Journal of carcinogenesis & mutagenesis最新文献

{"title":"Glutathione S Transferases: Biochemistry, Polymorphism and Role in Colorectal Carcinogenesis","authors":"S. Nissar, A. Sameer, R. Rasool, N. Chowdri, F. Rashid","doi":"10.4172/2157-2518.1000287","DOIUrl":"https://doi.org/10.4172/2157-2518.1000287","url":null,"abstract":"Glutathione S-transferases (GSTs) are enzymes detoxifying a wide range of hazardous substances both of endogenous or exogenous origin, such as reactive oxygen species (ROS) or xenobiotics and environmental carcinogens; thereby imparting protection to DNA against oxidative damage. GST gene polymorphisms on the other hand, exert an effect on the functioning of enzymes encoded by these genes at both gene expression level and the activity of the protein. In this way it may influence the possibility of detoxification of carcinogens, and consequently, the level of DNA damage; thus it may have an effect on the risk of development of cancer. In this review we aim to understand the function of GSTs in the xenobiotic metabolism and their role in modulation of colorectal cancer (CRC).","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"73 1","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83094745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Hypertension in Children with Cancer","authors":"Wissam Fakher Oda, Jawad Kadhum Atiya, Assim Alchalabi, J. G. Hasan","doi":"10.4172/2157-2518.1000285","DOIUrl":"https://doi.org/10.4172/2157-2518.1000285","url":null,"abstract":"Background: The advances in medicine have led to improved survival rates for children diagnosed with cancer. Despite these improvements, late mortality rates for cancer survivors exceed those of the general population. Leading causes of death in this population include subsequent cancer, followed by pulmonary and cardiovascular events. \u0000Objective: To study the frequency of pulmonary hypertension in children with cancer after finishing their treatments, and to study the effects of different determined factors like age of diagnosis or type of treatment on the development of pulmonary hypertension. \u0000Patient and methods: A cross-sectional study was carried out to focus on the frequency of pulmonary hypertension in patients with cancer after finishing their treatment in Basra Children’s Specialty Hospital, pediatric oncology center over 6 months; from the 1st of October, 2014 till 31th of March 2015. A total of 67 patients were included in the study, their age ranged from 6 months to 16 years, with 41 males and 26 females. The collected patients have been evaluated for development of pulmonary hypertension by Echocardiograph device in same hospital. \u0000Results: Acute lymphoblastic leukemia accounts for the greatest percentage (34.3%), followed by Acute myeloid leukemia (15%) then Hodgkin`s lymphoma, (13.4%) and the rest are solid tumors (37.3%). pulmonary hypertension is no statistically significant in relation to type of cancer, (P=0.729). The age of patient at time of diagnoses is statistically significant affects the development of pulmonary hypertension; the frequency tends to occur more in patients who have been diagnosed before the age of five years compared to those diagnosed at age older than 5 years, (P=0.035) but the sex of patient is statistically no significant effect (P=0.773) while no relation to type of treatment with chemotherapy (Methotrexate) radiotherapy is statistically significant (P=0.04). The occurrence of pulmonary hypertension also affected by period after the treatment ,cardiovascular complication is more seen in patient who completed two years after finishing treatment with statistically significant association (P=0.036). Pulmonary hypertension occurred more in patients who exposed to radiation for chest, cervical and brain areas (above diaphragm) than those exposed to abdomen (below diaphragm), but statistically no significant (P=0.264). Route of administration of chemotherapy (Methotrexate) either oral or intravenous on the occurrence of pulmonary hypertension is statistically no significant (P=0.432). \u0000Conclusion: The pulmonary hypertension is one of adverse cardiovascular effects that develop in patients who exposed to radiation or certain types of chemotherapy (Methotrexate) so the patient radiotherapy or should have regular screening programs for cardiac functions after complete the course of therapy.