OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells wer...OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.展开更多
Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenva...Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.展开更多
BACKGROUND Parthenolide(PTL),a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium,exhibits various biological effects by targeting NF-kB,STAT3,and other pathways.It has emerged as a promisi...BACKGROUND Parthenolide(PTL),a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium,exhibits various biological effects by targeting NF-kB,STAT3,and other pathways.It has emerged as a promising adjunct therapy for multiple malignancies.AIM To evaluate the in vitro and in vivo effect of PTL on cyclophosphamide(CTX)metronomic chemotherapy.METHODS The cytotoxicity of PTL and CTX on Lewis lung cancer cells(LLC cells)was assessed by measuring cell activity and apoptosis.The anti-tumor efficiency was evaluated using a tumor xenograft mice model,and the survival of mice and tumor volume were monitored.Additionally,the collected tumor tissues were analyzed for tumor microenvironment indicators and inflammatory factors.RESULTS In vitro,PTL demonstrated a synergistic effect with CTX in inhibiting the growth of LLC cells and promoting apoptosis.In vivo,metronomic chemotherapy com-bined with PTL and CTX improved the survival rate of tumor-bearing mice and reduced tumor growth rate.Furthermore,metronomic chemotherapy combined with PTL and CTX reduced NF-κB activation and improved the tumor immune microenvironment by decreasing tumor angiogenesis,reducing Transforming growth factorβ,andα-SMA positive cells.CONCLUSION PTL is an efficient compound that enhances the metronomic chemotherapy effects of CTX both in vitro and in vivo,suggesting its potential as a supplementary therapeutic strategy in metronomic chemotherapy to improve the chemotherapy effects.展开更多
The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue an...The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.展开更多
BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies...BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.展开更多
Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7...Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.展开更多
An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route th...An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route that could cause stable thrombocytopenia. A suitable drug dosage that could induce thrombocytopenia in mouse efficiently with the definite administration route was then investigated. BALB/c mice were randomly divided into Normal, Model A and Model B groups. To Model A, 200 mg/kg of cyclophosphamide was given by vena caudalis injection as first dose and 30 mg/kg as maintenance dose by intraperitoneal injection at the following 6 days. To Model B, 150 mg/kg of cyclophosphamide was given by subcutaneous injection once a day for consecutive 3 days. All groups were under investigation for 15 days. The result suggested that a decrease in the number of blood platelets of Model B at the 7th day were significantly than that of Normal. Other platelet related indices like platelet distribution width, mean platelet volume and platelet-large cell ratio of Model B increased significantly in comparison with those of Normal group. The platelets count was reduced but fluctuated greatly, and more than half of the mice died in Model A. Therefore, subcutaneous injection of cyclophosphamide for 3 days was used for the cyclophosphamide dosage test. BALB/c mice were randomly divided into Normal, cyclophosphamide low dose （100 mg/kg）, medium dose （120 mg/kg） and high dose （140 mg/kg） groups. All groups were under investigation for 11 days. Though all 3 dosages successfully initiated thrombocytopenia as the platelets number dropped at the 7th day, the low dose was considered to be a suitable one that was of high efficacy and low toxicity. Thus, BALB/c mice challenged by subcutaneous injection of cyclophosphamide 100 mg/kg per day for 3 consecutive day is one simple, feasible and stable mouse thrombocytopenia model that could be used for pharmacodynamic test of the drugs which are supposed to have platelets increasing effect.展开更多
The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated wit...The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated with cyclophosphamide (CY) 300 mg/kg once alone was 13.3 ± 7.2d(n=7) however,average survival time of mice treated with CY 300 mg/kg in com-bination with PAP-1 10 mg/kg,3 times/wk was 36.7± 16.4d(n=7,P<0.01).PAP-1,ip had benefi-cial effect on the recovery of the CY induced decrease of peripheral leukocyte number,and the nu-cleated bone marrow cell(BMC)number and[3￣H]TdR uptaken by BMC induced by rmGM-CSF in S180 bearing mice treated with CY,In mice,after the first ip treatment with CY 100 mg/kg on d7,the peripheral leukocyte number decreased on d9 and recovered to normal level about d13 to d15. Such recovery was accelerated by administrating PAP-1,10mg/kg, 3 times/wk.A significant in-crease of the activity to form colony in spleen(colony-forming unit in spleen, CFU-S_8, CUF-S12) in mice irradiated with 550 rad 6O￣Co γ-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with PAP-1,10mg/kg,3 times/wk, ip were observed.After PAP-1,10 mg/kg,ip once,a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor(CSF) were also confirmed.The types of CSF in serum were M-CSF and other hematopoietic growth factors,which were confirmed by using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of PAP-1 on hematopoiesis may be related to its activityinducing CSFs and other hematopoietic growth factors and warrant further evaluation of its use-fulness.展开更多
