BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported ...BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.展开更多
BACKGROUND Colorectal cancer ranks third and second among common and fatal cancers.The treatment of metastatic colorectal cancer(mCRC)is generally based on XELOX in clinical practice,which includes capecitabine(CAP)an...BACKGROUND Colorectal cancer ranks third and second among common and fatal cancers.The treatment of metastatic colorectal cancer(mCRC)is generally based on XELOX in clinical practice,which includes capecitabine(CAP)and oxaliplatin.Serum tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125 and CA199 are prognostic factors for various tumors.AIM To investigate evaluating combined bevacizumab(BEV)and XELOX in advanced colorectal cancer:Serum markers CEA,CA125,CA199 analysis.METHODS In this retrospective study,a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received.The control group was treated with XELOX plus CAP(n=47),while the observation group was treated with XELOX plus CAP and BEV(n=47).Several indexes were assessed in both groups,including disease control rate(DCR),incidence of adverse effects,serum marker levels(CEA,CA125,and CA19)and progression-free survival(PFS).RESULTS After 9 wk of treatment,the serum levels of CEA,CA199 and CA125 in the observation group were significantly lower than those in the control group(P<0.05).Moreover,the PFS of the observation group(9.12±0.90 mo)was significantly longer than that of the control group(6.49±0.64 mo).Meanwhile,there was no statistically significant difference in the incidence of adverse reactions and DCR between the two groups during maintenance therapy(P>0.05).CONCLUSION On the basis of XELOX treatment,the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.展开更多
Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabo...Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.展开更多
BACKGROUND Atezolizumab/bevacizumab is emerging as the new standard for advanced hepatocellular carcinoma(HCC),with ongoing real-world implementation to study its effectiveness.As the use of atezolizumab/bevacizumab i...BACKGROUND Atezolizumab/bevacizumab is emerging as the new standard for advanced hepatocellular carcinoma(HCC),with ongoing real-world implementation to study its effectiveness.As the use of atezolizumab/bevacizumab increases,various side effects have been reported in clinical practice,most notably increased bleeding caused by bevacizumab.CASE SUMMARY In this case report,we present a rare and fatal case of intratumoral hemorrhage in a patient with advanced HCC following successful treatment with atezolizumab/bevacizumab.A 63-year-old male diagnosed with HCC initially underwent four cycles of intra-arterial chemotherapy.However,follow-up abdominal computed tomography(CT)revealed disease progression.Subsequently,the treatment plan was modified to atezolizumab/bevacizumab.After the fifth cycle of atezolizumab/bevacizumab,CT showed partial regression of HCC.One week later,he visited the emergency room due to severe abrupt abdominal pain.Abdominal CT revealed focal rupture of HCC in the medial segment inferior portion with active bleeding and a large amount of hemoperitoneum.Angiography was performed on the same day,and embolization of A4 and A8 branches using lipiodol and gelfoam was implemented.Despite successful hemostasis,the patient subsequently developed liver failure and died.CONCLUSION Atezolizumab/bevacizumab for advanced HCC suggests that intratumoral hemorrhage may be crucial despite good tumor response after immunotherapy,emphasizing the continuous monitoring of this side effect.展开更多
BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
BACKGROUND At present,immune checkpoint inhibitors(ICIs)remain the 1st-line therapy me-thod for patients suffering from high microsatellite instability/deficient misma-tch repair metastatic colorectal cancer(mCRC).How...BACKGROUND At present,immune checkpoint inhibitors(ICIs)remain the 1st-line therapy me-thod for patients suffering from high microsatellite instability/deficient misma-tch repair metastatic colorectal cancer(mCRC).However,ICI treatments demon-strate minimal therapeutic efficacy against microsatellite stable(MSS)/proficient mismatch repair(pMMR)CRC.This is mainly because this type of tumor is a“cold tumor”with almost no lymphocyte infiltration.Anti-angiogenic drugs have been found to improve the immune microenvironment by promoting many immune cells to enter the immune microenvironment,thereby exerting anti-tumor effects.AIM To investigate the effects of ICIs combined with bevacizumab monoclonal anti-body on tumor immune cells in MSS/pMMR advanced CRC patients with first-line treatment failure.METHODS A total of 110 MSS/pMMR patients with advanced CRC after first-line treatment failure in the Affiliated Hospital of Qinghai University were enrolled for a ran-domized controlled trial.In short,patients in the experimental group(n=60)were given sintilimab plus bevacizumab for 4 cycles,and those in the control group(n=50)patients were treated with FOLFIRI combined with bevacizumab for 4 cycles.The expression levels of cluster of differentiation(CD)8(+)T cells,tumor-associated macrophages(TAMs),and cancer-associated fibroblasts(CAFs)were comprehensively evaluated to assess the effects of sintilimab combined with bevacizumab on MSS/pMMR advanced CRC sufferers following failure of 1st-line therapy.RESULTS The positive expression rates of CD8(+)T lymphocytes(30%vs 50%),TAMs(23.30%vs 60%),and CAFs(23.30%vs 50%)before and after treatment in both groups exhibited statistical significance(P<0.05).Additionally,the therapeutic effects of both groups(partial remission:26.67%vs 10%;objective response rate:26.70%vs 10%)were significantly different(P<0.05).Although the experimental group showed a higher progression-free survival,median progression-free survival,and disease control rate than the control group,the difference was not statist-ically significant.Moreover,no significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups was found(P>0.05).CONCLUSION ICIs in combination with bevacizumab can not only improve the patient’s prognosis but also yield safe and controllable adverse drug reactions in patients suffering from MSS/pMMR advanced CRC after failure to a 1st-line therapy.展开更多
文摘BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.
