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Sample records for metronomic cyclophosphamide therapy

  1. Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy

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    Anis Bandyopadhyay

    2014-01-01

    Full Text Available Primary adenocarcinoma of duodenum is a very rare tumour with a prevalence of only 0.3 to 1% of among all the tumours of gastrointestinal tracts. Localised tumours, if resected have good prognosis but those with metastates entails a poor prognosis, where generally palliation may be the only feasible option. Low dose continous cytotoxic treatment or metronomic chemotherapy prevents neoangiogenesis and chemoresistance thereby, provides excellent symptom relief and palliation in many advanced heavily pretreated solid malignancies. It offers as an affordable, less toxic therapy with moderate to good efficacy. Here we report a case of a 52 year female who, presented with history of maleana, pallor and pedal edema for last 2 months. Her performance status was poor (KPS 40 and she had enlarged left supraclavicular lymph node, palpable liver and vague mass in paraumbilical region. Upper GI endoscopy revealed large ulceroproliferative growth in the D2 segment and HPE showed moderately differentiated adenocarcinoma. CT scan revealed paratracheal and retroperitoneal lymphadenopathy and bone scan revealed vertebral metastasis. Patient received oral cyclophosphamide and hematinic and vitamin support, along with radiation to spine. There was near complete clinical response, and progression free period of about 32 weeks. Thus, single agent cyclophosphamide in the present case provided near total clinical response and prolonged period of freedom from disease progression with excellent palliation of symptoms. Hence in patient of advanced and metastatic small bowel cancer, with poor performance status metronomic therapy with single agent cyclophosphamide may provide viable option both for treatment and palliation.

  2. Metronomic therapy for gynecologic cancers

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    Wen-Hsiang Su

    2012-06-01

    Full Text Available Systemic administration of cytotoxic drugs is the primary treatment strategy for patients with advanced cancer. The effect of cytotoxic drugs is to disrupt the DNA of the cells, rendering them unable to replicate and finally killing them; therefore, the fundamental role of a wide range of treatment regimens is typically to induce lethal toxicity in the largest possible number of cancer cells. However, these cytotoxic drugs also damage the normal cells of the host, which limits the dose of the cytotoxic drug. Thus, cancer patients are usually treated at or near the maximum tolerated dose with the implicit intent of eradicating (curing the tumor after balancing between efficacy in tumor killing and toxicity to the host. With significantly improving patient care, most efforts are focused on the corollary, “The higher the dose, the better.” However, the concept that cancer could be considered as a chronic disease and might be treated like other chronic diseases to achieve a status called tumor dormancy is gaining popularity. In addition, there has been increasing interest in putting more effort into administering cytotoxic drugs on a more continuous basis, with a much shorter break period, or none at all, and generally lower doses of various cytotoxic drugs or combinations with other newer, targeted therapies, like anti-angiogenesis agents. This practice has come to be known as metronomic chemotherapy. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor type applications. This review will explore recent studies that have addressed the mechanism of metronomic chemotherapy in the management of various tumors, especially gynecologic cancers.

  3. Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide

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    Ellebaek, Eva; Engell-Noerregaard, Lotte; Iversen, Trine Zeeberg

    2012-01-01

    Dendritic cells (DC) are the most potent antigen presenting cells and have proven effective in stimulation of specific immune responses in vivo. Competing immune inhibition could limit the clinical efficacy of DC vaccination. In this phase II trial, metronomic Cyclophosphamide and a Cox-2 inhibit...

  4. VEGFR2 heterogeneity and response to anti-angiogenic low dose metronomic cyclophosphamide treatment

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    Skowronski Karolina

    2010-12-01

    stabilization of colorectal microvessels, but no such change in melanoma vessels. Conclusions Overall, our study suggests that while heterogeneous expression of VEGFR2 is a feature of human tumors, it may not affect response to low dose metronomic cyclophosphamide treatment and possibly other anti-angiogenic approaches. It remains to be seen whether this heterogeneity is partly responsible for the variable clinical success seen to date with targeted anti-VEGFR2 therapy.

  5. Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8(+) T-cell responses and immune memory.

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    Wu, Junjie; Waxman, David J

    2015-04-01

    Cancer chemotherapy using cytotoxic drugs can induce immunogenic tumor cell death; however, dosing regimens and schedules that enable single-agent chemotherapy to induce adaptive immune-dependent ablation of large, established tumors with activation of long-term immune memory have not been identified. Here, we investigate this issue in a syngeneic, implanted GL261 glioma model in immune-competent mice given cyclophosphamide on a 6-day repeating metronomic schedule. Two cycles of metronomic cyclophosphamide treatment induced sustained upregulation of tumor-associated CD8(+) cytotoxic T lymphocyte (CTL) cells, natural killer (NK) cells, macrophages, and other immune cells. Expression of CTL- and NK-cell-shared effectors peaked on Day 6, and then declined by Day 9 after the second cyclophosphamide injection and correlated inversely with the expression of the regulatory T cell (Treg) marker Foxp3. Sustained tumor regression leading to tumor ablation was achieved after several cyclophosphamide treatment cycles. Tumor ablation required CD8(+) T cells, as shown by immunodepletion studies, and was associated with immunity to re-challenge with GL261 glioma cells, but not B16-F10 melanoma or Lewis lung carcinoma cells. Rejection of GL261 tumor re-challenge was associated with elevated CTLs in blood and increased CTL infiltration in tumors, consistent with the induction of long-term, specific CD8(+) T-cell anti-GL261 tumor memory. Co-depletion of CD8(+) T cells and NK cells did not inhibit tumor regression beyond CD8(+) T-cell depletion alone, suggesting that the metronomic cyclophosphamide-activated NK cells function via CD8a(+) T cells. Taken together, these findings provide proof-of-concept that single-agent chemotherapy delivered on an optimized metronomic schedule can eradicate large, established tumors and induce long-term immune memory.

  6. mRNA-transfected dendritic cell vaccine in combination with metronomic cyclophosphamide as treatment for patients with advanced malignant melanoma

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    Borch, Troels Holz; Engell-Noerregaard, Lotte; Zeeberg Iversen, Trine;

    2016-01-01

    INTRODUCTION: Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs......). A metronomic regimen of cyclophosphamide (mCy) has been shown to selectively deplete Tregs. To test this in a clinical setting, we conducted a phase I trial to evaluate the feasibility and safety of vaccination with DCs transfected with mRNA in combination with mCy in patients with metastatic malignant......th vaccines. Immune monitoring consisted of IFNγ ELISpot assay, proliferation assay, and flow cytometry for enumeration of immune cell subsets. RESULTS: Toxicity was manageable. Eighteen patients were evaluable after six cycles. Of these, nine patients had progressive disease as best response...

  7. Pulse cyclophosphamide therapy for inflammatory bowel disease

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    Zsolt Barta; László Tóth; Margit Zeher

    2006-01-01

    AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD).METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800mg) per month.RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d).CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.

  8. Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy.

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    Nygaard, Randi; Kivivuori, Sanna-Maria

    2012-03-01

    The prognosis of recurrent medulloblastoma is dismal, with a median survival of less than 1 year. Our patient was initially diagnosed with high-risk medulloblastoma when he was 14 years old. He had a recurrence 18 months after the end of therapy. Recurrence treatment consisted of 13 intrathecal applications of liposomal cytarabine over an 18-month period, and oral metronomic antiangiogenic therapy with thalidomide, celecoxib, and etoposide. Side effects from the intrathecal treatment were most likely related to arachnoiditis despite prolonged prophylaxis with steroids. He also developed partial hearing loss. Neutropenia was the main side effect of the metronomic therapy. He remains alive, with a good quality of life and without evidence of disease 34 months from the start of recurrence therapy. This combination of local antineoplastic and systemic antiangiogenic therapy seems to be promising for recurrent medulloblastoma. However, more patients and standardized protocols are needed to verify the benefit of this combination therapy and to define the correct duration of treatment.

  9. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

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    Jorge L. Soriano

    2011-01-01

    Full Text Available The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily, in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum, followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD was 18,43 months (12,20–24,10 months, being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

  10. Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy – A single-arm phase II study

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    Hanan Shawky

    2014-12-01

    Conclusion: One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy.

  11. Cyclophosphamide

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    ... lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML, ANLL), and acute lymphoblastic leukemia (ALL). It ... a reliable method of birth control to prevent pregnancy. Cyclophosphamide may harm the fetus.if you are ...

  12. Clinical overview of metronomic chemotherapy in breast cancer.

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    Munzone, Elisabetta; Colleoni, Marco

    2015-11-01

    Over 15 years ago, low-dose metronomic chemotherapy was shown to induce disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy. Good response rates have been seen in heavily pre-treated patients for whom limited treatment options are available. Most patients prefer oral therapy and metronomic chemotherapy is a convenient alternative in patients with advanced-stage disease in which minimal toxicity and good tumour control are the overall aims of treatment. The addition of metronomic protocols to standard neoadjuvant chemotherapy regimens has produced promising pathological complete response rates. Ongoing trials including the SYSUCC-001 trial in patients with triple-negative breast cancer and the IBCSG 22-00 trial that is assessing a cyclophosphamide-methotrexate maintenance regimen after standard adjuvant therapy in hormone receptor-negative disease, will clarify the value of adding this approach to conventional therapies. The low cost associated with metronomic chemotherapy represents an opportunity for the utilization of this treatment option, especially in developing countries, and poses a challenge for the launch of large trials sponsored by industry. Using breast cancer as the principal example, we discuss the key clinical advances in this area, including new trial design, appropriate patient and end point selection, as well as the evolving rationale for metronomic chemotherapy combinations.

  13. Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

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    Cheryl A London

    Full Text Available We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI and overall survival (OS in dogs with appendicular osteosarcoma (OSA following amputation and carboplatin chemotherapy.This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126 received carboplatin chemotherapy (4 doses following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8 were removed from the study for therapy-associated adverse events compared to control dogs (n = 1. The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274; the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08. The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.The addition of toceranib to metronomic

  14. Dexamethasone-cyclophosphamide pulse therapy in systemic lupus erythematosus

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    Dhabhai Ravindra

    2005-01-01

    Full Text Available BACKGROUND AND AIMS: Therapy systemic lupus erythematosus (SLE has been generally discouraging. Methyl-prednisolone pulse therapy has been used for various connective tissue disorders. We used intravenous dexamethasone cyclophosphamide pulse therapy to treat SLE. METHODS: Fourteen patients (10 females and 4 males between the age of 15-48 years with definite or classical clinical criteria laid by American Rheumatism Association criteria were treated by Dexamethasone-Cyclophosphamide pulse (DCP therapy at our center. RESULTS: It was possible to induce a complete clinical remission with DCP therapy in most of the patients thereby offering them life free from disease and drugs. The side effects commonly observed with conventional daily dose regimen of corticosteroids were not present or were mild. CONCLUSIONS: Almost all patients had good response after 3-4 pulses to allow them a normal life style. Fever, malar rash and oral ulceration responded early but photosensitivity, discoid rash, alopecia and joint pains took some more time.

  15. Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: A prospective pilot study

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    Akhil Kapoor

    2016-01-01

    Full Text Available Introduction: Acute myeloid leukemia (AML in elderly patients differs biologically from that in younger patients and is known to have unfavorable chromosomal rearrangements, higher resistance, and lower tolerance to chemotherapy. In such circumstances, instead of giving full-blown chemotherapy, palliative metronomic chemotherapy (MCT could be a treatment option. Patients and Methods: We performed a prospective pilot study of old AML patients (age >60 years not amenable to curative treatment. Thirty-two patients were enrolled into the study and were treated with daily oral 6-mercaptopurine 75 mg/m 2 . The following inclusion criteria were used: age >60 years, nonpromyelocytic AML, the absence of uncontrolled comorbidities, and patient not amenable to curative treatment. Overall survival (OS was calculated using Kaplan-Meier method and Cox regression analysis were used to calculate the hazards ratio of significant factors. Results: The median age of the patients was 69 years (range: 61-86 years with male: female ratio of 2.5:1. About 59.4% of patients had Eastern Cooperative Oncology Group performance status of 2 while rest had the status of 3. The median OS was 6 months (95% confidence interval [CI]: 4.4-7.6. Males had median OS of 7 months (95% CI: 5.4-8.6 versus females with OS of 3 months (95% CI: 1.5-4.4; P = 0.008. There was no survival difference on the basis of baseline hemoglobin or French-American-British class. There were no Grade 4 toxicities and no episode of febrile neutropenia. Conclusions: MCT with oral 6-mercaptopurine is an attractive treatment option in elderly AML patients who are not amenable to curative therapy with minimal toxicities.

  16. Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients

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    Faurschou, Mikkel; Sørensen, Inge Juul; Mellemkjaer, Lene

    2008-01-01

    To describe the incidence of malignancies in a cohort of Danish patients with Wegener's granulomatosis (WG) and to investigate the cancer risk associated with cyclophosphamide (CYC) -therapy in WG.......To describe the incidence of malignancies in a cohort of Danish patients with Wegener's granulomatosis (WG) and to investigate the cancer risk associated with cyclophosphamide (CYC) -therapy in WG....

  17. Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: A preliminary prospective randomized controlled study

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    Nisha V Parmar

    2013-01-01

    Full Text Available Background: Dexamethasone cyclophosphamide pulse (DCP therapy is an established mode of treatment for pemphigus in India. Aims: To assess the therapeutic benefit of additional DCPs (phase II, consolidation phase versus immediate oral cyclophosphamide, usually used in phase III (maintenance phase, after initial DCP therapy (phase I and to assess which laboratory test (DIF or ELISA will reflect the clinical relapse best. Methods: Nineteen newly recruited patients of pemphigus vulgaris (PV received monthly DCPs in phase I and were then randomized into two groups. Group A (10 patients received monthly DCPs for nine months and Group B (nine patients received only oral cyclophosphamide for nine months. Direct immunofluorescence (DIF and enzyme-linked immunosorbent assay (ELISA were tested before starting DCP regimen, and at 0,3,6,9 months after randomization. Results: Clinical relapse by the end of follow-up period occurred in only one patient in each group. In these cases, DIF became (again positive before the relapse. No statistically significant difference between the two groups was found at three, six and nine months by ELISA indices and DIF grading. Conclusion: Although the DCP regimen is the standard therapy for pemphigus in India, we found no difference in the clinical outcome between patients receiving nine DCPs in phase II and patients shifted directly from phase I to III. Periodic testing using DIF and Dsg ELISA were found to be useful to monitor disease activity and predict a relapse. Further large scale studies are required to assess if patients can be shifted directly from phase I to III and maintained only on oral cyclophosphamide.

  18. Fertility preservation in patients receiving cyclophosphamide therapy for renal disease.

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    Gajjar, Radha; Miller, Steven D; Meyers, Kevin E; Ginsberg, Jill P

    2015-07-01

    Cyclophosphamide continues to have an important role in the treatment of renal disease, including nephrotic syndrome and lupus nephritis, despite known complications of gonadotoxicity and potential infertility in both male and female patients. It is important that the physician recommending this therapy mitigates the effect of the drug on fertility by adhering to recommendations on dosing limits and offering fertility-preserving strategies. In addition to well-established methods, such as sperm banking and embryo cryopreservation, advances in reproductive technology have yielded strategies such as oocyte cryopreservation, resulting in more fertility-preserving options for the pediatric patient. Despite these advances, there continues to be a significant barrier to referral and access to sperm banks and fertility specialists. These issues are further complicated by ethical issues associated with the treatment of pediatric patients. In this review we explore the development of recommended dosing limits and include a discussion of the available fertility-preserving methods, strategies for increasing access to fertility specialists, and the ethical considerations facing the pediatric healthcare provider.

  19. Combination Therapy With Pulse Cyclophosphamide Plus Corticosteroids Improves Renal Outcome In Patients With Lupus Nephritis

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    H. Mansouri Torghabeh

    2005-08-01

    Full Text Available Background: The prognosis of SLE is int1uenced by the onset of glomerulonephtitis. Clinical ttials in lupus nephritis have demonstrated that cyclophosphamide therapy is the superior regimen in the management oflupus nephritis for preserving renal function.Objective:The purpose of this study is to define the outcome of renal function with bolus pu lses of cyclophosphamide and steroid according to our protocol and also to determine an appropriate pattern of treatment of lupus nephritis. Methods: In this open-label clinical triaL to evaluate the results, the short-term prognosis and the rate of complications of an immunosuppressive regimen with corticosteroids and cyclophosphamide, twenty-five patients with biopsy-proven lupus nephritis were studied. Treatment was structured in 4 phases: I Induction with bolus methylprednisolone and cyclophosphamide. 2 Maintenance with oral prednisolone for 4 weeks and monthly cyclophosphamide pulses for 6 months. 3 Tapeting with reduction of prednisolone by 10% each month and continuing cyclophosphamide every other month till one year and for the second year every 3 months. 4 Discontinuation with oral prednisolone slowly tapered to the least effective daily dose and cyclophosphamide discontinued after 2 yr of therapy. We defined primary outcome measures according to these criteria: renal function return to normal limits or become stable, regression of systemic and local inflammatory symptoms. urine protein excretion h1lling below 0.3 gr/ elL or by at least SOo/c. RBC cast disappearance, C3, C4, Hb, and ESR return to notmallimits. Result: Twenty-three patients wi th lupus nephritis completed our therapeutic protocol. Renal biopsy was perfonned in 22 cases and indicated type IV in 20 patients (95.2%, and type V in 2 patients. After an average of 4+ 1.95 months 22 patients achieved remission (95.65% and only one case remained non-responsive. She became pregnant in her fourth month of therapy. Significant

  20. Pemetrexed and cyclophosphamide combination therapy for the treatment of non-small cell lung cancer.

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    Li, Dong; He, Song

    2015-01-01

    Lung cancer is the leading cause of cancer-related mortality. This study was undertaken to investigate the efficacy and safety of adding regulatory T cell inhibitor cyclophosphamide to pemetrexed therapy for the second-line treatment of NSCLC with wild-type epidermal growth factor receptor (EGFR). A total of 70 patients were screened between March 2011 and December 2013, out of which 62 patients were enrolled in the study. Patients were randomized to receive 500 mg/m(2) pemetrexed in combination with 20 mg/kg cyclophosphamide in a 21 day cycle (n=30) or 500 mg/m(2) pemetrexed (n=32), and followed up for 30 months. Disease progression was observed in 23 patients in the pemetrexed plus cyclophosphamide arm and 27 patients in the pemetrexed monotherapy arm. Median progression-free survival was 3.6 months (95% confidence interval [CI], 1.3 to 5.9 months) in the pemetrexed plus cyclophosphamide arm and 2.2 months (95% CI, 1.3 to 3.1 months) in the pemetrexed monotherapy arm. The 6-month PFS rates were 22% (95% CI, 10 to 34) and 14.5% (95% CI, 6 to 23) in the pemetrexed plus cyclophosphamide arm and pemetrexed monotherapy arm, respectively. Median overall survival was 9.8 months for the pemetrexed combination therapy arm and 8.8 months for the pemetrexed arm, and the 1-year survival rates were 46% and 33%, respectively. The present study showed that pemetrexed in combination with low-dose cyclophosphamide may be a better treatment approach than pemetrexed monotherapy when considering second-line treatment for wild-type EGFR NSCLC.

  1. Metronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells.

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    Vives, Marta; Ginestà, Mireia M; Gracova, Kristina; Graupera, Mariona; Casanovas, Oriol; Capellà, Gabriel; Serrano, Teresa; Laquente, Berta; Viñals, Francesc

    2013-11-15

    In this article, the effectiveness of a multi-targeted chemo-switch (C-S) schedule that combines metronomic chemotherapy (MET) after treatment with the maximum tolerated dose (MTD) is reported. This schedule was tested with gemcitabine in two distinct human pancreatic adenocarcinoma orthotopic models and with cyclophosphamide in an orthotopic ovarian cancer model. In both models, the C-S schedule had the most favourable effect, achieving at least 80% tumour growth inhibition without increased toxicity. Moreover, in the pancreatic cancer model, although peritoneal metastases were observed in control and MTD groups, no dissemination was observed in the MET and C-S groups. C-S treatment caused a decrease in angiogenesis, and its effect on tumour growth was similar to that produced by the MTD followed by anti-angiogenic DC101 treatment. C-S treatment combined an increase in thrombospondin-1 expression with a decrease in the number of CD133+ cancer cells and triple-positive CD133+/CD44+/CD24+ cancer stem cells (CSCs). These findings confirm that the C-S schedule is a challenging clinical strategy with demonstrable inhibitory effects on tumour dissemination, angiogenesis and CSCs.

  2. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia

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    Badoux, Xavier C.; Keating, Michael J.; Wang, Xuemei; O'Brien, Susan M.; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop

    2011-01-01

    Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes. PMID:21670470

  3. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

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    Ejlertsen, B.; Mouridsen, Henning Torbøl; Jensen, M.B.;

    2010-01-01

    .70 in the CMF arm (P = .01). The hazard ratio for death was 0.70 in both the C arm (P = .02) and the CMF arm (P = .02) at 10 years, and the overall survival (OS) benefit was maintained during 25 years of follow-up. No significant differences were observed in IDF5 or OS between the C arm and the CMF arm...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...... (the CMF arm). RESULTS: The 10-year invasive disease-free survival (IDFS) rate was 38.6% in the control arm compared with 55.5% in the C arm, 48.8% in the CMF arm, and 35.2% in the levamisole arm. Compared with the control arm, the hazard ratio for an IDFS event was 0.62 in the C arm (P = .001) and 0...

  4. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

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    Ejlertsen, Bent Laursen; Mouridsen, Henning T; Jensen, Maj-Britt;

    2010-01-01

    .70 in the CMF arm (P = .01). The hazard ratio for death was 0.70 in both the C arm (P = .02) and the CMF arm (P = .02) at 10 years, and the overall survival (OS) benefit was maintained during 25 years of follow-up. No significant differences were observed in IDFS or OS between the C arm and the CMF arm...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...... (the CMF arm). RESULTS: The 10-year invasive disease-free survival (IDFS) rate was 38.6% in the control arm compared with 55.5% in the C arm, 48.8% in the CMF arm, and 35.2% in the levamisole arm. Compared with the control arm, the hazard ratio for an IDFS event was 0.62 in the C arm (P = .001) and 0...

  5. Metronomic chemotherapy: an attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance.

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    Kareva, Irina; Waxman, David J; Lakka Klement, Giannoula

    2015-03-28

    The administration of chemotherapy at reduced doses given at regular, frequent time intervals, termed 'metronomic' chemotherapy, presents an alternative to standard maximal tolerated dose (MTD) chemotherapy. The primary target of metronomic chemotherapy was originally identified as endothelial cells supporting the tumor vasculature, and not the tumor cells themselves, consistent with the emerging concept of cancer as a systemic disease involving both tumor cells and their microenvironment. While anti-angiogenesis is an important mechanism of action of metronomic chemotherapy, other mechanisms, including activation of anti-tumor immunity and a decrease in acquired therapeutic resistance, have also been identified. Here we present evidence supporting a mechanistic explanation for the improved activity of cancer chemotherapy when administered on a metronomic, rather than an MTD schedule and discuss the implications of these findings for further translation into the clinic.

  6. Rituximab Therapy for Severe Cutaneous Leukocytoclastic Angiitis Refractory to Corticosteroids, Cellcept and Cyclophosphamide

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    Kamel El-Reshaid

    2013-04-01

    Full Text Available We report our clinical experience with rituximab in the treatment of 2 patients with idiopathic cutaneous angiitis who relapsed after treatment with high-dose corticosteroids and cyclophosphamide. A 39-year-old woman and a 51-year-old man presented with ulcerating maculopapular rash in both lower limbs which relapsed 6 months after treatment with a combination of high-dose corticosteroids and cyclophosphamide. After treatment with 2 g of rituximab, the first patient has still been in clinical remission for 32 months while the second has finished 28 months. Interestingly, CD19 which had dropped to 0.5% 8 months later in both patients. Despite that, our patients are still in clinical remission. No significant side effects were noted during infusions and up to the period of follow-up. In conclusion, rituximab is a useful and safe agent in the treatment of idiopathic cutaneous angiitis refractory to conventional therapy. Clinical remission persists years after improvement of B-cell suppression.

  7. Metronomic chemotherapy regimens in oncology

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

  8. Metronomic Chemotherapy: Low Dose Less Toxicity Anticancer Strategy

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    Anjan Khadka

    2016-06-01

    Full Text Available Metronomic chemotherapy is the frequent administration of chemotherapy drugs at doses below the maximum tolerated dose and with no prolonged drug‑free break. It thus achieves a sustained low blood level of the drug without significant toxic side‑effects. Metronomic therapy leads to sustained plasma concentration of the drug without significant toxic side‑effects and hence there is reduced need for supportive therapy. However in case of conventional therapy toxicity is a concern. Metronomic chemotherapy exerts both direct and indirect effects on tumor cells and their microenvironment. It can inhibit tumor angiogenesis, stimulate anticancer immune response and also induces tumor dormancy. Optimizing a metronomic anticancer therapy is still a challenging task. New strategies are being developed to combine metronomic chemotherapy with conventional chemotherapy, radiotherapy and/or targeted therapy. An important disadvantage of this type of regimen is the empiricism in finding the optimal ‘low‑dose’ and in monitoring therapeutic efficacy during the course of treatment.

  9. Combination therapy with rituximab and cyclophosphamide in the treatment of anti-neutrophil cytoplasmic antibodies (ANCA positive pulmonary hemorrhage: case report

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    Lehman Thomas JA

    2011-10-01

    Full Text Available Abstract Anti-neutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV with pulmonary hemorrhage is rare in childhood. Standard treatment includes corticosteroids and cyclophosphamide (CYC, which is associated with a high level of toxicity. We report a white female with ANCA positive pulmonary hemorrhage who was treated with cyclophosphamide (CYC and rituximab (RTX combination therapy.

  10. [A case of possible retroperitoneal metastasis of breast cancer successfully treated with oral S-1 and cyclophosphamide therapy after TC therapy].

    Science.gov (United States)

    Yoneyama, Kimiyasu; Takeshita, Toshio; Suzuki, Hiroshi; Morise, Masaki; Suzuki, Tetsutarou; Kishi, Shinya; Tsutsui, Atsuko; Matsumoto, Akiko

    2011-03-01

    We report a case of possible retroperitoneal metastasis of breast cancer successfully treated with oral S-1 and cyclophosphamide therapy after docetaxel and cyclophosphamide (TC) therapy. A 57-year-old woman with a history of bilateral breast cancer showed an increase in tumor markers during treatment with oral anastrozole as postoperative adjuvant therapy 4 years after her second cancer surgery. After careful examination, the patient was diagnosed as having multiple bone metastases and her medication was changed to oral letrozole. After 3 months, the patient developed left back pain and was referred to our hospital. CT scanning showed an enhanced mass in the region from the left perirenal and posterior pararenal spaces to the left psoas major muscle and the anterior aspect of the left iliacus muscle, suggesting retroperitoneal metastasis. TC therapy was performed and, as a result, tumor markers decreased and the mass disappeared on CT imaging. After discontinuation of TC therapy, the tumor markers increased again, following which oral S-1 and cyclophosphamide therapy were administered, and the tumor markers decreased. At the time of this writing, the patient is still undergoing therapy, and no recurrence has been observed. We concluded that oral S-1 and cyclophosphamide therapy were useful in the present case and were associated with few adverse effects.

  11. Treatment of refractory juvenile idiopathic arthritis via pulse therapy using methylprednisolone and cyclophosphamide

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    Tania Caroline Monteiro de Castro

    Full Text Available CONTEXT: Patients with refractory juvenile idiopathic arthritis can benefit from aggressive therapy. CASE REPORT: We followed the clinical course of 4 patients (2 male, 2 female aged 9.1-17.8 years (mean of 14.5 years with polyarticular onset of juvenile rheumatoid arthritis and one 16-year-old boy with juvenile spondyloarthropathy associated with inflammatory bowel disease. All the juvenile rheumatoid arthritis patients fulfilled the diagnostic criteria established by the American College of Rheumatology. All patients had unremitting arthritis despite maximum therapy. All patients began receiving treatment using intravenous cyclophosphamide at 500-750 mg/m² and intravenous methylprednisolone at 30 mg/kg, for 3 days monthly (1 g maximum. The patients received between 3 and 11 monthly treatments, and/or 3-5 treatments every two months for 12 months, according to the severity of the disease and/or response to the therapy. All but one patient were evaluated retrospectively at the start (time 0 and 6 months (time 1, and 12 months (time 2 after the beginning of the treatment. A rapid and clinically significant suppression of systemic and articular manifestations was seen in all patients. Our results showed the favorable effect of this treatment on the clinical and some laboratory manifestations of juvenile idiopathic arthritis.

  12. [Examination of the safety of docetaxel/cyclophosphamide combination therapy for advanced recurrent breast cancer].

    Science.gov (United States)

    Yoneyama, Kimiyasu; Koshida, Yoshitomo; Toriumi, Fumiki; Murayama, Takaya; Toeda, Hiroyuki; Imazu, Yoshihiro; Motegi, Katsuhiko; Akamatsu, Hidetoshi; Ohyama, Renpei

    2006-10-01

    In the treatment of recurrent breast cancer in patients previously treated with anthracycline drugs, taxane drugs are generally used. This time, we retrospectively studied the safety of docetaxel/cyclophosphamide combination therapy (hereinafter referred to as TC therapy). Ten patients (mean age: 52.8 years old) were included in the study. Metastatic/recurrent sites included 3 skin, 2 each of contralateral breast, lung and bone, and 1 each of liver, carcinomatous pleurisy and supraclavicular lymph node. Seven patients had a history of anthracycline treatment. The patients received TC at doses of 60 mg/m(2) and 500 mg/m(2), respectively, every 3 weeks. With regard to adverse events, non-hematotoxic events included alopecia in all the patients, generalized malaise in 5, and abnormal nail in 1. Hematotoxic events were grades 2 and 3 decreased neutrophil count in 5 patients. One patient had grade 4 pyrexia associated with oral candida. The patient was admitted and treated with fluid replacement and granulocyte colony-stimulating factor (G-CSF). There were no other patients in whom the treatment was prolonged or dosage was reduced due to adverse reactions. TC therapy is considered to be a beneficial treatment method in terms of safety since it can be instituted on an outpatient basis.

  13. Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug

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    Peter Woias

    2011-06-01

    Full Text Available The most fatal outcomes of prostate carcinoma (PCa result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24, spleen (3/24, kidney (4/24, liver (5/24, and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively. Preliminary data of orthotopic implantation (three animals showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes. Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4, lung (3/6 or lumbar spine (0/2, as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

  14. Metastasizing, Luciferase Transduced MAT-Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug

    Energy Technology Data Exchange (ETDEWEB)

    Jantscheff, Peter, E-mail: jantscheff@tumorbio.uni-freiburg.de [Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg (Germany); Esser, Norbert [ProQinase GmbH, Breisacher Str. 117, D-79106 Freiburg (Germany); Geipel, Andreas; Woias, Peter [Laboratory for Design of Microsystems, Department of Microsystems Engineering (IMTEK), Georges-Köhler-Allee 106, D-79110 Freiburg (Germany); Ziroli, Vittorio [Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg (Germany); Goldschmidtboing, Frank [Laboratory for Design of Microsystems, Department of Microsystems Engineering (IMTEK), Georges-Köhler-Allee 106, D-79110 Freiburg (Germany); Massing, Ulrich [Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg (Germany)

    2011-06-17

    The most fatal outcomes of prostate carcinoma (PCa) result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

  15. Dexamethasone cyclophosphamid pulse therapy in pemphigus-appraisal of its outcome

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    Prabhash Kulhari

    2012-01-01

    Full Text Available Introduction :- Pemphigus is the commonest autoimmune vesicobullous disorder on the the Indian subcontinent. the mainstay of treatment of the disease is systemic steroid and other immunosuppresive therapies. Dexamethasone-cyclophosphamide(DCP pulse therapy was designated by pasricha for pemphigus in 1981 with the aim of reducing toxicity of corticosteroid and also achieve better results. Method:- Thirty one patients admitted at department of dermatology ASSAM MEDICAL COLLEGE,DIBRUGARH were enrolled for study prospectively from 2008-2011.Diagnosis of pemphigus was based on clinical feature, tzanck smear and biopsy. Confirmation was carried out by direct immunofluorascence.DCP pulse was given to confirmed cases of pemphigus. we enrolled 31 patients with pemphigus for DCP pulse therapy in our hospital during this period out of which 27 patients were pemphigus vulgaris and 4 were pemphigus folIacious. male to female ratio was 1.2:1.Of 31 patients enrolled for this treatment,6 patients could not complete the treatment and 2 patient died due to cardiovascular failure(not related to treatment. Of remaining 23 patients ,15 have alredy completed the treatment and are free of disease even after withdrawl of all treatment. 5 patients are in remission but have not completed the treatment schedule whereas 3 patients are still having clinical evidence of disease although it has already become much milder .Various side effects seen in our patients were candidiasis (2,tuberculosis(1, acneiform eruption(2, osteoporosis(1, cataract(2, hair fall(2, gastritis(3, avascular necrosis(1.Our finding are very consistent with previous reports that DCP pulse therapy is very effective in pemphigus and having lesser side effects in comparison to daily steroid .

  16. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy.

    Science.gov (United States)

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-06-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

  17. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy

    OpenAIRE

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-01-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

  18. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy

    OpenAIRE

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-01-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

  19. ATP-binding cassette transporters in tumor endothelial cells and resistance to metronomic chemotherapy.

    Science.gov (United States)

    Hida, Kyoko; Kikuchi, Hiroshi; Maishi, Nako; Hida, Yasuhiro

    2017-02-16

    Drug resistance is a major problem in anticancer therapy. ATP-binding cassette (ABC) transporters have a role in the multidrug resistance. A new regimen of chemotherapy has been proposed, called "metronomic chemotherapy". Metronomic chemotherapy is the frequent, regular administration of drug doses designed to maintain low, but active, concentrations of chemotherapeutic drugs over prolonged periods of time, without causing serious toxicities. Metronomic chemotherapy regimens were developed to optimize the antitumor efficacy of agents that target the tumor vasculature instead of tumor cells, and to reduce toxicity of antineoplastic drugs [1]. Nevertheless, recent studies revealed that ABC transporters are expressed at a higher level in the endothelium in the tumor. To avoid resistance to metronomic anti-angiogenic chemotherapy, ABC transporter inhibition of tumor endothelial cells may be a promising strategy. In this mini-review, we discuss the possible mechanism of resistance to metronomic chemotherapy from the viewpoint of tumor endothelial cell biology, focusing on ABC transporters.

  20. The efficacy and safety of preoperative chemotherapy with triweekly abraxane and cyclophosphamide followed by 5-Fluorouracil, epirubicin, and cyclophosphamide therapy for resectable breast cancer: a multicenter clinical trial.

    Science.gov (United States)

    Shigematsu, Hideo; Kadoya, Takayuki; Masumoto, Norio; Sasada, Tatsunari; Emi, Akiko; Ohara, Masahiro; Kajitani, Keiko; Okada, Morihito

    2015-04-01

    It has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy, and that cyclophosphamide combined with taxane shows an enhanced antitumor effect. We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC. From September 2011 to September 2013, 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer. In patients with HER2-positive breast cancer, tri-weekly Trastuzumab was administered with TRI-ABC. The primary end point was the pathological complete response (pCR) rate in the breasts and lymph nodes. The treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy. All patients underwent radical surgery, and the overall pCR rate of 37% (20 of 54) was achieved. The pCR rates according to each subtype were 8% (2 of 24) in hormone receptor (HR)-positive HER2-negative breast cancer, 56% (5 of 9) in HR-positive HER2-positive breast cancer, 63% (5 of 8) in HR-negative HER2-positive breast cancer, and 62% (8 of 13) in triple-negative breast cancer. Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR. Clinical response was observed in 49 patients (91%). The safety profile was acceptable. Preoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety. Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane-anthracycline regimens. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Pulse cyclophosphamide therapy and clinical remission in atypical hemolytic uremic syndrome with anti-complement factor H autoantibodies.

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    Boyer, Olivia; Balzamo, Eve; Charbit, Marina; Biebuyck-Gougé, Nathalie; Salomon, Rémi; Dragon-Durey, Marie-Agnès; Frémeaux-Bacchi, Véronique; Niaudet, Patrick

    2010-05-01

    We report 3 children with atypical hemolytic uremic syndrome associated with anti-complement factor H (CFH) autoantibodies who presented with sustained remission with low antibody titers and normal kidney function after plasma exchanges (PEs) and cyclophosphamide pulses. The 3 children initially presented with acute vomiting, fatigue, gross hematuria, hypertension, hemolytic anemia, thrombocytopenia, nephrotic syndrome, and acute kidney injury. C3 levels were normal in patients 1 and 3 and low in patient 2 (0.376 mg/mL [0.376 g/L]). CFH antibody titers were increased (15,000 to > 32,000 arbitrary units [AU]). Patient 1, an 11-year-old boy, was treated with 12 PEs, leading to a decrease in CFH antibody titer (to 800 AU). A first relapse 1 month later was treated with 6 PEs and 4 rituximab infusions. A second relapse 3 months later required 5 PEs, and the patient received oral steroids (0.5 mg/d/kg body weight) and 5 cyclophosphamide pulses (1 g/1.73 m(2)), leading to sustained remission with normal kidney function (estimated glomerular filtration rate [eGFR], 120 mL/min/1.73 m(2) [2.0 mL/s/1.73 m(2)]) and a stable decrease in CFH antibody titer (to 2,000 AU) 3 years later. Patient 2, a 5-year-old boy, required dialysis therapy for 2 weeks. He received 3 plasma infusions without remission. Six PEs associated with 2 cyclophosphamide pulses (0.5 g/1.73 m(2)) and steroids (1 mg/d/kg body weight) led to rapid remission, with eGFR of 107 mL/min/1.73 m(2) [1.78 mL/s/1.73 m(2)] and a prolonged decrease in CFH antibody titer after 15 months (1,300 AU). Patient 3, a 16-month-old boy, was treated with oral steroids (1 mg/d/kg body weight), 2 PEs, and 2 cyclophosphamide pulses (0.5 g/1.73 m(2)), resulting in a stable decrease in CFH antibody titer to 276 AU. Kidney function quickly normalized (eGFR, 110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)]) and has remained normal after 14 months. All 3 patients show a homozygous deletion mutation of the CFHR1 and CFHR3 genes

  2. Cyclophosphamide-induced symptomatic hyponatraemia

    NARCIS (Netherlands)

    Bruining, D M; van Roon, E N; de Graaf, H; Hoogendoorn, M

    2011-01-01

    Cyclophosphamide is an alkylating agent used in antineoplastic and immunosuppressive therapies. Symptomatic hyponatraemia is a rare but life-threatening complication in patients treated with cyclophosphamide. We report the case of a 64-year-old woman with breast cancer who developed severe symptomat

  3. Cyclophosphamide Injection

    Science.gov (United States)

    ... lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML, ANLL), and acute lymphoblastic leukemia (ALL). It ... a reliable method of birth control to prevent pregnancy. Cyclophosphamide may harm the fetus.if you are ...

  4. Intermittent Metronomic Drug Schedule Is Essential for Activating Antitumor Innate Immunity and Tumor Xenograft Regression

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    Chong-Sheng Chen

    2014-01-01

    Full Text Available Metronomic chemotherapy using cyclophosphamide (CPA is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25% reduction in CPA dose. Moreover, an ~20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.

  5. Cyclophosphamide therapy for corticoresistant drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient with severe kidney and eye involvement and Epstein-Barr virus reactivation.

    Science.gov (United States)

    Laban, Emilie; Hainaut-Wierzbicka, Eva; Pourreau, François; Yacoub, Mokrane; Sztermer, Emilie; Guillet, Gérard; Touchard, Guy; Bridoux, Frank

    2010-03-01

    DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is a severe adverse drug reaction with significant mortality, characterized by erythroderma, fever, lymphadenopathy, and visceral involvement. We report a case of multivisceral DRESS syndrome with posterior multifocal placoid pigment epitheliopathy and acute tubulointerstitial nephritis responsible for dialysis-dependent acute kidney failure in the context of reactivation of Epstein-Barr virus infection. Because of resistance of the skin and kidney manifestations to prolonged corticosteroid therapy, a 6-month course of oral cyclophosphamide resulted in complete recovery of all symptoms. To our knowledge, this is the first case showing the efficacy of cyclophosphamide in severe DRESS syndrome.

  6. A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer.

    Directory of Open Access Journals (Sweden)

    Claudia Arce

    Full Text Available Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy.This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655. After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day -7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate.16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1-2. Five (31% patients had clinical CR and eight (50% PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6% had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively.Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the

  7. Mechanisms of Fatal Cardiotoxicity following High-Dose Cyclophosphamide Therapy and a Method for Its Prevention.

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    Takuro Nishikawa

    Full Text Available Observed only after administration of high doses, cardiotoxicity is the dose-limiting effect of cyclophosphamide (CY. We investigated the poorly understood cardiotoxic mechanisms of high-dose CY. A rat cardiac myocardial cell line, H9c2, was exposed to CY metabolized by S9 fraction of rat liver homogenate mixed with co-factors (CYS9. Cytotoxicity was then evaluated by 3-(4,5-dimethyl-2-thiazolyl¬2,5-diphenyl¬2H-tetrazolium bromide (MTT assay, lactate dehydrogenase release, production of reactive oxygen species (ROS, and incidence of apoptosis. We also investigated how the myocardial cellular effects of CYS9 were modified by acrolein scavenger N-acetylcysteine (NAC, antioxidant isorhamnetin (ISO, and CYP inhibitor β-ionone (BIO. Quantifying CY and CY metabolites by means of liquid chromatography coupled with electrospray tandem mass spectrometry, we assayed culture supernatants of CYS9 with and without candidate cardioprotectant agents. Assay results for MTT showed that treatment with CY (125-500 μM did not induce cytotoxicity. CYS9, however, exhibited myocardial cytotoxicity when CY concentration was 250 μM or more. After 250 μM of CY was metabolized in S9 mix for 2 h, the concentration of CY was 73.6 ± 8.0 μM, 4-hydroxy-cyclophosphamide (HCY 17.6 ± 4.3, o-carboxyethyl-phosphoramide (CEPM 26.6 ± 5.3 μM, and acrolein 26.7 ± 2.5 μM. Inhibition of CYS9-induced cytotoxicity occurred with NAC, ISO, and BIO. When treated with ISO or BIO, metabolism of CY was significantly inhibited. Pre-treatment with NAC, however, did not inhibit the metabolism of CY: compared to control samples, we observed no difference in HCY, a significant increase of CEPM, and a significant decrease of acrolein. Furthermore, NAC pre-treatment did not affect intracellular amounts of ROS produced by CYS9. Since acrolein seems to be heavily implicated in the onset of cardiotoxicity, any competitive metabolic processing of CY that reduces its transformation to acrolein

  8. A monocentric retrospective study comparing pulse cyclophosphamide therapy versus low dose rituximab in the treatment of refractory autoimmune hemolytic anemia in adults.

    Science.gov (United States)

    Fu, Rong; Yan, Siyang; Wang, Xiaoming; Wang, Guojin; Qu, Wen; Wang, Huaquan; Wu, Yuhong; Liu, Hong; Song, Jia; Guan, Jin; Xing, Limin; Ruan, Erbao; Li, Lijuan; Liu, Hui; Shao, Zonghong

    2016-10-01

    This retrospective study aims at confirming the efficacy and safety of low dose rituximab and pulse cyclophosphamide in the treatment of refractory AIHA in adults and making comparison of the two. Forty-nine adult patients with refractory AIHA have been enrolled. Results showed low dose rituximab combined with steroid therapy (group B) got more CR (78.9 %, 15/19) compared to that in intermittent intravenous cyclophosphamide combined with steroid therapy (group A) (42.1 %, 8/19) (P = 0.04) at 6 months after treatment. The hemoglobin level in group B was higher than group A at the time point of 1 month (P = 0.02) after treatments. The RFS in group A was 87.9 % at 6 months and 82.7 % at 12 months, which were no significant difference with group B (91.1 % at 6 months and 86.0 % at 12 months) (P = 0.81). Both the two therapies were well tolerated with pulmonary infections as the most common side effects. In conclusion, low dose rituximab combined with steroid therapy presents to be a better choice in the treatment of refractory AIHA in adults comparing with pulse cyclophosphamide therapy.

  9. Fludarabine, cyclophosphamide, and rituximab in salvage therapy of Waldenström's macroglobulinemia.

    Science.gov (United States)

    Tedeschi, Alessandra; Ricci, Francesca; Goldaniga, Maria Cecilia; Benevolo, Giulia; Varettoni, Marzia; Motta, Marina; Pioltelli, Pietro; Gini, Guido; Barate', Claudia; Luraschi, Annamaria; Vismara, Eleonora; Frustaci, Anna Maria; Nichelatti, Michele; Vitolo, Umberto; Baldini, Luca; Morra, Enrica

    2013-04-01

    The combination FCR (fludarabine, cyclophosphamide, and rituximab) proved to be active in Waldenström's macroglobulinemia in a mixed population of untreated and previously treated patients. Prolonged myelosuppression and concerns about purine analogue treatment led to the conclusion that this regimen should be avoided in younger patients in first-line treatment. In this retrospective study on 40 patients we observed a response rate of 80% (32) after FCR salvage treatment with 32.5% (13) of patients reaching at least a very good partial remission. None of the prognostic variables had a significant effect on response or good quality of response achievement. Median event-free survival was reached at 77 months; median progression-free survival was not reached after a median follow-up of 51 months with any difference when categorizing patients according to quality of response. The results of this study suggest that the FCR regimen might overcome poor prognostic features and should be taken into account as salvage treatment. Tardive immunosuppression and myelosuppression warrant accurate patient follow-up.

  10. Human Umbilical Cord Mesenchymal Stem Cells Therapy in Cyclophosphamide-Induced Premature Ovarian Failure Rat Model

    Directory of Open Access Journals (Sweden)

    Dan Song

    2016-01-01

    Full Text Available Premature ovarian failure (POF is one of the most common causes of infertility in women. In our present study, we established cyclophosphamide- (CTX- induced POF rat model and elucidated its effect on ovarian function. We detected the serum estrogen, follicle stimulating hormone, and anti-Müllerian hormone of mice models by ELISA and evaluated their folliculogenesis by histopathology examination. Our study revealed that CTX administration could severely disturb hormone secretion and influence folliculogenesis in rat. This study also detected ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL and demonstrated marked ovarian cells apoptosis in rat models following CTX administration. In order to explore the potential of human umbilical cord mesenchymal stem cells (UCMSCs in POF treatment, the above indexes were used to evaluate ovarian function. We found that human UCMSCs transplantation recovered disturbed hormone secretion and folliculogenesis in POF rat, in addition to reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by fluorescence in situ hybridization (FISH. The results manifested that the transplanted human UCMSCs could reside in ovarian tissues and could survive for a comparatively long time without obvious proliferation. Our present study provides new insights into the great clinical potential of human UCMSCs in POF treatment.

  11. Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes.

    Science.gov (United States)

    Benjamini, Ohad; Jain, Preetesh; Trinh, Long; Qiao, Wei; Strom, Sara S; Lerner, Susan; Wang, Xuemei; Burger, Jan; Ferrajoli, Alessandra; Kantarjian, Hagop; O'Brien, Susan; Wierda, William; Estrov, Zeev; Keating, Michael

    2015-06-01

    Patients with chronic lymphocytic leukemia (CLL) are known to have an increased incidence of second cancers, but the contribution of commonly used frontline therapies to the incidence of second cancers is unclear. We report on the characteristics, incidence, outcomes and factors associated with second cancers in 234 patients receiving fludarabine, cyclophosphamide and rituximab (FCR) based regimens in the frontline setting. The risk of second cancers was 2.38 times higher than the expected risk in the general population. Ninety-three patients (40%) had other cancers before and 66 patients (28%) after FCR. Rates of therapy related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) (5.1%) and Richter transformation (RT) (9%) were high, while solid tumors were not increased. Overall survival of patients with second cancers after frontline FCR was shorter (median of 4.5 years) compared to patients with and without prior cancers. Second cancer risk after frontline FCR is mainly due to high rates of t-AML/MDS and RT, and as speculated the survival of affected patients is shorter.

  12. Successful Use of Cyclophosphamide as an Add-On Therapy for Multiple Myeloma Patients with Acquired Resistance to Bortezomib or Lenalidomide

    Directory of Open Access Journals (Sweden)

    Shigeki Ito

    2013-01-01

    Full Text Available Novel agents such as thalidomide, lenalidomide, and bortezomib have been shown to possess potent activity against multiple myeloma. However, the treatment strategy for patients who acquired resistance to these agents has not been established. In addition to switching drug classes, intensified treatment strategy, including increase in the dosage of current agents and addition of other agents, may be considered for these patients. We here describe 2 myeloma patients with acquired resistance to bortezomib or lenalidomide, in whom add-on therapy with low-dose cyclophosphamide was effective and tolerable. These cases suggest that add-on therapy with cyclophosphamide is one of the treatment options to overcome resistance to novel agents in patients with multiple myeloma. A larger prospective study is needed to clarify the efficacy and safety of this strategy for novel agent-resistant multiple myeloma.

  13. Therapy-related myelodysplastic syndrome and acute myeloid leukemia in patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide.

    Science.gov (United States)

    Colović, M; Suvajdžić, N; Janković, G; Tomin, D; Colović, N; Fekete, M Denčić; Palibrk, V

    2011-08-01

    We retrospectively studied four cases of t-MDS/AML among 210 (1.9%) consecutive patients with CLL treated at a single center with fludarabine and cyclophosphamide (FC) either as the first- or second-line therapy. The median follow-up of the whole cohort of patients was 46months (range: 7-60). Two of these patients (2/130, 1.7%) had been treated with FC only, and two more (2/80, 2.3%) with CHOP and CHOP+FND, respectively, prior to FC. The median age was 61.5years (range: 49-71); three were male. They developed t-MDS/AML after a median latency period of 41months (range: 7-56) from the FC completion. Chromosomal aberrations with an adverse prognostic impact were present in the karyotype of all four patients, including abnormalities of chromosome 5 in three of them, and a rare chromosomal translocation in one patient. Median survival after t-MDS/AML diagnosis was 4months (range: 2-8). Although the agents administered prior to FC make it difficult to assess the risk of t-MDS/AML attributable to FC, this report might be a valuable addition to the literature.

  14. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy

    National Research Council Canada - National Science Library

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-01-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses...

  15. Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial.

    Science.gov (United States)

    Brown, Jennifer R; O'Brien, Susan; Kingsley, C Daniel; Eradat, Herbert; Pagel, John M; Lymp, James; Hirata, Jamie; Kipps, Thomas J

    2015-04-30

    Obinutuzumab is a type 2, glycoengineered, anti-CD20 antibody recently approved with chlorambucil for the initial therapy of chronic lymphocytic leukemia (CLL). In this nonrandomized, parallel-cohort, phase 1b, multicenter study, we explored the safety and preliminary efficacy of obinutuzumab-bendamustine (G-B) or obinutuzumab fludarabine cyclophosphamide (G-FC) for the therapy of previously untreated fit patients with CLL. Patients received up to 6 cycles of G-B (n = 20) or G-FC (n = 21). The primary end point was safety, with infusion-related reactions (88%, grade 3-4 20%) being the most common adverse event and grade 3-4 neutropenia in 55% on G-B and 48% on G-FC. Mean cycles completed were 5.7 for G-B and 5.1 for G-FC, with 2 and 7 early discontinuations, respectively. The objective response rate (ORR) for G-B was 90% (18/20) with 20% complete response (CR) and 25% CR with incomplete marrow recovery (CRi). The ORR for G-FC was 62% (13/21), with 10% CR and 14% CRi, including 4 patients not evaluable. With a median follow-up of 23.5 months in the G-B cohort and 20.7 months in the G-FC cohort, no patient has relapsed or died. We conclude that obinutuzumab with either B or FC shows manageable toxicity and has promising activity. This study was registered at www.clinicaltrials.gov as #NCT01300247.

  16. Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series.

    Science.gov (United States)

    Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L

    2017-02-01

    Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline. Complete remission was defined as a UPCR < 0.3 g/g. Secondary outcomes were serious adverse events and the change in proteinuria, serum creatinine, serum albumin, cholesterol, triglycerides, and immunoglobulin G levels after 1 year of treatment. Over a median follow-up time of 37 (IQR, 34-44) months, 100% of patients achieved partial remission and 93% of patients achieved complete remission at a median time of 2 and 13 months, respectively. After 1 year of treatment, median (IQR) UPCR declined from 8.2 (6.6-11.1) to 0.3 (0.2-0.7) g/g (P < 0.001). Three serious adverse events occurred over 51 patient years. No patients died or progressed to ESKD. Treatment of idiopathic membranous nephropathy with RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

  17. Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide.

    Science.gov (United States)

    Agrawal, Siddarth; Łuc, Mateusz; Ziółkowski, Piotr; Agrawal, Anil Kumar; Pielka, Ewa; Walaszek, Kinga; Zduniak, Krzysztof; Woźniak, Marta

    2017-06-01

    The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.

  18. Effect of Intravenous Cyclophosphamide Pulse Therapy on Renal Functions and Histopathology in Patients with Severe Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Huraib Sameer

    2000-01-01

    Full Text Available Despite the wide use of intravenous cyclophosphamide (IC in lupus nephritis (LN, there are few published studies showing the effect of this treatment on renal histology. In this prospective study, we report the effect of IC on the evolution of histopathologic features in successive renal biopsies in patients with LN. Thirty patients with class IV or V LN were started on IC (10-15 mg/kg administered once every month for six months followed by three monthly for another six doses making a total of two years of therapy. The clinical course of the disease, serum creatinine and 24 hours urinary protein and creatinine clearance were tested at entry and subsequently during each follow-up visit. Repeat renal biopsy was performed after completion of two years of therapy. The mean serum creatinine of the study patients was 166.3 + 42 tmol/L at entry which decreased to 104 + 46.4 tmol/L at two years (P < 0.01. The mean 24 hours proteinuria decreased from 2.81 + 2.4 g at entry to 1.39 + 1.54 g at two years (P < 0.003 and the mean creatinine clearance increased from 58 + 31 ml/min at the start of treatment to 64 + 32 ml/min at two years of therapy (P < 0.05. Nine patients had serum creatinine of > 200 tmol/L, of whom six progressed to variable degrees of chronic renal failure. Repeat renal biopsy was performed in 21 patients. The original biopsy of these patients showed class IV in 17 and class V in four patients. On repeat biopsy, five of class IV disease had progressed to advanced sclerosis, four to class V, and five remained unchanged. The remaining three patients with class IV LN changed to one each of class I, II and III. Of the four patients with class V, one progressed to advanced sclerosis, one changed to class III and two remained the same. There was a significant decrease (P < 0.05 in the activity index although there was a significant increase in the chronicity index (P < 0.001. Multivariat analysis for possible risk factors for progression to

  19. Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Walsh, M.; Faurschou, M.; Berden, A.;

    2014-01-01

    BACKGROUND AND OBJECTIVES: Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine...... after 3-6 months or after 12 months of cyclophosphamide treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time...

  20. A Case of Long-term Survival of Advanced Paratesticular Rhabdomyosarcoma Treated With a Multimodal Therapy Including a Combination of Cyclophosphamide, Vincristine, Doxorubicin and Dacarbazine

    Directory of Open Access Journals (Sweden)

    Makoto Isono

    2016-07-01

    Full Text Available There is no established treatment for advanced rhabdomyosarcoma (RMS with metastases at the time of diagnosis. A 17-year-old male was referred to our hospital because of a right scrotal mass. Computed tomography showed multiple lung metastases with pleural effusion and retroperitoneal lymph node metastasis, and bone scintigraphy revealed multiple bone metastases. Right high orchiectomy was performed and the tumor was diagnosed as paratesticular embryonal RMS. He was treated with a multimodal therapy including 17 cycles of combination chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin and dacarbazine (CYVADIC and achieved a long-term survival of 4 years.

  1. Efficacy of reduced dose of pegfilgrastim in Japanese breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide therapy.

    Science.gov (United States)

    Mizuno, Yoshio; Fuchikami, Hiromi; Takeda, Naoko; Iwai, Masaru; Sato, Kazuhiko

    2017-01-01

    This retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy. Patients treated with adjuvant or neoadjuvant chemotherapy for early-stage breast cancer at the Tokyo-West Tokushukai Hospital were included in this analysis. Because 6 mg pegfilgrastim has not yet been approved for use in Japan, we compared the outcomes of a dose-dense doxorubicin and cyclophosphamide regimen plus 3.6 mg pegfilgrastim support with a conventional dose epirubicin and cyclophosphamide regimen. The incidence of febrile neutropenia, relative dose intensity, dose delay, dose reduction, regimen change and hospitalization because of neutropenia were assessed. From November 2013 to March 2016, 97 patients with stage I-III invasive breast cancer were analyzed (dose-dense doxorubicin and cyclophosphamide plus 3.6-mg pegfilgrastim group, n  =  41; epirubicin and cyclophosphamide group, n  =  56; median ages, 49.0 and 48.5 years, respectively). Febrile neutropenia occurred during the first chemotherapy cycle in 7 of 56 patients (12.5%) in the epirubicin and cyclophosphamide group and 0 of 41 patients in the dose-dense doxorubicin and cyclophosphamide group (P  =  0.02). The average relative dose intensities were 97.9% and 96.8%, respectively (P  =  0.28), with corresponding dose delay rates of 4.9% (2/41) and 16.1% (9/56), respectively (P  =  0.11) and dose reduction rates of 0% (0/41) and 7.1% (4/56), respectively (P  =  0.16). Our results indicate the efficacy of a 3.6-mg pegfilgrastim dose for the primary prevention of febrile neutropenia in dose-dense doxorubicin- and cyclophosphamide-treated Japanese breast cancer patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy

    DEFF Research Database (Denmark)

    Comabella, M; Balashov, K; Issazadeh-Navikas, Shohreh

    1998-01-01

    Multiple sclerosis is postulated to be a Th1-type cell-mediated autoimmune disease. We investigated cytokine profiles in patients with progressive multiple sclerosis by using intracytoplasmic staining. We found increased IL-12 production by monocytes and increased IFN-gamma production by T cells...... in untreated patients as compared with controls. In patients treated with methotrexate, methylprednisolone, or cyclophosphamide/methylprednisolone (CY/MP), only CY/MP treatment normalized the elevated IL-12 production. Furthermore, CY/MP-treated patients had decreased IFN-gamma and increased IL-4, IL-5......, and TGF-beta expression. Patients followed prospectively before and after starting CY/MP treatment showed a gradual decrease in IL-12 and IFN-gamma production and an increase in IL-4 and IL-5. In vitro, addition of 4-hydroperoxycyclophosphamide, a metabolite of cyclophosphamide decreased IL-12 production...

  3. Circulating endothelial progenitor cells in metronomic chemotherapy using irinotecan and/or bevacizumab for colon carcinoma: Study of their clinical significance

    Science.gov (United States)

    MURAKAMI, HIDETSUGU; OGATA, YUTAKA; AKAGI, YOSHITO; ISHIBASHI, NOBUYA; SHIROUZU, KAZUO

    2011-01-01

    The aim of the present study was to clarify the antitumor efficacy of metronomic chemotherapy using irinotecan (CPT-11) combined with or without bevacizumab against colon cancer, and the significance of circulating endothelial cell (CECs) and endothelial progenitor cells (CEPs) as a surrogate marker for metronomic chemotherapy. KM12SM cells were implanted into the subcutis of nude mouse. After confirming that the implanted tumors had grown 5 mm in size, group A received an intraperitoneal injection of 40 mg/kg CPT-11 every two weeks for 4 weeks [conventional maximum-tolerated dose (MTD)], group B received 10 mg/kg twice weekly (metronomic), group C received 10 mg/kg twice weekly combined with 5 mg/kg bevacizumab twice weekly (metronomic + anti-angiogenic), and the control group received 0.2 ml of PBS every week. Serial changes of CECs and CEPs in peripheral blood and microvessel density (MVD) in the tumor tissues were evaluated. The results showed that the antitumor activity in group B and in group C was significantly higher than that in group A. A significant inhibition in CEPs on day 15 in the metronomic therapy groups B and C was noted when compared to that in the control group, while there was no significant difference in CECs and CEPs between the groups on days 4 and 8. The MVD on day 15 in metronomic groups was significantly lower than that in group A. In conclusion, metronomic chemotherapy of CPT-11 with or without bevacizumab for colon cancer was more effective than the MTD therapy via anti-angiogenic effects. Sequential measurement of CEPs may be a predictive factor for the efficacy and a decisive factor for the optimal dose of metronomic therapy in colon cancer. PMID:22977546

  4. Low-dose metronomic oral dosing of a prodrug of gemcitabine (LY2334737) causes antitumor effects in the absence of inhibition of systemic vasculogenesis.

    Science.gov (United States)

    Francia, Giulio; Shaked, Yuval; Hashimoto, Kae; Sun, John; Yin, Melissa; Cesta, Carolyn; Xu, Ping; Man, Shan; Hackl, Christina; Stewart, Julie; Uhlik, Mark; Dantzig, Anne H; Foster, F Stuart; Kerbel, Robert S

    2012-03-01

    Metronomic chemotherapy refers to the close, regular administration of conventional chemotherapy drugs at relatively low, minimally toxic doses, with no prolonged break periods; it is now showing encouraging results in various phase II clinical trials and is currently undergoing phase III trial evaluation. It is thought to cause antitumor effects primarily by antiangiogenic mechanisms, both locally by targeting endothelial cells of the tumor neovasculature and systemically by effects on bone marrow-derived cells, including circulating endothelial progenitor cells (CEP). Previous studies have shown reduction of CEPs by metronomic administration of a number of different chemotherapeutic drugs, including vinblastine, cyclophosphamide, paclitaxel, topotecan, and tegafur plus uracil (UFT). However in addition to, or even instead of, antiangiogenic effects, metronomic chemotherapy may cause suppression of tumor growth by other mechanisms such as stimulating cytotoxic T-cell responses or by direct antitumor effects. Here we report results evaluating the properties of metronomic administration of an oral prodrug of gemcitabine LY2334737 in nontumor-bearing mice and in preclinical models of human ovarian (SKOV3-13) and breast cancer (LM2-4) xenografts. Through daily gavage (at 6 mg/kg/d), the schedules tested were devoid of toxicity and caused antitumor effects; however, a suppressive effect on CEPs was not detected. Unexpectedly, metronomic LY2334737 administration caused increased blood flow in luciferase-tagged LM2-4 tumor xenografts, and this effect, readily measured using contrast micro-ultrasound, coincided with a relative increase in tumor bioluminescence. These results highlight the possibility of significant antitumor effects mediated by metronomic administration of some chemotherapy drugs without a concomitant inhibition of systemic angiogenesis.

  5. Early aggressive intra-venous pulse cyclophosphamide therapy for interstitial lung disease in a patient with systemic sclerosis. A case report.

