Search

Intraarterial chemotherapy (Ophthalmic Artery Chemosurgery/OAC) for retinoblastoma has transformed management of retinoblastoma worldwide since Pierre Gobin MD and I introduced it in 2006. Case reports, institutional series, meta-analyses, and randomized trials have validated its effectiveness and safety. It allows more eyes to be saved (at Memorial Sloan Kettering Cancer Center (MSKCC) as a result, we have gone from removing 96% of retinoblastoma eyes that presented with leukocoria (comparable to modern day International Classification “D” and “E” eyes) to saving 95% of these eyes with primary OAC management allows the majority of advanced intraocular eyes to be salvaged (both “D” and “E” eyes) prior to the chemoreduction era to saving 95% of these eyes with primary OAC management. OAC attains cures faster than intravenous protocols, has fewer systemic side effects, and is overall cheaper than intravenous approaches (because of the absence of side effects which are the main driver of cost in pediatric oncology). Unlike systemic chemotherapy no ports are needed (and no removal of ports for life threatening infections), it does not alter the immune system (so children can be immunized), it does not affect patient growth (and children who had received systemic chemotherapy catch up in growth during OAC), it does not affect hearing (which systemic Carboplatin does-especially in children <6 months of age), it eliminates the second cancers caused by radiation and systemic chemotherapy and does not compromise survival with all series showing patient survival >98%. [ABSTRACT FROM AUTHOR]

Background: One of the ailments with the greatest fatality rates in the 21st century is cancer. Globally, molecular methods are widely employed to treat cancer-related disorders, and the body of research on this subject is growing yearly. A thorough and critical summary of the data supporting molecular methods for illnesses linked to cancer is required. Objective: In order to guide clinical practice and future research, it is important to examine and summarize the systematic reviews (SRs) that evaluate the efficacy and safety of molecular methods for disorders associated to cancer. Methods: We developed a comprehensive search strategy to find relevant articles from electronic databases like PubMed, Google Scholar, Web of Science (WoS), or Scopus. We looked through the literature and determined which diagnostic methods in cancer genetics were particularly reliable. We used phrases like 'cancer genetics', genetic susceptibility, Hereditary cancer, cancer risk assessment, 'cancer diagnostic tools', cancer screening', biomarkers, and molecular diagnostics, reviews and meta-analyses evaluating the efficacy and safety of molecular therapies for cancer-related disorders. Research that only consider treatment modalities that don't necessitate genetic or molecular diagnostics fall under the exclusion criteria. Results: The results of this comprehensive review clearly demonstrate the transformative impact of molecular methods in the realm of cancer genetics. This review underscores how these technologies have empowered researchers and clinicians to identify and understand key genetic alterations that drive malignancy, ranging from point mutations to structural variations. Such insights are instrumental in pinpointing critical oncogenic drivers and potential therapeutic targets, thus opening the door for methods in precision medicine that can significantly improve patient outcomes. Limitation:: The search does not specify a timeframe for publication inclusion, it may have missed recent advancements or changes in the field's landscape of molecular methods for cancer. As a result, it may not have included the most recent developments in the field. Conclusion: After conducting an in-depth study on the molecular methods in cancer genetics, it is evident that these cutting-edge technologies have revolutionized the field of oncology, providing researchers and clinicians with powerful tools to unravel the complexities of cancer at the genetic level. The integration of molecular methods techniques has not only enhanced our understanding of cancer etiology, progression, and treatment response but has also opened new avenues for personalized medicine and targeted therapies, leading to improved patient outcomes. [ABSTRACT FROM AUTHOR]

Early diagnosis of hepatocellular carcinoma (HCC), a leading cause of cancer mortality, is decisive for successful treatment of this type of cancer and increasing the patients' survival rate. Alpha-fetoprotein (AFP) is a glycoprotein that has been currently employed as a potential serological biomarker for determination of HCC and several other cancers. Achieving highly sensitive and specific detection of this biomarker is an effective strategy to inhibit developing issues caused by the cancer. Though, traditional procedures cannot meet the requirements due to the technical drawbacks. Recently, growing number of aptamer-based biosensors (aptasensors) attracted important attention as superior diagnostic tools because of their unique properties such as high stability, target versatility and remarkable affinity and selectivity. Nanomaterials, which broadly employed in the structure of these aptasensors, can considerably enhance the detection limit and sensitivity of analytes determination. Therefore, this review selectively investigated the recent progresses in several different optical and electrochemical aptasensors and nano-aptasensors designed for AFP assay. [ABSTRACT FROM AUTHOR]

This article explores the role of progesterone in breast cancer, emphasizing the distinction between causing breast cancer and stimulating its growth. The authors highlight the mutagenicity of progesterone and its ability to stimulate the synthesis of mutagens in normal breast cells. They also discuss the relationship between menstrual cycles, reproductive hormones, and breast cancer occurrence. The article suggests that hormonal contraception and menopausal hormone therapy do not significantly increase breast cancer risk, but long-term use of progestogen-only contraception may have a higher risk. The protective effect of pregnancy on breast cancer is also discussed, as well as the lag time between a mutation and breast cancer diagnosis. The authors propose further research to fully understand the relationship between progesterone and breast cancer. [Extracted from the article]

Gastric cancer is a common cause of cancer death in the world. This study examined 120 rural women. The educational program included four sessions for each group based on the health belief model. The mean age of the women was 34.51 ± 9.16. The mean score of the perceived barriers significantly decreased in the experimental group (11.08 ± 0.37) compared to the control group (14.92 ± 0.42) (P <.001), and the mean score of knowledge, performance and HBM constructs, increased significantly 2 months after the education (P <.001).It is recommended that educational interventions be designed by HBM to improve nutritional behaviors related to GC in the female population. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is one of the most common malignant tumors of the upper gastrointestinal tract. The etiology of EC is complicated and increasing evidence has shown that microbial infection is closely related to the occurrence of various malignant tumors. Though many studies have been focused on this subject in recent years, the exact relationship between microbial infection and the occurrence of EC remains unclear. In this review, we searched all eligible literature reports, summarized the most recent studies in this research field, and analyzed the pathogenic microorganisms associated with EC, providing the latest evidence and references for the prevention of pathogenic microorganism-related EC. In recent years, increasing evidence has shown that pathogenic microbial infections are closely associated with the development of EC. Therefore, it is necessary to describe in detail the relationship between microbial infection and EC and clarify its possible pathogenic mechanism, which will shed a light on clinical prevention and treatment of cancer caused by pathogenic microbial infection. [ABSTRACT FROM AUTHOR]

