ROS1 oncogenic fusion is reported to be 1%</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"...ROS1 oncogenic fusion is reported to be 1%</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> - </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">2% of non-small cell lung cancers (NSCLCs) of the adenocarcinoma subgroup. Meanwhile, there are no records of squamous cell cancer patients with tumors harboring ROS1 fusions. The Foundation Medicine database indicates a frequency of ROS1 rearrangements is 0.2% among squamous NSCLC. Crizotinib is known to be very effective in these patients</span><b><span style="font-family:Verdana;">.</span></b></span></span></span><span><span><b><span style="font-family:""> </span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Here we present a non-smoker patient who had pure squamous NSCLC that was treated by combinational immunotherapy under a clinical trial and progressed after 2 cycles. Surprisingly, comprehensive genomic profiling detected a rare oncogenic EZR-ROS1 fusion, and the patient was treated by crizotinib with a significant response within 6 weeks. To date, the patient has been on therapy for 42 months</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and has achieved</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a complete metabolic response.展开更多
Background:Lung cancer is one of the leading causes of death despite improvement in treatment modalities such as immunotherapy with chemotherapy and precise radiotherapy.NSCLC is a heterogeneous group of diseases that...Background:Lung cancer is one of the leading causes of death despite improvement in treatment modalities such as immunotherapy with chemotherapy and precise radiotherapy.NSCLC is a heterogeneous group of diseases that differs in cytology and includes adenocarcinoma,squamous cell carcinoma,bronchioloalveolar carcinoma,and poorly differentiated carcinoma.Usually,NSCLC,in contrast to SCLC,spreads locally,and the doubling time of squamous cell carcinoma is 133 days which classifies it as a relatively slow-growing tumor.Case presentation:We present the case of a 72-year-old male,recently diagnosed with squamous cell carcinoma in the right upper lobe along with secondary deposits.Few days after diagnosis,the patient had severe respiratory distress.This endobronchial tumor has increased significantly in size upon bronchoscopic visualization causing a complete obstruction of his right main bronchus and hypoxemic respiratory failure requiring intubation.Conclusion:To our knowledge,there are few reported cases where lung adenocarcinoma progressed rapidly over days.Squamous cell carcinoma usually takes 3 to 6 months to double in size,but in our case,the progression was very fast.In the last decade,it was confirmed that the doubling time of a tumor is an independent factor in the prognosis of lung cancer patients.On the other hand,further studies are needed to identify genes associated with rapid progression and a worse prognosis for lung squamous cell carcinoma.Hence,this aggressive tumor is a“rapid killer.”展开更多
Objective:The E3 ligase,CRL4,plays diverse roles in different cellular processes,such as DNA damage,transcriptional regulation,cell cycle progression,and cell apoptosis.Our previous study showed that CUL4A and CUL4B h...Objective:The E3 ligase,CRL4,plays diverse roles in different cellular processes,such as DNA damage,transcriptional regulation,cell cycle progression,and cell apoptosis.Our previous study showed that CUL4A and CUL4B had a strong association with tobacco smoking risk in lung squamous cell carcinoma(SCC)and small cell lung carcinoma(SCLC).This study aimed to define the potential mechanism underlying the roles of CUL4A and CUL4B in the development of SCC and SCLC.Methods:We determined the role of CUL4A and CUL4B in the cell cycle and apoptosis of SCC and SCLC,and identified the key apoptosis-related gene involved in the oncogenic activity of CUL4B by Western blot,immunohistochemical staining,flow cytometry,and enzyme inhibition experiments.Results:We found that depletion of CUL4A and CUL4B reduced the proliferation of SCC and SCLC cells.cUL4Aknockdown but not CUL4Bknockdown arrested cells in Gl phase while upregulating P21 and cU L4Bknockdown promoted cell apoptosis through upregulation o f FOXO3A.Accordingly,CUL4B decreased FO X03A expression by activating the ERK signaling pathway and mediating FOXO3A degradation via the ubiquitin-proteasome pathway.Conclusions:These results identified the function of E3 ligase CRL4 in regulating SCC and SCLC cell proliferation,which provides a potential strategy for cancer therapy by targeting FOXO3A and the E3 ligase,CRL4.展开更多
Lung carcinoma is associated with a high mortality worldwide,being the leading cause of cancer death.It is mainly classified into squamous non-small cell lung cancer(NSCLC),non-squamous NSCLC,and small cell lung cance...Lung carcinoma is associated with a high mortality worldwide,being the leading cause of cancer death.It is mainly classified into squamous non-small cell lung cancer(NSCLC),non-squamous NSCLC,and small cell lung cancer.However,such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment.Therapies can be used in adjuvant and palliative settings.Regarding immunotherapy,it has been widely tested in both first or subsequent palliative lines.In this sense,drugs such as pembrolizumab,nivolumab,atezolizumab,ipilimumab,avelumab,and durvalumab have been assessed in large studies.Some of these trials have also studied these medicines in adjuvant and in maintenance therapy.In recent years,advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed.Immunotherapy has increased the overall survival in squamous NSCLC,non-squamous NSCLC,and small cell lung cancer.However,it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support.In order to show how immunotherapy is being applied in the treatment of lung carcinoma,we reviewed the main studies in adjuvant and palliative scenarios.What is the better scheme?What is the better combination?What is the better dose?When should we use immunotherapy?Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency?Some of these questions have already been answered,while others require more investigations.展开更多
Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcino...Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).展开更多
文摘ROS1 oncogenic fusion is reported to be 1%</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> - </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">2% of non-small cell lung cancers (NSCLCs) of the adenocarcinoma subgroup. Meanwhile, there are no records of squamous cell cancer patients with tumors harboring ROS1 fusions. The Foundation Medicine database indicates a frequency of ROS1 rearrangements is 0.2% among squamous NSCLC. Crizotinib is known to be very effective in these patients</span><b><span style="font-family:Verdana;">.</span></b></span></span></span><span><span><b><span style="font-family:""> </span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Here we present a non-smoker patient who had pure squamous NSCLC that was treated by combinational immunotherapy under a clinical trial and progressed after 2 cycles. Surprisingly, comprehensive genomic profiling detected a rare oncogenic EZR-ROS1 fusion, and the patient was treated by crizotinib with a significant response within 6 weeks. To date, the patient has been on therapy for 42 months</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and has achieved</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a complete metabolic response.