    LENUS (Irish Health Repository)

    Peshin, R

    2009-06-01

    Interstitial lung disease is an important cause of mortality and morbidity in patients with systemic sclerosis (SSc). There are currently no recommended guidelines for management of these patients. This is probably due to the rarity of this condition, as well as clinical trials with only a small number of cases. There are published case report and case series along with the two main trials, viz. Scleroderma Lung Study and the Fibrosing Alveolitis Study, but again, there is no consensus on treatment protocols. In this report, we present a case of aggressive interstitial lung disease in a patient with SSc, which improved dramatically on treatment with intra-venous cyclophosphamide and high dose prednisolone therapy.

  6. Cyclophosphamide-induced reversible posterior leukoencephalopathy syndrome.

    Science.gov (United States)

    Abenza-Abildua, Maria Jose; Fuentes, Blanca; Diaz, Domingo; Royo, Aranzazu; Olea, Teresa; Aguilar-Amat, Maria Jose; Diez-Tejedor, Exuperio

    2009-01-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical radiological syndrome, characterised by acute headache, altered consciousness, seizures and hypertension. The most frequent causes are hypertensive encephalopathy, eclampsia and some immunosuppressive therapies. The pathogenesis remains unclear, but it appears to be related to altered cerebral circulation, producing oedema that can be seen on MRI, and it resolves in 2 or 3 weeks. In the present report, a possible first reported case of cyclophosphamide-induced RPLS in a 27-year-old man with high blood pressure (HBP) and glomerulonephritis caused by Goodpasture syndrome, treated with cyclophosphamide during the last month and prednisone for glomerulonephritis resulting from Goodpasture syndrome without other immunosuppressive drugs, is described.Symptoms appeared during a hypertensive crisis, but when cyclophosphamide was replaced by rituximab and hypertension was controlled, the patient did not have neurological symptoms. Almost all reported cases induced by immunosuppressive therapy or other causes were associated with hypertension as well.

  7. Adenoviral delivery of pan-caspase inhibitor p35 enhances bystander killing by P450 gene-directed enzyme prodrug therapy using cyclophosphamide+

    Directory of Open Access Journals (Sweden)

    Doloff Joshua C

    2010-09-01

    Full Text Available Abstract Background Cytochrome P450-based suicide gene therapy for cancer using prodrugs such as cyclophosphamide (CPA increases anti-tumor activity, both directly and via a bystander killing mechanism. Bystander cell killing is essential for the clinical success of this treatment strategy, given the difficulty of achieving 100% efficient gene delivery in vivo using current technologies. Previous studies have shown that the pan-caspase inhibitor p35 significantly increases CPA-induced bystander killing by tumor cells that stably express P450 enzyme CYP2B6 (Schwartz et al, (2002 Cancer Res. 62: 6928-37. Methods To further develop this approach, we constructed and characterized a replication-defective adenovirus, Adeno-2B6/p35, which expresses p35 in combination with CYP2B6 and its electron transfer partner, P450 reductase. Results The expression of p35 in Adeno-2B6/p35-infected tumor cells inhibited caspase activation, delaying the death of the CYP2B6 "factory" cells that produce active CPA metabolites, and increased bystander tumor cell killing compared to that achieved in the absence of p35. Tumor cells infected with Adeno-2B6/p35 were readily killed by cisplatin and doxorubicin, indicating that p35 expression is not associated with acquisition of general drug resistance. Finally, p35 did not inhibit viral release when the replication-competent adenovirus ONYX-017 was used as a helper virus to facilitate co-replication and spread of Adeno-2B6/p35 and further increase CPA-induced bystander cell killing. Conclusions The introduction of p35 into gene therapeutic regimens constitutes an effective approach to increase bystander killing by cytochrome P450 gene therapy. This strategy may also be used to enhance other bystander cytotoxic therapies, including those involving the production of tumor cell toxic protein products.

  8. Sequential Therapy With Fludarabine, High-Dose Cyclophosphamide, and Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia Produces High-Quality Responses: Molecular Remissions Predict for Durable Complete Responses

    Science.gov (United States)

    Lamanna, Nicole; Jurcic, Joseph G.; Noy, Ariela; Maslak, Peter; Gencarelli, Alison N.; Panageas, Katherine S.; Heaney, Mark L.; Brentjens, Renier J.; Golde, David W.; Scheinberg, David A.; Zelenetz, Andrew D.; Weiss, Mark A.

    2009-01-01

    Purpose Modern combination strategies are active in chronic lymphocytic leukemia (CLL) but can have significant myelosuppression and immunosuppression that may require dose attenuation for safety. We explored a sequential treatment strategy to allow safe delivery of active agents at full doses. Previously, we studied sequential therapy with fludarabine followed by cyclophosphamide (F→C). In that study, cyclophosphamide consolidation improved the frequency of complete response (CR) four-fold. Subsequently, rituximab was added to this regimen (F→C→R). Patients and Methods Thirty-six previously untreated CLL patients received therapy with fludarabine 25 mg/m2 on days 1 through 5 every 4 weeks for six cycles, followed by consolidation with cyclophosphamide 3,000 mg/m2 administered every 3 weeks for three cycles, followed by consolidation with weekly rituximab 375 mg/m2 for four cycles. Evaluation for minimal residual disease included flow cytometry and a highly sensitive clonotypic polymerase chain reaction (PCR). The median age was 59 years (range, 37 to 71 years), 61% of patients had high-risk disease, and 58% had unmutated IgVH genes. Results There were 32 responses (89%), including 22 CRs (61%). Consolidation with cyclophosphamide improved responses in 13 patients (36%); nine patients (25%) further improved their response with rituximab. Twenty patients (56%) achieved flow cytometric CRs, and 12 patients (33%) achieved a molecular CR (PCR negative). Patients achieving molecular CRs had an excellent prognosis with a plateau in the response duration curve, and 90% remain in clinical CR at 5 years. For the entire group, 5-year survival rate is 71% compared with a rate of 48% with our prior F→C regimen (P = .10). Conclusion Sequential therapy with F→C→R yields improvement in quality of response, with many patients achieving a PCR-negative state. PMID:19075280

  9. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial

    DEFF Research Database (Denmark)

    de Groot, Kirsten; Harper, Lorraine; Jayne, David R W

    2009-01-01

    BACKGROUND: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. OBJECTIVE: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. DESIGN: Randomized, controlled trial. Random assignments were compu...

  10. Anthracycline-based induction chemotherapy followed by concurrent cyclophosphamide, methotrexate and 5-fluorouracil and radiation therapy in surgically resected axillary node-positive breast cancer.

    Science.gov (United States)

    Recchia, Francesco; Candeloro, Giampiero; Cesta, Alisia; DI Staso, Mario; Bonfili, Pierluigi; Gravina, Giovanni Luca; DI Cesare, Ernesto; Necozione, Stefano; Rea, Silvio

    2014-05-01

    The present study aimed to determine the toxicity and efficacy of 4 courses of anthracyclines-taxane (AT) chemotherapy followed by radiation therapy (XRT) concurrent with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in surgically resected axillary node-positive (N+) breast cancer. A total of 200 women with N+ breast cancer were treated with adriamycin and docetaxel followed by XRT concurrent with six courses of CMF. Two courses of dose-dense chemotherapy with ifosfamide, carboplatin and etoposide, supported by pegfilgrastim, were administered to patients with >5 histologically confirmed axillary lymph node metastases and patients with triple-negative disease. Additional treatments included 1 year of trastuzumab in human epidermal growth factor receptor 2-positive patients, 5 years of a luteinizing hormone-releasing hormone analogue in premenopausal women and 5 years of an aromatase inhibitor (AI) in estrogen receptor-positive (ER+) patients. The mean number of positive axillary lymph nodes was 4.4 (range, 2-37), 52% of the patients were premenopausal, 74% were ER+ and 26% had triple-negative disease. After a median follow-up of 73 months, grade 2 and 3 hematological toxicity was observed in 20% of the patients. The 10-year disease-free survival (DFS) and overall survival (OS) rates were 73 and 77%, respectively. There was no significant difference in DFS between ER+ and estrogen receptor-negative (ER-) patients (P>0.05), whereas the OS was better in ER+ vs. ER- patients (P<0.05) and in premenopausal vs. postmenopausal patients (P<0.005). In conclusion, induction AT concurrent CMF and XRT and dose-dense chemotherapy followed by AI in N+ high-risk breast cancer was associated with a low level of systemic and late cardiac toxicity and excellent local control, DFS and OS.

  11. Tacrolimus versus intravenous pulse cyclophosphamide therapy in Chinese adults with steroid-resistant idiopathic minimal change nephropathy: a multicenter, open-label, nonrandomized cohort trial.

    Science.gov (United States)

    Li, Heng; Shi, Xiangdong; Shen, Hong; Li, Xiayu; Wang, Huiping; Li, Hongmei; Xu, Guangbiao; Chen, Jianghua

    2012-05-01

    The treatment of steroid-resistant minimal change nephropathy (SR-MCN) in adults remains a challenge to nephrologists. Although immunosuppressants such as cyclophosphamide (CTX), chlorambucil, and cyclosporin A have been used in these patients, their use has been limited by low remission rates and severe adverse effects. Alternative immunosuppressive treatments for SR-MCN are therefore needed. The aim of this study was to compare the efficacy of tacrolimus (TAC) with that of intravenous (IV) pulse CTX therapy in the management of SR-MCN and to assess the tolerability of those treatments. This was a nonrandomized, case-matched trial in Chinese adults with SR-MCN. Patients were self-assigned to either: (1) combination therapy with prednisone and oral TAC; or (2) combination therapy with prednisone and IV CTX. TAC was initiated at 0.05 mg/kg/d and was adjusted to maintain a trough blood level of 5 to 10 ng/mL for 1 year. CTX was initiated at 1 g/1.73 m(2) for a total dosage of 10 g/1.73 m(2) over 1 year. In both groups, oral prednisone was initiated at 0.5 mg/kg/d for 3 months but was tapered off to complete cessation by 6 months. A total of 37 patients were enrolled (21 in the TAC group; 16 in the CTX group), of whom 33 (19 in the TAC group; 14 in the CTX group) completed the study. There were no significant difference in baseline demographic characteristics between the two treatment groups (The TAC group-mean age at onset, 28.8 [11.3]; mean age at trial, 29.6 [11.0]; male, 63.16%; The CTX group-mean age at onset, 34.4 [12.7]; mean age at trial, 35.9 [12.7]; male, 57.14%). The remission rates were 57.9%, 73.7%, and 78.9% in the TAC group and 14.3%, 42.9%, and 50.0% in the CTX group after 2, 4, and 6 months, respectively. The remission rate at 2 months was significantly higher in the TAC group than in the CTX group (P therapy and the 1-year follow-up were higher in the TAC group than in the CTX group (Kaplan-Meier curve, log-rank test, P therapy and 1-year follow

  12. Improved survival in young children with acute granulocytic leukemia treated with combination therapy using cyclophosphamide, oncovin, cytosine arabinoside, and prednisone.

    Science.gov (United States)

    Madanat, F F; Sullivan, M P

    1979-09-01

    Seven of 17 children (41%) under 5 years of age with acute granulocytic leukemia (AGL) treated with either cytosine arabinoside-cytoxan (CA-CYT) or Mini-COAP (CA-CYT with vincristine sulfate [VCR] and prednisone) have been in continuous complete remission 4 years or more. CA and CYT were each given in the dosage of 120 mg/m2 intravenously, daily in 3 divided doses, for 4 days. Induction consisted of two courses given at intervals of 2 weeks; during maintenance the courses were repeated at intervals of 4 weeks. In the Mini-COAP regimen, standard 28-day VCR-prednisone therapy was superimposed on CA-CYT induction and 4-day VCR-prednisone pulses were superimposed on CA-CYT maintenance. Transient moderate to severe myelosuppression was frequent; other manifestations of toxicity were mild. Administration of drugs at home was feasible in many instances. Mini-COAP was proved to be an effective therapeutic regimen for young children with AGL and should be considered as initial therapy.

  13. Effects of interactive metronome training on postural stability and upper extremity function in Parkinson’s disease: a case study

    Science.gov (United States)

    Kim, Arim; Lee, Hye-Sun; Song, Chiang-Soon

    2017-01-01

    [Purpose] The purpose of this study was to examine the effects of interactive metronome training on the postural stability and upper extremity function of an individual with Parkinson’s disease. [Subject and Methods] The participant of this case study was a 75-year-old female with Parkinson’s disease diagnosed 7 years prior. This study was a single-subject research with an A-B-A design. She received IM training during the treatment phase (B phase) for 40 minutes per session. She was assessed pretest and posttest using the Berg balance scale and Wolf motor function test, and at baseline and the treatment phase using the measured box-and-block test and a Tetrax system. [Results] After training, the patient’s static and dynamic balance, functional activity, and performance time of the upper extremity improved. Interactive metronome therapy improved the manual dexterity of both hands. Interactive metronome therapy also improved the limit of stability of the Parkinson’s disease. [Conclusion] Though a case study, the results of this study suggest that IM therapy is effective at restoring the postural stability and upper extremity function of patients with Parkinson’s disease. PMID:28210066

  14. Unusual nail pigmentation following cyclophosphamide-containing chemotherapy regimen

    Directory of Open Access Journals (Sweden)

    Kumar Santosh

    2010-01-01

    Full Text Available Cyclophosphamide therapy may rarely cause pigmentation of the nails which is of different patterns. We report a patient who developed pigmentation of nails after six cycles of cyclophosphamide, methotrexate, and 5-flourouracil chemotherapy, each repeated after 28 days for breast cancer. The patient developed nail pigmentation that started proximally and spread distally and involved all the nails of both hands and feet except the second and third toenails of right foot. Using Naranjo ADR Probability Scale, the case revealed a "probable" association with cyclophosphamide.

  15. From total empiricism to a rational design of metronomic chemotherapy phase I dosing trials.

    Science.gov (United States)

    Lam, Thomas; Hetherington, John W; Greenman, John; Maraveyas, Anthony

    2006-02-01

    'Metronomic chemotherapy' represents a novel anti-angiogenic strategy whereby low-dose chemotherapy is utilized in a continuous fashion in order to target tumor endothelium. There are many potential advantages of this strategy and clinical trials are already underway. However, although the scheduling of metronomic chemotherapy is relatively unequivocal, metronomic dosing principles are at present poorly defined. Arbitrarily, 10-33% of the maximum tolerated dose comprises 'the dose range'. We argue that this is too empirical and propose a set of phase I metronomic chemotherapy dosing strategies based on a principled approach which may help to reduce the problem of empiricism in dosing for metronomic chemotherapy trials.

  16. Cyclophosphamide-Induced Severe Acute Hyponatremic Encephalopathy in Patients with Breast Cancer: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Michelle Baker

    2014-07-01

    Full Text Available Background: Cyclophosphamide is an alkylating agent widely used in antineoplastic and immunosuppressive therapies. Symptomatic hyponatremia can be a rare but life-threatening complication in patients treated with cyclophosphamide. Case Presentations: We report 2 patients who presented with severe acute hyponatremic encephalopathy after receiving their first cycles of a low-dose cyclophosphamide-containing regimen for breast cancer. In case 1, a 58-year-old female received the combination of docetaxel and cyclophosphamide, and in case 2, a 56-year-old female received the combination of doxorubicin and cyclophosphamide. Both patients recovered after correction of their serum sodium concentration without neurological deficits. Future cycles of chemotherapy were well tolerated without recurrence of hyponatremia after cyclophosphamide was discontinued from the respective regimens. Conclusion: Clinicians must always keep in mind that acute hyponatremic encephalopathy can be induced by low-dose cyclophosphamide.

  17. Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience

    Directory of Open Access Journals (Sweden)

    Avinash Pandey

    2016-01-01

    Full Text Available Background: Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge. Aim: To evaluate outcomes of epithelial ovarian carcinoma. Objectives: To calculate disease-free survival (DFS, overall survival (OS, and factors affecting outcomes. Materials and Methods: Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan-Meir survival was used to determine disease-free and OS. Log-rank test used to evaluate factors affecting outcome. Results: Median follow-up is 26 months. 93/102 patients (91% underwent cytoreductive surgery, of which 37 had primary cytoreduction (40% while 56 had interval cytoreduction. 21/93 (23%, 57/93 (61%, and 15/93 (16% patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel-platinum was used in 35/63 (56% patients while 28/63 patients (44% received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01, OS was 54 versus 26 months (P = 0.01.40/88 (45% patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2-18 months. Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69. Conclusion: Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression.

  18. Cyclophosphamide in diffuse lung damage.

    Science.gov (United States)

    Musiatowicz, B; Sulkowska, M; Sulik, M; Famulski, W; Dziecioł, J; Sobaniec-Lotowska, M; Baltaziak, M; Arciuch, L; Rółkowski, R; Jabłońska, E

    1997-01-01

    Some cyclophosphamide toxic effects on lung tissue are presented. Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung tissue changes caused by that agent were characterized. Attention was focused on BAL evaluation as a useful method in the monitoring of lung tissue damage degree.

  19. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.

    Science.gov (United States)

    Mostafa, Heba H; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J

    2016-09-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus-specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential.

  20. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

    Science.gov (United States)

    Mostafa, Heba H.; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J.

    2016-01-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

  1. Cyclophosphamide in the treatment of toxic epidermal necrolysis.

    Science.gov (United States)

    Frangogiannis, N G; Boridy, I; Mazhar, M; Mathews, R; Gangopadhyay, S; Cate, T

    1996-10-01

    A patient with non-small cell lung carcinoma and recent radiotherapy for brain metastases developed toxic epidermal necrolysis (TEN) shortly after therapy with phenytoin was initiated for a seizure. Exfoliation progressed to involve 90% of her body surface despite treatment with high-dose corticosteroids for 5 days, but sloughing and systemic toxicity ceased within 2 days of initiating therapy with intravenous cyclophosphamide (300 mg/day). Reepithelialization rapidly followed. This experience and the reports of others suggest that intravenous cyclophosphamide is helpful in the treatment of TEN.

  2. Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study

    Science.gov (United States)

    Pasquier, Eddy; André, Nicolas; Street, Janine; Chougule, Anuradha; Rekhi, Bharat; Ghosh, Jaya; Philip, Deepa S.J.; Meurer, Marie; MacKenzie, Karen L.; Kavallaris, Maria; Banavali, Shripad D.

    2016-01-01

    Background Angiosarcomas are rare malignant tumors of vascular origin that represent a genuine therapeutic challenge. Recently, the combination of metronomic chemotherapy and drug repositioning has been proposed as an attractive alternative for cancer patients living in developing countries. Methods In vitro experiments with transformed endothelial cells were used to identify synergistic interactions between anti-hypertensive drug propranolol and chemotherapeutics. This led to the design of a pilot treatment protocol combining oral propranolol and metronomic chemotherapy. Seven consecutive patients with advanced/metastatic/recurrent angiosarcoma were treated with this combination for up to 12 months, followed by propranolol-containing maintenance therapy. Findings Gene expression analysis showed expression of ADRB1 and ADRB2 adrenergic receptor genes in transformed endothelial cells and in angiosarcoma tumors. Propranolol strongly synergized with the microtubule-targeting agent vinblastine in vitro, but only displayed additivity or slight antagonism with paclitaxel and doxorubicin. A combination treatment using bi-daily propranolol (40 mg) and weekly metronomic vinblastine (6 mg/m2) and methotrexate (35 mg/m2) was designed and used in 7 patients with advanced angiosarcoma. Treatment was well tolerated and resulted in 100% response rate, including 1 complete response and 3 very good partial responses, based on RECIST criteria. Median progression-free and overall survival was 11 months (range 5–24) and 16 months (range 10–30), respectively. Interpretation Our results provide a strong rationale for the combination of β-blockers and vinblastine-based metronomic chemotherapy for the treatment of advanced angiosarcoma. Furthermore, our study highlights the potential of drug repositioning in combination with metronomic chemotherapy in low- and middle-income country setting. Funding This study was funded by institutional and philanthropic grants. PMID:27211551

  3. Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study.

    Science.gov (United States)

    Tan, A R; Johannes, H; Rastogi, P; Jacobs, S A; Robidoux, A; Flynn, P J; Thirlwell, M P; Fehrenbacher, L; Stella, P J; Goel, R; Julian, T B; Provencher, L; Bury, M J; Bhatt, K; Geyer, C E; Swain, S M; Mamounas, E P; Wolmark, N

    2015-01-01

    This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA-C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.

  4. Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high-grade, operable osteosarcomas of the extremities: A report from the Latin American Group of Osteosarcoma Treatment.

    Science.gov (United States)

    Senerchia, Andreza A; Macedo, Carla Renata; Ferman, Sima; Scopinaro, Marcelo; Cacciavillano, Walter; Boldrini, Erica; Lins de Moraes, Vera Lúcia; Rey, Guadalupe; de Oliveira, Claudia T; Castillo, Luis; Almeida, Maria Tereza; Borsato, Maria Luisa; Lima, Eduardo; Lustosa, Daniel; Barreto, José Henrique; El-Jaick, Tatiana; Aguiar, Simone; Brunetto, Algemir; Greggiani, Lauro; Cogo-Moreira, Hugo; Atallah, Alvaro; Petrilli, Antonio Sergio

    2017-05-15

    Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high-grade operable osteosarcomas (OSTs) of the extremities was investigated. Patients with high-grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event-free survival (EFS) from randomization. There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP-MC group and the MAP-alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS. According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities. Cancer 2017;123:1003-10. © 2016 American Cancer Society. © 2016 American Cancer Society.

  5. The co-presence of deletion 7q, 20q and inversion 16 in therapy-related acute myeloid leukemia developed secondary to treatment of breast cancer with cyclophosphamide, doxorubicin, and radiotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Yonal Ipek

    2012-02-01

    Full Text Available Abstract Introduction Therapy-related acute myeloid leukemia occurs as a complication of treatment with chemotherapy, radiotherapy, immunosuppressive agents or exposure to environmental carcinogens. Case presentation We report a case of therapy-related acute myeloid leukemia in a 37-year-old Turkish woman in complete remission from breast cancer. Our patient presented to our facility with fatigue, fever, sore throat, peripheral lymphadenopathy, and moderate hepatosplenomegaly. On peripheral blood and bone marrow aspirate smears, monoblasts were present. Immunophenotypic analysis of the bone marrow showed expression of CD11b, CD13, CD14, CD15, CD33, CD34, CD45 and human leukocyte antigen-DR, findings compatible with the diagnosis of acute monoblastic leukemia (French-American-British classification M5a. Therapy-related acute myeloid leukemia developed three years after adjuvant chemotherapy consisting of an alkylating agent, cyclophosphamide and DNA topoisomerase II inhibitor, doxorubicin and adjuvant radiotherapy. Cytogenetic analysis revealed a 46, XX, deletion 7 (q22q34, deletion 20 (q11.2q13.1 karyotype in five out of 20 metaphases and inversion 16 was detected by fluorescence in situhybridization. There was no response to chemotherapy (cytarabine and idarubicin, FLAG-IDA protocol, azacitidine and our patient died in the 11th month after diagnosis. Conclusions The median survival in therapy-related acute myeloid leukemia is shorter compared to de novoacute myeloid leukemia. Also, the response to therapy is poor. In therapy-related acute myeloid leukemia, complex karyotypes have been associated with abnormalities of chromosome 5, rather than 7. To the best of our knowledge, this is the first case of therapy-related acute myeloid leukemia showing the co-presence of deletion 7q, 20q and the inversion 16 signal.

  6. Metronomic capecitabine in gastroenteropancreatic neuroendrocrine tumors: a suitable regimen and review of the literature

    Directory of Open Access Journals (Sweden)

    Bongiovanni A

    2014-10-01

    Full Text Available Alberto Bongiovanni,1 Nada Riva,1 Sebastiano Calpona,1 Marianna Ricci,1 Erica Gunelli,1 Chiara Liverani,1 Federico La Manna,1 Alessandro De Vita,1 Manuela Monti,1 Stefano Severi,2 Federica Pieri,3 Elena Amadori,1 Riccardo Galassi,1 Davide Cavaliere,4 Alberto Zaccaroni,5 Andreas Tartaglia,6 Veronica Lunedei,7 Andrea Gardini,8 Laura Mercatali,1 Dino Amadori,1 Toni Ibrahim11Osteoncology and Rare Tumors Center, 2Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST IRCCS, Meldola, 3Pathology Unit, 4Unit of Oncological Surgery and Advanced Therapies, 5Endocrine Surgery Unit, 6Endocrinology Unit, 7Gastroenterology and Digestive Endoscopy Unit, 8Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, ItalyBackground: We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs. A review of the literature is also presented.Methods: From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29–82 years. The median treatment duration was 8 months.Results: Five (50% patients achieved a partial radiographic response, four (40% showed stable disease, and one (10% progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively.Conclusion: Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective

  7. Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Petry, V.; Gagliato, D.M.; Leal, A.I.C.; Arai, R.J.; Longo, E. [Divisão de Oncologia Médica, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Andrade, F. [Núcleo de Mastologia, Hospital Sírio Libanês, São Paulo, SP (Brazil); Ricci, M.D.; Piato, J.R.; Barroso-Sousa, R.; Hoff, P.M.; Mano, M.S. [Divisão de Oncologia Médica, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-03-06

    Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m{sup 2} during 8 weeks followed by weekly doxorubicin at 24 mg/m{sup 2} for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

  8. Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

    Science.gov (United States)

    Guetz, Sylvia; Tufman, Amanda; von Pawel, Joachim; Rittmeyer, Achim; Borgmeier, Astrid; Ferré, Pierre; Edlich, Birgit; Huber, Rudolf Maria

    2017-01-01

    Micro-abstract In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo) in advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20–50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP), overall survival (OS) and tolerability. Results Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs). Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21 days and only marginal accumulation. The tolerability profile was acceptable (all dose levels – all grades: decreased appetite 33%, diarrhea 33%, leukopenia 33%, nausea 30%, vomiting 26%; ≥grade 3: leukopenia 30%, lymphopenia 19%, neutropenia 19%, febrile neutropenia 15%). Disease control rate, OS and TTP signaled a treatment effect. Conclusion Daily metronomic NVBo therapy in extensively pretreated patients with advanced NSCLC is feasible and safe at the recommended dose of 30 mg/d. Escalation to 40 mg/d in the second cycle is possible. The blood concentrations of vinorelbine after daily metronomic dosing reached lower peaks than intravenous or oral conventional

  9. Pro: Cyclophosphamide in lupus nephritis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2016-01-01

    Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up d

  10. Pro: Cyclophosphamide in lupus nephritis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2016-01-01

    Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up d

  11. Rhythmic synchronization tapping to an audio-visual metronome in budgerigars

    National Research Council Canada - National Science Library

    Hasegawa, Ai; Okanoya, Kazuo; Hasegawa, Toshikazu; Seki, Yoshimasa

    2011-01-01

    ... in understanding the evolution of musical entrainment. We trained eight budgerigars to perform isochronous tapping tasks in which they pecked a key to the rhythm of audio-visual metronome-like stimuli...

  12. Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer.

    Science.gov (United States)

    Colleoni, Marco; Cole, Bernard F; Viale, Giuseppe; Regan, Meredith M; Price, Karen N; Maiorano, Eugenio; Mastropasqua, Mauro G; Crivellari, Diana; Gelber, Richard D; Goldhirsch, Aron; Coates, Alan S; Gusterson, Barry A

    2010-06-20

    Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor-absent, and endocrine receptor-present subtypes. No clear chemotherapy benefit was observed in endocrine receptor-present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor-present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor-absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor-present disease). The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

  13. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Gruppo Interegionale Cooperativo Oncologico Ginecologia.

    Science.gov (United States)

    1987-08-15

    565 patients with stage III-IV epithelial ovarian cancer were randomly assigned to receive cisplatin (P), cyclophosphamide and cisplatin (CP), or cyclophosphamide, doxorubicin, and cisplatin (CAP). Data on 531 patients were analysed. Treatment with CAP resulted in a significantly higher overall (complete and partial) response rate (66 vs 56 vs 49% for CAP, CP, and P, respectively), but the rate of complete surgical response for the three treatment arms was similar (26, 21, and 20%). Size of residual tumour after first surgery and Karnofsky index were the best predictors of complete remission. Survival and disease-free survival were not significantly different in the three arms, although progression-free survival was significantly longer after CAP. However, tumour size, cell type, and Karnofsky index, but not therapy, were independent predictors for survival. Haematological toxicity was highest with CAP. The addition of cyclophosphamide or doxorubicin and cyclophosphamide to cisplatin does not substantially increase the number of potentially curable, advanced ovarian cancer patients.

  14. Center of cancer systems biology second annual workshop--tumor metronomics: timing and dose level dynamics.

    Science.gov (United States)

    Hahnfeldt, Philip; Hlatky, Lynn; Klement, Giannoula Lakka

    2013-05-15

    Metronomic chemotherapy, the delivery of doses in a low, regular manner so as to avoid toxic side effects, was introduced over 12 years ago in the face of substantial clinical and preclinical evidence supporting its tumor-suppressive capability. It constituted a marked departure from the classic maximum-tolerated dose (MTD) strategy, which, given its goal of rapid eradication, uses dosing sufficiently intense to require rest periods between cycles to limit toxicity. Even so, upfront tumor eradication is frequently not achieved with MTD, whereupon a de facto goal of longer-term tumor control is often pursued. As metronomic dosing has shown tumor control capability, even for cancers that have become resistant to the same drug delivered under MTD, the question arises whether it may be a preferable alternative dosing approach from the outset. To date, however, our knowledge of the coupled dynamics underlying metronomic dosing is neither sufficiently well developed nor widely enough disseminated to establish its actual potential. Meeting organizers thus felt the time was right, armed with new quantitative approaches, to call a workshop on "Tumor Metronomics: Timing and Dose Level Dynamics" to explore prospects for gaining a deeper, systems-level appreciation of the metronomics concept. The workshop proved to be a forum in which experts from the clinical, biologic, mathematical, and computational realms could work together to clarify the principles and underpinnings of metronomics. Among other things, the need for significant shifts in thinking regarding endpoints to be used as clinical standards of therapeutic progress was recognized.

  15. Dexamethasone-Cyclophosphamide Pulse Therapy In Pemphigus : An Appraisal OF Its Outcome In A Tertiary Health Care Center In South India

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2004-01-01

    Full Text Available Dexamethasone-cyclophoshamide pulse (DCP therapy, designed by Pasricha and Gupta for pemphigus was first used in 1981 with the aim of reducing the toxicity of corticosteroids and also to achieve better therapeutic results. We have been using the same pulse therapy and herewith are presenting the results of pulse therapy in pemphigus were included in the study over a period of 6 years. They consisted of 51 cases of pemphigus vulgaris and 4 cases of pemphigus foliaceous. The male to female ration was 1.2:1. The age distribution showed a bimodal pattern with peaks at 21-30 years and 51-60 years. The body surface area involved at the time of initiation of DCP was less than 25% in 25, 25-50% in 19 and more than 50% in 11 cases. Oral cavity was involved in all cases of pemphigus vulgaris and eyes were affected in 4 patients. Twentysix cases were managed with DCP pulses only and were in remission in phase II and three of our patients in remission in phase III relapsed at 6 to 9 months. Interpulse steroids were required to induce remission in 11 patients. The remaining 18 patients did not proceed to phase II as they was either defaulting or had active disease. Only four cases progressed into phase IV and were declared cured. The various complications seen in our patients were candidiasis (n=5, hiccups (2, acneiform eruption (2, iatrogenic Cushing’s syndrome (1, herpes zoster (1, striae distensae (1, umbilical abscess (1, alopecia (1, azoospermia (1 pneumonia (1 and deep vein thrombosis (1. Two Patients on pulse therapy died of septicemia.

  16. Kaposi's sarcoma in an elderly man with Wegener's granulomatosis treated with cyclophosphamide and corticosteroids.

    Science.gov (United States)

    Erban, S B; Sokas, R K

    1988-05-01

    The association of Kaposi's sarcoma with malignant lymphoreticular diseases and immunosuppressive therapy is well documented. This report describes an elderly man who presented with fulminant Wegener's granulomatosis that responded to treatment with cyclophosphamide and corticosteroids. Rapidly progressing cutaneous Kaposi's sarcoma developed ten weeks after the start of immunosuppressive therapy yet regressed on discontinuation of the corticosteroid therapy, despite continuation of cyclophosphamide therapy. To our knowledge, this is the first reported case of Kaposi's sarcoma occurring in association with Wegener's granulomatosis. The literature on Kaposi's sarcoma in immunosuppressed patients is reviewed.

  17. A comparative effectiveness research of azathioprine and cyclophosphamide on the clinical and serological response in pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Kabir Sardana

    2016-01-01

    Full Text Available Context: A prospective study was carried out to examine the efficacy of cyclophosphamide and azathioprine in pemphigus vulgaris. Aims: To compare the clinical and serological effect of azathioprine and cyclophosphamide in pemphigus patients. Materials and Methods: Prospective, institutional based study was conducted twenty-one patients of pemphigus vulgaris were initiated on either azathioprine (n = 9 or cyclophosphamide (n = 7 in addition to prednisolone and were evaluated clinically (mucosal and cutaneous severity and serologically enzyme-linked immunosorbent assay (ELISA at 0, 3 and 6 months. Results: Azathioprine had a slower onset of action with a statistically significant improvement seen by 6 months (P = 0.016. Cyclophosphamide had a faster onset of action (3 months though there was no statistical difference in the efficacy between the two at the end of 6 months. The (RonT was 33.3-44.4% for azathioprine and 28.8-42.9% for cyclophosphamide at 6 months. Though ELISA had a high sensitivity and specificity for diagnosis, as a tool for assessing therapeutic response a significant decrease was seen only till 3 months. This was restricted to Dsg1 for the azathioprine group and both Dsg3 and Dsg1 levels for the cyclophosphamide group. There were two deaths, both in the cyclophosphamide group. Conclusions: Azathiorpine and cyclophosphamide are equally effective for mucosal and cutaneous disease in pemphigus after 6 months of therapy. Dsg ELISA is useful for diagnosis of pemphigus but is not a useful tool for monitoring response to therapy.

  18. Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration

    Directory of Open Access Journals (Sweden)

    Catherine Weber

    2012-01-01

    Full Text Available Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG, and total body irradiation (TBI followed by an allogeneic hematopoietic stem cell transplant (HSCT for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

  19. Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

    Directory of Open Access Journals (Sweden)

    Guetz S

    2017-02-01

    days and only marginal accumulation. The tolerability profile was acceptable (all dose levels – all grades: decreased appetite 33%, diarrhea 33%, leukopenia 33%, nausea 30%, vomiting 26%; ≥grade 3: leukopenia 30%, lymphopenia 19%, neutropenia 19%, febrile neutropenia 15%. Disease control rate, OS and TTP signaled a treatment effect. Conclusion: Daily metronomic NVBo therapy in extensively pretreated patients with advanced NSCLC is feasible and safe at the recommended dose of 30 mg/d. Escalation to 40 mg/d in the second cycle is possible. The blood concentrations of vinorelbine after daily metronomic dosing reached lower peaks than intravenous or oral conventional dosing. Blood concentrations were consistent with anti-angiogenic or immune modulating pharmacologic properties of vinorelbine. Further studies are warranted to evaluate the safety and efficacy of this novel approach in specific patient populations. Keywords: NSCLC, dose escalation, lung carcinoma, vinca-alkaloid, anti-angiogenic treatment, cytotoxic therapy, vinorelbine capsules

  20. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

    DEFF Research Database (Denmark)

    Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

    2016-01-01

    BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less to...

  1. Metronomic chemotherapy in anaplastic thyroid carcinoma: A potentially feasible alternative to therapeutic nihilism

    Directory of Open Access Journals (Sweden)

    Swaroop Revannasiddaiah

    2015-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT, and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  2. Cyclophosphamide-induced temporomandibular synostosis.

    Science.gov (United States)

    Bacon, W

    1983-06-01

    The study of malformations helps toward a better understanding of normal development, which is of significance to the orthodontist. Experiments in teratology have induced an extensive variety of facial abnormalities, but temporomandibular joint (TMJ) synostosis has never been previously reported. Ten pregnant female rabbits were treated with a daily injection of 50 mg. cyclophosphamide (DNA synthesis inhibitor), from day 11 to day 14, which is the period that precedes formation of the face. The control sample comprised five female rabbits. The fetuses were obtained by cesarean section on day 28 and stained with alizarin. Six of the ten treated female animals produced offspring that had TMJ synostosis. The skull with TMJ synostosis showed a retrognathic mandibular pattern in relation to the maxilla, and the bony trabeculae in the mandibular angle showed a downward orientation instead of the horizontal orientation seen in animals without synostosis. The length of the heads was significantly smaller in the treatment group than in the control group; within the treatment group, the heads with synostosis were significantly smaller than those without synostosis. It could be hypothesized that the cyclophosphamide might have affected intrinsic factors in the temporomandibular mesenchyma; an impairment in the development and function of the mandibular musculature, which is a vital factor in joint development and maintenance, might also have contributed to the genesis of the malformation. The association of immobilization and mandibular hypodevelopment seems to be in agreement with today's theories on maxillofacial growth.

  3. Temporary elimination of IL-10 enhanced the effectiveness of cyclophosphamide and BMDC-based therapy by decrease of the suppressor activity of MDSCs and activation of antitumour immune response.

    Science.gov (United States)

    Rossowska, Joanna; Anger, Natalia; Kicielińska, Jagoda; Pajtasz-Piasecka, Elżbieta; Bielawska-Pohl, Aleksandra; Wojas-Turek, Justyna; Duś, Danuta

    2015-03-01

    The antitumour activity of the dendritic cell (DC)-based cellular vaccines is greatly reduced in hostile tumour microenvironment. Therefore, there are many attempts to eliminate or neutralize both suppressor cells and cytokines. The aim of the investigation was to verify if temporary elimination of IL-10 just before injection of bone marrow-derived DCs (BMDCs) enhance the antitumour activity of applied vaccines and help to overcome the immunosuppressive tumour barrier. Mice bearing colon carcinoma MC38 were given single dose of cyclophosphamide (CY) followed by alternate injections of anti-IL-10 antibodies and BMDC-based vaccines consisted of BMDCs stimulated with MC38 tumour antigen (BMDC/TAg) or the combination of BMDC/TAg with BMDCs transduced with IL-12 genes (BMDC/IL-12). The high tumour growth inhibition was observed in mice treated with CY+anti-IL-10+BMDC/TAg as well as CY±anti-IL-10+BMDC/TAg+BMDC/IL-12. However, the mechanisms of action of particular treatment schemes were diversified. Generally, it was observed that application of anti-IL-10 Abs reduced suppressor activity of myeloid-derived suppressor cells (MDSCs). However, anti-IL-10 Abs in combination with diversely composed BMDC-based vaccines induced different components of an antitumour response. The high cytotoxic activity of spleen-derived NK cells and increased influx of these cells into tumours of mice treated with CY+anti-IL-10+BMDC/TAg indicate that mice from the group developed strong NK-dependent response. Whereas, application of anti-IL-10 Abs just before injection of BMDC/TAg+BMDC/IL-12 did not enhanced NK cell activity. Furthermore, it significantly impaired effectiveness of therapy composed of CY+BMDC/TAg+BMDC/IL-12 vaccine in induction of Th1 type immune response. Taken together, our results indicate that temporary elimination of IL-10 is an important and effective way to decrease the immune suppression associated with MDSCs activity and represents a useful strategy for successful

  4. Experimental study of the irrational phase synchronization of coupled nonidentical mechanical metronomes.

    Directory of Open Access Journals (Sweden)

    Zhiwen Song

    Full Text Available It has recently been observed in numerical simulations that the phases of two coupled nonlinear oscillators can become locked into an irrational ratio, exhibiting the phenomenon of irrational phase synchronization (IPS [Phys. Rev. E 69, 056228 (2004]. Here, using two coupled nonidentical periodic mechanical metronomes, we revisit this interesting phenomenon through experimental studies. It is demonstrated that under suitable couplings, the phases of the metronomes indeed can become locked into irrational ratios. Numerical simulations confirm the experimental observations and also reveal that in the IPS state, the system dynamics are chaotic. Our studies provide a solid step toward further studies of IPS.

  5. A phase II trial of ixabepilone and cyclophosphamide as neoadjuvant therapy for patients with HER2-negative breast cancer: correlation of pathologic complete response with the 21-gene recurrence score.

    Science.gov (United States)

    Yardley, Denise A; Peacock, Nancy W; Shastry, Mythili; Burris, Howard A; Bechhold, Rebecca G; Hendricks, Carolyn B; Yoshizawa, Carl N; Sing, Amy P; Hainsworth, John D

    2015-11-01

    Ixabepilone and the taxanes have similar activity in the first-line treatment of metastatic breast cancer, and ixabepilone is sometimes effective in taxane-refractory patients. We conducted a phase 2 trial to evaluate ixabepilone in combination with cyclophosphamide as neoadjuvant treatment for patients with locally advanced HER2-negative breast cancer. Response to neoadjuvant treatment was correlated with the baseline 21-gene Recurrence Score® (Oncotype DX; Genomic Health Inc, Redwood City, CA). Eligible women with HER2-negative locally advanced breast cancer received ixabepilone 40 mg/m(2) plus cyclophosphamide 600 mg/m(2) on day 1 of each 21-day cycle. Following 6 cycles, patients underwent definitive surgery. Primary endpoint was rate of pathologic complete response (pCR). Breast biopsy tumor samples were obtained at pretreatment and at surgery in patients with residual disease. Tumor specimens were analyzed using the 21-gene assay. One hundred sixty-eight patients (median age 52 years; 45 % triple-negative) were enrolled; 161 (96 %) underwent definitive surgery following neoadjuvant ixabepilone/cyclophosphamide. Overall, 27 patients (17 %) achieved pCR, including 19 of 73 (26 %) triple-negative patients. The most frequently occurring grade 3/4 toxicity was neutropenia (98 patients; 58 %). Recurrence Scores were highly correlated with achievement of pCR (0/36 with low or intermediate Recurrence Scores vs. 19/72 with high Recurrence Scores; p = 0.002). There was high concordance between baseline and post-treatment Recurrence Scores in the 72 patients with paired samples. The combination of ixabepilone and cyclophosphamide yielded a pCR rate of 17 %, similar to other neoadjuvant chemotherapy regimens. Pathologic complete responses occurred only in patients with high-risk baseline Recurrence Scores.

  6. Compound list: cyclophosphamide [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available cyclophosphamide CPA 00024 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/cycloph...osphamide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/cycloph...osphamide.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATE...ST/Rat/in_vivo/Liver/Single/cyclophosphamide.Rat.in_vivo.Liver.Single.zip ftp://f...tp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/cyclophosphamide.Rat.in_vivo.Liver.

  7. Diagnostic accuracy of metronome-paced tachypnea to detect dynamic hyperinflation

    NARCIS (Netherlands)

    Lahaije, A.J.M.C.; Willems, L.M.; Hees, H.W. van; Dekhuijzen, P.N.R.; Helvoort, H.A.C. van; Heijdra, Y.F.

    2013-01-01

    INTRODUCTION: This prospective study was carried out to investigate if metronome-paced tachypnea (MPT) can serve as an accurate diagnostic tool to identify patients with chronic obstructive pulmonary disease (COPD) who are susceptible to develop dynamic hyperinflation during exercise. Commonly, this

  8. Dynamic hyperinflation after metronome-paced hyperventilation in COPD--a 2 year follow-up.

    NARCIS (Netherlands)

    Hannink, J.D.C.; Lahaije, A.; Bischoff, E.W.M.A.; Helvoort, H.A.C. van; Dekhuijzen, R.; Schermer, T.R.J.; Heijdra, Y.F.

    2010-01-01

    In contrast to the decline in FEV(1), the behavior of dynamic hyperinflation (DH) over time is unknown in patients with COPD. Metronome-paced hyperventilation (MPH) is a simple applicable surrogate for exercise to detect DH. OBJECTIVE: To evaluate changes in MPH-induced DH during two years follow-up

  9. How to Sync to the Beat of a Persistent Fractal Metronome without Falling Off the Treadmill?

    Directory of Open Access Journals (Sweden)

    Melvyn Roerdink

    Full Text Available In rehabilitation, rhythmic acoustic cues are often used to improve gait. However, stride-time fluctuations become anti-persistent with such pacing, thereby deviating from the characteristic persistent long-range correlations in stride times of self-paced walking healthy adults. Recent studies therefore experimented with metronomes with persistence in interbeat intervals and successfully evoked persistent stride-time fluctuations. The objective of this study was to examine how participants couple their gait to a persistent metronome, evoking persistently longer or shorter stride times over multiple consecutive strides, without wandering off the treadmill. Twelve healthy participants walked on a treadmill in self-paced, isochronously paced and non-isochronously paced conditions, the latter with anti-persistent, uncorrelated and persistent correlations in interbeat intervals. Stride-to-stride fluctuations of stride times, stride lengths and stride speeds were assessed with detrended fluctuation analysis, in conjunction with an examination of the coupling between stride times and stride lengths. Stride-speed fluctuations were anti-persistent for all conditions. Stride-time and stride-length fluctuations were persistent for self-paced walking and anti-persistent for isochronous pacing. Both stride times and stride lengths changed from anti-persistence to persistence over the four non-isochronous metronome conditions, accompanied by an increasingly stronger coupling between these gait parameters, with peak values for the persistent metronomes. These results revealed that participants were able to follow the beat of a persistent metronome without falling off the treadmill by strongly coupling stride-length fluctuations to the stride-time fluctuations elicited by persistent metronomes, so as to prevent large positional displacements along the treadmill. For self-paced walking, in contrast, this coupling was very weak. In combination, these results

  10. 来氟米特联合环磷酰胺冲击治疗重症顽固性狼疮肾炎疗效观察%Clinical observation of leflunomide combined with cyclophosphamide pulse therapy for severe refractory lupus ne-phritis

    Institute of Scientific and Technical Information of China (English)

    王瑞生; 李小红

    2015-01-01

    ObJective To investigate the effect of leflunomide combined with cyclophosphamide pulse therapy on patients with severe refractory lupus nephritis. Methods From May 2011 to May 2013,28 patients with severe refractory lupus nephritis were selected for the study,the patients were given leflunomide combined with cyclophosphamide pulse ther-apy. Results After treatment and follow-up of one year,the indicators showed significant improvement in patients,and the data before treatment,compared with the data of 6 month,1 years after the treatment,there were significant differences ( P﹤0. 05). Conclusions Leflunomide combined with cyclophosphamide pulse therapy for severe refractory lupus nephri-tis has significant therapeutic effect,high safety,so it is worth promoting in clinical use.%目的:探讨来氟米特联合环磷酰胺冲击治疗重症顽固狼疮肾炎的临床效果。方法选取2011年5月至2013年5月间收治的重症顽固性狼疮肾炎患者28例患者作为研究对象,采用来氟米特联合环磷酰胺冲击治疗。结果治疗并随访1年,患者的各项指标均有明显的改善,治疗前与治疗后6个月、1年间各项数据的比较差异有统计学意义( P﹤0.05)。结论来氟米特联合环磷酰胺冲击治疗重症顽固性狼疮肾炎具有治疗效果显著,安全性高等特点,值得临床推广应用。

  11. 环磷酰胺冲击联合激素与单纯激素治疗狼疮性肾炎的随机对照试验%Randomized Controlled Study on the Effects of Intensive Cyclophosphamide Therapy Plus Corticosteroids and Corticosteroids-alone Treatment for Lupus Nephritis

    Institute of Scientific and Technical Information of China (English)

    蒋志嵩

    2001-01-01

    目的:了解环磷酰胺间歇冲击加激素治疗狼疮性肾炎的短期和中期疗效。方法:将27例重症狼疮性肾炎患者随机分为两组。单纯治疗组用泼尼松治疗,联合治疗组用环磷酰胺间歇冲击加泼尼松治疗。疗程约1.5年,随访4年。结果:治疗结束时,两组的多个单项疗效指标和综合疗效指标的差异具有显著性(P<0.05);随访4年后,两组的复发率具有显著性差异(P<0.05)。结论:联合治疗组的短期和中期疗效优于单纯治疗组。%To investigate the short and long-term effects of intensive cyclophosphamide therapy plus corticosteroids on lupus mephritis, 27 patients with severe lupus nephritis were divided into two groups. Patients in group 1 received prednisone alone and patients in group 2 were given intensive cyclophosphamide therapy plus corticosteroids. The treatment course lasted for 1.5 years and the patients were followed up for 4 years. At the end of the treatment, the differences in indicators, single or comprehensive, of effieacy were statistically signifieant(P<0.05) between the two groups. A four-year follow-up showed that the difference in relapse was significant(P<0.05). It is concluded that the intensive cyclophosphamide therapy plus corticosteroids on lupus nephritis was better than that of predinison-alone treatment in our series in terms of short-term and long-term effects on lupus nephritis.

  12. Wirksamkeit und Verträglichkeit von Cyclophosphamid bei Multipler Sklerose: Eine retrospektive Analyse

    OpenAIRE

    2008-01-01

    Cyclophosphamid (Endoxan) ist ein zytostatisches Medikament, welches wegen seiner immunsuppressiven Wirkung eine breite Anwendung in der Therapie systemischer Autoimmunerkrankungen findet. Es wird als Medikation bei schwerer chronisch-progressiver Multipler Sklerose empfohlen, um die weitere Progredienz einzuschränken oder zu verhindern. Bisherige klinische Studien über den Wert dieses therapeutischen Einsatzes liefern aber kontroverse Ergebnisse. Aus diesem Grund erschien es sinnvoll...

  13. Is biopsy required prior to cyclophosphamide in steroid-sensitive nephrotic syndrome?

    NARCIS (Netherlands)

    Stadermann, M.B.; Lilien, M.R.; Kar, N.C.A.J. van de; Monnens, L.A.H.; Schröder, C.H.

    2003-01-01

    AIM: The present studywas designed to retrospectively evaluate the use of renal biopsies prior to cyclophosphamide therapy. The aim of the study was to determine in how many cases histological outcome of the biopsies had subsequently changed the decision to treat or refrain from treatment. PATIENTS

  14. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial

    NARCIS (Netherlands)

    Grootscholten, C.; Ligtenberg, G.; Hagen, E. C.; van den Wall Bake, A. W. L.; de Glas-Vos, J. W.; Bijl, M.; Assmann, K. J.; Bruijn, J. A.; van Houwelingen, H. C.; Derksen, R. H. W. M.; Berden, J. H. M.; Weening, J.J.

    2006-01-01

    Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), w

  15. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial.

    NARCIS (Netherlands)

    Grootscholten, C.; Ligtenberg, G.; Hagen, E.C.; Wall Bake, A.W. van den; Glas-Vos, J.W. de; Bijl, M.; Assmann, K.J.M.; Bruijn, J.A.; Weening, J.J.; Houwelingen, H.C. van; Derksen, R.H.W.M.; Berden, J.H.M.

    2006-01-01

    Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), w

  16. An open add-on study on cyclophosphamide in patients with refractory myasthenic crisis

    Institute of Scientific and Technical Information of China (English)

    蒋建明; 涂来慧; 吴涛; 张仁琴; 丁素菊; 蔡建英

    2003-01-01

    Objective: To assess the efficacy and side effects of cyclophosphamide on refractory myasthenic crisis.Methods: Five patients of myasthenic crisis refractory to usual comprehensive treatment, entered an open additional study with cyclophosphamide 200 mg VD q.d or 400 mg VD q.o.d with 6-10 g of total dosage.The patients were followed up for 1-8 years.Results: All the 5 patients were effectively treated with obvious remission in 3 and improvement in 2.Two patients have returned to partial work.The side effects were tolerable.Conclusion: The present clinical trial showed that cyclophosphamide was effective, particularly in a long term as an additional therapy for treating MG patients with refractory crisis of myasthenia gravis.

  17. A Comparative Effectiveness Research of Azathioprine and Cyclophosphamide on the Clinical and Serological Response in Pemphigus Vulgaris

    Science.gov (United States)

    Sardana, Kabir; Agarwal, Pooja; Bansal, Shivani; Uppal, Beena; Garg, Vijay K

    2016-01-01

    Context: A prospective study was carried out to examine the efficacy of cyclophosphamide and azathioprine in pemphigus vulgaris. Aims: To compare the clinical and serological effect of azathioprine and cyclophosphamide in pemphigus patients. Materials and Methods: Prospective, institutional based study was conducted twenty-one patients of pemphigus vulgaris were initiated on either azathioprine (n = 9) or cyclophosphamide (n = 7) in addition to prednisolone and were evaluated clinically (mucosal and cutaneous severity) and serologically enzyme-linked immunosorbent assay (ELISA) at 0, 3 and 6 months. Results: Azathioprine had a slower onset of action with a statistically significant improvement seen by 6 months (P = 0.016). Cyclophosphamide had a faster onset of action (3 months) though there was no statistical difference in the efficacy between the two at the end of 6 months. The (RonT) was 33.3–44.4% for azathioprine and 28.8–42.9% for cyclophosphamide at 6 months. Though ELISA had a high sensitivity and specificity for diagnosis, as a tool for assessing therapeutic response a significant decrease was seen only till 3 months. This was restricted to Dsg1 for the azathioprine group and both Dsg3 and Dsg1 levels for the cyclophosphamide group. There were two deaths, both in the cyclophosphamide group. Conclusions: Azathiorpine and cyclophosphamide are equally effective for mucosal and cutaneous disease in pemphigus after 6 months of therapy. Dsg ELISA is useful for diagnosis of pemphigus but is not a useful tool for monitoring response to therapy. PMID:27512188

  18. Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer.

    Science.gov (United States)

    Leach, T N; Childress, M O; Greene, S N; Mohamed, A S; Moore, G E; Schrempp, D R; Lahrman, S R; Knapp, D W

    2012-06-01

    The purpose of this study was to assess the toxicoses and antitumor activity of metronomic chlorambucil at a dosage of 4 mg m(-2) daily in dogs with naturally occurring cancer. Thirty-six dogs were enrolled in the study. The protocol was well tolerated with no grade 3 or 4 toxicoses noted. Complete remission was achieved, and lasted over 35 weeks in three dogs (mast cell tumour, soft tissue sarcoma and thyroid carcinoma). Partial remission was noted in 1 dog with histiocytic sarcoma (39 weeks duration) for an overall remission rate of 11% (4 of 36). Stable disease was noted in 17 dogs (47%) with various other cancers. The median progression-free interval was 61 days, and the median survival time was 153 days. Chlorambucil given in a metronomic protocol showed antitumor activity in dogs with a variety of naturally occurring cancers.

  19. Understanding the antiangiogenic effect of metronomic chemotherapy through a simple mathematical model

    Science.gov (United States)

    Rodrigues, Diego S.; Mancera, Paulo F. A.; Pinho, Suani T. R.

    2016-12-01

    Despite the current and increasingly successful fight against cancer, there are some important questions concerning the efficiency of its treatment - in particular, the design of oncology chemotherapy protocols. Seeking efficiency, schedules based on more frequent, low-doses of drugs, known as metronomic chemotherapy, have been proposed as an alternative to the classical standard protocol of chemotherapy administration. The in silico approach may be very useful for providing a comparative analysis of these two kinds of protocols. In so doing, we found that metronomic schedules are more effective in eliminating tumour cells mainly due to their chemotherapeutic action on endothelial cells and that more frequent, low drug doses also entail outcomes in which the survival time of patient is increased.

  20. Prednisone, cyclophosphamide, aspirin therapy clinical study of lupus nephritis%泼尼松、环磷酰胺、阿斯匹林治疗狼疮性肾炎的临床研究

    Institute of Scientific and Technical Information of China (English)

    李有跃; 华伟; 刘福文; 郭峰

    2011-01-01

    Objective To prednisone, cyclophosphamide, aspirin treatment of lupus nephritis clinical effects and adverse reactions. Methods 98 patients with lupus nephritis were randomly divided into treatment group and control group, two groups were given prednisone and regulation of blood lipids and other basic treatment group was treated with cyclophosphamide, aspirin treatment, the control group, only throwing Nepal Pine and regulation of blood lipids and other basic treatment; treatment: both 12 weeks. Results The treatment group 24h urine protein, blood urea nitrogen, serum creatinine, blood lipids, serum albumin, anti-nuclear antibodies, blood pressure, clinical symptoms and other indicators of improvement, prednisone dosage and recurrence rates significantly better than the control group. Conclusion Prednisone, cyclophosphamide, aspirin treatment of lupus nephritis significantly better than prednisone alone, regulate blood lipids and other therapeutic effects.%目的 探讨泼尼松、环磷酰胺、阿斯匹林治疗狼疮性肾炎的临床效果以及不良反应.方法 将98例狼疮性肾炎患者随机分为治疗组与对照组,两组均给予泼尼松和调节血脂等基础治疗,治疗组给予环磷酰胺、阿斯匹林治疗,对照组用泼尼松和调节血脂等基础治疗;疗程均为12周.结果 治疗组24h尿蛋白定量、尿素氮、血肌酐、血脂、血清清蛋白、抗核抗体、血压、临床症状等指标的改善、泼尼松的用量和复发率等明显优于对照组.结论 泼尼松、环磷酰胺、阿斯匹林治疗狼疮性肾炎的效果明显好于单纯泼尼松、调节血脂等治疗的效果.

  1. 环磷酰胺治疗儿童紫癜性肾炎的Meta分析%A meta-analysis of cyclophosphamide therapy for Henoch-Schönlein purpura nephritis in children

    Institute of Scientific and Technical Information of China (English)

    孙智才; 杨华彬; 曾海丽

    2014-01-01

    性研究进一步证实。%Objective To assess the efficacy and safety of cyclophosphamide(CTX) therapy for Henoch-Schönlein purpura nephritis(HSPN) in children. Methods Cochrane Library, ACP Journal Club, PubMed, OVID, EBSCO, CNKI, Wanfang Data and VIP Database were searched for studies, conference materials and dissertations concerning CTX therapy for HSPN in children without language restriction as completely as possible. Formulate the including and excluding criteria as well as the efficacy judgement criteria. According to the criterias and quality evaluation standards of Cochrane Handbook 5.1.0, articles were screened and evaluated with by two researchers respectively. Review Manager 5.2 software was used for meta-analysis. Results A total of 423 papers were included, containing 176 English articles and 247 Chinese articles. According to the including and excluding criteria, eight RCTs were enrolled for meta-analysis. Eight RCTs all didn’t describe the method of random allocation and didn’t use double blind method. All of them were lack of information about allocation concealment, withdrawal and loss of subject, selectively reporting and other bias, but all used established diagnostic criteria. The results were as follows:(1)The remission rate of CTX plus GC group was higher than that of GC group(RR=1.58, 95%CI:1.36, 1.85); (2)The 24 h urine protein of CTX plus GC group was lower than that of GC group(MD=-2.04, 95%CI: -2.92, -1.71), and albumin was higher than that of GC group(MD=7.61, 95%CI:4.69, 10.52);(3)Adverse effects: Hormone side effects incidence of CTX plus GC group was lower than that of GC group, gastrointestinal reaction incidence of CTX plus GC group was higher than that of GC group, but there was no significant difference in respiratory infection, leukopenia, hemorrhagic cystitis, alopecia and hepatic dysfunction between two groups. Conclusions Compared to GC, the remission rate in CTX plus GC group was higher and this treatment was more

  2. Metronomic administration of chlorambucil for treatment of dogs with urinary bladder transitional cell carcinoma.

    Science.gov (United States)

    Schrempp, Diane R; Childress, Michael O; Stewart, Jane C; Leach, Tiffany N; Tan, Kean Ming; Abbo, Andrew H; de Gortari, Amalia E; Bonney, Patty L; Knapp, Deborah W

    2013-06-01

    To determine the antitumor effects and toxicoses of metronomic oral administration of a low dose of chlorambucil in dogs with transitional cell carcinoma (TCC). Prospective clinical trial. 31 client-owned dogs with TCC for which prior treatments had failed or owners had declined other treatments. Procedures-Chlorambucil (4 mg/m2, PO, q 24 h) was administered to dogs. Before and at scheduled times during treatment, evaluations of dogs included physical examination, CBC, serum biochemical analyses, urinalysis, thoracic and abdominal imaging including cystosonography for measurement of TCCs, and grading of toxicoses. 29 of 31 dogs had failed prior TCC treatment. Of the 30 dogs with available data, 1 (3%) had partial remission (≥ 50% reduction in tumor volume), 20 (67%) had stable disease (chlorambucil treatment to the day progressive disease was detected) for the dogs was 119 days (range, 7 to 728 days). The median survival time of dogs from the time of the start of chlorambucil treatment was 221 days (range, 7 to 747 days). Few toxicoses were detected; chlorambucil administration was discontinued because of toxicoses in only 1 dog. Metronomic administration of chlorambucil was well tolerated, and 70% of dogs had partial remission or stable disease. Metronomic administration of chlorambucil may be a treatment option for dogs with TCC.

  3. FROM HUMANS TO DOGS AND BACK: THE TRANSLATIONAL LESSON OF METRONOMIC CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    Alessio Pierini

    2012-01-01

    Full Text Available The main priority in veterinary oncology is to maintain patient quality of life. It is important that new chemotherapy strategies aim to minimize side effects, thus making the treatment attractive for owners as well as their pets. Metronomic chemotherapy has been shown to have an important stabilizing effect on human cancer (including chemotherapy-resistant disease resulting in prolonged clinical benefit. In addition, this form of treatment has been shown to have positive effects on the quality of life of patients with various types of cancer. These positive effects are obtained without any indication of high grade toxicity. Moreover, low cost and oral administration (which reduces the need for hospitalization and enables patients to stay at home longer are key characteristics of this schedule, offering important advantages in frail subgroups of patients (e.g., old patients for whom new therapeutic options are greatly needed. From another perspective, use of metronomic chemotherapy in dogs could reveal new and innovative schedules that could be applied to humans. Veterinary oncology cases treated with metronomic schedules represent the unique opportunity to ethically investigate novel drugs or combination treatments that may be highly translatable to the human community. The aim of the present review was to describe how this new form of treatment has evolved in canine patients thus far."

