Prioritizing of potential environmental exposure carcinogens beyond IARC group 1-2B based on weight of evidence (WoE) approach.

Environmental exposures are the main cause of cancer, and their carcinogenicity has not been fully evaluated, identifying potential carcinogens that have not been evaluated is critical for safety. This study is the first to propose a weight of evidence (WoE) approach based on computational methods to prioritize potential carcinogens. Computational methods such as read across, structural alert, (Quantitative) structure-activity relationship and chemical-disease association were evaluated and integrated. Four different WoE approach was evaluated, compared to the best single method, the WoE-1 approach gained 0.21 and 0.39 improvement in the area under the receiver operating characteristic curve (AUC) and Matthew's correlation coefficient (MCC) value, respectively. The evaluation of 681 environmental exposures beyond IARC list 1-2B prioritized 52 chemicals of high carcinogenic concern, of which 21 compounds were known carcinogens or suspected carcinogens, and eight compounds were identified as potential carcinogens for the first time. This study illustrated that the WoE approach can effectively complement different computational methods, and can be used to prioritize chemicals of carcinogenic concern.

How to improve IARC's RF-EMF cancer hazard communication.

A crucial aspect of IARC's evaluation of the relative carcinogenicity of agents is the communication of its conclusions. The present paper addressed the experimental risk perception literature pertaining to IARC's radiofrequency electromagnetic field evaluation communication, and derived specific recommendations for improving it.

Serology Identifies LIPyV as a Feline Rather than a Human Polyomavirus.

The number of identified human polyomaviruses (HPyVs) has increased steadily over the last decade. Some of the novel HPyVs have been shown to cause disease in immunocompromised individuals. The Lyon-IARC polyomavirus (LIPyV) belonging to species Alphapolyomavirus quardecihominis was identified in 2017 in skin and saliva samples from healthy individuals. Since its initial discovery, LIPyV has rarely been detected in human clinical samples but has been detected in faeces from cats with diarrhoea. Serological studies show low LIPyV seroprevalence in human populations. To investigate the possibility that LIPyV is a feline rather than a human polyomavirus, we compared serum IgG responses against the VP1 major capsid protein of LIPyV and 13 other HPyVs among cats (n = 40), dogs (n = 38) and humans (n = 87) using an in-house immunoassay. Seropositivity among cats was very high (92.5%) compared to dogs (31.6%) and humans (2.3%). Furthermore, the median antibody titres against LIPyV were 100-10,000x higher in cats compared to dogs and humans. In conclusion, the high prevalence and intensity of measured seroresponses suggest LIPyV to be a feline rather than a human polyomavirus. Whether LIPyV infection induces diarrhoea or other symptoms in cats remains to be established.

Comparison between two cancer registry quality check systems: functional features and differences in an Italian network of cancer registries dataset.

Purpose: The aim of this study was to compare the functional characteristics of two computer-based systems for quality control of cancer registry data through analysis of their output differences. Methods: The study used cancer incidence data from 22 of the 49 registries of the Italian Network of Cancer Registries registered between 1986 and 2017. Two different data checking systems developed by the WHO International Agency for Research on Cancer (IARC) and the Joint Research Center (JRC) with the European Network of Cancer Registries (ENCR) and routinely used by registrars were used to check the quality of the data. The outputs generated by the two systems on the same dataset of each registry were analyzed and compared. Results: The study included a total of 1,305,689 cancer cases. The overall quality of the dataset was high, with 86% (81.7-94.1) microscopically verified cases and only 1.3% (0.03-3.06) cases with a diagnosis by death certificate only. The two check systems identified a low percentage of errors (JRC-ENCR 0.17% and IARC 0.003%) and about the same proportion of warnings (JRC-ENCR 2.79% and IARC 2.42%) in the dataset. Forty-two cases (2% of errors) and 7067 cases (11.5% of warnings) were identified by both systems in equivalent categories. 11.7% of warnings related to TNM staging were identified by the JRC-ENCR system only. The IARC system identified mainly incorrect combination of tumor grade and morphology (72.5% of warnings). Conclusion: Both systems apply checks on a common set of variables, but some variables are checked by only one of the systems (for example, checks on patient follow-up and tumor stage at diagnosis are included by the JRC-ENCR system only). Most errors and warnings were categorized differently by the two systems, but usually described the same issues, with warnings related to "morphology" (JRC-ENCR) and "histology" (IARC) being the most frequent. It is important to find the right balance between the need to maintain high standards of data quality and the workability of such systems in the daily routine of the cancer registry.