Cancer is a heterogeneous disease, and rapid progress in sequencing and -omics technologies has enabled researchers to characterize tumors comprehensively. This has stimulated an intensive interest in studying how risk factors are associated with various tumor heterogeneous features. The Cancer Prevention Study-II (CPS-II) cohort is one of the largest prospective studies, particularly valuable for elucidating associations between cancer and risk factors. In this article, we investigate the association of smoking with novel colorectal tumor markers obtained from targeted sequencing. However, due to cost and logistic difficulties, only a limited number of tumors can be assayed, which limits our capability for studying these associations. Meanwhile, there are extensive studies for assessing the association of smoking with overall cancer risk and established colorectal tumor markers. Importantly, such summary information is readily available from the literature. By linking this summary information to parameters of interest with proper constraints, we develop a generalized integration approach for polytomous logistic regression model with outcome characterized by tumor features. The proposed approach gains the efficiency through maximizing the joint likelihood of individual-level tumor data and external summary information under the constraints that narrow the parameter searching space. We apply the proposed method to the CPS-II data and identify the association of smoking with colorectal cancer risk differing by the mutational status of APC and RNF43 genes, neither of which is identified by the conventional analysis of CPS-II individual data only. These results help better understand the role of smoking in the etiology of colorectal cancer. for this article are available online. [ABSTRACT FROM AUTHOR]

Colon cancer is the fourth leading cause of cancer deaths around the world. Despite advances in understanding its etiology and in diagnosis and treatment, new therapeutic strategies are still required. In this sense, the Solanaceae and Cucurbitaceae families have been widely used to treat various pathologies, including cancer, for their bioactive components. The objective of this systematic review was to analyze the antitumor activity of the bioactive components present in extracts from Solanaceae and Cucurbitaceae families using different in in vitro models of colon cancer. 241 publications have been identified (published from January 2008 to January 2020) from different electronic data base. 44 articles were included, 26 of which examined the Solanaceae family. The antitumor activity exhibited by this family was due to the withanolide-type steroid compounds they harbor. 18 articles were related to the Cucurbitaceae family. This family is characterized by their production of cucurbitacin-type triterpenoid compounds and their derivatives, which confer antitumor activity. In conclusion, the different genera belonging to both families are an important source of bioactive compounds with relevant activity against colon cancer. More experimental and in vivo studies will be required to corroborate their antitumor activity and to leverage them in future clinical practice. [ABSTRACT FROM AUTHOR]

Although the cancer role is becoming increasingly studied within sports psychology research, there is a dearth of applied interventions for improving the negative consequences caused by the cancer role. Using insights from a previous pilot project drawing on Canadian interuniversity athletes' stories of a staff cancer and recommendations from athlete maltreatment literature, we provide MPCs with varying degrees of proactive interventions to empower coaches to modify their own behaviors to signify growth in their coaching practices and reactive interventions to be used if a cancer's influence is adversely impacting athletes. [ABSTRACT FROM AUTHOR]

This study was done to evaluate the anticancer potential of Achillea fragrantissima (Forssk.) Sch.Bip. leaves methanolic extract in detail for the first time, in addition to investigating its antimicrobial activity. The antimicrobial assay revealed that the extract exerted high activity against P. vulgaris (MIC = 156.25 µg/ml) and C. albicans (MIC = 625 µg/ml), while moderate activity was observed against other microbes. The extract was also screened against HepG2, A549, HCT116 and MCF7 cancer cells and was found to be active across all cells with highest selectivity and cytotoxic activity being observed for A549 cells (IC50 = 1.21 µg/ml). Further mechanistic studies on A549 cells showed that the extract resulted in S-phase arrest and induced apoptosis via activation of caspase-3, p53 and Bax, in addition to downregulation of Bcl-2. HR-LCMS analysis indicated the presence of 3-hydroxycoumarin, quercetin 3,3′-dimethyl ether and skullcapflavone II which might be responsible for the extract's bioactivity. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most prevalent primary cancer of the liver and it is the fourth most common cause of cancer related death worldwide. In Egypt, liver cancer constitutes the most common cause of mortality-related cancer. This study aimed to evaluate the immunohistochemical expression of SET oncoprotein in HCC tissues in comparison with its expression in non tumorous liver tissues and to correlate its expression with clinicopathological parameters. This study investigated 100 cases of HCC (including tumorous and non tumorous tissues). One hundred percent of tumorous and non-tumorous tissues were positive for SET expression. The mean and median values of H-score for SET expression were higher in tumorous than non tumorous tissues (P =.03). Higher SET expression was significantly correlated with larger tumor size (P =.012), positive lymphovascular invasion (P =.028), and shorter overall survival (P <.001). SET expression in tumor tissues is the most independent factor to affect the overall survival of HCC patients. SET plays a role in hepatocarcinogenesis proved by the increase of SET expression from non-tumorous to tumorous tissues. Also, SET can be used as a prognostic indicator and a novel target therapy in HCC patients [ABSTRACT FROM AUTHOR]

Alcohol causes cancer, but many alcohol consumers are not aware of this risk. Research is needed to identify effective communication strategies to increase risk perceptions and decrease alcohol consumption. This study examined the effects of threatening and hedging languages in communicating the cancer risk associated with alcohol use. Results from a between-subjects experiment (N = 584) revealed a significant interaction effect: Threatening language combined with lexical hedges led to a higher perceived threat to drinker identity competence, which predicted higher intentions to reduce and stop drinking. Moreover, threatening language increased perceived threat to freedom, predicting greater reactance and lower behavioral intentions. Lastly, hedging increased perceived message tentativeness, predicting lower risk perceptions and behavioral intentions. Implications of our study were discussed. [ABSTRACT FROM AUTHOR]

