Background:Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival.By binding with its ligand(inducible T-cell costimulator and its ligand[ICOSL]),an inducible T-cell co...Background:Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival.By binding with its ligand(inducible T-cell costimulator and its ligand[ICOSL]),an inducible T-cell co-stimulator(ICOS)could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.Methods:We selected 54 formalin-fixed,paraffin-embedded tumor tissues from cases with stage I–III lung adenocarcinoma cancer.Immunohistochemical expression of ICOS and ICOSL was evaluated.The correlation with clinical parameters in Chinese patients was also compared with TCGA results.Results:The positive rates of ICOS and ICOSL were 68%and 81.5%,respectively,in lung tumor tissues.Of these,9 cases had a low expression of ICOS,and 22 cases had a high expression of ICOS;ICOSL expression was low in 20 cases and high in 24 cases.According to the International Association for the Study of Lung Cancer(8th edition),phase I lesions were detected in 21 cases,phase II lesions in 15 cases,and phase III lesions in 18 cases.The median survival time of all patients was 44.5 months,and the median disease-free survival was 32 months.Univariate analysis showed that the factors significantly associated with overall survival were tumor size,regional lymph node involvement,stage,and expression level of ICOS/ICOSL.Survival analysis using log-rank test indicated that the lower ICOS+cell infiltration may predict poor prognosis,whereas lower ICOSL protein expression may be associated with better prognosis,but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction.Conclusion:ICOS/ICOSL might be associated with prognosis of lung cancer,and ICOS and its ligand may be potential therapeutic targets in non-small cell lung cancer.展开更多
Myeloid-derived suppressor cells(MDSCs)are bone marrow(BM)-derived immunosuppressive cells in the tumor microenvironment,but the mechanism of MDSC mobilization from the BM remains unclear.We investigated how BM stroma...Myeloid-derived suppressor cells(MDSCs)are bone marrow(BM)-derived immunosuppressive cells in the tumor microenvironment,but the mechanism of MDSC mobilization from the BM remains unclear.We investigated how BM stromal cell activation by PTH1R contributes to MDSC mobilization.PTH1R activation by parathyroid hormone(PTH)or PTH-related peptide(PTHrP),a tumor-derived counterpart,mobilized monocytic(M-)MDSCs from murine BM without increasing immunosuppressive activity.In vitro cell-binding assays demonstrated thatα4β1 integrin and vascular cell adhesion molecule(VCAM)-1,expressed on M-MDSCs and osteoblasts,respectively,are key to M-MDSC binding to osteoblasts.Upon PTH1R activation,osteoblasts express VEGF-A and IL6,leading to Src family kinase phosphorylation in M-MDSCs.Src inhibitors suppressed PTHrP-induced MDSC mobilization,and Src activation in M-MDSCs upregulated two proteases,ADAM-17 and MMP7,leading to VCAM1 shedding and subsequent disruption of M-MDSC tethering to osteoblasts.Collectively,our data provide the molecular mechanism of M-MDSC mobilization in the bones of tumor hosts.展开更多
Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besid...Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besides first and second generation tyrosine kinase inhibitors,immune checkpoint inhibitors have become central for the treatment of HCC.New modalities like epigenetic therapy using histone deacetylase inhibitors(HDACi)and cell therapy approaches with chimeric antigen receptor T cells(CAR-T cells)are currently under investigation in clinical trials.Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers.The current status of treatment options for advanced HCC,emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here.展开更多
Intramural duodenal hematoma is a rare cause of a proximal gastrointestinal tract obstruction.Presentation of intramural duodenal hematoma most often occurs following blunt abdominal trauma in children,but spontaneous...Intramural duodenal hematoma is a rare cause of a proximal gastrointestinal tract obstruction.Presentation of intramural duodenal hematoma most often occurs following blunt abdominal trauma in children,but spontaneous non-traumatic cases have been linked to anticoagulant therapy,pancreatitis,malignancy,vasculitis and endoscopy.We report an unusual case of spontaneous intramural duodenal hematoma presenting as an intestinal obstruction associated with acute pancreatitis in a patient with established von Willebrand disease,type 2B.The patient presented with abrupt onset of abdominal pain,nausea,and vomiting.Computed tomography imaging identified an intramural duodenal mass consistent with blood measuring 4.7 cm×8.7 cm in the second portion of the duodenum abutting on the head of the pancreas.Serum lipase was 3828 units/L.Patient was managed conservatively with bowel rest,continuous nasogastric decompression,total parenteral nutrition,recombinant factorⅧ(humateP)and transfusion.Symptoms resolved over the course of the hospitalization.This case highlights an important complication of an inherited coagulopathy.展开更多
