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Aspirin-induced long-term tumor remission in hepatocellular carcinoma with adenomatous polyposis coli stop-gain mutation:A case report

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World Journal of Clinical Cases 2021年第24期9卷 7189-7195页

作者： Qu Lin Ming-Jun Bai Hao-Fan Wang Xiang-Yuan Wu Ming-Sheng Huang Xing Li Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of Intervention and Guangdong Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina

BACKGROUND Targeted therapy based on pathway analysis of hepatitis B-related hepatocellular carcinoma(HCC)may be a promising remedy.CASE SUMMARY The present case involved an advanced hepatocellular carcinoma(HCC)patient who did not receive local regional therapy and was intolerant to sorafenib.Total RNA extracted from the patient’s tumor tissue was used to obtain the gene mutation profile.The c.3676A>T and c.4402A>T stop-gain mutations in adenomatous polyposis coli(APC)were the most prevalent(42.2%and 35.1%,respectively).MutationMapper analysis indicated that the functional domain of APC was lost in the two APC mutant genes.APC is a major suppressor of the Wnt signaling pathway.Thus,the Wnt pathway was exclusively activated due to APC dysfunction,as other elements of this pathway were not found to be mutated.Aspirin has been reported to suppress the Wnt pathway by inducingβ-catenin phosphorylation through the activation of glycogen synthase kinase 3 beta via cyclooxygenase-2 pathway inhibition.Therefore,aspirin was administered to the patient,which achieved four years of disease control.CONCLUSION Exclusive mutations of APC of all the Wnt pathway elements could be a therapeutic target in HCC,with aspirin as an effective treatment option.

关键词： Hepatocellular carcinoma Mutation Wnt pathway Aspirin adenomatous polyposis coli Case report

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β-catenin function affected by mutated adenomatous polyposis coli

β-catenin function affected by mutated adenomatous polyposi...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青...

作者： Lili Wang Chuanxin Wang Department of Clinical Laboratory Qilu HospitalShandong University The Second Hospital Shandong University

Objective: To study the role of mutated adenomatous polyposis coli(APC) on the regulation of β-catenin cellular transport kinetics in colorectal cancer. Methods: SW480, SW480 APC(cells expressing full length APC), and APC-depleted cells(APC-siRNA) were analyzed in this study. We transit transfected GFP, YFP-β-catenin plasmid into cells and also treated with LMB for 4 h and 8 h. The cellular transport of β-catenin were analyzed using fluorescence recovery after photobleaching(FRAP). Results: Compared with SW480 cells, the kinetics of β-catenin in SW480 APC cells in chronic recovery phase decreased, and the half-life time varied from 1 min to 5 min. We found that the expression of β-catenin was significantly higher than that of APC knockout cells, and the expression of β-catenin was significantly higher than that of APC knockout cells after 4 hours of LMB treatmen. Moreever, it did showed an effect on import of β-catenin with longer treatments(8 hrs). Conclusion: APC plays an important role in β-catenin cellular transportas a nuclear shuttle protein, which might have an effects on he nuclear function of β-catenin in tumor cells.

关键词： adenomatous polyposis coli β-catenin colorectal cancer

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Cumulative incidence and risk factors for pouch adenomas associated with familial adenomatous polyposis following restorative proctocolectomy

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World Journal of Gastroenterology 2022年第30期28卷 4152-4162页

作者： Hyo Seon Ryu Chang Sik Yu Young Il Kim Jong Lyul Lee Chan Wook Kim Yong Sik Yoon In Ja Park Seok-Byung Lim Jin Cheon Kim Division of Colon and Rectal Surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND The emergence of restorative total proctocolectomy has significantly reduced the lifetime colorectal cancer risk associated with familial adenomatous polyposis(FAP).However,adenomas may develop in the ileal pouch over time and may even progress to carcinoma.We evaluated the cumulative incidence,time to development,and risk factors associated with ileal pouch adenoma.AIM To evaluate the cumulative incidence,time to development,and risk factors associated with pouch adenoma.METHODS In this retrospective,observational study conducted at a tertiary center,95 patients with FAP who underwent restorative proctocolectomy at our center between 1989 and 2018 were consecutively included.The mean follow-up period was 88 mo.RESULTS Pouch adenomas were found in 24(25.3%)patients,with a median time of 52 mo to their first formation.Tubular adenomas were detected in most patients(95.9%).There were no high-grade dysplasia or malignancies.Of the 24 patients with pouch adenomas,13 had all detected adenomas removed.Among the 13 patients who underwent complete adenoma removal,four(38.5%)developed recurrence.Among 11(45.8%)patients with numerous polyps within the pouch,seven(63.6%)exhibited progression of pouch adenoma.The cumulative risks of pouch adenoma development at 5,10,and 15 years after pouch surgery were 15.2%,29.6%,and 44.1%,respectively.Severe colorectal polyposis(with more than 1000 polyps)was a significant risk factor for pouch adenoma development(hazard ratio,2.49;95% confidence interval:1.04-5.96;P=0.041).CONCLUSION Pouch adenomas occur at a fairly high rate in association with FAP after restorative proctocolectomy,and a high colorectal polyp count is associated with pouch adenoma development.

