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The risk of breast cancer development is believed to be attributed to the alterations of a number of key biological components. Within this context, elevated levels of some chemokines that act as growth factors and can promote cancer development. The current study was designed to evaluate CXCL3 (a chemokine CX-C Motif Ligand 3) and leptin (a peptide hormone synthesized by adipose tissue with cytokine activity) serum of Iraqi breast cancer patients in comparison to healthy controls. A total of 90 participants consisted of 60 patients diagnosed with breast cancer and 30 healthy women as control group were enrolled into this case-control study. Venous blood samples were collected from all participants to evaluate CXCL3 and leptin serum levels using ELISA. The results demonstrated significantly (P≤0.001) higher mean levels of CXCL3 and leptin in breast cancer patients (1.19±0.10 ng/mL and 130.44± 3.72pg/mL) compared to those of their healthy counterparts (0.430± 0.02\ng/mL and 57.1± 3.2pg/mL respectively). Interestingly, vast majority of the assessed breast cancer cases (up to 95-98%) showed to have elevated serum levels of both of the assessed potential biomarkers (CXCL3 and leptin). The present study results suggest an association of both CXCL3 and leptin in breast cancer pathogenicity . This supports the possibility of utilizing these potential biomarkers for breast cancer early detection and diagnosis. [ABSTRACT FROM AUTHOR]

Chemical safety testing plays a crucial role in product and pharmacological development, as well as chemoprevention; however, in vitro genotoxicity safety tests do not always accurately predict the chemicals that will be in vivo carcinogens. If chemicals test positive in vitro for genotoxicity but negative in vivo , this can contribute to unnecessary testing in animals used to confirm erroneous in vitro positive results. Current in vitro tests typically evaluate only genotoxicity endpoints, which limits their potential to detect non-genotoxic carcinogens. The frequency of misleading in vitro positive results can be high, leading to a requirement for more informative in vitro tests. It is now recognized that multiple-endpoint genotoxicity testing may aid more accurate detection of carcinogens and non-carcinogens. The objective of this review was to evaluate the utility of our novel, multiple-endpoint in vitro test, which uses multiple cancer-relevant endpoints to predict carcinogenic potential. The tool assessed micronucleus frequency, p53 expression, p21 expression, mitochondrial respiration, cell cycle abnormalities and, uniquely, cell morphology changes in human lymphoblastoid cell lines, TK6 and MCL-5. The endpoints were used to observe cellular responses to 18 chemicals within the following categories: genotoxic carcinogens, non-genotoxic carcinogens, toxic non-carcinogens, and misleading in vitro positive and negative agents. The number of endpoints significantly altered for each chemical was considered, alongside the holistic Integrated Signature of Carcinogenicity score, derived from the sum of fold changes for all endpoints. Following the calculation of an overall score from these measures, carcinogens exhibited greater potency than non-carcinogens. Genotoxic carcinogens were generally more potent than non-genotoxic carcinogens. This novel approach therefore demonstrated potential for correctly predicting whether chemicals with unknown mechanism may be considered carcinogens. Overall, while further validation is recommended, the test demonstrates potential for the identification of carcinogenic compounds. Adoption of the approach could enable reduced animal use in carcinogenicity testing. [ABSTRACT FROM AUTHOR]

Objectives Industry- and occupation-based carcinogen exposure matrices play a pivotal role in preventing occupational cancer. While the Korean CARcinogen EXposure (K-CAREX) has been developed in recent years to assess exposure prevalence and intensity by industry, the feasibility of constructing an occupation-based exposure matrix remains unexplored. Hence, the objective of this study is to explore the potential of combining the nationwide work environment measurement database (WEMD) and the special health examination database (SHED) to develop a comprehensive occupation-based exposure matrix. Methods The WEMD provides information on airborne lead measurements, including industry codes, but it does not include data related to occupations. In contrast, the SHED contains information on both occupation and blood lead levels. By integrating these 2 databases, we attempted to assess airborne lead exposure levels by occupation. Additionally, we performed a rank correlation analysis to compare the airborne exposure levels with corresponding blood lead levels according to occupation. Results A total of 35 425 workers who both wore air samplers for lead and underwent special health examinations for lead were extracted between 2019 and 2021. An occupation-based exposure matrix was developed to evaluate the intensity of lead exposure across a range of occupations, encompassing 51 minor occupations and 70-unit occupations. Rank correlation analyses showed strong positive correlations between airborne lead and blood lead measurements according to occupation. Conclusions Our study findings suggest that combining 2 nationwide surveillance databases can be an effective approach for creating an occupation-based exposure matrix. However, our results also highlight several limitations that need to be addressed in future studies to improve the accuracy and reliability of such matrices. [ABSTRACT FROM AUTHOR]

Background: Melanoma central nervous system (CNS) metastasis remains a leading cause of patient mortality, and the underlying pathological mechanism has not been fully elucidated, leading to a lack of effective therapeutic strategies. Materials and Methods: In this study, we conducted an integrated analysis of single‐cell transcriptomic data related to melanoma brain metastasis (MBM) and leptomeningeal metastasis (LMM). We focused on differences of subset composition and molecular expression of monocytes in blood, primary tumor, brain metastases, and leptomeningeal metastases. Results: Significant differences were observed among monocytes in blood, primary tumor, and different CNS metastatic tissues, particularly in terms of subset differentiation and gene expression patterns. Subsequent analysis revealed the upregulation of cell proportions of six monocyte subsets in brain metastasis and leptomeningeal metastasis. Based on differential gene analysis, four of these subsets exhibited increased expression of factors promoting tumor migration and survival, including AREG+ monocytes (AREG, EREG, THBS1), FABP5+ monocytes (SPP1, CCL2, CTSL), and CXCL3+ monocytes (CXCL3, IL8, IL1B). The proportions of TPSB2+ monocytes (IL32, CCL5) were notably elevated in melanoma leptomeningeal metastasis tissues. Pathway analysis indicated the activation of signaling pathways such as NOD‐like receptors, NFκB, and Toll‐like receptors in these metastasis‐related subsets. Conclusion: Our findings elucidate that AREG+, FABP5+ and CXCL3+ monocytes are associated with brain metastasis and TPSB2+ monocytes are associated with leptomeningeal metastasis in melanoma, which may be contribute to the development of therapeutic strategies focusing on monocytes or cytokines for melanoma CNS metastasis. [ABSTRACT FROM AUTHOR]

Tobacco smoke consists of over 5000 chemical components, most of them are carcinogenic, respiratory toxicants, cardiovascular toxicants, addictive, etc. In 2006 the Working Group on Tobacco Control identified substances in tobacco smoke, which are harmful and potentially harmful for human health (Priority List) and encouraged the development of methods for the analysis of these components. This review focuses on the different methods of evaluation of harmful and potentially harmful components in tobacco smoke used by the International Agency for Research on Cancer (IARC) and the U.S. Food and Drug Administration (FDA) and furthermore on the official methods proposed by the World Health Organization (WHO) and the Cooperation Center for Scientific Research Relative to Tobacco (CORESTA) for analysing these constituents. The various methods for the determination of the substances in tobacco smoke included in the Priority List are compared. In addition, the different evaluation of components from the Priority List is presented. The authors hope that this review will acquaint readers with the harmful components in tobacco smoke. Also, that it will help accredited or scientific laboratories to compare the different methods and to choose appropriate methods depending on their laboratory equipment and laboratory chemicals available. [ABSTRACT FROM AUTHOR]

