Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the devel...Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.展开更多
A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive...A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.展开更多
BACKGROUND Hepatic artery infusion chemotherapy(HAIC)is a widely used local therapeutic approach for intermediate to advanced-stage hepatocellular carcinoma(HCC),exhibiting considerable efficacy.However,the prevalence...BACKGROUND Hepatic artery infusion chemotherapy(HAIC)is a widely used local therapeutic approach for intermediate to advanced-stage hepatocellular carcinoma(HCC),exhibiting considerable efficacy.However,the prevalence of postoperative pain highlights the importance of pain management.Owing to the limitations inherent in existing pain management strategies,this study investigates and assesses the analgesic effectiveness of a multimodal treatment protocol in mitigating pain after HAIC procedures.AIM To provide patients with a more comprehensive and effective pain management strategy.METHODS A total of 100 patients with primary HCC who underwent HAIC were randomly assigned to a control group(n=50)and a multimodal group(n=50).Baseline characteristics and perioperative data were collected.Upon enrollment,patients in the multimodal group received parecoxib(40 mg)30 minutes before HAIC,followed by 48 hours of patient-controlled analgesia with sufentanil.In contrast,the control group underwent standard preoperative preparation(psychological support)and received dezocine(5 mg)intraoperatively,with intravenous flurbiprofen(100 mg)administered every 12 hours for 48 hours postoperatively.RESULTS Compared to the control group,the multimodal analgesia group exhibited significantly lower resting and movement visual analog scale pain scores at postoperative 0,2,4,6,and 12 hours(P<0.05).Furthermore,the multimodal group experienced a reduced incidence of postoperative nausea and vomiting,as well as a lower overall frequency of adverse events,compared to the control group(P<0.05).Patient satisfaction was also significantly higher in the multimodal group than in the control group(P<0.05).CONCLUSION Our study demonstrates that multimodal analgesia is effective in reducing postoperative pain,minimizing adverse reactions,and improving patient satisfaction in HCC patients undergoing HAIC.This approach provides valuable clinical strategies for optimizing pain management in this patient population.展开更多
Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for...Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for DLBCL is chemo-immunotherapy with rituximab,cyclophos-phamide,doxorubicin,vincristine,and prednisone,which cures 50%-60% of patients2.展开更多
BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of h...BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.展开更多
文摘Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.
文摘A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.
基金Supported by Beijing Medical Award Foundation of China,No.YXJL-2023-0638-0048.
文摘BACKGROUND Hepatic artery infusion chemotherapy(HAIC)is a widely used local therapeutic approach for intermediate to advanced-stage hepatocellular carcinoma(HCC),exhibiting considerable efficacy.However,the prevalence of postoperative pain highlights the importance of pain management.Owing to the limitations inherent in existing pain management strategies,this study investigates and assesses the analgesic effectiveness of a multimodal treatment protocol in mitigating pain after HAIC procedures.AIM To provide patients with a more comprehensive and effective pain management strategy.METHODS A total of 100 patients with primary HCC who underwent HAIC were randomly assigned to a control group(n=50)and a multimodal group(n=50).Baseline characteristics and perioperative data were collected.Upon enrollment,patients in the multimodal group received parecoxib(40 mg)30 minutes before HAIC,followed by 48 hours of patient-controlled analgesia with sufentanil.In contrast,the control group underwent standard preoperative preparation(psychological support)and received dezocine(5 mg)intraoperatively,with intravenous flurbiprofen(100 mg)administered every 12 hours for 48 hours postoperatively.RESULTS Compared to the control group,the multimodal analgesia group exhibited significantly lower resting and movement visual analog scale pain scores at postoperative 0,2,4,6,and 12 hours(P<0.05).Furthermore,the multimodal group experienced a reduced incidence of postoperative nausea and vomiting,as well as a lower overall frequency of adverse events,compared to the control group(P<0.05).Patient satisfaction was also significantly higher in the multimodal group than in the control group(P<0.05).CONCLUSION Our study demonstrates that multimodal analgesia is effective in reducing postoperative pain,minimizing adverse reactions,and improving patient satisfaction in HCC patients undergoing HAIC.This approach provides valuable clinical strategies for optimizing pain management in this patient population.
基金sponsored by Shanghai Roche Pharmaceuticals Ltd.
文摘Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for DLBCL is chemo-immunotherapy with rituximab,cyclophos-phamide,doxorubicin,vincristine,and prednisone,which cures 50%-60% of patients2.
基金This study was approved by the ethics committee of the First People’s Hospital of Fuzhou City(No.FZ202103).
文摘BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.