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"12 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85325512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ser/Thr Kinase MAP4K4 Controls Pro-Metastatic Cell Functions","authors":"Dimitra Tripolitsioti, M. Grotzer, M. Baumgartner","doi":"10.4172/2157-2518.1000284","DOIUrl":"https://doi.org/10.4172/2157-2518.1000284","url":null,"abstract":"The search for novel targeted therapies for major human conditions such as diabetes, cardiovascular diseases and cancer is a slow and costly process. Progress is often hampered by poor drug efficaciousness in the patients, low selectivity/specificity of the compounds and cellular evasion mechanism that are rather common in anti-cancer therapies. This is particularly true also for compounds inhibiting kinases, which in theory are optimal targets thanks to their druggable enzymatic activity. Novel targeting strategies are needed to reduce side effects and treatment failure caused by non-specific drug function and target resistance, respectively. An ideal compound will repress the relevant kinase effector function, while leaving kinase functions that are not disease-relevant unaltered. To achieve function-specific inhibition, the molecular mechanism of the drug target that governs the pathological process, must be identified. The Ser/Thr kinase MAP4K4 is implicated in inflammatory and metabolic disorders and cancer progression. In this review, we describe the molecular effector functions of MAP4K4 that exert those activities and how they have been identified and characterized both in invertebrate organisms and mammals. We discuss how the modulation of the cellular cytoskeleton by MAP4K4 may be connected to pathological conditions such as aberrant angiogenesis and cancer metastasis, and we describe the molecular mechanisms that are so far known to be mechanistically involved in these processes.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"46 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2017-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80739789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effects and Anti-Invasive Activities of Trehalose Liposomes on the Proliferation of Lung Carcinoma Cells","authors":"Keiji Kuwabara, H. Ichihara, Y. Matsumoto","doi":"10.4172/2157-2518.1000283","DOIUrl":"https://doi.org/10.4172/2157-2518.1000283","url":null,"abstract":"Inhibitory effects and anti-invasive activities of trehalose liposomes (DMTreC14) composed of L-α-dimyristoylphosphatidylcholine and α-D-glycopyranosyl-α-D-glucopiranoside monomyristate (TreC14) on the proliferation of human non-small cell lung carcinoma (A549) cells were examined in vitro. DMTreC14 with a hydrodynamic diameter less than 100 nm, were preserved for 4 weeks. The inhibitory effects of DMTreC14 on the proliferation of A549 cells accompanied with apoptosis were obtained. Enhancement of the accumulation of DMTreC14 into A549 membranes was observed. An increase in cellular membrane fluidity of A549 cell treated with DMTreC14 was observed on the basis of fluorescence depolarization method. DMTreC14 caused apoptosis for A549 cells through the activation of caspases and mitochondrial pathway. The anti-migration effects of DMTreC14 for A549 cells were observed through the inhibition of filopodia formation. The anti-invasion effects with the reduction of MMP-14 of DMTreC14 for A549 cells were obtained.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"120 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79437064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy Induced Nausea and Vomiting: Fear Makes the Wolf Bigger than He is","authors":"M. Sharma, J. Bajpai","doi":"10.4172/2157-2518.1000282","DOIUrl":"https://doi.org/10.4172/2157-2518.1000282","url":null,"abstract":"Chemotherapy induced nausea and vomiting (CINV) is one of the most feared and severe side effects of cancer treatment. It is broadly categorised as anticipatory (a conditioned reflex, due to past experience, generally triggered by same stimuli), acute (within 24 hours of chemotherapy administration), delayed (after 24 hours and lasting up to 7 days of chemotherapy), breakthrough (inspite of primary prophylaxis for CINV), and refractory (unresponsive to prophylactic and breakthrough medications). The chemotherapeutic regimens are having varying potential (high, moderate, low, or minimal) for CINV. Incidence and timing of CINV depends upon the emetogenic potential of chemotherapy and also patient factors. This perspective highlights the underlying mechanism of CINV, state of the art therapeutic options and nuances in the field to better control this dreaded complication and in turn enhance the quality of life of these patients.