Cancer In Many Organs Research Articles

Uneven Expression of 20 Human Papillomavirus Genes Associated with Oropharyngeal Carcinoma.

Human papillomavirus (HPV) is considered to be responsible for 95% of virus-related cancers in many organs. Oropharyngeal carcinoma (OC) is distinguished by the transformation of the healthy epithelium into precancerous cells. The current study sought to examine the uneven gene expression of 20 genes among those scanned by microarray for oropharyngeal cancer patients. The GSE56142 dataset was extracted from the Gene Expression Omnibus of the National Center for Biotechnology Information; 24 specimens were evaluated. Gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction (PPI) were used to depict the biological roles of the genes under investigation using types of software. Six genes out of 20 in patients with invasive OC had a binding correlation with high expression (PDGFRS, COL6A3, COL1A1, COL3A1, COL2A1, and COL4A1), and only two genes with low expression (CRCT1 and KRT78). The expression levels of 20 genes were examined for patients with OC versus head and neck squamous cell carcinoma (HNSCC). The correlation coefficient between highly expressed genes of the OC group was statistically significant at the P<0.05 level. High expression levels of specific genes may serve as diagnostic tumor markers, particularly in the early stages of cancer, and testing should be performed in OC and HNSCC patients.

Tuft cell-like carcinomas: novel cancer subsets present in multiple organs sharing a unique gene expression signature.

Tuft cells are chemosensory epithelial cells playing a role in innate immunity. Recent studies revealed cancers with a tuft cell-like gene expression signature in the thorax. We wondered whether this signature might also occur in extrathoracic cancers. We examined mRNA expression of tuft cell markers (POU2F3, GFI1B, TRPM5, SOX9, CHAT, and AVIL) in 19 different types of cancers in multiple extrathoracic organs with The Cancer Genome Atlas (TCGA) (N = 6322). Four different extrathoracic cancers in our local archives (N = 909) were analysed by immunohistochemistry. Twenty-two (0.35%) extrathoracic tumours with co-expression of POU2F3 and other tuft cell markers were identified in various TCGA datasets. Twelve of the 22 "tuft cell-like tumours" shared poor differentiation and a gene expression pattern, including KIT, anti-apoptotic BCL2, and ionocyte-associated genes. In our archival cases, eleven (1.21%) tumours co-expressing POU2F3, KIT, and BCL2 on immunohistochemistry, i.e., were presumable tuft cell-like cancers. In three among five TCGA cohorts, the tuft cell-like cancer subsets expressed SLFN11, a promising biomarker of PARP inhibitor susceptibility. Tuft cell-like carcinomas form distinct subsets in cancers of many organs. It appears warranted to investigate their shared gene expression signature as a predictive biomarker for novel therapeutic strategies.

Extra- and Intracellular Monitoring of TGF-β Using Single Immunoplasmonic Nanoprobes

Transforming growth factor-β (TGF-β) is a well-known disease-related biomarker associated with fibrotic diseases, and initiation and progression of cancer in many organs. Therefore, quantitative and sensitive detection of TGF-β and similar biomarkers is crucial for patient treatment in the early stages of diagnosis. In many studies, the detection of TGF-β, an important profibrotic and cancer promoting cytokine, has been generally conducted by fluorescence or absorbance-based immunoassays. However, conventional methods for detecting TGF-β have problems including use of time-consuming sample pretreatment steps and multiple reagents for signal amplification and difficulty in real-time detection from living cells. Herein, we present a plasmon-based immunoassay for TGF-β using antibody-conjugated single gold nanoparticles that act as optically excellent intracellular and extracellular detection probes that do not require additional signal amplification. To detect TGF-β sensitively and selectively, we exploited the localized surface plasmon resonance (LSPR) property of antibody-conjugated plasmonic gold nanoparticles at a single particle level. By measuring the LSPR spectral shifts of the single plasmonic nanoprobes, TGF-β can be detected down to the picomolar level, which is comparable with the conventional methods but without significant interference from other proteins. The optimized plasmonic nanoprobes were applied to quantify and monitor the extracellular TGF-β level secreted from the cells under stress conditions, such as cancer, and exposure to toxic environments. Owing to the ease of cellular internalization of the nanoprobes, we directly image and detect increases in intracellular TGF-β levels in living cells under the given stress conditions without cell lysis. We envision that this strategy of using individual nanoparticles as sensors to monitor protein biomarkers in living cells could be applied for various biological assays and diagnosis.

