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https://www.readbyqxmd.com/read/29545913/-mbd4-frameshift-mutation-caused-by-dna-mismatch-repair-deficiency-enhances-cytotoxicity-by-trifluridine-an-active-antitumor-agent-of-tas-102-in-colorectal-cancer-cells
#1
Satoshi Suzuki, Moriya Iwaizumi, Hidetaka Yamada, Tomohiro Sugiyama, Yasushi Hamaya, Takahisa Furuta, Shigeru Kanaoka, Haruhiko Sugimura, Hiroaki Miyajima, Satoshi Osawa, John M Carethers, Ken Sugimoto
Backgrounds: Trifluridine is an active antitumor component of TAS-102 that resembles 5-fluorouracil. Although patients with advanced colorectal cancer (CRC) exhibiting a mismatch repair (MMR) deficiency reportedly do not benefit from 5-fluorouracil-based chemotherapy and we previously reported that truncated methyl-CpG binding domain protein 4 (MBD4) enhances 5-fluorouracil cytotoxicity in MMR-deficient CRC cells, little is known regarding the effect of MMR deficiency on trifluridine cytotoxicity in CRC...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29375743/inflammation-associated-microsatellite-alterations-mechanisms-and-significance-in-the-prognosis-of-patients-with-colorectal-cancer
#2
REVIEW
Minoru Koi, Stephanie S Tseng-Rogenski, John M Carethers
Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair (MMR). About 15% of sporadic colorectal cancers (CRCs) manifest hypermethylation of the DNA MMR gene MLH1 , resulting in mono- and di-nucleotide frameshifts to classify it as microsatellite instability-high (MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic non-MSI-H CRCs demonstrate frameshifts at di- and tetra-nucleotide microsatellites to classify it as MSI-low/elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement...
January 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28951460/calcium-promotes-human-gastric-cancer-via-a-novel-coupling-of-calcium-sensing-receptor-and-trpv4-channel
#3
Rui Xie, Jingyu Xu, Yufeng Xiao, Jilin Wu, Hanxing Wan, Bo Tang, Jingjing Liu, Yahan Fan, Suming Wang, Yuyun Wu, Tobias Xiao Dong, Michael X Zhu, John M Carethers, Hui Dong, Shiming Yang
Although dietary calcium intake has long been recommended for disease prevention, the influence of calcium in development of cancer in the upper gastrointestinal tract has not been explored. Here, we assess the roles of calcium and calcium-sensing receptor (CaSR) in gastric cancer development. CaSR expression was enhanced in gastric cancer specimens, which positively correlated with serum calcium concentrations, tumor progression, poor survival, and male gender in gastric cancer patients. CaSR and transient receptor potential cation channel subfamily V member 4 (TRPV4) were colocalized in gastric cancer cells, and CaSR activation evoked TRPV4-mediated Ca2+ entry...
December 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28829193/the-colorectal-cancer-immune-microenvironment-and-approach-to-immunotherapies
#4
Minoru Koi, John M Carethers
No abstract text is available yet for this article.
August 2017: Future Oncology
https://www.readbyqxmd.com/read/28807841/racial-disparity-in-gastrointestinal-cancer-risk
#5
REVIEW
Hassan Ashktorab, Sonia S Kupfer, Hassan Brim, John M Carethers
Cancer from the gastrointestinal tract and its associated excretory organs will occur in more than 300,000 Americans in 2017, with colorectal cancer responsible for >40% of that burden; there will be more than 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to the incidence and mortality of these cancers exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in non-Hispanic whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among blacks...
October 2017: Gastroenterology
https://www.readbyqxmd.com/read/28739629/charting-the-future-of-cancer-health-disparities-research-a-position-statement-from-the-american-association-for-cancer-research-the-american-cancer-society-the-american-society-of-clinical-oncology-and-the-national-cancer-institute
#6
Blase N Polite, Lucile L Adams-Campbell, Otis W Brawley, Nina Bickell, John M Carethers, Christopher R Flowers, Margaret Foti, Scarlett Lin Gomez, Jennifer J Griggs, Christopher S Lathan, Christopher I Li, J Leonard Lichtenfeld, Worta McCaskill-Stevens, Electra D Paskett
No abstract text is available yet for this article.