Oral Cavity Squamous Cell Carcinoma Risk Factors: State of the Art.

Head and neck (HN) squamous cell carcinomas (SCCs) originate from the epithelial cells of the mucosal linings of the upper aerodigestive tract, which includes the oral cavity, the pharynx, the larynx, and the sinonasal cavities. There are many associated risk factors, including alcohol drinking coupled with tobacco use, which accounts for 70% to 80% of HNSCCs. Human papilloma virus (HPV) is another independent risk factor for oropharyngeal SCC, but it is only a minor contributor to oral cavity SCC (OSCC). Betel quid chewing is also an established risk factor in southeast Asian countries. However, OSCC, and especially oral tongue cancer, incidence has been reported to be increasing in several countries, suggesting risk factors that have not been identified yet. This review summarizes the established risk factors for oral cavity squamous cell carcinomas and examines other undemonstrated risk factors for HNSCC.

A brief review of the WHO reporting system for lung cytopathology.

The International Academy of Cytology has joined with the International Agency for Research on Cancer to bring together a group of experts in lung cytopathology to develop a WHO Reporting System for Lung Cytopathology (WHO System). This System aims to improve and standardize the reporting of cytopathology, facilitate communication between cytopathologists and clinicians, and improve patient care. The WHO System describes 5 categories for reporting lung cytopathology: 'Insufficient/Inadequate/Nondiagnostic', 'Benign', 'Atypical', 'Suspicious for malignancy', and 'Malignant', each one with a clear descriptive term, a definition, a risk of malignancy, and a suggested management algorithm. The key diagnostic cytopathologic features of each of the lesions within each category have been established by consensus through an Expert Editorial Board, who are also the authors of this review and selected for each reporting system and chosen based on their expertise in the field and/or diversity of geographical representation. Many other co-authors from around the world also contributed. The assignment of writing and editing responsibilities used the same model as that used for the WHO Classification of Tumours (https://whobluebooks.iarc.fr/about/faq/). The WHO System provides the best practice application of ancillary testing, including immunocytochemistry and molecular pathology, and guides in sampling and processing techniques to optimize the handling and preparation of specimens. The WHO System was created by the authors to be applicable globally and is based on cytomorphology with possibilities for additional diagnostic management of the patient. The authors are aware that local medical and pathology resources would differ, especially in low- and middle-income countries. The WHO Tumour Classification for Thoracic Tumors, Fifth Edition, is directly accessible through the online WHO System.

An update on the current status and prospects of nitrosation pathways and possible root causes of nitrosamine formation in various pharmaceuticals.

Over the last two years, global regulatory authorities have raised safety concerns on nitrosamine contamination in several drug classes, including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control limits for nitrosamine impurities in pharmaceuticals. In this review, nitrosation pathways and possible root causes of nitrosamine formation in pharmaceuticals are discussed. The control limits of nitrosamine impurities in pharmaceuticals proposed by national regulatory authorities are presented. Additionally, a practical and science-based strategy for implementing the well-established control limits is notably reviewed in terms of an alternative approach for drug product N-nitrosamines without published AI information from animal carcinogenicity testing. Finally, a novel risk evaluation strategy for predicting and investigating the possible nitrosation of amine precursors and amine pharmaceuticals as powerful prevention of nitrosamine contamination is addressed.

Exposures to pesticides and risk of cancer: Evaluation of recent epidemiological evidence in humans and paths forward.

Knowledge of the role in cancer etiology of environmental exposures as pesticides is a prerequisite for primary prevention. We review 63 epidemiological studies on exposure to pesticides and cancer risk in humans published from 2017 to 2021, with emphasis on new findings, methodological approaches, and gaps in the existing literature. While much of the recent evidence suggests causal relationships between pesticide exposure and cancer, the strongest evidence exists for acute myeloid leukemia (AML) and colorectal cancer (CRC), diseases in which the observed associations were consistent across several studies, including high-quality prospective studies and those using biomarkers for exposure assessment, with some observing dose-response relationships. Though high-quality studies have been published since the IARC monograph on organophosphate insecticides in 2017, there are still gaps in the literature on carcinogenic evidence in humans for a large number of pesticides. To further knowledge, we suggest leveraging new techniques and methods to increase sensitivity and precision of exposure assessment, incorporate multi-omics data, and investigate more thoroughly exposure to chemical mixtures. There is also a strong need for better and larger population-based cohort studies that include younger and nonoccupationally exposed individuals, particularly during developmental periods of susceptibility. Though the existing evidence has limitations, as always in science, there is sufficient evidence to implement policies and regulatory action that limit pesticide exposure in humans and, hence, further prevent a significant burden of cancers.