  4. Metronome Use for Coordination of Breaths and Cardiac Compressions Delivered by Minimally-Trained Caregivers During Two-Person CPR

    Science.gov (United States)

    Hurst, Victor, IV; West, Sarah; Austin, Paul; Branson, Richard; Beck, George

    2005-01-01

    Astronaut crew medical officers (CMO) aboard the International Space Station (ISS) receive 40 hours of medical training over 18 months before each mission, including two-person cardiopulmonary resuscitation (2CPR) as recommended by the American Heart Association (AHA). Recent studies have concluded that the use of metronomic tones improves the coordination of 2CPR by trained clinicians. 2CPR performance data for minimally-trained caregivers has been limited. The goal of this study was to determine whether use of a metronome by minimally-trained caregivers (CMO analogues) would improve 2CPR performance. 20 pairs of minimally-trained caregivers certified in 2CPR via AHA guidelines performed 2CPR for 4 minutes on an instrumented manikin using 3 interventions: 1) Standard 2CPR without a metronome [NONE], 2) Standard 2CPR plus a metronome for coordinating compression rate only [MET], 3) Standard 2CPR plus a metronome for coordinating both the compression rate and ventilation rate [BOTH]. Caregivers were evaluated for their ability to meet the AHA guideline of 32 breaths-240 compressions in 4 minutes. All (100%) caregivers using the BOTH intervention provided the required number of ventilation breaths as compared with the NONE caregivers (10%) and MET caregivers (0%). For compressions, 97.5% of the BOTH caregivers were not successful in meeting the AHA compression guideline; however, an average of 238 compressions of the desired 240 were completed. None of the caregivers were successful in meeting the compression guideline using the NONE and MET interventions. This study demonstrates that use of metronomic tones by minimally-trained caregivers for coordinating both compressions and breaths improves 2CPR performance. Meeting the breath guideline is important to minimize air entering the stomach, thus decreasing the likelihood of gastric aspiration. These results suggest that manifesting a metronome for the ISS may augment the performance of 2CPR on orbit and thus may

  5. The Risk of Sustained Amenorrhea in Patients with Systemic Lupus Erythematosus Receiving Intermittent Pulse Cyclophosphamide Therapy%大剂量环磷酰胺冲击治疗系统性红斑狼疮时的闭经危险

    Institute of Scientific and Technical Information of China (English)

    刘钢; 陈永涛; 王玲; 左川; 谢其冰; 王忠明; 林懋贤

    2001-01-01

    目的研究大剂量环磷酰胺冲击治疗系统性红斑狼疮时的闭经危险。方法前瞻性对比研究51例接受大剂量环磷酰胺冲击治疗的生育期女性患者与22例接受甲基强的松龙治疗的生育期女性患者的闭经发生率及其规律。结果大剂量环磷酰胺冲击治疗组闭经率19.6%,比甲基强的松龙治疗组的闭经率明显增高(P=0.025);大剂量环磷酰胺冲击治疗组中,年龄大于30岁组比30岁及30岁以下组闭经率高(P=0.0018)。结论大剂量环磷酰胺冲击治疗系统性红斑狼疮时,生育期女性患者闭经率升高。年龄愈大,闭经的危险愈高。%Objective To determine the risk of sustained amenorrhea in premenopausal women with systemic lupus erythematosus (SLE) receiving intermittent pulse cyclophosphamide (CTX) therapy. Methods Prospectively comparing the amenorrhea rate of 51 cases receiving intermittent pulse cyclophosphamide therapy versus that of 22 cases receiving intermittent pulse methylprednisolone (MP) therapy. Results The amenorrhea rate was higher in the CTX group (19.6%) than in the MP group (P=0.025).In the CTX group, the amenorrhea rate of patients aged over 30 was higher than that of patients aged 30 or below 30 (P=0.0018). Conclusion Pulse CTX therapy in fertile women with SLE is associated with increased rate of sustained amenorrhea, and the older the patient is, the higher risk for sustained amenorrhea the patient runs.

  6. Hyperbaric oxygen-A new horizon in treating cyclophosphamide-induced hemorrhagic cystitis

    Directory of Open Access Journals (Sweden)

    S Ajith Kumar

    2011-01-01

    Full Text Available Hemorrhagic cystitis consists of acute or insidious diffuse bleeding from the bladder mucosa. It can be caused by radiation, drugs, autoimmune diseases, viral and bacterial infections, etc. Hemorrhagic cystitis is a well-recognized complication of cyclophosphamide therapy and it can be potentially fatal. We discuss two cases of cyclophosphamide-induced hemorrhagic cystitis where outcome of conventional management was not satisfactory and a novel therapy using hyperbaric oxygen was used. Hyperbaric oxygen therapy (HBOT reduces inflammation, stimulates neoangiogenesis, maintains tissue oxygenation and heals tissue hypoxia and radio necrosis. Patients received 100% oxygen in a hyperbaric chamber at 2.5 atmosphere absolute (ATA for 90 minutes, 5 days a week. One patient was given 36 sessions and the other was given 19 sessions of HBOT. HBOT resulted in complete cessation of bleeding; no side effect was noted during the course of therapy. There was no relapse after 12 months of cessation of treatment. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.

  7. Dual effects of indoleamine 2,3-dioxygenase inhibitors on the therapeutic effects of cyclophosphamide and cycloplatam on Ehrlich ascites tumor in mice.

    Science.gov (United States)

    Bogdanova, L A; Morozkova, T S; Amitina, S A; Mazhukin, D G; Nikolin, V P; Popova, N A; Kaledin, V I

    2014-08-01

    Ethyl pyruvate, an inhibitor of indoleamine 2,3-dioxygenase, slightly suppressed the growth of transplantable Ehrlich tumor in mice and significantly potentiated the therapeutic effect of cyclophosphamide. Another inhibitor amidoxime produced a similar effect. However, both ethyl pyruvate and amidoxime significantly reduced the effect of cycloplatam therapy. The observed changes can be stipulated by different effects of cyclophosphamide and cycloplatam on the subpopulations of lymphoid cells taking part in the formation of antitumor immunity and resistance to tumors.

  8. Metronome LKM: An open source virtual keyboard driver to measure experiment software latencies.

    Science.gov (United States)

    Garaizar, Pablo; Vadillo, Miguel A

    2017-09-15

    Experiment software is often used to measure reaction times gathered with keyboards or other input devices. In previous studies, the accuracy and precision of time stamps has been assessed through several means: (a) generating accurate square wave signals from an external device connected to the parallel port of the computer running the experiment software, (b) triggering the typematic repeat feature of some keyboards to get an evenly separated series of keypress events, or (c) using a solenoid handled by a microcontroller to press the input device (keyboard, mouse button, touch screen) that will be used in the experimental setup. Despite the advantages of these approaches in some contexts, none of them can isolate the measurement error caused by the experiment software itself. Metronome LKM provides a virtual keyboard to assess an experiment's software. Using this open source driver, researchers can generate keypress events using high-resolution timers and compare the time stamps collected by the experiment software with those gathered by Metronome LKM (with nanosecond resolution). Our software is highly configurable (in terms of keys pressed, intervals, SysRq activation) and runs on 2.6-4.8 Linux kernels.

  9. Investigations with spectroscopy, zeta potential and molecular modeling of the non-cooperative behaviour between cyclophosphamide hydrochloride and aspirin upon interaction with human serum albumin: binary and ternary systems from multi-drug therapy.

    Science.gov (United States)

    Omidvar, Zahra; Parivar, Kazem; Sanee, Hamideh; Amiri-Tehranizadeh, Zeinab; Baratian, Ali; Saberi, Mohammad Reza; Asoodeh, Ahmad; Chamani, Jamshidkhan

    2011-08-01

    The interaction between cyclophosphamide hydrochloride (CYC) and aspirin (ASA) with human serum albumin (HSA) was studied by various kind of spectroscopic, ζ potential and molecular modeling under physiological conditions. The fluorescence data showed that the binding of drugs to proteins caused strong static fluorescence quenching. The analysis of the fluorescence quenching of HSA in the binary and ternary systems displayed that ASA was affected by the complex formed between CYC and HSA. Moreover, CYC was influenced by the HSA-ASA complex. The inherent binding information, including the quenching mechanism, binding constants, number of binding sites, effective quenching constant, fraction of the initial fluorescence and thermodynamic parameters were measured by the fluorescence quenching technique at various temperatures. In addition, according to the synchronous fluorescence spectra of HSA, the results showed that the fluorescence quenching of HSA originated from the Trp and Tyr residues, and indicated a conformational change of HSA with the addition of the drugs. Far-UV CD spectra of HSA were recorded before and after the addition of ASA and CYC as binary and ternary systems. An increase in intensity of the positive CD peak of HSA was observed in the presence of the drugs. The results were interpreted by excited interactions between the aromatic residues of the HSA binding sites and the drugs bound to them. The distance r between donor and acceptor was obtained by the Forster energy according to fluorescence resonance energy transfer (FRET) and found to be 2.35 nm and 1.78 nm for CYC and ASA, respectively. This confirmed the existence of static quenching for proteins in the presence of CYC and ASA. Furthermore, docking studies pointed at a reduction of the affinity of each of the drug compounds to the protein in the presence of the other in meaningful amounts. Pre-binding of any of the said compounds forced the second to bind in a non-optimized location and

  10. A study upon the influence of cyclophosphamide treatment on the red blood cells of the chicken embryo (Short Notes

    Directory of Open Access Journals (Sweden)

    Delia Anca HAS-LAZAU

    2006-05-01

    Full Text Available The aim of this study is to show the effect of cyclophosphamide on the eveloping red blood cells of the 3-4 days old chicken embryo, when the hematopoiesis is at its peack, located at the vitelline sack level.I have chosen to work with the chicken embryo red blood cells because they have an intense mitotic activity as well as a tumoural cell-like behaviour.It is vital to know the particularities of the cell cycle of the healthy and tumoural cells, keeping in mind that most of the cytostatics act upon the cell which are developing their cell cycle (Menkes B., Prelipceanu O., Checiu I., Căpălnăşan I. 1979.The cyclophosphamide is not stage-dependent, as it acts in all the stages of the cell cycle, its mutagen effect being accompanied also by a cell cycle stopping (Paşca C., Crăciun C., Ardelean A. 2000.Cyclophosphamide supply determines retrenchment of the cell division, transforming the normal cells into multinucleated cells, with normal ploydia. The cyclophosphamide is a cytostatic using for cancer therapy (Schiavoni G., Mattei F., Di Pucchio T., Santini S. M., Bracci L., Berardelli F., Proietti F. 2000.Reshearches have done lots of studies along the years both on mice and rats, concerning the effects of cyclophosphamide on: thymus and burse fabricio ( Giurgea R., Toma V., 1977, stromal cells of bone marrow (Anton E. 1997, pulmonary thrombocytopoiesis (Sulkowki S., Sulkowska M., Musiatowikz B. 1997.

  11. Replication and Pedagogy in the History of Psychology V: The Metronome and Wilhelm Wundt's Search for the Components of Consciousness

    Science.gov (United States)

    Ayala, Christopher; Borawski, Steven; Miller, Jonathon

    2008-01-01

    Wilhelm Wundt (1832-1920) believed that consciousness was represented by the interconnection of psychical processes comprised of temporal elements and compounds. To explore these processes, Wundt used a metronome to measure the amount of information that passed into consciousness across time. The current project replicated some of his procedures,…

  12. HLA Haplotype Mismatch Transplants and Posttransplant Cyclophosphamide

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    Andrea Bacigalupo

    2016-01-01

    Full Text Available The use of high dose posttransplant cyclophosphamide (PT-CY introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome. The current questions to be answered include the use of PT-CY for sibling and unrelated donors transplant, possibly in the context of prospective randomized trial.

  13. Con: Cyclophosphamide for the treatment of lupus nephritis.

    Science.gov (United States)

    Mok, Chi Chiu

    2016-07-01

    Kidney involvement is a major determinant for morbidity and mortality in patients with systemic lupus erythematosus. The treatment target of lupus renal disease is to induce and maintain remission and to minimize disease or treatment-related comorbidities. Cyclophosphamide (CYC), in conjunction with glucocorticoids, has conventionally been used for the initial treatment of lupus nephritis. However, the major concerns of CYC are its toxicities, such as infertility, urotoxicity and oncogenicity, which are particularly relevant in women of childbearing age. As a result, maintenance therapy of lupus nephritis with an extended course of CYC pulses has largely been replaced by other immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine. Recent randomized controlled trials have demonstrated non-inferiority of MMF to pulse CYC as induction therapy of lupus nephritis. Although MMF as induction-maintenance therapy has been increasingly used in lupus nephritis, its efficacy in the long-term preservation of renal function remains to be elucidated. MMF is not necessarily less toxic than CYC. Meta-analyses of clinical trials show similar incidence of infective complications and gastrointestinal adverse events in both MMF- and CYC-based regimens. However, considering the reduction in gonadal toxicity and the risk of oncogenicity, MMF may be used as first-line therapy of lupus nephritis. Tacrolimus (TAC) has recently been shown to be equivalent to either MMF or CYC for inducing remission of lupus nephritis and may be considered as another non-CYC alternative. Combined low-dose MMF and TAC appears to be more effective than CYC pulses in Chinese patients with lupus nephritis and has the potential to replace the more toxic CYC regimens in high-risk patients. Currently, CYC still plays an important role in the management of lupus nephritis patients with impaired or rapidly deteriorating renal function, crescentic glomerulonephritis or as salvage therapy for

  14. Successful treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in systemic lupus erythematosus (SLE) with oral cyclophosphamide.

    Science.gov (United States)

    Jasmin, R; Sockalingam, S; Shahrizaila, N; Cheah, T-E; Zain, A A; Goh, K-J

    2012-09-01

    Peripheral neuropathy is a known manifestation of systemic lupus erythematosus. However, the association of primary autoimmune inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) with SLE is uncommon. We report a 26-year-old man who simultaneously presented with severe CIDP and photosensitive rash, but was unresponsive to intravenous immunoglobulin infusion and continued to progress. He was found to have underlying SLE and improved with combined corticosteroid and immunosuppressive therapy with oral cyclophosphamide. CIDP with underlying SLE may be more resistant to conventional therapy with IVIG, requiring the addition of other immunosuppressive agents.

  15. Hepatic colorectal cancer metastases showing a distinctive pattern of pathological response after metronomic capecitabine and bevacizumab.

    Science.gov (United States)

    Pietrantonio, Filippo; Biondani, Pamela; Pellegrinelli, Alessandro; Marchianò, Alfonso; Dotti, Katia Fiorella; Buzzoni, Roberto; Di Bartolomeo, Maria

    2012-12-01

    A 48-year-old man was referred to our hospital with the diagnosis of colon cancer with multiple hepatic metastases. After right hemicolectomy, the rapid progression of liver disease was treated with metronomic capecitabine and bevacizumab according to a study protocol. A gradual regression of metastatic lesions was observed during a 9-month treatment period. After conversion of liver disease to resectability, the histological examination disclosed the complete necrosis of all lesions, with the exception of small neoplastic foci inside a single nodule. The comparison of this type of histological findings with the classic sclero-hyaline pathological response, as well as its importance as indicator of response to antiangiogenic treatment, is discussed.

  16. Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

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    Jochen Greiner

    2010-01-01

    Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

  17. The random parallel control study of cyclophosphamide combined with prednisone therapy for idiopathic interstitial pneumonia%环磷酰胺联合泼尼松治疗特发性间质性肺炎随机平行对照研究

    Institute of Scientific and Technical Information of China (English)

    罗田应

    2015-01-01

    orally,increased 25 mg every 7 ~ 12 days,until take the dose of 150 mg/ d;took prednisone orally at the dose of 0. 5 mg/ kg,for 4 weeks,then 0. 25 mg/ kg for 4 weeks,and then 0. 125 mg/ kg or 0. 25 mg/ kg each two days. 12 weeks as a treatment,then judge the curative effects including arterial partial pressure of oxygen(PaO2 )and vital capacity(VC),the score of CRP. Results Arterial oxygen partial pressure and lung capacity in each group were significant changed( P ﹤ 0. 05). The CRP scores were significantly lower( P ﹤ 0. 05),and group C treatment is better than A,B groups. Conclusion Cyclophosphamide combined with prednisone therapy for idiopathic interstitial pneumonia is more effective.

  18. Imaging enhancement of malignancy by cyclophosphamide: surprising chemotherapy opposite effects

    Science.gov (United States)

    Yamauchi, Kensuke; Yang, Meng; Hayashi, Katsuhiro; Jiang, Ping; Xu, Mingxu; Yamamoto, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro; Moossa, A. R.; Bouvet, Michael; Hoffman, Robert M.

    2008-02-01

    Although side effects of cancer chemotherapy are well known, "opposite effects" of chemotherapy which enhance the malignancy of the treated cancer are not well understood. We have observed a number of steps of malignancy that are enhanced by chemotherapy pre-treatment of mice before transplantation of human tumor cells. The induction of intravascular proliferation, extravasation, and colony formation by cancer cells, critical steps of metastasis was enhanced by pretreatment of host mice with the commonly-used chemotherapy drug cyclophosphamide. Cyclophosphamide appears to interfere with a host process that inhibits intravascular proliferation, extravasation, and extravascular colony formation by at least some tumor cells. Cyclophosphamide does not directly affect the cancer cells since cyclophosphamide has been cleared by the time the cancer cells were injected. Without cyclophosphamide pretreatment, human colon cancer cells died quickly after injection in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the cancer cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. However, when the host mice were pretreated with cyclophosphamide, the cancer cells survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the cancer cells. This review describes an important unexpected "opposite effects" of chemotherapy that enhances critical steps in malignancy rather than inhibiting them, suggesting that certain current approaches to cancer chemotherapy should be modified.

  19. Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review.

    Science.gov (United States)

    Teles, Kaian Amorim; Medeiros-Souza, Patrícia; Lima, Francisco Aires Correa; Araújo, Bruno Gedeon de; Lima, Rodrigo Aires Correa

    2016-09-17

    Cyclophosphamide (CPM) is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy (pre-ChT), administration of cyclophosphamide, and post-chemotherapy (post-ChT), taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare-but serious-side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

  20. Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie EMatologiche dell'Adulto Multiple Myeloma Working Party study.

    Science.gov (United States)

    Musto, Pellegrino; Simeon, Vittorio; Grossi, Alberto; Gay, Francesca; Bringhen, Sara; Larocca, Alessandra; Guariglia, Roberto; Pietrantuono, Giuseppe; Villani, Oreste; D'Arena, Giovanni; Cuomo, Carmela; Musto, Clelia; Morabito, Fortunato; Petrucci, Maria Teresa; Offidani, Massimo; Zamagni, Elena; Tacchetti, Paola; Conticello, Concetta; Milone, Giuseppe; Palumbo, Antonio; Cavo, Michele; Boccadoro, Mario

    2015-04-17

    A still not well defined proportion of patients with multiple myeloma (MM) and eligible for autologous stem cell transplantation (AuSCT) fails to mobilize CD34+ peripheral blood stem cells (PBSC) at all or to collect an adequate number for a safe procedure or sufficient for multiple transplants. These so-called "poor-mobilizers" are difficult to be predicted, due to marked difference across previous heterogeneous studies. We aimed to develop a method based on simple clinical parameters for predicting unsuccessful (<2×10(6)/kg) or sub-optimal (<5×10(6)/kg) collections of CD34+ PBSC in newly diagnosed MM patients eligible for AuSCT, treated with novel agents and receiving an homogeneous mobilizing therapy with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). To this purpose, 1,348 patients enrolled in five consecutive Italian clinical trials were retrospectively analysed. Age, baseline low peripheral blood cell counts, use of lenalidomide, and haematological toxicity developed during induction were taken into account as possible factors associated with poor mobilization. Overall, 280 patients (20.8%) showed either sub-optimal (167 patients, 12.4%) or unsuccessful (113 patients, 8.4%) collections. All analysed parameters negatively influenced the procedure, but only age and haematological toxicity during induction maintained their significance at multivariate analysis. Based on ordinal logistic regression model, we constructed a risk heat-map where the four parameters were pooled and weighted according to their relevance as single or combined variables. This model was predictive for different probabilities of failure, suboptimal or optimal outcomes. We found that about one fifth of newly diagnosed MM fails to collect an adequate number of PBSC. Our model, based on a large group of patients treated frontline with novel agents and receiving the most popular mobilizing approach currently employed in Europe, is applicable in individual subjects and

  1. Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide in a mouse model of breast cancer.

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    Xin Chen

    Full Text Available TGFβ is reportedly responsible for accumulation of CD4(+Foxp3(+ regulatory T cells (Tregs in tumor. Thus, we treated mouse 4T1 mammary carcinoma with 1D11, a neutralizing anti-TGFβ (1,2,3 antibody. The treatment delayed tumor growth, but unexpectedly increased the proportion of Tregs in tumor. In vitro, 1D11 enhanced while TGFβ potently inhibited the proliferation of Tregs. To enhance the anti-tumor effects, 1D11 was administered with cyclophosphamide which was reported to eliminate intratumoral Tregs. This combination resulted in long term tumor-free survival of up to 80% of mice, and the tumor-free mice were more resistant to re-challenge with tumor. To examine the phenotype of tumor infiltrating immune cells, 4T1-tumor bearing mice were treated with 1D11 and a lower dose of cyclophosphamide. This treatment markedly inhibited tumor growth, and was accompanied by massive infiltration of IFNγ-producing T cells. Furthermore, this combination markedly decreased the number of splenic CD11b(+Gr1(+ cells, and increased their expression levels of MHC II and CD80. In a spontaneous 4T1 lung metastasis model with resection of primary tumor, this combination therapy markedly increased the survival of mice, indicating it was effective in reducing lethal metastasis burden. Taken together, our data show that anti-TGFβ antibody and cyclophosphamide represents an effective chemoimmunotherapeutic combination.

  2. Effect of Cyclophosphamide on Neural Tube Development in Chick Embryos

    Directory of Open Access Journals (Sweden)

    SHABANA SULTANA

    2014-06-01

    Full Text Available Cyclophosphamide is a nitrogen mustard alkylating agent. CP has potent immunosuppressive properties and issued clinically in a number of autoimmune disorders like Wegener’s granulomatosis, rheumatoid arthritis, nephritic syndrome, systemic lupus erythematous and has also been used to prevent organ rejection after transplantation. In the present study fertilized eggs were administered with cyclophosphamide and the development of neural tube was studied after 21 days. The histological and gross features of neural tube were identified. Cyclophosphamide cytotoxicity results in depression of proliferation of cell activity associated with malformations and embryonic death. Injection of the drug causes depression of mitotic activity by day 2 which produces malformations.

  3. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma alveolitis.

    Science.gov (United States)

    Colaci, M; Sebastiani, M; Giuggioli, D; Manfredi, A; Spagnolo, P; Luppi, F; Richeldi, L; Ferri, Clodoveo

    2010-03-01

    Systemic sclerosis (SSc) is characterized by abnormal fibrosis of the skin and internal organs, particularly the lungs. Recent reports have revealed a lack of correlation between bronchoalveolar lavage (BAL) variations and response to cyclophosphamide (CYC) in patients with scleroderma-related alveolitis. Our study aimed to evaluate whether the normalization of BAL cellularity correlates with long-term response to CYC. We retrospectively studied 26 consecutive SSc patients with alveolitis diagnosed by BAL and treated with CYC therapy (cumulative dosage 26.5 +/- 11.7 g; 21.1 +/- 8.9 months of treatment). We evaluated high-resolution computed tomography (HRCT), forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) variations before and after CYC. Radiological and functional parameters were re-evaluated in 23 patients after 1-year follow-up. BAL cellularity normalized after CYC therapy in 12/26 (46.2%) patients (group 1), while it remained abnormal in 14/26 (53.8%) (group 2). FVC and DLCO of group 1 slightly increased after CYC (p = 0.014 and p = 0.07, respectively) and remained stable at follow-up, whereas in group 2 they did not change after CYC and at follow-up (p = not significant). Moreover, at the end of CYC, FVC and/or DLCO showed a clinical improvement/stabilization in all patients of group 1 versus 8/14 of group 2, while at the re-evaluation 1 year after completing CYC, 2/11 patients of group 1 worsened versus 5/12 of group 2. HRCT progression was observed in 1/11 of group 1 and 8/12 of group 2 (p = 0.009). BAL fluid normalization after CYC therapy correlated with long-term response to treatment, contrary to what is observed in individuals with persistent alveolitis.

  4. Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study.

    Science.gov (United States)

    Elling, D; Eggemann, H; Kümmel, S; Breitbach, P; Kohls, A; Morack, G; Schlosser, H; Krocker, J

    2003-06-01

    The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.

  5. Clinical Observation of Aprepitant Triple Therapy on Prevention of Nausea and Vomiting Caused by Anthracycline Combined Cyclophosphamide Chemotherapy Regimen for Breast Cancer%阿瑞匹坦三联用药预防乳腺癌蒽环类药物联合环磷酰胺化疗致恶心呕吐的效果观察

    Institute of Scientific and Technical Information of China (English)

    童雅兰; 韩涛; 宋树玺; 郑振东; 屈淑贤; 邱佳宁; 刘兆喆; 郭放; 谢晓冬

    2016-01-01

    Objective To investigate the effect of combined therapy consisting of aprepitant, tropisetron and dexam-ethasone in prevention of nausea and vomiting induced by breast cancer chemotherapy based on anthracycline and cyclophos-phamide. Methods A total of 62 cases of breast cancer collected from Oncology Department in General Hospital of Shenyang Military Area Command during January 2014 and June 2015 were selected, and those patients all underwent chemotherapy consisting of anthracycline (epirubicin or doxorubicin) combined cyclophosphamide and they were divided into experimental group ( n=31 ) and control group ( n =31 ) by CINV ( chemotherapy-induced nausea and vomiting ) regimen. The control group was given tropisetron and dexamethasone combined regimen in prevention of CINV while the experimental group was added with aprepitant based on the drug used by the control group. The effect and adverse reaction of two groups in acute phase (0-24 h) and delay period (24-120 h) on preventing nausea and vomiting were observed. Results The complete re-sponse rate and the control rate of acute phase had no statistical difference between the two groups (Z=-1. 579, P=0. 114);however, for the delayed vomiting, the complete response rate and control rate of the experimental group were higher than that of the control group and there was significant statistical difference (Z=-2. 196, P=0. 028). Adverse reactions were mild and tolerable with no significant differences between the 2 groups (P>0. 05). Conclusion The combined therapy of aprepitant is definitely effective for the delayed vomiting induced by anthracycline combined cyclophosphamide chemotherapy regimen of breast cancer, and the toxic reaction is tolerable.%目的:评估阿瑞匹坦、托烷司琼、地塞米松三联方案预防乳腺癌蒽环类药物联合环磷酰胺化疗致恶心呕吐的效果及安全性。方法选择2014年1月—2015年6月沈阳军区总医院肿瘤科收治的接收蒽环类药物(表柔

  6. Inhibition of conventional chemotherapy combined with metronomic chemotherapy on breast cancer xenografts in nude mice%常规化疗联合节拍化疗对乳腺癌裸鼠移植瘤的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘星; 陈伶; 史莉莉; 李丽

    2011-01-01

    microenvironment. It has been reported that metronomic chemotherapy enjoys obvious advantages in improving tumor microenvironment. The purpose of this study was to compare the antitumor effects in nude mice with human breast cancer with different cyclophosphamide chemotherapy regimens and to observe two balances: between pro-angiogenesis and anti-angiogenesis and between tumor cell proliferation and apoptosis. Methods: Breast ortho-topic transplantation tumor model was established. Twenty nude mice bearing carcinoma were divided into 4 groups randomly: metronomic chemotherapy group (LDM), conventional chemotherapy group (MTD), combination group (LDM+MTD) and control group. The general condition of mice was observed and the mice were weighed every other day, at the same time the volume of subcutaneous tumor was measured. WBC was counted every week. In the end, tumors were taken off and weighed to calculate inhibitory rates of each group. Immunohistochemistry was used to detect the tumor microvessel density (MVD), and the expressions of VEGF, TSP-1 and PCNA. TUNEL was used to detectthe apoptosis of the tumor cells. Results: All nude mice were in good condition throughout the trial period without significant side effects. Three chemotherapy regimens could inhibit the growth of xenografts in different degrees, whose inhibitory rates were 32.95%, 41.75% and 69.15%, respectively. LDM and MTD had similar tumor growth curve, while the xenografts in combination group appeared to grow significantly slower than the other groups. In the combination group and LDM group, xenografts expressed lower level VEGF and MVD and higher level TSP-1 than those in the other groups (P0.05). There was lower expression of PCNA in the combination group and MTD group than those in the LDM and control groups (P0.05). The apoptosis index (AI) in three chemotherapy groups had statically significant difference with control group (P<0.05). Furthermore, the AI in the combination group was the highest. Conclusion

  7. SPERM MATURATIONAL DEFECT AFTER CYCLOPHOSPHAMIDE TREATMENT

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    Z. N. Kashmiri

    2014-06-01

    Full Text Available During normal spermatogenesis, most of the round spermatid’s cytoplasm was phagocytosed as ‘residual bodies’ by the Sertoli cell at spermiogenesis, and only a small cytoplasmic residue i.e. ‘cytoplasmic droplet’ remains applied to the elongated spermatid after release from the germinal epithelium. A characteristic morphological change on spermatozoa during epididymal transit was the caudal migration of the cytoplasmic droplet away from the neck via the principal piece, however, while studying the Cyclophosphamide (CPA induced sperm morphological changes from the cauda epididymis in male Wistar rat, Rattus norvegicus using phase contrast microscope it was noticed that the sub-chronic and acute doses of CPA caused retention of cytoplasmic droplet on the mid-piece. Thus from the foregoing it was concluded that beside CPA being an inhibitor of spermatogenesis, it also interferes with the maturation of spermatozoa by the retention of cytoplasmic droplet perhaps due to alteration in epididymal secretory and absorptive functions thus leading to infertility.

  8. Enantioselective induction of cyclophosphamide metabolism by phenytoin.

    Science.gov (United States)

    Williams, M L; Wainer, I W; Embree, L; Barnett, M; Granvil, C L; Ducharme, M P

    1999-01-01

    The objective of this study was to investigate the effect of phenytoin (PHE) on cyclophosphamide (CP) disposition. CP was administered to 6 adult patients in a preparative regimen for bone marrow transplantation consisting of busulfan and CP. Three of the patients received PHE and the other 3 "control" patients received diazepam (DZP) as anti-epileptic prophylactic treatment. Plasma samples were collected at intervals up to 24 h after CP administration. The plasma concentrations of (R)- and (S)-CP and their respective N-dechloroethylated metabolites, (R)- and (S)-DCE-CP were simultaneously fitted using an enantiospecific 2-compartment pharmacokinetic (PK) model with Bayesian control estimation. DZP had no significant effect on the metabolism of CP and any of its PK parameters. PHE, however, increased significantly the formation of (S)-DCE-CP while having no effect on the formation of (R)-DCE-CP. These results suggest that different enzymes are responsible for the formation of (S)-DCE-CP from (S)-CP and (R)-DCE-CP from (R)-CP. Additionally, assuming that PHE does not affect the passive renal elimination of (R)- and (S)-CP, this analysis suggests that the clearance of both (R)- and (S)-CP to 4-hydroxy-CP (the activation pathway) is increased by PHE.

  9. 甲基强的松龙联合环磷酰胺冲击治疗难治性肾病对心功能的影响与护理%Effect of combination therapy of methylprednisolone and cyclophosphamide on heart function and nursing in patients with refractory nephritic syndrome

    Institute of Scientific and Technical Information of China (English)

    齐爱华; 张红; 曹荣

    2008-01-01

    0bjective To evaluate the heart function of patients with refractory nephmtic syndrome during a combination therapy of methylprednisolone(MP)and cyclophosphamide(CTX).Methods From January 2004 to December 2007.30 patients with refractory nephrotic syndrome.who were in hospital and received a combination therapy of MP and CTX.were recorded for their heart rate and blood pressure before and during treatment,as well as observed for the complications.ResulIs Comparing with those before treatment.patients' heart rates were much quickly and their blood pressure were remarkablv higher during the combination treatment. And there was a statistic siglnificance(P<0.05).When patients received MP treatment.complications.such as cardiopalmus and dizziness,proned to emerging in the third cycle.When they received CTX treatment, complications,just like sicchasia,vomit and cardiopalmus.appeared in the first cycle.In addition. Myelosuppression and lesion of liver function often occurred during the sequence therapy.Conclusions When patients received a combination therapy of MP and CTX,we should monitor their heart funcion SO as to promptly make propotional measure and prevent complications according to variation of heart rate and blood pressure.%目的 探讨甲基强的松龙(MP)联合环磷酰胺(CTX)冲击治疗难治性肾病对患儿心功能的影响.方法 对收治的30例难治性肾病患儿,在进行MP联合CTX冲击治疗时,监测患儿的心功能,记录治疗前、治疗中患儿的心率、血压变化,并观察并发症情况.结果 治疗中患儿的心率加快,血压升高,与治疗前比较有统计学意义(P<0.05).MP治疗时心悸、头晕等并发症易发生在第3次治疗中;CTX治疗时恶心、呕吐、心悸等并发症易发生在首次疗程中,骨髓抑制、肝功损害易发生在后续疗程中.结论 在MP联合CTX冲击治疗难治性肾病时,应监测患儿的心功能变化,根据心率、血压变化及时采取相应的措施,减少并发症的发生.

  10. Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy-era with plerixafor and G-CSF has superior efficacy but significantly higher costs compared to mobilization with low-dose cyclophosphamide and G-CSF.

    Science.gov (United States)

    Chaudhary, Lubna; Awan, Farrukh; Cumpston, Aaron; Leadmon, Sonia; Watkins, Kathy; Tse, William; Craig, Michael; Hamadani, Mehdi

    2013-10-01

    Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low-dose cyclophosphamide (LD-CY) and granulocyte-colony stimulating factor (G-CSF) against plerixafor and G-CSF, in multiple myeloma (MM) patients treated in the novel therapy-era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1-year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD-CY (1.5 gm/m(2)) and G-CSF (n = 74) were compared against patients receiving plerixafor and G-CSF (n = 33). Compared to plerixafor, LD-CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10(6)/kg vs. 2.4 × 10(6)/kg, P = 0.001). Six patients (8.1%) in the LD-CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10(6)/kg vs. 7 × 10(6)/kg; P-value = 0.001). Mobilization with LD-CY was associated with increased (albeit statistically non-significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD-CY group ($28,980 vs. $19,626.5 P-value mobilization has superior efficacy, but significantly higher mobilization costs compared to LD-CY mobilization. Our data caution against the use of LD-CY in MM patients for mobilization, especially after induction with lenalidomide-containing regimens.

  11. Metronomic Ceramide Analogs Inhibit Angiogenesis in Pancreatic Cancer through Up-regulation of Caveolin-1 and Thrombospondin-1 and Down-regulation of Cyclin D1

    Directory of Open Access Journals (Sweden)

    Guido Bocci

    2012-09-01

    Full Text Available AIMS: To evaluate the antitumor and antiangiogenic activity of metronomic ceramide analogs and their relevant molecular mechanisms. METHODS: Human endothelial cells [human dermal microvascular endothelial cells and human umbilical vascular endothelial cell (HUVEC] and pancreatic cancer cells (Capan-1 and MIA PaCa-2 were treated with the ceramide analogs (C2, AL6, C6, and C8, at low concentrations for 144 hours to evaluate any antiproliferative and proapoptotic effects and inhibition of migration and to measure the expression of caveolin-1 (CAV-1 and thrombospondin-1 (TSP-1 mRNAs by real-time reverse transcription-polymerase chain reaction. Assessment of extracellular signal-regulated kinases 1 and 2 (ERK1/2 and Akt phosphorylation and of CAV-1 and cyclin D1 protein expression was performed by ELISA. Maximum tolerated dose (MTD gemcitabine was compared against metronomic doses of the ceramide analogs by evaluating the inhibition of MIA PaCa-2 subcutaneous tumor growth in nude mice. RESULTS: Metronomic ceramide analogs preferentially inhibited cell proliferation and enhanced apoptosis in endothelial cells. Low concentrations of AL6 and C2 caused a significant inhibition of HUVEC migration. ERK1/2 and Akt phosphorylation were significantly decreased after metronomic ceramide analog treatment. Such treatment caused the overexpression of CAV-1 and TSP-1 mRNAs and proteins in endothelial cells, whereas cyclin D1 protein levels were reduced. The antiangiogenic and antitumor impact in vivo of metronomic C2 and AL6 regimens was similar to that caused by MTD gemcitabine. CONCLUSIONS: Metronomic C2 and AL6 analogs have antitumor and antiangiogenic activity, determining the up-regulation of CAV-1 and TSP-1 and the suppression of cyclin D1.

  12. The use of a metronome during cardiopulmonary resuscitation in the emergency room of a university hospital.

    Science.gov (United States)

    Botelho, Renata Maria de Oliveira; Campanharo, Cássia Regina Vancini; Lopes, Maria Carolina Barbosa Teixeira; Okuno, Meiry Fernanda Pinto; Góis, Aécio Flávio Teixeira de; Batista, Ruth Ester Assayag

    2016-11-21

    to compare the rate of return of spontaneous circulation (ROSC) and death after cardiac arrest, with and without the use of a metronome during cardiopulmonary resuscitation (CPR). case-control study nested in a cohort study including 285 adults who experienced cardiac arrest and received CPR in an emergency service. Data were collected using In-hospital Utstein Style. The control group (n=60) was selected by matching patients considering their neurological condition before cardiac arrest, the immediate cause, initial arrest rhythm, whether epinephrine was used, and the duration of CPR. The case group (n=51) received conventional CPR guided by a metronome set at 110 beats/min. Chi-square and likelihood ratio were used to compare ROSC rates considering p≤0.05. ROSC occurred in 57.7% of the cases, though 92.8% of these patients died in the following 24 hours. No statistically significant difference was found between groups in regard to ROSC (p=0.2017) or the occurrence of death (p=0.8112). the outcomes of patients after cardiac arrest with and without the use of a metronome during CPR were similar and no differences were found between groups in regard to survival rates and ROSC. comparar a taxa de retorno da circulação espontânea e óbito após parada cardiorrespiratória, com e sem a utilização do metrônomo durante ressuscitação cardiopulmonar. estudo caso-controle aninhado a estudo de coorte, com 285 adultos atendidos em parada cardíaca em um serviço de emergência e submetidos à ressuscitação cardiopulmonar. Os dados foram coletados por meio do In-hospital Utstein Style. O grupo controle (n=60) foi selecionado pelo pareamento dos pacientes considerando-se o estado neurológico pré-parada cardiorrespiratória, causa imediata e ritmo inicial da parada, utilização de epinefrina e duração da ressuscitação. O grupo caso (n=51) foi submetido à ressuscitação cardiopulmonar convencional com a utilização do metrônomo a 110sons/min. Para comparar

  13. Tolerability and safety of classic cyclophosphamide, methotrexate, and fluorouracil treatment in Japanese patients with early breast cancer.

    Science.gov (United States)

    Tada, Keiichiro; Ito, Yoshinori; Takahashi, Shunji; Iijima, Kohtaro; Miyagi, Yumi; Nishimura, Seiichiro; Takahashi, Kaoru; Makita, Masujiro; Iwase, Takuji; Yoshimoto, Masataka; Kasumi, Fujio

    2006-01-01

    Few reports have addressed the feasibility and safety of classic Cyclophosphamide, Methotrexate, and Fluorouracil (CMF) therapy in Japanese female breast cancer patients. Twenty-four Japanese patients who received classic CMF, identical to the originally described treatment regimen were studied in terms of treatment dose, treatment delay, and toxicity. Classic CMF was not discontinued in any of the cases. The median delay in treatment was 14 days, and the mean administered dose of cyclophosphamide was 98.2% of the planned dose. None of the patients suffered severe side-effects such as febrile neutropenia; however, in 22 patients in whom the effect of CMF on hair loss could be assessed, 7 (31.8%) had to wear hats or wigs. Classic CMF is a feasible and safe regimen in Japanese breast cancer patients. In Japan, this regimen is still available for some specific groups of early breast cancer patients.

  14. Cyclophosphamide and Doxorubicin Induced Melanonychia: A Case Report.

    Science.gov (United States)

    Prajapati, Vivek Bhanubhai; Madhyastha, Sharath; Acharya, Raviraj; Gopalaswamy, Vinaya; Doddamani, Akhila

    2017-01-01

    Chemotherapeutic agents may rarely cause discoloration and hyperpigmentation of the nails. We present a patient who developed blackish discoloration of nails also referred as melanonychia during six cycles of R-CHOP chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) for the treatment of Non Hodgkin Lymphoma (NHL) follicular type. The patient developed blackish brown discoloration in all the nails. As suggested by previous literature evidence the melanonychia could be associated with cyclophosphamide and doxorubicin. According to the Naranjo causality assessment scale, we established that there was a 'probable' association of nail discoloration with the drug.

  15. A randomized trial of cyclophosphamide, doxorubicin, and prednisone versus cyclophosphamide, 5-fluorouracil, and prednisone in patients with metastatic breast cancer.

    Science.gov (United States)

    Ahmann, D L; Schaid, D J; Ingle, J N; Bisel, H F; Schutt, A J; Buckner, J C; Long, H J; Rubin, J

    1991-06-01

    Ninety-four patients were entered in a clinical trial assessing the clinical activity of cyclophosphamide, doxorubicin, and prednisone (CAP) versus a combination of cyclophosphamide. 5-Fluorouracil, and prednisone (CFP) in patients with advanced breast cancer. Objective response rates were comparable, 49% for CFP and 46% for CAP. There was no statistical difference between the duration of response of the two regimens or in time to progression. Most importantly, survival differences were not apparent. Both regimens were clinically tolerable and toxicities, for the most part, were comparable. Thus, no therapeutic advantage existed for either of these polychemotherapy regimens in patients with advanced breast cancer.

  16. Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

    Science.gov (United States)

    DeZern, Amy E.; Zahurak, Marianna; Symons, Heather; Cooke, Kenneth; Jones, Richard J.; Brodsky, Robert A.

    2017-01-01

    Severe aplastic anemia (SAA) is a life-threatening hematopoietic stem cell disorder that is treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IST). The management of patients with refractory SAA after IST is a major challenge. Alternative donor BMT is the best chance for cure in refractory SAA, but morbidity and mortality from graft failure and complications of graft-versus-host disease (GVHD) have limited enthusiasm for this approach. Here, we employed post-transplantation high-dose cyclophosphamide in an effort to safely expand the donor pool in 16 consecutive patients with refractory SAA who did not have a matched sibling donor. Between July 2011 and August 2016, 16 patients underwent allogeneic (allo) BMT for refractory SAA from 13 haploidentical donors and 3 unrelated donors. The nonmyeloablative conditioning regimen consisted of antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation. Post-transplantation cyclophosphamide 50 mg/kg/day i.v. on days +3 and +4 was administered for GVHD prophylaxis. Additionally, patients received mycophenolate mofetil on days +5 through 35 and tacrolimus from day +5 through 1 year. The median age of the patients at the time of transplantation was 30 (range, 11 to 69) years. The median time to neutrophil recovery over 1000 × 103/mm3 for 3 consecutive days was 19 (range, 16 to 27) days, to red cell engraftment was 25 (range, 2 to 58) days, and to last platelet transfusion to keep platelets counts over 50 × 103/mm3 was 27.5 (range, 22 to 108) days. Graft failure, primary or secondary, was not seen in any of the patients. All 16 patients are alive, transfusion independent, and without evidence of clonality. The median follow-up is 21 (range, 3 to 64) months. Two patients had grade 1 or 2 skin-only acute GVHD. These same 2 also had mild chronic GVHD of the skin/mouth requiring systemic steroids. One of these GVHD patients was able to come off all IST by 15 months and the

  17. Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Beatriz Ursinos Catelan Schneider

    2016-06-01

    Full Text Available Abstract Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg alone or in combination with cyclophosphamide (100 mg/kg. The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide.

  18. Clinical efficacy of cyclophosphamide in treatment of primary sclerosing cholangitis

    Institute of Scientific and Technical Information of China (English)

    程鹏

    2014-01-01

    Objective To investigate the clinical efficacy of cy-clophosphamide in the treatment of primary sclerosing cholangitis(PSC).Methods Twenty-four patients with PSC who received treatment in the department of gastroenterology in our hospital from January 2004 to December2012 were selected as subjects and divided into observation group(n=13)and control

  19. Effects of chlordiazepoxide, diazepam and oxazepam on the antitumor activity, the lethality and the blood level of active metabolites of cyclophosphamide and cyclophosphamide oxidase activity in mice.

    Science.gov (United States)

    Sasaki, K; Furusawa, S; Takayanagi, G

    1983-10-01

    Effects of chlordiazepoxide, diazepam and oxazepam on the antitumor activity and acute toxicity of cyclophosphamide and the level of its active metabolites in the plasma were investigated in mice. Cyclophosphamide was administered 24 h after the final injection of chlordiazepoxide, diazepam or oxazepam (100 mg/kg/d for 3 d, i.p.). Pretreatment with these drugs increased the acute toxicity of cyclophosphamide (300 or 450 mg/kg, i.p.), whereas drugs had no effect on the antitumor activity of cyclophosphamide (100 mg/kg, i.p.) against Ehrlich solid carcinoma. A high level of active metabolites of cyclophosphamide in the plasma after the administration of cyclophosphamide (300 or 450 mg/kg, i.p.) was observed in chlordiazepoxide-, diazepam- or oxazepam-treated mice. On the other hand, chlordiazepoxide, diazepam or oxazepam enhanced significantly the activity of cyclophosphamide oxidase in hepatic microsomes. It is concluded that potentiation of the acute toxicity at a high dose of cyclophosphamide by chlordiazepoxide, diazepam and oxazepam is due to an induction of microsomal drug-metabolizing enzyme which are responsible for the in vivo activation of cyclophosphamide.

  20. 霉酚酸酯与间断环磷酰胺静脉冲击疗法治疗弥漫增生型狼疮性肾炎疗效的比较%Mycophenolate mofetil vs cyclophosphamide therapy for patients with di ffuse proliferative lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    胡伟新; 陈惠萍; 唐政; 王庆文; 沈克勤; 刘志红; 黎磊石

    2002-01-01

    目的比较霉酚酸酯(MMF)与间断环磷酰胺静脉冲击疗法(CYC)治疗弥漫增生型狼疮性肾炎(DP LN)的临床疗效.方法 46例患者均经临床和肾活检确定为活动性DPLN,23例采用激素联合MMF(1.0-1.5 g/d)治疗 (MMF组),另23例接受激素联合CYC治疗(CYC组).两组患者病情相似,随访≥6月.MMF 组及CYC组中分别有15例、12例在治疗3-6个月时进行重复肾活检.结果①临床疗效:治疗6月时MMF组尿蛋白及尿RBC下降程度大于CYC组,尿蛋白及尿RBC减少超过基础值50%者,MMF组分别占69.6%及91.3%,CYC组分别为47.8%和65.2%.尿蛋白转阴和血尿消失率MMF组分别为34.8% 43.5%, CYC组则分别为21.7%和39.1%.MMF降低血清冷球蛋白血症、抑制ANA及A-dsDNA产生的作用强于CYC组.②肾脏病理改变:重复肾活检显示MMF 组肾组织急性指数(AI)由16.4±7.8降至4.0±2.0,CYC组AI由12.3±4.0降至6.4 ±3.0.MMF组治疗后肾小球细胞浸润、免疫复合物沉积、袢坏死、袢内血栓均消失.间质活动性血管炎及细胞/细胞纤维性新月体显著减少,而CYC组仍有较多患者遗留上述病变.③副反应:MMF组胃肠道及感染并发症发生率低于CYC组.结论激素联合MMF控制DPLN临床活动及减轻肾脏活动性病变的作用强于CYC,MMF减轻肾血管病变的作用尤为明显.由此表明,MMF疗法可以作为DPLN的诱导期治疗,尤其适用于传统疗法治疗无效及伴有狼疮性肾血管病变的病例.%Objective To make an open label prospective trial for comparing the therapeutic effects of mycophenolate mofetil (MMF) vs cyclophosphamide (CYC) pulse therapy on patients with diffuse proliferative lupus nephritis (DPLN).Methods Forty-six patients with biopsy proven active DPLN were enrolled in this study. Twenty-three patients were given MMF orally at a dosage of 1.0-1.5 g/d (MMF Group). Another 23 cases received conventional intermittent CYC pulse therapy ( CYC Group). Supplemental steroid treatment was offered

  1. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

    Science.gov (United States)

    Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

    2004-01-01

    The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.

  2. Neoadjuvant chemotherapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and docetaxel.

    Science.gov (United States)

    Gu, Xi; Jia, Shi; Wei, Wei; Zhang, Wen-Hai

    2015-07-01

    Breast cancers (BC) are treated with surgery, radiotherapy, and chemotherapy. Neoadjuvant chemotherapy (NACT) is an emerging treatment option in many cancers and is given before primary therapy to shrink tumor size. The efficacy of NACT in varied settings of BC, such as inoperable tumors, borderline resectable tumors, and breast-conserving surgery, has been debated extensively in literature, and the results remain unclear and depended on a wide variety of factors such as cancer type, disease extent, and the specific combination of chemotherapy drugs. This study was performed to examine the efficacy, toxicity, and tolerability of pirarubicin (THP) and epirubicin (EPI) in combination with docetaxel and cyclophosphamide in a NACT setting for BC. A total of 48 patients with stage II or III breast cancers were randomly divided into two groups: THP group and EPI group. The patients in THP group received 2-4 cycles of neoadjuvant chemotherapy with DTC regimen (docetaxel, THP, cyclophosphamide), while patients in the EPI group received 2-4 cycles of DEC regimen (docetaxel, EPI, cyclophosphamide) before surgery. The incidence of adverse reactions and the efficacy of the treatment regimen were compared between the two groups. Prognostic evaluation indexes were estimated by Kaplan-Meier survival analysis, including the 5-year disease-free survival (DFS) and overall survival (OS). The overall response rate in THP group was 83.3 %, and the EPI group showed a response rate of 79.2 %, with no statistically significant difference in response rate between the two groups. The incidence of cardiac toxicity, myelosuppression, nausea, and vomiting in the THP group was significantly lower than the EPI group (all P < 0.05). The incidence of hepatic toxicity, alopecia, and diarrhea in the THP group was also lower than the EPI group, but these differences were not statistically significant. The 5-year DFS and OS in THP versus EPI groups were 80 versus 76 % (DFS) and 86 versus 81 % (OS

  3. Chemotherapeutic (cyclophosphamide) effects on rat breast tumor hemodynamics monitored by multi-channel NIRS

    Science.gov (United States)

    Kim, Jae G.; Zhao, Dawen; Mason, Ralph P.; Liu, Hanli

    2005-04-01

    We previously suggested that the two time constants quantified from the increase of tumor oxyhemoglobin concentration, ▵ [HbO2], during hyperoxic gas intervention are associated with two blood flow/perfusion rates in well perfused and poorly perfused regions of tumors. In this study, our hypothesis is that when cancer therapy is applied to a tumor, changes in blood perfusion will occur and be detected by the NIRS. For experiments, systemic chemotherapy, cyclophosphamide (CTX), was applied to two groups of rats bearing syngeneic 13762NF mammary adenocarcinomas: one group received a single high dose i. p. (200 mg/kg CTX) and the other group continuous low doses (20 mg/kg CTX i. p. for 10 days). Time courses of changes in tumor ▵ [HbO2] were measured at four different locations on the breast tumors non-invasively with an inhaled gas sequence of air-oxygen-air before and after CTX administration. Both rat body weight and tumor volume decreased after administration of high dose CTX, but continuous low doses showed decrease of tumor volume only. Baselines (without any therapy) intra- and inter-tumor heterogeneity of vascular oxygenation during oxygen inhalation were similar to our previous observations. After CTX treatment, significant changes in vascular hemodynamic response to oxygen inhalation were observed from both groups. By fitting the increase of ▵ [HbO2] during oxygen inhalation, we have obtained changes of vascular structure ratio and also of perfusion rate ratio before and after chemotherapy. The preliminary results suggest that cyclophosphamide has greatest effect on the well perfused tumor vasculature. Overall, our study supports our earlier hypothesis, proving that the effects of chemotherapy in tumor may be monitored non-invasively by using NIRS to detect changes of hemodynamics induced with respiratory challenges.

  4. Successful treatment of idiopathic pulmonary capillaritis with intravenous cyclophosphamide.

    LENUS (Irish Health Repository)

    Flanagan, Frances

    2013-03-01

    Idiopathic pulmonary hemosiderosis (IPH), a subtype of diffuse alveolar hemorrhage is a rare condition, first described by Virchow in 1864. Historically, it manifests in children in the first decade of life with the combination of hemoptysis, iron deficiency anemia, and alveolar infiltrates on chest radiograph. More recently, diffuse alveolar hemorrhage has been classified by the absence or presence of pulmonary capillaritis (PC), the latter carrying a potential for a poorer outcome. While systemic corticosteroids remain the first line treatment option, other immune modulators have been trailed including hydroxychloroquine, azathioprine, 6-mercaptopurine, and cyclophosphamide with varying results. Our case demonstrates for the first time, the successful use of intravenous cyclophosphamide in the management of chronic idiopathic PC.

  5. Treatment of Vasodilator-resistant Mixed Connective Tissue Disease-associated Pulmonary Arterial Hypertension with Glucocorticoid and Cyclophosphamide.

    Science.gov (United States)

    Sugawara, Eri; Kato, Masaru; Hisada, Ryo; Oku, Kenji; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-01-01

    Pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MTCD), in contrast to other types of PAH, may respond to immunosuppressive therapy. Most PAH cases with an immunosuppressant response were in the early stages of the disease (WHO functional class III or less). The present case was a 34-year-old woman with MCTD-associated PAH (WHO functional class IV) who was resistant to a combination of three vasodilators. Afterwards, she was treated with glucocorticoid and cyclophosphamide. This case suggested the potential benefit of immunosuppressants in patients with severe MCTD-associated PAH.

  6. Processed Aloe vera Gel Ameliorates Cyclophosphamide-Induced Immunotoxicity

    OpenAIRE

    Sun-A Im; Ki-Hyang Kim; Hee-Suk Kim; Ki-Hwa Lee; Eunju Shin; Seon-Gil Do; Tae Hyung Jo; Young In Park; Chong-Kil Lee

    2014-01-01

    The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer’s patch cells. Peyer’s patch cells isolated from C...

  7. Myelosuppression After Frontline Fludarabine, Cyclophosphamide, and Rituximab in Patients With Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Strati, Paolo; Wierda, William; Burger, Jan; Ferrajoli, Alessandra; Tam, Constantine; Lerner, Susan; Keating, Michael J.; O’Brien, Susan

    2015-01-01

    BACKGROUND The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced improved response rates and a prolonged survival in patients with chronic lymphocytic leukemia (CLL). However, its therapeutic power is counterbalanced by significant hematologic toxicity. Persistent and new-onset cytopenia after the completion of FCR raise concern about disease recurrence, the development of therapy-related myeloid malignancies (TRMM), and infections. METHODS A total of 207 patients with CLL who achieved complete response, complete response with incomplete bone marrow recovery, or nodular partial remission were analyzed after frontline FCR therapy. RESULTS Three months after the completion of therapy, 35% of patients had developed grade 2 to 4 cytopenia (according to Common Terminology Criteria for Adverse Events [version 4.0]). Factors found to be associated with cytopenia at 3 months after therapy were older age, advanced Rai stage disease, and lower baseline blood counts. Moreover, patients with cytopenia were less likely to have completed 6 courses of therapy with FCR. At 6 months and 9 months after therapy, the prevalence of grade 2 to 4 cytopenia was 24% and 12%, respectively. No differences in progression-free survival and overall survival were noted between cytopenic and noncytopenic patients or between patients with persistent and new-onset cytopenia. The prevalence of TRMM was 2.3% and did not differ significantly between cytopenic and noncytopenic patients or between those with persistent and new-onset disease. Late infections were more common in patients who were cytopenic at 9 months (38%) and were mostly bacterial (67%). CONCLUSIONS Cytopenia after the completion of therapy is a common complication of frontline FCR that improves over time, particularly for new-onset cases. The presence of persistent cytopenia (lasting up to 9 months after the completion of therapy) should not raise concern about CLL recurrence of the development of TRMM, but

  8. Levamisole vs. cyclophosphamide for frequently-relapsing steroid-dependent nephrotic syndrome.

    Science.gov (United States)

    Alsaran, K; Grisaru, S; Stephens, D; Arbus, G

    2001-10-01

    A retrospective analysis comparing the first-time use of levamisole (L) or cyclophosphamide (C) as second-line therapy for children with frequently relapsing, steroid-dependent (FR/SD) nephrotic syndrome, was conducted at our center. The relapse rate and the total cumulative dose of prednisone during the year prior to L/C therapy was compared to that during the year following the institution of therapy with L or C in 51 patients, between July 1992 and June 1997. An analysis of covariance was used to adjust the outcome for differences between the 2 groups of treatment in the year prior to second-line drug initiation. In the L group the mean relapse rate was lowered by 0.28 relapses/patient/month and the mean cumulative dose of prednisone was reduced by 336 mg/m2/month versus 0.32 relapses/patient/month and 387 mg/m2/month in the C group (p = 0.395. p = 0.577). No significant difference in the effectiveness of L vs. C for therapy of FR/SD nephrotic syndrome could be identified in our patients. We conclude that L may be considered an alternative for C as a first second-line agent for these patients.

  9. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL

    Science.gov (United States)

    Badoux, Xavier C.; Keating, Michael J.; Wang, Xuemei; O'Brien, Susan M.; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop

    2011-01-01

    Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute–Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population. PMID:21245487

  10. Neem leaf glycoprotein generates superior tumor specific central memory CD8(+) T cells than cyclophosphamide that averts post-surgery solid sarcoma recurrence.

    Science.gov (United States)

    Ghosh, Sarbari; Sarkar, Madhurima; Ghosh, Tithi; Guha, Ipsita; Bhuniya, Avishek; Saha, Akata; Dasgupta, Shayani; Barik, Subhasis; Bose, Anamika; Baral, Rathindranath

    2017-08-03

    The success of cancer vaccines is limited as most of them induce corrupted CD8(+) T cell memory populations. We reported earlier that a natural immunomodulator, neem leaf glycoprotein (NLGP), therapeutically restricts tumor growth in a CD8(+) T cell-dependent manner. Here, our objective is to study whether memory CD8(+) T cell population is generated in sarcoma hosts after therapeutic NLGP treatment and their role in prevention of post-surgery tumor recurrence, in comparison to the immunostimulatory metronomic cyclophosphamide (CTX) treatment. We found that therapeutic NLGP and CTX treatment generates central memory CD8(+) T (TCM) cells with characteristic CD44(+)CD62L(high)CCR7(high)IL-2(high) phenotypes. But these TCM cells are functionally impaired to prevent re-appearance of tumors along with compromised proliferative, IL-2 secretive and cytotoxic status. This might be due to the presence of tumor load, even a small one in the host, which serves as a persistent source of tumor antigens thereby corrupting the TCM cells so generated. Surgical removal of the persisting tumors from the host restored the functional characteristics of memory CD8(+) T cells, preventing tumor recurrence after surgery till end of the experiment. Moreover, we observed that generation of superior TCM cells in NLGP treated surgically removed tumor hosts is related to the activation of Wnt signalling in memory CD8(+) T cells with concomitant inhibition of GSK-3β and stabilisation of β-catenin, which ultimately activates transcription of Wnt target genes, like, eomesodermin, a signature molecule of CD8(+) TCM cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Severe multiorganic flare of systemic lupus erythematosus successfully treated with rituximab and cyclophosphamide avoiding high doses of prednisone.

    Science.gov (United States)

    Gonzalez-Echavarri, C; Pernas, B; Ugarte, A; Ruiz-Irastorza, G

    2014-03-01

    Both acute pancreatitis and diffuse alveolar haemorrhage are rare conditions associated with systemic lupus erythematosus (SLE). In this case report, a 23-year-old female with SLE was diagnosed with lupus-associated pancreatitis and, within a few days and despite initial therapy with pulse methyl-prednisolone, subsequently suffered an acute respiratory failure due to a diffuse alveolar haemorrhage. The patient was admitted to the intensive care unit and treatment was intensified with cyclophosphamide and rituximab, which shortly induced the complete remission of SLE with resolution of both clinical conditions. She completed treatment with six pulses of cyclophosphamide followed by azathioprine, hydroxychloroquine and prednisone at initial doses of 20 mg/d with rapid tapering to 5 mg/d, without relapse of the disease during the following year. This case can illustrate that, even in severe, life-threatening SLE flares, it is possible to avoid high-dose prednisone, which has been associated with severe side effects, including infections. Acute pancreatitis and diffuse alveolar haemorrhage are rare conditions caused by SLE. DAH can be a life-threatening complication, with an early mortality of at least 50%. When facing such severe SLE activity, there is a general tendency to use high doses of prednisone as the initial therapy, maintaining such high doses for long periods of time, even after the clinical situation has subsided. We report a case of a young woman with SLE, suffering from acute pancreatitis and diffuse alveolar haemorrhage, who was successfully treated with pulse methyl-prednisolone, hydroxychloroquine, cyclophosphamide and rituximab, combined with medium doses of prednisone.

  12. Enhanced selection of high affinity DNA-reactive B cells following cyclophosphamide treatment in mice.

    Directory of Open Access Journals (Sweden)

    Daisuke Kawabata

    Full Text Available A major goal for the treatment of patients with systemic lupus erythematosus with cytotoxic therapies is the induction of long-term remission. There is, however, a paucity of information concerning the effects of these therapies on the reconstituting B cell repertoire. Since there is recent evidence suggesting that B cell lymphopenia might attenuate negative selection of autoreactive B cells, we elected to investigate the effects of cyclophosphamide on the selection of the re-emerging B cell repertoire in wild type mice and transgenic mice that express the H chain of an anti-DNA antibody. The reconstituting B cell repertoire in wild type mice contained an increased frequency of DNA-reactive B cells; in heavy chain transgenic mice, the reconstituting repertoire was characterized by an increased frequency of mature, high affinity DNA-reactive B cells and the mice expressed increased levels of serum anti-DNA antibodies. This coincided with a significant increase in serum levels of BAFF. Treatment of transgene-expressing mice with a BAFF blocking agent or with DNase to reduce exposure to autoantigen limited the expansion of high affinity DNA-reactive B cells during B cell reconstitution. These studies suggest that during B cell reconstitution, not only is negative selection of high affinity DNA-reactive B cells impaired by increased BAFF, but also that B cells escaping negative selection are positively selected by autoantigen. There are significant implications for therapy.

  13. Prevention of the exposure by cyclophosphamide oral tablet

    OpenAIRE

    Hanada, Takae; Takami, Yoichiro; Moriyama, Kei; Oro, Masafumi; Ogawa, Takehiro; Moriyasu, Hiroko; Inoue, Yuka; Kanemitsu, Asako; Kawamoto, Eiko; Nagase, Ayaka; Hamahara, Anna; Yamamoto, Atsuko; Shimada, Kenichi; TAKAHASHI, Masashi; Egawa, Takashi

    2015-01-01

    Background Unintended exposure to antitumor agents from an oral medicine may place healthcare workers and patients taking medicine at risk. In this study, the exposure to blister pack by CP (cyclophosphamide) and appropriate preventive procedures were examined. Findings CP detected inside the blister pack of the tested seven lots by LC-MS/MS ranged from 8.2 to 199.6 ng. Raman imaging clearly showed that CP ingredient was completely covered by the tablet coating layer and had not leached out o...