Background: Mammary cancer is the most common type of cancer and the leading cause of cancer-related death in women. Despite of numerous therapeutic options, cancer remains associated with high mortality. Traditional herb medicine has been found effective with minimal or no side effects. Materials and Methods: The leaves of Dolichandrone falcata Seem. (Bignoniaceae family) contains chrysin-7-rutinoside, flavanoids which possess Anti-cancer potential. The extract obtained from Soxhlet extraction process is then assessed against the chemical carcinogen (7,12-Dimethyl benzene anthracene) induced mammary carcinoma in rats. Results and Conclusion: The dose dependent study and statistical comparison with the help of graph pad prism, version 8.03 by one way ANOVA followed by Dunnett's multiple comparison test has revealed that the significant reduction (p<0.05) is observed in the mammary tumor volume of the group treated with the extract and hence the Anti-cancer Potential of Dolichandrone falcata Seem. is justified. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer stem cells are crucial for tumorigenesis and cancer metastasis. Presently, long non-coding RNAs were found to be associated with Pancreatic Ductal Adenocarcinoma stemness characteristics but the underlying mechanism is largely known. Here, we aim to explore the function of LINC00909 in regulating pancreatic cancer stemness and cancer metastasis. Methods: The expression level and clinical characteristics of LINC00909 were verified in 80-paired normal pancreas and Pancreatic Ductal Adenocarcinoma tissues from Guangdong Provincial People's Hospital cohort by in situ hybridization. RNA sequencing of PANC-1 cells with empty vector or vector encoding LINC00909 was experimented for subsequent bioinformatics analysis. The effect of LINC00909 in cancer stemness and metastasis was examined by in vitro and in vivo experiments. The interaction between LINC00909 with SMAD4 and the pluripotency factors were studied. Results: LINC00909 was generally upregulated in pancreatic cancer tissues and was associated with inferior clinicopathologic features and outcome. Over-expression of LINC00909 enhanced the expression of pluripotency factors and cancer stem cells phenotype, while knock-down of LINC00909 decreased the expression of pluripotency factors and cancer stem cells phenotype. Moreover, LINC00909 inversely regulated SMAD4 expression, knock-down of SMAD4 rescued the effect of LINC00909-deletion inhibition on pluripotency factors and cancer stem cells phenotype. These indicated the effect of LINC00909 on pluripotency factors and CSC phenotype was dependent on SMAD4 and MAPK/JNK signaling pathway, another downstream pathway of SMAD4 was also activated by LINC00909. Specifically, LINC00909 was localized in the cytoplasm in pancreatic cancer cells and decreased the stability the SMAD4 mRNA. Finally, we found over-expression of LINC00909 not only accelerated tumor growth in subcutaneous mice models, but also facilitated tumorigenicity and spleen metastasis in orthotopic mice models. Conclusion: We demonstrate LINC00909 inhibits SMAD4 expression at the post-transcriptional level, which up-regulates the expression of pluripotency factors and activates the MAPK/JNK signaling pathway, leading to enrichment of cancer stem cells and cancer metastasis in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: CircRNAs and miRNAs are involved in the progression of tumor. CircMCTP2 is considered as a novel tumor promoter. However, the exact functions of circMCTP2 in bladder cancer are still unclear. This study was designed to explore the underlying mechanisms of circMCTP2-modulated tumor development in bladder cancer. Methods: The present study is an original research. The levels of circMCTP2 in a total of 39 bladder cancer specimens and cell lines were determined by RT-qPCR. The expression of FZD8 in T24 and RT-4 cells treated with miR-99a-5p mimics were examined using western blotting. In addition, the proliferative, migrative and invasive abilities of transfected cells were determined by CCK8 and Transwell assays. Furthermore, the apoptosis of transfected cells was evaluated using flow cytometry. Dual luciferase reporter assay was performed to elucidate the relationship between miR-99a-5p and circMCTP2/FZD8. Results: The levels of circMCTP2 were elevated in bladder cancer samples and cells, and this was related to worse survival rate. Downregulation of circMCTP2 suppressed growth and metastasis of cells, whereas the apoptotic rate of cells was enhanced. The levels of miR-99a-5rp was elevated after the downregulation of circMCTP2. Moreover, reverse correlation between the expression of miR-99a-5p and circMCTP2 was revealed in bladder cancer specimens. Additionally, FZD8 was the putative target of miR-99a-5p and the mimics of miR-99a-5p inhibited the proliferation, migration and invasion of bladder cancer cells via the FZD8/Wnt-b-catenin axis. Moreover, circMCTP2 regulated the growth and metastasis of bladder cancer cells potentially through regulating the miR-99a-5p/FZD8/Wnt-b-catenin axis. In summary, circMCTP2 was considered as an oncogenic factor through regulating the miR-99a-5p/FZD8/Wnt-b-catenin axis. Conclusions: This novel signaling could regulate the biological behaviours of bladder cancer cells, and these findings highlighted circMCTP2 as a critical target for treating bladder cancer. [ABSTRACT FROM AUTHOR]

On the one hand, ionizing radiation has been used to treat not only cancer, but also non-cancer diseases. On the other hand, associations with radiation exposure have increasingly been reported not only for cancer, but also non-cancer diseases, both at doses or dose rates much lower than previously suggested or considered. This underscores the need for considering both cancer and non-cancer effects of medical (diagnostic or therapeutic), occupational or environmental exposure to radiation. As such, this Special Issue aims to serve as a forum to gather the latest developments and discuss future prospects in the field of normal tissue responses to radiation exposure. The Special Issue is composed of 18 articles outlining the radiation effects arising in various tissues (e.g., those in the circulatory, sensory, nervous, respiratory, and reproductive systems). [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide, while it persists as the fourth most prevalent cause of cancer-related death in the United States of America. Although there are several novel therapeutic strategies for the approach of this intensely aggressive tumor, it remains a clinical challenge, as it is hard to identify in early stages, due to its asymptomatic course. A diagnosis is usually established when the disease is already in its late stages, while its chemoresistance constitutes an obstacle to the optimal management of this malignancy. The discovery of novel diagnostic and therapeutic tools is considered a necessity for this tumor, due to its low survival rates and treatment failures. One of the most extensively investigated potential diagnostic and therapeutic modalities is extracellular vesicles (EVs). These vesicles constitute nanosized double-lipid membraned particles that are characterized by a high heterogeneity that emerges from their distinct biogenesis route, their multi-variable sizes, and the particular cargoes that are embedded into these particles. Their pivotal role in cell-to-cell communication via their cargo and their implication in the pathophysiology of several diseases, including pancreatic cancer, opens new horizons in the management of this malignancy. Meanwhile, the interplay between pancreatic carcinogenesis and short non-coding RNA molecules (micro-RNAs or miRs) is in the spotlight of current studies, as they can have either a role as tumor suppressors or promoters. The deregulation of both of the aforementioned molecules leads to several aberrations in the function of pancreatic cells, leading to carcinogenesis. In this review, we will explore the role of extracellular vesicles and miRNAs in pancreatic cancer, as well as their potent utilization as diagnostic and therapeutic tools. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PAAD) is one of the most aggressive digestive system tumors in the world, with a low early diagnosis rate and a high mortality. Integrin beta 5 (ITGB5) is demonstrated to be a potent tumor promoter in several carcinomas. However, it is unknown whether ITGB5 participates in the occurrence and development of PAAD. In this study, we confirmed a high expression of ITGB5 in PAAD and its role in promoting invasiveness and transitivity in PAAD. Besides, the knockdown of ITGB5 increased cell sensitivity to radiation by promoting DNA damage repair and the MEK/ERK signaling pathway. Collectively, these results show that ITGB5 plays an essential role in pancreatic cancer growth and survival. [ABSTRACT FROM AUTHOR]