Long-term survival trends for primary liver and pancreatic cancers in the Nordic countries.

Background & Aims: Liver cancer (LC) and pancreatic cancer (PC) are often diagnosed at an advanced stage resulting in high mortality. High-quality survival data are rarely available for trend analyses over a long period. Methods: The Danish, Finnish, Norwegian, and Swedish cancer data were accessed at the NORDCAN database. We analysed relative 1- and 5-year survival trends in LC and PC between years 1970 and 2019. Results: Relative 1-year survival in LC for Nordic men and women was about 10% in the period between 1970 and 1974, and it increased moderately by year 2000 and steeply thereafter, eventually reaching 40-50%. The patterns in 5-year survival were similar, but after the year 2000, survival in Norway and Sweden increased steeply to 23%, whereas survival in Denmark and Finland lagged behind, reaching 10% to 15%. The patterns for PC also showed rapid improvement after the year 2000, with 1-year survival reaching 30% to 40% and 5-year survival reaching 10% for Finland and 15% for Norway and Sweden. Survival was best for patients diagnosed before age 50 years, and it was worst for older patients. For both cancers the difference between 1- and 5-year survival increased with time. Conclusions: Survival in LC and PC improved first modestly and then steeply over the 50-year period covered. The increase in 5-year survival was less than that of 1-year survival. The survival gains were most likely the result of earlier diagnosis, improved treatment, and better organised supportive care. The challenges are to keep up these positive trends, to extend survival benefits past Year 1, and to obtain similar results in elderly patients. Primary prevention through avoidance of risk factors would reduce case numbers. Lay summary: Liver and pancreatic cancers are among the most lethal of all cancers. In 50 years, survival in these cancers has slowly improved, and in the past 20 years, the development has been increasingly favourable. Widespread adoption of healthy lifestyles will be key to reducing the risk of these cancers.

Stark differences in cancer epidemiological data between GLOBOCAN and GBD: Emphasis on oral cancer and wider implications.

Background: GLOBOCAN 2020 and Global Burden of Disease (GBD) 2019 are the two most established global online cancer databases. It is important to examine the differences between the two platforms, to attempt to explain these differences, and to appraise the quality of the data. There are stark differences for lip and oral cancers (LOC) and we attempt to explain these by detailed analysis of ten countries at the extremes of differences. Methods: Age-standardised incidence rates (ASIR) of LOC were obtained from GLOBOCAN 2020 and GBD 2019. Five countries with the greatest and smallest fold differences were selected. A systematic search of PubMed and Embase electronic databases was then performed to identify publications reporting the incidence of LOC in the selected countries between 2015 and 2022. Specifically, data sources of the articles were examined and evaluated. Findings: For LOC, greatest differences were found in Papua New Guinea, Vietnam, China, Pakistan, and Indonesia (group A). In contrast, the United States of America (USA), Brazil, France, Germany, and India (group B) had the least differences between the two databases. Interpretation: It is not surprising that when GLOBOCAN and GBD could not obtain high-quality or accessible LOC data from national or local cancer registries, as in group A, discrepancies would be seen between the two online databases. In contrast, where only minor differences were seen between GLOBOCAN and GBD, as in group B, presumptively due to those countries having well-established cancer registries and healthcare administrative systems, the literature is more consistent. Moreover, many studies have grouped lip and oral cavity with pharynx and categorised outputs as "oral and oropharyngeal cancer" or "oral cavity and pharynx cancer". Those categorisations lacked subsite accuracy and failed to realise that oral cancer and oropharyngeal cancer have completely different etiological factors, pathogeneses, prognosis, and treatment outcomes. Funding: This research received no specific grant or funding from any funding agency in the public, commercial, or not-for-profit sectors, and the authors received no financial support for the research, authorship, and/or publication of this article.

Extrahepatic Manifestations in Alcoholic Liver Disease.