  14. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis : long-term follow-up

    NARCIS (Netherlands)

    Harper, Lorraine; Morgan, Matthew D.; Walsh, Michael; Hoglund, Peter; Westman, Kerstin; Flossmann, Oliver; Tesar, Vladimir; Vanhille, Phillipe; de Groot, Kirsten; Luqmani, Raashid; Felipe Flores-Suarez, Luis; Watts, Richard; Pusey, Charles; Bruchfeld, Annette; Rasmussen, Niels; Blockmans, Daniel; Savage, Caroline O.; Jayne, David

    2012-01-01

    Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were

  15. Effect of cyclophosphamide on the microanatomy of liver of albino rats

    Directory of Open Access Journals (Sweden)

    Javed Ahmad Khan

    2014-08-01

    Conclusion: Cyclophosphamide induces histological changes like fatty infiltration and central vein congestion in the liver. These changes are with low doses given for longer durations and manifest earlier when larger doses are used. Thus it is advised that patients receiving cyclophosphamide should be periodically evaluated for liver dysfunction. [Int J Res Med Sci 2014; 2(4.000: 1466-1469

  16. Photocatalytic oxidation of 5-fluorouracil and cyclophosphamide via UV/TiO2 in an aqueous environment.

    Science.gov (United States)

    Lin, Hank Hui-Hsiang; Lin, Angela Yu-Chen

    2014-01-01

    Cytostatic drugs are a class of pharmaceuticals that are increasingly used in cancer therapies; 5-fluorouracil is one of the most commonly used cytostatic (antineoplastic) drugs in the world. This study applied photocatalytic oxidation to remove 5-fluorouracil. Degussa P25 showed a higher photocatalytic degradation efficiency for 5-fluorouracil removal than Aldrich TiO2 and ZnO. Under optimal conditions (20 mg L(-1) TiO2 at pH 5.8), 200 μg L(-1) 5-fluorouracil can be removed within 2 h (k = 0.0375 min(-1)). 5-fluorouracil was found to be decomposed by near-surface OH free radicals produced from valence holes (hvb(+)). At a relatively high concentration, 5-fluorouracil (27.6 mg L(-1)) is >99.9% removed within 4 h by 300 mg L(-1) Degussa P25, while 24 h is required to reach complete mineralization with 96.7% fluoride recovery. Cyclophosphamide is another widely used cancer drug that follows a similar decomposition pathway. Cyclophosphamide (27.6 mg L(-1)) was also >99.9% eliminated within 4 h, but dechlorination and mineralization reached only 79.9% and 55.1%, respectively, after 16 h of irradiation. Together with the results for Microtox(®), it is suggested that the oxidation products of cyclophosphamide are even more recalcitrant and toxic. For engineering practices, despite the fact that photocatalytic oxidation can rapidly remove target antineoplastic, it is also important to further evaluate the treatment efficiency of the photoproducts.

  17. A retrospective comparison of cyclophosphamide plus antithymocyte globulin with cyclophosphamide plus busulfan as the conditioning regimen for severe aplastic anemia

    Directory of Open Access Journals (Sweden)

    L.V.M. Ommati

    2009-03-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (AHSCT is the treatment of choice for young patients with severe aplastic anemia (SAA. The association of antithymocyte globulin (ATG and cyclophosphamide (CY is the most frequently used conditioning regimen for this disease. We performed this retrospective study in order to compare the outcomes of HLA-matched sibling donor AHSCT in 41 patients with SAA receiving cyclophosphamide plus ATG (ATG-CY, N = 17 or cyclophosphamide plus busulfan (BU-CY, N = 24. The substitution of BU for ATG was motivated by the high cost of ATG. There were no differences in the clinical features between the two groups, including age, gender, cytomegalovirus status, ABO match, interval between diagnosis and transplant, and number of total nucleated cells infused. No differences were observed in the time to neutrophil and platelet engraftment, or in the risk of veno-occlusive disease and hemorrhage. However, there was a higher risk of mucositis in the BU-CY group (71 vs 24%, P = 0.004. There were no differences in the incidence of neutrophil and platelet engraftment, acute and chronic graft-versus-host disease, and transplant-related mortality. There was a higher incidence of late rejection in the ATG-CY group (41 vs 4%, P = 0.009. Although the ATG-CY group had a longer follow-up (101 months than the BU-CY group (67 months, P = 0.04, overall survival was similar between the groups (69 vs 58%, respectively, P = 0.32. We conclude that the association BU-CY is a feasible option to the conventional ATG-CY regimen in this population.

  18. Clinical Efficacy of Capecitabine and Cyclophosphamide (XC in Patients with Metastatic Breast Cancer

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    Shien,Tadahiko

    2011-08-01

    Full Text Available Combined low-dose therapy of oral capecitabine (Xeloda and cyclophosphamide (XC has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC and is aimed at symptomatic alleviation and prolongation of survival. Here, a retrospective review was conducted of MBC patients administered XC at the Okayama University Hospital (OUH, to evaluate responses to XC, adverse events and time to progression (TTP. Twenty patients with MBC received XC between 2006 and 2009. With the exception of 2 elderly patients who were over the age of 70 at the initial examination, all of the patients had received prior treatment with an anthracycline and/or a taxane. No complete response (CR cases were observed, but partial response (PR was achieved in 6 patients (30% and SD in 9 (45%, of whom 5 (20% sustained SD status for >12 months. The median TTP was 6 months (range:3-27 mo.. Three patients developed Grade 3 adverse events (diarrhea, nausea and stomatitis, but no other patients developed adverse reactions causing interruption of the therapy. XC was safe even in previously treated and elderly MBC patients;moreover, it yielded remarkable clinical responses.

  19. Clinical efficacy of capecitabine and cyclophosphamide (XC) in patients with metastatic breast cancer.

    Science.gov (United States)

    Shien, Tadahiko; Doihara, Hiroyoshi; Nishiyama, Keiko; Masuda, Hiroko; Nogami, Tomohiro; Ikeda, Hirokuni; Taira, Naruto

    2011-08-01

    Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC) has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and prolongation of survival. Here, a retrospective review was conducted of MBC patients administered XC at the Okayama University Hospital (OUH), to evaluate responses to XC, adverse events and time to progression (TTP). Twenty patients with MBC received XC between 2006 and 2009. With the exception of 2 elderly patients who were over the age of 70 at the initial examination, all of the patients had received prior treatment with an anthracycline and/or a taxane. No complete response (CR) cases were observed, but partial response (PR) was achieved in 6 patients (30%) and SD in 9 (45%), of whom 5 (20%) sustained SD status for >12 months. The median TTP was 6 months (range:3-27 mo.). Three patients developed Grade 3 adverse events (diarrhea, nausea and stomatitis), but no other patients developed adverse reactions causing interruption of the therapy. XC was safe even in previously treated and elderly MBC patients;moreover, it yielded remarkable clinical responses.

  20. Effects of cyclophosphamide on immune system and gut microbiota in mice.

    Science.gov (United States)

    Xu, Xiaofei; Zhang, Xuewu

    2015-02-01

    Cyclophosphamide (CP) is the most commonly used drug in autoimmune disease, cancer, blood and marrow transplantation. Recent data revealed that therapy efficacy of CP is gut microbiota-dependent. So, it is very important to understand how CP affects intestinal microbiota and immune function. In this study, the effects of CP on mice immuno-activity were firstly evaluated, then, the fecal microbiota from normal and CP-treated mice was compared, and the characteristic bacterial diversity and compositions were identified, using 454 pyrosequencing technology. The results showed that CP reduced the diversity and shifted the fecal microbiota composition. Specifically, CP treatment decreased the proportion of Bacteroidetes while increased the proportion of Firmictutes in the microbial community. Most importantly, specific microbiota signatures belonging to Bacteroides acidifaciens, Streptococcaceae and Alistipes were also identified, which would provide new insight into the efficacy and side effects in clinical usage of CP. This should be helpful for further demonstration of CP's action mechanism, development of personalized therapy strategies, and prediction of potential side effects related to various treatment regimens of CP. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. Pneumonitis and pulmonary fibrosis in a patient receiving adjuvant docetaxel and cyclophosphamide for stage 3 breast cancer: a case report and literature review

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    Ochoa Roberto

    2012-11-01

    Full Text Available Abstract Introduction Pulmonary toxicities associated with chemotherapeutic agents utilized as adjuvant therapy in patients with breast cancer are distinctly uncommon. The chemotherapy regimen of docetaxel/cyclophosphamide has a more favorable therapeutic index compared to anthracycline-based regimens due to a significantly lower incidence of heart failure and leukemia. Consequently, docetaxel/cyclophosphamide is the preferred adjuvant chemotherapy of choice in older women or in women where anthracyclines may be contraindicated. Pulmonary complications in patients with breast cancer receiving taxane-based adjuvant chemotherapy in the absence of radiation are distinctly uncommon. Here, we report the case of a patient receiving adjuvant docetaxel/cyclophosphamide who developed rapid-onset, biopsy-proven interstitial pneumonitis. Case presentation A 72-year-old Hispanic woman was diagnosed as having stage 3 hormone-receptor positive, human epidermal growth factor receptor 2/neu negative, invasive breast cancer. Due to the estimated 10-year risk of recurrence of approximately 80 percent, a decision was made to treat our patient with adjuvant chemotherapy. Due to her age and increased risk of cardiac toxicity with anthracycline-based chemotherapy regimens, our patient was treated with docetaxel/cyclophosphamide chemotherapy for a total of four planned cycles. However, approximately two weeks after receiving the third cycle of chemotherapy, our patient developed rapidly progressive dyspnea, and a non-productive cough and went to the emergency room at an outside medical facility. She was found to have mild hypoxemia, and new onset of peripheral, subpleural fibrotic changes not present on pre-treatment scans. A thorascopic-guided wedge biopsy of the lung tissue revealed subacute interstitial pneumonitis. Our patient made a rapid clinical recovery after treatment with corticosteroids. Conclusions Interstitial pneumonitis is a rare complication of

  2. Avocado fruit (Persea americana Mill) exhibits chemo-protective potentiality against cyclophosphamide induced genotoxicity in human lymphocyte culture.

    Science.gov (United States)

    Paul, Rajkumar; Kulkarni, Paresh; Ganesh, Narayan

    2011-01-01

    Diets rich in fruits and vegetables have been associated with reduced risks for many types of cancers. Avocado (Persea americana Mill.) is a widely consumed fruit containing many cancer preventing nutrients, vitamins and phytochemicals. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with 50% Methanol from avocado fruits help in proliferation of human lymphocyte cells and decrease chromosomal aberrations induced by cyclophosphamide. Among three concentrations (100 mg, 150 mg and 200 mg per Kg Body Weight), the most effective conc. of extract was 200 mg/Kg Body Wt. It decreased significant level of numerical and structural aberrations (breaks, premature centromeric division etc. up to 88%, p < 0.0001)), and accrocentric associtation within D & G group (up to 78%, p = 0.0008). These studies suggest that phytochemicals from the avocado fruit can be utilized for making active chemoprotective ingredient for lowering the side effect of chemotherapy like cyclophosphamide in cancer therapy.

  3. Treatment of diffuse histiocytic and diffuse mixed non-Hodgkin lymphomas with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP).

    Science.gov (United States)

    Cohen, Y; Epelbaum, R; Ben-Shahar, M; Ron, Y; Haim, N

    1988-01-01

    During 1977 to 1985 90 patients with large-cell non-Hodgkin lymphoma (diffuse histiocytic or diffuse mixed according to Rapport classification) were treated by the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) with a mean follow-up of 41 months. Thirty-four patients were treated with radiation therapy as well. The mean number of CHOP cycles to achieve complete response was 4.0 and the mean total number of cycles was 6.6. For 78 patients it was possible to calculate relative dose intensity (RDI) for each drug and the average RDI. Sixty-four patients (71%) achieved CR. The actuarial 5-year survival rate of all patients was 52%. The median RDI for cyclophosphamide was 0.72, for doxorubicin 0.70, for vincristine 0.69 and the median average RDI was 0.69. The following favorable prognostic factors were found to be of statistical significance: female sex and stages I-III as compared to stage IV. The 5-year survival rate for stage I & II patients treated by CHOP plus radiotherapy was 70% as compared to 55% for those treated by CHOP only; this difference was not statistically significant.

  4. TNF-alpha bioactivity-inhibiting therapy in ANCA-associated vasculitis : Clinical and experimental considerations

    NARCIS (Netherlands)

    Huugen, Dennis; Tervaert, Jan Willem Cohen; Heeringa, Peter

    2006-01-01

    Wegener's granulomatosis, microscopic polyangiitis, idiopathic necrotizing crescentic glomerulonephritis, and Churg-Strauss syndrome are associated with the presence of ANCA with specificity for myeloperoxidase or proteinase 3. Current therapy consists mainly of corticosteroids and cyclophosphamide,

  5. Legubicin, a Tumor-Activated Prodrug for Breast Cancer Therapy

    Science.gov (United States)

    2007-04-01

    Activated Prodrug for Breast Cancer Therapy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-05-1-0318 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Cheng...cyclophosphamide, non-lyophilized cyclophosphamide, cytarabine, daca dactinomycin, daunorubicin, diethyistilbestrol, epoetin alfa, esperamycin, etidronat...0562 (to R. Xiang) from the US Department of Defense; California Tobacco- Related Disease Research Program grant 12 RT-0002 (to R.A. Reisfeld

  6. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    Science.gov (United States)

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  7. [Combination chemotherapy with vincristine, melphalan, CCNA, cyclophosphamide, prednisone in myeloma].

    Science.gov (United States)

    Le Loët, X; Monconduit, M; Menard, J F; Deshayes, P; Grobois, B; Tanguy, A; Prevost, E; Piguet, H

    1984-05-01

    The authors report the results of a prospective, multi-centre trial involving 87 patients with previously untreated myeloma who were treated by combination chemotherapy consisting of melphalan, cyclophosphamide, CCNU, prednisone and vincristine. 83.1% of patients had a high tumour mass (stage III on Durie and Salmon's classification). The response to treatment could be evaluated in 76 patients and 70% were found to respond. The median actuarial survival of the whole population is 30 months. The survival is significantly longer (p less than 0.001) in responders (median 40 months) than in non-responders (median: 17 months); the survival is significantly shorter (p less than 0.01) in subjects with renal failure (median: 10 months) than in subjects without renal failure (median: 36 months). This treatment is sufficiently well tolerated to be administered on an outpatient basis. One case of acute monoblastic leukaemia was observed. These results are similar to those reported in the literature.

  8. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

    Science.gov (United States)

    Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

    2017-03-01

    Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571.

  9. A healthy heart is not a metronome: An integrative review of the heart’s anatomy and heart rate variability

    Directory of Open Access Journals (Sweden)

    Fredric Bruce Shaffer

    2014-09-01

    Full Text Available Heart rate variability (HRV, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operate on different time scales to adapt to challenges and achieve optimal performance. This article briefly reviews neural regulation of the heart, and its basic anatomy, the cardiac cycle, and the sinoatrial and atrioventricular pacemakers. The cardiovascular regulation center in the medulla integrates sensory information and input from higher brain centers, and afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. This article reviews sympathetic and parasympathetic influences on the heart, and examines the interpretation of HRV and the association between reduced HRV, risk of disease and mortality, and the loss of regulatory capacity. This article also discusses the intrinsic cardiac nervous system and the heart-brain connection, through which afferent information can influence activity in the subcortical and frontocortical areas, and motor cortex. It also considers new perspectives on the putative underlying physiological mechanisms and properties of the ultra-low-frequency (ULF, very-low-frequency (VLF, low-frequency (LF, and high-frequency (HF bands. Additionally, it reviews the most common time and frequency domain measurements as well as standardized data collection protocols. In its final section, this article integrates Porges’ polyvagal theory, Thayer and colleagues’ neurovisceral integration model, Lehrer, Vaschillo, and Vaschillo’s resonance frequency model, and the Institute of HeartMath’s coherence model. The authors conclude that a coherent heart is not a metronome because its rhythms are characterized by both complexity and stability over longer time scales. Future research should expand understanding of how the heart and its intrinsic nervous system influence the brain.

  10. A healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability.

    Science.gov (United States)

    Shaffer, Fred; McCraty, Rollin; Zerr, Christopher L

    2014-01-01

    Heart rate variability (HRV), the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operate on different time scales to adapt to challenges and achieve optimal performance. This article briefly reviews neural regulation of the heart, and its basic anatomy, the cardiac cycle, and the sinoatrial and atrioventricular pacemakers. The cardiovascular regulation center in the medulla integrates sensory information and input from higher brain centers, and afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. This article reviews sympathetic and parasympathetic influences on the heart, and examines the interpretation of HRV and the association between reduced HRV, risk of disease and mortality, and the loss of regulatory capacity. This article also discusses the intrinsic cardiac nervous system and the heart-brain connection, through which afferent information can influence activity in the subcortical and frontocortical areas, and motor cortex. It also considers new perspectives on the putative underlying physiological mechanisms and properties of the ultra-low-frequency (ULF), very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) bands. Additionally, it reviews the most common time and frequency domain measurements as well as standardized data collection protocols. In its final section, this article integrates Porges' polyvagal theory, Thayer and colleagues' neurovisceral integration model, Lehrer et al.'s resonance frequency model, and the Institute of HeartMath's coherence model. The authors conclude that a coherent heart is not a metronome because its rhythms are characterized by both complexity and stability over longer time scales. Future research should expand understanding of how the heart and its intrinsic nervous system influence the brain.

  11. Development of an oral solid dispersion formulation for use in low-dose metronomic chemotherapy of paclitaxel.

    Science.gov (United States)

    Moes, Johannes; Koolen, Stijn; Huitema, Alwin; Schellens, Jan; Beijnen, Jos; Nuijen, Bastiaan

    2013-01-01

    For the clinical development of low-dose metronomic (LDM) chemotherapy of paclitaxel, oral administration is vital. However, the development of an oral formulation is difficult due to paclitaxel's low oral bioavailability, caused by its low permeability and low solubility. We increased the oral bioavailability of paclitaxel by combining a pharmacokinetic booster, ritonavir, with a new oral solid dispersion formulation of paclitaxel. The combined use of Hansen solubility parameters and dissolution experiments resulted in the development of a solid dispersion formulation containing 1/11 w/w paclitaxel, 9/11 w/w polyvinylpyrrolidone (PVP) K30, and 1/11 w/w sodium lauryl sulfate (SLS). Analysis of the solid dispersion formulation by X-ray diffraction, Fourier transform infrared (FT-IR) spectroscopy, and modulated differential scanning calorimetry (mDSC) confirmed the amorphous nature of paclitaxel and the fine dispersion of paclitaxel in the matrix of PVP-K30 and SLS. Furthermore, in vitro tests showed a major increase in the apparent solubility and dissolution rate of paclitaxel. To test the clinical significance of these findings, the solid dispersion formulation of paclitaxel (ModraPac001 10mg capsule) was compared to the paclitaxel premix solution in four patients with advanced cancer. Although the mean systemic exposure to paclitaxel after oral administration of the solid dispersion formulation was slightly lower compared to the paclitaxel premix solution (190±63.1ng/mLh for vs. 247±100ng/mLh), the systemic exposure to paclitaxel is clinically relevant [1,2]. In addition to this, the favorable pharmaceutical characteristics, for example, neutral taste, dosing accuracy, and the 2-year ambient shelf life, make the ModraPac001 10mg capsule an attractive candidate for oral paclitaxel chemotherapy. Currently, the ModraPac001 formulation is applied in the first clinical trial with oral LDM chemotherapy of paclitaxel.

  12. Green tea infusion improves cyclophosphamide-induced damage on male mice reproductive system

    Directory of Open Access Journals (Sweden)

    Mariane Magalhães Zanchi

    2015-01-01

    Full Text Available Green tea presents catechins as its major components and it has a potential antioxidant activity. Cyclophosmamide (CP is an antineoplastic and immunosuppressive agent, known to reduce fertility. In the present study, we evaluated the effect of green tea infusion on cyclophosphamide-induced damage in male mice reproductive system. Mice received green tea infusion (250 mg/kg or vehicle by gavage for 14 days. Saline or CP were injected intraperitoneally at a single dose (100 mg/kg at the 14th day. Animals were euthanized 24 h after CP administration and testes and epididymis were removed for biochemical analysis and sperm evaluation. Catechins concentration in green tea infusion was evaluated by HPLC. CP increased lipid peroxidation, DNA damage and superoxide dismutase activity whereas sperm concentration, glutathione peroxidase (GPx, glutathione S-transferase (GST and 17β-hydroxysteroid (17β-HSD dehydrogenase activities were reduced in both tissues tested. Catalase activity and protein carbonyl levels were changed only in testes, after CP administration. Green tea pre-treatment reduced significantly lipid peroxidation, protein carbonylation, DNA damage and restored GPx and GST activity in testes. In epididymis, therapy significantly increased sperm concentration and restored GPx and 17β-HSD activity. Green tea improves CP-induced damage on reproductive system, probably due to their high catechins content.

  13. Busulfan,cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    张春阳

    2013-01-01

    Objective To evaluate the efficacy and safety of dose-reduced intravenous busulfan,cyclophosphamide and etoposide(BCV)as conditioning for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)

  14. Enantioselectivity in the Metabolism of Cyclophosphamide in Patients With Multiple or Systemic Sclerosis.

    Science.gov (United States)

    de Castro, Francine Attié; Simões, Belinda Pinto; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

    2017-01-13

    The aim of this study was to evaluate the enantioselective pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide and carboxyethylphosphoramide mustard in patients with systemic or multiple sclerosis. Patients with systemic sclerosis (n = 10) or multiple sclerosis (n = 10), genotyped for the allelic variants of CYP2C9*2 and CYP2C9*3 and of the CYP2B6 G516T polymorphism, were treated with 50 mg cyclophosphamide/kg daily for 4 days. Serial blood samples were collected up to 24 hours after administration of the last cyclophosphamide dose. Cyclophosphamide, 4-hydroxycyclophosphamide, and carboxyethylphosphoramide enantiomers were analyzed in plasma samples using liquid chromatography-tandem mass spectrometry coupled to chiral column Chiralcel OD-R or Chiralpak AD-RH. Cytokines IL-2, IL-4, IL-6, IL-8, IL-10, IL- 12p70, IL-17, TNF-α, and INT-δ in the plasma samples collected before cyclophosphamide infusion were analyzed by Milliplex MAP human cytokine/chemokine. Pharmacokinetic parameters showed higher plasma concentrations of (S)-(-)-cyclophosphamide (AUC 215.0 vs 186.2 μg·h/mL for multiple sclerosis patients and 219.1 vs 179.2 μg·h/mL for systemic sclerosis patients) and (R)-4-hydroxycyclophosphamide (AUC 5.6 vs 3.7 μg·h/mL for multiple sclerosis patients and 6.3 vs 5.6 μg·h/mL for systemic sclerosis patients) when compared to their enantiomers in both groups of patients, whereas the pharmacokinetics of the carboxyethylphosphoramide metabolite was not enantioselective. Cytokines' plasma concentrations were similar between multiple and systemic sclerosis groups. The pharmacokinetics of cyclophosphamide is enantioselective in patients with systemic sclerosis and multiple sclerosis, with higher plasma concentrations of the (S)-(-)-cyclophosphamide enantiomer due to the preferential formation of the (R)-4-hydroxycyclophosphamide metabolite.

  15. Hepatoprotective activity of white horehound (Marrubium vulgare) extract against cyclophosphamide toxicity in male rats.

    Science.gov (United States)

    Ettaya, Amani; Dhibi, Sabah; Samout, Noura; Elfeki, Abdelfettah; Hfaiedh, Najla

    2016-04-01

    The hepatoprotective activity of Marrubium vulgare against cyclophosphamide toxicity in Wistar rats was evaluated. Adult male rats were divided into 4 groups of 6 each: a control group, a group injected with cyclophosphamide (150 mg·kg(-1)) for 3 days, a group orally given a M. vulgare aqueous extract ((500 mg of dry leaves)·kg(-1)·day(-1)) for 30 days then treated with cyclophosphamide, and a group receiving only M. vulgare for 30 days. After 33 days of treatment, activities of alanine amino transferase (ALAT), aspartate amino transferase (ASAT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were determined in serum. Moreover, lipid peroxidation level and superoxide dismutase (SOD) activities, catalase (CAT) and glutathione peroxidase (GPx) were measured in liver. Alterations of these hepatic biomarkers and increased lipid peroxidation confirmed cyclophosphamide-induced liver toxicity. Cyclophosphamide also decreased the enzymatic defense system against oxidative stress. However, when this drug was administered in rats given M. vulgare extract, all the biological parameters underwent much less alteration. Administration of M. vulgare extract was found to be beneficial by attenuating cyclophosphamide-induced liver damage. The protective effect of the plant is mainly attributed to its antioxidant properties and the existence of phenolic acids and flavonoids, as highlighted by HPLC-based analysis.

  16. Cyclophosphamide-induced symptomatic hyponatremia, a rare but severe side effect: a case report

    Directory of Open Access Journals (Sweden)

    Elazzazy S

    2014-09-01

    Full Text Available Shereen Elazzazy,1 Asmaa Elhassan Mohamed,2 Amaal Gulied1 1Pharmacy Department, 2Oncology Hematology Department, National Center for Cancer Care and Research (NCCCR, Hamad Medical Corporation, Doha, QatarAbstract: Cyclophosphamide is commonly used in the treatment of malignant diseases. Symptomatic severe hyponatremia induced by low-dose cyclophosphamide is very uncommon worldwide. We report a case of severe symptomatic hyponatremia that developed in a female breast cancer patient following the first cycle of chemotherapy containing low-dose cyclophosphamide. Her laboratory test showed serum Na of 112 mmol/L. Her hyponatremia was initially treated with sodium bicarbonate. She completely recovered without neurological deficits after slow correction of the serum Na concentration. Although hyponatremia is a rare toxicity it should always be considered during the usage of cyclophosphamide, even if the dosage is low, especially with concurrent use of other medications that impair water excretion, like chlorthalidone. This report describes the first reported case of cyclophosphamide-induced hyponatremia in Qatar.Keywords: AC protocol, adjuvant chemotherapy, breast cancer, cyclophosphamide, hyponatremia, thiazides

  17. The Protective effect of Ellagic acid on rats’ ovarian fetus toxicity induced by cyclophosphamide

    Directory of Open Access Journals (Sweden)

    M Mousavi M

    2015-10-01

    Full Text Available Background & aim: Cyclophosphamide, an alkylating agent used in the treatment of cancer that has many side effects on different organs, including the gonads .The purpose of this study was to investigate the effects of an antioxidant Ellagic acid on cyclophosphamide -induced toxicity in rat fetal ovarian tissue. Methods: Forty two pregnant  female Wistar rats weighing 250-200 gr were randomly divided into seven groups.The first, second, third, fourth, fifth and sixth 5 mg/ kg cyclophosphamide on days 1, 13 and 18 were given intraperitoneal remote pregnancy .The fourth, fifth and sixth groups hour after receiving cyclophosphamide, Ellagic acid (10 mg/kg has received in the course of pregnancy.Control groups and seven group (normal during pregnancy daily orally received 0.5 mL of saline. After postpartum, Neonatal rats were anesthetized with ether. Animals were dissects, then Ovaries were removed and transferred to 10% formalin solution. After tissue processing, tissue sections were prepared and H&E stained.Data were analyzed by SPSSsoftware and One- way ANOVA test. Results: The groups that were exposed to cyclophosphamide ovarian mean of diameter, primordial follicle diameter and number of follicular cell of primordialin control group compared to ellagic acid treatments showed a significant decrease. Conclusion: The results showed that Ellagic acid due to its antioxidant properties could reduce the harmful effects caused by cyclophosphamide in the fetal ovary.

  18. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

    Directory of Open Access Journals (Sweden)

    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  19. Yangjing Capsule Ameliorates Spermatogenesis in Male Mice Exposed to Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Hongle Zhao

    2015-01-01

    Full Text Available Yangjing capsule (YC, a traditional Chinese compound herbal preparation, has been proven as an effective drug to improve spermatogenesis in clinical practice. However, its pharmacological mechanisms were not fully clarified. This study was designed to investigate the protective effects of YC on spermatogenesis in the mouse model of spermatogenesis dysfunction induced by cyclophosphamide (CP. The administration of YC significantly increased the epididymal index, sperm count, and sperm motility of model mice. Histopathological changes demonstrated that CP caused obvious structural damage to testis, which were reversed by the administration of YC. Results from TUNEL assay showed that treatment with YC dramatically decreased the apoptosis of spermatogenic cell induced by CP. Moreover, YC treatment could inhibit the mRNA and protein expression of Bax to Bcl-2 and also raised expression of AR at both mRNA and protein levels. These data suggest that YC might ameliorate spermatogenesis in male mice exposed to CP through inhibiting the apoptosis of spermatogenic cell and enhancing the actions of testosterone in spermatogenesis.

  20. Inhibition of cyclophosphamide-induced teratogenesis by beta-ionone.

    Science.gov (United States)

    Gomes-Carneiro, M R; De-Oliveira, A C A X; De-Carvalho, R R; Araujo, I B; Souza, C A M; Kuriyama, S N; Paumgartten, F J R

    2003-03-03

    Beta-ionone (BI) is a degraded (C 13) sesquiterpene found in plant essential oils. It has been used in the synthesis of perfume chemicals and vitamin A. Recently, it was reported that BI is a rather potent in vitro inhibitor of CYP2B1-catalysed reactions in rat liver microsomes. The present study was performed to investigate whether inhibition of CYP2B1 reactions by BI could lead to an attenuation of cyclophosphamide (CP)-induced embryotoxicity in the rat. In a preliminary experiment, a dose-dependent prolongation of pentobarbital sleeping time in male and female Wistar rats suggested that BI inhibits CYP2B1 in vivo as well. In a second experiment, rats were treated by gavage with BI (0, 250, 500, 750 or 1000 mg/kg body wt) 45 min prior to a subcutaneous injection of either CP (7.5 mg/kg body wt) or its vehicle (saline) on day 11 of pregnancy. BI alone, at the highest dose tested, caused a high proportion of resorptions. Lower doses of BI, however, clearly attenuated CP-induced embryolethality and teratogenicity. These results seem to support the view that, as far as rats are concerned, CYP2B1 plays an important role in the conversion of CP into its embryolethal and teratogenic metabolites.

  1. [Effect of cyclophosphamide in experimental histoplasmosis in the rat].

    Science.gov (United States)

    Gago, J G; Godio, C M; Ochoa, L B; Negroni, R; Nejamkis, M R

    1998-01-01

    Histoplasmosis is a fungal disease caused by the dimorphous fungus Histoplasma capsulatum (Hc). Cyclophosphamide (Cy) was used as an immunomodulator capable of modifying the course of the disease, as well as of regulating the mechanisms involved in T-lymphocyte mediated immune response. Rats were subjected to intracardiac inoculation of Hc followed by a fractionated treatment with a 100 mg/kg body weight dose of Cy on days +4, +5, +6, +7 and +11 pi. Until day 26 pi, treatment with Cy caused 85% mortality whereas no mortality was observed among animals only inoculated with Hc. On day 14 pi, the group of Hc animals showed a delayed hypersensitivity test (DH) of 26.60 + 13.96 as determined by the swelling of the leg. Conversely, DH was significantly depressed in rats inoculated with Hc and treated with Cy: 3.88 +/- 1.00 (p < 0.01). Colony forming units count in this group was 2020 CFU/g of spleen, and 24 CFU/g of spleen (p < 0.01) in controls. A macroscopic study of the organs revealed that the animals in the Hc+Cy group had spleenomegaly and lungs with granuloma and hemorrhagic spots. The controls only presented small lung abscesses. These findings lead to the conclusion that Cy causes a deterioration of cell mediated immune response which results in the manifestation of an acute, fatal experimental mycosis.

  2. Processed Aloe vera Gel Ameliorates Cyclophosphamide-Induced Immunotoxicity

    Directory of Open Access Journals (Sweden)

    Sun-A Im

    2014-10-01

    Full Text Available The effects of processed Aloe vera gel (PAG on cyclophosphamide (CP-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer’s patch cells. Peyer’s patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer’s patch cells isolated from normal mice to produce cytokines including interleukin (IL-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer’s patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects.

  3. Processed Aloe vera gel ameliorates cyclophosphamide-induced immunotoxicity.

    Science.gov (United States)

    Im, Sun-A; Kim, Ki-Hyang; Kim, Hee-Suk; Lee, Ki-Hwa; Shin, Eunju; Do, Seon-Gil; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil

    2014-10-24

    The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer's patch cells. Peyer's patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF) in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer's patch cells isolated from normal mice to produce cytokines including interleukin (IL)-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer's patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects.

  4. Cyclophosphamide alters the gene expression profile in patients treated with high doses prior to stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Ibrahim El-Serafi

    Full Text Available BACKGROUND: Hematopoietic stem cell transplantation is a curative treatment for several haematological malignancies. However, treatment related morbidity and mortality still is a limiting factor. Cyclophosphamide is widely used in condition regimens either in combination with other chemotherapy or with total body irradiation. METHODS: We present the gene expression profile during cyclophosphamide treatment in 11 patients conditioned with cyclophosphamide for 2 days followed by total body irradiation prior to hematopoietic stem cell transplantation. 299 genes were identified as specific for cyclophosphamide treatment and were arranged into 4 clusters highly down-regulated genes, highly up-regulated genes, early up-regulated but later normalized genes and moderately up-regulated genes. RESULTS: Cyclophosphamide treatment down-regulated expression of several genes mapped to immune/autoimmune activation and graft rejection including CD3, CD28, CTLA4, MHC II, PRF1, GZMB and IL-2R, and up-regulated immune-related receptor genes, e.g. IL1R2, IL18R1, and FLT3. Moreover, a high and significant expression of ANGPTL1 and c-JUN genes was observed independent of cyclophosphamide treatment. CONCLUSION: This is the first investigation to provide significant information about alterations in gene expression following cyclophosphamide treatment that may increase our understanding of the cyclophosphamide mechanism of action and hence, in part, avoid its toxicity. Furthermore, ANGPTL1 remained highly expressed throughout the treatment and, in contrast to several other alkylating agents, cyclophosphamide did not influence c-JUN expression.

  5. Population pharmacokinetics of cyclophosphamide and metabolites in children with neuroblastoma: a report from the Children's Oncology Group.

    Science.gov (United States)

    McCune, Jeannine S; Salinger, David H; Vicini, Paolo; Oglesby, Celeste; Blough, David K; Park, Julie R

    2009-01-01

    Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies; however, current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, the authors' objectives were (1) to quantify and explain the pharmacokinetic variability of cyclophosphamide and 2 of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM), and (2) to apply a population pharmacokinetic model to describe the disposition of cyclophosphamide and these metabolites. A total of 196 blood samples were obtained from 22 children with neuroblastoma receiving intravenous cyclophosphamide (400 mg/m2/d) and topotecan. Blood samples were quantitated for concentrations of cyclophosphamide, HCY, and CEPM using liquid chromatography-mass spectrometry and analyzed using nonlinear mixed-effects modeling with the NONMEM software system. After model building was complete, the area under the concentration-time curve (AUC) was computed using NONMEM. Cyclophosphamide elimination was described by noninducible and inducible routes, with the latter producing HCY. Glomerular filtration rate was a covariate for the fractional elimination of HCY and its conversion to CEPM. Considerable interpatient variability was observed in the AUC of cyclophosphamide, HCY, and CEPM. These results represent a critical first step in developing pharmacokinetic-linked pharmacodynamic studies in children receiving cyclophosphamide to determine the clinical relevance of the pharmacokinetic variability in cyclophosphamide and its metabolites.

  6. Population Pharmacokinetics of Cyclophosphamide and Metabolites in Children with Neuroblastoma: a Report from the Children’s Oncology Group

    Science.gov (United States)

    McCune, Jeannine S.; Salinger, David H.; Vicini, Paolo; Oglesby, Celeste; Blough, David K.; Park, Julie R.

    2009-01-01

    Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies, however current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, our objectives were to 1. quantify and explain the pharmacokinetic variability of cyclophosphamide, and two of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM); 2. apply a population pharmacokinetic model to describe the disposition of cyclophosphamide and these metabolites. A total of 196 blood samples were obtained from 22 children with neuroblastoma receiving intravenous (IV) cyclophosphamide (400 mg/m2/day) and topotecan. Blood samples were quantitated for concentrations of cyclophosphamide, HCY and CEPM using liquid chromatography-mass spectrometry and analyzed using nonlinear mixed effects modeling with NONMEM software system. After model building was complete, the area under the concentration-time curve (AUC) was computed using NONMEM. Cyclophosphamide elimination was described by noninducible and inducible routes with the latter producing HCY. Glomerular filtration rate (GFR) was a covariate for the fractional elimination of HCY and its conversion to CEPM. Considerable interpatient variability was observed in the AUC of cyclophosphamide, HCY and CEPM. These results represent a critical first step in developing pharmacokinetic-linked pharmacodynamic studies in children receiving cyclophosphamide to determine the clinical relevance of the pharmacokinetic variability in cyclophosphamide and its metabolites. PMID:18927240

  7. ORAL-THERAPY FOR SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    POSTMUS, PE; SMIT, EF

    After a remarkable improvement of the very poor prognosis of small cell lung cancer with very simple therapy such as iv and oral cyclophosphamide the role of oral therapy has become minimal. However, since more than a decade results of combination chemotherapy are at a plateau and it is necessary to

  8. Anti-tumor effect of tumor vaccine combined with metronomic chemotherapy on breast cancer in mice%肿瘤疫苗联合节拍化疗对小鼠乳腺癌作用的研究

    Institute of Scientific and Technical Information of China (English)

    史业辉; 周立艳; 魏枫; 于津浦; 贾勇圣; 佟仲生

    2014-01-01

    Objective:This study aimed to observe the synergistic effect of a new tumor vaccine combined with metronomic che-motherapy in vivo on breast cancer. This study was also conducted to investigate the mechanism of this combination. Methods:Balb/c mice inoculated with 4T1 mouse breast cancer cell were used as tumor models. High-mobility group nucleosome-binding protein 1 (HMGN1) gene was used to transfect 4T1 cell lines as cancer vaccines. After 4T1 cell was inoculated, the mice were randomized into four groups:normal saline (NS);metronomic gemcitabine (GEM) alone;cancer vaccine alone;and combination therapy group. Tumor growth and potential toxicities of these regimens were observed. The Foxp3 expression of regulatory T cells (Tregs) was detected by western blot and immunohistochemical staining. The microvessel density (MVD) of the tumor was also detected by immunohistochemi-cal staining. Results:The tumor volume of the mice was significantly lower in the combination group than in the MET group or cancer vaccine group (P<0.05). This result exhibited a higher significant difference than the tumor volume of the mice in the NS group (P<0.01). Foxp3 expression was significantly lower in the mice treated with GEM (combination or MET group). MVD was significantly lower in these two groups than in the cancer vaccine group or NS group (P<0.05). Furthermore, adverse reactions slightly occurred in each group. Conclusion: The combination of cancer vaccines and metronomic GEM is a very active and well-tolerated regimen for breast cancer in mice.%目的:研究新型肿瘤疫苗联合节拍化疗对晚期乳腺癌小鼠模型的治疗效果,并探讨其作用机制。方法:以小鼠乳腺癌细胞系4T1接种Balb/c小鼠建立模型。利用含高迁移率核小体蛋白1(high-mobility group nucleosome binding protein 1,HMGN1)基因的重组质粒转染4T1细胞,制备瘤苗。小鼠皮下接种4T1细胞,随机分成生理盐水对照组(NS组)、吉西他滨

  9. Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab).

    Science.gov (United States)

    Tam, Constantine S; O'Brien, Susan; Plunkett, William; Wierda, William; Ferrajoli, Alessandra; Wang, Xuemei; Do, Kim-Anh; Cortes, Jorge; Khouri, Issa; Kantarjian, Hagop; Lerner, Susan; Keating, Michael J

    2014-11-13

    Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (≥3 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care.

  10. Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation.

    Science.gov (United States)

    Hughes, Francis M; Vivar, Nivardo P; Kennis, James G; Pratt-Thomas, Jeffery D; Lowe, Danielle W; Shaner, Brooke E; Nietert, Paul J; Spruill, Laura S; Purves, J Todd

    2014-02-01

    Bladder inflammation (cystitis) underlies numerous bladder pathologies and is elicited by a plethora of agents such as urinary tract infections, bladder outlet obstruction, chemotherapies, and catheters. Pattern recognition receptors [Toll-like receptors (TLRs) and Nod-like receptors (NLRs)] that recognize pathogen- and/or damage-associated molecular patterns (PAMPs and/or DAMPs, respectively) are key components of the innate immune system that coordinates the production (TLRs) and maturation (NLRs) of proinflammatory IL-1β. Despite multiple studies of TLRs in the bladder, none have investigated NLRs beyond one small survey. We now demonstrate that NLRP3 and NLRC4, and their binding partners apoptosis-associated speck-like protein containing a COOH-terminal caspase recruitment domain (ASC) and NLR family apoptosis inhibitory protein (NAIP), are expressed in the bladder and localized predominantly to the urothelia. Activated NLRs form inflammasomes that activate caspase-1. Placement of a NLRP3- or NLRC4-activating PAMP or NLRP3-activating DAMPs into the lumen of the bladder stimulated caspase-1 activity. To investigate inflammasomes in vivo, we induced cystitis with cyclophosphamide (CP, 150 mg/kg ip) in the presence or absence of the inflammasome inhibitor glyburide. Glyburide completely blocked CP-induced activation of caspase-1 and the production of IL-1β at 4 h. At 24 h, glyburide reduced two markers of inflammation by 30-50% and reversed much of the inflammatory morphology. Furthermore, glyburide reversed changes in bladder physiology (cystometry) induced by CP. In conclusion, NLRs/inflammasomes are present in the bladder urothelia and respond to DAMPs and PAMPs, whereas NLRP3 inhibition blocks bladder dysfunction in the CP model. The coordinated response of NLRs and TLRs in the urothelia represents a first-line innate defense that may provide an important target for pharmacological intervention.

  11. Effects of cyclophosphamide on laser immunotherapy for the treatment of metastatic cancer

    Science.gov (United States)

    Bahavar, Cody F.; Acquaviva, Joseph T.; Rabei, Sheyla; Sikes, Allie; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2014-02-01

    Laser immunotherapy (LIT) is an innovative cancer modality that uses laser irradiation and immunological stimulation to treat late-stage, metastatic cancers. The current mode of operation in LIT is through interstitial laser irradiation. Although LIT is still in development, recent clinical trials have shown that it can be used to successfully treat patients with late-stage breast cancer and melanoma. Cyclophosphamide is a chemotherapy drug that suppresses regulatory T cells when used in low doses. In this study tumor-bearing rats were treated with LIT using an 805-nm laser with a power of 2.0 W and low-dose cyclophosphamide. Glycated chitosan was used as an immunological stimulant. The goal was to observe the effects of different doses of cyclophosphamide in addition to LIT on the survival of the tumor-bearing rats.

  12. Long-term outcome after cyclophosphamide treatment in children with steroid-dependent and frequently relapsing minimal change nephrotic syndrome.

    NARCIS (Netherlands)

    Kyrieleis, H.A.; Levtchenko, E.N.; Wetzels, J.F.M.

    2007-01-01

    BACKGROUND: Seventy percent of children with minimal change nephrotic syndrome (MCNS) have a steroid-dependent or frequent relapsing course of the disease, and most are treated with cyclophosphamide. We describe the clinical course of children with biopsy-proven MCNS treated with cyclophosphamide fo

  13. Chronic cyclophosphamide exposure alters the profile of rat sperm nuclear matrix proteins.

    Science.gov (United States)

    Codrington, Alexis M; Hales, Barbara F; Robaire, Bernard

    2007-08-01

    Chronic exposure of male rats to the alkylating agent cyclophosphamide, a well-known male-mediated developmental toxicant, alters gene expression in male germ cells as well as in early preimplantation embryos sired by cyclophosphamide-exposed males. Sperm DNA is organized by the nuclear matrix into loop-domains in a sequence-specific manner. In somatic cells, loop-domain organization is involved in gene regulation. Various structural and functional components of the nuclear matrix are targets for chemotherapeutic agents. Consequently, we hypothesized that cyclophosphamide treatment would alter the expression of sperm nuclear matrix proteins. Adult male rats were treated for 4 wk with saline or cyclophosphamide (6.0 mg kg(-1) day(-1)), and the nuclear matrix was extracted from cauda epididymal sperm. Proteins were analyzed by two-dimensional gel electrophoresis. Identified proteins within the nuclear matrix proteome were mainly involved in cell structure, transcription, translation, DNA binding, protein processing, signal transduction, metabolism, cell defense, or detoxification. Interestingly, cyclophosphamide selectively induced numerous changes in cell defense and detoxification proteins, most notably, in all known forms of the antioxidant enzyme glutathione peroxidase 4, in addition to an uncharacterized 54-kDa form; an overall increase in glutathione peroxidase 4 immunoreactivity was observed in the nuclear matrix extracts from cyclophosphamide-exposed spermatozoa. An increase in glutathione peroxidase 4 expression suggests a role for this enzyme in maintaining nuclear matrix stability and function. These results led us to propose that a change in composition of the nuclear matrix in response to drug exposure was a factor in altered sperm function and embryo development.

  14. Treatment of Acute Antibody-Mediated Renal Allograft Rejection With Cyclophosphamide.

    Science.gov (United States)

    Waiser, Johannes; Duerr, Michael; Budde, Klemens; Rudolph, Birgit; Wu, Kaiyin; Bachmann, Friederike; Halleck, Fabian; Schönemann, Constanze; Lachmann, Nils

    2017-10-01

    Antibody-mediated rejection (AMR) is a major risk for renal allograft survival. Throughout decades, cyclophosphamide treatment has been proven to be effective in patients with antibody-associated autoimmune diseases. We investigated whether cyclophosphamide combined with plasmapheresis and intravenous immunoglobulins is an option for patients with AMR. Between March 2013 and November 2015, we initiated treatment of 13 consecutive patients with biopsy-proven acute AMR with intravenous cyclophosphamide pulses (15 mg/kg adapted to age and renal function) at 3-week intervals, PPH (6×), and high-dose intravenous immunoglobulin (1.5 g/kg). Treatment was completed after 6 cyclophosphamide pulses or in case of return to baseline serum creatinine together with reduction of donor-specific HLA antibodies (DSA) below 500 mean fluorescence intensity. Eleven of 13 patients completed treatment. Median follow-up was 18 (12-44) months. At the end of follow-up, graft survival was 77% (10/13). The 3 graft losses were caused at least in part by nonadherence and premature termination of treatment. Serum creatinine increased from 1.7±0.4 mg/dL at 3 months before diagnosis to 3.7±2.4 mg/dL at diagnosis (P = 0.01), and decreased to 2.1 ± 0.7 mg/dL at 3 months after diagnosis (P = 0.01). In 7 (64%) of 11 patients, who completed treatment, DSA decreased, in 4 (36%) of 11 DSA were below 500 mean fluorescence intensity after treatment. Dose reductions had to be performed in 3 of 13 patients for leukopenia. We observed 14 hospitalizations in 9 of 13 patients. To our knowledge, this is the first systematic report on cyclophosphamide-based treatment of acute AMR based on modern diagnostics. Treatment was effective and relatively safe. Future studies will show, whether cyclophosphamide proves to be a valuable alternative for the treatment of AMR.

  15. Cyclophosphamide-induced changes of serum angiotensin converting enzyme activity and pulmonary microvessels ultrastructure.

    Science.gov (United States)

    Musiatowicz, B; Terlikowski, S; Sulik, M; Famulski, W; Giedrojć, J; Jakubowski, A; Sobaniec-Lotowska, M; Pasztaleniec, L; Baltaziak, M; Jabłońska, E

    1997-01-01

    The effect of cyclophosphamide (CP) on the ultrastructure of the lung tissue and the activity of angiotensin converting enzyme (ACE) in serum was evaluated in rats. The animals were given cyclophosphamide (CP) in a single intraperitoneal dose of 150 mg/kg b.w. ACE activity was evaluated in the blood serum collected from the left ventricle of the heart using the spectrophometric method. In all time subgroups, the CP-receiving animals showed a decrease in ACE activity. Ultrastructural examinations of CP-treated animals revealed increased adhesion of neutrophiles and monocytes to the damage endothelium of the alveolar septa vessels and focally accumulation of the platelets.

  16. The influence of the protector thiol L-cystein on the toxic and therapeutic responses of stabilized "activated" cyclophosphamide (4-(S-ethanol)-sulfido-cyclophosphamide).

    Science.gov (United States)

    Voelcker, G; Laber, P; Rockinger, H; Wientzek, C; Hohorst, H J

    1984-01-01

    The influence of L-cystein on the toxic and therapeutic responses of 4-(S-ethanol)-sulfido-cyclophosphamide (P1), a stabilized "activated" cyclophosphamide, was investigated. Stabilized "activated" cyclophosphamides hydrolyze under physiological conditions to 4-hydroxycyclophosphamide (4-OH-CP). The antitumor activity of P1 was investigated on a heterotransplanted human bladder sarcoma in nude mice and in perfusion experiments carried out on the isolated tumor bearing limb in rats. Due to its rapid hydrolysis to 4-OH-CP, P1 exhibits severe local toxicity which is decreased by the protector thiol L-cystein. Simultaneous application of double molar amounts of L-cystein reduces toxicity in nude mice to approximately one-third. Therapeutic activity is not affected by this ratio of L-cystein so that the protector thiol increases the therapeutic efficacy of P1. Higher amounts of L-cystein reduce both the acute toxicity in nude mice and the therapeutic efficacy against the human xenograft. The perfusion experiments demonstrate that a P1 concentration necessary to cure rats with tumor bearing limb is only tolerated in combination with L-cystein.

  17. Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be considered the drug of choice?

    Science.gov (United States)

    Rovin, Brad H; Parikh, Samir V; Hebert, Lee A; Chan, Tak Mao; Mok, Chi Chiu; Ginzler, Ellen M; Hooi, Lai Seong; Brunetta, Paul; Maciuca, Romeo; Solomons, Neil

    2013-01-01

    Severe lupus nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy. Nevertheless, the role of mycophenolate mofetil in treating severe lupus nephritis is unclear, because such patients were excluded from these trials. With this limitation as background, this work addresses the question of mycophenolate mofetil for induction therapy for severe lupus nephritis. We performed a systematic review of the outcomes of treating severe lupus nephritis with mycophenolate mofetil or cyclophosphamide. Because no studies directly addressed this question, these data were extracted from the published literature or obtained by personal communications from investigators. There is no universally accepted definition, and therefore, severe lupus nephritis was arbitrarily defined by renal histology, resistance to therapy, or level of kidney function at presentation. For each trial analyzed, we determined the partial and complete remission rates. Long-term outcomes were compared when available. The pooled results suggest that mycophenolate mofetil and cyclophosphamide are equally effective in inducing remission of severe lupus nephritis. However, relapse rates and risk of developing ESRD were higher for mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short term, mycophenolate mofetil and cyclophosphamide are about equal in inducing remission. However, long-term outcomes suggest better preservation of kidney function and fewer relapses with cyclophosphamide therapy. Therefore, mycophenolate mofetil should not yet be considered the induction drug of choice for severe lupus nephritis.

  18. EFFICIENT ACTIVATION OF ANTITUMOR IMMUNITY BY IL-6 GENE-MODIFIED LEUKEMIA VACCINE IN COMBINATION WITH LOW DOSE CYCLOPHOSPHAMIDE AND LOW DOSE IL-2

    Institute of Scientific and Technical Information of China (English)

    Cao Xuetao; Ge Lingfu; Ju Dianwen; Tao Qun; Yu Yizhi

    1998-01-01

    Objective:To investigate the antitumor effect of the IL-6 gene-modified erythroleukemia cells combined with low dose cyclophosphamide (Cy) and low dose IL-2.Methods: Mice inoculated with FBL-3-IL-6 in combination with low dose IL-2 and low dose cyclophosphamide (Cy). Results: Mice received combined therapy of FBL-3-IL-6, IL-2 and Cy developed tumors most slowly and survived much longer when compared with mice in control groups, with 5 out of 8leukemia-bearing mice being tumor free 100 days after the combined treatment. To further explain the mechanism of the antitumor effects by the combined therapy. It was found that combined therapy with low dose Cy, low dose IL-2 and FBL-3-IL-6 achieved maximal cytotoxic effects of nature killer cells and specific cytotoxic T lymphocytes, increased production IL-2, TNF and GM-CSF from spleen lymphocytes in tumor-bearing mice. Vaccination with the FBL3-IL-6 also enhanced the cytotoxic activity of the peritoneal macrophages. The results demonstrated that administration of low dose Cy and low dose IL-2 in combination with IL-6 genemodified leukemia vaccine could elicit potent antileukemia effects, and the mechanisms involved in the antitumor process may include the induction of specific and nonspecific antitumor immunity, reversal of T suppressor cells that mediated local immuno-suppression in tumor bearing mice. Conclusion: The combined therapy with cytokine gene-modified tumor vaccine, low dose of Cy and IL-2 might be a promising approach for the treatment of leukemia.

  19. Leukemia from dermal exposure to cyclophosphamide among nurses in the Netherlands: Quantitative assessment of the risk

    NARCIS (Netherlands)

    Fransman, W.; Kager, H.; Meijster, T.; Heederik, D.; Kromhout, H.; Portengen, L.; Blaauboer, B.J.

    2014-01-01

    Several studies showed that oncology nurses are exposed to antineoplastic drugs via the skin during daily activities. Several antineoplastic drugs (including cyclophosphamide) have been classified as carcinogenic to humans. This study aims to assess the leukemia risk of occupational exposure to

  20. Leukemia from dermal exposure to cyclophosphamide among nurses in the Netherlands : Quantitative assessment of the risk

    NARCIS (Netherlands)

    Fransman, Wouter; Kager, Hans; Meijster, Tim; Heederik, Dick; Kromhout, Hans; Portengen, Lützen; Blaauboer, Bas J.

    2014-01-01

    Several studies showed that oncology nurses are exposed to antineoplastic drugs via the skin during daily activities. Several antineoplastic drugs (including cyclophosphamide) have been classified as carcinogenic to humans. This study aims to assess the leukemia risk of occupational exposure to

  1. Cyclophosphamide for Rapid-Onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome

    OpenAIRE

    Paz-Priel, Ido; Cooke, David W.; Chen, Allen R

    2010-01-01

    Patients with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor syndrome have poor long-term outcomes. We report a patient who was treated successfully with high-dose cyclophosphamide immunoablation. This experience offers a novel therapeutic approach and an indirect insight into the underlying pathogenesis of this syndrome.

  2. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma.

    Science.gov (United States)

    Sidra, Gamal; Williams, Cathy D; Russell, Nigel H; Zaman, Sonya; Myers, Bethan; Byrne, Jennifer L

    2006-06-01

    We evaluated the combination of thalidomide, pulsed dexamethasone and weekly cyclophosphamide (CTD) for the treatment of patients with newly diagnosed, relapsed or VAD-refractory multiple myeloma. We found that this combination was highly effective in inducing responses in all treatment groups with an overall response rate of 83.8%. CTD was well tolerated and did not impair stem cell mobilization.

  3. Treatment of advanced seminoma with cyclophosphamide, vincristine and carboplatin on an outpatient basis

    NARCIS (Netherlands)

    Sleijfer, S; Willemse, PHB; deVries, EGE; vanderGraaf, WTA; Mulder, NH; Schraffordt Koops, H.

    This study describes the efficacy and toxicity of a combination regimen consisting of cyclophosphamide, vincristine (oncovin) and carboplatin (COC) for advanced seminoma on an outpatient basis. Twenty-seven patients (mean age 43 years, range 28-63 years) were classified as stage IIC (n = 5), stage

  4. Preventive and curative effects of cyclophosphamide in an animal model of Guillain Barrè syndrome

    DEFF Research Database (Denmark)

    Mangano, Katia; Dati, Gabriele; Quattrocchi, Cinzia

    2008-01-01

    The immunosuppressive agent cyclophosphamide (CY) was tested in rat experimental allergic neuritis (EAN), a preclinical model of Guillain Barrè syndrome (GBS). CY prophylaxis (day 0 and 14 post-immunization [p.i.]) effectively prevents clinical and histological signs of EAN and also reduces the c...

  5. Sialic acid changes in Dalton's lymphoma-bearing mice after cyclophosphamide and cisplatin treatment

    Directory of Open Access Journals (Sweden)

    Nicol B.M.

    2002-01-01

    Full Text Available Sialic acid changes in Dalton's lymphoma cells and other tissues of 10-12-week-old Swiss albino mice were investigated in relation to tumour growth in vivo and following cyclophosphamide (ip, 200 mg/kg body weight or cisplatin (ip, 8 mg/kg body weight treatment. Three to four animals of both sexes were used in each experimental group. The sialic acid level of tumour cells (0.88 µmol/g increased with tumour progression (1.44-1.59 µmol/g; P<=0.05 in mice. Sialic acid concentration in other tissues (liver, kidney, testes and brain also increased (~40, 10, 30 and 58%, respectively in the tumour-bearing hosts as compared with that in the respective tissues of normal mice. In vivo cyclophosphamide or cisplatin treatment resulted in an overall decrease of sialic acid contents in the tissues. Cyclophosphamide was more efficient in lowering tissue sialic acid than cisplatin (P<=0.01, ANOVA. It is suggested that sialic acid residues could be an important factor contributing to the manifestation of malignant properties in cancer cells in general and Dalton's lymphoma cells in particular. A significant decrease in the sialic acid content of Dalton's lymphoma cells after cisplatin or cyclophosphamide treatment may bring about specific changes in tumour cells which could be associated with tumour regression.

  6. Modulator effect of watercress against cyclophosphamide-induced oxidative stress in mice

    Directory of Open Access Journals (Sweden)

    Natalia A. Casanova

    2017-06-01

    Full Text Available Watercress (Nasturtium officinale, Cruciferae; W. Aiton is a vegetable widely consumed in our country, with nutritional and potentially chemopreventive properties. Previous reports from our laboratory demonstrated the protective effect of watercress juice against DNA damage induced by cyclophosphamide in vivo. In this study, we evaluated the in vivo effect of cress plant on the oxidative stress in mice. Animals were treated by gavage with different doses of watercress juice (0.5 and 1g/kg body weight for 15 consecutive days before intraperitoneal injection of cyclophosphamide (100 mg/kg body weight. After 24 h, mice were killed by cervical dislocation. The effect of watercress was investigated by assessing the following oxidative stress biomarkers: catalase activity, superoxide dismutase activity, lipid peroxidation, and glutathione balance. Intake of watercress prior to cyclophosphamide administration enhanced superoxide dismutase activity in erythrocytes with no effect on catalase activity. In bone marrow and liver tissues, watercress juice counteracted the effect of cyclophosphamide. Glutathione balance rose by watercress supplementation and lipid oxidation diminished in all matrixes when compared to the respective control groups. Our results support the role of watercress as a diet component with promising properties to be used as health promoter or protective agent against oxidative damage

  7. Antioxidative effect of ginseng stem-leaf saponins on oxidative stress induced by cyclophosphamide in chickens.

    Science.gov (United States)

    Yu, J; Chen, Y; Zhai, L; Zhang, L; Xu, Y; Wang, S; Hu, S

    2015-05-01

    Previous investigation demonstrated that oral administration of ginseng stem-leaf saponins in chickens could enhance the immune response. The present study was designed to evaluate the effects of ginseng stem-leaf saponins on oxidative stress induced by cyclophosphamide in chickens. One hundred and twenty chickens were randomly divided into 5 groups. Groups 1 to 4 received intramuscular injection of cyclophosphamide to induce oxidative stress while group 5 was injected with saline solution and served as control. Following administration of cyclophosphamide, groups 1 to 3 were orally administered ginseng stem-leaf saponins at 2.5, 5, and 10 mg/kg BW in drinking water for 7 d, respectively. After that, the spleen, thymus, bursa, and serum were collected to measure the indices of the organs and oxidative parameters. The results showed that ginseng stem-leaf saponins significantly inhibited cyclophosphamide-induced oxidative stress by increasing the organ indices, total antioxidant capacity, and the levels of glutathione, ascorbic acid, and α-tocopherol, while elevating the activity of total superoxide dismutase, catalase, and glutathione peroxidase, as well as decreasing the protein carbonyl content and malondialdehyde. Therefore, ginseng stem-leaf saponins could be a promising agent against oxidative stress in the poultry industry.

  8. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  9. Cyclophosphamide: effect in the biodistribution of the radiopharmaceutical in female mice

    Energy Technology Data Exchange (ETDEWEB)

    Alves, I.P. [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil); Paula, E.F. de; Correa, T.G.; Freitas, L.C. de; Fonseca, L. [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil); Bernardo Filho, M. [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia

    1995-12-31

    The effect of cyclophosphamide in the biological distribution of pertechnetate ({sup 99m} TcO{sub 4}), entered intravenously in mice (female) Balb/c in two doses with an interval of 48 hours. Then, a dose of {sup 99m} Tc, as Na{sup 99m} Tc O{sub 4} (250 kBq), milked from a {sup 99} Mo/{sup 99m} Tc generator was administered. These animals were sacrificed, the organs isolated and the activities determined in a well counter. The percentage of radioactivity was calculated dividing the activity in each organ by the sum of the activities in the isolated organs. The analysis of the results has shown that cyclophosphamide did not modify the radioactivity in heart, kidney and stomach. In the spleen the percentage of radioactivity per gram of tissue increased (6.83 to 9.14). Cyclophosphamide increased radioactivity in brain, thyroid, uterus, ovary, liver and lung. These results can be explained by the metabolic process and/or therapeutic effect of cyclophosphamide. (author). 13 refs, 4 tabs.

  10. Cyclophosphamide and IL-12-transduced DCs enhance the antitumor activity of tumor antigen-stimulated DCs and reduce Tregs and MDSCs number.

    Science.gov (United States)

    Rossowska, Joanna; Pajtasz-Piasecka, Elżbieta; Anger, Natalia; Wojas-Turek, Justyna; Kicielińska, Jagoda; Piasecki, Egbert; Duś, Danuta

    2014-01-01

    A hostile tumor microenvironment, characterized by an abundance of T regulatory cells and myeloid-derived suppressor cells (MDSCs), considerably limits the efficacy of dendritic cell (DC)-based vaccines. The intention of this study was to enhance the antitumor activity of vaccines consisting of bone marrow-derived DCs stimulated with TAg (BMDC/TAg) via single administration of cyclophosphamide and multiple injections of interleukin (IL)-12-transduced DCs (BMDC/IL-12). The combined chemoimmunotherapy was applied in the treatment of mice with subcutaneously (SC) growing, advanced MC38 colon carcinoma. The highest level of tumor growth inhibition, accompanied by high cytotoxic activity of effector cells, and their increased influx into tumor tissue, was observed after application of cyclophosphamide in combination with BMDC/TAg and BMDC/IL-12. The effect was probably associated with the elimination of T regulatory cells from spleens and tumors, but most of all with changes in the number and differentiation stage of MDSCs. After the therapy, the percentage of granulocytic and monocytic MDSCs in spleens was significantly lower than in the control group. Moreover, MDSCs derived from spleens and tumors showed increased expression of MHC class II, which may indicate the higher maturation stage of the myeloid cells as well as their enhanced capacity toward antigen presentation. The obtained data indicate that the optimal composition of antitumor vaccines able to limit the suppressor activity of MDSCs is essential to enhance the elimination of tumor cells and to achieve an optimal therapeutic effect.

  11. 音乐节拍器在辅助治疗痉挛性构音障碍中的应用%The Application of Musical Metronome to the Treatment of Spastic Dysarthria

    Institute of Scientific and Technical Information of China (English)

    赵艳玲; 杨勤

    2012-01-01

    Objective To explore the effects of musical metronome to the treatment of spastic dysarthria. Methods Twelve patients with spastic dysarthria were treated with musical metronome during routine speech training. Results After 3 months of treatment, all the patients showed different degrees of improvement. Conclusion Musical metronome treatment can improve the respiratory function and speech intelligibility of patients with spastic dysarthria.%目的 探讨音乐节拍器在辅助治疗痉挛性构音障碍中的作用.方法 对12例痉挛性构音障碍患者在常规构音障碍训练基础上加入音乐节拍器进行辅助治疗.结果 所有患者治疗3个月后均有不同程度的改善.结论 音乐节拍器辅助治疗可以提高痉挛性构音障碍患者的呼吸功能及言语清晰度.