Background: Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon. Methods: PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis's mechanism. Results: Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis. Conclusions: Our findings suggest that PKM2 may be a tumor's promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets. [ABSTRACT FROM AUTHOR]

Systematic review and evaluation of mechanistic evidence using the Key Characteristics approach was proposed by the International Agency for Research on Cancer (IARC) in 2012 and used by the IARC Monographs Working Groups since 2015. Key Characteristics are 10 features of agents known to cause cancer in humans. From 2015 to 2022, a total of 19 Monographs (73 agents combined) used Key Characteristics for cancer hazard classification. We hypothesized that a retrospective analysis of applications of the Key Characteristics approach to cancer hazard classification using heterogenous mechanistic data on diverse agents would be informative for systematic reviews in decision-making. We extracted information on the conclusions, data types, and the role mechanistic data played in the cancer hazard classification from each Monograph. Statistical analyses identified patterns in the use of Key Characteristics, as well as trends and correlations among Key Characteristics, data types, and ultimate decisions. Despite gaps in data for many agents and Key Characteristics, several significant results emerged. Mechanistic data from in vivo animal, in vitro animal, and in vitro human studies were most impactful in concluding that an agent could cause cancer via a Key Characteristic. To exclude the involvement of a Key Characteristic, data from large-scale systematic in vitro testing programs such as ToxCast, were most informative. Overall, increased availability of systemized data streams, such as human in vitro data, would provide the basis for more confident and informed conclusions about both positive and negative associations and inform expert judgments on cancer hazard. [ABSTRACT FROM AUTHOR]

Occupational skin cancer may manifest when employees are under exposure to one specific carcinogenic substance or more in the workplace. Workplaces often have higher concentrations of carcinogens compared to any other setting. The most common causes of skin cancer in the workplace are ultraviolet radiation, ionizing radiation, polycyclic aromatic hydrocarbons, and arsenic. However, there is only a limited number of studies on skin cancer from occupational exposure. Skin cancers that are considered mainly work-related are non- melanoma skin cancers. Their most common variants are basal cell carcinomas, squamous cell carcinomas, and actinic keratosis. Two factors that reduced the risk of occupational carcinogen exposure are as follows: a better understanding of skin cancer risk factors involved in industrial processes and better control of the use of ionizing radiation. However, the exposure risk to ultraviolet radiation at dangerous levels remains. Worse still, this risk is often not considered. Yet, the prevention and risk reduction for occupational skin cancer requires the elimination of the contact of all carcinogens present in the workplace with the employees' skin. Additionally, to encourage and facilitate the early recognition and management of premalignant and malignant skin lesions, training should be given to those working under higher skin cancer risk, and periodic examinations should be performed. [ABSTRACT FROM AUTHOR]

Background Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. Methods The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma. Results Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N' -Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users. Conclusion These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications. [ABSTRACT FROM AUTHOR]

Chemical agents can cause cancer in animals by damaging their DNA, mutating their genes, and modifying their epigenetic signatures. Carcinogen-induced preclinical cancer models are useful for understanding carcinogen-induced human cancers, as they can reproduce the diversity and complexity of tumor types, as well as the interactions with the host environment. However, these models also have some drawbacks that limit their applicability and validity. For instance, some chemicals may be more effective or toxic in animals than in humans, and the tumors may differ in their genetics and phenotypes. Some chemicals may also affect normal cells and tissues, such as by causing oxidative stress, inflammation, and cell death, which may alter the tumor behavior and response to therapy. Furthermore, some chemicals may have variable effects depending on the exposure conditions, such as dose, route, and duration, as well as the animal characteristics, such as genetics and hormones. Therefore, these models should be carefully chosen, validated, and standardized, and the results should be cautiously interpreted and compared with other models. This review covers the main features of chemically induced cancer models, such as genetic and epigenetic changes, tumor environment, angiogenesis, invasion and metastasis, and immune response. We also address the pros and cons of these models and the current and future challenges for their improvement. This review offers a comprehensive overview of the state of the art of carcinogen-induced cancer models and provides new perspectives for cancer research. [ABSTRACT FROM AUTHOR]

This article explores the debate between Causal Decision Theory (CDT) and Evidential Decision Theory (EDT) in the context of Newcomb problems. It introduces Conditional Causal Decision Theory (CCDT) as a version of CDT that aims to align with pre-theoretic judgments about rationality in these problems. However, the author argues that CCDT produces incorrect results, suggesting that it is not superior to CDT or EDT. The article also discusses the concept of expected value in decision-making, provides a formula for calculating expected value, and uses examples to illustrate the concept. It examines the application of CCDT to smoking and the Fisher case, concluding that CCDT recommends quitting smoking but suggests smoking in the Fisher case. The article evaluates the expected values of acts in these scenarios and addresses Edgington's analysis, arguing that it does not support CCDT's recommendation to quit smoking in the Fisher case. It also discusses the influence of different factors on the expected value of smoking and highlights the issue of aligning CCDT with different calculations. The article further explores the relationship between CDT and EDT, arguing that they yield the same results in adequately specified decision problems. It discusses the relationship between cause and effect in decision problems and emphasizes the importance of adequately specifying decision problems. The article also discusses the assumptions made in decision problem formulation and the use of CDT in decision-making situations. It explores the expected values of acts according to different decision theories and the importance of considering the influence of [Extracted from the article]

Introduction: Health care workers handling antineoplastic drugs (ADs) are at risk of carcinogenic, mutagenic and reproductive toxic risks (CMR). The aim of this study was to assess the impact of the lack of knowledge (K) on risk perception (P) and on protective practices (PP) related to the handling of home-based chemotherapy (HC) by home nurses. Methods: This study was conducted in Normandy among home nurses. A questionnaire was developed to explore the K, P and PP related to handling ADs by home nurses working with four different providers from two hospitals. Results: Among the 28 home nurses included, 25.93% had received initial training on the specific treatment of ADs, 48.15% scored below average on risk management K, 52.00% scored below average on personal PP. Conclusion: This study reveals the importance of adapted and regular training on the handling of ADs. It will help develop a climate of safety and reinforce adherence to wearing personal protective equipment to protect health care workers from contamination. [ABSTRACT FROM AUTHOR]