Assessing Geological Resource and Risk Associated Radiation While Refining Opal Minerals Using Local Mechanism

The current study concentrated on the risk associated with naturally occurring radioactive materials in opal minerals and the method of refinement from the opal deposit site. The study's goal was to raise awareness of people who cause disease, improper use of expectations, and of better income generated in scientific ways. Radiation exposure has been associated with most forms of leukemia and with cancers of many organs, such as the lung, breast and thyroid gland, but not with certain other organs, such as the prostate gland. Mineworkers are exposed to radiation when extracting minerals from the earth's crust, with the associated radiological risks being assessed. Earth mineralogy is associated with environmental risks during mining and refining, particularly in certain aspects. Opal is most commonly found in Wollo, Ethiopia's northernmost region. The mechanism people used to refine opal Minerals at Wegel Tena often use rudimentary tools, such as a hammer and chisel, to extract the opal from the exposed seam along the flank of the canyon. The people living in Wogel Tena unknowingly export opal minerals to traders. Nowadays, the government's energy and mineral ministers are concerned about the preservation of tourist attractions and commercial centers using scientific methods. The local opal trader was unconcerned about people's safety or the diversion of mining resources. The new opal deposit was discovered in the village of Wegel Tena. Unlike previous Ethiopian opals, the new material is mostly white, with a little brown opal, fire opal, and a colorless "crystal" opal thrown in for good measure. When soaked in water, the opaque-to-translucent opals become transparent, showing a remarkable hydrophane character.

Radiation Risks of Uterine Cancer in Atomic Bomb Survivors: 1958-2009.

BackgroundIonizing radiation is known to be capable of causing cancer of many organs, but its relationship with uterine cancer has not been well characterized.MethodsWe studied incidence of uterine cancer during 1958–2009 among 62 534 female atomic bomb survivors. Using Poisson regression analysis, we fitted excess relative risk (ERR) models to uterine cancer rates adjusted for several lifestyle and reproductive factors. Person-years at risk were also adjusted for the probability of prior hysterectomy, because it could affect the subsequent risk of uterine cancer. We assessed the modifying effect of age and other factors on the radiation risk. For analysis of the modifying effect of age at radiation exposure around menarche, we compared the radiation risk for several exposure-age categories as well as using parametric models.ResultsThere were 224 uterine corpus cancers and 982 cervical cancers. We found a significant association between radiation dose and risk of corpus cancer (ERR per Gray [ERR/Gy] = 0.73, 95% confidence interval [CI] = 0.03 to 1.87) but not for cervical cancer (ERR/Gy = 0.00, 95% CI = −0.22 to 0.31). For corpus cancer, we found statistically significant heterogeneity in ERR/Gy by age (Pheterogeneity = .001) with elevated risk for women exposed to radiation between ages 11 and 15 years (ERR/Gy = 4.10, 95% CI = 1.47 to 8.42) and no indication of a radiation effect for exposures before or after this exposure-age range.ConclusionsThe current data suggest that uterine corpus is especially sensitive to the carcinogenic effect of radiation exposure occurring during the mid-pubertal period preceding menarche. There is little evidence for a radiation effect on cervical cancer risk.

