Journal of carcinogenesis & mutagenesis最新文献

{"title":"EZH2 as a Therapeutic Target in Glioblastoma: A Cellular and Molecular Study","authors":"J. L. Rosa, Marta Iraburu, G. Gallo-Oller, M. H. Shahi, B. Meléndez, J. Rey, M. Idoate, J. Castresana","doi":"10.4172/2157-2518.1000278","DOIUrl":"https://doi.org/10.4172/2157-2518.1000278","url":null,"abstract":"Glioblastoma is the most common malignant brain tumor in adults and it is currently treated with a combination of surgery, radiotherapy and chemotherapy with temozolomide (TMZ). Many patients show resistance to TMZ, which is a challenge in the treatment of this type of brain cancer. New strategies are being tested, like the inhibition of EZH2, a histone methyltransferase which is overexpressed in cancer cells, leading to angiogenesis and metastasis. In this work, the EZH2 inhibitor DZNeP was tested in A172 glioblastoma cells and in A172-TMZ-resistant glioblastoma cells. Inhibition of cell proliferation, adhesion, colony formation, and migration was noted in control and TMZresistant glioblastoma cells after DZNeP treatment. At the level of EZH2 target gene expression, DZNeP decreased EZH2 expression, and increased the expression of its target genes (E-cadherin and TIMP3), which might probably contribute to inhibiting the development of a cancer metastatic phenotype. Finally, DZNeP negatively regulated the TGFβ pathway. In conclusion, we propose that inhibition of EZH2 might be considered as a therapeutic strategy against glioblastoma.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"21 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2016-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87616735","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":"Dual Parallel Sequence Progression as Vascular Pseudo-Reactivities to Tumor Necrosis and to Proliferation of Glioblastoma Cells","authors":"L. Agius","doi":"10.4172/2157-2518.1000277","DOIUrl":"https://doi.org/10.4172/2157-2518.1000277","url":null,"abstract":"Directional projections of glioblastoma biology include the constitutive clonality of a lesion that infiltrates in terms of its established potential proliferation involving predominantly poorly differentiated cell populations. In large measure, inclusive parameters correlate with the presence of contrastingly different types of genetic lesion, such as for example, the implication of p53 mutation versus the amplification/over-expression of the Epidermal Growth Factor Receptor (EGFR) in the neoplastic cells. Involvement of vasculature and of intense vascularization of multiple foci of the evolving glioblastoma emphasizes the distinctive link to multiple foci of tumor necrosis. Collaborative features include also an apparent propensity for pseudo-multifocality arising from processes of highly active foci of infiltration within the white matter. Cancer stem cells are believed to be the propagating cell component in gliomas and may differ from glioma initiating cells responsible for the establishment and survival of the neoplasm. Therapeutic resistance may specifically relate to resistance of the glioma stem cells that are found in small numbers in the tumor. Patient age is a distinctive feature of glioblastoma that progresses in close parallel with the vasculogenesis in neoplastic cell infiltration of adjacent tracts such as the corpus callosum and also the cerebral white matter of one or both cerebral hemispheres.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"580 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2016-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76414722","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":"Association between Exposure to Estrogenic Endocrine Disruptors - Polychlorinated Biphenyls, Phthalates, and Bisphenol A and Gynecologic Cancers- Cervical, Ovarian, Uterine Cancers","authors":"Marisa Morgan, A. Deoraj, Q. Felty, C. Yoo, D. Roy","doi":"10.4172/2157-2518.1000275","DOIUrl":"https://doi.org/10.4172/2157-2518.1000275","url":null,"abstract":"Introduction: Estrogen is a driver in the growth and progression of gynecologic cancers (cervical, ovarian, and uterine). A number of estrogenically active chemicals are suspected to contribute in the development of gynecologic lesions, including an increased risk of estrogen-dependent cancer in women. Humans are exposed to estrogenic endocrine disruptors (EEDs), such as- polychlorinated biphenyls (PCBs), phthalates and bisphenol A (BPA). Therefore, we examined the cross-sectional relationship between exposure to