Aim:To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate th...Aim:To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate the protective effect of ascorbic acid.Methods:The testicular△^(5),3β-hydroxysteroid dehydrogenase(HSD),17β-HSD,peroxidase and catalase activities along with the levels of malondialdehyde(MDA)and conjugated dienes in testicular tissue were measured for the evaluation of testicular oxidative stress.The plasma testosterone(T)level was measured by immunoassay.Various germ cells at stageⅦof spermatogenic cycle were quantified from testicular stained sections.Results:Cyclophosphamide treatment results in a significant inhibition in the testicular△^(5),3β-HSD and 17β-HSD activities,a decrease in plasma T level and a diminution in the counts of various germ cells.Moreover,this treatment was also associated with a significant inhibition of the peroxidase and catalase activities along with high levels of MDA and conjugated dienes in the testis.All these changes were reversed by ascorbic acid co-administration.Conclusion:Cyclophosphamide treatment at the dosage used caused testicular gametogenic and androgenic disorders as well as induced testicular oxidative stress that can be reversed by ascorbic acid co-administration.展开更多
Objective: To investigate the effects of a herb complex extract(HCE) prepared from Cornus officinalis Sieb. Et Zucc., Eriobotrya japonica Lindley, and olive leaves on immune response of mouse spleen NK cells in vitro ...Objective: To investigate the effects of a herb complex extract(HCE) prepared from Cornus officinalis Sieb. Et Zucc., Eriobotrya japonica Lindley, and olive leaves on immune response of mouse spleen NK cells in vitro and in vivo analysis. Methods: The activity of natural killer(NK) cells was measured in splenocytes and YAC-1 cells. Mice were immunosuppressed using cyclophosphamide(5 mg/kg body weight). Three different doses of HCE(200, 400, and 800 mg/kg body weight) and red ginseng extract(800 mg/kg body weight) which was used as standard immunomodulatory herb were administered orally for 4 weeks. The body weight, dietary, water intake, organs(liver, thymus, and spleen) weight, completed blood count, and cytokines(tumor necrosis factor alpha, interferon gamma, and interleukin-2) production was measured. Results: At the maximum concentration of HCE, the activity of NK cells was increased by 48.5%. HCE increased liver, spleen, and thymus weights without altering numbers of white blood cells, lymphocytes, and neutrophils in a cyclophosphamide-induced immunosuppression rat model. However, HCE recovered the inhibited cytokine expression; HCE(800 mg/kg) increased cytokines levels. The results indicate the immune enhancement potential of this HCE. Conclusion: The HCE enhances immunity by increasing NK cell activity, regulating cytokine levels, and maintaining spleen weight. Therefore, it may be used as a potential immunity enhancer.展开更多
Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d a...Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d at 150 mg/kg body weight through intraperitoneal route in rat model. Nephroprotective activity of Murraya koenigii(M. koenigii) extract(100 mg/kg and 200 mg/kg in intraperitoneal route) was measured, including nephrological source, oxidative stress parameters like superoxide dismutase, glutathione, the lipid peroxide and in vivo assay like blood urea nitrogen, creatinine were determined and analyzed by One way analysis of variance followed by Tukey's test. Results: The study result showed that important phytochemicals such as carbohydrates, flavonoids, tannin, alkaloids, glycosides, protein and steroids were found to be present in the extract of M. koenigii. The renal function markers like blood urea nitrogen and ceatinine level were found to be decreased significantly by M. koenigii extract treatment. A significant difference was found to be at P<0.01. Conclusions: The present study reveals the protective role of M. koenigii extract against Cyclophosphamide induced nephrotoxicity.展开更多