Lycopene as an antioxidant and its medicinal uses

An antioxidant molecule inhibits the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicle, which can start chain reactions. When this reaction occurs in cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents. The antioxidant effect include a considerable reactive oxygen species scavenging activity, which allows lycopene to prevent lipid per oxidation and DNA damage. It also induces enzymes of the cellular antioxidant defense systems by activating the antioxidant response element transcription system. The tetra terpene structure of lycopene with two unconjugated bonds is easily attacked by electrophilic reagents resulting in extreme poverty reactivity towards oxygen and free radicals. Lycopene is a bright red carotene and carotenoids pigment found in tomatoes, carrots, watermelons, papayas and other red fruits and vegetables. It reduces the risk of cancers of many organs, retards growth of tumors and also has a chemopreventive effect against diseases like cardiovascular disease, osteoporosis, male infertility, protection against damage caused by ionizing radiation and reduces negative effect on cancer radiotherapy.

Mechanisms of RAS/β-catenin interactions

Signaling through the WNT/β-catenin and the RAS (rat sarcoma)/MAPK (mitogen-activated protein kinase) pathways plays a key role in the regulation of various physiological cellular processes including proliferation, differentiation, and cell death. Aberrant mutational activation of these signaling pathways is closely linked to the development of cancer in many organs, in humans as well as in laboratory animals. Over the past years, more and more evidence for a close linkage of the two oncogenic signaling cascades has accumulated. Using different experimental approaches, model systems, and experimental conditions, a variety of molecular mechanisms have been identified by which signal transduction through WNT/β-catenin and RAS interact, either in a synergistic or an antagonistic manner. Mechanisms of interaction comprise an upstream crosstalk at the level of pathway-activating ligands and their receptors, interrelations of cytosolic kinases involved in either pathways, as well as interaction in the nucleus related to the joint regulation of target gene transcription. Here, we present a comprehensive review of the current knowledge on the interaction of RAS/MAPK- and WNT/β-catenin-driven signal transduction in mammalian cells.

An analysis of microvessel density in salivary gland tumours: A single centre study

BackgroundsMicrovessel density (MVD) can be used for determining neoplastic neovascularisation. Tumour angiogenesis correlates with prognosis of cancers in many organs. The aims of this study were to evaluate MVD as demonstrated by CD31 and CD105 in salivary gland tumours (SGTs), and to correlate the MVD results with clinicopathological characteristics of the tumours. Materials and methodsUsing a retrospective cohort study design, we enrolled SGTs patients at the Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand, over the 22-year period. The predictor variables included demographic, anatomic and histopathological parameters. The outcome measure was average CD31-MVD and CD105-MVD counted by the “hot spot” method. Descriptive, uni- and bivariate statistics were computed, and P <0.05 was considered statistically significant. ResultsThe study sample consisted of 43 subjects with a mean age of 39.6 ± 17.8 years (range, 9–82), including 26 females (60.5%), diagnosed with SGTs. In this cohort, 58.1% of the cases were benign, and 83.7% were minor SGTs. There was a significant correlation between CD31-MVD and CD105-MVD (r = 0.8, P < 0.001), but mean CD31-MVD and CD105-MVD were 17.7 ± 9.3 and 12.8 ± 7.4, respectively (P = 0.009). Age, gender and tumour site were not individually associated with significant differences between CD31-MVD and CD105-MVD. Tumours with myoepithelial cells had lower MVD than those without myoepithelial cells (P = 0.04 for CD31; P = 0.03 for CD105). Only CD105-MVD showed statistical difference between benign and malignant SGTs (P = 0.01). ConclusionsThese results suggest that MVD in SGTs can be demonstrated by CD31 and CD105. Despite a strong correlation, CD31-MVD is always higher than CD105-MVD and cannot differentiate between benign and malignant SGTs. The presence of myoepithelial cells within SGTs affects the MVD analysis using either CD31 or CD105, while age, gender and tumour location do not.