The monitoring of acidosis and hypoxia is crucial because both factors promote cancer progression and impact the efficacy of anti-cancer treatments. A phosphonated tetrathiatriarylmethyl (pTAM) has been previously described to monitor both parameters simultaneously, but the sensitivity to tackle subtle changes in oxygenation was limited. Here, we describe an innovative approach combining the pTAM radical and lithium phthalocyanine (LiPc) crystals to provide sensitive simultaneous measurements of extracellular pH (pH e) and pO 2. Both parameters can be measured simultaneously as both EPR spectra do not overlap, with a gain in sensitivity to pO 2 variations by a factor of 10. This procedure was applied to characterize the impact of carbogen breathing in a breast cancer 4T1 model as a proof-of-concept. No significant change in pH e and pO 2 was observed using pTAM alone, while LiPc detected a significant increase in tumor oxygenation. Interestingly, we observed that pTAM systematically overestimated the pO 2 compared to LiPc. In addition, we analyzed the impact of an inhibitor (UK-5099) of the mitochondrial pyruvate carrier (MPC) on the tumor microenvironment. In vitro , the exposure of 4T1 cells to UK-5099 for 24 h induced a decrease in pH e and oxygen consumption rate (OCR). In vivo , a significant decrease in tumor pH e was observed in UK-5099-treated mice, while there was no change for mice treated with the vehicle. Despite the change observed in OCR, no significant change in tumor oxygenation was observed after the UK-5099 treatment. This approach is promising for assessing in vivo the effect of treatments targeting tumor metabolism. [Display omitted] • Acidosis and hypoxia are detrimental factors in cancer progression. • Innovative EPR procedure to measure extracellular pH and pO 2 simultaneously. • Using both LiPc with pTAM allows a gain in sensitivity to oxygen variations by a factor of 10. • Proof-of-concept studies using carbogen breathing and MPC inhibition. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is putatively present in over half of the global human population and is recognized as a carcinogenic agent that increases the likelihood of infected patients developing gastric adenocarcinoma or gastric lymphoma. Although there are several means for testing for H. pylori, the gold standard remains the invasive histologic evaluation. The current most popular form of bariatric surgery is the laparoscopic sleeve gastrectomy (LSG) and is the only bariatric surgery which supplies a specimen for histologic evaluation. While non-invasive testing is effective in diagnosing and monitoring H. pylori infection, histological examination of biopsies and resections is the only way to grade chronic inflammation and evaluate specimens for additional pathologies such as intestinal metaplasia. The investigators evaluated 203 sequential LSG specimens collected from a major metropolitan hospital over the period of one year. Specimens were processed to paraffin, stained with hematoxylin and eosin, alcian blue, and immunohistochemistry to determine the presence of H. pylori, chronic inflammation, presence of secondary lymphoid follicles in the mucosa, mucosal thickness, and presence of intestinal metaplasia. Statistical analyses demonstrated a significant positive correlation among all factors examined. The overall positivity rate of H. pylori in LSG specimens was 18.2% but ranged from 6.9−23.8% depending on whether the treating clinician performed routine pre-surgical endoscopy. The presence of H. pylori was associated with a higher average chronic inflammation grade, intestinal metaplasia, thicker mucosa, and presence of lymphoid follicles with germinal centers in the mucosa. [ABSTRACT FROM AUTHOR]

Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers. Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined. The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5. The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent). [ABSTRACT FROM AUTHOR]

Purpose: Diesel exhaust (DE) is an established lung carcinogen. The association with leukemia is not well established. We conducted a systematic review and meta-analysis of cohort studies to determine the association between occupational DE exposure and risk of leukemia. Methods: A systematic literature review was performed to identify all cohort studies on occupational exposure to DE and associated risk of leukemia. STROBE guidelines and PECOS criteria were followed. Meta-analyses with fixed effects (and random-effects model in cases of high heterogeneity) were performed to calculate summary relative risks (RR) and 95% confidence intervals (CI), including subgroup analyses by outcome (mortality or incidence), sex, geographic region, industry type, and study quality. Study quality was assessed using the the Joanna Briggs Institute (JBI) critical appraisal checklist for cohort studies. Results: Of the 30 studies retained, 20 (8 from North America, 12 from Europe) reported a total of 33 estimates of the risk of leukemia. Overall, the relative risk (RR) of leukemia was 1.01 (95% CI = 0.97–1.05, I2 = 21.2%, n = 33); corresponding results for leukemia incidence and mortality were RR = 1.02 (95% CI = 0.98–1.06, I2 = 27.9%, n = 19) and RR = 0.91 (95% CI = 0.81–1.02, I2 = 0.0%, n = 15), respectively. The main results were confirmed in analyses by sex and geographic area. A statistically significant association was detected for miners (RR = 1.58, 95% CI = 1.15–2.15, I2 = 77.0%, n = 2) but not for other occupational groups. Publication bias was not detected (p = 0.7). Conclusion: Our results did not indicate an association between occupational DE exposure and leukemia, with the possible exception of miners. Residual confounding cannot be excluded. [ABSTRACT FROM AUTHOR]

In the European Union, Occupational Safety and Health legislation generally refers to European Regulation (CE) n. 1272/2008 to define and classify carcinogens of concern for occupational risk assessment and exposure assessment. In Europe, the current reference is Directive (UE) 2022/431, regarding carcinogen, mutagen, and reprotoxic agent (CMR) exposure. However, at the worldwide level, different classification approaches are used to establish carcinogenicity of substances and it is often difficult to compare the classifications of carcinogenicity (CoCs) proposed by different international bodies. This study aims to investigate a list of carcinogens of concern in occupational settings based on the CLP (Classification Labelling Packaging) CoC and to create a tool that allows a rapid translation–comparison of some international CoCs with the reference one. CoCs proposed by various sources were consulted and used to apply a translation method, to favor an alignment of different CoCs according to a reference. Results outlined that, considering diverse sources, CoCs can result in different classifications of the same chemicals. Overall, this may have implications for the hazard assessment process, which is the base of risk assessment. The proposed tool is expected to help risk assessors in the occupational field when it is needed to have a comparison with different CoC systems. [ABSTRACT FROM AUTHOR]

More than a dozen published articles have reported the presence of transgenes in Mexican maize and corn products, but the Mexican government and a sector of the population insist that 'Mexico is free of transgenics'. The moratorium of transgenic maize cultivation, experimentation, and almost any meaningful discussion on this debated topic, has created confusion and an illegal market of maize seed that contains transgenes. We studied under field conditions the productivity under multiple agronomic conditions, and the genetic segregation of multiple generations of the offspring of transgenic maize, the imported commodity that makes up to two thirds of the domestically consumed maize in Mexico. Herbicide and insect resistant transgenes are present in 55-73% of the imported maize from the United States, which is used in Mexico as feed, food, and for planting. These transgenes are now found in 35% of Mexican maize and their addition enhance the genetic diversity of the maize genome because they do not replace any genes. Particularly, genes that produce insecticidal proteins like those found in the bacterium Bacillus thuringiensis (Bt), a common 'organic' insecticide, protect 11-100% of Mexican maize plants from the attack of different pests, notoriously the fall armyworm, the most important maize pest in Mexico and many parts of the world. We provide evidence that hybrid transgenic maize and its offspring would require optimal agronomic inputs to make it profitable. Unfortunately, appropriate fertilization, weed control and irrigation only occur in less than half of the 7 million hectares grown in Mexico, effectively excluding most of the smallholders from the economic feasibility of planting hybrid seed, but not the imported offspring commodity. Maize cultivation under optimal and suboptimal agronomic conditions, reflecting commercial and subsistence production, influence the time and duration of pollen shed. Plants grown under optimal conditions pollinated for eight days, while stressed plants shed pollen for up to two weeks. The possible pollen exchange between these two conditions is only 40%, a gene isolation mechanism created by proper maize production. Plants protected by the expression of Bt genes produce more seeds, increasing their representation in the next generation, preserving maize diversity. Additionally, the introgression of Bt genes in Mexican maize protect the grain from developing toxic carcinogenic substances such as fumonisins and aflatoxins that affect human and animal health. Because Mexicans consume close to 400 grams of maize daily, of which 40-80% is yellow and imported, the direct consumption of transgenic maize has been more than 200 grams per day for the past decade, providing a healthier diet. We also provide counter arguments based on scientific evidence to many misconceptions and myths spread by different groups. Más de una docena de artículos publicados han reportado la presencia de transgenes en el maíz mexicano y sus derivados, pero el gobierno mexicano y un sector de la población insisten en que "México está libre de transgénicos". La moratoria al cultivo de maíz transgénico, a la experimentación y a casi cualquier discusión significativa sobre este debatido tema, ha creado confusión y un mercado ilegal de semilla de maíz que contiene transgenes. En condiciones de campo, estudiamos la productividad bajo múltiples condiciones agronómicas, y la segregación genética de múltiples generaciones de la descendencia del maíz transgénico, el producto importado que constituye hasta dos terceras partes del maíz que se consume en México. Los transgenes que hacen al maíz resistente a herbicidas e insectos están presentes en el 55-73 % del maíz importado de Estados Unidos, que se utiliza en México como pienso, alimento y para la siembra. Estos transgenes se encuentran ahora en 35 % del maíz mexicano y su incorporación aumenta la diversidad genética del genoma del maíz porque no sustituyen a ningún gen. En particular, los genes que producen proteínas insecticidas como las que se encuentran en la bacteria Bacillus thuringiensis (Bt), un insecticida "orgánico" común, protegen del 11 al 100 % de las plantas de maíz del ataque de diferentes plagas, en especial, el gusano cogollero, la plaga más importante del maíz en México y en muchas partes del mundo. Aportamos información empírica de que el maíz transgénico híbrido y su descendencia requerirían insumos agronómicos óptimos para hacerlos rentable. Desafortunadamente, la fertilización adecuada, el control de malezas y el riego solo se dan en menos de la mitad de los 7 millones de hectáreas cultivadas en México, excluyendo efectivamente a la mayoría de los pequeños agricultores de la viabilidad económica de la siembra de semilla híbrida, pero no del producto importado. El cultivo de maíz en condiciones agronómicas óptimas y subóptimas, que se reflejan en la producción comercial y de subsistencia, influye en el momento y la duración de la producción y movimiento del polen. Las plantas cultivadas en condiciones óptimas polinizaron durante ocho días, mientras que las plantas estresadas soltaron el polen durante hasta dos semanas. El posible intercambio de polen entre plantas de maíz con estas dos condiciones es solo del 40 %, un mecanismo de aislamiento genético creado por la producción adecuada de maíz. Las plantas protegidas por la expresión de genes Bt producen más semillas, lo que aumenta su representación en la siguiente generación, preservando la diversidad del maíz. Además, la introgresión de genes Bt en el maíz mexicano protege al grano del desarrollo de sustancias tóxicas cancerígenas como las fumonisinas y las aflatoxinas, que afectan a la salud humana y animal. Debido a que los mexicanos consumen cerca de 400 gramos diarios de maíz, de los cuales 40-80 % es amarillo e importado, el consumo directo de maíz transgénico ha sido de más de 200 gramos diarios durante la última década, proporcionando una dieta más saludable. También proporcionamos contraargumentos basados en evidencia científica a muchas ideas erróneas y mitos difundidos por diferentes grupos. Al final de este artículo, en el apéndice se encuentra un resumen más largo en español. [ABSTRACT FROM AUTHOR]