An 83-year-old Portuguese cancer survivor and amputee structures her illness narrative around the etiology of an upper limb's sarcoma, pointing to witchcraft as the root of her malignancy, through a prayer spoken by a neighbor. This is not a self-explanatory claim, since she must have the ability to blend the principles of a naturalistic thought – disrupted cells – with the supernatural, but with such a logical robustness that it can make sense to her and to others, convincingly grasping, containing and defining the ontological intricacy and interconnectedness of the multiple elements shaping her experience of bewitchment and illness. [ABSTRACT FROM AUTHOR]

From initiation through progression, cancer cells are subjected to a magnitude of endogenous and exogenous stresses, which aid in their neoplastic transformation. Exposure to these classes of stress induces imbalance in cellular homeostasis and, in response, cancer cells employ informative adaptive mechanisms to rebalance biochemical processes that facilitate survival and maintain their existence. Different kinds of stress stimuli trigger epigenetic alterations in cancer cells, which leads to changes in their transcriptome and metabolome, ultimately resulting in suppression of growth inhibition or induction of apoptosis. Whether cancer cells show a protective response to stress or succumb to cell death depends on the type of stress and duration of exposure. A thorough understanding of epigenetic and molecular architecture of cancer cell stress response pathways can unveil a plethora of information required to develop novel anticancer therapeutics. The present view highlights current knowledge about alterations in epigenome and transcriptome of cancer cells as a consequence of exposure to different physicochemical stressful stimuli such as reactive oxygen species (ROS), hypoxia, radiation, hyperthermia, genotoxic agents, and nutrient deprivation. Currently, an anticancer treatment scenario involving the imposition of stress to target cancer cells is gaining traction to augment or even replace conventional therapeutic regimens. Therefore, a comprehensive understanding of stress response pathways is crucial for devising and implementing novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Overexpression of c-myc via increased transcription or decreased protein degradation is common to many cancer etiologies. c-myc protein degradation is mediated by ubiquitin-dependent degradation, and this ubiquitylation is regulated by several E3 ligases. The primary regulator is Fbxw7, which binds to a phospho-degron within c-myc. Here, we identify a new E3 ligase for c-myc, Fbxl8 (F-box and Leucine Rich Repeat Protein 8), as an adaptor component of the SCF (Skp1-Cullin1-F-box protein) ubiquitin ligase complex, for selective c-myc degradation. SCFFbxl8 binds and ubiquitylates c-myc, independent of phosphorylation, revealing that it regulates a pool of c-myc distinct from SCFFbxw7. Loss of Fbxl8 increases c-myc protein levels, protein stability, and cell division, while overexpression of Fbxl8 reduces c-myc protein levels. Concurrent loss of Fbxl8 and Fbxw7 triggers a robust increase in c-myc protein levels consistent with targeting distinct pools of c-myc. This work highlights new mechanisms regulating c-myc degradation. [ABSTRACT FROM AUTHOR]

Overexpression of c-myc via increased transcription or decreased protein degradation is common to many cancer etiologies. c-myc protein degradation is mediated by ubiquitin-dependent degradation, and this ubiquitylation is regulated by several E3 ligases. The primary regulator is Fbxw7, which binds to a phospho-degron within c-myc. Here, we identify a new E3 ligase for c-myc, Fbxl8 (F-box and Leucine Rich Repeat Protein 8), as an adaptor component of the SCF (Skp1-Cullin1-F-box protein) ubiquitin ligase complex, for selective c-myc degradation. SCFFbxl8 binds and ubiquitylates c-myc, independent of phosphorylation, revealing that it regulates a pool of c-myc distinct from SCFFbxw7. Loss of Fbxl8 increases c-myc protein levels, protein stability, and cell division, while overexpression of Fbxl8 reduces c-myc protein levels. Concurrent loss of Fbxl8 and Fbxw7 triggers a robust increase in c-myc protein levels consistent with targeting distinct pools of c-myc. This work highlights new mechanisms regulating c-myc degradation. [ABSTRACT FROM AUTHOR]

Subcellular alteration of thyroid hormones (THs) signaling is proposed in many types of cancers. Some studies show deiodinase type 3, as an oncofetal protein, re-expresses in some cancer types. Therefore, we aimed to investigate the product of this enzyme, reverse triiodothyronine (rT3) in serum of newly diagnosed colorectal cancer (CRC) patients. In this cross-sectional study, blood from 38 laboratory-confirmed cases was taken, and serum levels of rT3, total T3 (triiodothyronine), total T4 (thyroxine), free T3, free T4, and thyroid-stimulating hormone (TSH) were detected by using an enzyme-linked immunosorbent assay. The results illustrated that rT3 and free T3 levels increased in patients with early stages of colorectal cancer, despite normal levels of total T3, total T4, free T4, and TSH. The elevation of rT3 in CRC patients can probably be due to the re-expression of deiodinase type 3 in CRC. Further research is needed to study the role of intracellular THs modulation in CRC and its impact on CRC treatment. [ABSTRACT FROM AUTHOR]

Advances in high-throughput genomic technologies coupled with large-scale studies including The Cancer Genome Atlas (TCGA) project have generated rich resources of diverse types of omics data to better understand cancer etiology and treatment responses. Clustering patients into subtypes with similar disease etiologies and/or treatment responses using multiple omics data types has the potential to improve the precision of clustering than using a single data type. However, in practice, patient clustering is still mostly based on a single type of omics data or ad hoc integration of clustering results from individual data types, leading to potential loss of information. By treating each omics data type as a different informative representation from patients, we propose a novel multi-view spectral clustering framework to integrate different omics data types measured from the same subject. We learn the weight of each data type as well as a similarity measure between patients via a nonconvex optimization framework. We solve the proposed nonconvex problem iteratively using the ADMM algorithm and show the convergence of the algorithm. The accuracy and robustness of the proposed clustering method is studied both in theory and through various synthetic data. When our method is applied to the TCGA data, the patient clusters inferred by our method show more significant differences in survival times between clusters than those inferred from existing clustering methods. for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement. [ABSTRACT FROM AUTHOR]

