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Asian Journal of Andrology 2002年第3期4卷 201-207页

作者： Ujjal Baran Das Mousumi Mallick Jogendra Mohan Debnath Debidas Ghosh Reproductive Endocrinology and Family Welfare Research Unit Department of Human Physiology with Community HealthVidyasagar UniversityMidnapore-721102West BengalIndia.

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 ***: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 *** plasma testosterone(T)level was measured by *** germ cells at stageⅦof spermatogenic cycle were quantified from testicular stained ***: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 ***,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 *** these changes were reversed by ascorbic acid ***: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.

关键词： cyclophosphamide androgenesis gametogenesis oxidative stress free radicals ascorbic acid catalase peroxidase testosterone

cyclophosphamide abrogates the expansion of CD4^(+)Foxp3^(+) regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas

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Cancer Biology & Medicine 2021年第4期18卷 1010-1020页

作者： Ping Li Fengyang Chen Jingbin Zheng Yang Yang Yuan Li Yifei Wang Xin Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical ScienceUniversity of MacaoMacao 999078China

Objective:Promotion of the proliferative expansion of CD4^(+)Foxp3^(+)regulatory T cells(Tregs)is one of the side effects that limits the use of bleomycin(BLM)in the treatment of *** this study,we examined the hypothesis that cyclophosphamide(CY),a chemotherapeutic agent with the capacity to eliminate tumor infiltrating Tregs,abrogated BLM-induced expansion of Tregs and consequently resulted in a better anti-tumor ***:The in vitro effects of BLM,with or without mafosfamide(MAF,the active metabolite of CY),on both TGF-β-induced differentiation of Tregs(iTregs),and TNF-induced expansion of naturally occurring Tregs(nTregs)were *** in vivo effect of low doses of BLM and CY on tumor-infiltrating Tregs,as well as on the growth of mouse B16-F10 melanomas,was also ***:In vitro treatment with BLM promoted the differentiation of iTregs,as well as TNF-induced expansion of *** effects of BLM were completely abrogated by ***,in the mouse B16-F10 melanoma model,treatment with low doses of BLM increased the number of tumor-infiltrating Tregs,and this effect of BLM was also abrogated by ***,combination therapy with low doses of BLM and CY showed synergistic anti-tumor ***:CY abrogated the effect of BLM on the expansion of *** combination of these 2 chemotherapeutic agents may represent a safer and more effective therapy in the treatment of cancer patients,and thus merits future clinical evaluation.

关键词： Bleomycin cyclophosphamide tumor necrosis factor Tregs TNFR2

cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum(Asteraceae) in male Wistar rats

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Journal of Integrative Medicine 2019年第5期17卷 366-373页

作者： Pierre Watcho Ismaelle Rosine Mpeck Patrick Brice Deeh Defo Modeste Wankeu-Nya Esther Ngadjui Georges Romeo Bonsou Fozin Pierre Kamtchouing Albert Kamanyi Animal Physiology and Phytopharmacology Laboratory University of DschangP.O. BOX 67DschangCameroon Department of Animal Organisms Biology University of DoualaP.O. BOX 24157DoualaCameroon Department of Animal Biology and Physiology University of YaoundeP.O. BOX 812YaoundeCameroon

Objective: cyclophosphamide(CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract(AE) and methanolic extract(ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male ***: In addition to a normal control(group 1), drugs or vehicles were administered orally to seven groups(n = 5) of rats that had already received 4-weeks of pre-treatment with CP(5 mg/[kgád], per oral administration);group 2 received CP + distilled water(10 m L/[kgád]);group 3 received CP + 5% tween 80(10 m L/[kgád]);group 4 received CP + clomiphene citrate(0.25 mg/[kgád]);groups 5 and 6 received CP + AE(50 and 100 mg/[kgád]) and groups 7 and 8 received CP + ME(50 and 100 mg/[kgád]). Animals were sacrificed on day 15, and body and sexual organ weights, sperm characteristics, testosterone level and testicular histology were ***: The CP-treated group showed a significant reduction(P < 0.001) in the body and seminal vesicle weights, testosterone level, sperm count, sperm motility and sperm viability, but elevated(P < 0.001)sperm morphological abnormalities and testicular structure alterations, compared to the control ***, these detrimental effects of CP were reversed by treatment with H. odoratissimum *** instance, both extracts and all doses of H. odoratissimum significantly increased the sperm count(P < 0.001), sperm motility(AE, 50 mg/kg, P < 0.05;ME, 50 and 100 mg/kg, P < 0.05) and sperm viability(AE, 50 mg/kg, P < 0.001;ME, 50 and 100 mg/kg, P < 0.001) compared to the CP group. H. odoratissimum also improved plasmatic and intratesticular testosterone levels and prevented histological alterations of the ***: H. odoratissimum might be considered as an alternative drug to alleviate/prevent reproductive damage in cancer patients receiving CP chemotherapy.

