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genetic markers in gastrointestinal cancer

Peyton Cramer, Robert S Bresalier
PURPOSE OF REVIEW: Gastrointestinal complications are very common in patients undergoing cancer treatment. Some of these complications can be life threatening and require prompt and appropriate diagnosis and treatment. The purpose of this review is to address luminal gastrointestinal and hepatic complications associated with a new class of anticancer drugs, immune checkpoint inhibitors (CPIs), and focuses on the identification, evaluation, and management of the complications associated with this class of drugs...
January 2017: Current Gastroenterology Reports
Jun-Yan Liu, Chen-Yue Qian, Yuan-Feng Gao, Juan Chen, Hong-Hao Zhou, Ji-Ye Yin
BACKGROUND: Chemotherapy toxicity is a serious problem from which non-small cell lung cancer (NSCLC) patients suffer. The mismatch repair (MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patients. In this study, we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients. METHODS: A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study...
January 16, 2017: Chinese Journal of Cancer
Manuela G Neuman, Samuel W French, Samir Zakhari, Stephen Malnick, Helmut K Seitz, Lawrence B Cohen, Mikko Salaspuro, Andreea Voinea-Griffin, Andrei Barasch, Irina A Kirpich, Paul G Thomes, Laura W Schrum, Terrence M Donohue, Kusum K Kharbanda, Marcus Cruz, Mihai Opris
This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases...
January 7, 2017: Experimental and Molecular Pathology
Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Nikolaos Tsoulos, Angeliki Tsirigoti, Chrisoula Efstathiadou, Angela Apessos, Konstantinos Agiannitopoulos, Georgia Pepe, Eugenia Bourkoula, George Nasioulas
Gastrointestinal malignancies are among the leading causes of cancer-related deaths worldwide. Like all human malignancies they are characterized by accumulation of mutations which lead to inactivation of tumor suppressor genes or activation of oncogenes. Advances in Molecular Biology techniques have allowed for more accurate analysis of tumors' genetic profiling using new breakthrough technologies such as next generation sequencing (NGS), leading to the development of targeted therapeutical approaches based upon biomarker-selection...
November 15, 2016: World Journal of Gastrointestinal Oncology
Chengxu Cui, Chang Shu, Dandan Cao, Yi Yang, Junbao Liu, Shuping Shi, Zhujun Shao, Nan Wang, Ting Yang, Hao Liang, Shanshan Zou, Songnian Hu
Irinotecan-induced severe neutropenia and diarrhea, which remain unpredictable, has restrained the dose and clinical efficiency of irinotecan administration. In the present study, a total of 70 irinotecan-treated patients with histologically confirmed metastatic gastrointestinal cancer were enrolled. Despite genotyping well-reported alleles, direct sequencing was specifically adopted to avoid ethnic heterogeneity and to identify novel variations. The promoter (-1000 bp) and exon 1 regions of UDP glucuronosyltransferase family 1 member A complex locus (UGT1A1) gene family members UGT1A1, UGT1A7 and UGT1A9 were sequenced, and comprehensive analysis of their genetic polymorphisms was performed to determine the association between inherited genetic variations and irinotecan-induced toxicity...
November 2016: Oncology Letters
Nader Bagheri, Fatemeh Azadegan-Dehkordi, Mahmoud Rafieian-Kopaei, Ghorbanali Rahimian, Majid Asadi-Samani, Hedaytollah Shirzad
Helicobacter pylori (H. pylori) usually colonizes the gastric mucosa of more than 50% of the human population, causing an infection that may appear in early childhood and can persist for life. H. pylori is suggested as the main cause of peptic ulcer and chronic gastritis. It is also associated with gastric cancer. Its severity and symptoms depend on environmental factors, host susceptibility and bacterial components, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori is genetically highly variable, and the variability which affects H...
November 2016: Microbial Pathogenesis
T Rau
The pathogenesis of precursor lesions of gastrointestinal tumors is manifested in many ways. In the esophagus an aberrant genetic expression of intestinal transcription factors, such as CDX2 is initiated by local environment factors. During the subsequent dysplasia to carcinoma sequence, chromosomal gain and loss of genes occurs. A 4-color fluorescence in situ hybridization (FISH) assay can be applied in dysplasia as well as in Barrett's adenocarcinoma to define prognostic marker combinations. In the gastric carcinogenesis sequence the gene expression of CDX1 is regulatively dependent on an interplay between inflammation and promotor methylation...
