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damage control AND colorectal

Chiara Fazio, Luigi Ricciardiello
The Notch cascade is a fundamental and highly conserved pathway able to control cell-fate. The Notch pathway arises from the interaction of one of the Notch receptors (Notch1-4) with different types of ligands; in particular, the Notch pathway can be activated canonically (through the ligands Jagged1, Jagged2, DLL1, DLL3 or DLL4) or non-canonically (through various molecules shared by other pathways). In the context of tumor biology, the deregulation of Notch signaling is found to be crucial, but it is still not clear if the activation of this pathway exerts a tumor-promoting or a tumor suppressing function in different cancer settings...
December 8, 2016: Cell Death & Disease
Lorraine Pelosof, Sashidhar Yerram, Todd Armstrong, Nina Chu, Ludmila Danilova, Breann Yanagisawa, Manuel Hidalgo, Nilofer Azad, James G Herman
Epigenetic control of gene expression is a major determinant of tumor phenotype and has been found to influence sensitivity to individual chemotherapeutic agents. Glutathione peroxidase 3 (GPX3, plasma glutathione peroxidase) is a key component of cellular antioxidant regulation and its gene has been reported to be methylated in specific tumor types. GPX3 role in oxidative damage has been associated with sensitivity to platinums in other tumors but its importance in colorectal cancer (CRC) has not been determined...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Markus S Anker, Nicole Ebner, Bert Hildebrandt, Jochen Springer, Marianne Sinn, Hanno Riess, Stefan D Anker, Ulf Landmesser, Wilhelm Haverkamp, Stephan von Haehling
AIMS: Patients with advanced cancer have been shown to suffer from abnormal cardiac function and impaired exercise capacity that may contribute to their impaired quality of life. As tachycardia is considered as a sign of potential early cardiac damage, we sought to determine whether resting heart rate and other ECG-derived variables have prognostic value. METHODS AND RESULTS: From 2005 to 2010, we enrolled 145 patients with histologically confirmed cancer (36 colorectal, 72 pancreatic, and 37 non-small cell lung cancer patients) and 59 healthy controls...
December 2016: European Journal of Heart Failure
Jiaquan Liu, Jeungphill Hanne, Brooke M Britton, Jared Bennett, Daehyung Kim, Jong-Bong Lee, Richard Fishel
Mismatched nucleotides arise from polymerase misincorporation errors, recombination between heteroallelic parents and chemical or physical DNA damage. Highly conserved MutS (MSH) and MutL (MLH/PMS) homologues initiate mismatch repair and, in higher eukaryotes, act as DNA damage sensors that can trigger apoptosis. Defects in human mismatch repair genes cause Lynch syndrome or hereditary non-polyposis colorectal cancer and 10-40% of related sporadic tumours. However, the collaborative mechanics of MSH and MLH/PMS proteins have not been resolved in any organism...
November 16, 2016: Nature
Rehab A Karam, Bilal O Al Jiffry, Mohamed Al Saeed, Tamer M Abd El Rahman, Mohamed Hatem, Mona G Amer
BACKGROUND AND STUDY AIMS: Polymorphisms in the DNA repair genes may influence individual capacity to repair DNA damage, which may be associated with increased genetic instability and carcinogenesis. Our aim was to evaluate the relation of genetic polymorphisms in 2 DNA repair genes, XPD Lys751Gln and XRCC1 (A399G), with colorectal cancer (CRC) susceptibility. We further investigated the potential effect of these DNA repair variants on clinicopathological parameters of CRC patients. PATIENTS AND METHODS: Both XPD and XRCC1 polymorphisms were characterised in one hundred CRC patients and one hundred healthy controls who had no history of any malignancy by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and PCR with confronting two-pair primers (PCR-CTPP), using DNA from peripheral blood in a case control study...
September 2016: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
Haisheng Guo, Yunhui Xing, Ailan Mu, Xia Li, Tingshan Li, Xia Bian, Chunmei Yang, Xiaolei Zhang, Yuefen Liu, Xunguo Wang
Proliferation, growth, and differentiation of cells are strictly controlled by the signal system of epidermal growth factor receptor (EGFR). If any link of the EGFR signals system is interfered with or damaged, the proliferation, growth, and differentiation of cells would become uncontrolled. EGFR is overexpressed in a variety of malignant tumors, such as non-small-cell lung cancer, colorectal cancer and breast cancer. Results of the study have proved that EGFR overexpression is closely associated with mutations and variants of the EGFR genes, whose mutations and variants are associated with occurrence, metastasis, and prognosis of different types of tumors, including lung cancer...