Piecewise-exponential excess-relative-risk (ERR) model is used for analysis of large cohort follow-up grouped data of exposure risk. Estimation method for the expected-acceleration-time (EAT) to failure by exposure is proposed using the ERR. Method is applied to all solid cancer mortality atomic-bomb survivor grouped data, and gives EAT to death, 9.9 y (95%CI: 8.4, 11.2 y), at 1 Gy during 50 y follow-up (1950–2000). Longevity (all causes of death) is shorter than the reported before. The exposed younger gives greater EAT. The EAT under carcinogenesis mechanistic model with single-point/chronic exposure is mentioned. Competing causes of cancer death may imply the proneness of double cancer. [ABSTRACT FROM AUTHOR]

Extreme variation in lifetime cancer risk among tissues has been a riddle of cancer etiology. Considering that cancer risks were found to be contributed heavily by environmental factors, levels of environmental carcinogens, such as metal/metalloid in tissues, may be an explanation of the variation. We analyzed the correlations between metal/metalloid concentrations in different tissues and the lifetime cumulative cancer risks of the corresponding tissues using the data of National Health Standards and National Central Cancer Registry of China. Cadmium (Cd) and rubidium (Rb) were found to be correlated with the lifetime cancer risks in a positive linear relationship while a U-shaped relationship was observed for cesium (Cs) and tin (Sn). A positive linear trend between the mixture of metals/metalloids and lifetime cancer risks was observed and cadmium (Cd) may be the main driving element. Our results indicated that Cd-based metal/metalloid levels may be an explanation for the variation in lifetime cancer risk among tissues. Furthermore, the analytical strategy may in turn help identify environmental factors involved in cancer etiology. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the serum levels of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 and 8 in patients diagnosed with endometrial cancer. Our study included 41 patients diagnosed with endometrial cancer. The control group consisted of 41 patients diagnosed with benign endometrial pathology. The serum samples were centrifuged and stored at -80 °C. The serum levels of ADAMTS were significantly higher (p<.001), whereas the levels of ADAMTS 8 were significantly lower in patients diagnosed with cancer (p<.001). In addition to the presence of known factors in the aetiology of endometrial cancer, the effect of inflammatory factors and some new proteins has centred on the causes of tumourigenesis in recent years. In this sense, these proteins, called the ADAMTS, are the source of new studies.Impact StatementWhat is already known on this subject? When the recent studies about endometrial cancer are evaluated, it is seen that the effects of chronic inflammation and cytokines have gained importance in its aetiology. The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) gene family consist of 19 proteases that play essential role in the formation of the extracellular matrix (ECM) and interact with inflammatory cytokines. These proteases and their substrates provide a wide range of functions in different tissues, including ECM remodelling, angiogenesis, fibrosis and coagulation.What the results of this study add? ADAMTS 5, which causes the degradation of the ECM with Aggrecanase activity, was found to be significantly higher in patients diagnosed with cancer and ADAMTS 8 with anti-angiogenesis activity was significantly lower in patients diagnosed with endometrial cancer.What the implications are of these findings for clinical practice and/or further research? In this study, it is understood that the effect of inflammatory mediators is remarkably important in the aetiology of endometrial cancer, as in many types of organ specific cancer. [ABSTRACT FROM AUTHOR]

Background: There are only a few and mostly small population-based epidemiological studies of primary sclerosing cholangitis (PSC). Objective: We aimed to estimate prevalence and incidence rates of PSC, and survival and malignancy risk for PSC patients in a large population-based study. Methods: We retrieved 632 PSC patients from 1990 to 2015 in the Hospital District of Helsinki and Uusimaa (HUS), comprising 29% of the Finnish population. Mortality information of the PSC patients was obtained from the national Population Registry, malignancy information from the Finnish Cancer Registry and the causes of death from the Statistics Finland. Standardized incidence ratio and standardized mortality ratio (SMR) were calculated for predefined malignancy types. Results: The crude incidence of PSC in the HUS area was 1.58/100,000 person-years, and the point prevalence in 2015 was 31.7/100,000 inhabitants. The mean time from diagnosis to death was 21.9 years. The risk for any malignancy was three-fold and the risk for colorectal carcinoma was five-fold when comparing with the general population. During the first year after diagnosis of PSC, the risk for cholangiocarcinoma is 900-fold compared to the general population and after that 150-fold. SMR for all malignant neoplasms was 5.9 (95% CI 4.2–8.1). Conclusion: We found that the incidence of PSC in the HUS area in Finland is similar or higher than previously reported from other countries. The prevalence is markedly higher than reported elsewhere, probably due to the active search of the disease, suggesting that the disease is underdiagnosed. [ABSTRACT FROM AUTHOR]

In previous studies, numerous dysregulated lncRNAs were identified using RNA-sequencing. Lung cancer is the most common malignant tumour worldwide and the second leading cause in cancer. The aim of this study is to investigate the function and mechanism of lincRNA00858 in the lung cancer. RT-PCR was used to detect the expression of lincRNA00858. Proliferation, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK8, transwell assay and western blot to evaluate the function of linc00858. Dual-luciferase reporter assay was used to identified the potential target of linc00858. Over-expression of linc00858 significantly promoted cell proliferation, invasion. We also found that linc00858 facilitated the EMT process. Dual-luciferase reporter assay revealed that linc00858 can bind with miR-3182 directly. Linc00858 can negatively regulate the expression of miR-3182. Further experiments demonstrated that MMP2 was the direct target of miR-3182. Rescue experiments revealed that linc00858 functioned through miR-3182/MMP2 axis. Taken together, we verified the role of an unknown linc00858 in lung cancer and provided its mechanism. Mechanistically, linc00858 acted as a competitive endogenous RNA to sponged miR-3182 and regulate MMP2 in lung cancer. Our study provided new clues for understanding the mechanism of lung cancer. [ABSTRACT FROM AUTHOR]

Orbital metastases are rare causes of orbital tumours, and may present with pain, photophobia, red eye, vision loss, diplopia, proptosis, or external ophthalmoplegia. Breast cancer is responsible for a great majority of orbital metastases. Herein, we report a 78-year-old female who had unilateral external ophthalmoplegia due to orbital metastasis of primary breast cancer. [ABSTRACT FROM AUTHOR]