Mutations and polymorphisms of genes moderate increase in gastric cancer risk

Results of studies performed in our center point at DNA changes of many cancer (mostly moderate) susceptibility genes. Association of weak mutations and polymorphism of many genes and additional influence of environmental factors can significantly increase the risk of cancer development. The preliminary studies performed in our department indicate, that increased risk of gastric cancer may be related to mutation in NOD2 and CHK2 genes predisposing to cancers of many organs. The CHEK2 gene encodes checkpoint kinase 2 (Chk2), it acts as a tumor suppressor whose functions are central to the induction of cell cycle arrest and apoptosis by DNA damage. Results of studies performed in our center indicate that the frequency of the IVS2+1G→A alteration was significantly increased in a group of 658 consecutive patients, especially in those under 50 years of age (OR=5.332, p=0.0174). I157T was over-represented in the group of familial gastric cancer patients, particularly in patients diagnosed at less than 50 years of age (OR=3.687, p=0.0011) and females. The specific group of intestinal and mixed histopathological subtype occurs more frequently (OR=1.671) in consecutive carriers of I157T mutation. Recently, the NOD2/CARD15, gene located on chromosome 16q12, has been associated with Crohn’s disease. It is believed to play a role both in intracellular recognition of lipopolysaccharides (LPS) typical of Gram negative bacteria and subsequent activation of NFkB. 3020insC NOD2 mutation causes an increased risk of developing chronic inflammatory diseases of the gastrointestinal tract and colorectal cancer in their course. In light of recent studies, in fact 3020insC mutation predisposes to cancers of many organs, including breast, ovarian, lung. Studies conducted in our center in the group of 103 patients with a family history of gastric cancer, have shown that NOD2 3020insC carriers in persons over 50 y of age more than doubled (OR=2.479, p=0.022) and among women almost 3-fold increased risk. In addition, NOD2 R702W alteration occurred almost three times more frequently (OR=2.816, p=0.0121) in the group of 241 consecutive patients with gastric cancer diagnosed before 50 years of age and over 2-times frequently (OR=2.268, p=0.0371) in gastric cancer selected histopathologically as intestinal type according to Lauren. There are a large number of reports describing the relationship between changes in the gene TP53, particularly polimomorfizm Arg72Pro, and risk of gastric cancer. Many researchers have found links between gene polymorphism of Interleukin-1, and the risk of stomach cancer. Gene polymorphism of angiotensin converting enzyme ACE, was recently linked with the pathogenesis and development of human cancers. Research Ebert MP, et al. conducted in a group of 88 patients shows that the insertion / deletion ACE gene may be associated with the development of early gastric cancer in the German population. In the Japanese population genetically distant, however, found no relationship between gastric cancer and ACE gene polymorphism). Sentences on the ACE polymorphism and risk of stomach cancer researchers are divided among different centers. XRCC1 gene is part of composite protein complex containing the s-polymerase DNA ligase I and PARP (polymerase poly (ADP-ribose). This multi-unit complex is involved in DNA repair pathway. T. Poplawski et al. indicate that the variant Gln / Gln XRCC1 gene polymorphism Arg399Gly occurred more frequently in patients with gastric cancer and family burden (OR=2.04, 95% CI=1,27-3,29) and the results obtained from studies in the group of 152 patients with a family history of gastric cancer suggest that gene XRCC1 399Gln allele may be considered a marker of gastric cancer. In terms of predisposition to gastric cancer has also been studied recently LAPTM4B gene associated with a genetic predisposition to liver cancer, having LAPTM4B alleles * 1 and LAPTM4B * 2. The risk of stomach cancer was increased 1.819 times in patients with genotype * 1 / 2 (CI=1.273-2.601) and 2.387 times in patients with genotype * 2 / 2 LAPTM4B (CI=1.195-4.767) compared with genotype * 1 / first. These studies indicate that allele * 2 LAPTM4B may be one of the genetic factors of gastric cancer. Further studies of newly described mutation moderately increased risk of stomach cancer may allow to estimate the real risk of gastric cancer associated with these mutations in the Polish population.

