Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years....Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.展开更多
AIM:To investigate cell type specific distribution ofβ-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.METHODS:β-actin is a housekeeping gene,frequently used as loa...AIM:To investigate cell type specific distribution ofβ-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.METHODS:β-actin is a housekeeping gene,frequently used as loading control,but,differentially expresses in cancer.In gastric cancer,an overall increased expression ofβ-actin has been reported using tissue disruptive techniques.At present,no histological data is available to indicate its cell type-specific expression and distribution pattern.In the present study,we analyzedβ-actin expression and distribution in paired normal and tumor tissue samples of gastric adenocarcinoma patients using immunohistochemistry(IHC),a tissue non-disruptive technique as well as tissue disruptive techniques like reverse transcriptase-polymerase chain reaction(RT-PCR)and western blotting.Correlation ofβ-actin level with clinicopathological parameters was done using univariate analysis.RESULTS:The results of this study showed significant overexpression,at both mRNA and protein level in tumor tissues as confirmed by RT-PCR(1.47±0.13 vs2.36±0.16;P<0.001)and western blotting(1.92±0.26 vs 2.88±0.32;P<0.01).IHC revealed thatβ-actin expression is majorly distributed between epithelial and inflammatory cells of the tissues.Inflammatory cells showed a significantly higher expression compared to epithelial cells in normal(2.46±0.13 vs 5.92±0.23,P<0.001),as well as,in tumor tissues(2.79±0.24 vs6.71±0.14,P<0.001).Further,comparison of immunostaining between normal and tumor tissues revealed that both epithelial and inflammatory cells overexpressβ-actin in tumor tissues,however,significant difference was observed only in inflammatory cells(5.92±0.23vs 6.71±0.14,P<0.01).Moreover,combined expression in epithelial and inflammatory cells also showed significant increase(4.19±0.15 vs 4.75±0.14,P<0.05)in tumor tissues.In addition,univariate analysis showed a positive correlation ofβ-actin level of inflammatory cells with tumor grade(P<0.05)while epithelial cells exhibited negative correlation(P>0.05).CONCLUSION:In gastric cancer,β-actin showed an overall higher expression predominantly contributed by inflammatory or tumor infiltrating immune cells of the tissue microenvironment and correlates with tumor grade.展开更多
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 f...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.展开更多
文摘Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.
基金Supported by TMH-IRG for project funding(account number-466),Advanced Center for Treatment Research and Education in Cancer,India for funding to Gupta lab
文摘AIM:To investigate cell type specific distribution ofβ-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.METHODS:β-actin is a housekeeping gene,frequently used as loading control,but,differentially expresses in cancer.In gastric cancer,an overall increased expression ofβ-actin has been reported using tissue disruptive techniques.At present,no histological data is available to indicate its cell type-specific expression and distribution pattern.In the present study,we analyzedβ-actin expression and distribution in paired normal and tumor tissue samples of gastric adenocarcinoma patients using immunohistochemistry(IHC),a tissue non-disruptive technique as well as tissue disruptive techniques like reverse transcriptase-polymerase chain reaction(RT-PCR)and western blotting.Correlation ofβ-actin level with clinicopathological parameters was done using univariate analysis.RESULTS:The results of this study showed significant overexpression,at both mRNA and protein level in tumor tissues as confirmed by RT-PCR(1.47±0.13 vs2.36±0.16;P<0.001)and western blotting(1.92±0.26 vs 2.88±0.32;P<0.01).IHC revealed thatβ-actin expression is majorly distributed between epithelial and inflammatory cells of the tissues.Inflammatory cells showed a significantly higher expression compared to epithelial cells in normal(2.46±0.13 vs 5.92±0.23,P<0.001),as well as,in tumor tissues(2.79±0.24 vs6.71±0.14,P<0.001).Further,comparison of immunostaining between normal and tumor tissues revealed that both epithelial and inflammatory cells overexpressβ-actin in tumor tissues,however,significant difference was observed only in inflammatory cells(5.92±0.23vs 6.71±0.14,P<0.01).Moreover,combined expression in epithelial and inflammatory cells also showed significant increase(4.19±0.15 vs 4.75±0.14,P<0.05)in tumor tissues.In addition,univariate analysis showed a positive correlation ofβ-actin level of inflammatory cells with tumor grade(P<0.05)while epithelial cells exhibited negative correlation(P>0.05).CONCLUSION:In gastric cancer,β-actin showed an overall higher expression predominantly contributed by inflammatory or tumor infiltrating immune cells of the tissue microenvironment and correlates with tumor grade.
基金Supported by TMH-IRG(account number-466/2012 and 164/2016)LTMT grant for project funding+1 种基金ACTREC-TMC for funding to Gupta labsupported by ACTREC fellowships
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.