Objective: microRNA‐450b (miR‐450b) plays an important role in cancer progression; however, its function in oral squamous cell carcinoma (OSCC) remains largely unknown. This study aimed to investigate the action mechanisms of miR‐450b in OSCC. Materials and Methods: OSCC animal model was established via continuous induction with single‐drug 7, 12‐dimethylbenzo[a]anthracene (DMBA). Animal tissue samples were pathologically typed using haematoxylin–eosin (HE) staining. The Cancer Genome Atlas (TCGA) database was used to predict miR‐450b and SERPINB2 expression in head and neck squamous cell carcinoma (HNSCC). qRT‐PCR and Western blotting were used to detect gene and protein expression in OSCC tissue and cells, respectively. OSCC cell proliferation, growth, migration and invasion were detected using CCK‐8, colony formation, transwell migration and matrigel invasion assays, respectively. Bioinformatic tools were used to predict miR‐450b target genes. Dual‐luciferase reporter assay was used to verify targeting between miR‐450b and SERPINB2. Finally, small interfering RNA (siRNA) was used to reduce SERPINB2 expression to detect its effect on tumourigenesis. Results: Four stages of OSCC carcinogenesis (normal oral epithelium, simple epithelial hyperplasia, dysplasia and OSCC) were identified. miR‐450b was found to be overexpressed in OSCC animal samples, HNSCC samples and human OSCC cells. Upregulation of miR‐450b significantly promoted OSCC cell proliferation, colony formation, migration and invasion, while its downregulation had the opposite effect. SERPINB2 was found to be a miR‐450b target gene, and its expression was negatively correlated with miR‐450b expression. Altering SERPINB2 expression effectively inhibited OSCC cell invasion, metastasis and epithelial‐mesenchymal transition (EMT). Conclusions: miR‐450b plays a key role in OSCC tumourigenesis by regulating OSCC cell migration, invasion and EMT via SERPINB2. [ABSTRACT FROM AUTHOR]

Objective: Manganese ion (Mn2+) is reported to promote the antitumor immune response by activating the cGAS‐STING pathway, but it is unknown whether Mn2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn2+ in treating oral leukoplakia (OLK) were explored in this work. Methods: Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP–AES). A coculture model of dendritic cells (DCs)/macrophages, CD8+ T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn2+ in a simulated OLK immune microenvironment. Western blot, RT–PCR, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn2+ in this model. 4‐nitroquinoline oxide (4NQO)‐induced OLK mice were used to assess the role of Mn2+ in suppressing OLK progression, and a novel Mn2+‐loaded guanosine‐tannic acid hydrogel (G‐TA@Mn2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. Results: The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8+ T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway. Moreover, Mn2+ suppressed the development of 4NQO–induced carcinogenesis in the mouse model. In addition, the G‐TA@Mn2+ hydrogel had better anti‐OLK effects. Conclusions: Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway, and the G‐TA@Mn2+ hydrogel is a potential novel therapeutic approach for OLK treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the fourth most common female malignancy in high socioeconomic index nations and the sixth most common cancer in women worldwide. The disease incidence has increased globally by 132% in the last 30 years, and this trend is set to continue in light of an ageing population and increasing levels of obesity and diabetes. Although more women than ever before are dying of endometrial cancer, the mortality rates are falling due to recent advances in early diagnosis and treatment. Our understanding of the molecular drivers of endometrial cancer has increased substantially, and doctors are now, for the first time, starting to translate this knowledge into the true personalisation of care. This review summarises the recent advances in the field and identifies avenues for future exploration. Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to the increasing incidence of hepatocellular carcinoma, which is a global problem, it is valuable to present the latest available literature that describes dietary options for preventing the development of hepatocellular carcinoma and the possibilities of dietary therapy for oncological patients. The authors firstly focus on discussing Metabolic Dysfunction-Associated Steatotic Liver Disease as a factor induced by improper dietary habits, while simultaneously suggesting the adoption of a Mediterranean diet as a model to counteract metabolic disorders resulting in HCC development. Subsequently, the authors discuss the potential for dietary modulation of autophagy processes, the necessity of supporting microbiota, the importance of providing selected vitamins and minerals, as well as compounds particularly valued for their anti-cancer properties, also observed in the case of HCC. The last aspect addressed is the consumption of products contributing to anti-tumor activity. Hepatocellular carcinoma (HCC) is diagnosed annually in nearly a million people worldwide, with approximately half of them being diagnosed at an advanced stage of the disease. Non-infectious risk factors for the development of HCC include an unbalanced lifestyle, including poor dietary choices characterized by a low intake of antioxidants, such as vitamins E and C, selenium, and polyphenols, as well as an excessive consumption of energy and harmful substances. Repeated bad dietary choices that contribute to an unbalanced lifestyle lead to the accumulation of fatty substances in the liver and to it entering an inflammatory state, which, without intervention, results in cirrhosis, the main cause of HCC. This review of the English language literature aims to present the food components that, when included in the daily diet, reduce the risk of developing HCC, as well as identifying foods that may have a carcinogenic effect on liver cells. [ABSTRACT FROM AUTHOR]