This review summarizes the carcinogenic mechanisms for 109 Group 1 human carcinogens identified as causes of human cancer through Volume 106 of the IARC Monographs. The International Agency for Research on Cancer (IARC) evaluates human, experimental and mechanistic evidence on agents suspected of inducing cancer in humans, using a well-established weight of evidence approach. The monographs provide detailed mechanistic information about all carcinogens. Carcinogens with closely similar mechanisms of action (e.g. agents emitting alpha particles) were combined into groups for the review. A narrative synopsis of the mechanistic profiles for the 86 carcinogens or carcinogen groups is presented, based primarily on information in the IARC monographs, supplemented with a non-systematic review. Most carcinogens included a genotoxic mechanism. [ABSTRACT FROM AUTHOR]

Can a single fiber of amphibole asbestos increase the risk of lung cancer or malignant mesothelioma (MM)? Traditional linear no-threshold (LNT) risk assessment assumptions imply that the answer is yes: there is no safe exposure level. This paper draws on recent scientific progress in inflammation biology, especially elucidation of the activation thresholds for NLRP3 inflammasomes and resulting chronic inflammation, to model dose-response relationships for malignant mesothelioma and lung cancer risks caused by asbestos exposures. The modeling integrates a physiologically based pharmacokinetics (PBPK) front end with inflammation-driven two-stage clonal expansion (I-TSCE) models of carcinogenesis to describe how exposure leads to chronic inflammation, which in turn promotes carcinogenesis. Together, the combined PBPK and I-TSCE modeling predict that there are practical thresholds for exposure concentration below which asbestos exposure does not cause chronic inflammation in less than a lifetime, and therefore does not increase chronic inflammation-dependent cancer risks. Quantitative examples using model parameter estimates drawn from the literature suggest that practical thresholds may be within about a factor of 2 of some past exposure levels for some workers. The I-TSCE modeling framework explains previous puzzling aspects of asbestos epidemiology, such as why age at first exposure is a better predictor of lifetime MM risk than exposure duration. It may be a valuable tool for risk analysts when LNT assumptions are not justified due to inflammation response thresholds mediating dose-response relationships. [ABSTRACT FROM AUTHOR]

Objective: Premature ovary insufficiency is frequent after chemotherapy/radiotherapy in cancer patients. Ovarian tissue (OT) cryopreservation and later retransplantation, the routine method in Europe, has recently been implemented at the first center in China. We investigated the protective effect of the antioxidant N-acetyl-l-cysteine (NAC) during the decisive freezing-thawing steps. Methods: Fifteen OT samples were obtained from each of 13 cancer patients prospectively and randomly assigned to a control group and four groups with different NAC concentrations (Group 1, 0 mM NAC; Group 2, 0.5 mM NAC; Group 3, 1 mM NAC; Group 4, 5 mM NAC; Group 5, 25 mM NAC). After thawing, the follicle viability, DNA fragmentation, levels of reactive oxygen species (ROS), and total antioxidant capacity (TAC) were evaluated. Results: OT cryopreserved and thawed with 25 mM NAC (Group 5) has the lowest proportion of apoptotic stroma cells, but the worst follicle viability. The other four groups show similar anti-apoptosis and good follicle viability. Group 4 presented the lowest ROS and highest TAC levels. Conclusions: OT cryopreserved and thawed in medium supplemented with 5 mM NAC shows the highest antioxidant and lowest ROS capability, good apoptotic parameters, and follicle viability. Our results need to be confirmed in larger patient cohorts prior to being accepted as a standard protocol. [ABSTRACT FROM AUTHOR]

Platelet hyperactivity is the hallmark of thrombosis and hemostasis disorders including atherosclerosis, diabetes, stroke, arthritis, and cancer causing significant mortality and morbidity. Therefore, regulating platelet hyperactivity is an ever growing interest. Very recently, basal autophagic process has been demonstrated to be essential for normal functioning of platelets. However, autophagy can be elevated above basal level under conditions like starvation, and how platelets respond in these settings remains to be elucidative. Therefore, in this study we demonstrate a substantial autophagy induction (above basal level) by starvation, which decreases platelet aggregation responses to various agonists. The decreased aggregation in starved platelets was restored in combination with autophagy inhibitors (3-methyladenine and NH4Cl) and acetate supplementation. Starved platelets also showed decreased calcium mobilization, granule release, and adhesive properties. Furthermore, ex vivo platelets obtained from starved rats showed increased autophagy markers and decreased aggregation responses to various agonists. Our results distinctly explain that enhanced autophagy and cellular energy depletion are the cause for decreased platelet activation and aggregation. The study emphasizes the cardinal role of starvation and autophagy in the management of diseases and disorders associated with platelet hyperactivity. [ABSTRACT FROM AUTHOR]

Background: The etiology of prostate cancer (PCa) involves environmental and genetic factors. Understanding the role of medication use on PCa risk may clarify the pathophysiological changes and mechanisms in development of cancer. Methods: This study investigated PCa risk in relation to overall use of anti-hypertensive drugs and those with specific mechanisms of action. The study cohort (78,615 men) was linked to the prescription database to obtain information on medication use during 20-year follow-up. Information was obtained on PCa diagnoses, causes of deaths, and for a sub-set on B.M.I. and use of non-prescription drugs. Time-dependent drug use variables hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regression analyses. Results: Use of antihypertensive drugs slightly increased PCa risk (HR = 1.16, 95% CI = 1.11-1.22). The risk increase was clearest for metastatic PCa (HR = 1.36, 95% CI = 1.14-1.62). ACE inhibitors, beta-blockers, and diuretics were all separately associated with a small excess risk (HR = 1.10, 95% CI = 1.01-1.19, HR = 1.14, 95% CI = 1.06-1.21, and HR = 1.16, 95% CI = 1.07-1.27, respectively). None of the other groups showed a clear association with PCa risk. Conclusions: The use of antihypertensive drugs was associated with increased prostate cancer risk. Similar risk association for multiple drug groups suggests that the findings may not reflect a direct medication effect, but may be due to underlying hypertension. [ABSTRACT FROM AUTHOR]

