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John carethers

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
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
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
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
M Bishr Omary, John M Carethers, Chung Owyang
No abstract text is available yet for this article.
June 2016: Gastroenterology
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
John M Carethers, Ajay Goel
No abstract text is available yet for this article.
June 2016: Gastroenterology
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
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
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
John M Carethers
No abstract text is available yet for this article.
June 2016: Digestive Diseases and Sciences
John M Carethers
No abstract text is available yet for this article.
June 2016: Digestive Diseases and Sciences
Minoru Koi, Melissa Garcia, Chan Choi, Hyeong-Rok Kim, Junichi Koike, Hiromichi Hemmi, Takeshi Nagasaka, Yoshinaga Okugawa, Yuji Toiyama, Takahito Kitajima, Hiroki Imaoka, Masato Kusunoki, Yin-Hsiu Chen, Bhramar Mukherjee, C Richard Boland, John M Carethers
BACKGROUND & AIMS: Molecular events that lead to recurrence and/or metastasis after curative treatment of patients with colorectal cancers (CRCs) are poorly understood. Patients with stage II or III primary CRC with elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability (E/L) are more likely to have disease recurrence after treatment. Hypoxia and/or inflammation not only promote metastasis, but also induce elevated microsatellite alterations at selected tetranucleotide repeats by causing deficiency of MSH3 in the cancer cell nucleus...
April 2016: Gastroenterology
John M Carethers
With advances in the understanding of the biology and genetics of colorectal cancer (CRC), diagnostic biomarkers that may predict the existence or future presence of cancer or a hereditary condition, and prognostic and treatment biomarkers that may direct the approach to therapy have been developed. Biomarkers can be ascertained and assayed from any tissue that may demonstrate the diagnostic or prognostic value, including from blood cells, epithelial cells via buccal swab, fresh or archival cancer tissue, as well as from cells shed into fecal material...
June 2015: Journal of Digestive Cancer Reports
John M Carethers, Jonathan Braun, Bruce E Sands
No abstract text is available yet for this article.
October 2015: Gastroenterology
John M Carethers, Elena M Stoffel
Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1)...
August 21, 2015: World Journal of Gastroenterology: WJG
Sonia S Kupfer, Rotonya M Carr, John M Carethers
No abstract text is available yet for this article.
November 2015: Gastroenterology
John M Carethers, Barbara H Jung
Sporadic colorectal cancer (CRC) is a somatic genetic disease in which pathogenesis is influenced by the local colonic environment and the patient's genetic background. Consolidating the knowledge of genetic and epigenetic events that occur with initiation, progression, and metastasis of sporadic CRC has identified some biomarkers that might be utilized to predict behavior and prognosis beyond staging, and inform treatment approaches. Modern next-generation sequencing of sporadic CRCs has confirmed prior identified genetic alterations and has classified new alterations...
October 2015: Gastroenterology
Yasushi Hamaya, Carla Guarinos, Stephanie S Tseng-Rogenski, Moriya Iwaizumi, Ritabrata Das, Rodrigo Jover, Antoni Castells, Xavier Llor, Montserrat Andreu, John M Carethers
Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone...
2015: PloS One
John M Carethers, Minoru Koi, Stephanie S Tseng-Rogenski
DNA mismatch repair (MMR) function is critical for correcting errors coincident with polymerase-driven DNA replication, and its proteins are frequent targets for inactivation (germline or somatic), generating a hypermutable tumor that drives cancer progression. The biomarker for defective DNA MMR is microsatellite instability-high (MSI-H), observed in ~15% of colorectal cancers, and defined by mono- and dinucleotide microsatellite frameshift mutations. MSI-H is highly correlated with loss of MMR protein expression, is commonly diploid, is often located in the right side of the colon, prognosticates good patient outcome, and predicts poor efficacy with 5-fluorouracil treatment...
March 31, 2015: Genes
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