PCBs, phthalates, and BPA and gynecologic cancers (cervical, ovarian, and uterine). Methods: We analyzed data from female participants (20 years of age and older) who provided blood and urine samples for the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES) between 1999 and 2010. Exposure was examined based on lipid adjusted serum levels of 6 individual PCB congeners (74, 99, 118, 138, 153, and 180), the sum of dioxin-like PCBs (074 and 118), the sum of non-dioxin-like PCBs (099+138+153+187), 8 urinary phthalate metabolites (MNP, MEP, MEHP, MBzP, MCPP, MEHHP, MEOHP, and MIB), the sum of DEHP metabolites (MHP+MHH+MOH), the sum of total phthalates, and urinary BPA in conjunction with data obtained from the medical and reproductive health questionnaires. We calculated geometric means to compare EEDs concentrations in women who self-reported a cervical, ovarian, or uterine cancer diagnosis vs. women who self-reported never being diagnosed with cancer. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between exposure to EEDs and r gynecologic cancers. We also evaluated age, race/ethnicity, body mass index (BMI; kg/m2), and age at menarche as potential confounding variables in our final models. Results: Separate analyses showed weighted geometric mean (GM) levels of individual PCB congeners to be significantly higher among women with ovarian cancer, and uterine cancer when compared to the rest of the study population. Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was found to be significantly higher and BPA was higher among women with ovarian cancer compared to women never diagnosed with any gynecologic cancer. After adjusting for age, race, BMI, and age at menarche, we found that PCB 138 was significantly associated with cervical cancer, and uterine cancer [odds ratios of 3.05, 95% CI: 1.21-7.69; and 5.83, 95% CI: 1.63-20.9], respectively. PCB 74 and 118 however, were significantly associated with ovarian cancer with an odds ratios of 6.47, 95% CI: 1.23-3.41 (for PCB 74) and 6.68, 95% CI: 1.39-32.3 (for PCB 118). We also found the sum of non-dioxin-like PCBs to be significantly associated with uterine cancer (OR of 1.12, 95% CI: 1.03-1.23) and the sum of dioxin-like PCBs to be significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85). We did not find significant associations between urinary phthalate","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"40 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73195288","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":"ALS and Cancer","authors":"M. Yamaguchi, Y. Azuma, H. Yoshida","doi":"10.4172/2157-2518.1000E122","DOIUrl":"https://doi.org/10.4172/2157-2518.1000E122","url":null,"abstract":"Amyotrophic Lateral Sclerosis (ALS) is a rare but very severe disease. In ALS patients, defect in motor neuron accompanied with muscle atrophy progresses rapidly that results in defect in locomotion, swallowing and respiration. Patients normally die in 2 to 5 years after the onset of disease, if the artificial ventilator is not equipped. However, up to now there is no effective therapy. A number of epidemiological studies suggested that ALS relates to cancer. It has been shown that prostate cancer survivors are associated with a decreased risk of ALS [1]. In the contrary, a significantly elevated risk of ALS among survivors of melanoma and tongue cancer has been also reported [1]. ALS and cancer share defects in various cellular processes including cell survival, cell death and cell cycle. However, in ALS the defects results in progressive defect of motor neuron, while in cancer it results in uncontrolled cell survival and proliferation [1]. More than thirty ALS-causing genes have been identified and every year still new ALS-causing gene is reported. Some of them appear to be involved in not only ALS but also cancer as summarized below and in Table 1.