Accurately assessing the public's knowledge about the human papilloma virus (HPV) and the HPV vaccine remains critical for informing health education interventions aimed at increasing vaccine uptake. Responding "don't know" (DK) to survey questions that assess knowledge is common and DK responders are often systematically different from other responders, resulting in potential for bias. This study aimed to advance our understanding of DK responding to HPV knowledge items. Data from the nationally representative Health Information National Trends Survey Wave 5 Cycle 1 (N = 2,034) were used. Information seeking about cancer, information avoidance, health-related self-efficacy, and several cancer beliefs were examined as predictors of DK responding to six items that assessed HPV knowledge. DKs represented nearly half of responses. Adjusting for demographic factors, lower health-related self-efficacy, and greater information avoidance, cancer-mortality salience, and perceived ambiguity were associated with more DK responding, ps < .05. Even participants with incorrect responses had greater health-related self-efficacy, and less information avoidance, perceived ambiguity, and cancer-mortality salience than those who responded with DK. DK responding to HPV knowledge items is common and reflects factors beyond insufficient knowledge or motivation. Addressing causes of DK responding may reduce bias and improve interventions informed by surveys. [ABSTRACT FROM AUTHOR]

Objective: Studies of the importance of perinatal factors for the development of irritable bowel syndrome (IBS) are sparse. We conducted a large national cohort study to examine perinatal and familial risk factors for IBS. Material and methods: A national cohort of 1,963,685 persons who were born in Sweden in 1973-1992 (identified from the Swedish Birth Registry) were followed up for adult (18 years and older) IBS incidence in the Swedish Patient Register through 2010 (maximum age 38 years). There were 24,633 IBS cases in 46,784,296 person-years of follow-up. Results: After adjusting for potential confounders, significant risk factors for IBS included caesarean (HR = 1.10, 95% confidence interval [CI] 1.05-1.11, p < .001), low birth weight (<2500g) (HR = 1.11, 95%CI 1.01-1.22, p = .02), being second in birth order (HR = 1.04, 95%CI 1.01-1.08, p = .01), foetal growth ≥1 SD (HR = 1.06, 95%CI 1.00-1.11, p = .05), young maternal age (<20 years) (HR= 1.09, 95%CI 1.02-1.17, p = .02), maternal marital status (divorced/widowed) (HR = 1.12, 95%CI 1.08-1.17, p < .001), maternal education of 10-11 years (HR = 1.04, 95%CI 1.01-1.08, p = .01), maternal education of 12-14 years (HR = 1.06, 95%CI 1.01-1.11, p = .03), parental history of IBS (HR = 1.54, 95%CI 1.42-1.66, p < .001), parental history of anxiety (HR = 1.21, 95%CI 1.17-1.26, p < .001) and parental history of depression (HR = 1.09, 95%CI 1.02-1.17, p = .02). Protective factors were male sex (HR = 0.36, 95%CI 0.35-0.37, p < .001) and old maternal at delivery (≥35 years) (HR = 0.95, 95%CI 0.90-1.00, p = .03). Conclusions: In this large cohort study, several perinatal and familial factors were associated with an increased risk of IBS independently, suggesting that perinatal and familial factors may play an important long-term role in the aetiology of IBS. [ABSTRACT FROM AUTHOR]

Ophthalmoplegia is a paralysis or weakness of extraocular muscles that have a variety of different etiologies including and not limited to Leptomeningeal Carcinomatosis (LC). LC is caused mainly by metastatic cancers and can cause a wide variety of symptoms. We present a case of LC with no preexisting condition who presented with a unilateral ophthalmoplegia as initial presentation who was found to have LC secondary to large B-cell lymphoma. [ABSTRACT FROM AUTHOR]

Current statistical methods for analyzing epidemiological data with disease subtype information allow us to acquire knowledge not only for risk factor-disease subtype association but also, on a more profound account, heterogeneity in these associations by multiple disease characteristics (so-called etiologic heterogeneity of the disease). Current interest, particularly in cancer epidemiology, lies in obtaining a valid p-value for testing the hypothesis whether a particular cancer is etiologically heterogeneous. We consider the two-stage logistic regression model along with pseudo-conditional likelihood estimation method and design a testing strategy based on Rao's score test. An extensive Monte Carlo simulation study is carried out, false discovery rate and statistical power of the suggested test are investigated. Simulation results indicate that applying the proposed testing strategy, even a small degree of true etiologic heterogeneity can be recovered with a large statistical power from the sampled data. The strategy is then applied on a breast cancer data set to illustrate its use in practice where there are multiple risk factors and multiple disease characteristics of simultaneous concern. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the association between the socio-demographic, lifestyle factors, and dietary habits with the risk of prostate cancer (PC) in a case–control study of Spanish men. None of the socio-demographic, lifestyle or dietetic variables was found predictors of PC risk. Body mass index was associated with an increased risk for aggressive PC and fruit consumption with lower Gleason scores, thus less aggressive cancers. Nonetheless, after applying Bonferroni correction, these variables were not still associated with PC aggressiveness. More adequately, powered epidemiological studies that measure the effect of lifestyle and dietary intake in PC risk and aggressiveness are warranted to further elucidate the role of these modifiable factors on PC etiology. [ABSTRACT FROM PUBLISHER]

Of 188 government-monitored air toxics, diesel particulate matter (DPM) causes seven times more cancer than all the other 187 air toxics combined, including benzene, lead, and mercury. Yet, DPM is the only air toxic not regulated more stringently under the Clean Air Act, as a hazardous air pollutant (HAP). One reason is that regulators use flawed standards of scientific evidence. The article argues (1) that DPM meets all six specified evidentiary criteria, any one of which is sufficient for HAP regulation and (2) that regulators’ standards of evidence for denying HAP status to DPM (no DPM unit-risk estimate, inadequate dose-response data, alleged weak mechanistic data) err logically and scientifically, set the evidence bar too high, delay regulation, and allow 21,000 avoidable DPM deaths annually in the U.S. [ABSTRACT FROM PUBLISHER]

