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Juan Yang, Cun Wang, Fengbo Zhao, Xiaoying Luo, Meilin Qin, Einthavy Arunachalam, Zhouhong Ge, Ning Wang, Xuan Deng, Guangzhi Jin, Wenming Cong, Wenxin Qin
Reprogrammed metabolism has been identified as an emerging hallmark in cancer cells. It has been demonstrated that fructose-1, 6-bisphosphatase 1 (FBP1) as a rate-limiting enzyme in gluconeogenesis plays critical roles in tumor initiation and progression in several cancer types. However, function of FBP1 in hepatocelluar carcinoma (HCC) is still not clear. In this study, we observed that the expression of FBP1 was obviously downregulated in the cell lines and tissues of HCC. Downregulation of FBP1 in HCC tissues was correlated with a lower overall survival rate and had a relatively higher tendency of tumor recurrence (n = 224)...
October 14, 2016: Carcinogenesis
Cynthia M Rigby, Srirupa Roy, Gagan Deep, Ruth Guillermo-Lagae, Anil K Jain, Deepanshi Dhar, David J Orlicky, Chapla Agarwal, Rajesh Agarwal
Non-melanoma skin cancers (NMSC) are a growing problem given that solar UVB radiation exposure is increasing most likely due to depletion of the atmospheric ozone layer and lack of adequate sun protection. Better preventive methods are urgently required to reduce UV-caused photodamage and NMSC incidence. Earlier, we have reported that silibinin treatment activates p53 and reduces photodamage and NMSC, both in vitro and in vivo; but whether silibinin exerts its protective effects primarily through p53 remain unknown...
October 11, 2016: Carcinogenesis
Jin Young Kim, Garam Kim, Sung-Chul Lim, Hong Seok Choi
LPIN1 is a protein that exhibits dual functions as a phosphatidic acid phosphatase enzyme in regulation of triglyceride and glycerophospholipid metabolism and a transcriptional coregulator. Through unknown tumour-promoting mechanism, LPIN1 frequently observed in various human cancer cell lines controls main cellular processes involved in cancer progression. Here, we demonstrate that LPIN1 enhances the tumour-promoting function of insulin receptor substrate 1 (IRS1) by controlling IRS1 stability. LPIN1 interacts with IRS1 in an insulin growth factor-1-dependent signalling pathway and inhibits its serine phosphorylation, and thereby eliminating ubiquitin-dependent degradation of IRS1 via proteasomal and lysosomal pathways...
October 11, 2016: Carcinogenesis
Jan Christian Kaiser, Reinhard Meckbach, Markus Eidemüller, Martin Selmansberger, Kristian Unger, Viktor Shpak, Maria Blettner, Horst Zitzelsberger, Peter Jacob
Strong evidence for the statistical association between radiation exposure and disease has been produced for thyroid cancer by epidemiological studies after the Chernobyl accident. However limitations of the epidemiological approach in order to explore health risks especially at low doses of radiation appear obvious. Statistical fluctuations due to small case numbers dominate the uncertainty of risk estimates. Molecular radiation markers have been searched extensively to separate radiation- induced cancer cases from sporadic cases...
October 11, 2016: Carcinogenesis
Imran Ali, Bettina Julin, Anders Glynn, Johan Högberg, Marika Berglund, Jan-Erik Johansson, Swen-Olof Andersson, Ove Andrén, Edward Giovannucci, Alicja Wolk, Ulla Stenius, Agneta Åkesson
Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases)...
October 7, 2016: Carcinogenesis
Julia Odenthal, Robert Takes, Peter Friedl
Tumor cell migration, the basis for metastatic dissemination, is an adaptive process which depends upon coordinated cell interaction with the environment, influencing cell-matrix and cell-cell adhesion, cytoskeletal dynamics and extracellular matrix remodeling. Growth factors and cytokines, released within the reactive tumor microenvironment and their intracellular effector signals strongly impact mechanocoupling functions in tumor cells and thereby control the mode and extent of tumor invasion, including collective and single-cell migration and their interconversions...
September 23, 2016: Carcinogenesis
Ana S Leal, Michael B Sporn, Patricia A Pioli, Karen T Liby
Because the 5-year survival rate for pancreatic cancer remains under 10%, new drugs are needed for the prevention and treatment of this devastating disease. Patients with chronic pancreatitis have a 12-fold higher risk of developing pancreatic cancer. LSL-Kras(G12D/+);Pdx-1-Cre (KC) mice replicate the genetics, symptoms and histopathology found in human pancreatic cancer. Immune cells infiltrate into the pancreas of these mice and produce inflammatory cytokines that promote tumor growth. KC mice are particularly sensitive to the effects of lipopolysaccharide (LPS), as only 48% of KC mice survived an LPS challenge while 100% of wildtype (WT) mice survived...
