Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulatio...Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target.Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails.Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients.Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies.Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance.Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions,and novel pharmacological strategies that target these components could potentially lead to breakthroughs.We aim to highlight the possibilities that exist and the potential therapeutic interventions.展开更多
BACKGROUND Smoking and chewing tobacco are associated with numerous oral mucosal lesions and conditions,often leading to cancer progression.AIM To investigate the prevalence of precancerous lesions and conditions amon...BACKGROUND Smoking and chewing tobacco are associated with numerous oral mucosal lesions and conditions,often leading to cancer progression.AIM To investigate the prevalence of precancerous lesions and conditions among the Indian population.METHODS Systematic search was conducted for population or community-based observational epidemiological studies in PubMed,EMBASE,Web of Science,IndMED,Google Scholar,reports of the WHO South-East Asia Region,MOHFW India reports,Science Citation Index,WHO Index Medicus of the South-East Asian Region,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Open Grey from the earliest available up to 31st January 2022.The effect size was calculated for the prevalence of precancerous lesions and conditions.RESULTS One hundred sixty-two estimates from 130 studies yielded 52 high,71 moderate,and seven low-quality studies from 823845.Point estimate based on crosssectional studies for leukoplakia was 4.3%(95%CI:4.0-4.6),oral submucous fibrosis was 2.7%(95%CI:2.5-3.0),palatal lesions in reverse smokers and nicotine palatine were 5.8%(95%CI:4.4-7.2),and Erythroplakia was 1.2%(95%CI:0.7-1.7),and lichen planus was 1.1%(95%CI:0.9-1.2).Amongst hospital-based studies,the pooled prevalence for Leukoplakia was 6.7%(95%CI:6.0-7.3),oral submucous fibrosis was 4.5%(95%CI:4.2-4.9),lichen planus was 7.5%(95%CI:5.3-9.6),and erythroplakia was 2.5%(95%CI:0.4-4.5),and palatal lesions in reverse smokers and nicotine palatini were 11.5%(95%CI:8.0-15.0).CONCLUSION Precancerous lesions and conditions are prevailing problems among the Indian population.It is mainly due to tobacco use,the smokeless form of tobacco.The meta-analysis indicates that hospital-based studies have a higher effect size of 6.7%than community-based studies.Patients who have already developed this condition may be advised to reduce their exposure to the risk factor to prevent the condition from progressing further.展开更多
AIM To investigate genotype variation among induced pluripotent stem cell(iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS Human iPSC lines wer...AIM To investigate genotype variation among induced pluripotent stem cell(iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS Human iPSC lines were clonally established by selecting independent single colonies expanded from heterogeneous primary cells of S-shaped colon cancer tissues by retroviral gene transfer(OCT3/4, SOX2, and KLF4). The ten iPSC lines, their starting cancer tissues, and the matched adjacent non-cancerous tissues were analyzed using nextgeneration sequencing and bioinformatics analysis using the human reference genome hg19. Non-synonymous single-nucleotide variants(SNVs)(missense, nonsense,and read-through) were identified within the target region of 612 genes related to cancer and the human kinome. All SNVs were annotated using dbS NP135, CCDS, RefSeq, GENCODE, and 1000 Genomes. The SNVs of the iPSC lines were compared with the genotypes of the cancerous and non-cancerous tissues. The putative genotypes were validated using allelic depth and genotype quality. For final confirmation, mutated genotypes were manually curated using the Integrative Genomics Viewer. RESULTS In eight of the ten iPSC lines, one or two non-synonymous SNVs in EIF2AK2, TTN, ULK4, TSSK1 B, FLT4, STK19, STK31, TRRAP, WNK1, PLK1 or PIK3R5 were identified as novel SNVs and were not identical to the genotypes found in the cancer and non-cancerous tissues. This result suggests that the SNVs were de novo or pre-existing mutations that originated from minor populations, such as multifocal pre-cancer(stem) cells or pre-metastatic cancer cells from multiple, different clonal evolutions, present within the heterogeneous cancer tissue. The genotypes of all ten iPSC lines were different from the mutated ERBB2 and MKNK2 genotypes of the cancer tissues and were identical to those of the noncancerous tissues and that found in the human reference genome hg19. Furthermore, two of the ten iPSC lines did not have any confirmed mutated genotypes, despite being derived from cancerous tissue. These results suggest that the traceability and preference of the starting single cells being derived from pre-cancer(stem) cells, stroma cells such as cancer-associated fibroblasts, and immune cells that co-existed in the tissues along with the mature cancer cells.CONCLUSION The genotypes of iPSC lines derived from heterogeneous cancer tissues can provide information on the type of starting cell that the iPSC line was generated from.展开更多
文摘Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target.Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails.Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients.Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies.Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance.Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions,and novel pharmacological strategies that target these components could potentially lead to breakthroughs.We aim to highlight the possibilities that exist and the potential therapeutic interventions.