Simple Summary: This exploratory narrative review investigates the association between exposure to per- and polyfluoroalkyl substances (PFAS), sociodemographic factors, stressors, and endometrial cancer risk. It explores the diverse sources of PFAS exposure and examines the role of income, education, occupation, ethnicity, and geographic location in influencing exposure levels and cancer risk. The review finds significant correlations between these sociodemographic factors and both PFAS exposure and endometrial cancer risk. It emphasizes the need for further interdisciplinary research and targeted interventions to understand and address these complex relationships, highlighting the importance of addressing health disparities for effective disease prevention and management. This exploratory narrative review paper delves into the intricate interplay between per- and polyfluoroalkyl substances (PFAS) exposure, sociodemographic factors, and the influence of stressors in the context of endometrial cancer. PFAS, ubiquitous environmental contaminants notorious for their persistence in the ecosystem, have garnered attention for their potential to disrupt endocrine systems and provoke immune responses. We comprehensively examine the various sources of PFAS exposure, encompassing household items, water, air, and soil, thus shedding light on the multifaceted routes through which individuals encounter these compounds. Furthermore, we explore the influence of sociodemographic factors, such as income, education, occupation, ethnicity/race, and geographical location and their relationship to endometrial cancer risk. We also investigated the role of stress on PFAS exposure and endometrial cancer risk. The results revealed a significant impact of sociodemographic factors on both PFAS levels and endometrial cancer risk. Stress emerged as a notable contributing factor influencing PFAS exposure and the development of endometrial cancer, further emphasizing the importance of stress management practices for overall well-being. By synthesizing evidence from diverse fields, this review underscores the need for interdisciplinary research and targeted interventions to comprehensively address the complex relationship between PFAS, sociodemographic factors, stressors, and endometrial cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: We were motivated by the need to improve early detection of bladder cancer (BLCA). Our aim was to uncover genetic alterations within the bladder's lining, called urothelium, where BLCA starts. We examined normal tissue margins near and far away from tumors, studying the abnormalities that may predispose to BLCA. Recognizing the post-zygotic variability in bladder urothelium resulting from exposure to carcinogens in urine, our novel approach examined up to eight fragments of normal epithelium from each individual. Using a sensitive computational method, we successfully identified novel, but also well-known cancer-related regions across normal samples, confirming the efficacy of our methodology. Additionally, we provide further evidence for the already recognized connection between the loss of chromosome Y in men and BLCA. This positions our method for broader use in larger cohorts and different cancer types. Looking ahead, our methodology holds promise for identifying biomarkers that predict BLCA in analysis of urine. Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA. [ABSTRACT FROM AUTHOR]

Simple Summary: The epithelial-to-mesenchymal transition (EMT) is a process taking place during carcinogenesis. The phenotypic changes include the acquisition of new properties such as increased motility and polarity, leading to invasiveness and the formation of metastasis and chemo- and radioresistance. During the process, epithelial markers are lost whilst mesenchymal markers are overexpressed. EMT-related transcription factors are induced and multiple signaling pathways are activated. Several microRNAs are altered during the transition. Many of these molecules are regulated by melatonin, the pineal hormone, thus behaving as an inhibitor of the EMT in cancer progression. In this review, we summarize the present knowledge on the actions of melatonin on the EMT. The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial–mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, ultimately leading cells to stemness, increased invasiveness, chemo- and radioresistance and the formation of cancer metastasis. Amongst the different existing types of the EMT, type 3 is directly involved in carcinogenesis. A type 3 EMT occurs in neoplastic cells that have previously acquired genetic and epigenetic alterations, specifically affecting genes involved in promoting clonal outgrowth and invasion. Markers such as E-cadherin; N-cadherin; vimentin; and transcription factors (TFs) like Twist, Snail and ZEB are considered key molecules in the transition. The EMT process is also regulated by microRNA expression. Many miRNAs have been reported to repress EMT-TFs. Thus, Snail 1 is repressed by miR-29, miR-30a and miR-34a; miR-200b downregulates Slug; and ZEB1 and ZEB2 are repressed by miR-200 and miR-205, respectively. Occasionally, some microRNA target genes act downstream of the EMT master TFs; thus, Twist1 upregulates the levels of miR-10b. Melatonin is an endogenously produced hormone released mainly by the pineal gland. It is widely accepted that melatonin exerts oncostatic actions in a large variety of tumors, inhibiting the initiation, progression and invasion phases of tumorigenesis. The molecular mechanisms underlying these inhibitory actions are complex and involve a great number of processes. In this review, we will focus our attention on the ability of melatonin to regulate some key EMT-related markers, transcription factors and micro-RNAs, summarizing the multiple ways by which this hormone can regulate the EMT. Since melatonin has no known toxic side effects and is also known to help overcome drug resistance, it is a good candidate to be considered as an adjuvant drug to conventional cancer therapies. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. Methods: Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. Results: We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. Conclusion: PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 is the most harmful food toxin for humans and animals. According to the International Agency for Research on Cancer, it is ranked as one of the most carcinogenic substances in the world, directly connected to hepatocarcinoma in both humans and animals. Aflatoxin B1 is also involved in the occurrence of pathologies, and aflatoxicoses. Aflatoxin B1 can be produced by fungi from the genus Aspergillus section Flavi in a variety of foods during storage. Once aflatoxins are present, food processing cannot eradicate them. The damage and lack of complete elimination of aflatoxins from foodstuffs make them the most monitored and controlled substances in the world. Given the high-risk of Aflatoxin B1 on both animal and human health, it is important to study their worldwide distribution and existing control methods through a systematic review. Articles published from 1945 to 2022 found on several databases as Scopus, PubMed, Dimensions, Google Scholar and an extraction sieve was used to select the relevant articles. Of the two hundred and twenty-eight (228) French and English scientific articles on aflatoxins identified, forty of the most relevant original articles were selected for inclusion in this review following a rigorous selection process. Several genes are involved in the synthesis of aflatoxin B1. Moreover, certain environmental conditions, in particular oxidative stress are propitious for fungus by over-expressing aflatoxins. However, the fungi defences can be controlled by several methods. Articles showed efficiency of various of them. Good cultural practices and awareness raising are part of the preventive control. Synthetic chemicals such as insecticides and fungicides are chronically used in chemical control of fungal growth and prevent aflatoxins from being produced. Biological control is based on allelic recombination between toxic and atoxic strains. The use of microbial competition is focused on the natural predators of aflatoxic molds, most often lactic acid bacteria, and the natural control relies on the use of natural plant substances. Natural substances like aqueous or organic plant extracts that contain proteins, polyphenols, tannins, antioxidants, flavonoids, terpenes, and chelating ion as well as caffeic acid, gallic acid and ascorbic acid can be used to control fungal contamination currently. These molecules interfere with free radicals to slow down or even inhibit the production of reactive oxygen species significantly reducing the production of aflatoxins making them inactive. Implementation of the means of controlling fungal growth and producing aflatoxins will help make agriculture globally competitive and ensure food security. [ABSTRACT FROM AUTHOR]

The research focused on risk assessment of some heavy metals in common vegetables and fish sold on open markets in three towns of Zambia. The mean level of heavy metals ranged as follows (mg/kg): 1.9 to 662.7, 3.0 to 3472.3 and 2.0 to 1698.7 of cadmium (lowest) and aluminium (highest) for samples from Kabwe, Kitwe and Lusaka, respectively. Statistical analysis indicated that the concentrations of samples from Kitwe and Lusaka towns were similar, P > 0.05. However, there were noteworthy differences in the mean amounts of heavy metals in samples from Kitwe and Kabwe, and samples from Kabwe and Lusaka towns, P <.0167. The health risk analysis indicates possible non-carcinogenic and carcinogenic risks to the consumer. This is because the hazard index (HI) for all metals in all samples from all towns was greater than 1 and the cancer risk (CR) for cadmium was above 10−4 in all samples from all towns. [ABSTRACT FROM AUTHOR]