November 2016: Der Pathologe
Junya Kitadani, Toshiyasu Ojima, Hiromitsu Iwamoto, Hiroaki Tabata, Mikihito Nakamori, Masaki Nakamura, Masahiro Katsuda, Motoki Miyazawa, Keiji Hayata, Hiroki Yamaue
The difficulty in obtaining a sufficient number of functional dendritic cells(DCs)is a well-known serious problem in DCbased immunotherapy. Therefore, we used induced pluripotent stem cell-derived DCs(iPSDCs). We have reported that mouse iPSDCs are equivalent to BMDCs, in terms of maturation and antigen presentation. In this study, the antitumor immune response of human iPSDCs expressing the carcinoembryonic antigen was examined, to determine its clinical application in gastrointestinal cancer. Human iPS cells were established from healthy human fibroblasts using a Sendai virus vector, and human iPSDCs were differentiated under a feeder-free culture...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Anastasia Katsiampoura, Scott Kopetz
Accumulating knowledge in colorectal cancer (CRC) biology has led to an understanding of the role of genetic and epigenetic alterations in tumorigenesis and progression of the disease. Numerous studies have focused on the identification of novel biomarkers in circulating free (cf)DNA that have the potential of guiding clinical practice. These markers are specifically attractive for the characterization of molecular profiles in patients with limited tissue access, the monitoring of therapeutic responses and the development of recurrent disease, the monitoring of the tumor evolution with therapy, and the response to therapy...
September 2014: Gastrointestinal Cancer Research: GCR
Matteo Astone, Marco Pizzi, Margherita Peron, Alice Domenichini, Vincenza Guzzardo, Sonja Töchterle, Natascia Tiso, Massimo Rugge, Dirk Meyer, Francesco Argenton, Andrea Vettori
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas, characterized by complex karyotypes. The molecular bases of such malignancy are poorly understood and efficient targeted molecular therapies are currently lacking. Here we describe a novel zebrafish model of MPNSTs, represented by the transgenic mutant line Tg(-8.5nkx2.2a:GFP)ia2. ia2 homozygous animals displayed embryonic lethality by 72 hpf, while the heterozygotes develop visible tumor masses with high frequency in adulthood...
2015: PloS One
Pratima Nangia-Makker, Yingjie Yu, Adhip Pn Majumdar
Colorectal cancer (CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging...
November 15, 2015: World Journal of Gastrointestinal Pathophysiology
Melissa R Junttila, Weiguang Mao, Xi Wang, Bu-Er Wang, Thinh Pham, John Flygare, Shang-Fan Yu, Sharon Yee, David Goldenberg, Carter Fields, Jeffrey Eastham-Anderson, Mallika Singh, Rajesh Vij, Jo-Anne Hongo, Ron Firestein, Melissa Schutten, Kelly Flagella, Paul Polakis, Andrew G Polson
Cancer stem cells (CSCs) are hypothesized to actively maintain tumors similarly to how their normal counterparts replenish differentiated cell types within tissues, making them an attractive therapeutic target for the treatment of cancer. Because most CSC markers also label normal tissue stem cells, it is unclear how to selectively target them without compromising normal tissue homeostasis. We evaluated a strategy that targets the cell surface leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a well-characterized tissue stem cell and CSC marker, with an antibody conjugated to distinct cytotoxic drugs...
November 18, 2015: Science Translational Medicine
Sarah Kraus, Daniel Sion, Nadir Arber
Aspirin has been extensively investigated in the context of the prevention of cardiovascular disease. It has one of the strongest cumulative evidence supporting its use in colorectal cancer (CRC) chemoprevention. Epidemiological, clinical, and observational studies have demonstrated that aspirin and non-steroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors, can protect against CRC and significantly reduce its incidence. Moreover, prospective randomized controlled trials of colorectal polyp recurrence and in patients with hereditary CRC syndromes have shown that aspirin can produce regression of existing colorectal adenomas and prevent the formation of new polyps...
2015: Current Pharmaceutical Design
Junqi Wang, Baoping Zhang, Zhi Yang, Long Zhou, Tingting Geng, Haipeng Li, Xiaowei Fu, Xiaolei Xue, Mingwei Liu, Ruifeng Tong, Tianbo Jin, Yong Zhang
Esophageal carcinoma (EC) is a common malignancy worldwide. Previous studies indicated that gastrointestinal gland cancer and EC share some susceptibility loci. Our aim was to identify new single nucleotide polymorphisms (SNPs) associated with EC by investigating whether known gastrointestinal cancers susceptibility loci are found in EC patients. A Chinese Han population case-control study was conducted to assess SNP associations with EC risk. Twenty-six SNPs were selected from gastrointestinal cancer susceptibility loci, and 360 EC patients and 310 controls were genotyped for these SNPs using Sequenom MassARRAY technology...
