Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK...Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.展开更多
Objective：Research has demonstrated that microRNA（miR）-106a is related to cisplatin resistance.We investigated the expression of miR-106a in the serum of patients with non-small cell lung cancer（NSCLC）and their s...Objective：Research has demonstrated that microRNA（miR）-106a is related to cisplatin resistance.We investigated the expression of miR-106a in the serum of patients with non-small cell lung cancer（NSCLC）and their sensitivity to chemotherapy by cisplatin combined with gemcitabine.Methods：Eighty-five NSCLC patients,who completed four cycles of gemcitabine and cisplatin chemotherapy,volunteered for this study and their serum samples were collected.Serum samples from 60 healthy subjects were used as controls.Real-time quantitative polymerase chain reaction（real-time q PCR）was used to quantify the level of miR-106a in the serum.Demographic and survival data of these patients were collected for the analysis.Results：The expression of miR-106a in the serum of NSCLC patients was significantly higher than that of healthy subjects（P＆lt;0.001）.The expression of miR-106a was not correlated with patients＇gender,age,tumor size,lymphatic metastasis,and pathological types;but was correlated with patients＇tumor staging（P=0.003）.After chemotherapy,serum miR-106a expression decreased in patients.The decrease in miR-106a expression in the chemotherapy-sensitive group was much higher than that in the chemotherapy-resistant group.Survival analysis shows that NSCLC patients with high expression of miR-106a have a poorer prognosis.The overall survival of NSCLC patients in the chemotherapy-sensitive group was significantly higher than that in the chemotherapy-resistant group.Conclusions：High expression of miR-106a may be involved in the development of NSCLC.Mi R-106a has significance in the prognosis of NSCLC.The level of miR-106a in the serum can be a useful parameter in screening for drug resistance during cisplatin-based chemotherapy.展开更多
Objective: Emerging evidence indicates that long non-coding RNAs(lnc RNAs) are critical in carcinogenesis and progression of ovarian cancer. This study aimed to explore the functions and molecular mechanisms of plasma...Objective: Emerging evidence indicates that long non-coding RNAs(lnc RNAs) are critical in carcinogenesis and progression of ovarian cancer. This study aimed to explore the functions and molecular mechanisms of plasmacytoma variant translocation I(PVT1) in ovarian cancer Methods: PVT1 and miR-214 were detected by qRT-PCR assays in ovarian cancer tissues and cells. The cell proliferation,migration, and invasion abilities were detected by cell functional experiments, respectively. Western blot assay was performed to detect epithelial-mesenchymal transition(EMT) markers. MiR-214 expression regulated by PVT1 was studied by RNA immunoprecipitation(RIP) and chromatin immunoprecipitation(Ch IP) assays.Results: The expression of PVT1 was up-regulated in ovarian cancer tissues and cell lines. Elevated PVT1 expression was associated with advanced stage and indicated poor prognosis for ovarian cancer patients. The knockdown of PVT1 impaired SKOV3 cell proliferation, migration, and invasion in vitro. The promotion of ovarian cancer progression by PVT1 involved in regulation of the epithelial-mesenchymal transition process and PVT1 interaction with EZH2 represses miR-214 expression in ovarian cancer cells.Conclusions: PVT1 plays an important role in ovarian cancer tumorigenesis, which might be as a novel diagnostic marker and therapeutic target for ovarian cancer.展开更多
文摘Crizotinib,a small molecular tyrosine kinase inhibitor,manifests dramatic responses in patients with non-small cell lung cancer with echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)rearrangements.ALK gene point mutation is the primary mechanism of acquired crizotinib resistance;however,the intrinsic mechanism is not fully understood.Here,we report a patient with a low mutant allele fraction(MAF)of EML4-ALK rearrangement,who experienced primary resistance to crizotinib treatment.The patient was a 66-year-old Chinese man,who had a history of metastatic lung cancer and was treated with first-and third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs).After 14 months of osimertinib treatment,his disease progressed,and next-generation sequencing was performed from a liquid biopsy of the patient’s blood.An EML4-ALK rearrangement was found and crizotinib was administered.The patient’s lung lesions continued to progress after one month of crizotinib treatment,and pemetrexed-bevacizumab was initiated.After two cycles of chemotherapy,the metastatic cancers shrunk,and the patient maintained stable disease at his last follow-up.EML4-ALK rearrangements can happen in patients with EGFR-positive NSCLC,after acquired resistance to EGFR TKI treatment.The EGFR T790M and C797G mutations occur in cis is a critical mechanism of resistance to osimertinib therapy.The MAF of EML4-ALK rearrangements in cancer cells might be a predictive factor for crizotinib treatment.
文摘Objective：Research has demonstrated that microRNA（miR）-106a is related to cisplatin resistance.We investigated the expression of miR-106a in the serum of patients with non-small cell lung cancer（NSCLC）and their sensitivity to chemotherapy by cisplatin combined with gemcitabine.Methods：Eighty-five NSCLC patients,who completed four cycles of gemcitabine and cisplatin chemotherapy,volunteered for this study and their serum samples were collected.Serum samples from 60 healthy subjects were used as controls.Real-time quantitative polymerase chain reaction（real-time q PCR）was used to quantify the level of miR-106a in the serum.Demographic and survival data of these patients were collected for the analysis.Results：The expression of miR-106a in the serum of NSCLC patients was significantly higher than that of healthy subjects（P＆lt;0.001）.The expression of miR-106a was not correlated with patients＇gender,age,tumor size,lymphatic metastasis,and pathological types;but was correlated with patients＇tumor staging（P=0.003）.After chemotherapy,serum miR-106a expression decreased in patients.The decrease in miR-106a expression in the chemotherapy-sensitive group was much higher than that in the chemotherapy-resistant group.Survival analysis shows that NSCLC patients with high expression of miR-106a have a poorer prognosis.The overall survival of NSCLC patients in the chemotherapy-sensitive group was significantly higher than that in the chemotherapy-resistant group.Conclusions：High expression of miR-106a may be involved in the development of NSCLC.Mi R-106a has significance in the prognosis of NSCLC.The level of miR-106a in the serum can be a useful parameter in screening for drug resistance during cisplatin-based chemotherapy.
文摘Objective: Emerging evidence indicates that long non-coding RNAs(lnc RNAs) are critical in carcinogenesis and progression of ovarian cancer. This study aimed to explore the functions and molecular mechanisms of plasmacytoma variant translocation I(PVT1) in ovarian cancer Methods: PVT1 and miR-214 were detected by qRT-PCR assays in ovarian cancer tissues and cells. The cell proliferation,migration, and invasion abilities were detected by cell functional experiments, respectively. Western blot assay was performed to detect epithelial-mesenchymal transition(EMT) markers. MiR-214 expression regulated by PVT1 was studied by RNA immunoprecipitation(RIP) and chromatin immunoprecipitation(Ch IP) assays.Results: The expression of PVT1 was up-regulated in ovarian cancer tissues and cell lines. Elevated PVT1 expression was associated with advanced stage and indicated poor prognosis for ovarian cancer patients. The knockdown of PVT1 impaired SKOV3 cell proliferation, migration, and invasion in vitro. The promotion of ovarian cancer progression by PVT1 involved in regulation of the epithelial-mesenchymal transition process and PVT1 interaction with EZH2 represses miR-214 expression in ovarian cancer cells.Conclusions: PVT1 plays an important role in ovarian cancer tumorigenesis, which might be as a novel diagnostic marker and therapeutic target for ovarian cancer.
