BACKGROUND Tuberous sclerosis complex(TSC)is a rare inherited disease with non-cancerous tumor growths in the skin,brain,kidneys,heart,and lungs.The co-occurrence of neuroendocrine neoplasm(NEN)with TSC is even rarer....BACKGROUND Tuberous sclerosis complex(TSC)is a rare inherited disease with non-cancerous tumor growths in the skin,brain,kidneys,heart,and lungs.The co-occurrence of neuroendocrine neoplasm(NEN)with TSC is even rarer.There have been few reports on the relationship between TSC and neuroendocrine tumors(NETs),and fewer on the relationship between TSC and neuroendocrine carcinoma(NEC),a subtype of NEN.This is the first reported case of NEC occurring at the esophagogastric junction in a patient with TSC.CASE SUMMARY A 46-year-old woman visiting our hospital for the treatment of TSC was admitted to the emergency department with tarry stools and dizziness.Computed tomography scans revealed thickness of the gastric cardia,multiple metastatic lesions of the liver,and enlarged lymph nodes near the lesser curvature of the stomach.Esophagogastroduodenoscopy revealed a type 3 tumor located from the esophagogastric junction to the fundus,and the pathological diagnosis by biopsy was NEC.The patient was treated with seven courses of cisplatin+irinotecan,followed by eight courses of ramucirumab+nab-paclitaxel,one course of nivolumab,and two courses of S-1+oxaliplatin.Twenty-three months after the first treatment,the patient died because of disease progression and deterioration of the general condition.CONCLUSION This case of NEC occurring in a patient with TSC indicates a difference in the occurrence of NETs and NECs.展开更多
AIM:To investigate the suppressive activity of MUTYH variant proteins against mutations caused by oxidative lesion,8-hydroxyguanine(8OHG),in human cells.METHODS:p.R154H,p.M255V,p.L360P,and p.P377L MUTYH variants,which...AIM:To investigate the suppressive activity of MUTYH variant proteins against mutations caused by oxidative lesion,8-hydroxyguanine(8OHG),in human cells.METHODS:p.R154H,p.M255V,p.L360P,and p.P377L MUTYH variants,which were previously found in patients with colorectal polyposis and cancer,were selected for use in this study.Human H1299 cancer cell lines inducibly expressing wild-type(WT) MUTYH(type 2) or one of the 4 above-mentioned MUTYH variants were established using the piggyBac transposon vector system,enabling the genomic integration of the transposon sequence for MUTYH expression.MUTYH expression was examined after cumate induction using Western blotting analysis and immunofluorescence analysis.The intracellular localization of MUTYH variants tagged with FLAG was also immunofluorescently examined.Next,the mutation frequency in the supF of the shuttle plasmid pMY189 containing a single 8OHG residue at position 159 of the supF was compared between empty vector cells and cells expressing WT MUTYH or one of the 4 MUTYH variants using a supF forward mutation assay.RESULTS:The successful establishment of human cell lines inducibly expressing WT MUTYH or one of the 4 MUTYH variants was concluded based on the detection of MUTYH expression in these cell lines after treatment with cumate.All of the MUTYH variants and WT MUTYH were localized in the nucleus,and nuclear localization was also observed for FLAG-tagged MUTYH.The mutation frequency of supF was 2.2 × 10-2 in the 8OHG-containing pMY189 plasmid and 2.5 × 10-4 in WT pMY189 in empty vector cells,which was an 86-fold increase with the introduction of 8OHG.The mutation frequency(4.7 × 10-3) of supF in the 8OHG-containing pMY189 plasmid in cells overexpressing WT MUTYH was significantly lower than in the empty vector cells(P < 0.01).However,the mutation frequencies of the supF in the 8OHG-containing pMY189 plasmid in cells overexpressing the p.R154H,p.M255V,p.L360P,or p.P377L MUTYH variant were 1.84 × 10-2,1.55 × 10-2,1.91 × 10-2,and 1.96 × 10-2,respectively,meaning that no significant difference was observed in the mutation frequency between the empty vector cells and cells overexpressing MUTYH mutants.CONCLUSION:The suppressive activities of p.R154H,p.M255V,p.L360P,and p.P377L MUTYH variants against mutations caused by 8OHG are thought to be severely impaired in human cells.展开更多
Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpres...Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.展开更多
AIM:To identify genetic polymorphisms in the promoter region of the human base excision repair gene NEIL1 in gastric cancer patients.METHODS:The NEIL1 promoter region in DNA from 80 Japanese patients with gastric canc...AIM:To identify genetic polymorphisms in the promoter region of the human base excision repair gene NEIL1 in gastric cancer patients.METHODS:The NEIL1 promoter region in DNA from 80 Japanese patients with gastric cancer was searched for genetic polymorphisms by polymerase chain reaction-single-strand conformation polymorphism and subsequent sequencing analyses.RESULTS:Three novel genetic polymorphisms,i.e.c.-3769C>T,c.-3170T>G,and c.-2681TA[8],were identified in the NEIL1 promoter region at an allele frequency of 0.6%,9.4%,and 4.4%,respectively,in Japanese gastric cancer patients.CONCLUSION:Three NEIL1 promoter polymorphisms detected in this study may be of importance in gastric carcinogenesis.展开更多
文摘BACKGROUND Tuberous sclerosis complex(TSC)is a rare inherited disease with non-cancerous tumor growths in the skin,brain,kidneys,heart,and lungs.The co-occurrence of neuroendocrine neoplasm(NEN)with TSC is even rarer.There have been few reports on the relationship between TSC and neuroendocrine tumors(NETs),and fewer on the relationship between TSC and neuroendocrine carcinoma(NEC),a subtype of NEN.This is the first reported case of NEC occurring at the esophagogastric junction in a patient with TSC.CASE SUMMARY A 46-year-old woman visiting our hospital for the treatment of TSC was admitted to the emergency department with tarry stools and dizziness.Computed tomography scans revealed thickness of the gastric cardia,multiple metastatic lesions of the liver,and enlarged lymph nodes near the lesser curvature of the stomach.Esophagogastroduodenoscopy revealed a type 3 tumor located from the esophagogastric junction to the fundus,and the pathological diagnosis by biopsy was NEC.The patient was treated with seven courses of cisplatin+irinotecan,followed by eight courses of ramucirumab+nab-paclitaxel,one course of nivolumab,and two courses of S-1+oxaliplatin.Twenty-three months after the first treatment,the patient died because of disease progression and deterioration of the general condition.CONCLUSION This case of NEC occurring in a patient with TSC indicates a difference in the occurrence of NETs and NECs.