关键词： Helichrysum odoratissimum cyclophosphamide Reproductive toxicity Rat

Nephroprotective effect of Murraya koenigii on cyclophosphamide induced nephrotoxicity in rats

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Asian Pacific Journal of Tropical Medicine 2017年第8期10卷 869-873页

作者： Patel Mahipal Pawar Rajesh Singh Pharmacognosy Phytochemistry&Ethnophamacology LaboratoryVNS Group of InstitutionFaculty of PharmacyVNS CampusVidya ViharNeelbudBhopalMadhya Pradesh462044India

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 Pcyclophosphamide induced nephrotoxicity.

关键词： Nephrotoxicity Murraya koenigii cyclophosphamide

cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis:A case report

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World Journal of Gastroenterology 2021年第20期27卷 2657-2663页

作者： Hiroko Sato Tsuyoshi Shirai Hiroshi Fujii Tomonori Ishii Hideo Harigae Department of Hematology and Rheumatology Tohoku University Graduate School of MedicineSendai 9808574Japan

BACKGROUND Although cyclophosphamide(CPA)is the key drug for the treatment of autoimmune diseases including vasculitides,it has some well-known adverse effects,such as myelosuppression,hemorrhagic cystitis,infertility,and ***,CPA-associated severe enteritis is a rare adverse effect,and only one case with a lethal clinical course has been ***,the appropriate management of patients with CPA-associated severe enteritis is *** SUMMARY We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear,lung,and,kidney with positive myeloperoxidase-antineutrophil cytoplasmic *** received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/*** days after the second course of intravenous CPA,she developed nausea,vomiting,and diarrhea,and was admitted to the *** testing revealed hypoalbuminemia,suggesting proteinlosing *** tomography revealed wall thickening of the stomach,small intestine,and colon with contrast enhancement on the lumen *** and immunosuppressive therapy were not effective,and the patient’s enteritis did not improve for>4 *** her condition became seriously exhausted,corticosteroids were tapered and supportive therapies including intravenous hyperalimentation,replenishment of albumin and gamma globulin,plasma exchange,and infection control were *** supportive therapies improved her condition,and her enteritis gradually *** was finally discharged 7 mo *** Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.

关键词： Antineutrophil cytoplasmic antibody cyclophosphamide Enteritis Granulomatosis with polyangiitis Plasma exchange Vasculitis Case report

cyclophosphamide loaded thermo-responsive hydrogel system synergize with a hydrogel cancer vaccine to amplify cancer immunotherapy in a prime-boost manner

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Bioactive Materials 2021年第10期6卷 3036-3048页

作者： Fan Yang Kun Shi Ying Hao Yanpeng Jia Qingya Liu Yu Chen Meng Pan Liping Yuan Yongyang Yu Zhiyong Qian State Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center for BiotherapyWest China HospitalSichuan UniversityChengdu610041PR China Department of Gastrointestinal Surgery West China HospitalSichuan UniversityChengdu610041PR China

Although neoantigen-based cancer vaccines show great potential in cancer immunotherapy due to their ability to induce effective and long-lasting anti-tumor immunity,their development is hindered by the limitations of neoantigens identification,low immunogenicity,and weak immune ***(CTX)not only directly kills tumors but also causes immunogenic cell death,providing a promising source of antigens for cancer ***,a combined immunotherapy strategy based on temperature-sensitive PLEL hydrogel is ***,CTX-loaded hydrogel is injected intratumorally into CT26 bearing mice to prime anti-tumor immunity,and then 3 days later,PLEL hydrogels loaded with CpG and tumor lysates are subcutaneously injected into both groins to further promote anti-tumor immune *** results confirm that this combined strategy reduces the toxicity of CTX,and produces the cytotoxic T lymphocyte response to effectively inhibit tumor growth,prolong survival,and significantly improve the tumor cure ***,a long-lasting immune memory response is observed in the *** 90%of the cured mice survive for at least 60 days after being re-inoculated with tumors,and the distant tumor growth is also well ***,this PLEL-based combination therapy may provide a promising reference for the clinical promotion of chemotherapy combined with cancer vaccines.

关键词： Immunotherapy Thermo-responsive hydrogels Immunogenic cell death Cancer vaccine cyclophosphamide

cyclophosphamide-associated enteritis: A rare association with severe enteritis

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World Journal of Gastroenterology 2016年第39期22卷 8844-8848页

作者： Linda S Yang Karla Cameron Tim Papaluca Chamara Basnayake Louise Jackett Penelope McKelvie David Goodman Barbara Demediuk Sally J Bell Alexander J Thompson Department of Gastroenterology St. Vincent’s HospitalFitzroy Department of Pathology St. Vincent’s HospitalFitzroy Department of Nephrology St. Vincent’s HospitalFitzroy

cyclophosphamide is a potent cytotoxic agent used in many clinical settings. The main risks of cyclophosphamide therapy include hematological disorders, infertility, hemorrhagic cystitis and malignancies. Gastrointestinal side effects reported to date are often non-specific and not severe. We present the first case of a fatal small bowel enteritis and pan-colitis which appears to be associated with cyclophosphamide. We aim to raise the readers' awareness of this significant adverse event to facilitate clinical suspicion and early recognition in potential future cases.