Cyclophosphamide(CYL)is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia.Though,CYL has been documented to induce lung toxicity.Mechanism of CYL toxicity is t...Cyclophosphamide(CYL)is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia.Though,CYL has been documented to induce lung toxicity.Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns(DAMPs).Sesamol(SES)is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet.This study aims to inves-tigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells,WI-38 cell line,without suppressing its efficacy.Cells were pretreated with SES and/or CYL for 24 h,then cell viability was estimated by MTS and trypan blue assays.The mode of cell death was determined by AO/EB staining.Additionally,caspase-3 level,oxidative stress,and inflammatory markers were evaluated by colorimetric and ELISA techniques.qRT-PCR was performed to evaluate RAGE,NF-κB,and Beclin-1 mRNA-expression.CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling,which were all attenuated after pretreatment with SES.Thus,we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling,which is a natural safe therapeutic option against CYL toxicities.展开更多
文摘OBJECTIVE To investigate the damage effect and mechanisms of cyclophosphamide(CTX)and its active metabolite derivative 4-hydroperoxycyclophosphamide(4-HC)to human neuroblas⁃toma SH-SY5Y cells.METHODS SH-SY5Y cells were treated with CTX[0(cell control),0.01,0.1,1,5,10,20,40 and 80 mmol·L^(-1)]and 4-HC[0(cell control),0.01,0.1,1,5,10,20,40 and 80μmol·L^(-1)]for 48 h.Cell confluence and morphology were observed by the IncuCyte ZOOM system.Cell viability was assessed by CCK-8 assay.Lactate dehydrogenase(LDH)release was measured by LDH assay kit.SH-SY5Y cells were treated with CTX(0,1,5,10 and 20 mmol·L^(-1))and 4-HC(0,1,5,10 and 20μmol·L^(-1))for 48 h before cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine(EdU)staining assay.Immunofluorescence was employed to assess the levels of the DNA double-strand break markerγ-H2AX and to evaluate changes in mitochondrial membrane potential.SH-SY5Y cells were treated with CTX(0,1,5 and 10 mmol·L^(-1))and 4-HC(0,1,5 and 10μmol·L^(-1))for 48 h,and the alterations in glycolysis and oxidative phosphorylation levels were analyzed using the Seahorse XFe96 Analyzer.RESULTS Compared with the cell control group,cell confluence and cell viability were significantly reduced in the CTX and 4-HC groups(P<0.01),and the half-maximal inhibitory concentrations(IC50)for CTX and 4-HC were 4.44 mmol·L^(-1) and 4.78μmol·L^(-1),respectively.The release rate of LDH was signif⁃icantly increased while the percentage of EdU+cells was significantly reduced in the CTX and 4-HC groups(P<0.01).The percentage ofγ-H2AX+cells was significantly increased and mitochondrial membrane potential significantly decreased in the CTX and 4-HC group(P<0.05).Treatment with CTX and 4-HC resulted in reduced levels of maximum glycolytic capacity,glycolytic reserve,maximal respi⁃ration,and ATP production(P<0.05).CONCLUSION CTX and 4-HC exert significant cytotoxic effects on SH-SY5Y cells by disrupting cell membrane structure,impeding cell proliferation,and reducing cell viability.The mechanisms underlying these effects may involve intracellular DNA damage,disturbance of energy metabolism and mitochondrial dysfunction.
基金financially supported by the Science and Technology Plan Project of Guangzhou (No. 202102010171)National Natural Science Foundation Cultivation Project of the Third Affiliated Hospital of Sun Yat-sen University (No. 2020GZRPYMS11)+2 种基金Natural Science Foundation of Guangdong Province (No. 2018A030313641)Natural Science Foundation of Guangdong Province (No. 2016A030313848)Science and Technology Plan Project of Guangzhou (No. 201704020175)。
文摘Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.
基金Supported by Joint Funding of Yunnan Ministry of Science and Technology,No.2019FF002-048and Beijing Heathco Clinical Oncology Research Foundation,No.Y-Q201802-048.
文摘BACKGROUND Parthenolide(PTL),a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium,exhibits various biological effects by targeting NF-kB,STAT3,and other pathways.It has emerged as a promising adjunct therapy for multiple malignancies.AIM To evaluate the in vitro and in vivo effect of PTL on cyclophosphamide(CTX)metronomic chemotherapy.METHODS The cytotoxicity of PTL and CTX on Lewis lung cancer cells(LLC cells)was assessed by measuring cell activity and apoptosis.The anti-tumor efficiency was evaluated using a tumor xenograft mice model,and the survival of mice and tumor volume were monitored.Additionally,the collected tumor tissues were analyzed for tumor microenvironment indicators and inflammatory factors.RESULTS In vitro,PTL demonstrated a synergistic effect with CTX in inhibiting the growth of LLC cells and promoting apoptosis.In vivo,metronomic chemotherapy com-bined with PTL and CTX improved the survival rate of tumor-bearing mice and reduced tumor growth rate.Furthermore,metronomic chemotherapy combined with PTL and CTX reduced NF-κB activation and improved the tumor immune microenvironment by decreasing tumor angiogenesis,reducing Transforming growth factorβ,andα-SMA positive cells.CONCLUSION PTL is an efficient compound that enhances the metronomic chemotherapy effects of CTX both in vitro and in vivo,suggesting its potential as a supplementary therapeutic strategy in metronomic chemotherapy to improve the chemotherapy effects.