  12. Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice

    Directory of Open Access Journals (Sweden)

    Masahiro Murakami-Nakayama

    2015-02-01

    Full Text Available Cav3.2 T-type Ca2+ channels targeted by H2S, a gasotransmitter, participate in cyclophosphamide-induced cystitis and bladder pain. Given that zinc selectively inhibits Cav3.2 among T-channel isoforms and also exhibits antioxidant activity, we examined whether polaprezinc (zinc-l-carnosine, a medicine for peptic ulcer treatment and zinc supplementation, reveals preventive or therapeutic effects on bladder inflammation and/or pain in the mouse with cyclophosphamide-induced cystitis, a model for interstitial cystitis. Systemic administration of cyclophosphamide caused cystitis-related symptoms including increased bladder weight and vascular permeability, and histological signs of bladder edema, accompanied by bladder pain-like nociceptive behavior/referred hyperalgesia. All these symptoms were significantly attenuated by oral preadministration of polaprezinc at 400 mg/kg. The same dose of polaprezinc also prevented the increased malondialdehyde level, an indicator of lipid peroxidation, and protein upregulation of cystathionine-γ-lyase, an H2S-generating enzyme, but not occludin, a tight junction-related membrane protein, in the bladder tissue of cyclophosphamide-treated mice. Oral posttreatment with polaprezinc at 30–100 mg/kg reversed the nociceptive behavior/referred hyperalgesia in a dose-dependent manner without affecting the increased bladder weight. Together, our data show that zinc supplementation with polaprezinc prevents the cyclophosphamide-induced cystitis probably through the antioxidant activity, and, like T-channel blockers, reverses the established cystitis-related bladder pain in mice, suggesting novel therapeutic usefulness of polaprezinc.

  13. A new synthetic resorcinolic lipid 3-heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one: evaluation of toxicology and ability to potentiate the mutagenic and apoptotic effects of cyclophosphamide.

    Science.gov (United States)

    Navarro, Stephanie Dynczuki; Beatriz, Adilson; Meza, Alisson; Pesarini, João Renato; Gomes, Roberto da Silva; Karaziack, Caroline Bilhar; Cunha-Laura, Andréa Luiza; Monreal, Antônio Carlos Duenhas; Romão, Wanderson; Lacerda Júnior, Valdemar; Mauro, Mariana de Oliveira; Oliveira, Rodrigo Juliano

    2014-03-21

    Resorcinolic lipids have important biological actions, including anti-carcinogenic activity. Therefore, we evaluated the mutagenic, genotoxic, immunomodulatory and apoptotic potential and the biochemical and histopathological changes caused by the synthetic resorcinolic lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one, (AMS35AA; 10, 20 and 40 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg) in Swiss mice. The results indicated that AMS35AA is not genotoxic or mutagenic and does not alter liver or kidney histology. However, the compound does cause an increase (p mutagenic damage (although the compound had anti-genotoxic activity), splenic phagocytosis, neutropenia and glutamic-oxaloacetic transaminase and creatinine levels (even in the absence of histological damage) and induced liver and kidney apoptosis. We conclude that this resorcinolic lipid may be an important chemotherapy adjuvant that can potentiate mutagenic damage and increase apoptosis caused by cyclophosphamide without causing adverse effects. In addition, the immunomodulatory activity of the compound should be noted, which counters reductions in lymphocyte number, a primary side effect of cyclophosphamide in cancer therapy.

  14. Urinary IgG and α2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Claudio Bazzi

    2013-01-01

    Full Text Available Objective. To assess whether high-molecular-weight proteins excretion predicts outcome and therapy-responsiveness in patients with FSGS and nephrotic syndrome. Research Design and Methods. Thirty-eight patients measured at biopsy fractional excretion of IgG (FEIgG and urinary α2-macroglobulin/creatinine ratio (α2m/C. Low and high risk groups were defined by cutoffs assessed by ROC analysis. In all patients first-line therapy was with steroids alone or in combination with cyclophosphamide. Results. α2m/C and FEIgG were correlated with segmental sclerosis (r=0.546; r=0.522. Twenty-three patients (61% entered Remission and 9 (24% progressed to ESRD. Comparing low and high risk groups, by univariate analysis remission was predicted by FEIgG (77% versus 25%, P=0.016 and α2m/C (81% versus 17%, P=0.007 and ESRD at best by FEIgG (0% versus 75%, P<0.0001 and α2m/C (4% versus 67%, P<0.0001. By multivariate analysis FEIgG was the only independent predictor of remission and α2m/C the most powerful predictor of ESRD. Low and high risk groups of FEIgG and α2m/C in combination had very high predictive value of sustained remission and ESRD in response to therapy. Conclusions. FEIgG and α2m/C are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide; their predictive value, if validated in prospective studies, may be useful in clinical practice suggesting first-line alternative treatments in high risk patients.

  15. A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2).

    Science.gov (United States)

    Boccia, Ralph V; Bessudo, Alberto; Agajanian, Richy; Conkling, Paul; Harb, Wael; Yang, Hui; Pinchasik, Dawn; Kimball, Amy S; Berenson, James R

    2017-07-01

    This phase 1b study evaluated the safety and efficacy of 3 dose levels of carfilzomib when provided with fixed dose oral cyclophosphamide and dexamethasone (KCyd) in patients with newly diagnosed multiple myeloma (MM). CHAMPION-2 was a multicenter single-arm study. Patients with newly diagnosed secretory MM were enrolled and received KCyd treatment for up to 8 cycles. A 3 + 3 dose escalation scheme was used to evaluate twice-weekly carfilzomib at 36, 45, and 56 mg/m(2) dose levels, followed by a dose expansion. No dose-limiting toxicities were observed in any of the dose evaluation cohorts. The KCyd regimen that included the maximum planned carfilzomib dose of 56 mg/m(2) twice weekly was brought forward into dose expansion. A total of 16 patients were treated at this dose level. At 56 mg/m(2) the overall response rate was 87.5% (95% confidence interval, 61.7-98.4), and the median time to response of 14 patients whose disease responded to therapy was 1 month. At this dose level, common adverse events of grade 3 or higher were anemia (25.0%), neutropenia (18.8%), acute kidney injury (12.5%), and decreased white blood cell count (12.5%). Ten of 16 patients who received carfilzomib at 56 mg/m(2) completed all 8 cycles, 5 patients discontinued study therapy before cycle 8 as a result of adverse events, and 1 patient discontinued therapy as a result of progressive disease. Carfilzomib in combination with cyclophosphamide and dexamethasone is effective and has manageable toxicity for patients with newly diagnosed MM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of active lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    Feng Xuebing; Gu Fei; Chen Weiwei; Liu Yan; Wei Hua; Liu Lin; Yin Songlou

    2014-01-01

    Background Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus.Although there have been substantial improvements in LN treatment over the last decade,the outcome remains unoptimistic in a considerable percentage of patients.The aim of this study was to evaluate the efficacy and safety of mizoribine (MZR),a novel selective inhibitor of inosine monophosphate dehydrogenase,as induction treatment for active LN in comparison with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC).Methods Ninety patients with active LN were observed.Thirty patients were given MZR orally at the dose of 300 mg every other day.Thirty patients took MMF at 2 g per day in two divided doses.Thirty patients received CYC intravenously 0.5 g every 2 weeks.Therapeutic effects and adverse events (AEs) were evaluated at the end of 24-week treatment.Oneway analysis of variance (ANOVA) followed by Dunn's test was applied to compare the difference among the groups.For comparing categorical data between two groups,X2 test was employed.Results Early responses at week 12 were achieved by 73.3%,90.0%,and 96.7% in MZR,MMF,and CYC groups,respectively.There was no significant difference in the complete remission rates (22.7%,24.0%,and 25.0%,respectively) or overall response rates (68.2%,72.0%,and 75.0%,respectively) among the three groups at week 24.The most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index scores was observed in MMF or CYC group,and the decline of health assessment questionnaire scores in MZR or MMF group was more prominent than that in the CYC group at week 12.Serum complement 3 (C3) or C4 levels were elevated in all groups after the treatments.CYC was more effective in inhibiting anti-double-stranded DNA antibody,while MZR was more effective in inhibiting antinuclear antibody.The incidences of AEs in patients treated with CYC were significantly higher than those in patients treated with MZR

  17. Simvastatin suppresses cyclophosphamide-induced changes in urodynamics and bladder inflammation.

    Science.gov (United States)

    Hughes, Francis M; McKeithan, Paige; Ellett, Justin; Armeson, Kent E; Purves, J Todd

    2013-01-01

    To assess the ability of daily oral simvastatin administration to reduce the negative urodynamic changes associated with cyclophosphamide (CP)-induced cystitis and to prevent bladder inflammation. Patients undergoing CP chemotherapy frequently develop cystitis, leading to urinary dysfunction and hemorrhage. Recent studies have suggested statins possess anti-inflammatory properties and might be uroprotective. Urodynamic properties were analyzed in 4 groups of female Sprague-Dawley rats: group 1, vehicle (300 μL, 0.5% methylcellulose, orally for 7 days); group 2, simvastatin (1 mg/rat/d); group 3, vehicle plus CP (intraperitoneally 80 mg/kg, 24 h before cystometry); and group 4, simvastatin plus CP. The inflammation in the groups was assessed using Evans blue extravasation. CP stimulated significant increases in the number of nonvoiding contractions (0.83±0.26 vs 4.97±1.90; P=.03) and decreases in the peak voiding pressure (53.46±5.08 vs 33.34±4.37 cm H2O; P=.01). Simvastatin returned these parameters to the control levels of 1.62±0.73 (P=.70) and 45.98±7.78 cm H2O (P=.38). CP at this level caused a slight, but significant, increase in the voided volume (0.82±0.13 vs 1.16±0.14 mL; P=.04), which returned to control levels (0.74±0.12 mL; P=.65) with simvastatin. Other urodynamic parameters, such as the threshold pressure, were not affected by simvastatin or CP, or the combination of the 2. CP-induced inflammation in the bladder (Evans blue extravasation) was suppressed by simvastatin. Simvastatin was effective at ameliorating the negative urodynamic changes and inflammation in the bladder after CP administration and is a potential therapy for preventing side effects in patients undergoing this chemotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

    Science.gov (United States)

    Dietrich, Fabrícia; Pietrobon Martins, Jerônimo; Kaiser, Samuel; Madeira Silva, Rodrigo Braccini; Rockenbach, Liliana; Albano Edelweiss, Maria Isabel; Ortega, George González; Morrone, Fernanda Bueno; Campos, Maria Martha; Battastini, Ana Maria Oliveira

    2015-01-01

    Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

  19. The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice

    Science.gov (United States)

    Dietrich, Fabrícia; Pietrobon Martins, Jerônimo; Kaiser, Samuel; Madeira Silva, Rodrigo Braccini; Rockenbach, Liliana; Albano Edelweiss, Maria Isabel; Ortega, George González; Morrone, Fernanda Bueno; Campos, Maria Martha; Battastini, Ana Maria Oliveira

    2015-01-01

    Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition. PMID:26154141

  20. Synergistic antitumor efficacy of antibacterial helvolic acid from Cordyceps taii and cyclophosphamide in a tumor mouse model.

    Science.gov (United States)

    Xiao, Jian-Hui; Zhang, Yao; Liang, Gui-You; Liu, Ru-Ming; Li, Xiao-Gang; Zhang, Ling-Tao; Chen, Dai-Xiong; Zhong, Jian-Jiang

    2017-01-01

    The antibacterial agent helvolic acid, which was isolated from the active antitumor fraction of Cordyceps taii, showed potent cytotoxicity against different human cancer cells. In the present study, the in vivo antitumor effect of helvolic acid was investigated in murine sarcoma S180 tumor-bearing mice. Doses of 10 and 20 mg/kg/day helvolic acid did not exert significant antitumor activity. Interestingly, co-administration of 10 mg/kg/day helvolic acid and 20 mg/kg/day cyclophosphamide (CTX) - a well-known chemotherapy drug - showed promising antitumor activity with a growth inhibitory rate of 70.90%, which was much higher than that of CTX alone (19.5%). Furthermore, the combination markedly prolonged the survival of tumor-bearing mice. In addition, helvolic acid enhanced the immune organ index. The protein expression levels of β-catenin, cyclin D1, and proliferating cell nuclear antigen were significantly suppressed in mice treated with 20 mg/kg/day helvolic acid and in those receiving combination therapy. Taken together, these results indicated that helvolic acid in combination with CTX showed potent in vivo synergistic antitumor efficacy, and its mechanism of action may involve the Wnt/ β-catenin signaling pathway.

  1. The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

    Directory of Open Access Journals (Sweden)

    Fabrícia Dietrich

    Full Text Available Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP. Sodium 2-mercaptoethanesulfonate (Mesna has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

  2. Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma

    Science.gov (United States)

    Veal, Gareth J.; Cole, Michael; Chinnaswamy, Girish; Sludden, Julieann; Jamieson, David; Errington, Julie; Malik, Ghada; Hill, Christopher R.; Chamberlain, Thomas; Boddy, Alan V.

    2016-01-01

    Introduction Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types. The current study in children with B-cell non-Hodgkin's lymphoma (NHL) was designed to corroborate previous findings in a large prospective study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology. Methods A total of 644 plasma samples collected over a 5 year period, from 49 B-cell NHL patients ≤18 years receiving cyclophosphamide (250 mg/m2), were used to characterise a population pharmacokinetic model. Polymorphisms in genes including CYP2B6 and CYP2C19 were analysed. Results A two-compartment model provided the best fit of the population analysis. The mean cyclophosphamide clearance value following dose 1 was significantly lower than following dose 5 (1.83 ± 1.07 versus 3.68 ± 1.43 L/h/m2, respectively; mean ± standard deviation from empirical Bayes estimates; P < 0.001). The presence of at least one CYP2B6*6 variant allele was associated with a lower cyclophosphamide clearance following both dose 1 (1.54 ± 0.11 L/h/m2 versus 2.20 ± 0.31 L/h/m2, P = 0.033) and dose 5 (3.12 ± 0.17 L/h/m2 versus 4.35 ± 0.37 L/h/m2, P = 0.0028), as compared to homozygous wild-type patients. No pharmacokinetic parameters investigated were shown to have a significant influence on progression free survival. Conclusion The results do not support previous findings of a link between cyclophosphamide pharmacokinetics or metabolism and disease recurrence in childhood B-cell NHL. While CYP2B6 genotype was shown to influence pharmacokinetics, there was no clear impact on clinical outcome. PMID:26773420

  3. Metronomic paclitaxel-loaded mPEG-PLA nanoparticles show enhanced anti-tumor efficacy compared to maximum tolerated dose administration

    Science.gov (United States)

    Fei, Tan; Yang, Lian-juan; Mo, Xiao-hui; Wang, Xiu-li; Jun, Gu

    2014-11-01

    Low-dose metronomic (LDM) chemotherapy with cytotoxic agents, aimed at disrupting tumor endothelial cells, is an alternative method to maximum tolerated dose chemotherapy targeting proliferating tumor cells in clinical practice. However, even in the LDM schedule, cytotoxic agents still exhibit serious side effects due to non-distribution and high accumulated doses in the body. Nanocarriers can maximize the efficacy of the encapsulated drug by adjusting the pharmacokinetics and bio-distribution pattern, and minimize excessive toxic side effects. In the present study, we prepared polyethylene glycol (PEG)-coated stealth nanoparticles containing paclitaxel (PTX-NP) in order to evaluate their accumulation in tumor and their anti-tumor activity following LDM administration. PTX-NPs were prepared by a modified emulsification/solvent diffusion method with methoxy PEG-poly(lactide). The in vitro viability, migration, and tube formation of primary human umbilical vein endothelial cells, in addition to thrombospondin-1 positive expression and microvessel density in vivo, confirmed the anti-angiogenic activity of PTX-NP. The cellular uptake and retention study, in addition to pharmacokinetics in Sprague-Dawley rats demonstrated sustained circulation of PTX-NP. The in vivo tumor accumulation of PTX-NP was monitored using the Xenogen IVIS 200 non-invasive optical imaging system. The anti-tumor activity of LDM PTX-NP was studied in B16 melanoma cancer-bearing mice in vivo. In conclusion, PTX-NP improved tumor accumulation and anti-tumor efficacy following LDM administration.

  4. Evaluation of Protective Effects of Crocin Onembyo Developing Process in in Vitro Fertilization (IVFin Cyclophosphamide Treated Mice

    Directory of Open Access Journals (Sweden)

    F Khan Mohammadi

    2014-05-01

    Conclusion: The co-administration of crocin with CP chemotherapy caused a significant improvement in fertilizing potential and promoted the embryo development. Key words: Cyclophosphamide, Crocin, Mice, Oocyte, In vitro fertilizing

  5. Curative effect observation of patients with primary systemic amyloidosis treated by the combination of bortezomib with dexmethasone and cyclophosphamide

    Institute of Scientific and Technical Information of China (English)

    路瑾

    2013-01-01

    Objective To analyze the efficacy and side effects of the combination regimen containing bortezomib,cyclophosphamide and dexamethasone(BCD)in the treatment of primary systemic amyloidosis(PSA).Methods

  6. Cyclophosphamide Perturbs Cytosine Methylation in Jurkat-T Cells through LSD1-mediated Stabilization of DNMT1 Protein

    OpenAIRE

    ZHANG Jing; Yuan, Bifeng; Zhang, Fan; Xiong, Lei; Wu, Jiang; Pradhan, Sriharsa; Wang, Yinsheng

    2011-01-01

    Aberrant cytosine methylation is known to be associated with cancer development. Here we assessed how common cancer chemotherapeutic agents perturb cytosine methylation in Jurkat-T acute lymphoblastic leukemia cells. We tested six anti-tumor agents and found that cyclophosphamide induced the most pronounced increase in global DNA cytosine methylation after a 24-hr treatment. Long-term treatment with cyclophosphamide led to a time-dependent increase in cytosine methylation level with up to 4 d...

  7. Hemorrhagic cystitis in children treated with alkylating agent cyclophosphamide: The experience of a medical center in Taiwan

    Directory of Open Access Journals (Sweden)

    Ching-Chia Wang

    2015-08-01

    Conclusion: Alteration serum uric acid level and BMT could be indicators for severe hemorrhagic cystitis. The elevated levels of urinary nitrite/nitrate and 8-iso-prostaglandin F2α may indicate the essential roles played by nitric oxide syntheses and reactive oxidative stress in cyclophosphamide-induced hemorrhagic cystitis. These findings may help clinicians formulate a better strategy for treating cyclophosphamide-induced hemorrhagic cystitis.

  8. Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Voss, Anne

    2015-01-01

    -melanoma skin cancers (NMSCs) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI 2.3, 16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer increased after 5-9, 10-14 and 15-19 years of follow......OBJECTIVE: The long-term cancer risk for patients treated for granulomatosis with polyangiitis (GPA) is not well characterized. We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA from 1973 to 1999 and followed throughout 2010. METHODS: Cancer incidence...... in the cohort was determined by linkage with the Danish Cancer Registry and compared with that in the general population by calculation of standardized incidence ratios (SIRs). RESULTS: The median duration of follow-up was 9.7 years (range 0-36). Seventy-three cancers occurred, of which 30 were non...

  9. Immunomodulatory effect of Moringa oleifera Lam. extract on cyclophosphamide induced toxicity in mice.

    Science.gov (United States)

    Gupta, Anamika; Gautam, Manish K; Singh, Rahul K; Kumar, M Vijay; Rao, Ch V; Goel, R K; Anupurba, Shampa

    2010-11-01

    Immunomodulatory effect of ethanolic extract (50%) of M. oleifera leaves (MOE) has been studied in normal and immunosuppressed mice models. Different doses of MOE i.e. 125, 250 and 500 mg/kg body weight of mice were administered orally for 15 days. Cyclophosphamide at a dose of 30 mg/kg body weight was administered orally for the next 3 days. On day 16 and 19, hematological parameters like white blood cell (WBC) count, red blood cell (RBC) count, haemoglobin level (Hb), percent neutrophils and organ weight were recorded. Effect of MOE on phagocytic activity of mice macrophages was determined by carbon clearance test. MOE showed significant dose dependent increase in WBC, percent neutrophils, weight of thymus and spleen along with phagocytic index in normal and immunosuppressed mice. The results indicate that MOE significantly reduced cyclophosphamide induced immunosuppression by stimulating both cellular and humoral immunity.

  10. Cyclophosphamide, doxorubicin, and cisplatin combined in the treatment of advanced sarcomas.

    Science.gov (United States)

    Edmonson, J H; Hahn, R G; Schutt, A J; Bisel, H F; Ingle, J N

    1983-01-01

    Twenty-five patients with evaluable histologically confirmed inoperable metastatic sarcomas were treated once every four weeks with cyclophosphamide, doxorubicin, and cisplatin in doses of 400, 40, and 60 mg/m2, respectively. Cyclophosphamide and doxorubicin were given by rapid intravenous injection followed immediately by cisplatin by slow intravenous infusion (2-6 hr) in 1 liter of 0.45% saline with mannitol added. Leukopenia, alopecia, and vomiting were common side effects and three patients refused further treatment because of vomiting following their initial courses. No drug-related deaths occurred and we removed no one from the study because of toxicity problems. Among the 9 patients who experienced objective tumor regression were 2 of 2 with hemangiosarcoma, 3 of 5 with malignant fibrous histiocytoma, 3 of 5 with osteosarcoma, and 1 of 1 with pleomorphic liposarcoma of bone. Although not therapeutically gratifying, these results appear to be better than any previously observed at our institution.

  11. Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

    Science.gov (United States)

    Conte, P F; Bruzzone, M; Chiara, S; Rosso, R; Giaccone, G; Carnino, F; Guercio, E; Ragni, N; Foglia, G; Bentivoglio, G

    1988-04-30

    Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

  12. Development of Reversible Posterior Leukoencephalopathy Syndrome after Cyclophosphamide Treatment in a Patient with Lupus Nephritis

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    Serkan YILDIZ

    2011-01-01

    Full Text Available Renal involvement in systemic lupus erythematosus is a frequent and serious complication that significantly increases morbidity and mortality. Despite all studies and usage of new drugs, treatment of lupus nephritis continues to be a problem. Diffuse proliferative lupus nephritis has a poor prognosis and aggressive treatment must be undertaken. Cyclophosphamide is commonly used in treatment despite its side effects. Reversible posterior leucoencephalopathy syndrome is a clinico-radiological syndrome manifested by blood pressure elevation, headache, visual disturbances, confusion, seizures and sometimes focal neurological signs that can develop due to usage of cytotoxic drugs. We present a case of lupus nephritis in which reversible posterior leucoencephalopathy syndrome developed after intravenous cyclophosphamide administration and recovered spontaneously by symptomatic treatment in this article.

  13. Chemotherapy of disseminated seminoma with combination of cis-diamminedichloroplatinum (II) and cyclophosphamide.

    Science.gov (United States)

    Vugrin, D; Whitemore, W J; Batata, M

    1981-01-01

    Nine patients with metastatic seminoma who had received no prior chemotherapy were induced with a combination containing cis-platinum 120 mg/m2 I.V. and cyclophosphamide 600 mg/m2 I.V. for three to six treatments at 4-6 weeks intervals, and then received maintenance with cyclophosphamide 600 mg/m2 I.V. every 3-4 weeks to complete 2 years of chemotherapy. Eight patients entered complete remission: five with chemotherapy alone and three with chemotherapy and radiation or resection of residual disease. Seven patients remain in CR with a minimum follow up of 17 months. Chemotherapy is effective in treatment of metastatic seminoma.

  14. Green tea extract increases cyclophosphamide-induced teratogenesis by modulating the expression of cytochrome P-450 mRNA.

    Science.gov (United States)

    Park, Dongsun; Jeon, Jeong Hee; Shin, Sunhee; Joo, Seong Soo; Kang, Dae-Hyuck; Moon, Seol-Hee; Jang, Min-Jung; Cho, Yeoung Mi; Kim, Jae Wook; Ji, Hyeong-Jin; Ahn, Byeongwoo; Oh, Ki-Wan; Kim, Yun-Bae

    2009-01-01

    The effects of green tea extract (GTE) on the fetal development and external, visceral and skeletal abnormalities induced by cyclophosphamide were investigated in rats. Pregnant rats were daily administered GTE (100mg/kg) by gavage for 7 d, from the 6th to 12th day of gestation, and intraperitoneally administered with cyclophosphamide (11mg/kg) 1h after the final treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarian section. Cyclophosphamide was found to reduce fetal and placental weights without increasing resorption or death. In addition, it induced malformations in live fetuses; 94.6%, 41.5% and 100% of the external (skull and limb defects), visceral (cleft palate and ureteric dilatation) and skeletal (acrania, vertebral/costal malformations and delayed ossification) abnormalities. When pre-treated with GTE, cyclophosphamide-induced body weight loss and abnormalities of fetuses were remarkably aggravated. Moreover, repeated treatment with GTE greatly increased mRNA expression and activity of hepatic cytochrome P-450 (CYP) 2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard, while reducing CYP3A expression (a detoxifying enzyme). The results suggest that repeated intake of GTE may aggravate cyclophosphamide-induced body weight loss and malformations of fetuses by modulating CYP2B and CYP3A.

  15. Place in therapy of rituximab in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis.

    Science.gov (United States)

    Shah, Shivani; Geetha, Duvuru

    2015-01-01

    Granulomatosis with polyangiitis and microscopic polyangiitis are small vessel vasculitides characterized by circulating antineutrophil circulating antibodies. Standard treatment for active severe disease has consisted of cyclophosphamide with glucocorticoids with or without plasmapheresis, which achieves approximately 75% sustained remission, but carries significant adverse effects such as malignancy, infertility, leukopenia, and infections. The role of B cells in the pathogenesis of anti-neutrophil circulating antibodies-associated vasculitis has been established, and as such, rituximab, a monoclonal anti-CD20 antibody, has been studied in treatment of active granulomatosis with polyangiitis and microscopic polyangiitis (induction) and in maintaining remission. Rituximab has been shown to be effective in inducing remission in several retrospective studies in patients with refractory disease or cyclophosphamide intolerance. The RAVE and RITUXVAS trials demonstrated rituximab is a noninferior alternative to standard cyclophosphamide-based therapy; however, its role in elderly patients and patients with severe renal disease warrants further investigation. Rituximab has been compared with azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction. Rituximab is not without risks and carries a similar adverse event risk rate as cyclophosphamide in randomized control trials. However, its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility.

  16. Survival and tumorigenesis in O6-methylguanine DNA methyltransferase-deficient mice following cyclophosphamide exposure

    OpenAIRE

    Nagasubramanian, Ramamoorthy; Hansen, Ryan J.; Delaney, Shannon M.; Cherian, Mathew M.; Samson, Leona D.; Kogan, Scott C.; Dolan, M Eileen

    2008-01-01

    O6-methylguanine DNA methyltransferase (MGMT) deficiency is associated with an increased susceptibility to alkylating agent toxicity. To understand the contribution of MGMT in protecting against cyclophosphamide (CP)-induced toxicity, mutagenesis and tumorigenesis, we compared the biological effects of this agent in transgenic Mgmt knockout and wild-type mice. In addition, neurofibromin (Nf1)+/− background was used to increase the likelihood of CP-induced tumorigenesis. Cohorts of Mgmt-profic...

  17. Safety and efficacy of combined cyclophosphamide and rituximab treatment in recalcitrant childhood lupus.

    Science.gov (United States)

    Ale'ed, Ashwaq; Alsonbul, Abdullah; Al-Mayouf, Sulaiman M

    2014-04-01

    To report the safety and efficacy of combined cyclophosphamide and rituximab treatment in Saudi children with systemic lupus erythematosus (SLE). Medical records of all children with SLE treated with cyclophosphamide and rituximab between June 2007 and June 2012 at King Faisal Specialist Hospital and Research Center, Riyadh, were reviewed for demographic characteristics, age at diagnosis, concomitant treatments, indication of using rituximab and adverse events during the treatment period. Clinical and serologic response parameters included SLE Disease Activity Index (SLEDAI), complement, anti-ds DNA antibody and ANA levels, and mean daily corticosteroid dose assessed 3 months before combined cyclophosphamide and rituximab infusion course and at 6-month interval afterward. Sixteen patients (13 girls) with refractory SLE treated with cyclophosphamide and rituximab were included. The mean age at onset of SLE was 7.8 + 3.3 years, while the mean age at diagnosis was 8.1 + 3.4 years; the mean disease duration was 4.7 + 3.2 years. All patients were treated with corticosteroid and immunosuppressive drugs. Nephritis (8 patients) was the most frequent indication; other indications included refractory arthritis, thrombocytopenia, severe mucocutaneous lesions and central nervous system involvement. All patients received 2 doses, but 4 required 4-8 extra doses. All patients showed improvement in response parameters. There was significant reduction in SLEDAI (P < 0.0002) and corticosteroid dose (P < 0.005). A total of 4 adverse events were notified; 2 developed infusion-related reactions. One patient had severe soft tissue fungal infection, and other patient had pancreatitis. Our data showed beneficial therapeutic and steroid-sparing effects of rituximab as adjunctive treatment for children with refractory SLE including both renal and extrarenal manifestations. Although rituximab was well tolerated by the majority of patients, it may associated with various adverse events.

  18. Protective effect of Satureja montana extract on cyclophosphamide-induced testicular injury in rats.

    Science.gov (United States)

    Abd El Tawab, Azza M; Shahin, Nancy N; AbdelMohsen, Mona M

    2014-12-05

    The present study investigated the protective effect of Satureja montana extract against cyclophosphamide-induced testicular injury in rats. Total phenolic and flavonoid contents of the extract were 1.03% and 0.34%w/w of dry herb expressed as chlorogenic acid and quercetin, respectively. HPLC analysis identified caffeic, syringic and rosmarinic acids as the chief phenolic acids, and rutin as the major flavonoid in the extract. Oral daily administration of S.montana extract (50mg/kg/day) for 7days before and 7days after an intraperitoneal injection of cyclophosphamide (200mg/kg) restored the reduced relative testicular weight, serum testosterone level and testicular alkaline phosphatase activity, raised the lowered testicular sorbitol dehydrogenase and acid phosphatase activities, and decreased the elevated testicular hemoglobin absorbance. It also attenuated lipid peroxidation, restored the lowered glutathione content, glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase activities, and improved total antioxidant capacity. Moreover, S.montana extract mitigated testicular DNA fragmentation, decreased the elevated Fas and Bax gene expression, up-regulated the decreased Bcl-2 and peroxisome proliferator-activated receptor-gamma (PPAR-γ) gene expression and normalized Akt1 protein level. Histopathological investigation confirmed the protective effects of the extract. Conclusively, S.montana extract protects the rat testis against cyclophosphamide-induced damage via anti-oxidative and anti-apoptotic mechanisms that seem to be mediated, at least in part, by PPAR-γ and Akt1 up-regulation.

  19. Mitigating Role of Quercetin Against Cyclophosphamide-Induced Lung Injury in Rats

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    Nora A. Asry

    2014-05-01

    Full Text Available Quercetin (Qur, a polyphenolic flavonoid compound present in large amounts in vegetables and fruits, plays important roles in human health through its antioxidant activity. This study was conducted to investigate the possible modulatory effect of Qur against cyclophosphamide (CP-induced lung oxidative damage and to highlight the underlying mechanisms of such effect. Male Sprague-Dawely rats were divided into four groups. Group I was control. Group II received Qur (100 mg/kg/d. p.o. for 14 consecutive days. Group III was injected once with CP (150 mg/kg, i.p.. Group IV received Qur for 7 consecutive days, before and after CP injection.A single i.p. injection of CP markedly increased the level of serum biomarkers; total protein, LDH. Cyclophosphamide significantly increased the lung content of lipid peroxides and decreased levels of reduced glutathione. Treatment of rats with Qur for 7 days prior to and 7 days after cyclophosphamide significantly ameliorated the alterations in lung and serum biomarkers associated with inflammatory reactions. Moreover, Qur attenuated the secretion of pro-inflammatory cytokine, TNF-α in rat serum. In addition, Qur slightly ameliorated CP-induced histopathological changes in lung tissue. Our results suggest that Qur produces a protective effect against CP-induced lung injury and suggest a role of oxidative stress and inflammation in the pathogenesis.

  20. Long term outcome of treatment of diffuse proliferative glomerulonephritis with pulse steroids and short course pulse cyclophosphamide

    Directory of Open Access Journals (Sweden)

    S. Bombardieri

    2011-06-01

    Full Text Available Objectives: To evaluate the long- term outcome of a group of systemic lupus erythematosus (SLE patients with diffuse proliferative glomerulonephritis (DPGN treated with pulse steroids and a short course of pulse cyclophosphamide (Cyc in order to find out baseline predictor variables of disease outcome at the end of the follow-up. Methods: Female SLE patients fulfilling ACR criteria with active DPGN treated with pulse steroids and pulse Cyc were enrolled in the study and retrospectively analyzed with particular interest to renal flares and poor renal outcome at the end of follow- up as outcome measures. Results: 30 female patients with DPGN were included, of these 20 (66,7% patients are actually in follow-up at our unit, 4 (13.3% died and 6 (20% were lost during the follow-up. Fourteen patients (46.6% presented at least one renal flare (RF during the follow up for a total of 21 flares. At our last observation, 18 (60% presented a good renal outcome while 12 (40% had a poor outcome. Lower age at kidney biopsy resulted an important prognostic factor for the occurrence of both RF and poor long- term renal outcome; additionally, a poor renal outcome resulted significantly correlated with an inadequate response at the end of the protocol and with the number of renal flares after remission. Conclusions: These data suggest that, in general, a short course therapy with Cyc might be effective in controlling disease activity but demonstrated high rate of RF and poor renal outcome over time; however, this protocol might represent an effective therapeutic strategy in a subgroup of patients with specific epidemiological and clinical characteristics and suggest the possibility of tailoring immunosuppressive therapy on the basis of prognostic factor at baseline.

  1. [Long term outcome of treatment of diffuse proliferative glomerulonephritis with pulse steroids and short course pulse cyclophosphamide].

    Science.gov (United States)

    Tani, C; Mosca, M; d'Ascanio, A; Neri, R; Tavoni, A; Carli, L; Bombardieri, S

    2010-01-01

    To evaluate the long- term outcome of a group of systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) treated with pulse steroids and a short course of pulse cyclophosphamide (Cyc) in order to find out baseline predictor variables of disease outcome at the end of the follow-up. Female SLE patients fulfilling ACR criteria with active DPGN treated with pulse steroids and pulse Cyc were enrolled in the study and retrospectively analyzed with particular interest to renal flares and poor renal outcome at the end of follow- up as outcome measures. 30 female patients with DPGN were included, of these 20 (66,7%) patients are actually in follow-up at our unit, 4 (13.3%) died and 6 (20%) were lost during the follow-up. Fourteen patients (46.6%) presented at least one renal flare (RF) during the follow up for a total of 21 flares. At our last observation, 18 (60%) presented a good renal outcome while 12 (40%) had a poor outcome. Lower age at kidney biopsy resulted an important prognostic factor for the occurrence of both RF and poor long- term renal outcome; additionally, a poor renal outcome resulted significantly correlated with an inadequate response at the end of the protocol and with the number of renal flares after remission. These data suggest that, in general, a short course therapy with Cyc might be effective in controlling disease activity but demonstrated high rate of RF and poor renal outcome over time; however, this protocol might represent an effective therapeutic strategy in a subgroup of patients with specific epidemiological and clinical characteristics and suggest the possibility of tailoring immunosuppressive therapy on the basis of prognostic factor at baseline.

  2. Study of action of cyclophosphamide and extract of mycelium of Pleurotus ostreatus in vivo on mice, bearing melanoma B16-F0-GFP

    Science.gov (United States)

    Meerovich, Irina G.; Yang, Meng; Jiang, Ping; Hoffman, Robert M.; Gerasimenya, Valery P.; Orlov, Alexander E.; Savitsky, Alexander P.; Popov, Vladimir O.

    2005-04-01

    In this work we studied in vivo the combined action of cyclophosphamide and the extract of mycelium of Pleurotus ostreatus on mice bearing melanoma B16-F0, expressing green fluorescent protein (GFP). This model allows to recognize small-size tumors and metastases, unrecognizable by other methods. It was found that combined administration of cyclophosphamide (300 mg/kg) and the extract of mycelium of Pleurotus ostreatus (100 mg/kg), administered for 10 days after cyclophosphamide injection, as well administration of cyclophosphamide alone, cause inhibition of tumor growth about 97%. It was shown that administration of the extract of mycelium of Pleurotus ostreatus alone leads to inhibition of tumor growth of 61%. It was found that in case of combined administration of cyclophosphamide and the extract of mycelium of Pleurotus ostreatus, leucopenia was less expressed than in case of administration of cyclophosphamide alone.

  3. Disease-modifying therapies in Chinese children with multiple sclerosis.

    Science.gov (United States)

    Yang, Fen; Huang, D Hui; Yang, Yang; Wu, Wei Ping

    2014-01-01

    Limited data are available about the use of disease-modifying therapies (DMTs) in children with multiple sclerosis (MS). This study aimed to present our experience using DMTs in Chinese children with MS and provide additional evidence to consider treating these patients with cyclophosphamide. A retrospective chart review was conducted and data were obtained from 25 children with MS. Only three (12%) of these patients received and responded well to first-line interferon β-1b therapy, while 10 (40%) chose cyclophosphamide and 12 (48%) refused to use DMTs. For the 10 patients being treated with cyclophosphamide, the median annualized relapse rate decreased from 3.0 to 1.0, and the median score on the Expanded Disability Status Scale decreased from 3.5 to 2.0. After 12 months of treatment, no gadolinium-enhancing lesions were reported in seven of the 10 patients. The use of DMTs plays an important role in the treatment of children with MS. If first-line therapies fail, cyclophosphamide may be a good option.

  4. Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model

    Science.gov (United States)

    Guo, Qin; Zhang, Ian; Gao, Hang; Yanyan, Song; Chen, Xuebo; Weng, Yiming; Da Fonseca, Anna; Shah, Sunny; Manuel, Edwin R.; Zhang, Leying; Vonderfecht, Steven L.; Alizadeh, Darya; Berlin, Jacob M.; Badie, Behnam

    2016-01-01

    Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs) can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261) tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc) that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG. PMID:26829221

  5. Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model.

    Directory of Open Access Journals (Sweden)

    Mao Ouyang

    Full Text Available Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261 tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG.

  6. 醋酸泼尼松联合环磷酰胺治疗甲亢浸润性突眼的疗效观察%Efficacy of Prednisone Plus Cyclophosphamide in Treatment of Inifltrative Exophthalmos of Hyperthyroidism

    Institute of Scientific and Technical Information of China (English)

    王玉风

    2015-01-01

    Objective Discussion of prednisone and cyclophosphamide to treat hyperthyroidism exophthalmos invasive clinical effect.Methods The control group received routine clinical treatment, research group on the basis of conventional therapy plus prednisone plus cyclophosphamide, recording the clinical efficacy of the two groups of patients with hyperthyroidism infiltrative exophthalmos.Results Study group after infiltrating exophthalmos hyperthyroidism treated patients receive up to 90.00% of the total efifciency of the clinical treatment, the control group received only 75.00% of the total efficiency of the clinical treatment (P <0.05).Conclusion By conventional therapy combined with prednisone, clinical efifcacy in patients with hyperthyroidism inifltrative exophthalmos obtained after cyclophosphamide significantly improved, their quality of life has been a strong guarantee.%目的:探讨醋酸泼尼松联合环磷酰胺治疗甲亢浸润性突眼临床应用效果。方法对照组给予常规临床治疗,研究组在常规治疗基础上加用醋酸泼尼松联合环磷酰胺,记录两组甲亢浸润性突眼患者临床疗效。结果研究组甲亢浸润性突眼患者经治疗后获得高达90.00%的临床治疗总有效率,对照组仅获得75.00%的临床治疗总有效率(P<0.05)。结论经常规治疗联合醋酸泼尼松、环磷酰胺后甲亢浸润性突眼患者临床疗效获得显著提高,其生活质量得到有利保障。

  7. Cost and clinical analysis of autologous hematopoietic stem cell mobilization with G-CSF and plerixafor compared to G-CSF and cyclophosphamide.

    Science.gov (United States)

    Shaughnessy, Paul; Islas-Ohlmayer, Miguel; Murphy, Julie; Hougham, Maureen; MacPherson, Jill; Winkler, Kurt; Silva, Matthew; Steinberg, Michael; Matous, Jeffrey; Selvey, Sheryl; Maris, Michael; McSweeney, Peter A

    2011-05-01

    Plerixafor plus granulocyte-colony stimulating factor (G-CSF) has been shown to mobilize more CD34(+) cells than G-CSF alone for autologous hematopoietic stem cell transplantation (HSCT). However, many centers use chemotherapy followed by G-CSF to mobilize CD34(+) cells prior to HSCT. We performed a retrospective study of patients who participated in the expanded access program (EAP) of plerixafor and G-CSF for initial mobilization of CD34(+) cells, and compared outcomes to matched historic controls mobilized with cyclophosphamide 3-5 g/m(2) and G-CSF at 2 centers that participated in the EAP Control patients were matched for age, sex, disease, disease stage, and number of prior therapies. Mobilization costs were defined to be the costs of medical procedures, resource utilization, and medications. Median national CMS reimbursement rates were used to establish the costs of procedures, hospitalization, provider visits, apheresis, CD34(+) cell processing and cryopreservation. Average sale price was used for G-CSF, plerixafor, cyclophosphamide, MESNA, antiemetics, and antimicrobials. A total of 33 patients from the EAP and 33 matched controls were studied. Two patients in the control group were hospitalized for neutropenic fever during the mobilization period. Apheresis started on the scheduled day in 33 (100%) study patients and in 29 (88%) control patients (P = 0.04). Sixteen (48%) control patients required weekend apheresis. There was no difference in number of CD34(+) cells collected between the groups, and all patients proceeded to HSCT with no difference in engraftment outcomes. Median total cost of mobilization was not different between the plerixafor/G-CSF and control groups ($14,224 versus $18,824; P = .45). In conclusion, plerixafor/G-CSF and cyclophosphamide/G-CSF for upfront mobilization of CD34(-) cells resulted in similar numbers of cells collected, costs of mobilization, and clinical outcomes. Additionally, plerixafor/G-CSF mobilization resulted in more

  8. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hagman, H; Frödin, J-E; Berglund, Å

    2016-01-01

    -free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. RESULTS: We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization...

  9. Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients.

    Science.gov (United States)

    Low, Siew-Kee; Kiyotani, Kazuma; Mushiroda, Taisei; Daigo, Yataro; Nakamura, Yusuke; Zembutsu, Hitoshi

    2009-10-01

    Cyclophosphamide (CPA)-based combination treatment has known to be effective for breast cancer, but often causes adverse drug reactions (ADRs). Hence, the identification of patients at risk for toxicity by CPA is clinically significant. In this study, a stepwise case-control association study was conducted using 403 patients with breast cancer who received the CPA combination therapy. A total of 143 genetic polymorphisms in 13 candidate genes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, ALDH1A1, ALDH3A1, GSTA1, GSTM1, GSTP1, GSTT1, ABCC2 and ABCC4), possibly involved in the activation, metabolism and transport of CPA, were genotyped using 184 cases who developed either > or =grade 3 leukopenia/neutropenia or > or =grade 2 gastrointestinal toxicity and 219 controls who did not show any ADRs throughout the treatment. The association study revealed that one SNP, rs9561778 in ABCC4, showed a significant association with CPA-induced ADRs (Cochran-Armitage trend's P-value=0.00031; odds ratio (OR)=2.06). Subgroup analysis also indicated that the SNP rs9561778 was significantly associated with two major ADR subgroups; gastrointestinal toxicity and leukopenia/neutropenia (Cochran-Armitage trend's P-value=0.00019 and 0.014; OR=2.31 and 1.83). Furthermore, the SNP rs9561778 showed an association with breast cancer patients who were treated with CA(F) drug regimen-induced ADR (Cochran-Armitage trend's P-value=0.00028; OR=3.13). The SNPs in ABCC4 might be applicable in predicting the risk of ADRs in patients receiving CPA combination chemotherapy.

  10. Rapamycin Prevents cyclophosphamide-induced Over-activation of Primordial Follicle pool through PI3K/Akt/mTOR Signaling Pathway in vivo.

    Science.gov (United States)

    Zhou, Linyan; Xie, Yanqiu; Li, Song; Liang, Yihua; Qiu, Qi; Lin, Haiyan; Zhang, Qingxue

    2017-08-16

    Primordial follicular depletion has thought to be a common adverse effect of chemotherapy especially for female of reproductive age. The study aimed to evaluate the protective effect of rapamycin on the primordial follicles and its potential mechanism for patients receiving chemotherapy. 8-week old BALB/c female mice were randomly assigned into four groups (control; rapamycin; cyclophosphamide; and rapamycin combined with cyclophosphamide). Hematoxylin staining, immunohistochemical, TUNEL, western blotting and ELISA were employed to assess inter-group differences using Student's t-test and Mann-Whitney test. Cyclophosphamide depleted the follicular reserve and induced the phosphorylation of the key proteins of PI3K/Akt/mTOR pathway in mice in a dose-dependent manner. Co-treatment with rapamycin significantly reduced primordial follicle loss at all cyclophosphamide dose groups and prevent the follicle growth wave caused by cyclophosphamide treatment (P primordial follicles in all groups and fewer apoptosis in large growing follicles were observed in ovaries from rapamycin + cyclophosphamide group compared to that received cyclophosphamide alone. Serum anti-Müllerian hormone (AMH) was significantly reduced in cyclophosphamide alone group, in contrast to the normal level in rapamycin + cyclophosphamide group. Compared to p-Akt/Akt and p-mtor/mtor, p-rps6/rps6 was significantly decreased in rapamycin + cyclophosphamide group (P primordial follicle activation induced by cyclophosphamide through PI3K/Akt/mTOR signaling pathway and thus plays a role in preserving the follicle pool. These results suggest that rapamycin may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of ovarian reserve and prevention of POF.

  11. Dynamics of early histopathological changes in GVHD after busulphan/cyclophosphamide conditioning regimen.

    Science.gov (United States)

    Al-Hashmi, Sulaiman; Hassan, Zuzana; Sadeghi, Behnam; Rozell, Björn; Hassan, Moustapha

    2011-08-15

    Hematopoietic stem cell transplantation (HSCT) is a curative treatment for otherwise incurable diseases. Conditioning regimen is an important part of HSCT and consists of chemotherapy with or without irradiation. Conditioning exerts myelosuppressive, immunosuppressive and antitumor effects, but also contributes to HSCT-related complications including graft-versus-host disease (GVHD). Since almost 50% of the transplanted patients are conditioned with cytostatics without irradiation, we developed and characterized a GVHD mouse model following conditioning with busulphan and cyclophosphamide. Recipient Balb/c female mice were treated with busulphan (20 mg/kg/day for 4 days) and cyclophosphamide (100 mg/kg/day for two days). After one day of rest, recipient mice were transplanted with 2×10(7) bone marrow and 3×10(7) spleen cells from male C57BL/6 (allogeneic group) or female Balb/c (syngeneic/control group) mice. The allogeneic, but not syngeneic transplanted mice developed GVHD. Histopathology of the major internal organs (liver, pancreas, spleen, lungs, heart and kidney) was examined before conditioning start, after conditioning's end and 5, 7 and 21 days after transplantation using hematoxylin-eosin staining. Decreased spleen cellularity and diminished glycogen content in the liver were observed after conditioning regimen. Histopathological changes such as vasculitis, inflammation and apoptotic cell forms in liver, spleen, pancreas, lungs and heart were observed in allogeneic transplanted mice, however, only hypocellular spleen and extramedullar hematopoiesis were detected in syngeneic transplanted animals. No morphological changes were observed in kidney in either HSCT setting. This is the first study describing early histopathological changes after conditioning regimen with busulphan/cyclophosphamide and dynamics of GVHD development in several major internal organs.

  12. Efficacy of H, antihistamine, corticosteroids and cyclophosphamide in the treatment of chronic dermographic urticaria

    Directory of Open Access Journals (Sweden)

    Kumar Rajesh

    2002-01-01

    Full Text Available H, antihistamines relieve urticaria by blocking the action of histamine on the target tissue, while demonstration of autoantibodies in the sera of a proportion of the patients having chronic idiopathic urticaria, use of immunosuppressive drugs for the treatment of these patients has acquired the greater rationality. We evaluated the role of corticosteroids and cyclophosphamide in the treatment of chronic dermographic urticaria. Twenty-five patients, 13 males and 12 females, between 18-53 years in age, having chronic dermographic urticaria were taken up for this study. The patients were divided into three groups. Group I patients (n=9 were treated with cetirizine hydrochloride 10 mg per day orally, group II patients (n=7 were treated with betamethasone 2 mg along with cyclophosphamide 50 mg along with cetirizine 10 mg per day for a total period of 4 weeks. The patients were evaluated every week to record the therapeutic response and side effects, and then followed up without treatment for a period of 6 months to look for recurrence of the urticaria, if any. Six patients in group I and all the patients in group II and group III had complete remission while the remaining patients in group I had partial relief. The side effects included drowsiness in 4 patients. All the patients in group II had weight gain, 4 patients had acne and 2 patients developed cushingoid features. Majority of the patients relapsed within 3 days after stopping the treatment. Supplementation of the treatment with oral corticosteroids or cyclophosphamide was more effective in controlling the symptoms as compared to cetirizine alone. But a four weeks supplementation was not adequate for preventing the relapses when the drugs were withdrawn.

  13. Urodynamic investigation of cyclophosphamide-induced overactive bladder in conscious rats

    Institute of Scientific and Technical Information of China (English)

    PAN Feng; LIU Di; HAN Xiao-min; LI Wen-cheng; PANG Zi-li; LI Bing; ZHANG Xiao-ping; XIAO Ya-jun; ZENG Fu-qing

    2012-01-01

    Background Overactive bladder (OAB) can be caused by many factors such as inflammation,bladder outlet obstruction,neurogenic factors.We performed an intraperitoneal (ip) injection of cyclophosphamide to induce cystitis in rats,which causes their detrusors to overact,to provide a valuable disease model for discussing OAB pathogenesis and to study effective curing methods.Methods Female Sprague-Dawley rats were induced to form cystitis by cyclophosphamide (200 mg/kg,ip).The day after the injection,two catheters were inserted into each rat's bladder to study its urodynamics.The BL-410 model bio-function experimental system was used to monitor bladder pressure while the rats were conscious.Unstable detrusor contractions appear in the urine storage period as a standard to determine OAB,and the positive rate was calculated.Urodynamic parameters such as bladder basal pressure (BP),maximum voiding pressure (MVP),intercontraction interval (ICI),spontaneous activity (SA),maximum cystometric capacity (MCC),and bladder compliance (BC) were recorded in each group,and a light microscope was used to observe the pathological changes in the rat bladder tissue.Results The detrusor instability rate of the model group was 83.33%.The MVP,MCC and BC of rats in the model group were lower than the control group (P <0.01),and the BP,ICI and SA of the model group rats were higher than the control group (P <0.01).The difference between the control group and the model group is statistically significant.The model group rats' bladder walls swelled and bled,the submucosa thickened and leukocyte infiltration became serious.Conclusions Acute cystitis and OAB symptoms can be induced by ip injections of cyclophosphamide in rats.This can provide a valuable animal model to study OAB in human beings.

  14. Paternal cyclophosphamide exposure induces the formation of functional micronuclei during the first zygotic division.

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    Lisanne Grenier

    Full Text Available Paternal exposures to cancer chemotherapeutics or environmental chemicals may have adverse effects on progeny outcome that are manifested in the preimplantation embryo. The objectives of this study were to determine the impact of paternal exposure to cyclophosphamide, an anticancer alkylating agent, on the formation, chromatin origin and function of micronuclei in cleavage stage rat embryos. Male Sprague-Dawley rats were gavaged with saline or cyclophosphamide (6 mg/kg/day for 4 weeks and mated to naturally cycling females to collect pronuclear zygotes and 2 to 8 cell embryos. Micronuclear chromatin structure was characterized using confocal microscopy to detect immunoreactivities for H3K9me3, a marker for maternal chromatin, and lamin B, a nuclear membrane marker. DNA synthesis was monitored using EdU (5-ethynyl-2'-deoxyuridine incorporation. Fertilization by cyclophosphamide-exposed spermatozoa led to a dramatic elevation in micronuclei in cleavage stage embryos (control embryos: 1% to 5%; embryos sired by treated males: 70%. The formation of micronuclei occurred during the first zygotic division and was associated with a subsequent developmental delay. The absence of H3K9me3 indicated that these micronuclei were of paternal origin. The micronuclei had incomplete peri-nuclear and peri-nucleolar lamin B1 membrane formation but incorporated EdU into DNA to the same extent as the main nucleus. The formation of micronuclei in response to the presence of a damaged paternal genome may play a role in increasing the rate of embryo loss that is associated with the use of assisted reproductive technologies, parenthood among cancer survivors, and paternal aging.

  15. Cyclophosphamide and epirubicin-induced diabetes mellitus in breast cancer: A rare occurrence.

    Science.gov (United States)

    Sharma, Pramod Kumar; Misra, Arup Kumar; Singh, Vikram; Gupta, Ajay; Saroha, Shrishti; Singh, Surjit

    2016-01-01

    Breast cancer is the leading cause of death in women. Epirubicin and cyclophosphamide (EC) is one of the chemotherapeutic regimens used for the treatment of breast cancer. We describe a case treated with EC regimen and who presented to us with symptoms suggestive of diabetes mellitus postchemotherapy. Absence of family history of diabetes and normal blood sugar level, prechemotherapy points toward drug-induced hyperglycemia. These chemotherapeutic agents capable of altering immune response and might act synergistically to cause immunological damage to the islets of pancreas which might precipitate diabetes mellitus. Causality analysis on Naranjo's scale indicates a possible association with regimen.

  16. Cyclophosphamide and epirubicin-induced diabetes mellitus in breast cancer: A rare occurrence

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Sharma

    2016-01-01

    Full Text Available Breast cancer is the leading cause of death in women. Epirubicin and cyclophosphamide (EC is one of the chemotherapeutic regimens used for the treatment of breast cancer. We describe a case treated with EC regimen and who presented to us with symptoms suggestive of diabetes mellitus postchemotherapy. Absence of family history of diabetes and normal blood sugar level, prechemotherapy points toward drug-induced hyperglycemia. These chemotherapeutic agents capable of altering immune response and might act synergistically to cause immunological damage to the islets of pancreas which might precipitate diabetes mellitus. Causality analysis on Naranjo′s scale indicates a possible association with regimen.

  17. Can propolis and caffeic acid phenethyl ester be promising agents against cyclophosphamide toxicity?

    Science.gov (United States)

    Akyol, Sumeyya; Gulec, Mehmet Akif; Erdemli, Haci Kemal; Akyol, Omer

    2016-01-01

    Propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester (CAPE). They have been using in several medical conditions/diseases in both in vitro and in vivo experimental setup. Cyclophosphamide (CP) has been used to treat a broad of malignancies including Hodgkin’s and non-Hodgkin’s lymphoma, Burkitt’s lymphoma, chronic lymphocytic leukemia, Ewing’s sarcoma, breast cancer, testicular cancer, etc. It may cause several side effects after treatment. In this mini review, the protective effects of propolis and CAPE were compared each other in terms of effectiveness against CP-induced injuries. PMID:27069732

  18. Modulation of parasitemia and antibody responce to Trypanosoma cruzy by cyclophosphamide in Calomys callosus (Rodentia, Cricetidae)

    OpenAIRE

    1992-01-01

    Calomys callosus a wild rodent, previously described as harboring Trypanosoma cruzi, has a low susceptibility to infection by this protozoan. Experiments were designed to evaluate the contribution of the immune response to the resistance to T. cruzi infection exhibited by C. calossus. Animals were submitted to injections of high (200 mg/kg body weight) and low (20 mg/kg body weight) doses of cyclophosphamide on days -1 or -1 and +5, and inoculated with 4 x 10³ T. cruzi on day O. Parasitemia, ...

  19. Effect ofBuchanania lanzan Spreng. bark extract on cyclophosphamide induced genotoxicity and oxidative stress in mice

    Institute of Scientific and Technical Information of China (English)

    Ritesh Jain; Sanmati Kumar Jain

    2012-01-01

    Objective:To elucidate the effect of ethanolic extract ofBuchanania lanzan Spreng. (B. lanan) bark against cyclophosphamide induced genotoxicity and oxidative stress in mice.Methods:The prevalence of micronuclei in bone marrow, the extent of lipid peroxidation, reduced glutathione and the status of the antioxidant enzymes, superoxide dismutase and catalase in liver of mice were used as intermediate biomarkers for chemoprotection. Lipid peroxidation and associated compromised antioxidant defenses in cyclophosphamide treated mice were observed in the liver.Results: Pre-treatment withB. lanzan250, 500 and1 000mg/ kg,p.o., daily for7 days significantly reduced the chromosomal damage and lipid peroxidation with concomitant changes in antioxidants and detoxification systems.Conclusions: These results point out the presence of chemopreventive phytoconstituents in the crude extract offering protection against cyclophosphamide induced genotoxicity and oxidative stress in mice.

  20. Manganese Superoxide Dismutase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cencer Patients Treated with Cyclophosphamide Epirubicin and 5-Fluororacil

    DEFF Research Database (Denmark)

    Ording, Anne Gulbech; Cronin Fenton, Deirdre; Christensen, Mariann

    2012-01-01

    Manganese Superoxide Dismutase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cencer Patients Treated with Cyclophosphamide Epirubicin and 5-Fluororacil......Manganese Superoxide Dismutase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cencer Patients Treated with Cyclophosphamide Epirubicin and 5-Fluororacil...

  1. Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil

    DEFF Research Database (Denmark)

    Ording, Anne Gulbech; Cronin Fenton, Deirdre; Christensen, Mariann

    2013-01-01

    Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil......Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil...

  2. Human CD4+CD25+ regulatory T cells are sensitive to low dose cyclophosphamide: implications for the immune response.

    Directory of Open Access Journals (Sweden)

    Daniel Heylmann

    Full Text Available Regulatory T cells (Treg play a pivotal role in the immune system since they inhibit the T cell response. It is well known that cyclophosphamide applied at low dose is able to stimulate the immune response while high dose cyclophosphamide exerts inhibitory activity. Data obtained in mice indicate that cyclophosphamide provokes a reduction in the number of Treg and impairs their suppressive activity, resulting in immune stimulation. Here, we addressed the question of the sensitivity of human Treg to cyclophosphamide, comparing Treg with cytotoxic T cells (CTL and T helper cells (Th. We show that Treg are more sensitive than CTL and Th to mafosfamide, which is an active derivative of cyclophosphamide, which does not need metabolic activation. The high sensitivity of Treg was due to the induction of apoptosis. Treg compared to CTL and Th were not more sensitive to the alkylating drugs temozolomide and nimustine and also not to mitomycin C, indicating a specific Treg response to mafosfamide. The high sensitivity of Treg to mafosfamide resulted not only in enhanced cell death, but also in impaired Treg function as demonstrated by a decline in the suppressor activity of Treg in a co-culture model with Th and Helios positive Treg. Treatment of Treg with mafosfamide gave rise to a high level of DNA crosslinks, which were not repaired to the same extent as observed in Th and CTL. Also, Treg showed a low level of γH2AX foci up to 6 h and a high level 24 h after treatment, indicating alterations in the DNA damage response. Overall, this is the first demonstration that human Treg are, in comparison with Th and CTL, hypersensitive to cyclophosphamide, which is presumably due to a DNA repair defect.

  3. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant

    Science.gov (United States)

    Ruggeri, Annalisa; Sun, Yuqian; Labopin, Myriam; Bacigalupo, Andrea; Lorentino, Francesca; Arcese, William; Santarone, Stella; Gülbas, Zafer; Blaise, Didier; Messina, Giuseppe; Ghavamzadeh, Ardeshi; Malard, Florent; Bruno, Benedetto; Diez-Martin, Jose Luis; Koc, Yener; Ciceri, Fabio; Mohty, Mohamad; Nagler, Arnon

    2017-01-01

    Severe graft-versus-host disease is a major barrier for non-T-cell-depleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs. the anti-thymocyte globulin-based) in adults with acute myeloid leukemia reported to the European Society for Blood and Bone Marrow Transplantation. A total of 308 patients were analyzed; 193 received post-transplant cyclophosphamide-based regimen and 115 anti-thymocyte globulin-based regimen as anti-graft-versus-host disease prophylaxis. The post-transplant cyclophosphamide-based regimen was more likely to be associated to bone marrow as graft source (60% vs. 40%; P=0.01). Patients in the post-transplant cyclophosphamide-based regimen group had significantly less grade 3–4 acute graft-versus-host disease than those in the anti-thymocyte globulin-based group (5% vs. 12%, respectively; P=0.01), comparable to chronic graft-versus-host disease. Multivariate analysis showed that non-relapse mortality was lower in the post-transplant cyclophosphamide-based regimen group [22% vs. 30%, Hazard ratio (HR) 1.77(95%CI: 1.09–2.86); P=0.02] with no difference in relapse incidence. Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45 (95%CI: 1.04–2.02); P=0.03] and leukemia-free survival [HR 1.48 (95%CI: 1.03–2.12); P=0.03] than those in the anti-thymocyte globulin-based group. In the multivariate analysis, there was also a trend for a higher overall survival [HR 1.43 (95%CI: 0.98–2.09); P=0.06] for post-transplant cyclophosphamide-based regimen versus the anti-thymocyte globulin-based group. Notably, center experience was also associated with non-relapse mortality and graft-versus-host disease-free, relapse-free survival. Haplo-SCT using a post

  4. Effects of cyclophosphamide on the prognosis of Japanese patients with renal vasculitis associated with anti-neutrophil cytoplasmic antibody-positive microscopic polyangiitis.

    Science.gov (United States)

    Iwabuchi, Masashi; Nakaya, Izaya; Tsuchiya, Yoshinori; Shibagaki, Yugo; Yamaguchi, Takuhiro; Fukuhara, Shunichi; Oe, Yuji; Sakuma, Tsutomu; Sato, Toshinobu; Taguma, Yoshio; Soma, Jun

    2016-10-01

    The aim of this study was to determine the efficacy of cyclophosphamide (CY) on anti-neutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA) with renal involvement in Japanese patients. Eighty-two patients with newly diagnosed ANCA-positive MPA were enrolled in this retrospective study. Patients were divided into two groups based on whether they received combination therapy with a corticosteroid (CS) plus CY (CY group) or CS alone or with other therapies (non-CY group). The primary outcome was defined as the combination of death and end-stage renal disease (ESRD). The CY and non-CY groups included 29 and 53 patients, respectively. In the non-CY group, 31 patients were treated with CS alone, and 22 with a combination of CS and other therapeutics. The percentage of males and mean Birmingham vasculitis activity scores were higher in the CY group than those in the non-CY group, but other factors such as age, serum creatinine, serum albumin, or CRP at baseline were equivalent in the two groups. No differences were observed in remission rates using induction therapy for the two groups. However, the survival rate 5 years after induction therapy was lower in the CY group than in the non-CY group (0.50 vs. 0.73; P = 0.041), although the hazard ratio of CY for the primary outcome adjusted for all confounding factors was 1.321 [95 % confidence interval (CI), 0.662-2.637; P = 0.171]. CY may not have an additive effect on induction therapy with CS for Japanese patients with renal vasculitis associated with ANCA-positive MPA.