关键词： Enteritis Colitis cyclophosphamide Small bowel Pan-colitis

Ganoderma Lucidum Spore Oil enhances the effect of cyclophosphamide via inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice

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Journal of Traditional Chinese Medicine 2024年第4期44卷 652-659页

作者： JIANG Zhaojian CAI Hongfei YUAN Cheng CAO Lin XU Wendong HAN Yaming ZHANG Qin LI Jing WANG Qin LIU Juyan Guangzhou HanFang Pharmaceutical Company Limited National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug InnovationGuangdong Provincial Key Laboratory of Medicinal LipidsGuangzhou 510240China Zhongshan Medical College Sun Yat-sen UniversityGuangzhou 510080China Guangzhou Pharmaceutical Holdings Limited Guangzhou 510130China National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation Guangzhou 510240China

OBJECTIVE:To investigate the effect of Ganoderma Lucidum Spore Oil(GLSO)on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide(CTX),and explore the underlying ***:Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals,and Kaplan-Meier survival analysis was used to analyze the life *** biochemical examination was used to determine the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea(UREA)and creatinine(CRE).Western blot analysis was performed to detect Programmed Death-1(PD-1),Programmed Death Ligand 1(PD-L1),Janus Kinase 2(JAK2),phosphorylated Signal Transducer and Activator of Transcription 3(p-STAT3),and Signal Transducer and Activator of Transcription 3(STAT3)***:GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with ***,GLSO increased the thymus index and showed no obvious toxicity to liver functions of *** also decreased the level of UREA in H22 tumor-bearing mice treated with ***,GLSO could inhibit the expression of PD-1 in spleen,which was independent of JAK2 expression and STAT3 ***,GLSO did not affect the expression of PD-L1,JAK2,and p-STAT3 in tumor ***:GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumorbearing mice,while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in ***,these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.

关键词： carcinoma,hepatocellular cyclophosphamide survival programmed cell death 1 receptor Ganoderma Lucidum SporeOil

cyclophosphamide,fluorouracil and low-dose interleukin-2 and salvage combination chemotherapy in advanced cutaneous squamous cell carcinoma

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 168-176页

作者： Giovanni Lo Re Paolo Doretto Francesco Lo Re Fabio Matrone Anna Ermacora Wally Marus Maria Antonietta Pizzichetta Sandro Sulfaro Medical Oncology and Immune-Related Tumors Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAvianoPN 33081Italy Clinical Pathology AAS5 PordenonesePN 33170Italy Pharmacology and Clinical Toxicology University of MilanMilanMI 20129Italy Radiotherapy Unit Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAvianoPN 33081Italy Internal Medicine AAS5 PordenonesePN 33170Italy Pathology AAS5 PordenonesePN 33170Italy Medical oncology and Cancer prevention Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAvianoPN 33081Italy

A 70-year-old female with metastatic cutaneous squamous cell carcinoma(cSCC)and low-grade non-Hodgkin’s lymphoma,not amenable to cisplatin combination therapy,was treated with cyclophoshamide(Cyc)-fluorouracil(FU)-interleukin-2(IL-2)in light of high tumor immunogenicity and the potential activity of this *** 300 mg/m^(2)and FU 500 mg/m^(2)intravenously on day 1 and IL-24.5 MIU/day on days 3-6 and 17-20 subcutaneously every 4 weeks;Carboplatin(C)AUC 2 and paclitaxel(P)85 mg/m^(2)on days 1,8 and 15±capecitabine(Cape)every 4 *** partial remission(PR)of lung metastases and local control with two cycles of first therapy followed by PR with five cycles of CP±Cape,right mastectomy was performed with evidence of viable ***,the patient underwent 3 cycles of chlorambucil and is alive after 13 months of *** and activity of chemo-immunotherapy and salvage treatment can be achieved in cSCC.

关键词： Cutaneous squamous cell carcinoma cyclophosphamide fluorouracil interleukin-2 regulatory T cells myeloid-derived suppressor cells

Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways

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Asian Journal of Andrology 2021年第4期23卷 386-391页

作者： Xiao-Bin Guo Jia-Wen Zhai Hui Xia Jian-Kun Yang Jun-Hao Zhou Wen-Bin Guo Cheng Yang Ming Xia Kang-Yi Xue Cun-Dong Liu Qi-Zhao Zhou Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China

Spermatogenic dysfunction caused by cyclophosphamide(CP)chemotherapy has seriously influenced the life quality of ***,treatments for CP-induced testicular spermatogenic dysfunction are limited,and the molecular mechanisms are not fully *** the first time,here,we explored the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-exos)on CP-induced testicular spermatogenic dysfunction in vitro and in ***-exos could be taken up by spermatogonia(GC1-spg cells).CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses,and then,cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)*** addition,photophosphorylation of extracellular-regulated kinase(ERK),p38 mitogen-activated protein kinase(p38MAPK),and protein kinase B(AKT)proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow *** with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg *** levels of ERK,AKT,and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos,indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling *** experiments in vivo,CP-treated rats received BMSC-exos by injection into the tail vein,and testis morphology was compared between treated and control *** showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured ***,BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling *** findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.

关键词： bone marrow mesenchymal stem cells cyclophosphamide exosomes reproductive toxicity