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| 1 | NKX6.3 protects against gastric mucosal atrophy by downregulatingβ-amyloid production显示文摘BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis.Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β(Aβ)production.AIM To determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production.METHODS We identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzymelinked immunosorbent assay, Western blot, immunoprecipitation, real-timequantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E(ApoE), and β-secretase 1(Bace1) in 55 gastric mucosae.RESULTS NKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3,-9, and poly ADP ribose polymerase were elevated in floating HFE-145^(shNKX6.3) cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145^(shNKX6.3) cells. In gastric mucosae with atrophy, expression of Aβpeptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβoligomeric forms and decreased cell viability in HFE-145^(shNKX6.3) cells. Additionally,NKX6.3 depletion increased expression of inflammatory cytokines and cyclooxygenase-2.CONCLUSION NKX6.3 inhibits gastric mucosal atrophy by regulating Aβ accumulation and inflammatory reaction in gastric epithelial cells. | Jung Hwan Yoon Yeon Soo Lee Olga Kim Hassan Ashktorab Duane T Smoot Suk Woo Nam Won Sang Park | 2019 | World Journal of Gastroenterology2019，25，3： | 6 |
| 2 | Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer显示文摘BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis. | Ramchandra Vigay Amnekar Shafqat Ali Khan Mudasir Rashid Bharat Khade Rahul Thorat Poonam Gera Shailesh V Shrikhande Duane T Smoot Hassan Ashktorab Sanjay Gupta | 2020 | World Journal of Gastroenterology2020，26，6： | 3 |
| 3 | Identification of novel mutations by exome sequencing in Afri- can American colorectal cancer patients 显示文摘 | ASHKTORAB H DAREM DEVANEY J | 2015 | Cancer2015，121，1： | 1 |
| 4 | Preva- lence of colorectal neoplasia among young African Americans and Hispanic Americans 显示文摘 | ASHKTORAB H PAYDAR M NAMIN H H | 2014 | Dig Dis Sci2014，59，2： | 1 |
| 5 | MicroRNA - 211 expression- promotes eolorectal cancer cell growthin vitro and in vivo by targe- ting tumor suppressor CHD5 显示文摘 | Cai C Ashktorab H Pang X | 2012 | PLoS One2012，7，29： | 1 |
| 6 | Clinicopathological features and microsatellite instability (MSI) in colorectal cancers from African Americans显示文摘 | Ashktorab H Smoot DT Farzanmehr H a al | 2005 | Int J Cancer2005，116，6： | 1 |
| 7 | 显示文摘 | Ashktorab H Allen CR Reeves B | 1997 | Gastroenterology1997，112，： | 1 |
| 8 | MicroRNA-211 expression promotes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5显示文摘 | Cai C Ashktorab H Pang X | 2012 | PLoS One2012，7，29： | 1 |
| 9 | Energy balance determinations close to the soil surface using a micro-Bowen system 显示文摘 | Ashktorab H Pruitt W O Paw U K T | 1989 | Agricultural and Forest Meteorology1989，46，： | 1 |
| 10 | Helicobacter pylori protection against reflux esophagitis显示文摘 | Ashktorab H Entezari O Nouraie M | 2012 | Dig Dis Sci2012，57，11： | 1 |
| 11 | MicroRNA-155 expression pro- motes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5 显示文摘 | Cai C Ashktorab H Pang X | 2012 | PLo S One2012，7，29： | 1 |
| 12 | Clinicopathological Features of Colon Polyps from African-Americans显示文摘 | Mehdi Nouraie Fatemeh Hosseinkhah Hassan Brim Behrouz Zamanifekri Duane T. Smoot Hassan Ashktorab | 2010 | Digestive Diseases and Sciences2010，，5： | 1 |
| 13 | Religion, faith and the empowerment process: Stories of iranian people with diabetes 显示文摘 | Abdoli S Ashktorab Thereh T | 2011 | Int J Nuts Pract2011，17，3： | 1 |
| 14 | High incidence of microsatellite instability in colorectal cancer from African Americans显示文摘 | Ashktorab H Smoot DT Carethers JM | 2003 | Clin Cancer Res2003，9，3： | 1 |
| 15 | Toward a comprehensive and systematic methylome signature in colorectal cancers显示文摘 | Ashktorab H Rahi H Wansley D | 2013 | Epigenetics2013，8，8： | 1 |
| 16 | Excitation function of K+ and π+ production in Au+Au reaction at 2-10 GeV显示文摘 | Ahle L Akiba 31 Ashktorab K (E866) | 2000 | Phys Lett2000，476，： | 1 |
| 17 | Esophageal carcinoma in Afri- can Americans : a five-decade experience 显示文摘 | Ashktorab H Nouri Z Nouraie M | 2011 | Dig Dis Sci2011，56，12： | 1 |
| 18 | The BRAHMS experiment at RHIC显示文摘 | ADAMCZYK M ANTVORSKOV L ASHKTORAB K | 2003 | Nuel Instr Meth: A2003，499，： | 1 |
| 19 | Outcome of Colonoscopy in Elderly African-American Patients显示文摘 | Duane T. Smoot Jason Collins Sharif Dunlap Amira Ali-Ibrahim Mehdi Nouraie Edward L. Lee Hassan Ashktorab | 2009 | Digestive Diseases and Sciences2009，，11： | 1 |
| 20 | High incidence of microsatellite instability in eoloreetal cancer from African Americans 显示文摘 | Ashktorab H Smoot DT Naab T | 2003 | Clin Cancer Rcs2003，9，3： | 1 |
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