September 22, 2016: Carcinogenesis
Vikas Bhardwaj, Andela Horvat, Olga Korolkova, Kay M Washington, Wael El-Rifai, Sergey I Dikalov, Alexander I Zaika
Esophageal adenocarcinoma (EA) is one of the fastest rising tumors in the US. The major risk factor for EA is gastroesophageal reflux disease (GERD). During GERD, esophageal cells are exposed to refluxate which contains gastric acid frequently mixed with duodenal bile. This may lead to mucosal injury and Barrett's metaplasia (BE) that are important factors contributing to development of EA. In this study, we investigated DNA damage in BE cells exposed to acidic bile salts and explored for potential protective strategies...
September 21, 2016: Carcinogenesis
Zeli Shen, Yan Feng, Sureshkumar Muthupalani, Alexander Sheh, Lenzie E Cheaney, Christian A Kaufman, Guanyu Gong, Bruce J Paster, James G Fox
A novel Helicobacter species Helicobacter japonicum was isolated from the stomach and intestines of clinically normal mice received from three institutes from Japan. The novel Helicobacter sp. was microaerobic, grew at 37°C and 42°C, was catalase and oxidase positive, but urease negative. It is most closely related to the 16S rRNA gene of H.muridarum (98.6%); to the 23S rRNA gene of H.hepaticus (97.9%); to the hsp60 gene of H.typhlonius (87%). The novel Helicobacter sp. has in vitro cytolethal distending toxin (CDT) activity; its cdtB gene sequence has 83...
September 21, 2016: Carcinogenesis
Warapen Treekitkarnmongkol, Hiroshi Katayama, Kazuharu Kai, Kaori Sasai, Jennifer Carter Jones, Jing Wang, Li Shen, Aysegul A Sahin, Mihai Gagea, Naoto T Ueno, Chad J Creighton, Subrata Sen
Recent data from The Cancer Genome Atlas analysis have revealed that Aurora kinase A (AURKA) amplification and overexpression characterize a distinct subset of human tumors across multiple cancer types. Although elevated expression of AURKA has been shown to induce oncogenic phenotypes in cells in vitro, findings from transgenic mouse models of Aurora-A overexpression in mammary glands have been distinct depending on the models generated. In the present study, we report that prolonged overexpression of AURKA transgene in mammary epithelium driven by ovine β-lactoglobulin promoter, activated through multiple pregnancy and lactation cycles, results in the development of mammary adenocarcinomas with alterations in cancer-relevant genes and epithelial-to-mesenchymal transition...
September 13, 2016: Carcinogenesis
Courey Averett, Arun Bhardwaj, Sumit Arora, Sanjeev K Srivastava, Mohammad Aslam Khan, Aamir Ahmad, Seema Singh, James E Carter, Moh'd Khushman, Ajay P Singh
The poor clinical outcome of pancreatic cancer (PC) is largely attributed to its aggressive nature and refractoriness to currently available therapeutic modalities. We previously reported antitumor efficacy of honokiol (HNK), a phytochemical isolated from various parts of Magnolia plant, against PC cells in short-term in vitro growth assays. Here, we report that HNK reduces plating efficiency and anchorage-independent growth of PC cells and suppresses their migration and invasiveness. Furthermore, significant inhibition of pancreatic tumor growth by HNK is observed in orthotopic mouse model along with complete-blockage of distant metastases...
September 8, 2016: Carcinogenesis
Yuncheng Li, Erich M Sturgis, Ying Yuan, Meixia Lu, Xiaoli Cao, Qingyi Wei, Guojun Li
Given roles of HPV and genetic factors in cancer risk, we evaluated associations of HPV16 seropositivity and five E2F2 promoter variants with squamous cell carcinoma of oropharynx (SCCOP) and squamous cell carcinoma of oral cavity (SCCOC) risk in a case-control study of 325 patients and 335 cancer-free matched controls. We found that HPV16 seropositivity was significantly associated with SCCOP risk (aOR, 5.4, 95%CI, 3.7-8.9) but not SCCOC (aOR, 0.8, 95%CI, 0.4-1.5), while each E2F2 polymorphism had no significant main effect on SCCOP and SCCOC risk...
September 8, 2016: Carcinogenesis
Raja M Flores, Bian Liu, Emanuela Taioli
This study was performed to quantify the association between mortality and known and unknown secondhand smoke (SHS) exposure as measured by cotinine levels in non-smokers. Data collected from 1999 to 2010 in the National Health and Nutrition Examination Survey (NHANES) were linked to the National Death Index. Self-reported non-smokers aged ≥20 years (N = 20 175) were studied. Serum cotinine was measured at recruitment; non-smokers were those with cotinine below the reported race-specific cut-off points (5...