The chronic dietary risk assessment for 34 pesticides suspected of acting as endocrine disrupters in Iran was assessed by comparing TMDI with the Acceptable Daily Intakes (ADI). Of 34 investigated endocrine-disrupting pesticides (EDPs), 6 had TMDI > ADI. In addition, potential non-carcinogenic and carcinogenic health risk assessments were evaluated using Monte Carlo simulation. HQ in wheat was 17.40 and 20.29 in adults and children, respectively. Due to dimethoate residue in wheat, HQ was 2.78, and for fenitrothion residue, 3.22. HI was 21.22 for adults and 24.76 for children in wheat, more than 1. Total Carcinogenic risk (TCR) due to EDPs residues was 6.40 × 10−5 in apples, in citrus fruits 5.97 × 10−5, 3.33 × 10−5 in cucumber, 5.30 × 10−5 in lettuce, in potato was 2.36 × 10−5, in rice was 1.61 × 10−5, 1.78 × 10−5 in tomato, and due to epoxiconazole residues in wheat was 3.18 × 10−5, more than acceptable limit 1.0 × 10−6. Therefore, consumers were at significant risk of carcinogenesis. Abbreviations: PCBs: polychlorinated biphenyls; BPA: Bisphenol A; ED: Endocrine Disrupting; EDCs: Endocrine Disrupting Chemicals; EDPs: Endocrine Disrupting Pesticides; ADI: Acceptable Daily Intake; TMDI: Theoretical Maximum Daily Intake; FAO: Food and Agriculture Organization; WHO: World Health Organization; MRL: Maximum Residue Limit; HQ: Hazard Quotient; HI: Hazard Index; CR: Cancer Risk; TCR: Total Cancer Risk; PPP: plant protection products [ABSTRACT FROM AUTHOR]

The lichen Usnea articulata collected from an unpolluted area was exposed for 6 months at 26 sites for the sample chosenusing a stratified random design, and the content of potentially toxic elements (PTEs) including As, Cd, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sn, V, and Zn, was assessed using ICP-MS. The health risk for both adults and children was then calculated using the PTEs concentrations. The results showed that despite the hostile urban conditions, transplanted lichens depicted clear deposition patterns of airborne PTEs, mostly associated with industrial sites, where As and other elements showed remarkably high values. The cumulative hazard index was below the risk threshold, both for adults and children. For the entire population (particularly children) residing in areas surrounding industrial sites, As and Cr appeared to be potentially carcinogenic elements. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a class I carcinogen that infects more than 100 million individuals in the United States. Antimicrobial therapy for H. pylori has typically been prescribed empirically rather than based on susceptibility testing. Until recently, therapeutic recommendations have generally ignored the principles of antibiotic stewardship. A combination of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin (triple therapy) remains popular despite increasing clarithromycin resistance and poor cure rates. Concomitant therapy (a PPI, amoxicillin, clarithromycin, and metronidazole) is recommended and widely used despite all patients receiving at least one unneeded antibiotic. In 2020, the Food and Drug Administration approved vonoprazan, amoxicillin, and clarithromycin triple therapy, which administers unneeded clarithromycin to >90% of patients (i.e., ~6 tons of unneeded clarithromycin/million treatments). In the late 1980s, the infectious disease community functionally transferred responsibility for the management of H. pylori to gastroenterology, which has managed the infection as another common gastrointestinal disease such as constipation. In 2022, both traditional and noninvasive molecular-based susceptibility testing for H. pylori became available in the United States. In order to reduce and prevent antibiotic misuse, the infectious disease community should reclaim responsibility for the management of this important infectious disease. [ABSTRACT FROM AUTHOR]

Fibroblast activation protein (FAP) is a known promoter of tumor development and is associated with poor clinical outcome for various cancer types. Being specifically expressed in pathological conditions including multiple types of fibrosis and cancers, FAP is an optimal target for diagnostics and treatment. Treatment strategies utilizing the unique proteolytic activity of FAP are emerging, thus emphasizing the importance of biomarkers to directly assess FAP activity. FAP is a type II transmembrane serine protease that has been shown to cleave collagens and other ECM components. In this study, we developed an ELISA assay (C3F) targeting a circulating type III collagen fragment derived from FAP cleavage to reflect FAP activity. We demonstrated that C3F was specific to the neoepitope of the cleavage site and that the fragment was generated through FAP cleavage of type III collagen. We measured C3F in serum from a cohort of patients with non-small cell lung cancer (NSCLC) (n = 109) matched to healthy subjects (n = 42) and a cohort of patients with spondyloarthritis (SpA) (n = 17) matched to healthy subjects (n = 19). We found that C3F was significantly elevated in patients with NSCLC and in patients with SpA compared to healthy controls (p < 0.0001 and p = 0.0015, respectively). These findings suggest that C3F is a promising non-invasive biomarker reflecting FAP activity, which may aid in understanding tumor heterogeneity and potentially FAP-targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Multi-factorial reasons are an induction to cause cancer. Different infections and infestations with viruses, bacteria, and parasites have been detected for many years to be related to human carcinogenesis. Purpose: The study aimed to review all ideas of tumor carcinogenesis and its associations with parasitic infections and infestations. Methods: We reviewed several articles (published and imprinted) by selecting, extracting, and synthesizing data about the relationship between cancers and parasites. Results: Several helminths infections as schistosomiasis, are highly carcinogenic agents for bladder cancer, whereas trypanosomiasis has a bi-model role in cancer development. Leishmaniasis may be a cause of hepatocarcinoma, skin cancer, and lymphomas. In addition, malaria appears to be causative in the carcinogenesis of some cancers; as Burkitt lymphoma. Also, data from previous studies suggested that Strongyloides stercoralis may be a relevant co-factor in lymphomas. Conclusion: There are different mechanisms of parasitic infection to be enhancing in carcinogenesis of cancer in human. [ABSTRACT FROM AUTHOR]

Background: Diesel exhaust (DE) is human carcinogen with sufficient evidence only for lung cancer. Systematic evidence on other cancer types is scarce, thus we aimed to systematically review current literature on the association between occupational DE exposure and risk of liver and pancreatic cancers. Methods: We performed a systematic literature review to identify cohort studies on occupational DE exposure and risk of cancers other than lung. We computed pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for liver and pancreatic cancers using DerSimonian and Laird random-effects model. Results: Fifteen studies reporting results on pancreatic cancer and fourteen on liver cancer were included. We found a weakly increased risk of pancreatic cancer in workers exposed to DE (RR: 1.07, 95% CI: 1.00, 1.14), mainly driven by results on incidence (RR: 1.11, 95% CI: 1.02, 1.22). As for liver cancer, results were suggestive of a positive association (RR: 1.09; 95% CI: 0.99, 1.19), although a significant estimate was present in studies published before 2000 (RR: 1.41; 95% CI: 1.09, 1.82). We found no compelling evidence of publication bias. Conclusions: Our findings suggest an association between occupational DE exposure and liver and pancreatic cancer. Further studies with detailed exposure assessment, environmental monitoring data, and appropriate control for confounders are warranted. [ABSTRACT FROM AUTHOR]

Objective: This survey aimed to investigate exposure to welding fume in Australian workplaces and the use of protective and control measures among workers. Methods: Data were collected via a cross-sectional online survey of workers and employers involved in welding in Australia. Survey questions focused on the determinants of exposure to welding fume, welding experience and qualifications, and use of control measures. Results: There were 634 respondents to the survey across Australia of whom 577 (91%) were assessed as being exposed to welding fume, most at high levels. Welders undertook a wide range of types of welding, and higher-risk welding such as in confined and restricted spaces was common. Most workplaces did not have any form of mechanical ventilation, and use of air-supplied respiratory protection was poor even when ventilation was not used. Conclusion: Welders in Australia are exposed to several carcinogens, particularly welding fume, hexavalent chromium (CrVI) and nickel, and the use of control measures is sub-optimal. Implications for Public Health: Higher-order controls are the best way to reduce exposure to carcinogens in the workplace. The lack of use of these controls by Australian welders is concerning and needs to be a focus of attention by regulators and companies.