关键词： adenomatous polyposis coli Familial adenomatous polyposis Adenoma Intestinal polyps Proctocolectomy,restorative Ileal pouch anal anastomosis

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Attenuated adenomatous polyposis of the large bowel: Present and future

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World Journal of Gastroenterology 2017年第23期23卷 4135-4139页

作者： luca roncucci monica pedroni francesco mariani Department of Diagnostic and Clinical Medicine and Public Health University of Modena and Reggio Emilia

Attenuated adenomatous polyposis(AAP) is a poorly understood syndrome, that can be defined as the presence of 10-99 synchronous adenomas in the large bowel, and it is considered a phenotypic variant of familial adenomatous polyposis(FAP). This definition has the advantage of simplicity, but it may include sporadic multiple adenomas of the large bowel at an extreme, or FAP cases on the other side. AAP shows a milder phenotype than FAP, with an older age of onset of adenomas and cancer, and less frequent extracolonic manifestations. AAP may be diagnosed as a single case in a family or, less frequently, it may be present in other family members, and it shows distinct pattern of inheritance. In less than 50% of cases, it may be caused by adenomatous polyposis coli(APC) or MUTYH mutations, referred to as APC-associated polyposis, inherited as an autosomal dominant trait, or MUTYH-associated polyposis, which shows an autosomal recessive mechanism of inheritance, respectively. Surveillance should rely on colonoscopy at regular intervals, with removal of adenomas and careful histological examination. When removal of polyps is not possible or advanced lesions are observed, the surgical approach is mandatory, being subtotal colectomy with ileo-rectal anastomosis the treatment of choice. Studies on this syndrome are lacking, and controversies are still present on many issues, thus, other clinical and genetic studies are requested.

关键词：稀释 adenomatous polyposis 基因测试监视稀释家庭 adenomatous polyposis adenomatous polyposis coli MUTYH

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A Drosophila model of intestinal tumorigenesis

A Drosophila model of intestinal tumorigenesis

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第二届全国发育生物学大会

作者： Rongwen Xi National Institute of Biological Sciences

The Drosophila midgut has emerged as an attractive system to study intestinal homeostasis and intestinal physiology and function as the midgut shows great similarities to the mammalian intestine in both structural components and regulatory mechanisms.Similar to mammals,Wnt and EGFR signaling pathways have pivotal roles in maintaining proliferative activity of Drosophila midgut stem cells,and dysregulation of those pathways lead to epithelial hyperplasia.We have used this system to study the initiation and progression of intestinal tumors caused by the loss of adenomatous polyposis coli(APC),whose mutation in humans is responsible for familial adenomatous polyposis(FAP),a dominantly inherited disease characterized by early onset of intestinal polyps that eventually develop into carcinoma if left untreated.We find that loss of APC alone is able to initiate intestinal hyperplasia,but the mutant cells display no sign of invasion to other tissues.However,Ras activation in combination is able to produce large,invasive-like tumors.Our results indicate that both parallel and cooperative mechanisms of Wnt and Ras signaling are responsible for the initiation and progression of intestinal tumorigenesis after APC loss.Using this system,we have performed an RNAi genetic screen for suppressors of the tumor phenotype,aiming to identify novel targets that could be used for the prevention and treatment of FAP and colorectal cancers.

关键词： Wnt adenomatous polyposis coli Ras tumorigenesis

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TBL inhibits the proliferation of colon cancer cells through downregulating the expression of miR-135a&b

TBL inhibits the proliferation of colon cancer cells through...

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第六届泛环渤海生物化学与分子生物学会学术交流会

作者： Peiyu Guo Xiaodong Cui Zhuanhua Wang Key Laboratory of Chemical Biology and Molecular Engineering Ministry of Education Institute of BiotechnologyShanxi University

Using ion exchange and molecular exclusion chromatography,we firstly purified the TBL(tatary buckwheat lectin) from tatary buckwheat seeds.Previous works have demonstrated that TBL can down-regulate the expression of some oncomiRs including miR-135 a&b and inhibit the proliferation of colorectal cancer cells HCT116.Accordingly,we speculate that TBL can suppress the proliferation of HCT116 with oncomiRs regulation.By searching TargetScan Release 6.2 and TargetMiner,we find the APC(adenomatous polyposis coli) as a potential miR-135 a&b target gene.Afterwards we seek out three variants of APC from NCBI Nucleotide and their 3’UTRs are completely conserved.In this study,we cloned 3’UTR of APC with potential miR-135 a&b binding site into dual luciferase reporter in the first place.When treated with TBL,the luciferase activity of experiment group was higher than the control group.And the anti-sense oligonucleotides of miR-135 a&b had the same effect with TBL.Western Blot made clear that,when treated with TBL,APC and p-β-catenin was upregulated,total β-catenin was downregulated in dose-dependent manner,GSK-3β was unaffected.Collectively,TBL can negatively regulate Wnt signal pathway of HCT116.This indicated that TBL can modulate the expression of miR-135 a&b and then affect the Wnt signal pathway and inhibit the proliferation of colon cancer cells.

关键词： tatary buckwheat lectin miR-135a＆b adenomatous polyposis coli HCT116 Wnt

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