BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)...BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.展开更多
BACKGROUND In recent years,targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer(NSCLC).However,the clinical evidence for successful off-label use o...BACKGROUND In recent years,targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer(NSCLC).However,the clinical evidence for successful off-label use of targeted drugs for patients with NSCLC following progression on multiple lines of treatment is still lacking.CASE SUMMARY We describe a 62-year-old male patient with a right lung adenocarcinoma who harbored an EGFR exon 19 deletion mutation.He received gefitinib combined with six cycles of vinorelbine,cisplatin,and recombinant human endostatin as the first-line therapy.Then gefitinib was administered in combination with recombinant human endostatin as maintenance therapy,resulting in a progression-free survival(PFS)of 14 mo.Chemoradiotherapy was added following progression(enlarged brain metastases)on maintenance treatment.Unfortunately,the brain lesions were highly refractory and progressed again after 15 mo,at which time next-generation sequencing(NGS)of 1021 cancer-related genes was performed using peripheral blood to identify potential actionable mutations.NGS revealed that the patient harbored a BRCA2 germline mutation,the EGFR exon 19 deletion mutation disappeared,and no additional targetable genetic variant was detected.Therefore,the patient received olaparib combined with gefitinib and recombinant human endostatin,with a rapid and long-lasting clinical response(PFS=13.5 mo).CONCLUSION This is a rare case of lung adenocarcinoma in a patient with a BRCA2 germline mutation who had long-term benefit from olaparib combination treatment,suggesting that NGS-based genetic testing may render the possibility of long-term survival in NSCLC patients after disease progression.展开更多
文摘BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.
文摘BACKGROUND In recent years,targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer(NSCLC).However,the clinical evidence for successful off-label use of targeted drugs for patients with NSCLC following progression on multiple lines of treatment is still lacking.CASE SUMMARY We describe a 62-year-old male patient with a right lung adenocarcinoma who harbored an EGFR exon 19 deletion mutation.He received gefitinib combined with six cycles of vinorelbine,cisplatin,and recombinant human endostatin as the first-line therapy.Then gefitinib was administered in combination with recombinant human endostatin as maintenance therapy,resulting in a progression-free survival(PFS)of 14 mo.Chemoradiotherapy was added following progression(enlarged brain metastases)on maintenance treatment.Unfortunately,the brain lesions were highly refractory and progressed again after 15 mo,at which time next-generation sequencing(NGS)of 1021 cancer-related genes was performed using peripheral blood to identify potential actionable mutations.NGS revealed that the patient harbored a BRCA2 germline mutation,the EGFR exon 19 deletion mutation disappeared,and no additional targetable genetic variant was detected.Therefore,the patient received olaparib combined with gefitinib and recombinant human endostatin,with a rapid and long-lasting clinical response(PFS=13.5 mo).CONCLUSION This is a rare case of lung adenocarcinoma in a patient with a BRCA2 germline mutation who had long-term benefit from olaparib combination treatment,suggesting that NGS-based genetic testing may render the possibility of long-term survival in NSCLC patients after disease progression.