2016: OncoTargets and Therapy
Xihan Guo, Xu Wang
The fruit of Phyllanthus emblica Linn. (PE) has been widely consumed as a functional food and folk medicine in Southeast Asia due to its remarkable nutritional and pharmacological effects. Previous research showed PE delays mitotic progress and increases genomic instability (GIN) in human colorectal cancer cells. This study aimed to investigate the similar effects of PE by the biomarkers related to spindle assembly checkpoint (SAC), mitotic aberrations and GIN in human NCM460 normal colon epithelial cells. Cells were treated with PE and harvested differently according to the biomarkers observed...
2016: International Journal of Molecular Sciences
Cheng Guo, Xiaofen Li, Rong Wang, Jiekai Yu, Minfeng Ye, Lingna Mao, Suzhan Zhang, Shu Zheng
Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis...
2016: Scientific Reports
Daniele Fanale, Marta Castiglia, Viviana Bazan, Antonio Russo
Despite recent progress in understanding the cancer signaling pathways and in developing new therapeutic strategies, however, the resistance of colorectal cancer (CRC) cells to chemo- and radiotherapy represents the main hurdle to the successful treatment, leading to tumor recurrence and, consequently, a poor prognosis. Therefore, overcoming drug and radiation resistance, enhancing drug and radiation sensitivity of CRC cells, and improving the efficacy of chemo- and radiotherapy have an important significance in the treatment of CRC...
2016: Advances in Experimental Medicine and Biology
Alexandra M Mowday, Amir Ashoorzadeh, Elsie M Williams, Janine N Copp, Shevan Silva, Matthew R Bull, Maria R Abbattista, Robert F Anderson, Jack U Flanagan, Christopher P Guise, David F Ackerley, Jeff B Smaill, Adam V Patterson
The clinical stage anti-cancer agent PR-104 has potential utility as a cytotoxic prodrug for exogenous bacterial nitroreductases expressed from replicating vector platforms. However substrate selectivity is compromised due to metabolism by the human one- and two-electron oxidoreductases cytochrome P450 oxidoreductase (POR) and aldo-keto reductase 1C3 (AKR1C3). Using rational drug design we developed a novel mono-nitro analog of PR-104A that is essentially free of this off-target activity in vitro and in vivo...
September 15, 2016: Biochemical Pharmacology
Rodrigo C Surjan, Fabio F Makdissi, Tiago Basseres, Denise Leite, Luiz F Charles, Regis O Bezerra, Erik Schadde, Marcel Autran Machado
BACKGROUND: ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) is a new surgical approach for the treatment of liver tumors. It is indicated in cases where the future liver remnant is not sufficient to maintain postoperative liver function. We report a totally laparoscopic ALPPS with selective hepatic artery clamping. Pneumoperitoneum itself results in up to 53% of portal vein flow and selective hepatic artery clamping can reduce blood loss while maintaining hepatocellular function...
July 2016: Medicine (Baltimore)
Gracie Vargas, Kathleen Listiak Vincent, Jingna Wei, Nigel Bourne, Massoud Motamedi
BACKGROUND: Concern regarding the effect of epithelial damage to the colorectal surface and possible impact on sexually transmitted infection transmission prompts the need for methods to evaluate the mucosal microscopic surface in preclinical studies examining such injury. This includes determining the effect of topical HIV prevention products on mucosal barrier integrity. In vivo imaging with high-resolution endomicroscopy could reveal defects in the mucosal barrier resulting from injury/surface trauma...
November 2016: Journal of Microscopy
Xiao-Li Huang, Xin Zhang, Xian-Yan Fei, Zhao-Gui Chen, Yan-Ping Hao, Shu Zhang, Ming-Ming Zhang, Yan-Qiu Yu, Cheng-Gong Yu
AIM: To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii (F. prausnitzii) supernatant on dextran sulfate sodium (DSS) induced colitis in mice. METHODS: Forty C57BL/6J male mice were randomly divided into four groups: control group, model group, treatment group, and prevention group. Mice were weighed daily. On day 10, the colon length was measured, the colorectal histopathologic damage score (HDS) was assessed, and plasma interleukin (IL)-17A, IL-6, and IL-4 levels were detected by enzyme-linked immunosorbent assay...
June 14, 2016: World Journal of Gastroenterology: WJG
Yunyi Yang, Zi Liu, Juan Wang, Yanlan Chai, Jin Su, Fan Shi, Jiquan Wang, Shao Min Che
We aim to investigate the effect of interferon gamma (IFN-γ) on conventional fractionated radiation-induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-γ group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-γ and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-γ group were administered 250,000 U/kg IFN-γ intramuscularly once a week for 5 weeks...