Diffuse large B cell primary hepatic lymphoma is a rare disease with limited available information regarding treatment strategy. Although the liver contains lymphoid tissue and is an important site for lymphocytes act...Diffuse large B cell primary hepatic lymphoma is a rare disease with limited available information regarding treatment strategy. Although the liver contains lymphoid tissue and is an important site for lymphocytes activation, primary hepatic lymphoma is rare. Host factors make the liver a poor environment for malignant lymphoma development. Its coexistence with human immunodeficiency virus(HIV) infection increases morbidity and mortality risks. Additionally, jaundice increases chances of developing adverse effects from chemotherapy. Here, we report a case of diffuse large B cell primary hepatic lymphoma in a 32-year-old HIV positive man. Due to elevated liver enzyme levels and jaundice, the patient was initially treated with an R-DHAP regimen, which was replaced with an R-CHOP regimen. Restaging images with a positron emission tomography scan after the latest chemotherapy cycle confirmed remission. This is the first report of complete remission of primary hepatic diffuse large B cell lymphoma in an HIV positive patient in the English literature.展开更多
Small cell lung cancer(SCLC)is an aggressive subtype of neuroendocrine tumor.It is characterized by a rapid doubling time and early development of metastatic disease.Despite being responsive to initial chemotherapy,mo...Small cell lung cancer(SCLC)is an aggressive subtype of neuroendocrine tumor.It is characterized by a rapid doubling time and early development of metastatic disease.Despite being responsive to initial chemotherapy,most of the patients will have relapse of the disease within a few months.The prognosis of SCLC is dismal with a 5-year survival rate of less than 5%.For that reason,management of SCLC has been an active area of research.The utilization of immunotherapy has provided promising results in treatment of SCLC in the front-line setting.Therefore,utilization of immunotherapy and targeted therapy is being studied in the setting of relapsed/refractory disease,and currently,different clinical trials are exploring new drugs and further options.In this review,we will explore the latest updates in management of relapsed/refractory SCLC.展开更多
基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS,nos:2022-I2M-JB-011,2022-I2M-1-014)the National Natural Science Foundation of China(82293684)the National Key R&D Program of China(2022YFA0806400).
文摘Background:Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival.By binding with its ligand(inducible T-cell costimulator and its ligand[ICOSL]),an inducible T-cell co-stimulator(ICOS)could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.Methods:We selected 54 formalin-fixed,paraffin-embedded tumor tissues from cases with stage I–III lung adenocarcinoma cancer.Immunohistochemical expression of ICOS and ICOSL was evaluated.The correlation with clinical parameters in Chinese patients was also compared with TCGA results.Results:The positive rates of ICOS and ICOSL were 68%and 81.5%,respectively,in lung tumor tissues.Of these,9 cases had a low expression of ICOS,and 22 cases had a high expression of ICOS;ICOSL expression was low in 20 cases and high in 24 cases.According to the International Association for the Study of Lung Cancer(8th edition),phase I lesions were detected in 21 cases,phase II lesions in 15 cases,and phase III lesions in 18 cases.The median survival time of all patients was 44.5 months,and the median disease-free survival was 32 months.Univariate analysis showed that the factors significantly associated with overall survival were tumor size,regional lymph node involvement,stage,and expression level of ICOS/ICOSL.Survival analysis using log-rank test indicated that the lower ICOS+cell infiltration may predict poor prognosis,whereas lower ICOSL protein expression may be associated with better prognosis,but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction.Conclusion:ICOS/ICOSL might be associated with prognosis of lung cancer,and ICOS and its ligand may be potential therapeutic targets in non-small cell lung cancer.