Though liver is the most commonly affected organ in patients with chronic and excessive intake of alcohol, no organ is immune to toxic effects of alcohol and patients with alcohol-related liver disease (ALD) can suffer from a wide list of extrahepatic manifestations involving gastrointestinal tract, central and peripheral nervous systems, cardio vascular system, musculo-skeletal system, disruption of nutritional status, endocrinological abnormalities, hematological abnormalities and immune dysfunction. These extrahepatic organ involvements are usually overlooked by hepatologists and physicians who are mostly focused on managing life threatening complications of ALD. As a result, there is delayed diagnosis, delay in the initiation of appropriate treatment and late referral to other specialists. Some of these manifestations are of utmost clinical importance (e.g. delirium tremans and Wernicke's encephalopathy) because an early diagnosis and treatment can lead to full recovery while delayed or no treatment can result in death. On the other hand, several extrahepatic manifestations are of prognostic significance (such as alcoholic cardiomyopathy and malignancies) in which there is an increased risk of morbidity and mortality. Hence, a clear understanding and awareness of the extrahepatic manifestations of ALD is quintessential for proper management of these patients.

Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.

BACKGROUND: Gastric cancer imposes a substantial global health burden despite its overall incidence decrease. A broad spectrum of inherited, environmental and infectious factors contributes to the development of gastric cancer. A profound understanding of the molecular underpinnings of gastric cancer has lagged compared to several other tumors with similar incidence and morbidity rates, owing to our limited knowledge of the role of carcinogens in this malignancy. The International Agency for Research on Cancer (IARC) has classified gastric carcinogenic agents into four groups based on scientific evidence from human and experimental animal studies. This review aims to explore the potential comprehensive molecular and biological impacts of carcinogens on gastric cancer development and their interactions and interferences with various cellular signaling pathways. CONCLUSIONS: In this review, we highlight recent clinical trial data reported in the literature dealing with different ways to target various carcinogens in gastric cancer. Moreover, we touch upon other multidisciplinary therapeutic approaches such as surgery, adjuvant and neoadjuvant chemotherapy. Rational clinical trials focusing on identifying suitable patient populations are imperative to the success of single-agent therapeutics. Novel insights regarding signaling pathways that regulate gastric cancer can potentially improve treatment responses to targeted therapy alone or in combination with other/conventional treatments. Preventive strategies such as control of H. pylori infection through eradication or immunization as well as dietary habit and lifestyle changes may reduce the incidence of this multifactorial disease, especially in high prevalence areas. Further in-depth understanding of the molecular mechanisms involved in the role of carcinogenic agents in gastric cancer development may offer valuable information and update state-of-the-art resources for physicians and researchers to explore novel ways to combat this disease, from bench to bedside. A schematic outlining of the interaction between gastric carcinogenic agents and intracellular pathways in gastric cancer H. pylori stimulates multiple intracellular pathways, including PI3K/AKT, NF-κB, Wnt, Shh, Ras/Raf, c-MET, and JAK/STAT, leading to epithelial cell proliferation and differentiation, apoptosis, survival, motility, and inflammatory cytokine release. EBV can stimulate intracellular pathways such as the PI3K/Akt, RAS/RAF, JAK/STAT, Notch, TGF-ß, and NF-κB, leading to cell survival and motility, proliferation, invasion, metastasis, and the transcription of anti-apoptotic genes and pro-inflammatory cytokines. Nicotine and alcohol can lead to angiogenesis, metastasis, survival, proliferation, pro-inflammatory, migration, and chemotactic by stimulating various intracellular signaling pathways such as PI3K/AKT, NF-κB, Ras/Raf, ROS, and JAK/STAT. Processed meat contains numerous carcinogenic compounds that affect multiple intracellular pathways such as sGC/cGMP, p38 MAPK, ERK, and PI3K/AKT, leading to anti-apoptosis, angiogenesis, metastasis, inflammatory responses, proliferation, and invasion. Lead compounds may interact with multiple signaling pathways such as PI3K/AKT, NF-κB, Ras/Raf, DNA methylation-dependent, and epigenetic-dependent, leading to tumorigenesis, carcinogenesis, malignancy, angiogenesis, DNA hypermethylation, cell survival, and cell proliferation. Stimulating signaling pathways such as PI3K/Akt, RAS/RAF, JAK/STAT, WNT, TGF-ß, EGF, FGFR2, and E-cadherin through UV ionizing radiation leads to cell survival, proliferation, and immortalization in gastric cancer. The consequence of PI3K/AKT, NF-κB, Ras/Raf, ROS, JAK/STAT, and WNT signaling stimulation by the carcinogenic component of Pickled vegetables and salted fish is the Warburg effect, tumorigenesis, angiogenesis, proliferation, inflammatory response, and migration.