基金Supported by Grants from the Ministry of Health,Labour and Welfare(21-1)the Japan Society for the Promotion of Science (22590356 and 22790378)+3 种基金the Hamamatsu Foundation for Science and Technology Promotion,the Ministry of Education, Culture,Sports,Science and Technology(221S0001)the Takeda Science Foundationthe Aichi Cancer Research Foundationthe Smoking Research Foundation
文摘AIM:To investigate the suppressive activity of MUTYH variant proteins against mutations caused by oxidative lesion,8-hydroxyguanine(8OHG),in human cells.METHODS:p.R154H,p.M255V,p.L360P,and p.P377L MUTYH variants,which were previously found in patients with colorectal polyposis and cancer,were selected for use in this study.Human H1299 cancer cell lines inducibly expressing wild-type(WT) MUTYH(type 2) or one of the 4 above-mentioned MUTYH variants were established using the piggyBac transposon vector system,enabling the genomic integration of the transposon sequence for MUTYH expression.MUTYH expression was examined after cumate induction using Western blotting analysis and immunofluorescence analysis.The intracellular localization of MUTYH variants tagged with FLAG was also immunofluorescently examined.Next,the mutation frequency in the supF of the shuttle plasmid pMY189 containing a single 8OHG residue at position 159 of the supF was compared between empty vector cells and cells expressing WT MUTYH or one of the 4 MUTYH variants using a supF forward mutation assay.RESULTS:The successful establishment of human cell lines inducibly expressing WT MUTYH or one of the 4 MUTYH variants was concluded based on the detection of MUTYH expression in these cell lines after treatment with cumate.All of the MUTYH variants and WT MUTYH were localized in the nucleus,and nuclear localization was also observed for FLAG-tagged MUTYH.The mutation frequency of supF was 2.2 × 10-2 in the 8OHG-containing pMY189 plasmid and 2.5 × 10-4 in WT pMY189 in empty vector cells,which was an 86-fold increase with the introduction of 8OHG.The mutation frequency(4.7 × 10-3) of supF in the 8OHG-containing pMY189 plasmid in cells overexpressing WT MUTYH was significantly lower than in the empty vector cells(P < 0.01).However,the mutation frequencies of the supF in the 8OHG-containing pMY189 plasmid in cells overexpressing the p.R154H,p.M255V,p.L360P,or p.P377L MUTYH variant were 1.84 × 10-2,1.55 × 10-2,1.91 × 10-2,and 1.96 × 10-2,respectively,meaning that no significant difference was observed in the mutation frequency between the empty vector cells and cells overexpressing MUTYH mutants.CONCLUSION:The suppressive activities of p.R154H,p.M255V,p.L360P,and p.P377L MUTYH variants against mutations caused by 8OHG are thought to be severely impaired in human cells.
基金Supported by A Grant in Aid for Scientific Research (2001407, 22659072, 22590356, 22790378, 221S0001) from the Ministry of Education, Culture, Sports, Science and Technology of Japana Grant in Aid for the 3rd anti-Cancer from the Ministry of Health, Labour and Welfare (H22-017) and from the Smoking Research Foundation
文摘Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.
基金Supported by Grants-in-Aid from Ministry of Health, Labour and Welfare for the Comprehensive 10-Year Strategy for Cancer Control (19-19)Japan Society for the Promotion of Science for Scientific Research, No. 19790286+1 种基金Ministry of Education, Culture,Sports, Science and Technology for priority area, No. 20014007the 21st century COE program
文摘AIM:To identify genetic polymorphisms in the promoter region of the human base excision repair gene NEIL1 in gastric cancer patients.METHODS:The NEIL1 promoter region in DNA from 80 Japanese patients with gastric cancer was searched for genetic polymorphisms by polymerase chain reaction-single-strand conformation polymorphism and subsequent sequencing analyses.RESULTS:Three novel genetic polymorphisms,i.e.c.-3769C>T,c.-3170T>G,and c.-2681TA[8],were identified in the NEIL1 promoter region at an allele frequency of 0.6%,9.4%,and 4.4%,respectively,in Japanese gastric cancer patients.CONCLUSION:Three NEIL1 promoter polymorphisms detected in this study may be of importance in gastric carcinogenesis.