  5. Protective Effect of Quercetin Against Oxidative Stress-induced Toxicity Associated With Doxorubicin and Cyclophosphamide in Rat Kidney and Liver Tissue.

    Science.gov (United States)

    Kocahan, Sayad; Dogan, Zumrut; Erdemli, Erman; Taskin, Eylem

    2017-03-01

    Doxorubicin and cyclophosphamide are widely used anticancer drugs with substantial toxicity in noncancerous tissue resulting from oxidative damage. Quercetin is a potent antioxidant compound. We hypothesized that quercetin administration would ameliorate the toxic effects of doxorubicin and cyclophosphamide prior to pregnancy. Cyclophosphamide, 27 mg/kg, and doxorubicin, 1.8 mg/kg, were administered to rats as intraperitoneal doses once every 3 weeks for a total of 10 weeks with or without concurrent treatment with quercetin, 10 mg/kg/d. Oxidative stress parameters were evaluated in maternal kidney and liver tissues after gestation. Doxorubicin was associated with elevated kidney tissue malondialdehyde relative to the controls and quercetin only treatment (P doxorubicin were associated with elevated malondialdehyde levels in the liver tissue (P Doxorubicin treatment was associated with decreased liver glutathione peroxidase (P doxorubicin and cyclophosphamide treatment (P doxorubicin and cyclophosphamide results in therapeutic restoration of homeostatic expression of the antioxidant parameters, reducing oxidative damage to the liver and kidney.

  6. Immunostimulative effects of Cyperus rotundus, Alpinia calcarata, Solanum surattense, Clerodendrum infortunatum and Croton laccifer extracts combination on cyclophosphamide-induced immunosupression in rats

    Directory of Open Access Journals (Sweden)

    Ediriweera P. S. Chandana

    2015-06-01

    Results: Hematological analyses revealed that total WBC and leukocyte adhesion were not significantly different in control and extract-treated groups. Expression of IL-4 and IL-10 was significantly different in treated and control groups while expression of IL-12 was not significantly different. Cyclophosphamide-induced immunosuppression of the control group caused moderate to severe skin lesions while the rats in the extract-treated group did not sustain any skin lesions. All the rats in the cyclophosphamide-treated control group died after three months while 83.33% of the cyclophosphamide + plant extract received group survived, indicating the ability of the plant combination to alleviate the immunosuppression induced by cyclophosphamide. Conclusions: Treating with ethanolic extract combination of above plant species might exert their immunomodulatory effect via cytokine expression and can attenuate the immunosuppression induced by cyclophosphamide. [J Exp Integr Med 2015; 5(2.000: 110-113

  7. Place in therapy of rituximab in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis

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    Shah S

    2015-08-01

    Full Text Available Shivani Shah, Duvuru Geetha Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Granulomatosis with polyangiitis and microscopic polyangiitis are small vessel vasculitides characterized by circulating antineutrophil circulating antibodies. Standard treatment for active severe disease has consisted of cyclophosphamide with glucocorticoids with or without plasmapheresis, which achieves approximately 75% sustained remission, but carries significant adverse effects such as malignancy, infertility, leukopenia, and infections. The role of B cells in the pathogenesis of anti-neutrophil circulating antibodies-associated vasculitis has been established, and as such, rituximab, a monoclonal anti-CD20 antibody, has been studied in treatment of active granulomatosis with polyangiitis and microscopic polyangiitis (induction and in maintaining remission. Rituximab has been shown to be effective in inducing remission in several retrospective studies in patients with refractory disease or cyclophosphamide intolerance. The RAVE and RITUXVAS trials demonstrated rituximab is a noninferior alternative to standard cyclophosphamide-based therapy; however, its role in elderly patients and patients with severe renal disease warrants further investigation. Rituximab has been compared with azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction. Rituximab is not without risks and carries a similar adverse event risk rate as cyclophosphamide in randomized control trials. However, its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility. Keywords: rituximab, ANCA-associated vasculitis, GPA, MPA, induction therapy, maintenance therapy

  8. Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats.

    Science.gov (United States)

    Oyagbemi, A A; Omobowale, T O; Saba, A B; Adedara, I A; Olowu, E R; Akinrinde, A S; Dada, R O

    2016-05-01

    The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg(-1) on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg(-1) ) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione-S-transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA-treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.

  9. Crataegus Monogyna Aqueous Extract Ameliorates Cyclophosphamide-Induced Toxicity in Rat Testis: Stereological Evidences

    Directory of Open Access Journals (Sweden)

    Hassan Malekinejad

    2012-01-01

    Full Text Available Cyclophosphamide (CP is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.

  10. A Case of Polyarteritis Nodosa Associated with Vertebral Artery Vasculitis Treated Successfully with Tocilizumab and Cyclophosphamide

    Science.gov (United States)

    Watanabe, Kae; Rajderkar, Dhanashree A.; Modica, Renee F.

    2016-01-01

    Pediatric polyarteritis nodosa is rare systemic necrotizing arteritis involving small- and medium-sized muscular arteries characterized by aneurysmal dilatations involving the vessel wall. Aneurysms associated with polyarteritis nodosa are common in visceral arteries; however intracranial aneurysms have also been reported and can be associated with central nervous system symptoms, significant morbidity, and mortality. To our knowledge extracranial involvement of the vertebral arteries has not been reported but has the potential to be deleterious due to fact that they supply the central nervous system vasculature. We present a case of a 3-year-old Haitian boy with polyarteritis nodosa that presented with extracranial vessel involvement of his vertebral arteries. After thorough diagnostic imaging, including a bone scan, ultrasound, Magnetic Resonance Imaging/Angiography, and Computed Tomography Angiography, he was noted to have vertebral artery vasculitis, periostitis, subacute epididymoorchitis, arthritis, and myositis. He met diagnostic criteria for polyarteritis nodosa and was treated with cyclophosphamide, methylprednisolone, and tocilizumab, which resulted in improvement of his inflammatory markers, radiographic findings, and physical symptoms after treatment. To the authors' knowledge, this is the first report of vertebral artery vasculitis in polyarteritis nodosa as well as successful treatment of the condition using the combination cyclophosphamide and tocilizumab for this condition. PMID:27018080

  11. A Case of Polyarteritis Nodosa Associated with Vertebral Artery Vasculitis Treated Successfully with Tocilizumab and Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Kae Watanabe

    2016-01-01

    Full Text Available Pediatric polyarteritis nodosa is rare systemic necrotizing arteritis involving small- and medium-sized muscular arteries characterized by aneurysmal dilatations involving the vessel wall. Aneurysms associated with polyarteritis nodosa are common in visceral arteries; however intracranial aneurysms have also been reported and can be associated with central nervous system symptoms, significant morbidity, and mortality. To our knowledge extracranial involvement of the vertebral arteries has not been reported but has the potential to be deleterious due to fact that they supply the central nervous system vasculature. We present a case of a 3-year-old Haitian boy with polyarteritis nodosa that presented with extracranial vessel involvement of his vertebral arteries. After thorough diagnostic imaging, including a bone scan, ultrasound, Magnetic Resonance Imaging/Angiography, and Computed Tomography Angiography, he was noted to have vertebral artery vasculitis, periostitis, subacute epididymoorchitis, arthritis, and myositis. He met diagnostic criteria for polyarteritis nodosa and was treated with cyclophosphamide, methylprednisolone, and tocilizumab, which resulted in improvement of his inflammatory markers, radiographic findings, and physical symptoms after treatment. To the authors’ knowledge, this is the first report of vertebral artery vasculitis in polyarteritis nodosa as well as successful treatment of the condition using the combination cyclophosphamide and tocilizumab for this condition.

  12. Antimutagenic effects of piperine on cyclophosphamide-induced chromosome aberrations in rat bone marrow cells.

    Science.gov (United States)

    Wongpa, Sareeya; Himakoun, Lakana; Soontornchai, Sarisak; Temcharoen, Punya

    2007-01-01

    Piperine is a major pungent substance and active component of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). Both plants are used worldwide as household spices and condiments. They are also used as important ingredients in folklore medicine in many Asian countries. Therefore, it is of interest to study antimutagenic effects of piperine. In this study, its influence on chromosomes was investigated in rat bone marrow cells. Male Wistar rats were orally administered piperine at the doses of 100, 400 and 800 mg/kg body weight for 24 hours then challenged with cyclophosphamide at a dose of 50 mg/kg body weight by intraperitoneal injection. Twenty-four hours thereafter, all animals were sacrificed and bone marrow samples were collected for chromosomal analysis. The results demonstrated that piperine at a dose of 100 mg/kg body weight gave a statistically significant reduction in cyclophosphamide-induced chromosomal aberrations. In conclusion, piperine may have antimutagenic potential. The underlying molecular mechanisms now require attention.

  13. Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice

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    Tatiane Yumi Nakamura Kanno

    2009-06-01

    Full Text Available The cyclophosphamide is used in cancer treatment. The aim of this study was evaluating the effect of different doses of this drug on male mice reproductive parameters. The cyclophosphamide was administered in the doses 100, 150, 200 e 250 mg.kg-1, intraperitoneal route, for six weeks. As a result, it was observed a decrease in body mass and a decrease in testicles and kidney's weight, in all animals treated with cyclophosphamide. Only the groups that received the doses 100, 150 mg.kg-1 of cyclophosphamide were able to fertilize their females. There was higher incidence of post- implantation losses, reabsorptions and decrease in fetal viability in the group that received the dose of 150 mg.kg-1. It was observed a reduction in epididymis and liver's weight of the animals treated with the doses 150, 200 e 250 mg.kg-1. Abnormal spermatozoa were found in the doses 200 e 250 mg.kg-1. Based on the methodology used and results obtained, it was concluded that the cyclophosphamide was toxic, considering the decrease in animal's body mass and testicle's weight; promoted hepatotoxicity and nephrotoxic effect; influenced in the animals spermatogenesis taking them to infertility and/or subfertility; decreased fetal viability, despite it didn't cause significant malformations in the offspring.A ciclofosfamida é utilizada no tratamento de câncer. Este estudo visa avaliar os efeitos das diferentes doses do fármaco nos parâmetros reprodutivos de camundongos machos. A ciclofosfamida foi administrada nas doses de 100, 150, 200 e 250 mg kg-1, via intraperitoneal por seis semanas. Como resultado observou-se diminuição de massa corporal, redução no peso de testículos e rins em todos os animais tratados com a ciclofosfamida. Apenas os grupos que receberam as doses de 100 e 150 mg kg-1 do quimioterápico foram capazes de fertilizar as fêmeas. Houve maior incidência de perdas pós-implantação, reabsorção e diminuição da viabilidade fetal no grupo que

  14. EBV-positive immunodeficiency lymphoma after alemtuzumab-CHOP therapy for peripheral T-cell lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke C.; Coenen, Jules L.; Boers, James E.; van Imhoff, Gustaaf W.; Rosati, Stefano

    2008-01-01

    Chemotherapy with alemtuzumab and the combination of cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP) has become experimental trial therapy for aggressive T-cell lymphoma. Several multicenter phase 3 trials; will incorporate this scheme. As part of an ongoing phase 2 trial in which we re

  15. Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: A long-term randomized controlled trial

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    Ahmed H Mitwalli

    2011-01-01

    Full Text Available To evaluate the outcome of low doses of cyclophosphamide (Cyclo therapy in lupus nephritis (LN patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73 received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44 received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min compared with Group II (55.1 ± 30.1 mL/min, P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05. At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03. The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2. Complete remission was observed in 25 (34.2% patients in Group I vs. 11 (25% in Group II (P = 0.288, while partial remission was similar in both groups; 43 (58.9% patients in Group I vs. 26 (59% patients in Group II. End-stage renal disease was observed in 10 (13.7% patients in Group I vs. 9 (20.4% patients in Group II (P = 0.359. Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000. Moreover, different infections occurred in 23 (31.3% patients vs. six (13.6%, digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective

  16. PERSONALIZED DOSING OF CYCLOPHOSPHAMIDE IN THE TOTAL BODY IRRADIATION - CYCLOPHOSPHAMIDE CONDITIONING REGIMEN: A PHASE II TRIAL IN PATIENTS WITH HEMATOLOGIC MALIGNANCY

    Science.gov (United States)

    McCune, Jeannine S.; Batchelder, Ami; Guthrie, Katherine A.; Witherspoon, Robert; Appelbaum, Frederick R.; Phillips, Brian; Vicini, Paolo; Salinger, David H.; McDonald, George B.

    2009-01-01

    This study investigates the efficacy and safety of personalized cyclophosphamide (CY) dosing in 50 patients receiving CY with total body irradiation (TBI). Participants received CY 45 mg/kg with subsequent therapeutic drug monitoring with Bayesian parameter estimation to personalize the second CY dose to a target area under the curve for carboxyethylphosphoramide mustard (a reporter for CY-derived toxins) and for hydroxycyclophosphamide (to ensure engraftment). The mean second CY dose was 66 mg/kg; the total dose ranged from 45–145 mg/kg. After completion of this phase II study, we compared participants’ clinical outcomes to those of concurrent controls (N=100) who received TBI with standard CY doses of 120 mg/kg. Patients receiving personalized CY dosing had significantly lower post-conditioning peak total serum bilirubin (p=0.03); a 38% reduction in the hazard of acute kidney injury (p=0.03); and similar non-relapse and overall survival (p=0.70 and 0.63, respectively) despite lower doses of CY in most patients. PMID:19295506

  17. Treatment of Systemic Sclerosis-related Interstitial Lung Disease: A Review of Existing and Emerging Therapies.

    Science.gov (United States)

    Volkmann, Elizabeth R; Tashkin, Donald P

    2016-11-01

    Although interstitial lung disease accounts for the majority of deaths of patients with systemic sclerosis, treatment options for this manifestation of the disease are limited. Few high-quality, randomized, controlled trials exist for systemic sclerosis-related interstitial lung disease, and historically, studies have favored the use of cyclophosphamide. However, the benefit of cyclophosphamide for this disease is tempered by its complex adverse event profile. More recent studies have demonstrated the effectiveness of mycophenolate for systemic sclerosis-related interstitial lung disease, including Scleroderma Lung Study II. This review highlights the findings of this study, which was the first randomized controlled trial to compare cyclophosphamide with mycophenolate for the treatment of systemic sclerosis-related interstitial lung disease. The results reported in this trial suggest that there is no difference in treatment efficacy between mycophenolate and cyclophosphamide; however, mycophenolate appears to be safer and more tolerable than cyclophosphamide. In light of the ongoing advances in our understanding of the pathogenic mechanisms underlying interstitial lung disease in systemic sclerosis, this review also summarizes novel treatment approaches, presenting clinical and preclinical evidence for rituximab, tocilizumab, pirfenidone, and nintedanib, as well as hematopoietic stem cell transplantation and lung transplantation. This review further explores how reaching a consensus on appropriate study end points, as well as trial enrichment criteria, is central to improving our ability to judiciously evaluate the safety and efficacy of emerging experimental therapies for systemic sclerosis-related interstitial lung disease.

  18. Mycophenolate mofetil in idiopathic membranous nephropathy: a clinical trial with comparison to a historic control group treated with cyclophosphamide.

    NARCIS (Netherlands)

    Branten, A.J.W.; Buf-Vereijken, P.W.G. du; Vervloet, M.; Wetzels, J.F.M.

    2007-01-01

    BACKGROUND: Cyclophosphamide can decrease proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a high risk of side effects. We studied whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effects. STUDY DESIGN: Clinical t

  19. Combined thalidomide and cyclophosphamide treatment for refractory or relapsed multiple myeloma patients : a prospective phase II study

    NARCIS (Netherlands)

    Hovenga, S; Daenen, SMGJ; de Wolf, JTM; van Imhoff, GW; Kluin-Nelemans, HC; Sluiter, WJ; Vellenga, E

    2005-01-01

    refractory multiple myeloma ( MM) with a response rate of 30-40% at doses of 200-800 mg but with considerable side effects. We questioned whether lower doses of thalidomide in combination with a daily dose of cyclophosphamide might be an effective regimen with fewer side effects. We included 38 pati

  20. Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer : A single-arm phase II study

    NARCIS (Netherlands)

    Vermeij, Renee; Leffers, Ninke; Hoogeboom, Baukje-Nynke; Hamming, Ineke L. E.; Wolf, Rinze; Reyners, Anna K. L.; Molmans, Barbara H. W.; Hollema, Harry; Bart, Joost; Drijfhout, Jan W.; Oostendorp, Jaap; van der Zee, Ate G. J.; Melief, Cornelis J.; van der Burg, Sjoerd H.; Daemen, Toos; Nijman, Hans W.

    2012-01-01

    The purpose of the current phase II single-arm clinical trial was to evaluate whether pretreatment with low-dose cyclophosphamide improves immunogenicity of a p53-synthetic long peptide (SLP) vaccine in patients with recurrent ovarian cancer. Patients with ovarian cancer with elevated serum levels

  1. Study on the Antiradiation role of Melatonin: An investigation on Induced Oxidative Stress Mice by Radiomimetic Drug Cyclophosphamide

    Energy Technology Data Exchange (ETDEWEB)

    Manda, K.; Bhatia, A. L.

    2004-07-01

    Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the document antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor the effect of higher blood levels of melatonin, the most important pineal hormone, which could be applied in relation to the response to chemotherapy in human neoplasms. Cyclophosphamide is a commonly used chemotherapeutic drug and well-known mutagen and clastogen. It is an alkylating agent, producing highly active carbonium ion, which the extremely electron-rich area of the nucleic acids and proteins. The present study aimed to investigate the protective effect of melatonin against cyclophosphamide induced oxidative stress in mice tissues. Lipid perioxidation. Reduced glutathione (GSH), Glutathione disulphide (GSSG), Glutathione peroxidase (GSH-Px) and serum phosphatase level taken as endpoints. Twenty days oral administration with melatonin (0.25 mg/Kg body weight) followed by an acute treatment with cyclophosphamide (75 mg/kg b. w.) inhibited the radiomimetic drug-induced augmented level of lipid peroxidation, Blood GSSG and acid phosphatase. Cyclophosphamide induced depletion in the level of GSH, GSH-Px and alkaline phosphatase is ameliorated significantly by melatonin administration. The findings support the results showing melatonin as a free radical scavenger, and singlet oxygen quencher. Results clearly indicate the antioxidative properties of melatonin against the radiomimetic drug which could be effectively used selectively for the protection of normal tissue during chemotherapy. (Author) 34 refs.

  2. Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL).

    Science.gov (United States)

    Kröger, N; Bornhäuser, M; Stelljes, M; Pichlmeier, U; Trenschel, R; Schmid, C; Arnold, R; Martin, H; Heinzelmann, M; Wolschke, C; Meyer, R G; Bethge, W; Kobbe, G; Ayuk, F; Gökbuget, N; Hölzer, D; Zander, A; Beelen, D

    2015-12-01

    TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).

  3. NF-κB DNA-binding activity in embryos responding to a teratogen, cyclophosphamide

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    Brill Alexander

    2002-02-01

    Full Text Available Abstract Background The Rel/NF-κB transcription factors have been shown to regulate apoptosis in different cell types, acting as inducers or blockers in a stimuli- and cell type-dependent fashion. One of the Rel/NF-κB subunits, RelA, has been shown to be crucial for normal embryonic development, in which it functions in the embryonic liver as a protector against TNFα-induced physiological apoptosis. This study assesses whether NF-κB may be involved in the embryo's response to teratogens. Fot this, we evaluated how NF-KappaB DNA binding activity in embryonic organs demonstraiting differential sensitivity to a reference teratogen, cyclophosphamide, correlates with dysmorphic events induced by the teratogen at the cellular level (excessive apoptosis and at the organ level (structural anomalies. Results The embryonic brain and liver were used as target organs. We observed that the Cyclophosphamide-induced excessive apoptosis in the brain, followed by the formation of severe craniofacial structural anomalies, was accompanied by suppression of NF-κB DNA-binding activity as well as by a significant and lasting increase in the activity of caspases 3 and 8. However, in the liver, in which cyclophosphamide induced transient apoptosis was not followed by dysmorphogenesis, no suppression of NF-κB DNA-binding activity was registered and the level of active caspases 3 and 8 was significantly lower than in the brain. It has also been observed that both the brain and liver became much more sensitive to the CP-induced teratogenic insult if the embryos were exposed to a combined treatment with the teratogen and sodium salicylate that suppressed NF-κB DNA-binding activity in these organs. Conclusion The results of this study demonstrate that suppression of NF-κB DNA-binding activity in embryos responding to the teratogenic insult may be associated with their decreased resistance to this insult. They also suggest that teratogens may suppress NF-κB DNA

  4. 老年女性晚期乳腺癌卡培他滨节律化疗与常规化疗的临床疗效比较%Comparison of the Clinical Efficacy of Capecitabine Metronomic Chemotherapy and Conventional ;Chemotherapy in the Treatment of Elderly Female Patients with Advanced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    蒋琳; 谭榜宪; 赵妍丽; 刘芳; 杜国波; 侯敏; 皈燕; 柳弥

    2015-01-01

    目的:评价以小剂量卡培他滨持续给药的节律化疗方式与常规化疗方式治疗老年女性晚期乳腺癌的临床疗效和不良反应,了解前者是否存在优势。方法:研究对象为2013年4月-2014年10月本院收治的54例老年女性晚期乳腺癌患者。其中31例给予小剂量卡培他滨的持续给药方式(口服卡培他滨1500 mg/m2,1次/d,连服4周,休息1周,每5周为1个化疗周期)进行治疗,共完成2~12个化疗周期,中位化疗周期数为3个。23例给予卡培他滨单药常规化疗(卡培他滨1250 mg/m2,2次/d,连服2周,休息1周,每3周为1个化疗周期),共完成2~19个化疗周期,中位化疗周期数为4个。对至少接受过2个化疗周期的患者进行疗效评估。结果:卡培他滨节律化疗组,疾病控制率(DCR)为38.7%(12/31),中位TTP为3.8个月,中位OS为7.1个月;卡培他滨常规化疗组,疾病控制率(DCR)为39.1%(9/23),中位TTP为3.0个月,中位OS为7.3个月。两者比较差异均无统计学意义(P>0.05)。卡培他滨节律化疗组,消化系统不良反应、骨髓抑制、手足综合征大多为Ⅰ~Ⅱ度,患者能够很好耐受治疗,中途无需中断治疗。常规化疗组Ⅲ~Ⅳ度毒性反应明显,主要表现在白细胞降低、血小板下降、乏力、手足综合征等。卡培他滨节律化疗组患者生活质量较卡培他滨常规化疗组明显改善,差异有统计学意义(P0.05).In Capecitabine metronomic chemotherapy group,hand foot syndrome,bone marrow depression, digestive system adverse reactions were atⅠ-Ⅱdegree mostly.Patients could tolerate the therapy without stopping drug.In conventional chemotherapy group,the toxicity ofⅢ-Ⅳdegree were obvious,mainly in the decrease of white blood cell,platelet decrease,fatigue,hand foot syndrome.The life quality of patients in Capecitabine metronomic chemotherapy group was significantly improved

  5. Phase 1 and Extension Study of Clofarabine plus Cyclophosphamide in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

    Science.gov (United States)

    Faderl, S; Balakrishnan, K; Thomas, DA; Ravandi, F; Borthakur, G; Burger, J; Ferrajoli, A; Cortes, J; O’Brien, S; Kadia, T; Feliu, J; Plunkett, W; Gandhi, V; Kantarjian, HM

    2014-01-01

    Background Clofarabine is a nucleoside analog with activity in children with ALL. Based on the hypothesis that clofarabine inhibits DNA repair following exposure to DNA damaging agents, we designed a phase 1 and extension study to evaluate the combination of clofarabine with cyclophosphamide in adult patients with relapsed/refractory ALL. Methods The continual reassessment method (CRM) was used to define the maximum tolerated dose (MTD). Results Fifty patients with a median age of 30 years (range 21–72 years) were enrolled of whom 30 patients were part of the phase 1 group. Clofarabine 40 mg/m2 iv daily x 3 days and cyclophosphamide 200 mg/m2 iv q 12 hours x 3 days were established as the MTD. Dose limiting toxicities were diarrhea, transaminase elevations, and skin rashes. The response rate of the whole study group was 14% including 10% of patients who achieved complete remission (CR) or CR without platelet recovery. Three responses occurred in patients with primary refractory disease. Early mortality (< 30 days) was 6%. The median response duration was 69 days (range 5–315 days). Median overall survival was about 3 months. Compared to day 1 (cyclophosphamide alone), H2AX phosphorylation was increased on day 2 when clofarabine and cyclophosphamide were administered as a couplet (n = 8). Conclusions The combination of clofarabine plus cyclophosphamide at the doses used in this study and in a group of heavily pretreated patients with ALL is only moderately effective. Other doses, alternative schedules, or a more favorable patient population may achieve better results. (Word count: 248) PMID:24440659

  6. The Effect of Hydro-alcoholic Extract of Hyperricum PerforatumL. on Some Blood Parameters in Male Rats Treated with Cyclophosphamide

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    L yaghobi

    2016-05-01

    Full Text Available Background & aim: Cyclophosphamide is an anti cancer drug which causes alkylation of DNA in cells. The side effects of cyclophosphamide are bone marrow damages and anemia. Hypericum perforatum is a medicinal plant which widely used in traditional medicine. In this study the hemotopoetic effect of Hypericum perforatum leaf extract (HPE on bone marrow function and blood parameters in male rat were treated with cyclophosphamide was investigated. Methods: Forty two male Wistar rats with an average body weight of 220±25 gr were randomly divided into 6 groups (n=7: control group taking normal saline,0.5ml/day, i,p ,witness group taking cyclophosphamide (15mg/kg/day, i.p., positive control group taking HPE (200mg/kg, i.p/day,  treated groups 1, 2 and 3 recieved cyclophosphamide ,(15mg/kg/day, i.p. + 100mg/Kg, 200mg/Kg and 400mg/kg  HPE /day for 10 days, i,p. At the end of study blood samples were collected from heart directly. RBC, WBC, Hct, Hb and PL were meseaured. Data are presented as mean ± standard deviation and were analyzed using ANOVA and Tukey tests. Results: The results indicated that cyclophosphamide caused damage on bone marrow, which in this case significantly reduced the number of blood cells and platelets in the group treated with cyclophosphamide (P<0.001. Blood parameters in the groups treated with HPE increased significantly compared with the group which received cyclophosphamide alone (P<0.001. Conclusion: The Hypericum perforatum hydoethanolic extract contains antioxidant and flavonoids compounds which could protect the bone marrow tissues against cyclophosphamide.       

  7. AMELIORATIVE EFFECT OF PUNICA GRANATUM ETHANOLIC EXTRACT IN CYCLOPHOSPHAMIDE INDUCED TESTICULAR TOXICITY IN MALE WISTAR RATS

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    Divya Bhargavan

    2015-07-01

    Full Text Available Aim: To explore the potential role of Punica granatum ethanolic extract (PGEE in Cyclophosphamide (CP induced testicular toxicity. Methods: Healthy male Wistar rats were allotted to 4 groups (N=6, each Group I: Control, Group II: CP 15mg/kg twice a week, Group III: PGEE 100mg/kg, Group IV: CP and PGEE for 28 days. At the end of the treatment period, organ weight, body weight, epididymal sperm count, motility, morphology, SOD, catalase, GSH, ACP & testosterone level in the testis were evaluated. Results: The CP treated rats showed toxicity evidenced by decreased organ and body weight, decreased sperm quality and testosterone level also increase in MDA and decrease in antioxidants SOD, GSH indicating oxidative stress. In contrast PGEE co-treatment with CP resulted in significant restoration of the above mentioned parameters. Conclusion: These results indicate that PGEE attenuates CP induced testicular toxicity through its ROS scavenging activity.

  8. Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

    Science.gov (United States)

    Sallan, S E; Camitta, B M; Chan, D M; Traggis, D; Jaffe, N

    1977-01-01

    Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.

  9. Antihepatotoxic efficacy of Mangifera indica L. polysaccharides against cyclophosphamide in rats.

    Science.gov (United States)

    Fahmy, Sohair R; Amien, Ahmed I; Abd-Elgleel, Fathi M; Elaskalany, Sara M

    2016-01-25

    The present study aims to evaluate the possible protective role of polysaccharides extracted from the Egyptian mango Mangifera indica L. (MPS) and/or silymarine against cyclophosphamide (CP) toxicity in male albino rats. The MPS and/or silymarin significantly decreased the activities of serum ASAT and ALAT. However, MPS (1000 mg/kg) normalized their activities towards the normal levels recording 28.75 and 78.75 U/ml respectively. The recorded data also showed the antioxidant effect of MPS by decreasing the level of malondialdehyde (MDA) and increasing the level of reduced glutathione (GSH) as well as normalized the activities of the antioxidant enzyme GST and SOD. Histopathological examinations also confirmed the protective efficacy of MPS against liver toxicity of CP. In conclusion, the recorded results of the present study support the protective role of MPS and/or silymarin against CP-induced hepatic damage.

  10. Changes in the adhesive phenotype of regional lymphocytes in rats with adjuvant arthritis: alteration by cyclophosphamide.

    Science.gov (United States)

    Altankov, G; Marinova-Mutafchieva, L; Nikolaeva, N; Penkova, R

    1991-05-01

    A quantitative spectrophotometrical method was used to study the adhesive phenotype of lymphocytes from regional lymph nodes of rats with early stage adjuvant-induced arthritis (AA), pretreated or not with cyclophosphamide (CY). The results showed that adhesion of lymphocytes from AA-sensitized lymph nodes to gelatin and collagens (type I, II, III and IV) was enhanced, especially to collagen type II. However, adhesion to fibronectin and to fibrinogen did not differ from adhesion in nontreated rats. Application of CY was found to aggravate AA development and influence the lymphocytes' adhesiveness. Adhesion was inhibited in all cases except to fibrinogen, where it was augmented, compared to the adhesion in both AA and control groups. Relationships between the lymphocyte adhesive phenotype and the expression of histological changes suggest that lymphocyte-matrix interactions could play an important role in the pathogenesis of AA development and the mechanism of CY action.

  11. Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

    Science.gov (United States)

    Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

    2016-02-01

    Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties.

  12. Treatment of Goodpasture syndrome with cyclophosphamide, prednisone and plasma exchange transfusions.

    Science.gov (United States)

    Rossen, R D; Duffy, J; McCredie, K B; Reisberg, M A; Sharp, J T; Hersh, E M; Eknoyan, G; Suki, W N

    1976-01-01

    Repeated plasm exchanges were performed in a 44-year-old man with Goodpasture syndrome, also treated with cyclophosphamide and prednisone. Improvement was observed within 3 weeks of starting the protocol, and by the 76th week, endogenous creatinine clearance had increased from 30 to 56 ml/min/1.73 M2 and serum albumin from 2.7 to 3.7 g/dl. Prior treatment with immunosuppressive drugs had not significantly influenced circulating antibody levels. But sustained suppression of antibody was achieved after the plasma exchanges were begun, suggesting that physical removal of circulating antibody combined with antiproliferative drug treatment may be a useful way to control undesirable humoral immune responses. PMID:949874

  13. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation. [X-ray

    Energy Technology Data Exchange (ETDEWEB)

    Hoogenhout, J. (St. Radbond Academic Hospital, Nijmegen, Netherlands); Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  14. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.; de Jong, J.; Kal, H.B.; van Munster, P.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  15. Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation.

    Science.gov (United States)

    Lin, Chien-Jung; Vader, Justin M; Slade, Michael; DiPersio, John F; Westervelt, Peter; Romee, Rizwan

    2017-05-15

    The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen-matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy-based HCT. A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model. Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non-PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy. The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy-based HCT. Cancer 2017;123:1800-1809. © 2017 American Cancer Society. © 2017 American Cancer

  16. Immunomodulating Effect of Cyclophosphamide on the Mice Infected with Candida albicans

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    aziz japoni

    2014-03-01

    Full Text Available Background & Objectives: Cyclophosphamide is an alkylating agent that stops the replication of DNA, which is used to treat various types of cancer and some autoimmune disorders. This study was aimed at then evaluating the immunomodulating effect of cyclophosphamide (Cy on the immune system of vaccinated and non-vaccinated mice.Materials & Methods: The  study was performed on three groups of mice consisting of vaccinated, non-vaccinated and control groups. Vaccination was carried out by three separated courses of C. albicans injection intraperitoneally.  Then,  the  vaccinated group  received Cy  on  day  zero  and  were  challenged  with  lethal  doses of  C. albicans  on  days  zero, one, 3, 6 and 12 post-Cy injection. Non-vaccinated group received Cy on day zero and similar to vaccinated ones were challenged with lethal doses of the organism. The control groups received  just  Cy  on  day  zero  and  were  sacrificed  on days  post-Cy injection. Then, the hemogram and the spleen and the renal tissues were studied microscopically and macroscopically.Results: In the vaccinated group, an increase in survival time, the number of polymorphonuclear and the significant hyperplasia in the white pulp on days 6 and 12 post-Cy injection were noticed. In non-vaccinated ones, these factors had significant decrease on days 1 and 3. Conclusion: It is concluded that the hyperplasia in the white pulp of spleen and an increasing in peripheral polymorphonuclear due to the selective effects of Cy could effectively protect the animal against C. albicans infection.

  17. Chemoprotective effect of Crataegus monogyna aqueous extract against cyclophosphamide-induced reproductive toxicity

    Directory of Open Access Journals (Sweden)

    Ali Shalizar Jalali

    2011-11-01

    Full Text Available AbstractCyclophosphamide (CP is extensively used as an antineoplastic agent for treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity in humans and experimental animals. Crataegus monogyna is one of the oldest medicinal plant has been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 mL saline kg-1 per day for 28 days by oral gavages. One of the groups received Crataegus monogyna aqueous extract at a dose of 20 mg kg-1 per day orally four hours after cyclophosphamide administration. A vehicle-treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body and organ weights and spermatogenic activities as well as many histological alterations. CP treatment also caused a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK and SGOT were observed in CP-treated rats. Notably, Crataegus coadministration caused a partial recovery in above-mentioned parameters. These findings indicated that Crataegus might be partially protective against CP-induced reproductive toxicity.

  18. Role of the KATP channel in the protective effect of nicorandil on cyclophosphamide-induced lung and testicular toxicity in rats

    OpenAIRE

    Ahmed, Lamiaa A.; El-Maraghy, Shohda A.; Rizk, Sherine M.

    2015-01-01

    This study is the first to investigate the role of the KATP channel in the possible protection mediated by nicorandil against cyclophosphamide-induced lung and testicular toxicity in rats. Animals received cyclophosphamide (150 mg/kg/day, i.p.) for 2 consecutive days and then were untreated for the following 5 days. Nicorandil (3 mg/kg/day, p.o.) was administered starting from the day of cyclophosphamide injection with or without glibenclamide (5 mg/kg/day, p.o.). Nicorandil administration si...

  19. Targeting Protein Kinase CK2: Evaluating CX-4945 Potential for GL261 Glioblastoma Therapy in Immunocompetent Mice

    Directory of Open Access Journals (Sweden)

    Laura Ferrer-Font

    2017-02-01

    Full Text Available Glioblastoma (GBM causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2 contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro. CX-4945 was found to decrease CK2 activity and Akt(S129 phosphorylation in GL261 cells. Longitudinal in vivo studies with CX-4945 alone or in combination with TMZ were performed in tumour-bearing mice. Increase in survival (p < 0.05 was found with combined CX-4945 and TMZ metronomic treatment (54.7 ± 11.9 days, n = 6 when compared to individual metronomic treatments (CX-4945: 24.5 ± 2.0 and TMZ: 38.7 ± 2.7, n = 6 and controls (22.5 ± 1.2, n = 6. Despite this, CX-4945 did not improve mice outcome when administered on every/alternate days, either alone or in combination with 3-cycle TMZ. The highest survival rate was obtained with the metronomic combined TMZ+CX-4945 every 6 days, pointing to the participation of the immune system or other ancillary mechanism in therapy response.

  20. Targeting Protein Kinase CK2: Evaluating CX-4945 Potential for GL261 Glioblastoma Therapy in Immunocompetent Mice

    Science.gov (United States)

    Ferrer-Font, Laura; Villamañan, Lucia; Arias-Ramos, Nuria; Vilardell, Jordi; Plana, Maria; Ruzzene, Maria; Pinna, Lorenzo A.; Itarte, Emilio; Arús, Carles; Candiota, Ana Paula

    2017-01-01

    Glioblastoma (GBM) causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2) contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s) could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro. CX-4945 was found to decrease CK2 activity and Akt(S129) phosphorylation in GL261 cells. Longitudinal in vivo studies with CX-4945 alone or in combination with TMZ were performed in tumour-bearing mice. Increase in survival (p < 0.05) was found with combined CX-4945 and TMZ metronomic treatment (54.7 ± 11.9 days, n = 6) when compared to individual metronomic treatments (CX-4945: 24.5 ± 2.0 and TMZ: 38.7 ± 2.7, n = 6) and controls (22.5 ± 1.2, n = 6). Despite this, CX-4945 did not improve mice outcome when administered on every/alternate days, either alone or in combination with 3-cycle TMZ. The highest survival rate was obtained with the metronomic combined TMZ+CX-4945 every 6 days, pointing to the participation of the immune system or other ancillary mechanism in therapy response. PMID:28208677

  1. Continuous infusion cyclophosphamide and low-dose total body irradiation is a safe and effective conditioning regimen for autologous transplant in multiple myeloma.

    Science.gov (United States)

    Byrne, M; Wingard, J R; Moreb, J S

    2013-11-01

    We present the results of a novel conditioning regimen in multiple myeloma (MM) patients undergoing tandem autologous stem cell transplant (ASCT). MM patients were enrolled in a prospective phase II clinical trial. After initial ASCT, disease response was assessed by day +100. Patients achieving very good partial remission (VGPR) were offered maintenance therapy. If patients achieved VGPR, they were offered a second ASCT using continuous intravenous cyclophosphamide (CICy) 6 g/m(2) over 4 days and low-dose total body irradiation (ldTBI) 600 rads over 2 days. Total body irradiation was replaced by melphalan 140 mg/m(2) if patients had received prior radiation. Twenty-one patients received tandem ASCT. Three patients received CICy and melphalan. Median duration of neutropenia with CICy/ldTBI was 11 days. Fifteen patients (71.4%) developed febrile neutropenia while grade 1 to 2 diarrhea was the next most common adverse event (42.9%). There was no treatment-related mortality. Four patients had entered complete remission (19%) and 6 achieved VGPR (28.6%). In conclusion, this conditioning regimen is safe and effective and may be useful in patients who do not benefit from first ASCT using more traditional conditioning regimen.

  2. Safety and efficacy of total body irradiation, cyclophosphamide, and cytarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Mori, Takehiko; Aisa, Yoshinobu; Kato, Jun; Yamane, Akiko; Nakazato, Tomonori; Shigematsu, Naoyuki; Okamoto, Shinichiro

    2012-04-01

    Disease relapse still greatly interferes with the success of allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL). This study retrospectively evaluated the long-term safety and efficacy of a conditioning regimen consisting of total body irradiation (TBI; 12 Gy), cyclophosphamide (CY; 60 mg kg(-1) , two doses), and high-dose cytarabine (Ara-C; 2 g m(-2) ; four doses) for patients with ALL. Fifty-five patients (median age: 31-years old) were evaluated. Stem cells were from human leukocyte antigen-identical siblings in 22 patients and from alternative donors in 33. There were no cases of early death before engraftment, and 100-day transplant-related mortality was 7.3%. With a median follow-up period of 9.6 years, 5-year overall and disease-free survival were 63.2% (95% CI: 46.5-79.9%) and 63.6% (95% CI: 47.1-80.1%) in patients with complete remission, respectively, both of which were significantly higher than the values of 27.3% (95% CI: 8.7-46.0%) and 22.7% (95% CI: 5.3-40.1%) for patients in advanced stages (P < 0.01). These results suggest that TBI and CY (TBI-CY) plus Ara-C could be a feasible and effective conditioning regimen for adult patients with ALL both in remission and in advanced stages, and a future study to compare this combination therapy with TBI-CY is required.

  3. Efficacy of continuous low-dose cyclophosphamide and prednisone regimen in refractory multiple myeloma patients with severe heart failure%持续口服小剂量环磷酰胺联合泼尼松治疗复发/难治性多发性骨髓瘤伴严重心功能不全患者疗效观察

    Institute of Scientific and Technical Information of China (English)

    周帆; 韦苇; 凌晨晖; 郭列平; 石昊天; 李璐; 陈小玲; 侯健

    2015-01-01

    目的 观察小剂量环磷酰胺联合泼尼松持续口服治疗复发/难治性多发性骨髓瘤(MM)伴严重心功能不全患者的临床疗效、安全性及心功能改善情况.方法 选择75例MM伴心功能不全患者,给予环磷酰胺片(50 mg/d)联合泼尼松片(15 mg/d)进行小剂量化疗.结果 75例患者中,失访2例,在可评估的73例患者中总有效率为64.4%,其中完全缓解(CR)2例(2.7%),很好的部分缓解(VGPR)4例(5.5%),部分缓解(PR)24例(32.9%).中位生存时间为12(1~70)个月,中位治疗起效时间为90(16~120)d,中位无进展生存时间为12(1~60)个月.与治疗前比较,临床有效组患者血清B型脑钠肽下降[(906.4±104.8) ng/L对(336.6±30.3)ng/L,P<0.01].患者常见的不良反应为骨髓抑制(32/73,43.8%)、感染(26/73,35.6%)和Cushing综合征(7/73,9.6%),一般可耐受或经对症处理后可缓解.结论 小剂量环磷酰胺联合泼尼松持续口服治疗复发/难治性MM伴严重心功能不全患者可取得较好的疗效,并能改善患者心功能,具有良好的安全性.%Objective To observe treatment response,survival,safety and the improvement of ECOG in patients with refractory multiple myeloma (MM) with serious heart failure after the administration of continuous low-dose of cyclophosphamide combined with prednisone (CP).Methods From January 2005 to September 2013,a total of 75 patients were treated by metronomic chemotherapy with continuous low-dose cyclophosphamide (50 mg/d) and prednisone (15 mg/d).Results Among the 75 patients,2 were lost for follow-up.In the 73 available patients,the overall response was 64.4%,including 2 patients (2.7%) with complete remission (CR),4 cases (5.5%) very good partial remission (VGPR),and 24 patients (32.9%) partial remission (PR).The median survival was 12 months (1-70 months) with a median onset time of 90 days (16-120) and a median progressive freedom survival of 12 months (1-60).The level of B-type natriuretic

  4. Use of cultured rat embryos to evaluate the teratogenic activity of serum: cadmium and cyclophosphamide. [Serum-based culture media for growing rat embryos is used to determine the teratogenicity of cadmium and cyclophosphamide

    Energy Technology Data Exchange (ETDEWEB)

    Klein, N. W.; Vogler, M. A.; Chatot, C. L.; Pierro, L. J.

    1979-01-01

    Head fold stage rat embryos were cultured for 48 hrs in vitro on serum taken at various intervals from rats that had been injected ip with either cadmium or cyclophosphamide. Their response was compared to that of embryos cultured for the same period on control serum to which these substances were added directly. One and 4 hr sera from cadmium injected rats (2.13 mg Cd/sup + +//kg) were lethal. Eight hr serum allowed survival but embryos were exencephalic and contained reduced amounts of protein and DNA. The response to direct cadmium was characteristically different and was related to dosage and the extent to which zero-time embryos had progressed through the head fold stage. At 1.6 ..mu..M, Cd/sup + +/-susceptible embryos were hemorrhagic but not exencephalic. One hr serum from rats given cyclophosphamide (180 mg/kg) was lethal. On 4 hr serum, embryos survived but were exencephalic and contained less protein and DNA than controls. Embryos were resistant to direct cyclophosphamide up to 800 ..mu..g per ml of medium. At this concentration, embryos appeared morphologically normal but contained reduced amounts of protein.

  5. Chemotherapy of acute leukemia: a comparison of vincristine, cytarabine, and prednisone alone and in combination with cyclophosphamide or daunorubicin.

    Science.gov (United States)

    Coltman, C A; Bodey, G P; Hewlett, J S; Haut, A; Bickers, J; Balcerzak, S P; Costanzi, J J; Freireich, E J; McCredie, K B; Groppe, C; Smith, T L; Gehan, E A

    1978-09-01

    Adults (274) with acute leukemia (AML) were randomly assigned to one of three treatment regimens: vincristine, prednisone, cytarabine--(1) 100 mg/sq m/day with cyclophosphamide (COAP); (2) 100 mg/sq m/day with daunorubicin (DOAP); and 200 mg/sq m/day (OAP). Cytarabine was infused continuously for five days. Patients entering complete remission randomly received maintenance treatment with COAP or OAP. For 197 previously untreated AML patients given COAP, DOAP, or OAP, remission rates were 37%, 35%, and 43%, respectively; median lengths, 40, 45, and 90 weeks; median survival, 7, 11, and 8 weeks. No statistically significant difference was found among treatments. Therefore, adding cyclophosphamide or daunorubicin, or using the COAP regimen with continuously infused cytarabine, produced no significant improvement over previously reported regimens. There was no significant difference in remission lengths in previously untreated AML patients maintained on OAP (median 81 weeks) or COAP (median 65 weeks).

  6. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Merchant, Michael L. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Division of Nephrology, Department of Medicine, University of Louisville, Louisville, KY 40292 (United States); Prough, Russell A. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States); Williams, Jessica D. [University of Cincinnati College of Medicine, Internal Medicine, Cincinnati, OH 45267 (United States); Prabhu, Sumanth D. [Division of Cardiovascular Disease, University of Alabama-Birmingham, Birmingham, AL 35294 (United States); Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States)

    2015-06-01

    High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

  7. Protective effect of methanolic extracts of Thymus vulgaris L. against cyclophosphamide-induced DNA damage in mouse bone marrow cells using the micronucleus test

    Directory of Open Access Journals (Sweden)

    Abbas Salmani

    2015-12-01

    Full Text Available Cyclophosphamide is a chemo-therapeutic agent used in the treatment of various cancers and autoimmune diseases. This composition has cytotoxic and clastogenic properties. The purpose of this study was to evaluate the protective effect of methanol extracts of Thymus vulgaris L. against DNA damage induced by cyclophosphamide in mouse bone marrow cells by the micronucleus test. The extract concentrations of 375, 750, 1500 mg/kg were injected intraperitoneally (Ip into mice for 7 consecutive days. One hour after the last injection, cyclophosphamide 50 mg/kg Ip was injected. 24 hours after cyclophosphamide injection, the animals were killed and the samples of bone marrow were prepared and stained using the standard methods. For each sample, 1000 cells of polychromatic erythrocytes (PCE and the same number of normochromatic erythrocyte (NCE and the cells containing their micronucleus were counted. Cyclophosphamide increased the frequency of micronuclei polychromatic erythrocytes (MnPCE and decreased cell proliferation (PCE/PCE+NCE. All doses of extracts significantly reduced the micronucleus frequency ratio (P<0.05. The cells proliferation ratio (PCE/PCE+NCE was also increased. The best effect in reducing the micronucleus frequency was at 1500 mg/kg dosage. Thymus extract is able to reduce the clastogenic and cytotoxic effects of cyclophosphamide, due to its antioxidant properties, playing a protective role.

  8. Effect of Hydro Alcoholic Ginger Extracts on the Body Weight, Testis Weight and Spermatogenesis in Male Rats Undergoing Chemotherapy with Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    E Sharifi

    2010-03-01

    Full Text Available Introduction: Cyclophosphamide is used as an anti cancer medicine in chemotherapy. This is an alkalizing medicine and causes the binding of DNA strands, breaking of DNA and control of protein synthesis and RNA. The side effects of this medicine include lack of appetite, nausea, reduction in activity of sexual lymph nodes, causing amenorrhea, azoospermia and oligospermia. Ginger includes many compounds, some of which are shogaols, gingerols, pyrogallols and sesquiterpenes. Ginger has anti nauseating, anti cancer, anti oxidant effects and eliminates free radicals. This medicine is used along with cyclophosphamide to reduce its destructive side effects in the body. Methods: For 21 days, the rats were fed with ginger and cyclophosphamide. After 21 days, the animals were weighed and rendered unconscious. Their testes were removed and tissue samples were provided from their testes. Results: The results showed that cyclophosphamide alone reduces body weight, testes weight and spermatogenesis as compared to the control group. In other experimental groups that were fed with ginger and cyclophosphamide, increased dosage of ginger increased the body weight, the testes weight and spermatogenesis in comparison to the other experimental groups. Conclusion: It seems that compounds present in ginger are anti tumoral and control the production of active metabolites. Therefore, if administered together with Cyclophosphamide, it can be useful and effective in patients undergoing chemotherapy.

  9. Age, anti-müllerian hormone, antral follicles count to predict amenorrhea or oligomenorrhea after chemotherapy with cyclophosphamide

    OpenAIRE

    2015-01-01

    Background A cohort study was performed to identify ovarian reserve markers (ORM) that predicts amenorrhea or oligomenorrhea 6 months after cyclophosphamide CTX in women with breast cancer. Methods 52 eumenorrheic patients with breast cancer were enrolled. FSH, anti-Müllerian hormone (AMH), antral follicles count (AFC) were measured before and 6 months after CTX. A logistic regression for independent samples and determination of the ROC curve were performed. Results The age of 32 years presen...

  10. High-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone for remission induction in refractory adult acute leukemia.

    Science.gov (United States)

    Guthrie, T H

    1987-04-01

    Fifteen consecutive patients with refractory adult acute leukemia (RAAL) were treated with a combination of high-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone (Hi-COAP). The initial nine patients received cyclophosphamide 350 mg/m2 as a 24-hour intravenous (IV) infusion over 5 days; cytarabine, 100 mg/m2 IV bolus every 12 hours for ten doses; vincristine, 2.0 mg IV bolus on day 1; and prednisone, 100 mg orally for 7 days. The last six patients had the cyclophosphamide infusion lengthened to 7 days, and the cytarabine increased to 14 doses. All patients were evaluable for toxicity and response. Seven patients (47%) obtained a complete remission and six patients (40%) a partial remission. Median duration of all remissions has been 7.0 months with a range of 1 to 32 months. Toxicity has been limited to primarily myelosuppression with no hemorrhagic cystitis, central nervous system (CNS), hepatic, or pulmonary toxicity noted. Gastrointestinal toxicity was mild, with no effect on nutritional status noted. Median duration of complete responders was 8.5 months. Thus, Hi-COAP demonstrates promising efficacy with minimal toxicity in RAAL and warrants further exploration in multiinstitutional trials.

  11. Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis.

    Science.gov (United States)

    Okinami, Takeshi; Imamura, Masaaki; Nishikawa, Nobuyuki; Negoro, Hiromitsu; Sugino, Yoshio; Yoshimura, Koji; Kanematsu, Akihiro; Hashitani, Hikaru; Ogawa, Osamu

    2014-01-01

    Lower urinary tract symptoms (LUTS) include storage, voiding and post-micturition symptoms, featuring many urological diseases. Storage symptoms are the most frequent among these and associated with overactive bladder and non-bacterial bladder inflammation such as interstitial cystitis/bladder pain syndrome (IC/BPS). Gap junction, a key regulator of hyperactive conditions in the bladder, has been reported to be involved in pathological bladder inflammation. Here we report involvement of gap junction in the etiology of storage symptoms in bladder inflammation. In this study, cyclophosphamide-induced cystitis was adapted as a model of bladder inflammation. Cyclophosphamide-treated mice showed typical storage symptoms including increased urinary frequency and reduced bladder capacity, with concurrent up-regulation of connexin 43 (GJA1), one of the major gap junction proteins in the bladder. In isometric tension study, bladder smooth muscle strips taken from the treated mice showed more pronounced spontaneous contraction than controls, which was attenuated by carbenoxolone, a gap junction inhibitor. In voiding behavior studies, the storage symptoms in the treated mice characterized by frequent voiding were alleviated by 18α-glycyrrhetinic acid, another gap junction inhibitor. These results demonstrate that cyclophosphamide-induced mouse model of cystitis shows clinical storage symptoms related with bladder inflammation and that gap junction in the bladder may be a key molecule of these storage symptoms. Therefore, gap junction in the bladder might be an alternative therapeutic target for storage symptoms in bladder inflammation.

  12. Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis.

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    Takeshi Okinami

    Full Text Available Lower urinary tract symptoms (LUTS include storage, voiding and post-micturition symptoms, featuring many urological diseases. Storage symptoms are the most frequent among these and associated with overactive bladder and non-bacterial bladder inflammation such as interstitial cystitis/bladder pain syndrome (IC/BPS. Gap junction, a key regulator of hyperactive conditions in the bladder, has been reported to be involved in pathological bladder inflammation. Here we report involvement of gap junction in the etiology of storage symptoms in bladder inflammation. In this study, cyclophosphamide-induced cystitis was adapted as a model of bladder inflammation. Cyclophosphamide-treated mice showed typical storage symptoms including increased urinary frequency and reduced bladder capacity, with concurrent up-regulation of connexin 43 (GJA1, one of the major gap junction proteins in the bladder. In isometric tension study, bladder smooth muscle strips taken from the treated mice showed more pronounced spontaneous contraction than controls, which was attenuated by carbenoxolone, a gap junction inhibitor. In voiding behavior studies, the storage symptoms in the treated mice characterized by frequent voiding were alleviated by 18α-glycyrrhetinic acid, another gap junction inhibitor. These results demonstrate that cyclophosphamide-induced mouse model of cystitis shows clinical storage symptoms related with bladder inflammation and that gap junction in the bladder may be a key molecule of these storage symptoms. Therefore, gap junction in the bladder might be an alternative therapeutic target for storage symptoms in bladder inflammation.

  13. The effects of cyclophosphamide on neurotransmission in the urinary bladder of Suncus murinus, the house musk shrew.

    Science.gov (United States)

    Mok, M H; Knight, G E; Andrews, P L; Hoyle, C H; Burnstock, G

    2000-05-12

    This study has shown that cyclophosphamide treatment of the insectivore Suncus murinus, causes a down regulation in both muscarinic and P2X receptors, together with a reduced responsiveness to exogenous histamine (0.3 mM) in the urinary bladder. Electrical field stimulation (70 V, 0.3 ms, 0.5-16 Hz, 10 s every 5 min) of bladders from both control and cyclophosphamide-treated animals showed identical responses. Since post-junctional alterations have been revealed by the reduced responsiveness to exogenous carbachol (0.1 microM-3 mM) and beta,gamma-methylene ATP (0.3-300 microM), it would appear that in the bladders of cyclophosphamide-treated animals there is also a pre-junctional effect, increased transmitter release compensating for the down regulation of the receptors. As the pattern of neurotransmission of the bladder of suncus more closely resembles that of human detrusor than other commonly studied laboratory animals, this insectivore appears to be a useful animal model for the study of bladder neurotransmission in pathophysiological conditions.

  14. Music-supported motor training after stroke reveals no superiority of synchronisation in group therapy

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    Floris Tijmen Van Vugt

    2014-05-01

    Full Text Available Background. Music-supported therapy has been shown to be an effective tool for rehabilitation of motor deficits after stroke. A unique feature of music performance is that it is inherently social: music can be played together in synchrony.Aim. The present study explored the potential of synchronised music playing during therapy, asking whether synchronised playing could improve fine motor rehabilitation and mood.Method. Twenty-eight patients in neurological early rehabilitation after stroke with no previous musical background were included. Patients learned to play simple finger exercises and familiar children’s songs on the piano for ten sessions of half an hour. Patients first received three individual therapy sessions and then continued in pairs. The patient pairs were divided into two groups. Patients in one group played synchronously (together group whereas the patients in the other group played one after the other (in-turn group. To assess fine motor skill recovery the patients performed standard clinical tests such as the nine-hole-pegboard test (9HPT and index finger-tapping speed and regularity, and metronome-paced finger tapping. Patients' mood was established using the Profile of Mood States (POMS.Results. Both groups showed improvements in fine motor control. In metronome-paced finger tapping, patients in both groups improved significantly. Mood tests revealed reductions in depression and fatigue in both groups. During therapy, patients in the in-turn group rated their partner as more sympathetic than the together-group in a visual-analogue scale.Conclusions. Our results suggest that music-supported stroke rehabilitation can improve fine motor control and mood not only individually but also in patient pairs. Patients who were playing in turn rather than simultaneously tended to reveal greater improvement in fine motor skill. We speculate that patients in the former group may benefit from the opportunity to learn from observation.

  15. Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide

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    Murlas, C.; Roum, J.H.

    1985-05-01

    The effects of cyclophosphamide and cortisone acetate treatment on O/sub 3/-induced changes in airway mucosal morphology and bronchial reactivity were assessed in guinea pigs. Animals in groups of four were studied at 2 or 6 h after O/sub 3/ (3.0 ppm, 2 h) and in one control group. Reactivity was determined by measuring specific airway resistance during intravenous acetylcholine infusion in intact, unanesthetized, spontaneously breathing animals. After testing, tracheal tissue was obtained from all animals for light microscopic examination. Another group of 10 drug-treated and 10 normal animals were tested at 2 h, 6 h, 1 day, and 4 days after O/sub 3/. Drug treatment resulted in substantial decreases in both circulating and airway mucosal granulocytes. Two hours after O/sub 3/, a marked decrease in airway mucosal goblet cells as well as ciliated cell damage occurred in both normal and treated animals. However, only in normal animals did neutrophilic infiltration develop thereafter. Nonetheless, hyperreactivity postozone occurred and progressed similarly in both groups. Our results indicate that acute O/sub 3/-induced bronchial hyperreactivity at 2 h is associated with signs of airway mucosal injury but appears independent of granulocyte changes. Airway neutrophilic infiltration and eosinophil depletion seem to be consequences of mucosal injury from O/sub 3/ and not causes of the bronchial hyperreactivity that results.

  16. Renoprotective effect of Mangifera indica polysaccharides and silymarin against cyclophosphamide toxicity in rats

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    Ahmed I. Amien

    2015-10-01

    Full Text Available The present study aims to evaluate the possible protective role of polysaccharides extracted from the Egyptian mango Mangifera indica L. (MPS and silymarin against cyclophosphamide (CP nephrotoxicity in male albino rats. Male rats were randomly divided into, control group (administered distilled water orally for 10 days and MPS (500, 1000 mg/kg, p.o. and/or silymarin (150 mg/kg, p.o. treated groups for 10 days. In the last 5 days of treatment rats were administered CP (150 mg/kg, i.p. The MPS revealed significant prophylactic effect against kidney injury induced by CP as demonstrated by enhancement of the kidney function via decreasing serum creatinine, urea and uric acid. Treatment of rats with MPS extract and/or silymarin significantly increased the level of reduced glutathione (GSH and superoxide dismutase (SOD activity while decreased the level of total malondialdehyde (MDA and glutathione-S-transferase (GST. Also, histopathological examinations confirmed the protective efficacy of MPS and/or silymarin against CP nephrotoxicity. In conclusion, the obtained results of the present study support the protective antioxidant role of MPS and/or silymarin against CP-induced kidney disorder in rats.

  17. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study.

    Science.gov (United States)

    Bringhen, Sara; Petrucci, Maria Teresa; Larocca, Alessandra; Conticello, Concetta; Rossi, Davide; Magarotto, Valeria; Musto, Pellegrino; Boccadifuoco, Luana; Offidani, Massimo; Omedé, Paola; Gentilini, Fabiana; Ciccone, Giovannino; Benevolo, Giulia; Genuardi, Mariella; Montefusco, Vittorio; Oliva, Stefania; Caravita, Tommaso; Tacchetti, Paola; Boccadoro, Mario; Sonneveld, Pieter; Palumbo, Antonio

    2014-07-03

    This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) ≥65 years of age or who were ineligible for autologous stem cell transplantation. Patients (N = 58) received CCyd for up to 9 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 76% and 87%, respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued treatment because of adverse events, and 21% of patients required carfilzomib dose reductions. In summary, results showed high complete response rates and a good safety profile. This trial was registered at clinicaltrials.gov as #NCT01346787.

  18. Chemoprotective effects of Ganoderma atrum polysaccharide in cyclophosphamide-induced mice.

    Science.gov (United States)

    Yu, Qiang; Nie, Shao-Ping; Wang, Jun-Qiao; Liu, Xiao-Zhen; Yin, Peng-Fei; Huang, Dan-Fei; Li, Wen-Juan; Gong, De-Ming; Xie, Ming-Yong

    2014-03-01

    In this study, the chemoprotective effects of Ganoderma atrum polysaccharide (PSG-1) in cyclophosphamide (Cy) treated mice were investigated. In Cy-treated mice, PSG-1 treatment accelerated recovery dose-dependently of peripheral red blood cells, white blood cells and platelets, enhanced splenic natural killer cell activity and cytotoxic T lymphocyte activity. In addition, PSG-1 elevated CD4(+) T lymphocyte counts as well as the CD4(+)/CD8(+) ratio dose-dependently. Furthermore, PSG-1 restored the levels of IL-2, INF-γ, IL-10, IgA, IgM and IgG, as well as hemolysin in the sera. Finally, PSG-1 can also significantly increase the total antioxidant capacity, activities of superoxidase dismutase, catalase and glutathione peroxidase, and decrease the malondialdehyde level in vivo. These findings indicate that PSG-1 plays an important role in the protection against myelosuppression and immunosuppression and oxidative stress in Cy-treated mice and could be a potential immunomodulatory agent.

  19. Blueberry Anthocyanins-Enriched Extracts Attenuate Cyclophosphamide-Induced Cardiac Injury.

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    Yunen Liu

    Full Text Available We sought to explore the effect of blueberry anthocyanins-enriched extracts (BAE on cyclophosphamide (CTX-induced cardiac injury. The rats were divided randomly into five groups including normal control, CTX 100 mg/kg, BAE 80mg/kg, CTX+BAE 20mg/kg and CTX+BAE 80mg/kg groups. The rats in the three BAE-treated groups were administered BAE for four weeks. Seven days after BAE administration, rats in CTX group and two BAE-treated groups were intraperitoneally injected with a single dose of 100 mg/kg CTX. Cardiac injury was assessed using physiological parameters, Echo, morphological staining, real-time PCR and western blot. In addition, cardiotoxicity indices, inflammatory cytokines expression and oxidative stress markers were also detected. Four weeks 20mg/kg and 80mg/kg dose of BAE treatment following CTX exposure attenuated mean arterial blood pressure, heart rate and activities of heart enzymes, improved cardiac dysfunction, left ventricular hypertrophy and fibrosis. Importantly, BAE also attenuated CTX-induced LV leukocyte infiltration and inflammatory cytokines expression, ameliorated oxidative stress as well as cardiomyocyte apoptosis. In conclusion, BAE attenuated the CTX-induced cardiac injury and the protective mechanisms were related closely to the anti-inflammatory, antioxidant and anti-inflammatory characteristics of BAE.