February 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Santosh Shenoy
Spindle cell neoplasms are rare mesenchymal tumors of the gastrointestinal tract. GIST (Gastrointestinal stromal tumor) and leiomyosarcoma share similar clinical presentations, gross and microscopic characteristics making distinction difficult in the absence of immunohistochemical (IHC) studies. A multidisciplinary approach is required for treatment planning and ensuring best outcomes. Surgery remains the mainstay of curative treatment for both tumors. Significant advances in targeted molecular therapies have occurred in the past decade in the treatment of GIST with improvement in morbidity and mortality...
September 2015: Surgical Oncology
Małgorzata Kołos, Anna Wasążnik-Jędras, Anna Nasierowska-Guttmejer
Colorectal cancer (CRC) is the most common type of gastrointestinal cancer and has three major pathways of carcinogenesis. About 80% of genomic instability concerns chromosomal instability (CIN); the rest is connected with either microsatellite instability (MSI) or CpG island methylation. Some MSI-related cancers are associated with Lynch syndrome, whereas others are caused by sporadic, acquired hypermethylation of the promoter of the MLH1 gene. These tumours have distinctive clinical and histopathological features...
June 2015: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Veronika Vymetalkova, Pavel Soucek, Tereza Kunicka, Katerina Jiraskova, Veronika Brynychova, Barbara Pardini, Vendula Novosadova, Zdena Polivkova, Katerina Kubackova, Renata Kozevnikovova, Miloslav Ambrus, Ludmila Vodickova, Alessio Naccarati, Pavel Vodicka
Variations in the TP53 gene have been suggested to play a role in many cancers, including breast. We previously observed an association between TP53 haplotypes based on four polymorphisms (rs17878362, rs1042522, rs12947788, and rs17884306) and the risk of colorectal and pancreatic cancer. Based on these results, in the present study, we have investigated the same polymorphisms and their haplotypes in 705 breast cancer cases and 611 healthy controls in relation to the disease risk, histopathological features of the tumor and clinical outcomes...
2015: PloS One
Silvia Martina Ferrari, Ugo Politti, Roberto Spisni, Gabriele Materazzi, Enke Baldini, Salvatore Ulisse, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Sorafenib has been evaluated in several Phase II and III studies in patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid carcinomas (DTCs), reporting partial responses, stabilization of the disease and improvement of progression-free survival. Best responses were observed in lung metastases and minimal responses in bone lesions. On the basis of these studies, sorafenib was approved for the treatment of metastatic DTC in November 2013. Few studies suggested that reduction of thyroglobulin levels, or of average standardized uptake value at the fluorodeoxyglucose-PET, could be helpful for the identification of responding patients; but further studies are needed to confirm these results...
2015: Expert Review of Anticancer Therapy
Rong Xu, QuanQiu Wang, Li Li
BACKGROUND: Dietary intakes of red meat and fat are established risk factors for both colorectal cancer (CRC) and cardiovascular disease (CVDs). Recent studies have shown a mechanistic link between TMAO, an intestinal microbial metabolite of red meat and fat, and risk of CVDs. Data linking TMAO directly to CRC is, however, lacking. Here, we present an unbiased data-driven network-based systems approach to uncover a potential genetic relationship between TMAO and CRC. MATERIALS AND METHODS: We constructed two different epigenetic interaction networks (EINs) using chemical-gene, disease-gene and protein-protein interaction data from multiple large-scale data resources...
2015: BMC Genomics
Alisa D Kjaergaard, Børge G Nordestgaard, Julia S Johansen, Stig E Bojesen
Plasma YKL-40 is high in patients with cancer and in individuals who later develop cancer. Whether YKL-40 is only a marker or indeed a cause of cancer is presently unknown. We tested the hypothesis that observationally and genetically, high plasma YKL-40 is associated with high risk of cancer. For this purpose, we performed cohort and Mendelian randomization studies in 96,099 individuals from the Danish general population. Plasma levels of YKL-40 were measured in 21,643 and CHI3L1 rs4950928 was genotyped in 94,568 individuals...
December 1, 2015: International Journal of Cancer. Journal International du Cancer
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