Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper...Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.展开更多
The retrospective study by Lew et al(2022)examined the rising hospitalization rates for chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC),revealing significant ethno-racial dispar...The retrospective study by Lew et al(2022)examined the rising hospitalization rates for chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC),revealing significant ethno-racial disparities and risk factors.Overweight black men aged 40-59 years and white men over 40 years with higher incomes showed an elevated risk of PDAC among CP patients.The study,which included 14.2 million admissions from 2016-2017,found that 2.6%of adult patients were diagnosed with CP,with white males being the majority.Multivariate regression analysis identified men,black individuals,those aged 40-59 years,and individuals with a body mass index(BMI)between 25 and 29.9 as having an increased risk for CP.Moreover,0.78%of CP patients also had PDAC,with older age and BMI being significant risk factors for developing PDAC in CP patients.The study also highlighted disparities in healthcare access and utilization among different socioeconomic and ethno-racial groups,which may impact the risk and outcomes of CP and PDAC.展开更多
Pancreatic cancer(PanCa)is a catastrophic disease,being third lethal in both the genders around the globe.The possible reasons are extreme disease invasiveness,highly fibrotic and desmoplastic stroma,dearth of confirm...Pancreatic cancer(PanCa)is a catastrophic disease,being third lethal in both the genders around the globe.The possible reasons are extreme disease invasiveness,highly fibrotic and desmoplastic stroma,dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics.This inimitable tumor microenvironment(TME)or desmoplasia with excessive extracellular matrix accumulation,create an extremely hypovascular,hypoxic and nutrient-deficient zone inside the tumor.To survive,grow and proliferate in such tough TME,pancreatic tumor and stromal cells transform their metabolism.Transformed glucose,glu-tamine,fat,nucleotide metabolism and inter-metabolite communication between tumor and TME in synergism,impart therapy resistance,and immunosuppression in PanCa.Thus,a finer knowledge of altered metabolism would uncover its metabolic susceptibilities.These unique metabolic targets may help to device novel diagnostic/prognostic markers and therapeutic strategies for better management of PanCa.In this review,we sum up reshaped metabolic pathways in PanCa to formulate detection and remedial strategies of this devastating disease.展开更多
A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;howeve...A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;however,they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting.Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures.The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians.Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages.In this review,we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.展开更多
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:Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality.In addition to having genetic causes,cancer can also be considered an epigenetic disease.DNA methylation ...Background:Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality.In addition to having genetic causes,cancer can also be considered an epigenetic disease.DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor.In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma(PDAC),the epigenetic changes play a significant role.Data sources:Relevant studies for this review were derived via an extensive literature search in Pub Med via using various keywords such as pancreatic ductal adenocarcinoma,precancerous lesions,methylation profile,epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest.The literature search was intensively done considering a time frame of 20 years(1998–2018).Result:In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions(pancreatic intra-epithelial neoplasia,intraductal papillary mucinous neoplasm,mucinous cystic neoplasm and chronic pancreatitis)and PDAC along with the potential biomarkers.We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC.A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC(pp ENK,APC,p14/5/16/17,h MLH1 and MGMT)are also documented.We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy.Epigenetic inactivation occurs by hypermethylation of Cp G islands in the promoter regions of tumor suppressor genes.We listed all hyper-and hypomethylation of Cp G islands of several genes in PDAC including its precancerous lesions.Conclusions:The concept of the review would help to understand their biological effects,and to determine whether they may be successfully combined with other epigenetic drugs.However,we need to continue our research to develop more specific DNA-demethylating agents,which are the targets for hypermethylated Cp G methylation sites.展开更多
基金Supported by Department of Biotechnology,Government of India,No.RLS/BT/Re-entry/05/2012.
文摘Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.
文摘The retrospective study by Lew et al(2022)examined the rising hospitalization rates for chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC),revealing significant ethno-racial disparities and risk factors.Overweight black men aged 40-59 years and white men over 40 years with higher incomes showed an elevated risk of PDAC among CP patients.The study,which included 14.2 million admissions from 2016-2017,found that 2.6%of adult patients were diagnosed with CP,with white males being the majority.Multivariate regression analysis identified men,black individuals,those aged 40-59 years,and individuals with a body mass index(BMI)between 25 and 29.9 as having an increased risk for CP.Moreover,0.78%of CP patients also had PDAC,with older age and BMI being significant risk factors for developing PDAC in CP patients.The study also highlighted disparities in healthcare access and utilization among different socioeconomic and ethno-racial groups,which may impact the risk and outcomes of CP and PDAC.
基金Supported by the Department of Biotechnology,Government of India,Ramalingaswami Re-entry Fellowship,No.RLS/BT/Reentry/05/2012and Department of Higher,Education,Science&Technology and Biotechnology,Government of West Bengal,India,No.BT/P/Budget/RD-37/2016.
文摘Pancreatic cancer(PanCa)is a catastrophic disease,being third lethal in both the genders around the globe.The possible reasons are extreme disease invasiveness,highly fibrotic and desmoplastic stroma,dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics.This inimitable tumor microenvironment(TME)or desmoplasia with excessive extracellular matrix accumulation,create an extremely hypovascular,hypoxic and nutrient-deficient zone inside the tumor.To survive,grow and proliferate in such tough TME,pancreatic tumor and stromal cells transform their metabolism.Transformed glucose,glu-tamine,fat,nucleotide metabolism and inter-metabolite communication between tumor and TME in synergism,impart therapy resistance,and immunosuppression in PanCa.Thus,a finer knowledge of altered metabolism would uncover its metabolic susceptibilities.These unique metabolic targets may help to device novel diagnostic/prognostic markers and therapeutic strategies for better management of PanCa.In this review,we sum up reshaped metabolic pathways in PanCa to formulate detection and remedial strategies of this devastating disease.
基金Supported by the Department of Biotechnology,Government of India Grant Sanction,Ramalingaswami Re-entry Fellowship,No.RLS/BT/Re-entry/05/2012.
文摘A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;however,they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting.Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures.The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians.Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages.In this review,we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.
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.
基金supported by grants from Department of Biotechnology,Government ofIndia(RLS/BT/Re-entry/05/2012)Department of Higher,Education,Science&Technology and Biotechnology,Government of West Bengal,India(BT/P/Budget/RD-37/2016)。
文摘Background:Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality.In addition to having genetic causes,cancer can also be considered an epigenetic disease.DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor.In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma(PDAC),the epigenetic changes play a significant role.Data sources:Relevant studies for this review were derived via an extensive literature search in Pub Med via using various keywords such as pancreatic ductal adenocarcinoma,precancerous lesions,methylation profile,epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest.The literature search was intensively done considering a time frame of 20 years(1998–2018).Result:In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions(pancreatic intra-epithelial neoplasia,intraductal papillary mucinous neoplasm,mucinous cystic neoplasm and chronic pancreatitis)and PDAC along with the potential biomarkers.We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC.A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC(pp ENK,APC,p14/5/16/17,h MLH1 and MGMT)are also documented.We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy.Epigenetic inactivation occurs by hypermethylation of Cp G islands in the promoter regions of tumor suppressor genes.We listed all hyper-and hypomethylation of Cp G islands of several genes in PDAC including its precancerous lesions.Conclusions:The concept of the review would help to understand their biological effects,and to determine whether they may be successfully combined with other epigenetic drugs.However,we need to continue our research to develop more specific DNA-demethylating agents,which are the targets for hypermethylated Cp G methylation sites.