文摘BACKGROUND Colorectal cancer ranks third and second among common and fatal cancers.The treatment of metastatic colorectal cancer(mCRC)is generally based on XELOX in clinical practice,which includes capecitabine(CAP)and oxaliplatin.Serum tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125 and CA199 are prognostic factors for various tumors.AIM To investigate evaluating combined bevacizumab(BEV)and XELOX in advanced colorectal cancer:Serum markers CEA,CA125,CA199 analysis.METHODS In this retrospective study,a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received.The control group was treated with XELOX plus CAP(n=47),while the observation group was treated with XELOX plus CAP and BEV(n=47).Several indexes were assessed in both groups,including disease control rate(DCR),incidence of adverse effects,serum marker levels(CEA,CA125,and CA19)and progression-free survival(PFS).RESULTS After 9 wk of treatment,the serum levels of CEA,CA199 and CA125 in the observation group were significantly lower than those in the control group(P<0.05).Moreover,the PFS of the observation group(9.12±0.90 mo)was significantly longer than that of the control group(6.49±0.64 mo).Meanwhile,there was no statistically significant difference in the incidence of adverse reactions and DCR between the two groups during maintenance therapy(P>0.05).CONCLUSION On the basis of XELOX treatment,the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.
文摘Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.
基金Supported by Soonchunhyang University Research Fund,No.20240007.
文摘BACKGROUND Atezolizumab/bevacizumab is emerging as the new standard for advanced hepatocellular carcinoma(HCC),with ongoing real-world implementation to study its effectiveness.As the use of atezolizumab/bevacizumab increases,various side effects have been reported in clinical practice,most notably increased bleeding caused by bevacizumab.CASE SUMMARY In this case report,we present a rare and fatal case of intratumoral hemorrhage in a patient with advanced HCC following successful treatment with atezolizumab/bevacizumab.A 63-year-old male diagnosed with HCC initially underwent four cycles of intra-arterial chemotherapy.However,follow-up abdominal computed tomography(CT)revealed disease progression.Subsequently,the treatment plan was modified to atezolizumab/bevacizumab.After the fifth cycle of atezolizumab/bevacizumab,CT showed partial regression of HCC.One week later,he visited the emergency room due to severe abrupt abdominal pain.Abdominal CT revealed focal rupture of HCC in the medial segment inferior portion with active bleeding and a large amount of hemoperitoneum.Angiography was performed on the same day,and embolization of A4 and A8 branches using lipiodol and gelfoam was implemented.Despite successful hemostasis,the patient subsequently developed liver failure and died.CONCLUSION Atezolizumab/bevacizumab for advanced HCC suggests that intratumoral hemorrhage may be crucial despite good tumor response after immunotherapy,emphasizing the continuous monitoring of this side effect.
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
基金Supported by the 2021 Key Topic of the Qinghai Provincial Health System-Guiding Plan Topic,No.2021-WJZDX-43.
文摘BACKGROUND At present,immune checkpoint inhibitors(ICIs)remain the 1st-line therapy me-thod for patients suffering from high microsatellite instability/deficient misma-tch repair metastatic colorectal cancer(mCRC).However,ICI treatments demon-strate minimal therapeutic efficacy against microsatellite stable(MSS)/proficient mismatch repair(pMMR)CRC.This is mainly because this type of tumor is a“cold tumor”with almost no lymphocyte infiltration.Anti-angiogenic drugs have been found to improve the immune microenvironment by promoting many immune cells to enter the immune microenvironment,thereby exerting anti-tumor effects.AIM To investigate the effects of ICIs combined with bevacizumab monoclonal anti-body on tumor immune cells in MSS/pMMR advanced CRC patients with first-line treatment failure.METHODS A total of 110 MSS/pMMR patients with advanced CRC after first-line treatment failure in the Affiliated Hospital of Qinghai University were enrolled for a ran-domized controlled trial.In short,patients in the experimental group(n=60)were given sintilimab plus bevacizumab for 4 cycles,and those in the control group(n=50)patients were treated with FOLFIRI combined with bevacizumab for 4 cycles.The expression levels of cluster of differentiation(CD)8(+)T cells,tumor-associated macrophages(TAMs),and cancer-associated fibroblasts(CAFs)were comprehensively evaluated to assess the effects of sintilimab combined with bevacizumab on MSS/pMMR advanced CRC sufferers following failure of 1st-line therapy.RESULTS The positive expression rates of CD8(+)T lymphocytes(30%vs 50%),TAMs(23.30%vs 60%),and CAFs(23.30%vs 50%)before and after treatment in both groups exhibited statistical significance(P<0.05).Additionally,the therapeutic effects of both groups(partial remission:26.67%vs 10%;objective response rate:26.70%vs 10%)were significantly different(P<0.05).Although the experimental group showed a higher progression-free survival,median progression-free survival,and disease control rate than the control group,the difference was not statist-ically significant.Moreover,no significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups was found(P>0.05).CONCLUSION ICIs in combination with bevacizumab can not only improve the patient’s prognosis but also yield safe and controllable adverse drug reactions in patients suffering from MSS/pMMR advanced CRC after failure to a 1st-line therapy.