Opium, Street Opium, and Cancer Risk.

Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10% morphine and 2% codeine. It is commonly used to prepare opium tinctures for people with chronic diarrhea. Morphine and related opioids are powerful but highly addictive analgesics; designing less addictive opioids is an active area of pharmaceutical research that may lead to significant improvements in chronic pain management. Recently, the International Agency for Research on Cancer (IARC) has classified opium consumption as carcinogenic to humans (Group 1) based on sufficient evidence of carcinogenicity in human studies. However, all human studies analyzed by the IARC Working Group included participants who consumed opium that was mixed, adulterated, and/or contaminated with known and probable human carcinogens (e.g., tarry residues of combusted opium, arsenic, lead, and chromium). The working group considered that these carcinogens were part of the complex mixture that opium is, rather than co-exposure or confounders. No evidence of carcinogenicity was available for pure opium in human, animal, or mechanistic studies. To avoid confusion and concern among health professionals and patients using medicinal opium preparations and in scientists involved in the design and development of new opium derivatives, opium should be classified in Group 3 (not classifiable as to its carcinogenicity to humans). The term 'street opium' could be used to refer to opium that probably contains human carcinogens not present in pure opium and should remain in Group 1 (carcinogenic to humans).

Lyon IARC Polyomavirus Displays Transforming Activities in Primary Human Cells.

Several studies reported the presence of a recently discovered polyomavirus (PyV), Lyon IARC PyV (LIPyV), in human and domestic animal specimens. LIPyV has some structural similarities to well-established animal and human oncogenic PyVs, such as raccoon PyV and Merkel cell PyV (MCPyV), respectively. In this study, we demonstrate that LIPyV early proteins immortalize human foreskin keratinocytes. LIPyV LT binds pRb, accordingly cell cycle checkpoints are altered in primary human fibroblasts and keratinocytes expressing LIPyV early genes. Mutation of the pRb binding site in LT strongly affected the ability of LIPyV ER to induced HFK immortalization. LIPyV LT also binds p53 and alters p53 functions activated by cellular stresses. Finally, LIPyV early proteins activate telomerase reverse transcriptase (hTERT) gene expression, via accumulation of the Sp1 transcription factor. Sp1 recruitment to the hTERT promoter is controlled by its phosphorylation, which is mediated by ERK1 and CDK2. Together, these data highlight the transforming properties of LIPyV in in vitro experimental models, supporting its possible oncogenic nature. IMPORTANCE Lyon IARC PyV is a recently discovered polyomavirus that shows some structural similarities to well-established animal and human oncogenic PyVs, such as raccoon PyV and Merkel cell PyV, respectively. Here, we show the capability of LIPyV to efficiently promote cellular transformation of primary human cells, suggesting a possible oncogenic role of this virus in domestic animals and/or humans. Our study identified a novel virus-mediated mechanism of activation of telomerase reverse transcriptase gene expression, via accumulation of the Sp1 transcription factor. In addition, because the persistence of infection is a key event in virus-mediated carcinogenesis, it will be important to determine whether LIPyV can deregulate immune-related pathways, similarly to the well-established oncogenic viruses.

Histological changes of cervical tumours following Zanthoxylum acanthopodium DC treatment, and its impact on cytokine expression.

Cervical cancer is the second most lethal cancer in Indonesia, behind breast cancer. One of the reasons cancer cells are difficult to treat is that the immune system is sometimes unable to recognise them as foreign. Cytokinin therapy is carried out so that the immune system can strengthen its response to cancer cells, with the aim of slowing or stopping the development of malignant cells. Zanthoxylum acanthopodium DC, also known as andaliman, is an Indonesian herb and a member of the Rutaceae family. It is rich in antioxidants and has anti-inflammatory and anti-cancer properties. The current study aimed to investigate the histological changes and changes in the expression of cytokines, such as IL-10, IL1ß, VEGFR1, and TGFß1, associated with andaliman treatment. Sample tissues and serums extracted from cervical cancer rat models were used. Rats were divided into five groups: a control group (C-), cancer model group (C+), cancer with a dose of Z. acanthopodium methanolic extract (ZAM) 100 mg/body weight (BW) ZAM (ZAM100), cancer with a dose of ZAM 200 mg/BW ZAM (ZAM200), and cancer with a dose of ZAM 400 mg/BW ZAM (ZAM400). Treatment lasted for 1 month. Blood samples were prepared for ELISA analysis, and cervical tissue was stained for immunohistochemistry using antibodies against IL-10, IL-1ß, VEGFR1, and TGFß1. Administration of ZAM had no significant effect on rat body weight and cervical organs (p > 0.05). However, it impacted haematological parameters in rats with cervical cancer (p < 0.05). Elevated malondialdehyde levels may be linked to superoxide dismutase deficiency in tumour tissue. ZAM significantly decreased the expression of IL1ß, TGFß1, and VEGFR1 (p < 0.01), while it increased the expression of IL-10. Therefore, ZAM may be a potential target for molecular cytokine therapy for cervical cancer.