文摘BACKGROUND Smoking and chewing tobacco are associated with numerous oral mucosal lesions and conditions,often leading to cancer progression.AIM To investigate the prevalence of precancerous lesions and conditions among the Indian population.METHODS Systematic search was conducted for population or community-based observational epidemiological studies in PubMed,EMBASE,Web of Science,IndMED,Google Scholar,reports of the WHO South-East Asia Region,MOHFW India reports,Science Citation Index,WHO Index Medicus of the South-East Asian Region,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Open Grey from the earliest available up to 31st January 2022.The effect size was calculated for the prevalence of precancerous lesions and conditions.RESULTS One hundred sixty-two estimates from 130 studies yielded 52 high,71 moderate,and seven low-quality studies from 823845.Point estimate based on crosssectional studies for leukoplakia was 4.3%(95%CI:4.0-4.6),oral submucous fibrosis was 2.7%(95%CI:2.5-3.0),palatal lesions in reverse smokers and nicotine palatine were 5.8%(95%CI:4.4-7.2),and Erythroplakia was 1.2%(95%CI:0.7-1.7),and lichen planus was 1.1%(95%CI:0.9-1.2).Amongst hospital-based studies,the pooled prevalence for Leukoplakia was 6.7%(95%CI:6.0-7.3),oral submucous fibrosis was 4.5%(95%CI:4.2-4.9),lichen planus was 7.5%(95%CI:5.3-9.6),and erythroplakia was 2.5%(95%CI:0.4-4.5),and palatal lesions in reverse smokers and nicotine palatini were 11.5%(95%CI:8.0-15.0).CONCLUSION Precancerous lesions and conditions are prevailing problems among the Indian population.It is mainly due to tobacco use,the smokeless form of tobacco.The meta-analysis indicates that hospital-based studies have a higher effect size of 6.7%than community-based studies.Patients who have already developed this condition may be advised to reduce their exposure to the risk factor to prevent the condition from progressing further.
文摘AIM To investigate genotype variation among induced pluripotent stem cell(iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS Human iPSC lines were clonally established by selecting independent single colonies expanded from heterogeneous primary cells of S-shaped colon cancer tissues by retroviral gene transfer(OCT3/4, SOX2, and KLF4). The ten iPSC lines, their starting cancer tissues, and the matched adjacent non-cancerous tissues were analyzed using nextgeneration sequencing and bioinformatics analysis using the human reference genome hg19. Non-synonymous single-nucleotide variants(SNVs)(missense, nonsense,and read-through) were identified within the target region of 612 genes related to cancer and the human kinome. All SNVs were annotated using dbS NP135, CCDS, RefSeq, GENCODE, and 1000 Genomes. The SNVs of the iPSC lines were compared with the genotypes of the cancerous and non-cancerous tissues. The putative genotypes were validated using allelic depth and genotype quality. For final confirmation, mutated genotypes were manually curated using the Integrative Genomics Viewer. RESULTS In eight of the ten iPSC lines, one or two non-synonymous SNVs in EIF2AK2, TTN, ULK4, TSSK1 B, FLT4, STK19, STK31, TRRAP, WNK1, PLK1 or PIK3R5 were identified as novel SNVs and were not identical to the genotypes found in the cancer and non-cancerous tissues. This result suggests that the SNVs were de novo or pre-existing mutations that originated from minor populations, such as multifocal pre-cancer(stem) cells or pre-metastatic cancer cells from multiple, different clonal evolutions, present within the heterogeneous cancer tissue. The genotypes of all ten iPSC lines were different from the mutated ERBB2 and MKNK2 genotypes of the cancer tissues and were identical to those of the noncancerous tissues and that found in the human reference genome hg19. Furthermore, two of the ten iPSC lines did not have any confirmed mutated genotypes, despite being derived from cancerous tissue. These results suggest that the traceability and preference of the starting single cells being derived from pre-cancer(stem) cells, stroma cells such as cancer-associated fibroblasts, and immune cells that co-existed in the tissues along with the mature cancer cells.CONCLUSION The genotypes of iPSC lines derived from heterogeneous cancer tissues can provide information on the type of starting cell that the iPSC line was generated from.