Human carbonic anhydrase (CA) I and II are cytosolic proteins, where their expression disorders can cause diseases such as glaucoma, edema, epilepsy or cancer. There are numerous inhibitors that target these isozymes, but it is difficult to design compounds that could bind to one of these proteins specifically. The binding of sulfonamide inhibitor to a CA is linked to several protonation reactions, namely, deprotonation of the sulfonamide group, protonation of the active site zinc hydroxide and the compensating protonation-deprotonation of buffer. By performing binding experiments at various pHs and buffers, all those contributions were dissected and the 'intrinsic' binding parameters were calculated. Intrinsic thermodynamic binding parameters to CA I and II were determined for such widely studied drugs as acetazolamide, ethoxzolamide, methazolamide, trifluoromethanesulfonamide and dichlorophenamide. The assignment of all contributions should enhance our understanding of the underlying energetics and increase our capability to design more potent and specific CA inhibitors. [ABSTRACT FROM AUTHOR]

Identification of specific molecular changes (fingerprints) is important to identify cancer etiology. Exploitable biomarkers are related to DNA, epigenetics, and proteins. DNA adducts are the turning point between environmental exposures and biological damage. DNA mutational fingerprints are induced by carcinogens in tumor suppressor and oncogenes. In an epigenetic domain, methylation changes occurs in specific genes for arsenic, benzene, chromium, and cigarette smoke. Alteration of specific microRNA has been reported for environmental carcinogens. Benzo(a)pyrene, cadmium, coal, and wood dust hits specific heat-shock proteins and metalloproteases. The multiple analysis of these biomarkers provides information on the carcinogenic mechanisms activated by exposure to environmental carcinogens. [ABSTRACT FROM PUBLISHER]

Environmental pollution is a growing public health concern worldwide and adverse pollutants are associated with a variety of cancers. microRNAs (miRNAs), a class of small non-coding RNAs, act as powerful and sensitive posttranscriptional regulators of gene expression. Recent reports demonstrate that miRNAs play important roles in apoptosis and senescence, both of which are regarded as protective mechanisms against the carcinogenesis. Here, we will give an overview on the expression profile and regulatory role of miRNA in response to environmental pollution. This review will provide better understanding of the potential of miRNAs as novel biomarkers and therapeutic targets for human cancers caused by environmental pollutants. [ABSTRACT FROM AUTHOR]

Sperm protein 17 (Sp17) was originally identified in the flagellum of spermatozoa and subsequently included in the subfamily of tumor-associated antigens known as cancer-testes antigens (CTA). Sp17 has been associated with the motility and migratory capacity in tumor cells, representing a link between gene expression patterns in germinal and tumor cells of different histological origins. Here we review the relevance of Sp17 expression in the mouse embryo and cancerous tissues, and present additional data demonstrating Sp17 complex expression pattern in this murine model. The expression of Sp17 in embryonic as well as adult neoplastic cells, but not normal tissues, suggests this protein should be considered an 'oncofetal antigen.' Further investigations are necessary to elucidate the mechanisms and functional significance of Sp17 aberrant expression in human adult cells and its implication in the pathobiology of cancer. [ABSTRACT FROM AUTHOR]

Over the past 30 years, human papilloma virus (HPV) has been shown to play a role in the development of various cancers. Most notably, HPV has been linked to malignant progression in neoplasms of the anogenital region. However, high-risk HPV has also been suggested to play a significant role in the development of cancers in other anatomic locations, such as the head and neck, lung, breast and bladder. In 2006, the first vaccine for HPV, Gardasil, was approved for the prevention of subtypes 6, 11, 16 and 18. A few years later, Cevarix was approved for the prevention of subtypes 16 and 18, the HPV subtypes most frequently implicated in malignant progression. Although increased awareness and vaccination could drastically decrease the incidence of HPV-positive cancers, these approaches do not benefit patients who have already contracted HPV and developed cancer as a result. For this reason, researchers need to continue developing treatment modalities, such as targeted immunotherapies, for HPV-positive lesions. Here, we review the potential evidence linking HPV infection with the development of non-anogenital cancers and the potential role of immunotherapy in the prevention and eradication of HPV infection and its oncogenic sequela. [ABSTRACT FROM AUTHOR]

Tobacco smoke plays a dominant role in the epidemiology of lung cancer, cancer at other sites, and a variety of other chronic diseases. It is the leading cause of death in developed countries, and the global burden of cancer is escalating in less developed regions. For a rational implementation of strategies exploitable for the prevention smoking-related diseases, it is crucial to elucidate both the mechanisms of action of cigarette smoke and the protective mechanisms of the host organism. The imperative primary prevention goal is to avoid any type of exposure to smoke. Epidemiological studies have shown that a decrease in the consumption of cigarettes can be successful in attenuating the epidemic of lung cancer in several countries. Chemoprevention by means of dietary and/or pharmacological agents provides a complementary strategy aimed at decreasing the risk of developing smoking-associated diseases in addicted current smokers, who are unable to quit smoking, and especially in involuntary smokers and ex-smokers. The availability of new animal models that are suitable to detect the carcinogenicity of cigarette smoke and to assess the underlying molecular mechanisms provides new tools for evaluating both safety and efficacy of putative chemopreventive agents. [ABSTRACT FROM PUBLISHER]

The article explores the journalistic coverage of the public crisis that developed following the publication of Yediot Aharonot's investigative report about the diving practices of Israel's sea commandos in the polluted Kishon River. The coverage of the Kishon diving crisis is probed via two complementing research trajectories. The first trajectory looks at the construction of the newsworthiness of the Kishon diving crisis in comparison to two similar crises while addressing the interpretations provided by various involved factors. The second trajectory explores the various frames through which the Kishon diving crises were narrated. The article's concluding section discusses the complex interrelations between newsworthiness and framing. [ABSTRACT FROM PUBLISHER]

Sirtuins are involved in the control of the cell cycle and regulation of gene transcription. While some sirtuins have tumor suppressor effects, others regulate tumors metabolism. Within this perspective, the present article is a review of the current role of sirtuins in the etiology and physiopathology of cancer. Sirtuins show strong potential to become a valuable predictive and prognostic marker for cancer and are eligible as therapeutic targets for a variety of tumors. Investigation of new molecules able to modulate sirtuins activity must be encouraged. [ABSTRACT FROM AUTHOR]