Experimental hepatotoxicity produced by ethinyl estradiol

Ethinyl oestradiol (EO) is the most commonly used as a component of oral contraceptive and hormonal replacement therapy (HRT) in women. However, its excessive and prolonged use may cause cytotoxicity, including cancer of many organs. Hence, the present study was performed to produce the experimental hepatotoxicity in female albino rats. EO was administered to different groups of rats, respectively @ 250, 500 and 750 μg/kg body weight, orally, weekly for 16 and 20 weeks. One group of rats was administered with saline alone to serve as control. The rats were sacrificed after their respective experimental periods, and the livers were collected and preserved in 10% buffered formalin. Later on, the histopathological study of liver tissues was done. On the 17th week, the hepatic tissues showed severe congestion, focal areas of hemorrhage, extreme vacuolation of cytoplasm, distended sinusoids with dilated central veins. Degeneration and necrosis of hepatocytes as evidenced by increased cytoplasmic granularity, and dissolution of nuclear materials were seen. On the 21st weeks, these changes were extremely severe and quite conspicuous. Distinct fibrosis was also noticed. EO caused hepatotoxicity, the extent and severity of which were dose and time dependent, indicating that this drug at higher dose after prolonged duration (500 or 750 μg/kg, orally, weekly for 20 weeks) may cause the standard experimental hepatotoxicity in rats.

Enhancing effects of a high fat diet on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline-induced lung tumorigenesis in female A/J mice

Both heterocyclic amines and a high fat diet are associated with an increased risk of cancer in many organs. Female A/J mice were fed a diet supplemented with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and a high fat diet to test for the development of lung tumors. In experiment 1, the mice were divided into 6 groups. Groups 1, 2, 3 and 4 were fed a diet supplemented with MeIQx at a concentration of 600?ppm for 0-12 weeks. A high fat diet containing 20% corn oil was given to Groups 1 and 5 for 0-32 weeks, Group?2 for 12-32 weeks and Group 3 for 0-12 weeks. Group 6 was fed a basal diet without supplements. MeIQx-treated groups (Groups?1, 2, 3 and 4) showed a significant increase in macroscopic and microscopic lung nodules compared with the control (Group 6). Areas of adenomas were increased dependent on the duration of exposure to the high fat diet. In experiment 2, Group 1 mice were fed MeIQx and a high fat diet, Group?2 a MeIQx alone diet, Group 3 a high fat alone diet, and Group?4 a basal diet without supplements. CYP1A2 mRNA in the liver was significantly decreased by a high fat diet (Group?3). The MeIQx alone group (Group 2) showed a tendency towards increased CYP1A2 expression, which was partially reduced in the MeIQx + high fat-treated group (Group 1). In the lungs, CYP1A2 mRNA expression was at an extremely low level, with no intergroup differences. In conclusion, MeIQx exerts tumorigenic potential in the lungs, and a high fat diet increases the size of induced lesions. The expression level of CYP1A2 in relation to MeIQx and a high fat diet may be associated with lung carcinogenesis.