July 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28738442/charting-the-future-of-cancer-health-disparities-research-a-position-statement-from-the-american-association-for-cancer-research-the-american-cancer-society-the-american-society-of-clinical-oncology-and-the-national-cancer-institute
#7
Blase N Polite, Lucile L Adams-Campbell, Otis W Brawley, Nina Bickell, John M Carethers, Christopher R Flowers, Margaret Foti, Scarlett Lin Gomez, Jennifer J Griggs, Christopher S Lathan, Christopher I Li, J Leonard Lichtenfeld, Worta McCaskill-Stevens, Electra D Paskett
No abstract text is available yet for this article.
September 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28737975/charting-the-future-of-cancer-health-disparities-research-a-position-statement-from-the-american-association-for-cancer-research-the-american-cancer-society-the-american-society-of-clinical-oncology-and-the-national-cancer-institute
#8
Blase N Polite, Lucile L Adams-Campbell, Otis W Brawley, Nina Bickell, John M Carethers, Christopher R Flowers, Margaret Foti, Scarlett Lin Gomez, Jennifer J Griggs, Christopher S Lathan, Christopher I Li, J Leonard Lichtenfeld, Worta McCaskill-Stevens, Electra D Paskett
No abstract text is available yet for this article.
September 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28550303/anti-proliferative-effects-of-nucleotides-on-gastric-cancer-via-a-novel-p2y6-soce-ca-2-%C3%AE-catenin-pathway
#9
Hanxing Wan, Rui Xie, Jiangyu Xu, Jialin He, Bo Tang, Qingqing Liu, Sumin Wang, Yanjun Guo, Xin Yang, Tobias Xiao Dong, John M Carethers, Shiming Yang, Hui Dong
Although purinegic signaling is important in regulating gastric physiological functions, it is currently unknown for its role in gastric cancer (GC). We demonstrate for the first time that the expression of P2Y6 receptors was markedly down-regulated in human GC cells and primary GC tissues compared to normal tissues, while the expression of P2Y2 and P2Y4 receptors was up-regulated in GC cells. Moreover, the expression levels of P2Y6 receptors in GC tissues were correlated to tumor size, differentiation, metastasis to lymph nodes, and the survival rate of the patients with GC...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28367107/microsatellite-instability-pathway-and-emast-in-colorectal-cancer
#10
John M Carethers
Microsatellite instability (MSI) refers to the biochemical detection of frameshifted microsatellite sequences from genomic DNA. Genesis of MSI is due to defective DNA mismatch repair (MMR) that fails to correct post DNA replicative slippage mistakes at microsatellites. Most of the estimated 100,000 genomic microsatellites are non-coding; however, ~150-300 microsatellites are coding such that, when frameshifted during the pathogenesis of an MSI tumor, can generate immunogenic neopeptide antigens that limit the growth of tumor and prolong patient survival...
February 2017: Current Colorectal Cancer Reports
https://www.readbyqxmd.com/read/28146413/international-exchange-and-american-medicine
#11
Katrina Armstrong, Mark E Anderson, John M Carethers, Joseph Loscalzo, Michael S Parmacek, Robert M Wachter, Mark L Zeidel
On January 27, 2017, President Donald Trump issued an executive order suspending "entry into the United States, as immigrants and nonimmigrants" of aliens from Iraq, Iran, Libya, Somalia, Sudan, Syria, and Yemen for 90 days, suspending the U.S. Refugee Admissions Program for 120 days, and..
May 11, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/27310868/decreased-anti-tumor-cytotoxic-immunity-among-microsatellite-stable-colon-cancers-from-african-americans
#12
Ranor C B Basa, Vince Davies, Xiaoxiao Li, Bhavya Murali, Jinel Shah, Bing Yang, Shi Li, Mohammad W Khan, Mengxi Tian, Ruth Tejada, Avan Hassan, Allen Washington, Bhramar Mukherjee, John M Carethers, Kathleen L McGuire
Colorectal cancer is a leading cause of cancer related deaths in the U.S., with African-Americans having higher incidence and mortality rates than Caucasian-Americans. Recent studies have demonstrated that anti-tumor cytotoxic T lymphocytes provide protection to patients with colon cancer while patients deficient in these responses have significantly worse prognosis. To determine if differences in cytotoxic immunity might play a role in racial disparities in colorectal cancer 258 microsatellite-stable colon tumors were examined for infiltrating immune biomarkers via immunohistochemistry...
2016: PloS One
https://www.readbyqxmd.com/read/27302536/gastroenterology-2011-2016-looking-back-and-forward
#13
EDITORIAL
M Bishr Omary, John M Carethers, Chung Owyang
No abstract text is available yet for this article.