  20. Oral cyclophosphamide improves pulmonary function in scleroderma patients with fibrosing alveolitis: experience in one centre.

    Science.gov (United States)

    Beretta, Lorenzo; Caronni, Monica; Raimondi, Massimo; Ponti, Alessandra; Viscuso, Tiziana; Origgi, Laura; Scorza, Raffaella

    2007-02-01

    Lung involvement constitutes nowadays the major cause of morbidity and mortality in scleroderma patients. Pulmonary fibrosis in systemic sclerosis (SSc) is thought to be the consequence of interstitial inflammation. Early diagnosis and treatment of active alveolitis is essential to prevent the deterioration of pulmonary function, improving outcome in SSc patients. The aim of the study was to investigate the effect of 1-year treatment with oral cyclophosphamide (CYC) on the evolution of interstitial lung disease in scleroderma patients with a diagnosis of active alveolitis. An open-label one-arm monocenteric study was conducted on 33 scleroderma patients with active alveolitis--defined as the presence of areas of 'ground-glass attenuation' on high-resolution computed tomography and a recent deterioration in lung function-treated with oral CYC 2 mg kg-1 day-1 for 1 year and medium-low dose steroids (prednisone 25 mg for 3 months and then tapered to 5 mg/day). Results showed that diffusing capacity for carbon monoxide (DLco) values remained stable after 6 months of treatment and significantly increased after 12 months (2.06+/-1.38, 2.21+/-1.62 and 2.39+/-1.64 mmol/min/kPa, at baseline/6/12 months, respectively; palveolitis, with beneficial effects lasting up to 1 year after interruption. The higher efficacy in those patients with an early pulmonary disease stage and a lower radiological grade underlies the importance of an early diagnosis and intervention.

  1. Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats.

    Science.gov (United States)

    Ince, Sinan; Kucukkurt, Ismail; Demirel, Hasan Huseyin; Acaroz, Damla Arslan; Akbel, Erten; Cigerci, Ibrahim Hakki

    2014-08-01

    The aim of the present study was to evaluate the possible protective effect of boron (B) on cyclophosphamide (CYC) induced oxidative stress in rats. Totally, thirty Wistar albino male rats were fed standard rodent diet and divided into 5 equal groups: physiological saline was given intraperitoneally (i.p.) to the control group (vehicle treated), to the second group only 75 mg kg(-1) CYC was given i.p. on the 14th d, and boron was administered (5, 10, and 20 mg kg(-1), i.p.) to the other groups for 14 d and CYC (75 mg kg(-1), i.p.) on the 14th d. CYC caused increase of malondialdehyde and decrease of glutathione levels, decrease of superoxide dismutase activities in erythrocyte and tissues, decrease of erythrocyte, heart, lung, and brain catalase, and plasma antioxidant activities. Also, CYC treatment caused to DNA damage in mononuclear leukocytes. Moreover, B exhibited protective action against the CYC-induced histopathological changes in tissues. However, treatment of B decreased severity of CYC-induced lipid peroxidation and genotoxicity on tissues. In conclusion, B has ameliorative effects against CYC-induced lipid peroxidation and genotoxicity by enhancing antioxidant defence mechanism in rat.

  2. Antigenotoxic effects of a polyherbal drug septilin against the genotoxicity of cyclophosphamide in mice

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    S. Shruthi

    2016-01-01

    Full Text Available Septilin (Spt is a polyherbal drug formulation from Himalaya Drug Company, consisting of extracts from different medicinal plants and minerals. In the traditional system of medicine, septilin is being used as immunomodulatory, antioxidant and anti-inflammatory agent. In the present study, the protective effects of septilin against the genotoxicity of cyclophosphamide (CP a widely used alkylating anticancer drug was evaluated by using in vivo micronucleus (MN and sperm shape abnormality assays in Swiss albino mice. CP administered intraperitoneally at a dose of 50 mg/kg b.w. was used as positive mutagen. Different doses of septilin viz., 125, 250 and 500 mg/kg b.w. was orally administered for 5 consecutive days. CP was administered intraperitoneally on 5th day. MN and sperm preparations were made after 24 h and 35 days respectively. CP induced significant MN in both bone marrow and peripheral blood cells and also a high frequency of abnormal sperms. In septilin supplemented animals, no significant induction of MN and abnormal sperms was recorded. In septilin supplemented groups, a dose dependent significant decrease in CP induced clastogenicity was observed. Thus the current in vivo study revealed the antigenotoxic effects of septilin against CP induced damage, in both somatic and germ cells of Swiss albino mice.

  3. Comparison of doxorubicin-cyclophosphamide with doxorubicin-dacarbazine for the adjuvant treatment of canine hemangiosarcoma.

    Science.gov (United States)

    Finotello, R; Stefanello, D; Zini, E; Marconato, L

    2017-03-01

    Canine hemangiosarcoma (HSA) is a neoplasm of vascular endothelial origin that has an aggressive biological behaviour, with less than 10% of dogs alive at 12-months postdiagnosis. Treatment of choice consists of surgery followed by adjuvant doxorubicin-based chemotherapy. We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). Twenty-seven dogs were enrolled; following staging work-up, 18 were treated with AC and 9 with ADTIC. Median TTM and survival time were longer for dogs treated with ADTIC compared with those receiving AC (>550 versus 112 days, P = 0.021 and >550 versus 142 days, P = 0.011, respectively). Both protocols were well tolerated, without need for dose reduction or increased interval between treatments. A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time. © 2015 John Wiley & Sons Ltd.

  4. Effect of melatonin on apoptosis, proliferation and differentiation of urothelial cells after cyclophosphamide treatment.

    Science.gov (United States)

    Zupancic, Dasa; Jezernik, Kristijan; Vidmar, Gaj

    2008-04-01

    Melatonin was recently shown to have protective effects against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) by diminishing bladder oxidative stress. HC is accompanied by destruction of the bladder urothelium and followed by apoptosis and rapid regeneration via proliferation and differentiation of urothelial cells, reaching complete restoration of normal urothelium in three weeks. Therefore, the effect of melatonin on apoptosis, proliferation and differentiation of urothelial cells, during destruction and regeneration of the urothelium three-weeks after a single dose CP treatment, was studied. F344 male rats were injected intraperitoneally with saline (control group) or melatonin (Mel group) or a single dose of CP (100 mg/kg; CP group) or melatonin (10 mg/kg) with CP (Mel + CP group). Melatonin co-treatment with CP significantly reduced apoptosis and increased proliferation of urothelial cells at day 1 and thus prevented extensive loss of cells from the urothelium. However, proliferation indices at days 4 and 7 after melatonin and CP co-treatment suddenly dropped and therefore the development of hyperplasia was prevented. Melatonin co-treatment with CP also resulted in earlier differentiation of superficial urothelial cells. Melatonin seems to have protective effect against CP-induced urothelial damage and a favorable impact on regeneration and restoration of normal urothelium, since it reduces the number of apoptotic and proliferating urothelial cells and results in their earlier differentiation.

  5. Melatonin prevents the development of hyperplastic urothelium induced by repeated doses of cyclophosphamide.

    Science.gov (United States)

    Zupancic, Dasa; Vidmar, Gaj; Jezernik, Kristijan

    2009-06-01

    Repeated cyclophosphamide (CP) chemotherapy increases the risk of developing bladder cancer, which could be due to the extremely rapid proliferation of urothelial cells observed in hyperplastic urothelium induced by CP treatment. We investigated the effect of melatonin on the development of urothelial hyperplasia induced by repeated CP treatment. Male ICR mice were injected with CP (150 mg/kg) or melatonin (10 mg/kg) with CP once a week for 3, 4 and 5 weeks. Transmission and scanning electron microscopy, immunohistochemistry and Western blot analysis were used to study the ultrastructure, apoptosis, proliferation and differentiation of urothelial cells. Repeated doses of CP caused the development of hyperplastic urothelium with up to ten cell layers and increased proliferation and apoptotic indices regarding Ki-67 and active caspase-3 immunohistochemistry, respectively. Scanning electron microscopy observations, cytokeratin and asymmetrical unit membrane immunohistochemistry and Western blot analysis showed a lower differentiation state of superficial urothelial cells. Melatonin co-treatment prevented the development of hyperplastic urothelium, statistically significantly decreased proliferation and apoptotic indices after four and five doses of CP and caused higher differentiation state of superficial urothelial cells.

  6. Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide

    Institute of Scientific and Technical Information of China (English)

    Yan JIANG; Jing ZHAO; Hui-jing QI; Xiao-lin LI; Shi-rong ZHANG; Daniel W.SONG; Chi-yang YU

    2013-01-01

    Busulfan/cyclophosphamide (Bu/Cy) conditioning regimen has been widely used to treat cancer patients,while their effects on major internal organs in females are not fully understood.We treated female mice with Bu/Cy,and examined the histopathology of major internal organs on Day 30 after the treatment.The results show that Bu/Cy treatment affected the ovaries most extensively,while it had less effect on the spleen,lungs,and kidneys,and no effect on the heart,liver,stomach,and pancreas.To better understand the effect of Bu/Cy on the ovaries,we counted follicles,and determined the levels of ovarian steroids.The Bu/Cy-treated mice showed a reduction of primordial and primary follicles (P<0.01) on Day 30 and a marked loss of follicles at all developmental stages (P<0.01) on Day 60.Plasma levels of estradiol and progesterone in Bu/Cy-treated mice decreased by 43.9% and 61.4%,respectively.Thus,there was a gradual process of follicle loss and low estradiol in Bu/Cy-treated mice; this is a profile similar to what is found in women with premature ovarian failure (POF).The Bu/Cy-treated mice may serve as a useful animal model to study the dynamics of follicle loss in women undergoing POF.

  7. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia

    Science.gov (United States)

    Parikh, Sameer A.; Keating, Michael J.; O'Brien, Susan; Wang, Xuemei; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Estrov, Zeev; Badoux, Xavier; Lerner, Susan

    2011-01-01

    Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) is associated with superior overall survival (OS) for patients with chronic lymphocytic leukemia (CLL). Alemtuzumab (A) was added to FCR (CFAR) in a phase 2 trial for high-risk untreated patients < 70 years with serum β-2 microglobulin (β2M) ≥ 4 mg/L. Sixty patients were enrolled; median age was 59 years (range, 42-69); 75% were male; median β2M was 5.1 mg/L (range, 4-11.6); and 51% were Rai III-IV. Complete remission (CR) was achieved in 70%, partial remission (PR) in 18%, nodular PR in 3%, for an overall response of 92%. Of 14 patients with 17p deletion, CR was achieved by 8 (57%). Of 57 BM samples evaluated by 3-color flow cytometry at the end of treatment, 41 (72%) were negative for residual disease. Grade 3-4 neutropenia and thrombocytopenia occurred with 33% and 13% courses, respectively. The median progression-free survival was 38 months and median OS was not reached. In conclusion, CFAR is an active frontline regimen for high-risk CLL. Response rates and survival are comparable with historic high-risk FCR-treated patients. CFAR may be a useful frontline regimen to achieve CR in patients with 17p deletion before allogeneic stem cell transplantation. PMID:21750315

  8. Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the Urothelium.

    Science.gov (United States)

    Hughes, Francis M; Corn, Alexa G; Nimmich, Andrew R; Pratt-Thomas, Jeffery D; Purves, J Todd

    2013-08-01

    Hemorrhagic cystitis (HC or bladder inflammation) affects a significant number of patients undergoing cyclophosphamide (CP) chemotherapy despite treatment with 2-mercaptoethane sulfonate (Mesna) to inactivate the metabolite acrolein. While the mechanism is unknown, there is clearly acrolein-independent damage to the urothelium. In this study we have explored the induction of apoptosis in the urothelium as a marker of damage and the mechanism underlying the acrolein-independent apoptosis. Apoptosis in urothelium (caspase-3/7 activity and Poly (ADP-ribosyl) polymerase (PARP) cleavage) was measured following CP administration (80 mg/kg). Sodium 2-mercaptoethane sulfonate (Mesna) was used to mask acrolein's effect. An IL-1β receptor antagonist and a cell-permeable caspase-1 inhibitor were used to assess the involvement of IL-1β and caspase-1, respectively. Two waves of apoptosis were detected following CP administration, one peaking at 2 h and a second at 48 h. The first wave was independent of acrolein. Caspase-1 was also active at 2 h and activation of caspase-3/7 was blocked by a caspase-1 inhibitor but not an IL-1β receptor antagonist suggesting the direct activation of caspase-3/7 by caspase-1 without the need for IL-1β as an intermediate. Our results indicate that CP initiates an early, acrolein-independent wave of apoptosis that results from direct cleavage of caspase-3/7 by caspase-1.

  9. Gonadal status following bone marrow transplantation with low dose busulfan-cyclophosphamide regimen

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    Mohsen Khosh niat Nikoo

    2006-02-01

    Full Text Available Background: Gonadal dysfunction is one of the short and long-term side effects following bone marrow transplantation (BMT. We assessed hypophyseal-gonadal axis after BMT by low dose busulfan-cyclophosphamide conditioning regimen (120 mg/kg. Methods: In this cohort study, we evaluated gonadal function in 48 patients (25 pubert males and 23 pubert females. Data were obtained by history, physical examination, LH, FSH, prolactin, estradiol (E2, progesterone, testosterone and semen analysis before BMT and in 6 and 12 months of post-BMT. Results: Gonadal axis in 16 male subjects (64% was normal before BMT and remained normal in 6 subjects (37% 12 months post BMT. In another 10 patients (63%, hypogonadism was started in 6 months post BMT. Spermatogenesis failure (31%, low level of testosterone (25% and spermatogenesis failure plus low level of testosterone in 12.5% were found. Gonadal axis in 20 female subjects (87% was normal before BMT, but remained normal only in 10% of subject until the end of the study. Other patients (90% had primary hypogonadism in 6 months of post BMT. Conclusion: There is a high prevalence of gonadal dysfunction following BMT in both adult sexes (especially in female patients. Therefore, regular gonadal assessment is recommended following BMT.

  10. Immune response against large tumors eradicated by treatment with cyclophosphamide and IL-12.

    Science.gov (United States)

    Tsung, K; Meko, J B; Tsung, Y L; Peplinski, G R; Norton, J A

    1998-02-01

    Previous studies have demonstrated eradication of small (4-8 mm) established murine MCA207 sarcomas by treatment with systemic IL-12. Analysis of the mechanism has revealed a cellular and molecular immune response at the tumor typical of a Th1 cell-mediated, macrophage-effected, delayed-type hypersensitivity (DTH) response. In the current study we investigate the immune response against long term established, large MCA207 tumors induced by combined treatment with IL-12 and cyclophosphamide (Cy), an agent known to potentiate the DTH response. Our results demonstrate that s.c. large MCA207 tumors (15-20 mm) that are refractory to treatment by either IL-12 or Cy alone can be completely eradicated by the combination of Cy and IL-12. IL-12 is apparently the only cytokine capable of mediating tumor eradication, and the effect is dependent on IFN-gamma. The contribution of Cy is probably due to immunopotentiation of DTH rather than to direct cytotoxicity to the tumor. The regression of these large tumors takes >4 wk and, in many cases, is self-sustained, in that little or no additional IL-12 is needed beyond the initial week of administration. Analysis of the cellular and molecular events at the tumor site suggests that the mechanism is a Th1-mediated antitumor immune response.

  11. Transplacental inhibitory effect of carrot juice on the clastogenicity of cyclophosphamide in mice

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    Gimmler-Luz Maria Clara

    1999-01-01

    Full Text Available Genetic damage during the prenatal period can provoke important neoplastic alterations and other diseases in postnatal life. Beta-carotene (ßC is considered to be one of the most important anticarcinogens in the diet and can protect mammalian cells against genotoxic events. As carrots are important dietary source of ßC, we decided to test the effect of fresh carrot juice (CaJ on cyclophosphamide (CP-induced genotoxicity in maternal and fetal erythropoietic tissues. The treatment with CaJ started on the 7th day of the pregnancy of BALB/c female mice. We observed, on the 16th gestational day, that this treatment did not modify the spontaneous frequency of micronucleated polychromatic erythrocytes (mPCE in the bone marrow of the females nor in the livers of their fetuses. The mPCE frequency observed 24 h after an intraperitoneal injection of CP (40 mg/kg on the 15th day was significantly lower in CaJ-pretreated pregnant female bone marrow and in the liver of their fetuses than those observed in the group treated with CP only. These results demonstrate the presence of natural anticlastogens in carrots.

  12. A European multicentre and open-label controlled randomized trial to evaluate the efficacy of Sequential treatment with TAcrolimus–Rituximab versus steroids plus cyclophosphamide in patients with primary MEmbranous Nephropathy: the STARMEN study

    Science.gov (United States)

    Rojas-Rivera, Jorge; Fernández-Juárez, Gema; Ortiz, Alberto; Hofstra, Julia; Gesualdo, Loreto; Tesar, Vladimir; Wetzels, Jack; Segarra, Alfons; Egido, Jesus; Praga, Manuel

    2015-01-01

    Background Patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome have a high risk of progression to end-stage renal disease. The Ponticelli protocol (steroids with alkylating agents) is the most effective immunosuppressive therapy for this condition, but it has severe adverse effects. Tacrolimus and rituximab have demonstrated efficacy for remission of nephrotic syndrome in MN with a safer profile. However, the published evidence is largely based on small or short-term observational studies, historical cohorts, comparisons with conservative therapy or clinical trials without appropriate control groups, and there is no head-to-head comparison with the Ponticelli protocol. Methods The STARMEN randomized clinical trial will compare the efficacy of sequential tacrolimus–rituximab therapy with a modified Ponticelli protocol (steroids plus cyclophosphamide). The trial will also evaluate the role of antibodies against the M-type phospholipase A2 receptor (anti-PLA2R) and other antibodies as markers of response to treatment and long-term prognosis. Results The trial has already started with 23 patients having been enrolled as of 1 April 2015, an estimated 21.7% of the estimated sample. PMID:26413273

  13. Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial

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    Brown, Jennifer R.; O’Brien, Susan; Kingsley, C. Daniel; Eradat, Herbert; Pagel, John M.; Lymp, James; Hirata, Jamie; Kipps, Thomas J.

    2015-01-01

    In this phase 1b study, obinutuzumab plus FC or B had acceptable safety, with infusion reactions the most common adverse event.Obinutuzumab plus FC or B showed promising clinical activity in the initial treatment of CLL, with no relapses to date.

  14. Effects of melatonin on DNA damage induced by cyclophosphamide in rats

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    Ferreira, S.G.; Peliciari-Garcia, R.A. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas I, Universidade de São Paulo, São Paulo, SP (Brazil); Takahashi-Hyodo, S.A. [Área de Ciências da Saúde, Universidade Braz Cubas, Mogi das Cruzes, SP (Brazil); Rodrigues, A.C. [Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil); Amaral, F.G. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas I, Universidade de São Paulo, São Paulo, SP (Brazil); Berra, C.M. [Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil); Bordin, S.; Curi, R.; Cipolla-Neto, J. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas I, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-03-08

    The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.

  15. Stem Cell Mobilization with G-CSF versus Cyclophosphamide plus G-CSF in Mexican Children

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    José Eugenio Vázquez Meraz

    2016-01-01

    Full Text Available Fifty-six aphaereses were performed in 23 pediatric patients with malignant hematological and solid tumors, following three different protocols for PBPC mobilization and distributed as follows: A: seventeen mobilized with 4 g/m2 of cyclophosphamide (CFA and 10 μg/kg/day of granulocyte colony stimulating factor (G-CSF, B: nineteen with CFA + G-CSF, and C: twenty only with G-CSF when the WBC count exceeded 10 × 109/L. The average number of MNC/kg body weight (BW/aphaeresis was 0.4 × 108 (0.1–1.4, 2.25 × 108 (0.56–6.28, and 1.02 × 108 (0.34–2.5 whereas the average number of CD34+ cells/kg BW/aphaeresis was 0.18 × 106/kg (0.09–0.34, 1.04 × 106 (0.19–9.3, and 0.59 × 106 (0.17–0.87 and the count of CFU/kg BW/aphaeresis was 1.11 × 105 (0.31–2.12, 1.16 × 105 (0.64–2.97, and 1.12 × 105 (0.3–6.63 in groups A, B, and C, respectively. The collection was better in group B versus group A (p=0.007 and p=0.05, resp. and in group C versus group A (p=0.08 and p=0.05, resp.. The collection of PBPCs was more effective in the group mobilized with CFM + G-CSF when the WBC exceeded 10 × 103/μL in terms of MNC and CD34+ cells and there was no toxicity of the chemotherapy.

  16. Speman®, A Proprietary Ayurvedic Formulation, Reverses Cyclophosphamide-Induced Oligospermia In Rats.

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    Mohd. Azeemuddin Mukram

    2013-04-01

    Full Text Available Background: This investigation was aimed to evaluate the effect of Speman®, a well known ayurvedic proprietary preparation, in an experimental model of cyclophosphamide-(CP induced oligospermia in rats.Materials and Methods: Thirty male rats were randomized in to five, equally-sized groups. Rats in group 1 served as a normal control; group 2 served as an untreated positive control; groups 3, 4, 5 received  Speman® granules  at doses of 300, 600, and 900mg/kg body weight p.o. respectively, once daily for 13 days. On day four, one hour after the respective treatment, oligospermia was induced by administering a single dose of CP (100mg/kg body weight p.o.  to all the groups except group1. At the end of the study period the rats were euthanised and accessory reproductive organs were weighed and subjected to histopathological examination. The semen samples were subject to enumeration of sperms.  Weight of the reproductive organs, histopathological examination of the tissues, and sperm count were the parameters studied to understand the effect of Speman® on rats with CP-induced oligospermia.Results: Changes that occurred due to the administration of CP at a dose of 100 mg/kg body weight were dose dependently reversed with Speman® at a dose of 300, 600, and 900 mg/kg body weight. There was a statistically significant increase in sperm count and the weight of the seminal vesicle, epididymis, and prostate.Conclusion: Findings of this investigation indicate that Speman® dose dependently reversed the CP-induced derangement of various parameters pertaining to the reproductive system.  This could explain the total beneficial actions of Speman® reported in several other clinical trials.

  17. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats.

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    Abraham, Premila; Isaac, Bina

    2011-07-01

    Nephrotoxicity is one of the adverse side effects of cyclophosphamide (CP) chemotherapy. In a recent study, we have demonstrated that oxidative stress and glutathione depletion play important roles in CP-induced renal damage. The aim of the study was to verify whether glutamine, the precursor for glutathione synthesis, prevents CP-induced oxidative stress and renal damage using a rat model. Adult male rats were administered a single dose of 150 mg/ kg body weight of CP intraperitoneally. The glutamine-pretreated rats were administered 1 gm/kg body weight of glutamine orally 2 h before the administration of CP. Vehicle/glutamine-treated rats served as controls. All the rats were killed 16 h after the dose of CP/vehicle. The kidneys were removed and used for light microscopic and biochemical studies. The markers of oxidative stress including malondialdehyde content, protein carbonyl content, protein thiol, reduced glutathione and myeloperoxidase activity, a marker of neutrophil infiltration, were measured in kidney homogenates. CP treatment-induced damage to kidney involved the glomeruli and the tubules. Pretreatment with glutamine reduced CP-induced glutathione depletion and increased myeloperoxidase activity. However, it did not prevent CP-induced lipid peroxidation, protein carbonylation and renal damage. The results of the present study suggest that glutamine pretreatment does not prevent CP-induced lipid peroxidation and renal damage, although it prevents CP-induced glutathione depletion and neutrophil infiltration significantly. It is suggested that mechanisms other than oxidative stress may also be involved and/or oxidative stress may be consequence and not the cause of CP induced renal damage.

  18. The protective effect of Moringa oleifera leaves against cyclophosphamide-induced urinary bladder toxicity in rats.

    Science.gov (United States)

    Taha, Nevine R; Amin, Hanan Ali; Sultan, Asrar A

    2015-02-01

    Cyclophosphamide (CP), an alkylating antineoplastic agent is widely used in the treatment of solid tumors and B-cell malignant disease. It is known to cause urinary bladder damage due to inducing oxidative stress. Moringa oleifera (Mof) is commonly known as drumstick tree. Moringa leaves have been reported to be a rich source of β-carotene, protein, vitamin C, calcium, and potassium. It acts as a good source of natural antioxidants; due to the presence of various types of antioxidant compounds such as ascorbic acid, flavonoids, phenolics and carotenoids. The aim of this work was to test the possible antioxidant protective effects of M. oleifera leaves against CP induced urinary bladder toxicity in rats. Female Wister albino rats were divided into 4 groups. Group I served as control, received orally normal saline, group II received a single dose CP 100mg/kg intraperitoneally, group III and VI both received orally hydroethanolic extract of Mof; 500 mg/kg and 1000 mg/kg respectively daily for a week, 1h before and 4h after CP administration. Rats were sacrificed 24h after CP injection. The bladder was removed, sectioned, and subjected to light, transition electron microscopic studies, and biochemical studies (measuring the parameter of lipid peroxidation; malondialdehyde along with the activities of the antioxidant enzyme reduced glutathione). The bladders of CP treated rats showed ulcered mucosa, edematous, hemorrhagic, and fibrotic submucosa by light microscopy. Ultrastructure observation showed; losing large areas of uroepithelium, extended intercellular gaps, junction complexes were affected as well as damage of mitochondria in the form of swelling and destruction of cristae. Biochemical analysis showed significant elevation of malondialdhyde, while reduced glutathione activity was significantly lowered. From the results obtained in this work, we can say that Moringa leaves play an important role in ameliorating and protecting the bladder from CP toxicity.

  19. Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

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    Paul B Comish

    Full Text Available Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1 mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2% and to 80% in the male offspring of L1 (control value 33%. These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i DNA damage is a common mechanism leading to induction of testicular cancer, ii increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

  20. Preserved learning and memory following 5-fluorouracil and cyclophosphamide treatment in rats.

    Science.gov (United States)

    Long, Jeffrey M; Lee, Garrick D; Kelley-Bell, Bennett; Spangler, Edward L; Perez, Evelyn J; Longo, Dan L; de Cabo, Rafael; Zou, Sige; Rapp, Peter R

    2011-11-01

    Some patients experience enduring cognitive impairment after cancer treatment, a condition termed "chemofog". Animal models allow assessment of chemotherapy effects on learning and memory per se, independent of changes due to cancer itself or associated health consequences such as depression. The present study examined the long-term learning and memory effects of a chemotherapy cocktail used widely in the treatment of breast cancer, consisting of 5-fluorouracil (5FU) and cyclophosphamide (CYP). Eighty 5-month old male F344 rats received contextual and cued fear conditioning before treatment with saline, or a low or high dose drug cocktail (50mg/kg CYP and 75 mg/kg 5FU, or 75 mg/kg CYP and 120 mg/kg 5FU, i.p., respectively) every 30 days for 2 months. After a 2-month, no-drug recovery, both long-term retention and new task acquisition in the water maze and 14-unit T-maze were assessed. Neither dose of the CYP/5FU cocktail impaired retrograde fear memory despite marked toxicity documented by enduring weight loss and 50% mortality at the higher dose. Acquisition in the water maze and Stone maze was also normal relative to controls in rats treated with CYP/5FU. The results contribute to a growing literature suggesting that learning and memory mediated by the hippocampus can be relatively resistant to chemotherapy. Future investigation may need to focus on assessments of processing speed, executive function and attention, and the possible interactive contribution of cancer itself and aging to the post-treatment development of cognitive impairment. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

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    Alexandra Audemard-Verger

    Full Text Available To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs in lupus nephritis (LN treated with cyclophosphamide (CYC. CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST.We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline.Most patients were women (84% and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR (OR = 5.01 95% CI [1.02-24.51] and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]. No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed.This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

  2. Distinct effects of mycophenolate mofetil and cyclophosphamide on renal fibrosis in NZBWF1/J mice.

    Science.gov (United States)

    Yung, Susan; Zhang, Qing; Chau, Mel K M; Chan, Tak Mao

    2015-01-01

    Progression to chronic renal failure varies between patients with lupus nephritis. We compared the effects of mycophenolate mofetil (MMF) and cyclophosphamide (CTX), on renal histology and cellular pathways of fibrosis in murine lupus nephritis. Female NZBWF1/J mice were randomized to treatment with vehicle, methylprednisolone (MP) alone, MMF + MP or CTX + MP for up to 12 weeks, and the effects on clinical parameters, renal histology, and fibrotic processes were investigated. Treatment with MMF + MP or CTX + MP both improved survival, renal function, and decreased anti-dsDNA antibody level and immune complex deposition in kidneys of mice with active nephritis. Vehicle-treated mice showed progressive increase in mesangial proliferation, inflammatory cell infiltration and renal tubular atrophy, associated with PKC-α activation, increased TGF-β1 expression and increased matrix protein deposition. MP treatment alone did not have any significant effect. MMF + MP or CTX + MP treatment for 12 weeks reduced these abnormalities. MMF + MP was more effective than CTX + MP in suppressing fibrotic mediators, histological fibrosis score and expression of TGF-β1, fibronectin and collagen I in the kidney. Results from in vitro experiments on human mesangial cells (HMC) showed that mycophenolic acid (MPA) was more effective than CTX in suppressing PKC-α activation and TGF-β1 secretion induced by human polyclonal anti-dsDNA antibodies. While both MPA and CTX decreased TGF-β1- and TNF-α-induced fibronectin synthesis, only MPA decreased IL-6 induced fibronectin synthesis. MPA and CTX show distinct effects on fibrotic and inflammatory processes in NZBWF1/J murine lupus nephritis, suggesting that MMF + MP may be more effective than CTX + MP in preserving normal renal histology in lupus nephritis.

  3. Lung damage following bone marrow transplantation. II. The contribution of cyclophosphamide

    Energy Technology Data Exchange (ETDEWEB)

    Varekamp, A.E.; de Vries, A.J.; Zurcher, C.; Hagenbeek, A.

    1987-10-01

    The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose rate (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy.

  4. Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses

    Science.gov (United States)

    Khaksary Mahabady, Mahmood; Gholami, Mohammad Reza; Najafzadeh Varzi, Hossein; Zendedel, Abolfazl; Doostizadeh, Mona

    2016-01-01

    Cyclophosphamide (CP) is a drug commonly used to treat neoplastic disease and some autoimmune diseases. It is also a well-known and well-studied teratogen causing a variety of birth defects in fetuses of pregnant women treated with the drug. There are many reports that show the adverse effects of CP can be decreased by use of antioxidant drugs. It appears that, quercetin has antioxidant effect. The aim of this study was prevention or decrease of teratogenicity of CP in fetuses of rats by quercetin. This study was performed on 35 pregnant rats divided into six groups. Control group was received normal saline (5 mL kg-1, intraperitoneally) and 2-6 groups received a single dose of CP (15 mg kg-1), a single dose of quercetin (75 or 200 mg kg-1), CP plus quercetin (75 or 200 mg kg-1) intraperitoneally at 9th day of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and crown rump length were stained by alizarin red – alcian blue method and skeletal system were examined by stereomicroscope. The results showed that the cleft palate, exencephaly, spina bifida and omphalocele incidence were 55.56%, 27.77%, 33.34% and 11.11%, in fetuses of rat that received only CP, respectively. However, it decreased to 16.00%, 16.00%, 16.00% and 8.00% by quercetin (75 mg kg-1) and so to 12.90%, 12.90%, 6.45% and 3.28% by quercetin (200 mg kg-1), respectively. On the basis of results, quercetin significantly can decrease teratogenicity induced by CP. PMID:27482358

  5. Effects of melatonin on DNA damage induced by cyclophosphamide in rats

    Directory of Open Access Journals (Sweden)

    S.G. Ferreira

    2013-03-01

    Full Text Available The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP, an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg. Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water. Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE of chromosomal aberrations in pinealectomized (PINX animals treated with melatonin and CP (2.50 ± 0.50/100 cells was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells, thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.

  6. Effects of melatonin on DNA damage induced by cyclophosphamide in rats

    Directory of Open Access Journals (Sweden)

    S.G. Ferreira

    2013-08-01

    Full Text Available The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP, an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg. Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water. Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE of chromosomal aberrations in pinealectomized (PINX animals treated with melatonin and CP (2.50 ± 0.50/100 cells was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells, thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.

  7. Efficacy of Rosmarinus officinalis leaves extract against cyclophosphamide-induced hepatotoxicity.

    Science.gov (United States)

    El-Naggar, Sabry A; Abdel-Farid, Ibrahim B; Germoush, Mousa O; Elgebaly, Hassan A; Alm-Eldeen, Abeer A

    2016-10-01

    Context Cyclophosphamide (CTX) is used to treat different cancer types, although it causes severe hepatotoxicity due to its oxidative stress effect. Rosmarinus officinalis, L. (Lamiaceae) has a therapeutic potential against hepatotoxicity due to its antioxidant activity. Objective The objective of this study is to investigate the phytochemical analysis of the methanol extract of Rosmarinus officianalis leaves (MEROL) and its efficacy against CTX-induced hepatotoxicity. Materials and methods The phytochemical analyses were assessed spectrophotometericaly. To assess the MEROL efficacy, 72 Swiss albino mice were divided into six groups. Group 1 was control, groups 2 and 3 included mice which were injected intraperitoneally (i.p.) with 100 or 200 mg/kg of MEROL at days 1, 4, 7, 10, 13 and 16; group 4 was injected (i.p.) with CTX (200 mg/kg) at day 17, groups 5 and 6 were injected (i.p.) with MEROL as groups 3 and 4 followed by 200 mg/kg CTX at day 17, respectively. At day 22, six mice from each group were sacrificed and the others were sacrificed at day 37. Results MEROL has a high content of total phenolics, saponins, total antioxidant capacity and DPPH radical scavenging activity. The median lethal dose (LD50) value of MEROL was 4.125 g/kg b.w. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 55 μg/mL. Pretreatment with 100 mg/kg MEROL for 16 d ameliorated CTX-induced hepatotoxicity represented in lowering the levels of the aspartate aminotransferase (AST) and lipid profile and minimizing the histological damage. Conclusions Pretreatment with 100 mg/kg b.w. MEROL mitigated CTX-induced hepatotoxicity due to its antioxidant activity.

  8. Toxicity and antitumor activity of the vitamin D analogs PRI-1906 and PRI-1907 in combined treatment with cyclophosphamide in a mouse mammary cancer model.

    Science.gov (United States)

    Wietrzyk, Joanna; Nevozhay, Dmitry; Milczarek, Magdalena; Filip, Beata; Kutner, Andrzej

    2008-10-01

    Active and less toxic vitamin D analogs could be useful for clinical applications. In the present study, we evaluated the toxicity and antitumor effect of two new synthetic analogs of vitamin D, namely PRI-1906 [(24E)-24a-Homo-(1S)-1,25-dihydroxyergocalciferol] and its side-chain unsaturated homo analog PRI-1907. The toxicity and calcemic activity, as well as antitumor effect of calcitriol analogs was investigated in vivo. The studies were performed in a mouse mammary 16/C cancer model. Since calcitriol and its analogs inhibited 16/C tumor growth only slightly, we applied them in the combined therapy with cyclophosphamide (CY). Moreover, cell cycle analysis and VDR and p27 expression were investigated. The LD50 values after five daily subcutaneous (s.c.) injections were 7.8, 10.0 and 2.4 microg/kg per day for calcitriol, PRI-1906 and PRI-1907, respectively. The serum calcium level increased to 40, 23 and 63% over the control for these compounds. We also compare the antitumor activity of the PRI-1906 with the calcitriol and previously studied PRI-2191 (1,24-dihydroxyvitamin D3, tacalcitol). Statistically significant inhibition of tumor growth by calcitriol up to the eighth day was observed in all schedules applied. PRI-1906 inhibited the tumor growth at doses 1 and 5 microg/kg per day, and PRI-2191 only at the dose 5 microg/kg per day. Addition of vitamin D analogs increased the antitumor effect of CY. PRI-1906 exhibited toxicity higher than PRI-2191 but lower than calcitriol and antitumor activity similar to both PRI-2191 and calcitriol. This new analog seems to be a good candidate for the combined treatment of mammary cancer.

  9. High-dose cyclophosphamide followed by autologous peripheral blood progenitor cell transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma

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    Baldissera R.C.

    2002-01-01

    Full Text Available Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16 and methotrexate (MTX in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65 affected by aggressive non-Hodgkin's lymphoma (NHL (60.6% or persistent or relapsed Hodgkin's disease (39.4% were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233. Thirty-one patients underwent autografting and received a median of 6.19 x 10(6/kg (1.07-29.3 CD34+ cells. Patients who were chemosensitive to HDCY (N = 22 and patients who were chemoresistant (N = 11 presented an overall survival of 96 and 15%, respectively (P<0.0001. Overall survival was 92% for chemosensitive patients and 0% for patients who were still chemoresistant before transplantation (P<0.0001. Toxicity-related mortality was 12% (four patients, related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment.

  10. Amifostine (WR-2721, a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study

    Directory of Open Access Journals (Sweden)

    De Souza C.A.

    2000-01-01

    Full Text Available Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY (7 g/m2, used to mobilize peripheral blood progenitor cells (PBPC and to reduce tumor burden. We enrolled 29 patients, 22 (75.9% affected by aggressive and 7 (24.1% by indolent non-Hodgkin's lymphoma (NHL, who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04. None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively. Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.

  11. Improvement of neurological symptoms and memory and emotional status in a case of seronegative Sneddon syndrome with cyclophosphamide.

    Science.gov (United States)

    Hannon, Peter M; Kuo, Sheng-Han; Strutt, Adriana M; York, Michele K; Kass, Joseph S

    2010-07-01

    Sneddon syndrome (SS) is characterized by livedo racemosa, recurrent ischemic strokes, and often progressive vascular dementia. Treatment options for SS center on either anticoagulation or immunosuppression to prevent strokes and to dissipate the skin findings, with these modalities based historically on the presence or absence of antiphospholipid antibodies (APA) respectively. However, few effective treatments have been reported to reverse the cognitive decline in SS. We report a case of a woman with seronegative SS (absence of APA) with cognitive decline who demonstrated objective and subjective improvements in her memory and emotional functioning after treatment with cyclophosphamide.

  12. Macrophage activation syndrome as the initial manifestation of severe juvenile onset systemic lupus erythematosus. Favorable response to cyclophosphamide.

    Science.gov (United States)

    Torres Jiménez, Alfonso; Solís Vallejo, Eunice; Zeferino Cruz, Maritza; Céspedes Cruz, Adriana; Sánchez Jara, Berenice

    2014-01-01

    The macrophage activation syndrome is a rare but potentially fatal complication of patients with autoimmune rheumatic diseases. This is a clinicopathological entity characterized by activation of histiocytes with prominent hemophagocytosis in the bone marrow and other reticuloendothelial systems. In patients with lupus it may mimic an exacerbation of the disease or infection. We report the case of a 7-year-old girl in whom the diagnosis of lupus erythematosus and macrophage activation syndrome was simultaneously made with response to the use of cyclophosphamide.

  13. Glucocorticoid combined with cyclophosphamide treating paraquat poisoning%糖皮质激素联合环磷酰胺治疗百草枯中毒疗效的Meta分析

    Institute of Scientific and Technical Information of China (English)

    陈本敦; 林庆明; 林世荣; 陈锋

    2013-01-01

    combined with cyclophosphamide (mortality rate:56.8%) in decreasing mortality of paraquat poisoning was 0.56 (95% CI 0.29-1.05,P =0.07),compared with basic therapy (mortality rate:81.9%).There were significant heterogeneity and publication bias.Conclusions Combined treatment with glucocorticoid and cyclophosphamide may decrease mortality of patients with moderate to severe paraquat poisoning.Due to the small number of RCTs,significant heterogeneity and publication bias,a large RCT which is well designed is required to validate the efficacy of combined treatment with glucocorticoid and cyclophosphamide in patients with moderate to severe paraquat poisoning.

  14. Sleep disturbances and prevalence of depression in systemic lupus erythematosus patients receiving intravenous cyclophosphamide Alterações do sono e prevalência de depressão em pacientes lúpicos em uso de pulsoterapia com ciclofosfamida

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    Rafael Carvalho Mesquita

    2007-12-01

    Full Text Available BACKGROUND: Pulse i.v. cyclophosphamide is a therapeutic option in severe forms of systemic lupus erythematosus (SLE. However, the overall toxicity and risk profile are yet to be adequately defined. OBJECTIVE: To evaluate the occurrence of sleep disturbances in SLE patients subjected to i.v. cyclophosphamide. METHODS: We studied thirty consecutive SLE patients (27 female age range 14 to 53 years (mean 30.5 ± 10 years that received i.v. cyclophosphamide (mg (mean 948.27 ± 221.39. Depressive symptoms, quality of sleep, and the presence of excessive daytime sleepiness were evaluated. Disease severity was assessed by the SLEDAI. Quality of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI and excessive daytime sleepiness (EDS by the Epworth Sleepiness Scale (ESS. Depressive symptoms were evaluated using the 21-item Beck Depression Inventory (BDI. RESULTS: SLEDAI values ranged from 2 to 46 (mean 17 ± 11.4. The most common comorbidities were systemic arterial hypertension (30%, anemia (23.3%, osteoporosis (23.3%, and cardiomyopathy (6.6%. Seizures occurred in one patient (3.3%. Poor quality of sleep (PSQI e" 6 and EDS (ESS >10 were found in 66.7% and 30% of the patients, respectively. Depressive symptoms (BDI >19 were present in 40% of the patients and were associated with poor sleep quality (P = 0.03. CONCLUSIONS: Our findings show an increased prevalence of poor sleep quality and depressive symptoms in SLE patients receiving pulse i.v. cyclophosphamide. These findings were similar to other previously reported series of SLE patients regardless of the therapies used.INTRODUÇÃO: O uso de ciclofosfamida endovenosa é uma opção terapêutica nas formas graves de lúpus eritematoso sistêmico (LES. No entanto, a toxicidade e o perfil de risco ainda não estão adequadamente definidos. OBJETIVO: Avaliar sobre a ocorrência de alterações do sono em pacientes portadores de LES submetidos à terapia com ciclofosfamida endovenosa. M

  15. Achillea millefolium inflorescence aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis: stereological evidences%Achillea millefolium inflorescence aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis:stereological evidences

    Institute of Scientific and Technical Information of China (English)

    Ali Shalizar Jalali; Shapour Hasanzadeh; Hassan Malekinejad

    2012-01-01

    Cyclophosphamide (CP) is extensively used for the treatment of various cancers,as well as an immunosuppressive agent.However,CP is known to cause several adverse effects including reproductive toxicity.Achillea millefolium,a widely distributed medicinal plant,is highly regarded for its medicinal activities,including antioxidant and anti-inflammatory properties.The present study was conducted to assess whether Achillea millefolium inflorescences aqueous extract with antioxidant and anti-inflammatory activities could serve as a protective agent against reproductive toxicity during CP treatment.Male Wistar rats were categorized into four groups.Two groups of rats were administered CP at a dose of 5mg·kg-1·d-1 for 28 d by oral gavages.One of these groups received Achillea aqueous extract at a dose of 1.2 g·kg-1·d-1 orally 4 h after cyclophosphamide administration.A vehicle treated control group and an Achillea control group were also included.Thc CP-trcatcd group showed significant decreases in the body,testes and epididymides weights as well as many histological alterations.Stereological parameters,spermatogenic activities and testicular antioxidant capacity along with epididymal sperm count and serum testosterone concentration were also significantly decreased by CP treatment.Notably,Achillea co-administration caused a partial recovery in above-mentioned parameters.These findings indicate that Achillea millefolium inflorescence aqueous extract may be partially protective against CP-induced testicular toxicity.

  16. Long-term results of a randomized trial comparing cisplatin with cisplatin and cyclophosphamide with cisplatin, cyclophosphamide, and adriamycin in advanced ovarian cancer. GICOG (Gruppo Interregionale Cooperativo Oncologico Ginecologia), Italy.

    Science.gov (United States)

    1992-05-01

    We report the long-term results of a randomized trial comparing cisplatin (P) with cisplatin and cyclophosphamide (CP) with cisplatin, cyclophosphamide, and adriamycin (CAP) in advanced ovarian cancer. Overall, this update confirms previously published data on 529 cases. Median survival times for the three treatments--CAP, CP, and P--are, respectively, 23, 20, and 19 months. The differences among the three arms are still nonsignificant and the estimated percentage survival at 7 years and confidence limits are, respectively, 21.7 (14.9-28.4), 17.0 (11.0-22.9), and 12.2 (6.9-17.4). According to the results of the Cox regression model on prognostic factors, higher grading, a larger residual tumor size, and performance status less than 80 (Karnovsky) all were independently associated with a poorer outcome, while a serous histotype was related to a better prognosis. The other variables (age, stage, center, type of surgery) initially included in the model did not appear to be significantly related to prognosis. The implications of these long-terms results relative to the application of combination chemotherapy with CAP or CP are discussed.

  17. The Effect of Hydro-Alcoholic Garlic Extract on Testis Weight and Spermatogenesis in Mature Male Rats under Chemotherapy with Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Marzie Mirfard

    2011-12-01

    Full Text Available Background & Objectives: Cyclophosphamide (with the brand name of Endoxana is an anti-cancer drug used in chemotherapy. The side effects of this drug include anoretic, nausea, decrease in genital gland function, creating amenorrhea, azoospermia and oligospermia. Garlic has been used throughout history as a medicinal drug and a beneficial spice in cooking. The beneficial effects of garlic which have been studied are its anti-oxidant, antibacterial, anti- atherosclerosis, anti-blood platelet effects as well as its role in reducing blood glucose and fat. Garlic has many compounds mostly contain a sulfuric content such as Di-alkyl Di-sulfide (Alicin, Di alyl Di sulfide (DAS, that caused antioxidant and protective properties. Materials & Methods: Cyclophosphamide and garlic extract were given to 56 rats for a period of 28 days. The rats were weighted and after anesthesia, their testis was taken out and tissue dissections were obtained, Student t-test was applied for the statistical analysis. Results: The results show that cyclophosphamide alone leads to a reduction in body and testis weight, and spermatogenesis compared to the control group. In the group that used cyclophosphamide along with garlic extract, as the dose of extract increased, the body and testis weight and spermatogenesis increased in the rats. Conclusion: It seems, the existing compounds in garlic extract can control active metabolites caused by cyclophosphamide and the destructive effect of this drug. Prescribing garlic extract along with cyclophosphamide can possibly be beneficial and effective due to the anti-oxidant characteristics of garlic and also its effect on reducing harmful metabolites.

  18. Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy

    Science.gov (United States)

    2008-08-01

    4th Affiliated Hospital , Harbin Medical University, Harbin, China; 3Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford...tumor-targeting properties of 99mTc-labeled glucosamino RGD and effect of paclitaxel therapy. J Nucl Med. 2006;47:2000–2007. 34. Morrison MS, Ricketts SA...11. Picardi M, De Renzo A, Pane F, et al. Randomized comparison of consolidation radiation versus observation in bulky Hodgkin’s lymphoma with post

  19. Hypertension and Afro-descendant ethnicity: a bad interaction for lupus nephritis treated with cyclophosphamide?

    Science.gov (United States)

    de Castro, W P; Morales, J V; Wagner, M B; Graudenz, M; Edelweiss, M I; Gonçalves, L F

    2007-01-01

    Hypertension and ethnicity are important prognostic factors in evolution of lupus nephritis. A cohort of 75 patients with lupus nephritis treated with cyclophosphamide was conducted to investigate the evolution of creatinine levels between Caucasians and Afro-descendants. A multiple linear model was used to evaluate the combined effects of ethnicity and hypertension over delta creatinine controlling confounders. Sample characteristics were: 85% females; mean (+/-SD) age of 33.6 +/- 12.0 years; 77% Caucasians; 40% hypertensive at renal biopsy; 91% WHO class IV; mean basal creatinine: 1.5 +/- 1.3 mg/dL; mean final creatinine: 2.1 +/- 2.5 mg/dL; 40% anaemia; proteinuria: 5.4 +/- 4.8 g/day. Comparing Caucasians and Afro-descendants, it was found: 28.1% versus 72.2% for hypertension (P = 0.002); 31.6% versus 66.7% for anaemia (P = 0.018); 5.9 +/- 5.0 versus 3.8 +/- 4.0. g/day (P = 0.02) for proteinuria. Other comparisons including basal creatinine did not reach statistical significance. Comparing outcomes between Caucasians and Afro-descendants, it was found: 10.5% versus 22.2% for doubling of creatinine (P = 0.24); 0.41 +/- 2.03 versus 1.05 +/- 2.41 for delta creatinine ( P = 0.29); 8.8% versus 22.2% for haemodialysis (P = 0.21) and 3.5% versus 5.6% for death (P = 0.99). Analysing delta creatinine with multiple linear regression showed that hypertension had a significant overall effect (b = 0.80; SE = 0.32; P = 0.015), ethnicity alone was not significant (b = 0.35; SE = 0.29; P = 0.228); however, the effect of hypertension on delta creatinine was more intense among Afro-descendants than among Caucasians (interaction term b = - 0.83; SE = 0.37; P = 0.027). Afro-descendants lupus patients experience worst prognosis of renal function probably due to the effect of hypertension and not ethnicity per se.

  20. Occurrence of cyclophosphamide and ifosfamide in aqueous environment and their removal by biological and abiotic wastewater treatment processes.

    Science.gov (United States)

    Česen, Marjeta; Kosjek, Tina; Laimou-Geraniou, Maria; Kompare, Boris; Širok, Brane; Lambropolou, Dimitra; Heath, Ester

    2015-09-15

    Cytostatic drug residues in the aqueous environment are of concern due to their possible adverse effects on non-target organisms. Here we report the occurrence and removal efficiency of cyclophosphamide (CP) and ifosfamide (IF) by biological and abiotic treatments including advanced oxidation processes (AOPs). Cyclophosphamide was detected in hospital wastewaters (14-22,000 ng L(-1)), wastewater treatment plant influents (19-27 ng L(-1)) and effluent (17 ng L(-1)), whereas IF was detected only in hospital wastewaters (48-6800 ng L(-1)). The highest removal efficiency during biological treatment (attached growth biomass in a flow through bioreactor) was 59 ± 15% and 35 ± 9.3% for CP and IF, respectively. Also reported are the removal efficiencies of both compounds from wastewater using hydrodynamic cavitation (HC), ozonation (O3) and/or UV, either individually or in combination with hydrogen peroxide (H2O2). Hydrodynamic cavitation did not remove CP and IF to any significant degree. The highest removal efficiencies: 99 ± 0.71% for CP and 94 ± 2.4% for IF, were achieved using UV/O3/H2O2 at 5 g L(-1) for 120 min. When combined with biological treatment, removal efficiencies were >99% for both compounds. This is the first report of combined biological and AOP treatment of CP and IF from wastewater with a removal efficiency >99%.

  1. Protective effect of curcumin and chlorophyllin against DNA mutation induced by cyclophosphamide or benzo[a]pyrene

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, M.A.; Elbehairy, A.M.; Ghoneim, M.A.; Amer, H.A. [Cairo Univ., Giza (Egypt). Biochemistry Dept. and Biotechnology Center

    2007-03-15

    The current study was carried out to evaluate the potency of curcumin and chlorophyllin as natural antioxidants to reduce the oxidative stress markers induced by cyclophosphamide (CP) and benzo[a]pyrene [B(a)P] which were used as free radical inducers. For this purpose, 126 male albino rats were used. The animals were assigned into 4 main groups: negative control group; oxidant-treated group (subdivided into two subgroups: cyclophosphamide- treated group and benzo[a]pyrene-treated group); curcumin-treated group; and chlorophyllin-treated group. Liver samples were collected after two days post the oxidant inoculation and at the end of the experimental period (10 weeks). These samples were examined for determination of liver microsomal malondialdehyde (MDA), DNA fragmentation, restriction fragment length polymorphism (RFLP) and 8-hydroxy deoxyguanosine (8-OHdG) concentration. Both CP and B(a)P caused increments in DNA fragmentation percentages, liver microsomal MDA, concentration of 8-OHdG and induced point mutation. Treatment of rats with either curcumin or chlorophyllin revealed lower DNA fragmentation percentages, liver microsomal MDA concentration, concentration of 8-OHdG and prevented induction of mutations, i. e., reversed the oxidative stress induced by CP and B(a)P and proved that they were capable of protecting rats against the oxidative damage evoked by these oxidants. (orig.)

  2. Protective effect of curcumin and chlorophyllin against DNA mutation induced by cyclophosphamide or benzo[a]pyrene.

    Science.gov (United States)

    Ibrahim, Marwa A; Elbehairy, Adel M; Ghoneim, Magdy A; Amer, Hassan A

    2007-01-01

    The current study was carried out to evaluate the potency of curcumin and chlorophyllin as natural antioxidants to reduce the oxidative stress markers induced by cyclophosphamide (CP) and benzo[a]pyrene [B(a)P] which were used as free radical inducers. For this purpose, 126 male albino rats were used. The animals were assigned into 4 main groups: negative control group; oxidant-treated group (subdivided into two subgroups: cyclophosphamide-treated group and benzo[a]pyrene-treated group); curcumin-treated group; and chlorophyllin-treated group. Liver samples were collected after two days post the oxidant inoculation and at the end of the experimental period (10 weeks). These samples were examined for determination of liver microsomal malondialdehyde (MDA), DNA fragmentation, restriction fragment length polymorphism (RFLP) and 8-hydroxy deoxyguanosine (8-OHdG) concentration. Both CP and B(a)P caused increments in DNA fragmentation percentages, liver microsomal MDA, concentration of 8-OHdG and induced point mutation. Treatment of rats with either curcumin or chlorophyllin revealed lower DNA fragmentation percentages, liver microsomal MDA concentration, concentration of 8-OHdG and prevented induction of mutations, i.e., reversed the oxidative stress induced by CP and B(a)P and proved that they were capable of protecting rats against the oxidative damage evoked by these oxidants.

  3. High content analysis of an in vitro model for metabolic toxicity: results with the model toxicants 4-aminophenol and cyclophosphamide.

    Science.gov (United States)

    Cole, Stephanie D; Madren-Whalley, Janna S; Li, Albert P; Dorsey, Russell; Salem, Harry

    2014-12-01

    In vitro models that accurately and rapidly assess hepatotoxicity and the effects of hepatic metabolism on nonliver cell types are needed by the U.S. Department of Defense and the pharmaceutical industry to screen compound libraries. Here, we report the first use of high content analysis on the Integrated Discrete Multiple Organ Co-Culture (IdMOC) system, a high-throughput method for such studies. We cultured 3T3-L1 cells in the presence and absence of primary human hepatocytes, and exposed the cultures to 4-aminophenol and cyclophosphamide, model toxicants that are respectively detoxified and activated by the liver. Following staining with calcein-AM, ethidium homodimer-1, and Hoechst 33342, high content analysis of the cultures revealed four cytotoxic endpoints: fluorescence intensities of calcein-AM and ethidium homodimer-1, nuclear area, and cell density. Using these endpoints, we observed that the cytotoxicity of 4-aminophenol in 3T3-L1 cells in co-culture was less than that observed for 3T3-L1 monocultures, consistent with the known detoxification of 4-aminophenol by hepatocytes. Conversely, cyclophosphamide cytotoxicity for 3T3-L1 cells was enhanced by co-culturing with hepatocytes, consistent with the known metabolic activation of this toxicant. The use of IdMOC plates combined with high content analysis is therefore a multi-endpoint, high-throughput capability for measuring the effects of metabolism on toxicity.

  4. VINDESINE WITH CYCLOPHOSPHAMIDE-EPIRUBICIN-CISPLATIN IN THE TREATMENT LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    HU Yan-ping; KE Yu-hua; FU Xiao-yu

    1999-01-01

    Objective: To evaluate the addition of vindesine to a cyclophosphamide-epirubicin-cisplatin (CAP) regimen for treating the patients with locally advanced non-small cell lung cancer (NSCLC). Methods: From May 1994to August 1998, 59 previously untreated patients with stage Ⅲa and Ⅲb non-small cell lung cancer were enrolled into this trial. Patients characteristics were the following: the median age was 52 years; the median performance status was 1; there were 19 stage Ⅲa and 40 stage Ⅲb; there were 47 adenocarcinoma, 10squamous cell carcinoma and 2 large cell carcinoma. All patients were treated with vindesine (2 mg/m2, on day 1and day 8), cyclophosphamide (0.6/m2, on day 1),epirubicin (40 mg/m2, on day 1) and cisplatin (60 mg/m2,on day 1) every 3 or 4 weeks. Results: Four achieved a complete response (6.8%), 29 achieved a partial response (49.2%), 15 had stable disease, and 10 had progressive disease. A clinical improvement was in 45 of 59 patients (76.3%). The most frequent major toxic effects were myelosuppression, nausea and vomiting.Conclusion: The vindesine with CAP regimen was active combination chemotherapy in patients with locally advanced NSCLC accompanied by the limited side effects.

  5. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Twu, Chih-Wen [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Wen-Yi [Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan (China); Chen, Chien-Chih [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Liang, Kai-Li; Jiang, Rong-San [Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wu, Ching-Te [Department of Radiation Oncology, Taichung Veterans General Hospital–Chiayi Branch, Chiayi, Taiwan (China); Shih, Yi-Ting [Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan (China); Lin, Po-Ju; Liu, Yi-Chun [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lin, Jin-Ching, E-mail: jclin@vghtc.gov.tw [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, China Medical University, Taichung, Taiwan (China)

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  6. Chlorophyllin in the intra-uterine development of mice exposed or not to cyclophosphamide - doi: 10.4025/actascihealthsci.v35i2.12470

    Directory of Open Access Journals (Sweden)

    Vessia Silva Leite

    2013-06-01

    Full Text Available Chlorophyllin, a sodium-copper salt synthesized from chlorophyll, has already proved to have anticlastogenic, antimutagenic and anticarcinogenic activity, however few are the studies in the teratogenicity area. The present study evaluated the effects of chlorophyllin in intra-uterine development of mice exposed or not to cyclophosphamide. Pregnant females were divided into 8 groups of 15 animals each, G01 - PBS (0.1 mL 10.0-1 g orally; G02 – cyclophosphamide (20.0 mg kg-1 i.p.; G03, G04 and G05 - chlorophyllin at concentrations of (5.0, 10.0 and 15.0 mg kg-1 orally; G06, G07 and G08 (5.0, 10.0 and 15.0 mg kg-1 orally, of chlorophyllin, respectively, and (20.0 mg kg-1 i.p. of cyclophosphamide. In the 18th day the females were submitted to laparotomy and females and fetuses analyzed. The results showed that the chlorophyllin was not effective in protecting the reproductive parameters as well as teratogenicity. Finally, it was observed that the presence of chlorophyllin increased the frequency of some malformations when combined with cyclophosphamide. However, it was not teratogenic and not embryo lethal in this experimental design.

  7. Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy.

    Science.gov (United States)

    van der Most, Robbert G; Currie, Andrew J; Mahendran, Sathish; Prosser, Amy; Darabi, Anna; Robinson, Bruce W S; Nowak, Anna K; Lake, Richard A

    2009-08-01

    Tumor cell death potentially engages with the immune system. However, the efficacy of anti-tumor chemotherapy may be limited by tumor-driven immunosuppression, e.g., through CD25+ regulatory T cells. We addressed this question in a mouse model of mesothelioma by depleting or reconstituting CD25+ regulatory T cells in combination with two different chemotherapeutic drugs. We found that the efficacy of cyclophosphamide to eradicate established tumors, which has been linked to regulatory T cell depletion, was negated by adoptive transfer of CD25+ regulatory T cells. Analysis of post-chemotherapy regulatory T cell populations revealed that cyclophosphamide depleted cycling (Ki-67(hi)) T cells, including foxp3+ regulatory CD4+ T cells. Ki-67(hi) CD4+ T cells expressed increased levels of two markers, TNFR2 and ICOS, that have been associated with a maximally suppressive phenotype according to recently published studies. This suggest that cyclophosphamide depletes a population of maximally suppressive regulatory T cells, which may explain its superior anti-tumor efficacy in our model. Our data suggest that regulatory T cell depletion could be used to improve the efficacy of anti-cancer chemotherapy regimens. Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25+ CD4+ T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy.

  8. Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats.

    Science.gov (United States)

    Kitamura, Yoshihisa; Kanemoto, Erika; Sugimoto, Misaki; Machida, Ayumi; Nakamura, Yuka; Naito, Nanami; Kanzaki, Hirotaka; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki

    2017-04-01

    In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective α7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-β-erythroidine, a selective α4β2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-β-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal α7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via α7 nAChR and α4β2 nAChR, and also enhances hippocampal neurogenesis.

  9. Quantitative and qualitative aspects of topoisomerase I and II alpha and beta in untreated and platinum/cyclophosphamide treated malignant ovarian tumors

    NARCIS (Netherlands)

    van der Zee, A G; de Jong, Steven; Keith, W N; Hollema, H; Boonstra, H; de Vries, Liesbeth

    1994-01-01

    Quantitative and qualitative aspects of topoisomerase (Topo) I and II were studied in 17 malignant ovarian tumors [eight untreated and nine after platinum/cyclophosphamide (Pt/Cy) chemotherapy]. Median Topo II catalytic activity was lower (P <0.05) in tumors after Pt/Cv chemotherapy in comparison to

  10. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis

    NARCIS (Netherlands)

    Arends, Suzanne; Grootscholten, Cecile; Derksen, Ronald H. W. M.; Berger, Stefan P.; de Sevaux, Ruud G. L.; Voskuyl, Alexandre E.; Bijl, Marc; Berden, Jo H. M.

    2012-01-01

    Objectives The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evaluat

  11. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis.

    NARCIS (Netherlands)

    Arends, S.; Grootscholten, C.; Derksen, R.H.W.M.; Berger, S.P.; Sevaux, R.G.L. de; Voskuyl, A.E.; Bijl, M. van der; Berden, J.H.M.