Population Screening of CHEK2 Mutations in Poland

Mutations in the CHEK2 gene confer an approximately two-fold increase in the risk of cancer in many organs including the breast, colon, kidney, prostate and thyroid. In addition, we have recently identified a positive association of similar magnitude between a CHEK2 mutation and bladder cancer, endometrial cancer and low-grade ovarian cancer (unpublished data). Surveillance is available for most CHEK2-associated cancers. CHEK2 is not a high-risk gene, but it is associated with multi-cancer susceptibility, and founder alleles in CHEK2 are common in Poland (5.5% of the general population); therefore CHEK2 is responsible for development of more cases of cancer in Poland than founder mutations known to date in high-risk genes (including those in BRCA1, MSH2 and MLH1). In 2005 in cooperation with the Center of Medical Diagnosis and Hematology (BIOS) and the journal Wprost we performed population screening of CHEK2 mutations in Warsaw. This study was started by publication of an article describing the association of the CHEK2 gene and multi-site cancer predisposition. Readers of Wprost journal were invited for genetic consultation and CHEK2 gene testing. Patients who responded to the invitation were interviewed in the BIOS centre. During the interview the goals of the study were explained, informed consent was obtained, a first session of genetic counselling was given and a blood sample was obtained for DNA analysis. A detailed family history of cancer was taken from all patients (first and second-degree relatives included). During a period of 6 months, 3,826 individuals participated in this study. We identified: 192 carriers of a CHEK2 mutation, 240 families with hereditary susceptibility to breast and/or ovarian cancer, 62 families with familial colorectal cancer (including HNPCC). In addition, BRAC1 testing was performed in all individuals with a positive family history of breast or ovarian cancer. Twenty-one BRCA1 mutation carriers were identified. CHEK2 and BRCA1 mutation status was investigated using two independent blood samples. Then, all patients were invited for a second session and final genetic counselling was given. Appropriate surveillance was recommended for patients with familial cancer aggregations, as well as for BRAC1 and CHEK2 mutation carriers. We believe that this action broadened the knowledge about the role of genetic counselling and DNA testing in cancer prevention in Poland. It has also shown that many people in our population need such counselling and surveillance. We believe that this action will help reduce cancer morbidity and mortality in Poland.

Prostate Radiotherapy Is Associated With Second Cancers in Many Organs, not Just the Colorectum

The recent study by Baxter et al1 on rectal cancer associated with prostate cancer radiotherapy extended by several years the follow-up period from our earlier study,2 based on the same SEER cancer registry database. The more extended follow-up confirms our earlier conclusion that rectal cancer is significantly elevated in long-term survivors of prostate cancer radiotherapy, compared with a comparison group of prostate cancer patients who underwent surgery alone. Baxter et al1 report risks for radiation-associated rectal cancer that are very similar to our earlier estimates; specifically, they estimate a hazard ratio (radiotherapy vs.