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"12 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80932856","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":"Importance of a Multidisciplinary Approach to Breast Cancer Treatment in Pregnancy: Case Report of New Diagnosis of Pregnancy-Associated Breast Cancer","authors":"J. Grant, C. Dicarlo, J. Woessner-Hoyson","doi":"10.4172/2157-2518.1000279","DOIUrl":"https://doi.org/10.4172/2157-2518.1000279","url":null,"abstract":"Pregnancy-Associated Breast Cancer (PABC) is a rare diagnosis and includes new diagnoses of cancer both during pregnancy as well as within the first year post-delivery. Due to its rarity, there is of yet no gold standard treatment nor is there a standardized regimen of treatment during pregnancy according to the American College of Obstetrics and Gynecology (ACOG). We report a case involving a 35-year-old gravida 2 para 1-0-0-1 who was diagnosed with clinical stage II (T2 N1) breast cancer in the early third trimester of pregnancy after physical examination revealed a palpable mass. Ultrasound-guided biopsy revealed poorly differentiated infiltrating ductal carcinoma, nuclear grade 3, with micropapillary features, estrogen receptor (ER 90%), progesterone receptor (PR 25%) positive, HER2 positive 3+ with Ki67 index 75%. After extensive counseling and discussion between Obstetrics, Maternal Fetal Medicine, Breast Surgery, Neonatal ICU, and Oncology, a decision was made to initiate neoadjuvant chemotherapy (NAC) with adriamycin and cyclophosphamide. Our patient completed 4 total NAC treatments prior to delivery followed by a regimen of weekly taxol plus herceptin and perjeta postpartum. This patient strongly desired to carry the pregnancy to term and began treatment prior to delivery, making this case unique in comparison to other publications in which treatment was delayed until after delivery, or the pregnancy was terminated prior to beginning treatment. Our case highlights the importance of a multi-disciplinary approach to counseling patients in this unique situation to allow them the autonomy to choose the treatment best for them and their baby.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"46 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2016-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86693010","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":"2,3,7,8-Tetrachlorodibenzo-p-dioxin: Genotoxicity and Oxidative Damage Potential in Human Peripheral Blood Lymphocytes","authors":"G. Güler, A. Çelik","doi":"10.4172/2157-2518.1000274","DOIUrl":"https://doi.org/10.4172/2157-2518.1000274","url":null,"abstract":"Dioxin-like compounds, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzo-furans (PCDFs) and dioxin-like polychlorinated biphenyls (PCBs) are a widespread and diverse group of persistent, lipophilic and hazardous environmental pollutants. Additionally, because they are by-products of chlorine- containing manufacturing process and incineration, they represent a serious environmental problem. In this research study; we investigated the genotoxic and oxidative effects of TCDD using single cell gel electrophoresis/COMET assay and measuring levels of catalase, superoxide dismutase enzymes, and malondialdehyde values for lipid peroxidation in peripheral blood lymphocyte cultures at three different doses. Blood samples were taken from healthy non-smoking male subjects by venipuncture. In this study, the three doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin were used as 62.5 ng/ml, 31.25 ng/ml, 15.625 ng/ml. In comet assay, two different parameters were evaluated. Damaged cell percent (DCP). Genetic damage index (GDI). Both GDI and DCP significantly increased in a dose-dependent manner at statistical level. There is no statistically significant difference the levels of catalase, superoxide dismutase enzymes, malondialdehyde values compared with negative control.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"80 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2016-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83863543","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":"Water: The First Archaic Mutagen of Evolution, the Adoptive Mother of Currently Nucleic Acids","authors":"F. Caradonna","doi":"10.4172/2157-2518.1000E121","DOIUrl":"https://doi.org/10.4172/2157-2518.1000E121","url":null,"abstract":"Within the series of evolutions which start from the origin of the universe and still cannot, by definition, be considered concluded, certainly among the geothermal evolution end and the beginning of the chemical one, on Earth, the moment was favorable for the arrival of the first proto-nucleotides: from underground deposits of methanehydrate [1] and phosphate, with the support of all known pre-biotic physical-chemical conditions, were made the monomeric components of nucleic acids. The cradle of nucleic acids does not seem to have been so fundamentally aqueous, but organic. In fact, thinking back that “all the major biopolymers are metastable in aqueous solution” [2], it is easy to conclude that in those days a proto-nucleotide, or better its carbohydrate, in the aqueous phase would have shown