Global patterns of Hodgkin lymphoma incidence and mortality in 2020 and a prediction of the future burden in 2040.

Our study examines global patterns of Hodgkin lymphoma (HL) in 2020 and predicts the future incidence and mortality burden in 2040 using IARC's GLOBOCAN estimates of the number of new cases and deaths of HL in 185 countries. A total of 83 000 new cases of HL and 23 000 deaths from HL were estimated in 2020. In general, incidence and mortality rates were consistently higher in males (50% more cases and deaths than females) across world regions and countries. Incidence rates varied markedly by world region, at least 10-fold in both sexes, with the highest incidence rates observed in Southern Europe. Mortality exhibited an inverse pattern compared to incidence, with rates elevated in Western Asia and Northern Africa. The number of HL incident cases is predicted to rise to around 107 000 cases (a 30% increase) by 2040 due to demographic changes, assuming global rates in 2020 remains unchanged. The findings provide a baseline and impetus for developing strategies that aim to reduce the burden of HL in future decades.

Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?

Natural bioactive compounds with anti-carcinogenic activity are gaining tremendous interest in the field of oncology. Cinnamon, an aromatic condiment commonly used in tropical regions, appeared incredibly promising as an adjuvant for cancer therapy. Indeed, its whole or active parts (e.g., bark, leaf) exhibited significant anti-carcinogenic activity, which is mainly due to two cinnamaldehyde derivatives, namely 2-hydroxycinnaldehyde (HCA) and 2- benzoyloxycinnamaldehyde (BCA). In addition to their anti-cancer activity, HCA and BCA exert immunomodulatory, anti-platelets, and anti-inflammatory activities. The highly reactive α,ßunsaturated carbonyl pharmacophore, called Michael acceptor, contributes to their therapeutic effects. The molecular mechanisms underlying their anti-tumoral and anti-metastatic effects are miscellaneous, strongly suggesting that these compounds are multi-targeting compounds. Nevertheless, unravelling the exact molecular mechanisms of HCA and BCA remains a challenging matter which is necessary for optimal controlled-drug targeting delivery, safety, and efficiency. Eventually, their poor pharmacological properties (e.g., systemic bioavailability and solubility) represent a limitation and depend both on their administration route (e.g., per os, intravenously) and the nature of the formulation (e.g., free, smart nano-). This concise review focused on the potential of HCA and BCA as adjuvants in cancer. We describe their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.

Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre crystal-chemical and physical parameters to the key characteristics of cancer.

Airborne fibres and particularly asbestos represent hazards of great concern for human health because exposure to these peculiar particulates may cause malignancies such as lung cancer and mesothelioma. Currently, many researchers worldwide are focussed on fully understanding the patho-biological mechanisms leading to carcinogenesis prompted by pathogenic fibres. Along this line, the present work introduces a novel approach to correlate how and to what extent the physical/crystal-chemical and morphological parameters (including length, chemistry, biodurability, and surface properties) of mineral fibres cause major adverse effects with an emphasis on asbestos. The model described below conceptually attempts to bridge the gap between toxicity and carcinogenicity of mineral fibres and has several implications: 1) it provides a tool to measure the toxicity and pathogenic potential of asbestos minerals, allowing a quantitative rank of the different types (e.g. chrysotile vs. crocidolite); 2) it can predict the toxicity and pathogenicity of "unregulated" or unclassified fibres; 3) it reveals the parameters of a mineral fibre that are active in stimulating key characteristics of cancer, thus offering a strategy for developing specific cancer prevention strategies and therapies. Chrysotile, crocidolite and fibrous glaucophane are described here as mineral fibres of interest.