and discuss how this interplay might impact the processes of drug resistance and tumor relapse. We also address the potential benefits of CSC-targeted strategies, in combination with conventional drugs, for improving melanoma treatment strategies. Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are a small subpopulation of cells in different tumors, including melanoma, endowed with distinctive capacities of self-renewal and differentiation into bulk tumor cells. Melanoma CSCs are characterized by the expression of specific biomarkers and intracellular pathways; moreover, they play a pivotal role in tumor onset, progression and drug resistance. In recent years, great efforts have been made to dissect the molecular mechanisms underlying the protumor activities of melanoma CSCs to provide the basis for novel CSC-targeted therapies. Herein, we highlight the intricate crosstalk between melanoma CSCs and bystander cells in the tumor microenvironment (TME), including immune cells, endothelial cells and cancer-associated fibroblasts (CAFs), and its role in melanoma progression. Specifically, we discuss the peculiar capacities of melanoma CSCs to escape the host immune surveillance, to recruit immunosuppressive cells and to educate immune cells toward an immunosuppressive and protumor phenotype. We also address currently investigated CSC-targeted strategies that could pave the way for new promising therapeutic approaches for melanoma care. [ABSTRACT FROM AUTHOR]

Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies. [ABSTRACT FROM AUTHOR]

The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs. The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC). Despite recent advances, it remains challenging to establish causal relationships between microbes and CRC carcinogenesis. In this perspective, we discuss current challenges, recent developments, and research needs. [ABSTRACT FROM AUTHOR]

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Background: Cervical cancer (CC) stands as a significant health threat to women globally, with high-risk human papillomaviruses as major etiologic agents. The DNA damage repair (DDR) protein topoisomerase I (TOP1) has been linked to various cancers, yet its distinct roles and mechanisms in CC are not fully elucidated. Methods: We investigated TOP1 expression in cervical intraepithelial neoplasia (CIN) and CC tissues utilizing qRT-PCR and IHC, correlating findings with patient prognosis. Subsequent knockdown studies were performed in vitro and in vivo to evaluate the influence of TOP1 on tumor growth, DNA repair, and inflammatory responses. Results: TOP1 was highly expressed in CIN and CC, negatively correlating with patient prognosis. Inhibition of TOP1 impeded CC cell growth and disrupted DNA repair. TOP1 was shown to regulate tumor-promoting inflammation and programmed death-ligand 1 (PD-L1) production in a cGAS-dependent manner. HPV oncoproteins E6 and E7 upregulated TOP1 and activated the cGAS-PD-L1 pathway. Conclusions: TOP1 acts as a DNA repair mediator, promoting CC development and immune evasion. Targeting the TOP1-cGAS-PD-L1 axis could be a potential therapeutic strategy for CC. [ABSTRACT FROM AUTHOR]

Dysregulation of epidermal growth factor receptor (EGFR) is one of the most common mechanisms associated with the pathogenesis of various cancers. Mitogen‐inducible gene 6 [MIG6; also known as ERBB receptor feedback inhibitor 1 (ERRFI1)], identified as a feedback inhibitor of EGFR, negatively regulates EGFR by directly inhibiting its kinase activity and facilitating its internalization, subsequently leading to degradation. Despite its proposed role as an EGFR‐dependent tumor suppressor, the functional consequences and clinical relevance in cancer etiology remain incompletely understood. Here, we identify that the stoichiometric balance between MIG6 and EGFR is crucial in promoting EGFR‐dependent oncogenic growth in various experimental model systems. In addition, a subset of ERRFI1 (the official gene symbol of MIG6) mutations exhibit impaired ability to suppress the enzymatic activation of EGFR at multiple levels. In summary, our data suggest that decreased or loss of MIG6 activity can lead to abnormal activation of EGFR, potentially contributing to cellular transformation. We propose that the mutation status of ERRFI1 and the expression levels of MIG6 can serve as additional biomarkers for guiding EGFR‐targeted cancer therapies, including glioblastoma. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. Methods: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. Results: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. Conclusions: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3. [ABSTRACT FROM AUTHOR]

Gastrointestinal malignancies are one of the major worldwide health concerns. In the present review, we have assessed the plausible therapeutic implication of Ursolic Acid (UA) against gastrointestinal cancer. By modulating several signaling pathways critical in cancer development, UA could offer anti-inflammatory, antiproliferative, and anti-metastatic properties. However, being of low oral bioavailability and poor permeability, its clinical value is restricted. To deliver and protect the drug, liposomes and polymer micelles are two UA nanoformulations that can effectively increase medicine stability. The use of UA for treating cancers is safe and appropriate with low toxicity characteristics and a predictable pharmacokinetic profile. Although the bioavailability of UA is limited, its nanoformulations could emerge as an alternative to enhance its efficacy in treating GI cancers. Further optimization and validation in the clinical trials are necessary. The combination of molecular profiling with nanoparticle-based drug delivery technologies holds the potential for bringing UA to maximum efficacy, looking for good prospects with GI cancer treatment. [ABSTRACT FROM AUTHOR]

Bounded count response data arise naturally in health applications. In general, the well-known beta-binomial regression model form the basis for analyzing this data, specially when we have overdispersed data. Little attention, however, has been given to the literature on the possibility of having extreme observations and overdispersed data. We propose in this work an extension of the beta-binomial regression model, named the beta-2-binomial regression model, which provides a rather flexible approach for fitting a regression model with a wide spectrum of bounded count response data sets under the presence of overdispersion, outliers, or excess of extreme observations. This distribution possesses more skewness and kurtosis than the beta-binomial model but preserves the same mean and variance form of the beta-binomial model. Additional properties of the beta-2-binomial distribution are derived including its behavior on the limits of its parametric space. A penalized maximum likelihood approach is considered to estimate parameters of this model and a residual analysis is included to assess departures from model assumptions as well as to detect outlier observations. Simulation studies, considering the robustness to outliers, are presented confirming that the beta-2-binomial regression model is a better robust alternative, in comparison with the binomial and beta-binomial regression models. We also found that the beta-2-binomial regression model outperformed the binomial and beta-binomial regression models in our applications of predicting liver cancer development in mice and the number of inappropriate days a patient spent in a hospital. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common malignancy and the fourth most common malignancy causing death in the world. The development of colorectal cancer is influenced by several factors, including external, internal environmental, and genetic factors. One of the environmental factors recently known to be associated with colorectal cancer is gut microbiota. Generally, gut microbiota has various functions and is influenced by several factors, such as food, drugs, activities, habits, and diseases. Microbiota may become imbalanced, otherwise known as dysbiosis, which may lead to several changes and disturbances that can initiate the development of malignancy. There were differences in the composition and diversity of the types of microbiota in colorectal cancer patients. This difference has the potential to be used as a diagnostic marker and also the development of treatment in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]