June 2016: Gastroenterology
https://www.readbyqxmd.com/read/27166395/cancer-stem-like-properties-in-colorectal-cancer-cells-with-low-proteasome-activity
#14
Koji Munakata, Mamoru Uemura, Shinji Tanaka, Kenji Kawai, Tomohiro Kitahara, Masaaki Miyo, Yoshihiro Kano, Shinpei Nishikawa, Takahito Fukusumi, Yusuke Takahashi, Taishi Hata, Junichi Nishimura, Ichiro Takemasa, Tsunekazu Mizushima, Masakazu Ikenaga, Takeshi Kato, Kohei Murata, John M Carethers, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
PURPOSE: One of the main reasons for cancer treatment resistance is the existence of cancer stem-like cells (CSCs). Here, we elucidated the relationship between low proteasome activity cells (LPACs) and CSCs. EXPERIMENTAL DESIGN: The human colorectal cancer cell lines HCT116, SW480, DLD1, and KM12SM were engineered to stably express a green fluorescent molecule fused to the degron of ornithine decarboxylase, resulting in an accumulation of the fluorescence in LPACs...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27138978/presentation-of-the-julius-m-friedenwald-medal-to-c-richard-boland-md-agaf
#15
John M Carethers, Ajay Goel
No abstract text is available yet for this article.
June 2016: Gastroenterology
https://www.readbyqxmd.com/read/27120810/a-meta-analysis-of-msi-frequency-and-race-in-colorectal-cancer
#16
Hassan Ashktorab, Sadhna Ahuja, Lakshmi Kannan, Xavier Llor, Nathan A Ellis, Rosa M Xicola, Adeyinka O Laiyemo, John M Carethers, Hassan Brim, Mehdi Nouraie
PURPOSE: African Americans (AA) are at a higher risk of colorectal cancer (CRC) and some studies report a higher frequency of microsatellite instability (MSI) in this population while others report lower frequency compared to Caucasians. AIM: To determine and evaluate the association of race and clinical factors with MSI frequency through meta- analysis. METHODS: Twenty-two studies out of 15,105 (1997-2015) were evaluated after a search in different literature databases, using keywords "colorectal cancer, microsatellite instability, African Americans, Caucasians and Hispanics"...
April 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27115207/production-of-truncated-mbd4-protein-by-frameshift-mutation-in-dna-mismatch-repair-deficient-cells-enhances-5-fluorouracil-sensitivity-that-is-independent-of-hmlh1-status
#17
Satoshi Suzuki, Moriya Iwaizumi, Stephanie Tseng-Rogenski, Yasushi Hamaya, Hiroaki Miyajima, Shigeru Kanaoka, Ken Sugimoto, John M Carethers
Methyl-CpG binding domain protein 4 (MBD4) is a DNA glycosylase that can remove 5-fluorodeoxyuracil from DNA as well as repair T:G or U:G mismatches. MBD4 is a target for frameshift mutation with DNA mismatch repair (MMR) deficiency, creating a truncated MBD4 protein (TruMBD4) that lacks its glycosylase domain. Here we show that TruMBD4 plays an important role for enhancing 5-fluorouracil (5FU) sensitivity in MMR-deficient colorectal cancer cells. We found biochemically that TruMBD4 binds to 5FU incorporated into DNA with higher affinity than MBD4...
July 2, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27108064/calcium-sensing-receptor-suppresses-human-pancreatic-tumorigenesis-through-a-novel-ncx1-ca-2-%C3%AE-catenin-signaling-pathway
#18
Bo Tang, Jimmy Y C Chow, Tobias Xiao Dong, Shi-Ming Yang, De-Sheng Lu, John M Carethers, Hui Dong
The calcium sensing receptor (CaSR) is functionally expressed in normal human pancreases, but its pathological role in pancreatic tumorigenesis is currently unknown. We sought to investigate the role of CaSR in pancreatic cancer (PC) and the underlying molecular mechanisms. We revealed that the expression of CaSR was consistently downregulated in the primary cancer tissues from PC patients, which was correlated with tumor size, differentiation and poor survival of the patients. CaSR activation markedly suppressed pancreatic tumorigenesis in vitro and in vivo likely through the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger 1 (NCX1) to induce Ca(2+) entry into PC cells...
July 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/26856718/facilitating-minority-medical-education-research-and-faculty
#19
EDITORIAL
John M Carethers
No abstract text is available yet for this article.
June 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/26846119/grg-profiles-john-m-carethers
#20
EDITORIAL
John M Carethers
No abstract text is available yet for this article.
June 2016: Digestive Diseases and Sciences
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