September 7, 2016: Carcinogenesis
Rachel A Hesler, Jennifer J Huang, Mark D Starr, Victoria M Treboschi, Alyssa G Bernanke, Andrew B Nixon, Shannon J McCall, Rebekah R White, Gerard C Blobe
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer in part due to inherent resistance to chemotherapy, including the first-line drug gemcitabine. While low expression of the nucleoside transporters hENT1 and hCNT3 that mediate cellular uptake of gemcitabine has been linked to gemcitabine resistance, the mechanisms regulating their expression in the PDAC tumor microenvironment are largely unknown. Here, we report that the matricellular protein cysteine-rich angiogenic inducer 61 (CYR61) negatively regulates the nucleoside transporters hENT1 and hCNT3...
September 7, 2016: Carcinogenesis
Shoba Iyer, Ya Wang, Wei Xiong, Deliang Tang, Wieslaw Jedrychowski, Stephen Chanock, Shuang Wang, Laura Stigter, Elzbieta Mróz, Frederica Perera
Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a known human carcinogen. Within our Polish cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn single nucleotide polymorphisms (SNPs) in plausible B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples...
August 26, 2016: Carcinogenesis
Yu Ri Jung, Jung-Jin Park, Yeung Bae Jin, Yuan Jie Cao, Myung-Jin Park, Eun Ju Kim, Minyoung Lee
Aberrant sialylation has long been correlated with human cancer. Increased ST6 Gal I (β-galactoside α 2, 6 sialyltransferase) and consequently higher levels of cell-surface α 2, 6 sialylation has been associated with human colorectal cancer (CRC) metastasis. We have extensive circumstantial data that sialylation is connected to cancer metastasis, but we do not understand in detail how sialylation can switch on/off multiple steps in cancer metastasis. To investigate the molecular mechanism underlying the ST6Gal I-mediated metastasis of CRC, we silenced the ST6Gal I gene in a metastatic SW620 CRC cell line (SW620-shST6Gal I) and examined the metastatic behavior of the cells...
August 24, 2016: Carcinogenesis
Tatsuo Kakiuchi, Taishi Takahara, Yumiko Kasugai, Kotaro Arita, Noriaki Yoshida, Kennosuke Karube, Miyuki Suguro, Keitaro Matsuo, Hayao Nakanishi, Tohru Kiyono, Shigeo Nakamura, Hirotaka Osada, Yoshitaka Sekido, Masao Seto, Shinobu Tsuzuki
Mesotheliomas are frequently characterized by disruption of Hippo pathway due to deletion and/or mutation in genes, such as neurofibromin 2 (NF2). Hippo disruption attenuates yes-associated protein (YAP) phosphorylation allowing YAP to translocate to the nucleus and regulate gene expression. The role of disrupted Hippo pathway in maintenance of established mesotheliomas has been extensively investigated using cell lines; however, its involvement in development of human mesothelioma has not been explored much...
August 24, 2016: Carcinogenesis
Zhong Xiong, Meng Guo, Yun Yu, Fei-Fei Zhang, Meng-Kai Ge, Guo-Qiang Chen, Shao-Ming Shen
Recently, we have reported that apoptosis-inducing factor (AIF) regulates the epithelial-mesenchymal transition (EMT) process of cancers, but the mechanisms underlying the regulation of AIF expression in cancers remain greatly unknown. Here, we report that hypoxia inversely correlates with the expression of AIF in tumor tissues from a cohort of colon cancer patients and inhibits AIF expression in multiple colon cancer cell lines. This inhibition is mediated by hypoxia-inducible factor-1 (HIF-1), which transcriptionally represses AIF through direct binding to the hypoxia-response element in AIF promoter as revealed by luciferase reporter and chromatin immunoprecipitation assays...
August 19, 2016: Carcinogenesis
Anup Kumar Singh, Shikha S Chauhan, Sudhir Kumar Singh, Vedvrat Verma, Akhilesh Singh, Rakesh Kumar Arya, Shrankhla Maheshwari, Md Sohail Akhtar, Jayanta Sarkar, Vivek M Rangnekar, Prem M S Chauhan, Dipak Datta
MDM2 protein functionally inactivates the tumor suppressor p53 in human cancer. Conventional MDM2 inhibitors provide limited clinical application as they interfere only with the MDM2-p53 interaction to release p53 from MDM2 sequestration but do not prevent activated p53 from transcriptionally inducing MDM2 expression. Here, we report a rationally synthesized chalcone based pyrido[b]indole, CPI-7c, as a unique small molecule inhibitor of MDM2, which not only inhibited MDM2-p53 interaction but also promoted MDM2 degradation...
August 19, 2016: Carcinogenesis
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October 2016: Carcinogenesis
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