基金in part supported by the National R&D Program for Cancer Control,the Ministry of Health and Welfare,the Republic of Korea(HA17C0040 to SIP)the National Research Foundation of the Republic of Korea(2018R1D1A1B07050329 and2020R1A2C1012966 to SIP,and 2020R1F1A1076996 to SPJ)the Korea University Research Grants(SIP)。
文摘Myeloid-derived suppressor cells(MDSCs)are bone marrow(BM)-derived immunosuppressive cells in the tumor microenvironment,but the mechanism of MDSC mobilization from the BM remains unclear.We investigated how BM stromal cell activation by PTH1R contributes to MDSC mobilization.PTH1R activation by parathyroid hormone(PTH)or PTH-related peptide(PTHrP),a tumor-derived counterpart,mobilized monocytic(M-)MDSCs from murine BM without increasing immunosuppressive activity.In vitro cell-binding assays demonstrated thatα4β1 integrin and vascular cell adhesion molecule(VCAM)-1,expressed on M-MDSCs and osteoblasts,respectively,are key to M-MDSC binding to osteoblasts.Upon PTH1R activation,osteoblasts express VEGF-A and IL6,leading to Src family kinase phosphorylation in M-MDSCs.Src inhibitors suppressed PTHrP-induced MDSC mobilization,and Src activation in M-MDSCs upregulated two proteases,ADAM-17 and MMP7,leading to VCAM1 shedding and subsequent disruption of M-MDSC tethering to osteoblasts.Collectively,our data provide the molecular mechanism of M-MDSC mobilization in the bones of tumor hosts.
文摘Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besides first and second generation tyrosine kinase inhibitors,immune checkpoint inhibitors have become central for the treatment of HCC.New modalities like epigenetic therapy using histone deacetylase inhibitors(HDACi)and cell therapy approaches with chimeric antigen receptor T cells(CAR-T cells)are currently under investigation in clinical trials.Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers.The current status of treatment options for advanced HCC,emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here.
文摘Intramural duodenal hematoma is a rare cause of a proximal gastrointestinal tract obstruction.Presentation of intramural duodenal hematoma most often occurs following blunt abdominal trauma in children,but spontaneous non-traumatic cases have been linked to anticoagulant therapy,pancreatitis,malignancy,vasculitis and endoscopy.We report an unusual case of spontaneous intramural duodenal hematoma presenting as an intestinal obstruction associated with acute pancreatitis in a patient with established von Willebrand disease,type 2B.The patient presented with abrupt onset of abdominal pain,nausea,and vomiting.Computed tomography imaging identified an intramural duodenal mass consistent with blood measuring 4.7 cm×8.7 cm in the second portion of the duodenum abutting on the head of the pancreas.Serum lipase was 3828 units/L.Patient was managed conservatively with bowel rest,continuous nasogastric decompression,total parenteral nutrition,recombinant factorⅧ(humateP)and transfusion.Symptoms resolved over the course of the hospitalization.This case highlights an important complication of an inherited coagulopathy.
文摘Diffuse large B cell primary hepatic lymphoma is a rare disease with limited available information regarding treatment strategy. Although the liver contains lymphoid tissue and is an important site for lymphocytes activation, primary hepatic lymphoma is rare. Host factors make the liver a poor environment for malignant lymphoma development. Its coexistence with human immunodeficiency virus(HIV) infection increases morbidity and mortality risks. Additionally, jaundice increases chances of developing adverse effects from chemotherapy. Here, we report a case of diffuse large B cell primary hepatic lymphoma in a 32-year-old HIV positive man. Due to elevated liver enzyme levels and jaundice, the patient was initially treated with an R-DHAP regimen, which was replaced with an R-CHOP regimen. Restaging images with a positron emission tomography scan after the latest chemotherapy cycle confirmed remission. This is the first report of complete remission of primary hepatic diffuse large B cell lymphoma in an HIV positive patient in the English literature.
文摘Small cell lung cancer(SCLC)is an aggressive subtype of neuroendocrine tumor.It is characterized by a rapid doubling time and early development of metastatic disease.Despite being responsive to initial chemotherapy,most of the patients will have relapse of the disease within a few months.The prognosis of SCLC is dismal with a 5-year survival rate of less than 5%.For that reason,management of SCLC has been an active area of research.The utilization of immunotherapy has provided promising results in treatment of SCLC in the front-line setting.Therefore,utilization of immunotherapy and targeted therapy is being studied in the setting of relapsed/refractory disease,and currently,different clinical trials are exploring new drugs and further options.In this review,we will explore the latest updates in management of relapsed/refractory SCLC.