all its inadequacy. However, knowing how today is made a nucleic acid, it is evident that the fine evolutionary strategy has distinguished, for this event, two necessities and consequently has chosen two evolutionary times and two different environments to achieve them:","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"43 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2016-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86242728","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":"Multiple Myeloma Relapsed with Skull Involvement in Plasmacytoma","authors":"Y. Kayar, Nuket Bayram Kayar, I. Ekinci, G. Çoban, N. Unver","doi":"10.4172/2157-2518.1000273","DOIUrl":"https://doi.org/10.4172/2157-2518.1000273","url":null,"abstract":"Extra medullary plasmacytomas occurring as solitary (primary) tumours or secondary manifestations of multiple myeloma most often involve the upper airways and paranasal sinuses. The skull is one of the rarest sites of extra medullary plasmacytoma. Myelomatous deposits in dural reflections distant from the bony skull, i.e. tentorium and falx, are rarer, and probably result from dissection along layers of meninges. Osseous and pachymeningeal masses in the cranial vault or in the skull base may result in tumefaction, pain, headache, single or multiple cranial nerve palsies or seizure. A case of multiple myeloma relapsed with extra medullary plasmacytoma in the skull; forehead and ear involvement is reported.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"7 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2016-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91246279","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":"Juvenile Granulosa Cell Tumor - A Rare Neoplasm in Newborns","authors":"O. Oral, E. Ozer, E. Kaymaz, S. Hucumenoglu","doi":"10.4172/2157-2518.1000I101","DOIUrl":"https://doi.org/10.4172/2157-2518.1000I101","url":null,"abstract":"","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"5 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2016-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75223493","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":"Carcinoma Associated Fibroblast: A Paradoxical Role in Pancreatic Cancer Microenvironment and a Promising Target for Therapy","authors":"J. Yang, X. Bail, T. Liang","doi":"10.4172/2157-2518.1000271","DOIUrl":"https://doi.org/10.4172/2157-2518.1000271","url":null,"abstract":"Pancreatic cancer is a grave malignancy showing an upward trend in morbidity and mortality during the recent decades. For reasons of late diagnosis, chemoresistance, low potential respectable rate and high post-operative recurrence rate, it has been the 6th most common cause of cancer death in China. As one of the most aggressive malignancies and the most common type of pancreatic cancer, pancreatic adenocarcinoma (PDAC) represents a significant therapeutic challenge. Conventional chemotherapeutic cytotoxic agents are proved to be with a poor survival benefit. Though the current first-line therapy FOLFIRINOX increased the median survival time compared with gemcitabine, it has been still unsatisfactory. Another direction enlighted by the treatement experience in other tumors is targeting certain molecules that participate in specific signaling pathways mediating cancer cell proliferating, angiogenesis, chemoresistance or metastasis. Unfortunately, none of the established \"targeted\" therapy agents that have been approved to be effective in some other tumors has a similar effect on PDAC, suggesting that there are some unique and decisive elements in the microenvironment of PDAC to facilitate its extensive drugresistance. Thus, the spotlight has been turned on immunotherapy, which is theoretically curative regardless of the complex molecular and cellular heterogeneity while the concrete strategies on PDAC are still in the dark. Revisiting the complex biology of PDAC, three prime characteristics will never be missed: almost 90% of patients with oncogene mutation of KRAS, as well as loss of tumor suppressor genesTP53 and SMAD4; mostly hypovascular; and tumor desmoplasia by persistent activation of fibroblasts/ pancreatic stellate cells (PSC). The last one, which is the defining feature of PDAC, as the target of therapy is the focus of this review.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"78 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2016-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82474864","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}