2016: Therapeutics and Clinical Risk Management
Linda Kinzel, Anne Ernst, Michael Orth, Valerie Albrecht, Roman Hennel, Nikko Brix, Benjamin Frey, Udo S Gaipl, Gabriele Zuchtriegel, Christoph A Reichel, Andreas Blutke, Daniela Schilling, Gabriele Multhoff, Minglun Li, Maximilian Niyazi, Anna A Friedl, Nicolas Winssinger, Claus Belka, Kirsten Lauber
The chaperone heat shock protein 90 (HSP90) crucially supports the maturation, folding, and stability of a variety of client proteins which are of pivotal importance for the survival and proliferation of cancer cells. Consequently, targeting of HSP90 has emerged as an attractive strategy of anti-cancer therapy, and it appears to be particularly effective in the context of molecular sensitization towards radiotherapy as has been proven in preclinical models of different cancer entities. However, so far the clinical translation has largely been hampered by suboptimal pharmacological properties and serious hepatotoxicity of first- and second-generation HSP90 inhibitors...
June 1, 2016: Oncotarget
Tetsuro Isozaki, Mayumi Fujita, Shigeru Yamada, Kaori Imadome, Yoshimi Shoji, Takeshi Yasuda, Fumiaki Nakayama, Takashi Imai, Hisahiro Matsubara
C-ion radiotherapy is associated with improved local control and survival in several types of tumors. Although C-ion irradiation is widely reported to effectively induce DNA damage in tumor cells, the effects of irradiation on proteins, such as protein stability or degradation in response to radiation stress, remain unknown. We aimed to compare the effects of C-ion and X-ray irradiation focusing on the cellular accumulation of ubiquitylated proteins. Cells from two human colorectal cancer cell lines, SW620 and SW480, were subjected to C-ion or X-ray irradiation and determination of ubiquitylated protein levels...
July 2016: International Journal of Oncology
Pi-Yueh Chang, Jinn-Shiun Chen, Nai-Chung Chang, Shih-Cheng Chang, Mei-Chia Wang, Shu-Hui Tsai, Ying-Hao Wen, Wen-Sy Tsai, Err-Cheng Chan, Jang-Jih Lu
Colorectal cancer (CRC) arises from mutations in a subset of genes. We investigated the germline and somatic mutation spectrum of patients with CRC in Taiwan by using the AmpliSeq Cancer Hotspot Panel V2. Fifty paired freshly frozen stage 0-IV CRC tumors and adjacent normal tissue were collected. Blood DNA from 20 healthy donors were used for comparison of germline mutations. Variants were identified using an ion-torrent personal genomic machine and subsequently confirmed by Sanger sequencing or pyrosequencing...
June 21, 2016: Oncotarget
Yong Wang, Yunsheng Cheng, Gang Yu, Benli Jia, Zhihang Hu, Lijiu Zhang
As typical clock gene machinery, period (PER1, PER2, and PER3), cryptochrome (CRY1 and CRY2), and timeless (TIM), could control proliferation, cellular metabolism, and many key functions, such as recognition and repair of DNA damage, dysfunction of the circadian clock could result in tumorigenesis of colorectal cancer (CRC). In this study, the expression levels of PER1, PER2, and PER3, as well as CRY1, CRY2, and TIM in the tumor tissue and apparently healthy mucosa from CRC patients were examined and compared via quantitative real-time polymerase chain reaction...
2016: OncoTargets and Therapy
Saiho Ko, Yuuki Kirihataya, Yayoi Matsumoto, Tadataka Takagi, Masanori Matsusaka, Tomohide Mukogawa, Hirofumi Ishikawa, Akihiko Watanabe
AIM: To evaluate the efficacy of technical modifications of total hepatic vascular exclusion (THVE) for hepatectomy involving inferior vena cava (IVC). METHODS: Of 301 patients who underwent hepatectomy during the immediate previous 5-year period, 8 (2.7%) required THVE or modified methods of IVC cross-clamping for resection of liver tumors with massive involvement of the IVC. Seven of the patients had diagnosis of colorectal liver metastases and 1 had diagnosis of hepatocellular carcinoma...
March 18, 2016: World Journal of Hepatology
Xuyu Zu, Ruilan Yan, Jishen Pan, Linlin Zhong, Yu Cao, Jun Ma, Chuan Cai, Dan Huang, Jianghua Liu, Fung-Lung Chung, Duan-Fang Liao, Deliang Cao
Electrophilic carbonyl compounds are highly cytotoxic and genotoxic. Aldo-keto reductase 1B10 (AKR1B10) is an enzyme catalyzing reduction of carbonyl compounds to less toxic alcoholic forms. This study presents novel evidence that AKR1B10 protects colon cells from DNA damage induced by electrophilic carbonyl compounds. AKR1B10 is specifically expressed in epithelial cells of the human colon, but this study found that AKR1B10 expression was lost or markedly diminished in colorectal cancer, precancerous tissues, and a notable portion of normal adjacent tissues (NAT)...
January 2017: Molecular Carcinogenesis
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