An electronic cigarette is a rechargeable device that produces an inhaled aerosol containing varying levels of nicotine, and inorganic and organic toxicants and carcinogenic compounds. The aerosol is generated by heating a solution of propylene glycol and glycerin with nicotine and flavoring ingredients at a high temperature. The e-cigarette was developed and marketed as a safer alternative to the regular cigarette which is known to be injurious to human health. However, published studies suggest that the aerosol of e-cigarette can also have adverse health effects. The main objective of this review is to briefly describe some consequences of e-cigarette smoking, and to present data showing that the resulting increased oxidative stress and inflammation are likely to be involved in effecting to lung damage. Other organs are also likely to be affected. The aerosol contains varying amounts of organic and inorganic toxicants as well as carcinogens, which might serve as the source of such deleterious events. In addition, the aerosol also contains nicotine, which is known to be addictive. E-cigarette smoking releases these toxicants into the air leading to inhalation by nonsmokers in residential or work place areas. Unlike regular tobacco smoke, the long-term consequences of direct and secondhand exposure to e-cigarette aerosol have not been extensively studied but based on available data, e-cigarette aerosol should be considered harmful to human health.

BackgroundKey characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents.ObjectivesThe goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs.MethodsA committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity.DiscussionKCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800.

Tobacco-specific nitrosamines (TSNAs) are emitted during smoking and form indoors by nitrosation of nicotine. Two of them, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are human carcinogens with No Significant Risk Levels (NSRLs) of 500 and 14 ng day-1, respectively. Another TSNA, 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity in vitro. Here, we present additional evidence of genotoxicity of NNA, an assessment of TSNA dermal uptake, and predicted exposure risks through different pathways. Dermal uptake was investigated by evaluating the penetration of NNK and nicotine through mice skin. Comparable mouse urine metabolite profiles suggested that both compounds were absorbed and metabolized via similar mechanisms. We then investigated the effects of skin constituents on the reaction of adsorbed nicotine with nitrous acid (epidermal chemistry). Higher TSNA concentrations were formed on cellulose and cotton substrates that were precoated with human skin oils and sweat compared to clean substrates. These results were combined with reported air, dust, and surface concentrations to assess NNK intake. Five different exposure pathways exceeded the NSRL under realistic scenarios, including inhalation, dust ingestion, direct dermal contact, gas-to-skin deposition, and epidermal nitrosation of nicotine. These results illustrate potential long-term health risks for nonsmokers in homes contaminated with thirdhand tobacco smoke.

In the European Union, Occupational Safety and Health legislation generally refers to European Regulation (CE) n. 1272/2008 to define and classify carcinogens of concern for occupational risk assessment and exposure assessment. In Europe, the current reference is Directive (UE) 2022/431, regarding carcinogen, mutagen, and reprotoxic agent (CMR) exposure. However, at the worldwide level, different classification approaches are used to establish carcinogenicity of substances and it is often difficult to compare the classifications of carcinogenicity (CoCs) proposed by different international bodies. This study aims to investigate a list of carcinogens of concern in occupational settings based on the CLP (Classification Labelling Packaging) CoC and to create a tool that allows a rapid translation–comparison of some international CoCs with the reference one. CoCs proposed by various sources were consulted and used to apply a translation method, to favor an alignment of different CoCs according to a reference. Results outlined that, considering diverse sources, CoCs can result in different classifications of the same chemicals. Overall, this may have implications for the hazard assessment process, which is the base of risk assessment. The proposed tool is expected to help risk assessors in the occupational field when it is needed to have a comparison with different CoC systems.

Background Central register of data on exposure to carcinogenic or mutagenic chemical substances, their mixtures, agents or technological processes (CRCR) conducted by Nofer Institute of Occupational Medicine (NIOM) enables monitoring of such agents occurrence in working environment in Poland. The NIOM conducts CRCR based on the provisions of the Regulation of the Minister of Health of 24 July 2012 on chemical substances, their mixtures, agents or technological processes with carcinogenic or mutagenic effects in the work environment. The work summarizes the information reported to CRCR in 2018–2021. Material and Methods The data were extracted from CRCR, to which it was transferred by sanitary inspections. The data were extracted from CRCR. Data in this register is gathered based on employers’ notifications to sanitary inspection. The study includes the number of reported agents (chemical substances and technological processes), the number of enterprises and the number of persons exposed to particular groups of agents (chemical substances, technological processes, ionizing radiation). Results The number of substances notified to the CRCR increases, from 382 reported substances in 2018 to 444 in 2021. Significant increase in the number of enterprises reporting technological processes (from 981 in 2018 to 5422 in 2021) and the number of exposed persons results from the law amendments extending the list of carcinogenic or mutagenic processes. Conclusions The CRCR is a unique database on the occurrence and exposure to occupational carcinogens and mutagens, in which data from over 20 years has been collected. The increase in the number of reports to the register was mainly influenced by legislative changes regarding carcinogenic or mutagenic agents. Due to amount and complexity of data, they can be used for analysis in projects and programs aimed at raising awareness and reducing risk of occupational exposure to carcinogens and also during legislative works in Poland and in the EU. Med Pr Work Health Saf. 2023;74(5):399–407.

The collapse of the World Trade Center (WTC) buildings in New York City generated a large plume of dust and smoke. WTC dust contained human carcinogens including metals, asbestos, polycyclic aromatic hydrocarbons (PAHs), persistent organic pollutants (POPs, including polychlorinated biphenyls (PCBs) and dioxins), and benzene. Excess levels of many of these carcinogens have been detected in biological samples of WTC-exposed persons, for whom cancer risk is elevated. As confirmed in this structured literature review (n studies = 80), all carcinogens present in the settled WTC dust (metals, asbestos, benzene, PAHs, POPs) have previously been shown to be associated with DNA methylation dysregulation of key cancer-related genes and pathways. DNA methylation is, therefore, a likely molecular mechanism through which WTC exposures may influence the process of carcinogenesis.

BackgroundThe Food and Drug Administration (FDA) has recently banned flavours from pod-style electronic cigarettes (e-cigarettes), except for menthol and tobacco. JUUL customers have quickly discovered that flavoured disposable e-cigarettes from other manufacturers, such as Puff, are readily available. Our goal was to compare flavour chemicals, synthetic coolants and pulegone in mint-flavoured/menthol-flavoured e-cigarettes from JUUL and Puff, evaluate the cytotoxicity of the coolants and perform a cancer risk assessment for pulegone, which is present in both JUUL pods and disposable Puff products.MethodsIdentification and quantification of chemicals were performed using gas chromatography/mass spectrometry. Cytotoxicity of the coolants was evaluated with BEAS-2B cells using the MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cancer risk of pulegone was calculated using the margin of exposure (MOE).ResultsMenthol was the dominant flavour chemical (>1 mg/mL) in all products from both manufacturers. Minor flavour chemicals (