文摘Background:Lung cancer is one of the leading causes of death despite improvement in treatment modalities such as immunotherapy with chemotherapy and precise radiotherapy.NSCLC is a heterogeneous group of diseases that differs in cytology and includes adenocarcinoma,squamous cell carcinoma,bronchioloalveolar carcinoma,and poorly differentiated carcinoma.Usually,NSCLC,in contrast to SCLC,spreads locally,and the doubling time of squamous cell carcinoma is 133 days which classifies it as a relatively slow-growing tumor.Case presentation:We present the case of a 72-year-old male,recently diagnosed with squamous cell carcinoma in the right upper lobe along with secondary deposits.Few days after diagnosis,the patient had severe respiratory distress.This endobronchial tumor has increased significantly in size upon bronchoscopic visualization causing a complete obstruction of his right main bronchus and hypoxemic respiratory failure requiring intubation.Conclusion:To our knowledge,there are few reported cases where lung adenocarcinoma progressed rapidly over days.Squamous cell carcinoma usually takes 3 to 6 months to double in size,but in our case,the progression was very fast.In the last decade,it was confirmed that the doubling time of a tumor is an independent factor in the prognosis of lung cancer patients.On the other hand,further studies are needed to identify genes associated with rapid progression and a worse prognosis for lung squamous cell carcinoma.Hence,this aggressive tumor is a“rapid killer.”
基金The National Natural Science Foundation of China(Grant No.81772620 and 31471341)the Key Science and Technology Project of Tianjin Chronic Disease Prevention and Control(Grant No.17XXMFSY00130)the National Science and Technology Major Project(Grant No.2018ZX09201-015).
文摘Objective:The E3 ligase,CRL4,plays diverse roles in different cellular processes,such as DNA damage,transcriptional regulation,cell cycle progression,and cell apoptosis.Our previous study showed that CUL4A and CUL4B had a strong association with tobacco smoking risk in lung squamous cell carcinoma(SCC)and small cell lung carcinoma(SCLC).This study aimed to define the potential mechanism underlying the roles of CUL4A and CUL4B in the development of SCC and SCLC.Methods:We determined the role of CUL4A and CUL4B in the cell cycle and apoptosis of SCC and SCLC,and identified the key apoptosis-related gene involved in the oncogenic activity of CUL4B by Western blot,immunohistochemical staining,flow cytometry,and enzyme inhibition experiments.Results:We found that depletion of CUL4A and CUL4B reduced the proliferation of SCC and SCLC cells.cUL4Aknockdown but not CUL4Bknockdown arrested cells in Gl phase while upregulating P21 and cU L4Bknockdown promoted cell apoptosis through upregulation o f FOXO3A.Accordingly,CUL4B decreased FO X03A expression by activating the ERK signaling pathway and mediating FOXO3A degradation via the ubiquitin-proteasome pathway.Conclusions:These results identified the function of E3 ligase CRL4 in regulating SCC and SCLC cell proliferation,which provides a potential strategy for cancer therapy by targeting FOXO3A and the E3 ligase,CRL4.
文摘Lung carcinoma is associated with a high mortality worldwide,being the leading cause of cancer death.It is mainly classified into squamous non-small cell lung cancer(NSCLC),non-squamous NSCLC,and small cell lung cancer.However,such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment.Therapies can be used in adjuvant and palliative settings.Regarding immunotherapy,it has been widely tested in both first or subsequent palliative lines.In this sense,drugs such as pembrolizumab,nivolumab,atezolizumab,ipilimumab,avelumab,and durvalumab have been assessed in large studies.Some of these trials have also studied these medicines in adjuvant and in maintenance therapy.In recent years,advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed.Immunotherapy has increased the overall survival in squamous NSCLC,non-squamous NSCLC,and small cell lung cancer.However,it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support.In order to show how immunotherapy is being applied in the treatment of lung carcinoma,we reviewed the main studies in adjuvant and palliative scenarios.What is the better scheme?What is the better combination?What is the better dose?When should we use immunotherapy?Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency?Some of these questions have already been answered,while others require more investigations.
文摘Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).