Reply

We would like to thank Brenner et al1Brenner D.J. Curtis R.E. Hall E.J. Ron E. Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery.Cancer. 2000; 88: 398-406Google Scholar for their comments supporting the findings of our study. While we agree that a radiation dose is given to tissues outside of the high-dose radiation volumesduring radiation therapy for cancer, most studies have demonstrated that the major carcinogenic effect from radiation is within the high-dose region.1Brenner D.J. Curtis R.E. Hall E.J. Ron E. Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery.Cancer. 2000; 88: 398-406Google Scholar, 2Kleinerman R.A. Boice Jr, J.D. Storm H.H. Sparen P. Andersen A. Pukkala E. Lynch C.F. Hankey B.F. Flannery J.T. Second primary cancer after treatment for cervical cancer. An international cancer registries study.Cancer. 1995; 76: 442-452Google Scholar We certainly agree that organs other than the rectum are exposed to a high does of radiation during radiation therapy for prostate cancer, particularly the bladder, and this must be considered for surveillance after prostate irradiation. The increased risk of lung cancer in patients who undergo irradiation for prostate cancer lung is an intriguing finding. Although the lung receives a radiation dose (combination of scatter and leakage) of approximately 60 cGy during prostate cancer treatment, this dose does not produce a major increase in cancer formation in most organs; other exposures, such as cigarette smoking, may act synergistically with irradiation to increase lung cancer incidence (as has been shown in radium miners).3Morrison H.I. Villeneuve P.J. Lubin J.H. Schaubel D.E. Radon-progeny exposure and lung cancer risk in a cohort of Newfoundland fluorspar miners.Radiat Res. 1998; 150: 58-65Google Scholar However, important risk factors for lung cancer, particularly cigarette smoking, may not be equally distributed between those treated with radiation therapy and those treated with surgery, and this may result in an apparent increased risk of lung cancer in the irradiated group due to confounding. Our study4Baxter N.N. Tepper J.E. Durham S.B. Rothenberger D.A. Virnig B.A. Increased risk of rectal cancer after prostate radiation a population-based study.Gastroenterology. 2005; 128: 819-824Abstract Full Text Full Text PDF Scopus (166) Google Scholar and Brenner’s study1Brenner D.J. Curtis R.E. Hall E.J. Ron E. Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery.Cancer. 2000; 88: 398-406Google Scholar employed cohort designs and therefore confounding due to selection bias is a concern and may account for apparent differences in rectal cancer rates between those who undergo surgery and those who undergo irradiation. For example, in our study, we found that patients undergoing irradiation were significantly older than those undergoing surgery. As increasing age is a known risk factor for rectal cancer, patients undergoing irradiation in both studies were at a higher baseline risk of rectal cancer than patients who had surgery only. Although we controlled for age in our analysis, we could not control for unmeasured confounders, and thus the potential for selection bias remained. By demonstrating a significant increase in cancer in the area in the high-dose region (the rectum) but no significant increase in areas outside the high-dose region (the remainder of the colon), we were able to conclude that irradiation has a direct effect on rectal carcinogenesis, and this effect cannot be explained by any baseline higher risk of colorectal cancer in those undergoing radiation therapy. Our consideration of the potential influence of selection bias represents a major improvement over the methods of previous research in this area1Brenner D.J. Curtis R.E. Hall E.J. Ron E. Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery.Cancer. 2000; 88: 398-406Google Scholar, 5Neugut A.I. Ahsan H. Robinson E. Ennis R.D. Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma.Cancer. 1997; 79: 1600-1604Google Scholar, 6Pickles T. Phillips N. The risk of second malignancy in men with prostate cancer treated with or without radiation in British Columbia, 1984–2000.Radiother Oncol. 2002; 65: 145-151Google Scholar and greatly strengthens our conclusions. Prostate Radiotherapy Is Associated With Second Cancers in Many Organs, not Just the ColorectumGastroenterologyVol. 129Issue 2PreviewThe recent study by Baxter et al1 on rectal cancer associated with prostate cancer radiotherapy extended by several years the follow-up period from our earlier study,2 based on the same SEER cancer registry database. The more extended follow-up confirms our earlier conclusion that rectal cancer is significantly elevated in long-term survivors of prostate cancer radiotherapy, compared with a comparison group of prostate cancer patients who underwent surgery alone. Baxter et al1 report risks for radiation-associated rectal cancer that are very similar to our earlier estimates; specifically, they estimate a hazard ratio (radiotherapy vs. Full-Text PDF

Mechanisms of alcohol-associated cancers: introduction and summary of the symposium

Chronic alcohol consumption is associated with an increased risk for cancers of many organs, such as oral cavity, pharynx, larynx, and esophagus; breast; liver; ovary; colon; rectum; stomach; and pancreas. An understanding of the underlying mechanisms by which chronic alcohol consumption promotes carcinogenesis is important for development of appropriate strategies for prevention and treatment of alcohol-associated cancers. The National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, Office of Rare Diseases, National Cancer Institute, National Institute on Drug Abuse, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, sponsored an international symposium on Mechanisms of Alcohol-Associated Cancers in Bethesda, Maryland, USA, October 2004. The following is a summary of the symposium. Chronic ethanol consumption may promote carcinogenesis by (1) production of acetaldehyde, which is a weak mutagen and carcinogen; (2) induction of cytochrome P450 2E1 and associated oxidative stress and conversion of procarcinogens to carcinogens; (3) depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation; (4) induction of increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase–mitogen-activated protein kinase signaling; (5) accumulation of iron and associated oxidative stress; (6) inactivation of the tumor suppressor gene BRCA1 and increased estrogen responsiveness (primarily in breast); and (7) impairment of retinoic acid metabolism. Nicotine may promote carcinogenesis through activation of extracellular signal-regulated kinase/cyclooxygenase-2/vascular endothelial growth factor signaling pathway.