基金supported by grants from the National Natural Science Foundation of China(21566024)。
文摘The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.
基金Supported by Beijing Municipal Administration of Hospitals’Ascent Plan,No.DFL20180701and Beijing Municipal Grant for Medical Talents Group on Peritoneal Surface Oncology,No.2017400003235J007。
文摘BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.
文摘Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.
基金Supported by the 211 Project of Jinan Universitythe Team Project of Natural Science Foundation of Guangdong Province (8351063201000003)+3 种基金the Popular Science Foundation of Science & Technology Bureau of Guangzhou City (2008KP055)the Natural Science Foundation of Guangdong Province (06025198)the Jinan University Natural Science Foundation (51204017)the Science and Technology Innovation Project for Undergraduates (cx08120)
文摘An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route that could cause stable thrombocytopenia. A suitable drug dosage that could induce thrombocytopenia in mouse efficiently with the definite administration route was then investigated. BALB/c mice were randomly divided into Normal, Model A and Model B groups. To Model A, 200 mg/kg of cyclophosphamide was given by vena caudalis injection as first dose and 30 mg/kg as maintenance dose by intraperitoneal injection at the following 6 days. To Model B, 150 mg/kg of cyclophosphamide was given by subcutaneous injection once a day for consecutive 3 days. All groups were under investigation for 15 days. The result suggested that a decrease in the number of blood platelets of Model B at the 7th day were significantly than that of Normal. Other platelet related indices like platelet distribution width, mean platelet volume and platelet-large cell ratio of Model B increased significantly in comparison with those of Normal group. The platelets count was reduced but fluctuated greatly, and more than half of the mice died in Model A. Therefore, subcutaneous injection of cyclophosphamide for 3 days was used for the cyclophosphamide dosage test. BALB/c mice were randomly divided into Normal, cyclophosphamide low dose （100 mg/kg）, medium dose （120 mg/kg） and high dose （140 mg/kg） groups. All groups were under investigation for 11 days. Though all 3 dosages successfully initiated thrombocytopenia as the platelets number dropped at the 7th day, the low dose was considered to be a suitable one that was of high efficacy and low toxicity. Thus, BALB/c mice challenged by subcutaneous injection of cyclophosphamide 100 mg/kg per day for 3 consecutive day is one simple, feasible and stable mouse thrombocytopenia model that could be used for pharmacodynamic test of the drugs which are supposed to have platelets increasing effect.
文摘The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated with cyclophosphamide (CY) 300 mg/kg once alone was 13.3 ± 7.2d(n=7) however,average survival time of mice treated with CY 300 mg/kg in com-bination with PAP-1 10 mg/kg,3 times/wk was 36.7± 16.4d(n=7,P<0.01).PAP-1,ip had benefi-cial effect on the recovery of the CY induced decrease of peripheral leukocyte number,and the nu-cleated bone marrow cell(BMC)number and[3￣H]TdR uptaken by BMC induced by rmGM-CSF in S180 bearing mice treated with CY,In mice,after the first ip treatment with CY 100 mg/kg on d7,the peripheral leukocyte number decreased on d9 and recovered to normal level about d13 to d15. Such recovery was accelerated by administrating PAP-1,10mg/kg, 3 times/wk.A significant in-crease of the activity to form colony in spleen(colony-forming unit in spleen, CFU-S_8, CUF-S12) in mice irradiated with 550 rad 6O￣Co γ-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with PAP-1,10mg/kg,3 times/wk, ip were observed.After PAP-1,10 mg/kg,ip once,a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor(CSF) were also confirmed.The types of CSF in serum were M-CSF and other hematopoietic growth factors,which were confirmed by using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of PAP-1 on hematopoiesis may be related to its activityinducing CSFs and other hematopoietic growth factors and warrant further evaluation of its use-fulness.