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"28 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74798486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanism of Checkpoint Inhibitors in Gynecologic Cancer","authors":"Karoutsos Petros, Karoutsos Dimitrios, Karoutsou Eftychia","doi":"10.4172/2157-2518.1000281","DOIUrl":"https://doi.org/10.4172/2157-2518.1000281","url":null,"abstract":"Currently, immunomodulators are used in different cancer entities, including gynecologic malignancies. Toxicity is variable but of narrow extent. Among immunomodulators, checkpoint inhibitors are used to enhance the immune system and significantly improve therapeutic results of advanced disease, mounting tumor progression.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"3 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2017-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73610159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extraskeletal Myxoid Chondrosarcomas are not Characterized by Loss of INI1/SMARCB1: Immunohistochemical Analysis of 16 Cases","authors":"B. Rekhi, M. Ramadwar, J. Bajpai","doi":"10.4172/2157-2518.1000280","DOIUrl":"https://doi.org/10.4172/2157-2518.1000280","url":null,"abstract":"Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, characterized by t (9; 22) translocation, including EWSR1 and NR4A3 gene rearrangements, observed in most cases. On histopathologic examination, an EMC has certain diagnostic mimics, such as myoepithelial tumors, epithelioid malignant peripheral nerve sheath tumor and epithelioid sarcomas. All these tumors are included in the category of INI1/SMARCB1- deficient tumors. Lately, few studies have shown loss of INI1 in certain EMCs. Considering there is preclinical data regarding role of EZH2 inhibitor in “INI1 deficient” tumors, it is crucial to recognize such tumors. \u0000Objectives: To evaluate immunohistochemical features, including INI1/SMARCB1 immunostaining results in 16 prospectively diagnosed cases of EMC. \u0000Methods: Immunohistochemical staining was performed on formalin-fixed paraffin embedded tissue sections by immunoperoxidase method using a MACH 2 Universal HRP-Polymer detection kit. Two cases were tested for EWSR1 rearrangement by fluorescent in-situ hybridization (FISH) technique. \u0000Results: Sixteen EMCs occurred in 13 males and 3 females, most commonly in lower extremities; followed by chest wall, pelvis, including iliac fossa, shoulder and parasapinal region; in patients within age-range of 17-72 years (median=47.5). On histopathologic examination, most tumors displayed round to polygonal cells arranged in cords, trabeculae and pseudoglandular pattern in an abundant myxoid stroma. Three tumors revealed “rhabdoid” cells. By immunohistochemistry, tumor cells were positive for NSE (13/13) (100%), S100 protein (10/15) (66.6%), EMA (2/12) (16.6%), AE1/AE3 (0/9), P63 (0/2) and SMA (2/3), the latter in tumors containing rhabdoid-like cells. INI1/SMARCB1 was diffusely retained in all 16 tumors (100%). Two cases tested for EWSR1 rearrangement, were found to be positive for the same. \u0000Conclusion: An optimal immunohistochemical panel for differentiating an EMC from its diagnostic mimics may include antibody markers, such as NSE, S100 protein, AE1/AE3, EMA and SMA. EMCs, including those containing rhabdoid cells do not seem to be in the category of INI1-deficient tumors.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"4 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90921070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Serum Levels of Estradiol Induce Endometrial Hyperplasia Rather than Carcinoma in a Mouse Model Using a Carcinogen","authors":"R. Asaka, T. Miyamoto, Yasushi Yamada, Hirofumi Ando, D. H. Mvunta, Hisanori Kobara, H. Kashima, T. Shiozawa","doi":"10.4172/2157-2518.1000308","DOIUrl":"https://doi.org/10.4172/2157-2518.1000308","url":null,"abstract":"Objective: Although estrogen has been regarded as a risk factor for endometrial carcinoma, its concentrationdependent carcinogenetic effects remain unclear, because most endometrial carcinomas occur in post-menopausal women, whose serum estrogen levels are relatively low. We previously reported that high levels of estradiol (E2) may suppress endometrial carcinogenesis by up-regulating DNA mismatch