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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 | Clinieopathological features and microsatellhe instability (MSI) in colorectal cancers from african americans显示文摘 | Hassan Ashktorab Duane T Smoot Haleh Farzanmehr | 2005 | Int J Cancer2005，116，6： | 1 |
| 4 | Race and colorectal cancer screening compliance among persons with a family history of cancer显示文摘AIM: To determine compliance to colorectal cancer(CRC) screening guidelines among persons with a family history of any type of cancer and investigate racial differences in screening compliance.METHODS: We used the 2007 Health Information National Trends Survey and identified 1094(27.4%)respondents(weighted population size = 21959672) without a family history of cancer and 3138(72.6%) respondents(weighted population size = 58201479) with a family history of cancer who were 50 years and older. We defined compliance with CRC screening as the use of fecal occult blood testing within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared compliance with CRC screening among those with and without a family member with a history of cancer. RESULTS: Overall, those with a family member with cancer were more likely to be compliant with CRC screening(64.9% vs 55.1%; OR = 1.45; 95%CI: 1.20-1.74). The absolute increase in screening rates associated with family history of cancer was 8.2% among whites. Hispanics had lowest screening rates among those without family history of cancer 41.9% but had highest absolute increase(14.7%) in CRC screening rate when they have a family member with cancer. Blacks had the lowest absolute increase in CRC screening(5.3%) when a family member has a known history of cancer. However, the noted increase in screening rates among blacks and Hispanics when they have a family member with cancer were not higher than whites without a family history of cancer:(54.5% vs 58.7%; OR = 1.16; 95%CI: 0.72-1.88) for blacks and(56.7% vs 58.7%; OR = 1.25; 95%CI: 0.72-2.18) for Hispanics.CONCLUSION: While adults with a family history of any cancer were more likely to be compliant with CRC screening guidelines irrespective of race/ethnicity, blacks and Hispanics with a family history of cancer were less likely to be compliant than whites without a family history. Increased burden from CRC among blacks may be related to poor uptake of screening among high-risk groups. | Adeyinka O Laiyemo Nicole Thompson Carla D Williams Kolapo A Idowu Kathy Bull-Henry Zaki A Sherif Edward L Lee Hassan Brim Hassan Ashktorab Elizabeth A Platz Duane T Smoot | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，18： | 0 |
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