基金The authors gratefully acknowledge the financial assistance from the Major Research Project(Project No.F-3/50/99 dated 3l-3-99)provided by the University Grants Commission(UGC),New Delhi,India
文摘Aim:To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate the protective effect of ascorbic acid.Methods:The testicular△^(5),3β-hydroxysteroid dehydrogenase(HSD),17β-HSD,peroxidase and catalase activities along with the levels of malondialdehyde(MDA)and conjugated dienes in testicular tissue were measured for the evaluation of testicular oxidative stress.The plasma testosterone(T)level was measured by immunoassay.Various germ cells at stageⅦof spermatogenic cycle were quantified from testicular stained sections.Results:Cyclophosphamide treatment results in a significant inhibition in the testicular△^(5),3β-HSD and 17β-HSD activities,a decrease in plasma T level and a diminution in the counts of various germ cells.Moreover,this treatment was also associated with a significant inhibition of the peroxidase and catalase activities along with high levels of MDA and conjugated dienes in the testis.All these changes were reversed by ascorbic acid co-administration.Conclusion:Cyclophosphamide treatment at the dosage used caused testicular gametogenic and androgenic disorders as well as induced testicular oxidative stress that can be reversed by ascorbic acid co-administration.
基金Cooperative Research Program for Agriculture Science and Technology Development(Project No.PJ01321501) Rural Development Administration,Republic of Korea
文摘Objective: To investigate the effects of a herb complex extract(HCE) prepared from Cornus officinalis Sieb. Et Zucc., Eriobotrya japonica Lindley, and olive leaves on immune response of mouse spleen NK cells in vitro and in vivo analysis. Methods: The activity of natural killer(NK) cells was measured in splenocytes and YAC-1 cells. Mice were immunosuppressed using cyclophosphamide(5 mg/kg body weight). Three different doses of HCE(200, 400, and 800 mg/kg body weight) and red ginseng extract(800 mg/kg body weight) which was used as standard immunomodulatory herb were administered orally for 4 weeks. The body weight, dietary, water intake, organs(liver, thymus, and spleen) weight, completed blood count, and cytokines(tumor necrosis factor alpha, interferon gamma, and interleukin-2) production was measured. Results: At the maximum concentration of HCE, the activity of NK cells was increased by 48.5%. HCE increased liver, spleen, and thymus weights without altering numbers of white blood cells, lymphocytes, and neutrophils in a cyclophosphamide-induced immunosuppression rat model. However, HCE recovered the inhibited cytokine expression; HCE(800 mg/kg) increased cytokines levels. The results indicate the immune enhancement potential of this HCE. Conclusion: The HCE enhances immunity by increasing NK cell activity, regulating cytokine levels, and maintaining spleen weight. Therefore, it may be used as a potential immunity enhancer.
基金supported by All India Council for Technical Education,New Delhi,India for providing JRF awarded grants(No.355118293)(GPAT-Exam)for the completion of M.Pharm research project
文摘Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d at 150 mg/kg body weight through intraperitoneal route in rat model. Nephroprotective activity of Murraya koenigii(M. koenigii) extract(100 mg/kg and 200 mg/kg in intraperitoneal route) was measured, including nephrological source, oxidative stress parameters like superoxide dismutase, glutathione, the lipid peroxide and in vivo assay like blood urea nitrogen, creatinine were determined and analyzed by One way analysis of variance followed by Tukey's test. Results: The study result showed that important phytochemicals such as carbohydrates, flavonoids, tannin, alkaloids, glycosides, protein and steroids were found to be present in the extract of M. koenigii. The renal function markers like blood urea nitrogen and ceatinine level were found to be decreased significantly by M. koenigii extract treatment. A significant difference was found to be at P<0.01. Conclusions: The present study reveals the protective role of M. koenigii extract against Cyclophosphamide induced nephrotoxicity.
基金This research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors.
文摘Cyclophosphamide(CYL)is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia.Though,CYL has been documented to induce lung toxicity.Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns(DAMPs).Sesamol(SES)is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet.This study aims to inves-tigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells,WI-38 cell line,without suppressing its efficacy.Cells were pretreated with SES and/or CYL for 24 h,then cell viability was estimated by MTS and trypan blue assays.The mode of cell death was determined by AO/EB staining.Additionally,caspase-3 level,oxidative stress,and inflammatory markers were evaluated by colorimetric and ELISA techniques.qRT-PCR was performed to evaluate RAGE,NF-κB,and Beclin-1 mRNA-expression.CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling,which were all attenuated after pretreatment with SES.Thus,we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling,which is a natural safe therapeutic option against CYL toxicities.