Dietary Cancer Chemoprevention: An Overview

KEYWORDS Environmental carcinogenic agents; epidemiology; vegetables and fruits; molecular targeted agents ABSTRACT Cancer is a major cause of mortality and morbidity worldwide. The majority of cancers are reported to be caused by environmental carcinogenic agents, occupational environment and dietary habits. Dietary habits are one of the major contributory factors for the genesis of cancer. The optimal way of dealing with any disease is by prevention, this is particularly relevant for cancer. Despite decade of basis and clinical research and trial of promising new therapy, overall cancer survival has only improved marginally. Molecular targeted agents are currently being studied in all treatment settings including chemoprevention, which is defined as the use of natural or synthetic agents to interrupt the process of carcinogenesis and to prevent or delay tumor growth. Epidemiological and experimental studies have indicated that dietary fat has an influence on carcinogenesis process. However, it has been observed that individuals who consume relatively large amounts of vegetables and fruits are at decrease risk of cancer of many organs. Several epidemiological studies suggest that consumption of cruciferous vegetables may be particularly effective in reducing cancer risk. Glucosinolates in crucifers are converted to isothiocyanates by plant myrosinase and gastrointestinal microflora, these are potent inducer of phase II proteins and is effective to block chemical carcinogenesis in animal models. Some dietary constituents are reported to act as naturally occurring cancer prevention agents and may explain some of the differences in cancer incidence seen in populations with varying dietary intake. Long term supplementation of the diet with folate, seems to lower the risk of colorectal cancer. Curcumin in the spice turmeric, genistein in soya, and catechins in tea have tumor-suppressing properties in rodent models of carcinogenesis. Although the results of clinical interventions trials of β-carotene to prevent lung cancer, and of dietary augmentation with fiber or fruits and vegetables to reduce the occurrence of colonic polyps have so far been negative, a structured path for the development of diet-derived constituents as cancer chemoprevention is emerging. By applying chemoprevention approaches from the use of single nutrients to multiple dietary constituents and functional foods, the scope of future cancer prevention strategies will be broadened. A new paradigm for diet, nutrient and cancer prevention can be developed using a multidisciplinary approach that includes lifestyle and environmental changes, dietary modification and physical activities consciousness to reduce the burden of cancer.

Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.

Reduction of scar formation in full-thickness wounds with topical celecoxib treatment.

Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.

Clinical Significance of c-met Oncogene Alterations in Human Colorectal Cancer

Abnormalities of the c-met oncogene have been studied in cancers of many organs including thyroid, lung, pancreas, and stomach. However, little is known about the clinical significance of c-met oncogene abnormalities in colorectal cancer. We investigated the amplification and overexpression of the c-met gene in surgically resected samples from 43 patients with colorectal cancer using Southern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Four of 33 (12%) samples of colorectal cancer showed amplification of the c-met gene. Twelve of 43 (30%) exhibited overexpression of the c-met gene. The patients with c-met overexpression showed greater tumor size, compared to those without c-met overexpression (p < 0.05). However, there were no differences in clinical stage, histological differentiation, tumor markers, or overall survival between two groups. The findings of the present study suggest that overexpression of c-met gene plays an important role in growth of colorectal cancer.

Review: Etiologic Links between Chronic Pancreatitis and Pancreatic Cancer

In all forms of pancreatitis there appears to be a cellular dysfunction, glandular destruction, and, presumably, increased cell turnover. Increased cell division has been suggested as a potential precursor of cancer in many organs. The excess risk of pancreatic cancer that has been documented in epidemiologic studies in patients with various types of pancreatitis is consistent with this hypothesis. The uncertainties in epidemiologic studies notwithstanding, the existence of a clear association between pancreatitis and the subsequent risk of pancreatic cancer is found too often to be only randomized. The clinical relevance of a causal relationship between chronic pancreatitis and pancreatic cancer is, however, limited, since the prognosis of chronic pancreatitis cannot be separated from that of chronic alcoholism.