Due to its unique aetiology and pathology, cancer cannot simply be understood in the typical diagnosis-treatment-prognosis trajectory. To a post-surgical patient, living with cancer usually implies living with the fear of its recurrence. Cancer, in other words, is a constant invisible presence that haunts. In this article, I focus on cancer's haunting and propose that we turn away from the narrative timeline to a narrative space, in which a ‘ghostly encounter’ with the unspeakable aspect of the cancer experience is possible. I then use Dorothea Lynch's and Eugene Richards'Exploding into Life(1986), a photo-journal of Lynch's breast cancer experience as an example. I use the text to illustrate how it is within this ‘ghostly space’ that we can direct our attention to thenot therethat is present in the cancer story. As such, it embodies not only Lynch's story of cancer, but also what is repressed (in the others), and how the repressed can return in different (ghostly) forms. And finally, I show how it is through these encounters with the cancer ghosts that a collective story of cancer can be shared and witnessed. [ABSTRACT FROM PUBLISHER]

Cyclin D1--cyclin-dependent kinase 4/6 (CDK4/6) dysregulation is a major contributor to melanoma genesis. Clinical evidence has revealed that p16INK4A, an allosteric inhibitor of CDK4/6, is inactivated in over half of human melanomas, and numerous animal models have demonstrated that p16INK4A deletion promotes melanoma. FBXO4, a specificity factor for the E3 ligase that directs timely cyclin D1 proteolysis, has not been studied in melanoma. We demonstrate that Fbxo4 deficiency induces Braf driven melanoma and that this phenotype depends on cyclin D1 accumulation in mice, underscoring the importance of this ubiquitin ligase in tumor suppression. Furthermore, we have identified a substrate-binding mutation, FBXO4 I377M, that selectively disrupts cyclin D1 degradation while preserving proteolysis of the other known FBXO4 substrate, TRF1. The I377M mutation and Fbxo4 deficiency result in nuclear accumulation of cyclin D1, a key transforming neoplastic event. Collectively, these data provide evidence that FBXO4 dysfunction, as a mechanism for cyclin D1 overexpression, is a contributor to human malignancy. [ABSTRACT FROM AUTHOR]

We report analyses of regional trends in overall and cause-specific mortality in Belarus for the period 1990–2007. We explore the respective spatial patterns and attempt to determine the factors responsible for the regional mortality variation. The results show that inter-regional mortality differentials tend to rise, mainly because of the growing advantage of the capital over other regions. The increasing variation is associated with diverging trends in mortality from external causes of death. Mortality tends to be higher in the eastern part of the country. Regional data show that changes in mortality are largely explained by alcohol and socio-economic conditions, as measured by unemployment and poverty rates. Cardiovascular and external-cause mortality are strongly associated with alcohol and unemployment, while poverty is an important predictor of suicide and homicide mortality. Clusters of elevated mortality from certain cancers located in the contaminated zone point to the possible impact of the Chernobyl accident. [ABSTRACT FROM AUTHOR]

The etiology of cancer is unclear. Recent studies indicate that some cytokines, such as interleukin (IL)-17, and regulatory T cells are involved in the development of cancer. This study aims to detect a subset of T cell, IL17++Foxp3++ T cell, in the pathogenesis of esophageal cancer (Eca). Twelve patients with squamous Eca were recruited in this study. The surgically removed Eca tissue was collected. Cells isolated from Eca tissue were analyzed by flow cytometry. The results showed that 2--10%% Eca tissue-derived CD4++ T cells expressed Foxp3; only 0.2--0.8%% non-ca tissue-derived CD4++ T cells expressed Foxp3. Further analysis showed that 3--15%% Eca-isolated CD4++ T cells were also IL-17 positive whereas only 0.4--1.5%% non-ca tissue-isolated CD4++ T cells were IL-17 positive. We also found that about 4.8--11.2%% Foxp3++ IL-17++ T cells in isolated CD4++ T cells from Eca tissue that were significantly less than in non-ca tissue derived CD4++ T cells. Less than 1%% Foxp3++ IL-17++ T cells in isolated CD4++ T cells in both Eca patients and healthy controls. Treatment with hypoxia markedly increased the expression of IL-6 in peripheral CD68++ cells. Coculturing CD68++ cells and Foxp3++ T cells under hypoxic environment resulted in abundant expression of IL-17 in Foxp3++ T cells that could be blocked by pretreatment with either anti-IL-17 or anti-transforming growth factor beta antibodies. We conclude that IL-17++Foxp3++ T cells may contribute to the development of Eca. [ABSTRACT FROM AUTHOR]

Introduction: Since Jean-Nicolas Marjolin reported carcinoma arising in post-traumatic scars in 1828, the term 'Marjolin ulcer' has been applied to malignant changes in burn scars. Although many papers have been published already in this field, there are few reports from Oriental people. Methods: From 1989 to 2008, there were 11 cases noted as burn scar carcinoma in Chang Gung Memorial Hospital. Ten were reported as squamous cell carcinoma (SCC) and the one was verrucous carcinoma. Most of the cases occurred in the extremities (10/11). Results: Ten cases underwent an operation initially with wide excision and skin graft or local flap for coverage. Forefoot amputation was performed in one patient. One patient received above-knee amputation and adjuvant therapy because recurrent verrucous carcinoma occurred 2 years later. One patient suffered from a new lesion 8 years later and another case had inguinal lymph node metastasis 8 months later. Five patients were lost to follow-up and six cases were tumor-free during the follow-up period. Most scar malignancies are SCC while other cell types are rarer. Conclusion: The casual association between burn injuries and a later risk of basal cell carcinoma is questionable. Owing to poor prognosis in advanced scar cancer, the best treatment for scar carcinoma is to prevent the scar from developing repeated ulceration by performing aggressive initial burn wound care: early grafting by surgeons and daily scar care with regular follow-up for patients. This may be why a lower incidence has been noted in recent years. [ABSTRACT FROM AUTHOR]

Breast cancer is the second most common cancer in American women, and lung cancer is the deadliest. The etiology of breast cancer is not clear, although 85% of lung cancers are explained by cigarette smoking. A research review of the social perception of serious illness has shown that causal explanations fall into two categories: (1) patient behavior and (2) factors outside the patient's control. Presented in this review are questions concerning (1) patient coping, (2) stigma, and (3) the responses of the health care and research communities. Suggestions are made for further study of the social perception of lung and breast cancers. [ABSTRACT FROM AUTHOR]