repair (MMR) in vitro. The present study was undertaken to further examine the carcinogenetic role of estrogen at various concentrations in vivo. Methods: N-methyl-N-nitrosourea (MNU) was injected into the uterine cavity of 29 mice, and E2 was administered by pellets or orally. Uteri were removed for histological examinations 24 weeks later, and serum E2 levels were measured. The immunohistochemical expression of MMR proteins in uterine epithelia was investigated. Results: Of 29 mice, 8, 8, 8, and 5 showed atrophic, normal, hyperplastic, and carcinomatous endometria, respectively. The mean E2 levels of each group were 0.2 pg/ml, 3.8 pg/ml, 190.0 pg/ml, and 6.7 pg/ml, with significant differences. The expression of the MMR proteins was stronger in mice with elevated E2. Conclusion: Elevated E2 levels preferentially induced endometrial hyperplasia rather than carcinoma, and this may be mediated by MMR proteins. These results indicate that modest E2 is needed, whereas elevated E2 levels are not necessarily advantageous for carcinogenesis, suggesting the importance of low-chronic (un-opposed) estrogen in human endometrial carcinogenesis.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"125 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85714331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of E18 Cell Model to Quantify DNA Strand Break Associated Bystander Effect (DSB-ABE)","authors":"J. Nasir","doi":"10.4172/2157-2518.1000295","DOIUrl":"https://doi.org/10.4172/2157-2518.1000295","url":null,"abstract":"The lymphoblast cell line E18 is a derivative of TK6 and has an I-Sce1 insert in the intron 2 of heterozygous TK1/ tk1 gene. E18 can be targeted with I-Sce1 restriction endonuclease to induce double strand breaks at the I-Sce1 site to measure radiation independent DNA damage and the associated bystander effect. For construction of E18 cell line an Eco47III site was inserted into the pTK-UAS linearized plasmid backbone and annealed with blunt-ended oligonucleotides of ISce1 restriction sequence in the presence of DNA ligase. DH5-α cells were transformed by heat transfecting the cells with pTK-UAS-Eco47III-Sce1 and selecting ampicillin resistant colonies. Plasmid DNA was extracted and analyzed for the presence of Eco47III and I-Sce1 sites. A clone with I-Sce site in intron 2 of the thymidine kinase active allele was selected for further experimentation and named E18. This model was tested to demonstrate the double strand break induced mutations and these strand breaks can also produce DNA strand break associated bystander effect (DSB-ABE) as measured by increased mutation frequency in naive cells. The plasmid pAdTrackCMV I-Sce1 carrying GFP marker was electroporated in E18 cells to express the I-Sce1 restriction endonuclease which specifically targets the I-Sce1 site at intron 2 of the active TK allele. Mutation fraction assay was employed to measure direct mutation fraction (DMF) or accompanied by conditioned medium transfer to naive cells for measuring bystander mutation fraction (BMF) as an end-point of targeting E18 with an exogenous I-Sce1 expression via pAdTrackCMV I-Sce1 to induce DNA damage and quantify DMF and BMF.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"16 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73440354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caveats in Diagnosis of Helicobacter Pylori Infection can be Avoided by a Panel of Serum Biomarkers (GastroPanelÃÂ","authors":"K. Syrjänen","doi":"10.4172/2157-2518.1000E123","DOIUrl":"https://doi.org/10.4172/2157-2518.1000E123","url":null,"abstract":"The understanding on the important role played by Helicobacter pylori (HP) infection in pathogenesis of gastric cancer (GC) and peptic ulcer disease has increased progressively since the discovery of the bacteria in 1984 by Marshall and Warren [1]. According to the current concepts, GC develops from HP-infection through precursor lesions of progressively increasing severity: mild, moderate and severe atrophic gastritis (AG), accompanied by intestinal metaplasia (IM) and dysplasia. This sequence of events is generally known as the “Correa cascade”, and estimated to be involved in around 50% of GC cases, particularly the intestinal type of GC [2-4].","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"56 97 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2016-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73604121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}