    2012-01-01

    OBJECTIVES: The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evalua

  12. Cyclophosphamide effect on paracoccidioidomycosis in the rat Efecto de la ciclofosfamida en ratas con paracoccidioidomicosis

    Directory of Open Access Journals (Sweden)

    J. L. Blejer

    1995-06-01

    Full Text Available Paracoccidioidomycosis is an endemic fungal disease widely distributed throughout Latin America. The potent immunosuppressor cyclophosphamide (CY has been used to modulate host immune response to Paracoccidioides brasiliensis in an experimental model. Inbred male Buffalo/Sim rats weighing 250-300 g were inoculated with 5 x 10(6 P. brasiliensis cells of the yeast phase form by intracardiac route. One group of animals was treated with 20 mg/kg body weight at days +4, +5, +6, +7, +11 and +12 post-infection (pi., while a control group was infected alone. No mortality was recorded in either group. Treated rats presented: a a decrease in granuloma size, which contained less fungal cells; b a lack of specific antibodies up to 35 days pi., and c a significant increase in the footpad swelling test (DTH against paracoccidioidin. Splenic cell transfer from CY-treated P. brasiliensis-infected donors to recipients infected alone led to a significant increase in DTH response in the latter versus untreated infected controls. Likewise, in treated infected recipients transferred with untreated infected donor spleen cells, footpad swelling proved greater than in controls. Thus, it would seem that each successive suppressor T lymphocyte subset belonging to the respective cascade may be sensitive to repeated CY doses administered up to 12 days pi.. Alternatively, such CY schedule may induce the appearance of a T cell population capable of amplifying DTH response.La paracoccidioidomicosis es una enfermedad endémica fúngica ampliamente distribuida en Latino-América. La ciclofosfamida ha sido usada como potente inmunosupresor para modular la respuesta inmune, en un modelo experimental infectado con Paracoccidioides brasiliensis. Ratas machos Buffalo/Sim endocriadas de 250-300 gr. de peso, fueron inoculadas por via intracardiaca con 5.10 6 células de P. brasiliensis en fase levaduriforme. Un grupo de animales fue tratado con 20 mg/kg de peso de ciclofosfamida en

  13. Comparing the interaction of cyclophosphamide monohydrate to human serum albumin as opposed to holo-transferrin by spectroscopic and molecular modeling methods: evidence for allocating the binding site.

    Science.gov (United States)

    Tousi, Shirin Hamed-Akbari; Saberi, Mohammad Reza; Chamani, Jamshidkhan

    2010-12-01

    The interaction between cyclophosphamide monohydrate with human serum albumin (HSA) and human serum transferrin (hTf) was studied with UV absorption, fluorescence and circular dichroism (CD) spectroscopies as well as molecular modeling. Based on the fluorescence quenching results, it was determined that HSA and hTf had two classes of apparent binding constants and binding sites at physiological conditions. The K(SV1), K(SV2), n(1) and n(2) values for HSA were found to be 8.6 x 10(8) Lmol(-1), 6.34 x 10(8) Lmol(-1), 0.7 and 0.8, respectively, and the corresponding results for hTf were 6.08 x 10(7) Lmol(-1), 4.65 x 10(7) Lmol(-1), 1.3 and 2.6, respectively. However, the binding affinity of cyclophosphamide monohydrate to HSA was more significant than to hTf. Circular dichroism results demonstrated that the binding of cyclophosphamide to HSA and hTf induced secondary changes in the structure and that the a-helix content became altered into b-sheet, turn and random coil forms. The participation of tyrosyl and tryptophan residues of proteins was also estimated in the drug-HSA and hTf complexes by synchronous fluorescence. The micro-environment of the HSA and hTf fluorophores was transferred to hydrophobic and hydrophilic conditions, respectively. The distance r between donor and acceptor was obtained by the Forster energy according to fluorescence resonance energy transfer (FRET) and found to be 1.84 nm and 1.73 nm for HSA and hTf, respectively. This confirmed the existence of static quenching for both proteins in the presence of cyclophosphamide monohydrate. Site marker competitive displacement experiments demonstrated that cyclophosphamide bound with high affinity to Site II, sub-domain IIIA of HSA, and for hTf, the C-lobe constituted the binding site. Furthermore, a study of molecular modeling showed that cyclophosphamide situated in domain II in HSA was bound through hydrogen bonding with Arg 257 and Ser 287, and that cyclophosphamide was situated in the C-lobe in h

  14. Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-hui; LU Dao-pei; HUANG Xiao-jun; LIU Kai-yan; XU Lan-ping; LIU Dai-hong; CHEN Huan; CHEN Yu-hong; WANG Jing-zhi; HAN Wei

    2007-01-01

    Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma.The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma.Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine.Ten patients underwent allogeneic transplantation among them hydroxyurea (40 mg/kg) was administered twice on day -10 and cytarabine (2 g/m2) was given on day -9, busulfan was administered orally in four divided doses daily for 3 days (days -8 to -6). The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1hour on days -5 and -4 (1.8 g/m2), and with semustine (Me-CCNU) 250 mg/m2 on day -3.Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease (GVHD, 36.4%; 95% CI:13.9%-38.6%). Two patients (18.2%) developed grade Ⅰ acute GVHD (95% CI:10.9%-35.9%) and grade Ⅱ acute GVHD occurred in one patient (9.1%;95% CI: 8.4%-32.3%). Severe grade Iva GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% (95% CI: 11.7%-36.7%), among them one died of severe grade IV GVHD and one developed multiorgan failure on day +170; the treatment-related mortality was 22.0% (95% CI: 10.3%-34.1%). The overall 4-year survival rate was 67.8% (95% CI: 16.3%-46.7%). The estimated 4-year

  15. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    Science.gov (United States)

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  16. A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer.

    Science.gov (United States)

    Chen, Gang; Gupta, Richa; Petrik, Silvia; Laiko, Marina; Leatherman, James M; Asquith, Justin M; Daphtary, Maithili M; Garrett-Mayer, Elizabeth; Davidson, Nancy E; Hirt, Kellie; Berg, Maureen; Uram, Jennifer N; Dauses, Tianna; Fetting, John; Duus, Elizabeth M; Atay-Rosenthal, Saadet; Ye, Xiaobu; Wolff, Antonio C; Stearns, Vered; Jaffee, Elizabeth M; Emens, Leisha A

    2014-10-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination

  17. Treatment of advanced breast cancer with cyclophosphamide, 5-fluorouracil, and prednisone with and without methanol-extracted residue of BCG.

    Science.gov (United States)

    Britell, J C; Ahmann, D L; Bisel, H F; Frytak, S; Ingle, J N; Rubin, J; O'Fallon, J R

    1979-01-01

    The value of immunotherapy as an adjuvant to chemotherapy for advanced breast cancer is an unsettled question. To clarify this issue, 71 women with measurable or evaluable metastatic breast cancer were randomized to receive cyclophosphamide, 5-fluorouracil, and prednisone (CFP) with or without methanol-extracted residue of Bacillus Calmette-Guerin (MER). The total regression rates were 52% (CFP) and 39% (CFP + MER), including complete regression rates of 13% (CFP) and 65% (CFP + MER). The median duration of regressions for CFP-treated patients was 257-261 days and for CFP + MER-treated patients was 385 days. The median time to progression was 248-261 days in the CFP group and 159 days in the CFP-MER group. Projected median survival for both treatment groups is 20 months. Immunotherapy (MER) as used in this study does not appear to augment regression rates or vurvival for patients with advanced breast cancer receiving CFP.

  18. [Successful treatment of B-cell prolymphocytic leukemia (B-PLL) with FCR-Lite (fludarabine, cyclophosphamide, rituximab) protocol].

    Science.gov (United States)

    Telek, Béla; Batár, Péter; Rejto, László; Udvardy, Miklós

    2010-08-01

    B-cell prolymphocytic leukemia (B-PLL) is a rare disorder characterized by marked lymphocytosis in the peripheral blood, matured lymphocytic infiltration in the bone marrow and splenomegaly. It has a distinct immunophenotype (CD19, CD20, CD22, FMC7, intensive surface immunoglobulin positivity) which helps to differentiate from other lymphoproliferative malignancies. It has a poor prognosis and its treatment is unsettled. The authors present a case of a patient with typical B-PLL treated with FCR-Lite (fludarabine, cyclophosphamide, rituximab) protocol achieving complete hematological (and immunophenotypic) remission. The treatment was well tolerated. Neither major infective complication nor tumor lysis syndrome was observed. According to the author's experience the FCR-Lite protocol can not only be used in patients with CLL but it also can be effective in patients with B-PLL. No clinical experience has been reported yet in the literature with this protocol.

  19. Mechanism on activation of mouse liver microsomal glutathione S—transferase—I by cyclophosphamide treatment in vivo

    Institute of Scientific and Technical Information of China (English)

    ZhenY; LouYJ

    2002-01-01

    Membrane-associated microsomal glutathione S-transferase-I (mGST-I) is activated easily by alkyl agent or electrophilic metabolite.It was expected that toxic drugs and their metabolites derived from biotransformation by cytochrome P-450 maybe bind to and activate the mGST-I that can accelerate the metabolism of drugs to form inactive metabolites and simultaneously protect cell from damages.The aim of the present study was to investigate whether mGST-I is activated by cyclophosphamide(CP) treatment and to explore the possible mechanism in vivo.The results suggested that the main mechanism of mGST-I activation caused by overdose CP treatment is the unique sulfhydryl modification on its Cys-49.

  20. [A case of sarcomatoid malignant peritoneal mesothelioma responding to combination chemotherapy of cyclophosphamide, vincristine, adriamycin and dacarbazine(CYVADIC)].

    Science.gov (United States)

    Kusama, Toshiyuki; Kodaka, Taiichi; Tsunemine, Hiroko; Akasaka, Hiroshi; Koizumi, Naoki; Fujimoto, Koji; Sakano, Shigeru; Ito, Rieko; Kondo, Takeshi; Kitazawa, Sohei; Yamamura, Hisako; Takahashi, Katsuhito

    2009-03-01

    A 66-year-old woman was seen at our hospital because of abdominal fullness. A computed tomography(CT)revealed massive tumors in abdominal cavity. The patient underwent surgery consisting of tumorectomy, segmental gastrectomy, partial resection of small intestin, transverse colectomy, left oophorectomy and gastrostomy. By using immunohistochemical staining, the patient was diagnosed as sarcomatoid malignant peritoneal mesothelioma. Rapidly abdominal fullness occurred as of 22 days after the operation, and an abdominal CT revealed the massive recurrent tumors. We started a combination chemotherapy of cyclophosphamide, vincristine, adriamycin and dacarbazine (CYVADIC). The recurrent tumors showed remarkable reduction after the two courses of CYVADIC chemotherapy. Although we next started carboplatin and paclitaxel combination chemotherapy, she died due to rapidly progression of the disease with disseminated intravascular coagulation after 132 days of the operation. Malignant mesothelioma, especially sarcomatoid mesothelioma, is known to have a poor prognosis. However, our case suggests that we could improve the prognosis of sarcomatoid malignant mesothelioma by aggressive chemotherapy.

  1. Fludarabine, cyclophosphamide and rituximab plus granulocyte macrophage colony-stimulating factor as frontline treatment for patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Ferrajoli, Alessandra; Lerner, Susan; O'Brien, Susan; Wierda, William; Keating, Michael J; Faderl, Stefan

    2014-04-01

    Fludarabine, cyclophosphamide and rituximab (FCR), the standard of care for the frontline treatment of patients with chronic lymphocytic leukemia (CLL), is associated with a high rate of neutropenia and infectious complications. Granulocyte macrophage colony-stimulating factor (GM-CSF) reduces myelosuppression and can potentiate rituximab activity. We conducted a clinical trial combining GM-CSF with FCR for frontline treatment of 60 patients with CLL. Eighty-six percent completed all six courses and 18% discontinued GM-CSF for toxicity: grade 3-4 neutropenia was observed in 30% of cycles, and severe infections in 16% of cases. The overall response rate was 100%. Both median event-free survival (EFS) and overall survival (OS) have not been reached. Longer EFS was associated with favorable cytogenetics. GM-CSF led to a lower frequency of infectious complications than in the historical FCR group, albeit similar EFS and OS.

  2. Recrudescence induced by cyclophosphamide of chronic Trypanosoma cruzi infection in mice is influenced by the parasite strain

    Directory of Open Access Journals (Sweden)

    Maria Elizabeth S Pereira

    1996-02-01

    Full Text Available Reactivation of chronic chagasic patients may occur upon use of immunosuppressive drugs related to kidney or heart transplantation or when they are affected by concomitant HIV infection. This recrudescence, however, does not occur in all chagasic patients exposed to immunosuppressive agents. We therefore investigated the influence of Trypanosoma cruzi strains in the recrudescence of the parasitism in mice at the chronic phase treated with cyclophosphamide, an immunosuppressor that blocks lymphocytes DNA synthesis and therefore controls B cells response. A large variation was detected in the percentages of newly established acute phases in the groups of mice inoculated with the different strains. We suggest that reactivation of chronic T. cruzi infections is influenced by the parasite intrinsic characteristics, a phenomenon that might occur in the human disease.

  3. Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL

    DEFF Research Database (Denmark)

    Geisler, Christian H; van T' Veer, Mars B; Jurlander, Jesper

    2014-01-01

    heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133......). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85% vs 76%, P = .035...

  4. Effect of the molecular mass of tremella polysaccharides on accelerated recovery from cyclophosphamide-induced leucopenia in rats.

    Science.gov (United States)

    Jiang, Rui-Zhi; Wang, Ying; Luo, Hao-Ming; Cheng, Yan-Qiu; Chen, Ying-Hong; Gao, Yang; Gao, Qi-Pin

    2012-03-23

    The body of tremella were decocted with water, and hydrolyzed with 0.1 mol/L hydrochloric acid for different times, giving tremella polysaccharides with six molecular mass values. The structures of all the tremella polysaccharides had non-reducing terminals of β-D-pyranglucuronide, the backbone was composed of (1 → 3)-linked β-D-manno-pyranoside, and the side chain composed of (1 → 6)-linked β-D-xylopyranoside was attached to the C(2) of the backbone mannopyranoside. Immunomodulatory effect studies indicated that tremella polysaccharides increased the counts of leukocytes in the peripheral blood which were significantly lowered by cyclophosphamide, and the lower the molecular mass of the tremella polysaccharide, the better this effect was.

  5. Effect of the Molecular Mass of Tremella Polysaccharides on Accelerated Recovery from Cyclophosphamide-Induced Leucopenia in Rats

    Directory of Open Access Journals (Sweden)

    Qi-Pin Gao

    2012-03-01

    Full Text Available The body of tremella were decocted with water, and hydrolyzed with 0.1 mol/L hydrochloric acid for different times, giving tremella polysaccharides with six molecular mass values. The structures of all the tremella polysaccharides had non-reducing terminals of β-D-pyranglucuronide, the backbone was composed of (1→3-linked β-D-manno-pyranoside, and the side chain composed of (1→6-linked β-D-xylopyranoside was attached to the C2 of the backbone mannopyranoside. Immunomodulatory effect studies indicated that tremella polysaccharides increased the counts of leukocytes in the peripheral blood which were significantly lowered by cyclophosphamide, and the lower the molecular mass of the tremella polysaccharide, the better this effect was.

  6. Should we consider MMF therapy after rituximab for nephrotic syndrome?

    Science.gov (United States)

    Filler, Guido; Huang, Shih-Han Susan; Sharma, Ajay P

    2011-10-01

    The management of steroid-dependent nephrotic syndrome, especially in patients who have failed to respond to cytotoxic drugs, such as cyclophosphamide, remains challenging. Rituximab represents a new (off-label) therapeutic option. In a significant portion of patients, it has a short serum half-life following the recovery of CD20-positive cells. The addition of mycophenolate mofetil (MMF) as a maintenance therapy is also an attractive option, but one which requires testing in a prospective randomized clinical trial with therapeutic drug monitoring and mechanistic ancillary studies.

  7. Cyclophosphamide-induced cystitis increases bladder CXCR4 expression and CXCR4-macrophage migration inhibitory factor association.

    Directory of Open Access Journals (Sweden)

    Pedro L Vera

    Full Text Available BACKGROUND: Macrophage migration inhibitory factor (MIF is a pro-inflammatory cytokine involved in cystitis and a non-cognate ligand of the chemokine receptor CXCR4 in vitro. We studied whether CXCR4-MIF associations occur in rat bladder and the effect of experimental cystitis. METHODS AND FINDINGS: Twenty male rats received saline or cyclophosphamide (40 mg/kg; i.p.; every 3(rd day to induce persistent cystitis. After eight days, urine was collected and bladders excised under anesthesia. Bladder CXCR4 and CXCR4-MIF co-localization were examined with immunhistochemistry. ELISA determined MIF and stromal derived factor-1 (SDF-1; cognate ligand for CXCR4 levels. Bladder CXCR4 expression (real-time RTC-PCR and protein levels (Western blotting were examined. Co-immunoprecipitations studied MIF-CXCR4 associations.Urothelial basal and intermediate (but not superficial cells in saline-treated rats contained CXCR4, co-localized with MIF. Cyclophosphamide treatment caused: 1 significant redistribution of CXCR4 immunostaining to all urothelial layers (especially apical surface of superficial cells and increased bladder CXCR4 expression; 2 increased urine MIF with decreased bladder MIF; 3 increased bladder SDF-1; 4 increased CXCR4-MIF associations. CONCLUSIONS: These data demonstrate CXCR4-MIF associations occur in vivo in rat bladder and increase in experimental cystitis. Thus, CXCR4 represents an alternative pathway for MIF-mediated signal transduction during bladder inflammation. In the bladder, MIF may compete with SDF-1 (cognate ligand to activate signal transduction mediated by CXCR4.

  8. Occupational exposures among nurses caring for chemotherapy patients -Quantitative analysis of cyclophosphamide and α-fluoro-β-alanine in urine.

    Science.gov (United States)

    Sasaki, Makiko; Ishii, Noriko; Kikuchi, Yukiko; Kudoh, Yukiko; Sugiyama, Reiko; Hasebe, Makiko

    2016-10-07

    The aim of this study was to measure the antineoplastic drug content in urine and verify the situation of occupational exposure of the antineoplastic drug among nurses who care for patients undergoing chemotherapy. Ten female nurses who were caring for patients receiving chemotherapy were the subjects of this study. Urine samples were collected over 24-hour periods, and each sample was analyzed. The excretion of cyclophosphamide (CP) and α-fluoro-β-alanine (FBAL) were measured in the urine of the 10 nurses. CP and FBAL were detected separately using gas chromatography tandem mass spectrometry (GC-MSMS) methods (Exposure Control, the Netherlands). CP was detected in 24 urine samples of 9 nurses. The total amount of CP excreted ranged from 5.4 to 44.2 ng/24-hours. The mean amount of CP excreted per nurse was 16.8 ng/24-hours. No significant difference was observed between the hospital I and II. FBAL was not detected in any of the urine samples. CP was detected in the urine of the nurses prior to their work shift. Moreover, CP was detected in the urine of the nurses who were not caring for patients in the intravenous drip of CP. There was most what answered that there was hair loss in health condition. The results reveal that almost all nurses were exposed to cyclophosphamide. Even when the patient in the intravenous drip of CP was not being cared for, it became clear that exposure by CP existed. As the route of the exposure to CP, the inhalation or dermal absorption can be considered. To ensure minimum exposed to antineoplastic drugs, suitable personal protective equipment needs to be equipped also of various scenes of caring for chemotherapy patients. Moreover, it is important to keep an eye on the monitoring of the antineoplastic drug in the environment and a nurse's health condition periodically going forward.

  9. Treatment of malignant phaeochromocytoma with a combination of cyclophosphamide, vincristine and dacarbazine: own experience and overview of the contemporary literature.

    Science.gov (United States)

    Deutschbein, Timo; Fassnacht, Martin; Weismann, Dirk; Reincke, Martin; Mann, Klaus; Petersenn, Stephan

    2015-01-01

    Malignant phaeochromocytomas are rare and highly aggressive tumours. This retrospective study evaluated the outcome of combined chemotherapy with cyclophosphamide, vincristine and dacarbazine (also known as CVD regimen). Patients with histologically and radiologically confirmed malignant phaeochromocytoma who were treated with the CVD regimen for progressive disease were retrospectively identified from chart review. Treatment cycles were usually repeated at 21-day intervals, with cyclophosphamide (750 mg/m(2) ), vincristine (1·4 mg/m(2) ) and dacarbazine (600 mg/m(2) ) on day 1, and dacarbazine only (600 mg/m(2) ) on day 2. The main outcome measures were best response during treatment and progression-free survival. Eight patients (4 males; median age 55·5 (range 31-77) years) with progressive disease underwent a median of 6 (range 3-11) cycles. Best treatment responses were as follows: partial response, n = 2 (25%); stable disease, n = 3 (38%); and progressive disease, n = 3 (38%). The median progression-free survival was 5·4 (range 2·5-26·8) months. After the initial administration of 6 cycles, two patients received a second course of chemotherapy with another 6 cycles after new progressive disease had been detected. Subsequently, these patients were progression-free for another 6·0 and 6·4 months. Mild gastrointestinal symptoms and fatigue were the most common adverse events. Although objective tumour response rates were lower than previously reported in small series, the CVD regimen allowed disease stabilization for a substantial period of time and may therefore be considered as a treatment option in advanced stages. To improve disease outcome, however, new therapeutic approaches and larger multicentre studies are needed. © 2014 John Wiley & Sons Ltd.

  10. Immunosuppression in sheep induced by cyclophosphamide, bluetongue virus and their combination: Effect on clinical reaction and viremia.

    Science.gov (United States)

    Chatzinasiou, Evangelia; Chaintoutis, Serafeim C; Dovas, Chrysostomos I; Papanastassopoulou, Maria; Papadopoulos, Orestis

    2017-03-01

    The main purpose of this work was to establish an experimental model for immunosuppression in sheep, and evaluate its possible effects on bluetongue viremia. Animals were allocated in 4 groups: Cy (cyclophosphamide), BT (bluetongue), CyBT (combined Cy and BT) and Co (control), and underwent clinical evaluations, virological testing, peripheral blood immunophenotyping and determination of antiviral humoral immune responses. Intravenous administration of cyclophosphamide (37.5 mg/kg body weight) resulted in immunosuppresion induction, as significant drops were observed in blood leukocytes and lymphocyte subset counts (CD2(+), CD4(+), CD8(+), CD19(+)), lasting 3-10 days after its administration. Reduction in B-cell (CD19(+)) counts was more pronounced than in T-/NK-cell (CD2(+)) counts (92% and 59%, respectively). BTV-9 inoculation resulted in pronounced lymphocytopenia observed from day 1 post-inoculation. Their combined administration resulted in a more intense immunosuppressive effect, as indicated by the greater reduction in lymphocyte, granulocyte, CD4(+) and CD8(+) cell counts. In group CyBT, earlier initiation of fever by one day (day 6 p.i.) compared to group BT (day 7 p.i.), and delay in antibody responses by one day was observed, compared to group BT. Neutralizing antibodies in both groups (BT, CyBT) were detectable from day 10 p.i., but no significant titer differences were observed. Infectious virus titers were detected from day 4 p.i. in group BT and from day 3 in group CyBT. Statistical significances in virus titers were also observed (greatest mean titer difference: 1.4 log10 CEID50/ml RBCs at day 5 p.i., P bluetongue. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Gender-based reciprocal expression of transforming growth factor-β1 and the inducible nitric oxide synthase in a rat model of cyclophosphamide-induced cystitis

    Directory of Open Access Journals (Sweden)

    Loughran Patricia A

    2009-08-01

    Full Text Available Abstract Background The pluripotent cytokine transforming growth factor-β1 (TGF-β1 is the central regulator of inducible Nitric Oxide Synthase (iNOS that is responsible for nitric oxide (NO production in inflammatory settings. Previous studies have implicated a role for NO, presumably derived from iNOS, in cyclophosphamide (CYP-induced cystitis in the bladder. TGF-β1 is produced in latent form and requires dissociation from the latency-associated peptide (LAP to act as primary anti-inflammatory and pro-healing modulator following tissue injury in the upper urinary tract. Since the role of TGF-β1 in lower urinary tract inflammation is currently unknown, and since gender-based differences exist in the setting of interstitial cystitis (IC, the present study examined the relationship between TGF-β1 and iNOS/NO in the pathogenesis of CYP-induced cystitis in both male and female rats. Methods Sprague-Dawley rats, 4 months of age, of either gender were given 150 mg/kg CYP intraperitoneally. Urinary and bladder tissue TGF-β1 and NO reaction products (NO2-/NO3- were quantified as a function of time following CYP. Expression of active and latent TGF-β1 as well as iNOS in harvested bladder tissue was assessed by immunohistochemistry. Results Female rats had significantly higher levels of NO2-/NO3- in urine even at baseline as compared to male rats (p 2-/NO3- and TGF-β1. Male rats responded to CYP with significantly lower levels of NO2-/NO3- and significantly higher levels of TGF-β1 in urine (p 2-/NO3- after CYP were inversely correlated to latent and active TGF-β1 (Pearson coefficient of -0.72 and -0.69 in females and -0.89 and -0.76 in males, respectively; p Conclusion The results of this study suggest that there exists an inverse relationship between the expression of TGF-β1 and iNOS/NO2-/NO3- in CYP-inflamed bladder. The gender of the animal appears to magnify the differences in urine levels of TGF-β1 and NO2-/NO3- in this inflammatory

  12. Clinicopathologic significance of tumor microenvironment CD11c, and FOXP3 expression in diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy.

    Science.gov (United States)

    Lee, Seul; Kim, Dong Hyun; Oh, Sung Yong; Kim, So Yeon; Koh, Myeong Seok; Lee, Ji Hyun; Lee, Suee; Kim, Sung-Hyun; Kwak, Jong-Young; Pak, Min Gyoung; Ju, Mi Ha; Kim, Hyo-Jin; Jeong, Jin Sook

    2017-03-01

    CD11c is a dendritic cell marker in humans, which potentially induces a cytotoxic effect on lymphoma cells. Forkhead boxP3 (FOXP3) is a regulator of T lymphocyte in the microenvironment of the lymphoma. The principal objective of this study was to determine whether the tumors' microenvironment expressions of CD11c and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy. The study population consisted of 100 patients with DLBCL. The CD11c and FOXP3 expression in primary tumors' microenvironment were evaluated using an immunohistochemistry (IHC). CD11c and FOXP3 expression positivity in microenvironment were 25% and 35%, respectively. Each one counted for 1 point. In CD11c and FOXP3 stain, positive was counted as 0 and negative was 1. The points were separated into low risk (0 to 1) and high risk (2) groups. Only the extranodal DLBCL patient group analysis conveyed significant differences of progression-free survival (p = 0.019) and overall survival (p = 0.039) between the two groups. We can achieve possible clinical significance of lymphoma tumor microenvironments through CD11c and FOXP3 IHC stains in extranodal DLBCL patients receiving R-CHOP therapy.

  13. Novel approaches to therapy for systemic lupus erythematosus: update 2005.

    Science.gov (United States)

    Zandman-Goddard, Gisele; Orbach, Hedi; Shoenfeld, Yehuda

    2005-07-01

    This review covers the major advances in the therapeutic potentials related to systemic lupus erythematosus published in Medline between 2000 and February 2005. Controlled, open and Phase I-III trials were included. Anecdotal reports were excluded. Several trials have defined the role of cyclophosphamide, methotrexate, antimalarials, hormonal treatment and mycophenolate mofetil (Cellcept) in the management of systemic lupus erythematosus. The aims of novel biologics for systemic lupus erythematosus are to target the autoimmune disease at different points: B-cell depletion (rituximab [Rituxan], anti-BLys antibodies [Lymphostat-B]), inhibition of T-B interaction (rituximab), blockade of cytokines (anti-interleukin-10 antibodies), manipulation of idiotypes (intravenous immunoglobulin), tolerance induction to DNA and immunoglobulin-peptides and peptide therapy (abetimus sodium [Riquent]). Low-dose intravenous cyclophosphamide (Euro-Lupus protocol) is as effective as the conventional National Institutes of Health protocol and is also associated with less toxicity. Stem cell transplantation for severe disease induces remission in most patients, however, the relapse rate in a third of patients and the associated morbity and mortality restricts its use to selected patients with life-threatening disease. Intravenous immunoglobulin, although utilized in open trials, is effective and safe for various manifestations of systemic lupus erythematosus. Major advances have been associated with mycophenolate mofetil and rituximab. Mycophenolate mofetil is effective for induction and maintenance therapy of lupus proliferative glomerulonephritis and is associated with fewer adverse events than monthly intravenous cyclophosphamide. Rituximab is a promising agent, and although its utilization is presently limited, it appears to be effective for lupus patients with severe disease.

  14. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    Directory of Open Access Journals (Sweden)

    Zhang MM

    2016-06-01

    Full Text Available Minmin Zhang,* Wei Wei,* Jianlun Liu, Huawei Yang, Yi Jiang, Wei Tang, Qiuyun Li, Xiaoming Liao Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC, followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT vs taxotere (T, in axillary lymph node (LN-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1 who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1 to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027 and objective remission rate (87% vs 73%, P=0.048 compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001 and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034 but less phlebitis (3% vs 14%, P=0.035. XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. Keywords: breast cancer, capecitabine, docetaxel, neoadjuvant chemotherapy, curative effect, toxic side effects

  15. MODERN THERAPY OF THE RETINA VASCULITIS

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    Milena Vujanovic

    2001-07-01

    Full Text Available The therapy of the retina vasculitis is very complex. The basic therapeuticprinciple is to find a balance between the medicament toxicity and the seriousness ofthe retina disease. In easy forms of the disease, with a good seeing sharpness, it issufficient to observe a patient with no therapy at ali. For serious diseases themedicaments to be chosen are corticosteroids. Tf there is no favorable response to thecorticosteroid therapy, in bilateral serious forms of the retina vasculitis and especiallyin the Behchet disease, a therapy with cytostatics is applied. The most frequently usedare cyclophosphamide and chlorambucil. In the last few years s highly-selectiveimmunosuppressive cyclosporine A in small doses is used combined withcorticosteroids. A new approach to suppressing the auto-aggressive Ag-specific Tcellsand their pro-inflammatory products implies the use of a new generation of immunosuppressive medicaments such as tacrolimus (FK 506 and T-cell specificantimetabolites. More recently the desensibilization by the retina S-antigen has beenused in the therapy of the retina vasculitis.

  16. Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-10-01

    We would like to report our experience of using rituximab in cyclophosphamide refractory, rapidly progressive interstitial lung disease (ILD) in a patient with limited scleroderma. A 40-year-old man presented with 10-week history of inflammatory polyarthritis, which responded to a short course of oral corticosteroids. However, 3 weeks later, he developed new onset of exertional dyspnoea. High-resolution CT of the thorax was suggestive of early ILD. Surgical lung biopsy showed features of fibrotic non-specific interstitial pneumonia. He was diagnosed with scleroderma on the basis of: presence of anticentromere antibodies, Raynaud\\'s phenomenon, pulmonary fibrosis, digital oedema and hypomotility along with a dilated oesophagus. He was treated aggressively with pulse doses of corticosteroids and cyclophosphamide; however, his ILD continued to deteriorate. At this stage, he received rituximab (two pulses of 1 g each), which led to a gradual clinical improvement. Now, 12 months since his rituximab infusion, he walks 2 miles daily without any exertional dyspnoea.

  17. Baseline proteinuria, urinary osmotic pressure, and renal function as positive predictors of corticosteroids plus cyclophosphamide treatment efficacy in IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    Fang Jing; Li Wenge; Li Duo; Tan Zhao

    2014-01-01

    Background Very limited data are available on factors predictive of corticosteroids plus cyclophosphamide treatment efficacy on IgA nephropathy (IgAN).The aim of the study was to research the clinical factors predictive of treatment efficacy in IgAN.Methods One hundred and fifty-nine patients with IgAN (proteinuria ≥2 g/d and estimated glomerular filtration rate 30-89 ml·min-1·1.73 m-2) were treated with corticosteroids/cyclophosphamide followed by a 12-month follow-up.According to their response,these patients were divided into remission group (proteinuria <0.5 g/d) and non-remission group (proteinuria ≥0.5 g/d),and their clinical data collected.Results In the present study,72.96% of the individuals underwent a complete remission,and their response was related to baseline proteinuria,urinary osmotic pressure,and renal function (P <0.05).Patients with baseline proteinuria more than 3 g/d,urinary osmotic pressure greater than 600 mOsm/L,and eGFR 60-89 ml·min-1·1.73 m-2 responded well to the combination of corticosteroids and cyclophosphamide (86.90% vs.57.33%,P=0.000; 81.48% vs.64.10%,P=0.014; 83.17% vs.55.17%,P=0.000).Conclusion The response to the combination of corticosteroids and cyclophosphamide might be well associated with baseline proteinuria,urinary osmotic pressure,and renal function in patients with IgAN.

  18. The influence of glutathion S-transferase P-1 polymorphism A313G rs1695 on the susceptibility to cyclophosphamide hematologic toxicity in Indonesian patients

    Directory of Open Access Journals (Sweden)

    Dita Hasni

    2016-07-01

    Full Text Available Background: Chemotherapy often causes side effects such as hematologic toxicity. The degree of toxicity is often associated with genetic polymorphism. This study aims to determine the influence of GSTP1 A313G polymorphism, an enzyme responsible for detoxifying cyclophosphamid, on incidence and severity of cyclophosphamid hematologic toxicity.Methods: 91 Indonesian females diagnosed with breast cancer at Haji Adam Malik Central General Hospital, Medan, receiving cyclophosphamide, doxorubicin/epirubicin and 5-FU were included in this retrospective cohort study. DNA was extracted from peripheral leukocytes and GSTP1 A313G genotyping was analyzed using polymerase chain reaction-restriction length fragment polymorphism (PCR-RFLP. Genotype deviation and allele frequencies were also determined by Hardy-Weinberg Equilibrium. The degrees of hematologic toxicity (leucopenia and neutropenia data after chemotherapy cycles 1 and 3 were collected from the patient medical records. The data were analyzed using chi-square test.Results: 60.4% of the patients had the wildtype (A/A, while 29.7% were heterozygous (A/G, and 9.9% were homozygous mutant (G/G. There was no significant deviation of allele and genotype frequency from Hardy-Weinberg Equilibrium. The G allele (A/G & G/G contributes to more severe degree of leukopenia compared to patients with wild type allele (A/A  (p<0.05 after the 3rd chemotherapy cycles.Conclusion: There was association between GSTP1 polymorphism with the degree of hematologic toxicity in breast cancer patients receiving cyclophosphamide chemotherapy regimen.

  19. A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation

    OpenAIRE

    Alyamkina, Ekaterina A; Nikolin, Valeriy P; Popova, Nelly A.; Dolgova, Evgenia V; Proskurina, Anastasia S; Orishchenko, Konstantin E.; Efremov, Yaroslav R.; Chernykh, Elena R.; Ostanin, Alexandr A.; Sidorov, Sergey V; Ponomarenko, Dmitriy M.; Zagrebelniy, Stanislav N; Bogachev, Sergey S.; Shurdov, Mikhail A

    2010-01-01

    Background Immunization of mice with tumor homogenate after combined treatment with cyclophosphamide (CP) and double-stranded DNA (dsDNA) preparation is effective at inhibition of growth of tumor challenged after the treatment. It was assumed that this inhibition might be due to activation of the antigen-presenting cells. The purpose was to develop improved antitumor strategy using mice. We studied the combined action of cytostatics doxorubicin (Dox) plus CP with subsequent dsDNA preparation ...

  20. Protective effects of a by-product of the pecan nut industry (Carya illinoensis) on the toxicity induced by cyclophosphamide in rats Carya illinoensis protects against cyclophosphamide-induced toxicity.

    Science.gov (United States)

    Benvegnú, D; Barcelos, R C S; Boufleur, N; Reckziegel, P; Pase, C S; Müller, L G; Martins, N M B; Vareli, C; Bürger, M E

    2010-01-01

    This study investigated the antioxidant effects of pecan nut (Carya illinoensis) shell aqueous extract (AE) on toxicity induced by cyclophosphamide (CP) in the heart, kidney, liver, bladder, plasma and erythrocytes of rats. Rats were treated with water or pecan shell AE (5%) ad libitum, replacing drinking water for 37 days up to the end of the experiment. On day 30, half of each group received a single administration of vehicle or CP 200 mg/kg-ip. After 7 days, the organs were removed. Rats treated with CP showed an increase in lipid peroxidation (LP) and decrease in reduced glutathione (GSH) levels in all structures. Catalase (CAT) activity was increased in the heart and decreased in liver and kidney. Besides, CP treatment decreased plasmatic vitamin C (VIT C) levels and induced bladder macroscopical and microscopical damages. In contrast, co-treatment with pecan shell AE prevented the LP development and the GSH depletion in all structures, except in the heart and plasma, respectively. CAT activity in the heart and liver as well as the plasmatic VIT C levels remained unchanged. Finally, AE prevented CP-induced bladder injury. These findings revealed the protective role of pecan shell AE in CP-induced multiple organ toxicity.

  1. Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun J.; Brown, Matthew S. [David Geffen School of Medicine, UCLA, Center for Computer Vision and Imaging Biomarker, Department of Radiological Sciences, Los Angeles, CA (United States); Elashoff, Robert [David Geffen School of Medicine, UCLA, Department of Biostatistics and Biomathematics, Los Angeles, CA (United States); Li, Gang [School of Public Health, UCLA, Department of Biostatistics, Los Angeles, CA (United States); Gjertson, David W. [School of Public Health and David Geffen School of Medicine, UCLA, Department of Biostatistics and Pathology, Los Angeles (United States); Lynch, David A. [National Jewish Health, Radiology Department, Denver, CO (United States); Strollo, Diane C. [UPMC Presbyterian, Radiology Department, Pittsburgh, PA (United States); Kleerup, Eric; Tashkin, Donald P. [David Geffen School of Medicine, UCLA, Department of Med-Pul and Critical Care, Los Angeles, CA (United States); Chong, Daniel; Shah, Sumit K.; Ahmad, Shama; Abtin, Fereidoun; Goldin, Jonathan G. [David Geffen School of Medicine, UCLA, Department of Radiological Sciences, Los Angeles, CA (United States)

    2011-12-15

    The Scleroderma Lung Study showed the efficacy of cyclophosphamide in modestly improving the forced vital capacity (FVC) compared with placebo over 1 year. Using changes in texture-based scores that quantify lung fibrosis as the percentage involvement of reticulation patterns, the effectiveness of cyclophosphamide was re-assessed by examining its impact on quantitative lung fibrosis (QLF). Axial HRCT images were acquired (1-mm slice thickness, 10-mm increments) in the prone position at inspiration. A validated model for quantifying interstitial disease patterns was applied to images from 83 subjects at baseline and 12 months. Scores were calculated for six zones (upper, mid, lower of the right/left lung) and the whole lung. Average changes were compared. Correlations were performed between QLF and physiological and clinical scores. From the most severe zones identified at baseline, QLF scores decreased by 2.6% in the cyclophosphamide group, whereas they increased by 9.1% in the placebo group, leading to {proportional_to}12% difference (p = 0.0027). Between-treatment difference in whole lung QLF was {proportional_to}5% (p = 0.0190). Significant associations were observed between changes in QLF and FVC (r = -0.33), dyspnea score (r = -0.29), and consensus visual score (p = 0.0001). QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease. (orig.)

  2. Role of {sup 18}F-FDG PET-CT in monitoring the cyclophosphamide induced pulmonary toxicity in patients with breast cancer - 2 Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Taywade, Sameer Kamalakar; Kumar, Rakesh; Bhethanabhotla, Sainath; Bal, Chandrasekhar [A.I.I.M.S, New Delhi (India)

    2016-09-15

    Drug induced pulmonary toxicity is not uncommon with the use of various chemotherapeutic agents. Cyclophosphamide is a widely used chemotherapeutic drug in the treatment of breast cancer. Although rare, lung toxicity has been reported with cyclophosphamide use. Detection of bleomycin induced pulmonary toxicity and pattern of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) uptake in lungs on fluorodeoxyglucose positron emission tomography-computed tomography ({sup 18}F-FDG PET-CT) has been elicited in literature in relation to lymphoma. However, limited data is available regarding the role of {sup 18}F-FDG PET-CT in monitoring drug induced pulmonary toxicity in breast cancer. We here present two cases of cyclophosphamide induced drug toxicity. Interim {sup 18}F-FDG PET-CT demonstrated diffusely increased tracer uptake in bilateral lung fields in both these patients. Subsequently there was resolution of lung uptake on {sup 18}F-FDG PET-CT scan post completion of chemotherapy. These patients did not develop significant respiratory symptoms during chemotherapy treatment and in follow up.

  3. The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis.

    Science.gov (United States)

    Baskin, Esra; Ozen, Seza; Cakar, Nilgun; Bayrakci, Umut S; Demirkaya, Erkan; Bakkaloglu, Aysin

    2010-01-01

    Cyclophosphamide (CYC) has been the landmark in the treatment of lupus nephritis. However, long-term treatment with CYC is associated with significant side effects. We aimed to evaluate the efficacy of short-term intravenous (IV) CYC treatment as a remission induction treatment followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as a maintenance treatment. Twenty patients (18 girls) with biopsy-proven class III (5) and IV (15) lupus nephritis were included in to the study. Detailed clinical and laboratory data and patient outcomes were evaluated. All patients received three methylprednisolone (MP) IV pulses, followed by oral prednisone 0.5-1 mg/kg per day and one IV pulse of CYC per month for 6 months. Azathioprine was started as a remission-maintaining treatment. In ten of 20 patients, treatment was switched to MMF. The mean age at the time of diagnosis was 16.11 +/- 3.49 years, and the mean duration of follow-up was 49.6 +/- 27 months. Fourteen patients (70%) had complete remission, three (15%) had partial remission, one (5%) continued to have active disease, and two (10%) progressed to end-stage renal disease. Nine of the patients (45%) with complete remission had received AZA, and switching to MMF increased complete remission rate (additional five patients; 25%). In conclusion, short-term (6-month) IV bolus CYC treatment followed by AZA is a safe and effective treatment in children with severe lupus nephritis, and using MMF increases remission rate in resistant cases.

  4. Quantitation of anticancer drugs – Cyclophosphamide and ifosfamide in urine and water sewage samples by gas chromatography–mass spectrometry

    Directory of Open Access Journals (Sweden)

    Veeravan Lekskulchai

    2016-10-01

    Full Text Available Objectives: Cyclophosphamide (CP and ifosfamide (IF are effective anti-cancer drugs but their genotoxicity can harm everyone contacting them occupationally or environmentally. Therefore, a sensitive method for monitoring their amounts in biological and environmental samples is needed. This has aimed to develop a method for analyzing these drugs in urine and water sewage samples. Material and Methods: The drug spiked samples were extracted, derivatized, and analyzed by gas chromatography–mass spectrometry and the analytical parameters were validated. Results: The method gave linear calibration curves at the concentrations of 0–190 nmol/l. It had the quantitation limit of 3.8 nmol/l and showed acceptable specificity, accuracy, recovery and precision. Conclusions: The developed method can be used reliably for monitoring CP and IF concentrations in urine and water sewage. The method will be applied for preventing health risk from occupational and environmental exposures to these drugs. Int J Occup Med Environ Health 2016;29(5:815–822

  5. The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.

    Science.gov (United States)

    Holter-Chakrabarty, Jennifer L; Pierson, Namali; Zhang, Mei-Jie; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud D; Artz, Andrew S; Baron, Frédéric; Bredeson, Christopher N; Dvorak, Christopher C; Epstein, Robert B; Lazarus, Hillard M; Olsson, Richard F; Selby, George B; Williams, Kirsten M; Cooke, Kenneth R; Pasquini, Marcelo C; McCarthy, Philip L

    2015-07-01

    Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning.

  6. Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Camargos Aroldo F

    2010-05-01

    Full Text Available Abstract Background Reproductive function following chemotherapy is of increasing importance given that survival rates are improving. We assessed whether a gonadotropin-releasing hormone antagonist (GnRHant; cetrorelix could promote ovarian protection against damage due to chemotherapy. Methods Forty-two female Wistar rats were used in this study. Animals were divided into four groups: group I (n = 9 received placebo twice; group II (n = 12 received placebo + cyclophosphamide (CPA; group III (n = 12 received GnRHant + CPA; and group IV (n = 9 received GnRHant + placebo. After medication, the estrous cycle was studied through vaginal smears. Rats were mated, pregnancy was documented and the number of live pups evaluated. Afterwards, rat ovaries were removed and prepared for histological studies. The ovarian cross-sectional area was measured and follicles were counted. Results Cyclic changes in vaginal smears were observed in all but one animal after treatment, but group II had a significantly lower rate of animals with proestrus or estrus (p Conclusion The use of a GnRHant before CPA chemotherapy provided protection of fertility.

  7. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Directory of Open Access Journals (Sweden)

    Belinda C. Gómez-Meda

    2016-01-01

    Full Text Available Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs and micronucleated polychromatic erythrocytes (MNPCEs in the samples from pups in the experimental groups (P<0.02 and increased MNPCE frequencies in the samples from the dams (P<0.05. These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects.

  8. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma.

    Science.gov (United States)

    Kumar, Shaji; Flinn, Ian; Richardson, Paul G; Hari, Parameswaran; Callander, Natalie; Noga, Stephen J; Stewart, A Keith; Turturro, Francesco; Rifkin, Robert; Wolf, Jeffrey; Estevam, Jose; Mulligan, George; Shi, Hongliang; Webb, Iain J; Rajkumar, S Vincent

    2012-05-10

    Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms)≥very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442).

  9. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Science.gov (United States)

    Bañales-Martínez, Luis R.; Lemus-Varela, María de Lourdes; Trujillo, Xóchitl; Sánchez-Parada, María G.; Armendáriz-Borunda, Juan; Zúñiga-González, Guillermo M.

    2016-01-01

    Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs) and micronucleated polychromatic erythrocytes (MNPCEs) in the samples from pups in the experimental groups (P < 0.02) and increased MNPCE frequencies in the samples from the dams (P < 0.05). These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects. PMID:28018917

  10. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update.

    Science.gov (United States)

    Bacigalupo, A; Dominietto, A; Ghiso, A; Di Grazia, C; Lamparelli, T; Gualandi, F; Bregante, S; Van Lint, M T; Geroldi, S; Luchetti, S; Grasso, R; Pozzi, S; Colombo, N; Tedone, E; Varaldo, R; Raiola, A M

    2015-06-01

    This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n=92) or TBI, fludarabine (n=56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n=75), myelodisplastic syndrome (n=24), myelofibrosis (n=16), high-grade lymphoma (n=15) and others (n=18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (Ptransplant.

  11. Effects of pentoxifylline on some peripheral blood parameters and haemostasis in acute pulmonary tissue injury after cyclophosphamide.

    Science.gov (United States)

    Sulkowska, M; Musiatowicz, B; Sulkowski, S; Giedrojć, J; Sulik, M; Jakubowski, A; Terlikowski, S; Pasztaleniec, L; Baltaziak, M; Sobaniec-Lotowska, M

    1997-01-01

    Cyclophosphamide (CP) is one of the widely used cytostatic drugs, with a strong toxic influence on pulmonary tissue. Experimental works have shown that a single high dose of CP causes injury to all elements of the interalveolar septum, especially to the alveolar endothelial and epithelial cells. The aim of this work was to evaluate the influence of pentoxifylline (PTXF) (30 mg/kg b.w.) on the ultrastructure of lungs capillaries and blood cell count as well as plasma fibrinogen levels in Wistar rats after intraperitoneal injection of 150 mg/b.w. CP. We established that in the doses applied PTXF had no statistically significant influence on the number of leukocytes and erythrocytes determined in the left ventricular blood of rats receiving CP, while the number of white cells from animals given PTXF only was higher than in controls. There was a smaller decrease in the number of platelets (p < 0.05) and smaller reduction in fibrinogen level (p < 0.01) in the serum of PTXF-CP animals than in the CP group. The results obtained suggest a protective effect of PTXF on CP induced changes, which have been evidenced in some of the parameters examined. Ultrastructural examinations found the lungs to be the organ of extramedullary thrombocytopoiesis in CP-treated animals and revealed that platelet accumulation in the system of lung capillaries was a potential cause of the decrease observed in the number of blood platelets following CP administration.

  12. Sperm abnormalities induced by pre-pubertal exposure to cyclophosphamide are effectively mitigated by Moringa oleifera leaf extract.

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    Nayak, G; Vadinkar, A; Nair, S; Kalthur, S G; D'Souza, A S; Shetty, P K; Mutalik, S; Shetty, M M; Kalthur, G; Adiga, S K

    2016-03-01

    Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy.

  13. Omega-3 fatty acids are able to modulate the painful symptoms associated to cyclophosphamide-induced-hemorrhagic cystitis in mice.

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    Freitas, Raquel D S; Costa, Kesiane M; Nicoletti, Natália F; Kist, Luiza W; Bogo, Maurício R; Campos, Maria M

    2016-01-01

    This study investigated the effects of the long-term dietary fish oil supplementation or the acute administration of the omega-3 fatty acid docosahexaenoic acid (DHA) in the mouse hemorrhagic cystitis (HC) induced by the anticancer drug cyclophosphamide (CYP). HC was induced in mice by a single CYP injection (300mg/kg ip). Animals received four different diets containing 10% and 20% of corn or fish oil, during 21days. Separated groups received DHA by ip (1μmol/kg) or intrathecal (i.t.; 10μg/site) routes, 1h or 15min before CYP. The behavioral tests (spontaneous nociception and mechanical allodynia) were carried out from 1h to 6h following CYP injection. Bladder inflammatory changes, blood cell counts and serum cytokines were evaluated after euthanasia (at 6h). Immunohistochemistry analysis was performed for assessing spinal astrocyte and microglia activation or GPR40/FFAR1 expression. Either fish oil supplementation or DHA treatment (ip and i.t.) markedly prevented visceral pain, without affecting CYP-evoked bladder inflammatory changes. Moreover, systemic DHA significantly prevented the neutrophilia/lymphopenia caused by CYP, whereas this fatty acid did not significantly affect serum cytokines. DHA also modulated the spinal astrocyte activation and the GPR40/FFAR1 expression. The supplementation with fish oil enriched in omega-3 fatty acids or parenteral DHA might be interesting nutritional approaches for cancer patients under chemotherapy schemes with CYP.

  14. Effects of Spirulina on Cyclophosphamide-Induced Ovarian Toxicity in Rats: Biochemical and Histomorphometric Evaluation of the Ovary

    Science.gov (United States)

    Yener, Nese Arzu; Sinanoglu, Orhun; Ilter, Erdin; Celik, Aygen; Sezgin, Gulbuz; Midi, Ahmet; Aksungar, Fehime

    2013-01-01

    Cyclophosphamide (Cyc) is known to cause ovotoxicity and infertility in women. Our aim is to investigate the possible ovotoxic effects of Cyc and possible antioxidant and protective effects of blue-green algae, Spirulina (Sp), in rat ovaries. Eighteen rats were given: group I (n = 6, control); group II (n = 6, CP), a single dose Cyc; group III (n = 6, Sp+Cyc), 7 days Sp+single dose Cyc. Tissue malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities are assessed biochemically. Normal and atretic primordial and primary follicle counts for all sections obtained for each ovary are calculated. Mean number of follicle counts for each group are compared. In Sp+Cyc group, tissue MDA levels were significantly lower than those in the CP and higher than those in the C group (CP > Sp+Cyc > C). Tissue SOD activity was significantly higher in Sp+Cyc group than that in the CP group and lower than that in the C group (C > Sp+Cyc > C). No statistically significant difference was found between the ovarian CAT activities in any group. Histomorphometrically, there was also no significant difference between the mean numbers of normal and atretic small follicle counts. Our results suggest that single dose Cyc has adverse effects on oxidant status of the ovaries and Sp has protective effects in Cyc-induced ovotoxicity. PMID:23762559

  15. Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage.

    Science.gov (United States)

    Nayak, Guruprasad; Honguntikar, Sachin D; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Mutalik, Srinivas; Setty, Manjunath M; Kalyankumar, Raksha; Krishnamurthy, Hanumanthappa; Kalthur, Guruprasad; Adiga, Satish Kumar

    2016-04-22

    Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities. Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection. CP induced a significant decrease in testicular weight (p<0.01) and depletion of germ cells (p<0.001) and higher level of DNA damage (p<0.001) compared to control. The expression of P53, Bax, Cytochrome C (Cyt C) was increased while there was a decrease in the expression of Bcl2, c-Kit and Oct4. Administration of MOE 24h prior to CP treatment ameliorated the depletion (p<0.001), DNA damage (p<0.001) and apoptosis (p<0.01) of germ cells induced by CP. The mitigating effect of MOE appears to be mediated by up-regulating the expression of c-Kit and Oct4 transcripts in P53-independent manner. MOE protects the spermatogonial cells from CP-induced damage by modulating the apoptotic response elicited by CP and therefore can be considered as an efficient method of male fertility preservation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Cyclophosphamide-induced blood and tissue eosinophilia in contact sensitivity: mechanism of hapten-induced eosinophil recruitment into the skin.

    Science.gov (United States)

    Satoh, T; Chen, Q J; Sasaki, G; Yokozeki, H; Katayama, I; Nishioka, K

    1997-01-01

    The mechanism leading to selective production and accumulation of eosinophils in certain allergic skin diseases is unknown. Cyclophosphamide treatment (150 mg/kg) of BALB/c mice 48 h before sensitization with picryl chloride (PCl) resulted in striking blood and tissue eosinophilia, maximal at 13 days. Blood eosinophilia was not induced by the sensitization with oxazolone and 2,4-dinitrofluorobenzene. Challenge with 1 % PCl, but not croton oil caused preferential eosinophil accumulation into the dermis, which was associated with the enhanced expression of vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells. Intravenous administration of anti-VCAM-1 monoclonal antibody abrogated eosinophil infiltration. In this murine model, we examined the role of several cytokines, including chemokines in inducing selective tissue eosinophilia in vivo. Local administration of antibodies against interleukin (IL)-1beta, IL-4, tumor necrosis factor (TNF)-alpha, and RANTES, but not against IL-5 before challenge inhibited hapten-induced eosinophil recruitment. Intradermal injection of recombinant (r)IL-1beta, rIL-4, rTNF-alpha, rRANTES, and rMIP-1alpha induced marked eosinophil accumulation. Nonetheless, intradermal rIL-5 was not a chemoattractant for eosinophils in vivo. Our findings suggest that IL-1beta, IL-4, TNF-alpha, and RANTES contribute to the selective accumulation of eosinophils in contact sensitivity reaction. Although circulating IL-5 can activate eosinophils and prolong their survival, locally secreted IL-5 is not crucial for inducing eosinophil recruitment into the skin.

  17. Therapeutic drug monitoring for either oral or intravenous busulfan when combined with pre- and post-transplantation cyclophosphamide.

    Science.gov (United States)

    Lombardi, Lindsey R; Kanakry, Christopher G; Zahurak, Marianna; Durakovic, Nadira; Bolaños-Meade, Javier; Kasamon, Yvette L; Gladstone, Douglas E; Matsui, William; Borrello, Ivan; Huff, Carol Ann; Swinnen, Lode J; Brodsky, Robert A; Ambinder, Richard F; Fuchs, Ephraim J; Rosner, Gary L; Jones, Richard J; Luznik, Leo

    2016-01-01

    Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for allogeneic transplantation. We developed a strategy separating the Cy into two pre/post-transplantation doses (PTCy), providing myeloablative conditioning and single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the impact of Bu route on treatment-related toxicity for 131 consecutive adult patients. Busulfan was administered in four daily divided doses either orally (n = 72) or intravenously (n = 59) with pharmacokinetics on the first-dose and as necessary on subsequent doses to achieve a target area-under-the-concentration-curve (AUC) of 800-1400 μmol*min/L per dose. BuCy/PTCy with pharmacokinetics is well-tolerated with low treatment-related toxicity. Hepatic veno-occlusive disease incidence was 6% with two fatal events. Bu administration route in the context of BuCy/PTCy did not statistically impact hepatotoxicity, GVHD, relapse, disease-free survival, or overall survival. The BuCy/PTCy platform has a low incidence of treatment-related toxicity, including hepatotoxicity, in hematologic malignancies when using pharmacokinetics for a target AUC of 800-1400 μmol*min/L, irrespective of Bu administration route.

  18. Investigation of antimutagenic potential of Foeniculum vulgare essential oil on cyclophosphamide induced genotoxicity and oxidative stress in mice.

    Science.gov (United States)

    Tripathi, Pankaj; Tripathi, Rina; Patel, Rakesh K; Pancholi, Shyam S

    2013-01-01

    The present study investigated the protective effects of Foeniculum vulgare (fennel) essential oil (FEO) against genotoxicity induced by cyclophosphamide (CP). Mice bone marrow chromosomal aberration (CA), micronucleus, and sperm abnormality assays were employed to measure genotoxicity and cytotoxicity, respectively. The activities of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) content in the liver were also investigated spectrophotometrically. Animals were administered two different doses of FEO (1 and 2 mL/kg) continuously for 3 days at intervals of 24 hours by the oral route before tissue sampling. The results showed that CP produced a significant increase in the average percentage of aberrant metaphases and CAs, excluding gap and micronuclei formation in polychromatic erythrocytes (PCEs), produced cytotoxicity in mouse bone marrow cells, and induced abnormal sperms in the male germ line. CP also markedly inhibited the activities of SOD, CAT, and GSH and increased MDA content. Pretreatments with FEO significantly inhibited the frequencies of aberrant metaphases, CAs, micronuclei formation, and cytotoxicity in mouse bone marrow cells induced by CP and also produced a significant reduction of abnormal sperm and antagonized the reduction of CP-induced SOD, CAT, and GSH activities and inhibited increased MDA content in the liver. FEO inhibits genotoxicity and oxidative stress induced by CP.

  19. Ipomoea obscura ameliorates cyclophosphamide-induced toxicity by modulating the immune system and levels of proinflammatory cytokine and GSH.

    Science.gov (United States)

    Hamsa, T P; Kuttan, Girija

    2010-11-01

    Ipomoea obscura L. is a widely used medicinal plant. The objective of this study was to investigate its protective activity against cyclophosphamide (CTX)-induced toxicity in mouse models. Swiss albino mice were treated intraperitoneally with CTX (25 mg/kg body weight) along with I. obscura extract (10 mg/kg body weight) for 10 days. Extract significantly reduced myelosuppression caused by CTX and improved the relative organ weight, total white blood cell count, and bone marrow cellularity. The elevated levels of parameters related to pathophysiology of the liver, namely glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation, were significantly reduced by extract treatment. Reduction of liver and intestinal glutathione levels of CTX-treated animals was reversed by I. obscura. The lowered levels of cytokines, namely IFN-γ, IL-2, and granulocyte-monocyte colony-stimulating factor after CTX treatment were found to be increased in I. obscura treated animals. Treatment with I. obscura could also decrease the level of proinflammatory cytokine TNF-α. The data suggested that I. obscura can act as a potent chemoprotective agent and can be used as an adjuvant in chemotherapeutic applications.

  20. The Mitigating Effect of Citrullus colocynthis (L. Fruit Extract against Genotoxicity Induced by Cyclophosphamide in Mice Bone Marrow Cells

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    Mohammad Shokrzadeh

    2013-01-01

    Full Text Available Possible genoprotective effect of Citrullus colocynthis (L. (CCT fruits extract against cyclophosphamide- (CP-induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70 mg/kg b.w. 1 hr after the last injection of CCT. After 24 hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs. In addition, the number of polychromatic erythrocytes (PCEs among 1000 normochromatic erythrocytes (NCEs per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P<0.0001. At 200 mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.

  1. Cyclophosphamide effect on coccidioidomycosis in the rat Efecto de la ciclofosfamida en la infección por Coccidioides immitis en la rata

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    Mirta C. Remesar

    1989-12-01

    Full Text Available Coccidioidomycosis is a systemic mycosis, endemic in arid areas of the American continent. The rat was employed as an experimental host, since it had been shown to reproduce human lesions and present a chronic course of disease with granulomas mainly restricted to lungs. Given the influence of immunosuppressive therapy on the clinical course of human coccidioidomycosis, we studied the effect of cyclophosphamide (CY in the experimental rat model. Accordingly, animals were inoculated with 400 Coccidioides immitis arthroconidia of the Acosta strain, by intracardiacal route. As single CY doses failed to alter the course of disease, three schedules were used: A 4 daily doses of 20 mg/kg each, prior to C. immitis inoculation; B 4 similar daily doses after infection; and C; 6 doses of 20 mg/kg each, given from day +1 to +4, then on days +8 and +9, post infection (pi, taking day 0 as the time of fungal inoculation. The first two schedules inhibited antibody formation up to day 28 pi, without modifying cellular response to coccidioidin as measured by foodpad swelling. Initially, there was greater fungal spread than in controls receiving C. immitis alone, which proved self-limiting in the latter. In contrast, schedule C led to 559r mortality, with both humoral and cellular response abrogation, accompanied by extensive C. immitis dissemination. Histology disclosed significant alterations, such as the persistence of primary infection sporangia, corresponding to the acute stage of coccidioidomycosis in the absence of granuloma development. Therefore, the observed depression in cellular immunity seems responsible for the lack of inflammatory reaction capable of restricting sporangia proliferation in tissues which, in turn, enhances pathogen spread and mortality rate.El propósito de este trabajo fue estudiar el efecto de la inmunosupresión causada por la droga ciclofosfamida (CY sobre la infección de la rata con Coccidioides immitis por vía intracard

  2. [Tapering and termination of immunosuppressive therapy : Systemic lupus erythematosus].

    Science.gov (United States)

    Aringer, M; Leuchten, N; Fischer-Betz, R

    2017-02-01

    Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine. The individual risk of flares is often difficult to estimate but clinical remission and at least 3 years of immunosuppression are recommended for lupus nephritis. The duration of remission can also be shorter in cases of milder forms of disease. This review article tries to put the available evidence into a clinical perspective and to derive concrete recommendations.

  3. Electroconvulsive therapy for catatonia in juvenile neuropsychiatric lupus.

    Science.gov (United States)

    Leon, T; Aguirre, A; Pesce, C; Sanhueza, P; Toro, P

    2014-09-01

    Neuropsychiatric manifestations are serious and frequent complications of systemic lupus erythematous (SLE). Catatonia is a neuropsychiatric disorder characterized by motor disturbance (including waxy flexibility and catalepsy), stupor, excitement, negativism, mutism, echopraxia and echolalia. Catatonia associated with SLE has been only rarely reported, especially in children. Here we present a case of a 14-year-old patient encountered in consultation-liaison psychiatry who presented catatonia associated with SLE. Her catatonia was refractory to treatment with pulse methylprednisolone, intravenous cyclophosphamide and rituximab. The patient responded to a combined therapy of electroconvulsive therapy and benzodiazepines. The present case suggests that although rarely reported, catatonia seen in the background of SLE should be promptly identified and treated to reduce the morbidity.

  4. A randomized phase II trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer.

    Science.gov (United States)

    Shirahama, Takahisa; Muroya, Daisuke; Matsueda, Satoko; Yamada, Akira; Shichijo, Shigeki; Naito, Masayasu; Yamashita, Takuto; Sakamoto, Shinjiro; Okuda, Koji; Itoh, Kyogo; Sasada, Tetsuro; Yutani, Shigeru

    2017-02-11

    Since the prognosis of advanced biliary tract cancer (aBTC) still remains very poor, new therapeutic approaches, including immunotherapies, need to be developed. In the current study, we conducted an open-label randomized phase II study to test whether low dose cyclophosphamide (CPA) could improve antigen-specific immune responses and clinical efficacy of personalized peptide vaccination (PPV) in 49 previously treated aBTC patients. Patients with aBTC refractory to at least one regimen of chemotherapies were randomly assigned to receive PPV with low dose CPA (100 mg/ day for 7 days before vaccination) (PPV/CPA, n=24) or PPV alone (n=25). A maximum of four HLA-matched peptides were selected based on the pre-existing peptide-specific IgG responses, followed by subcutaneous administration. T cell responses to the vaccinated peptides in the PPV/CPA arm tended to be greater than those in the PPV alone arm. The PPV/CPA arm showed significantly better progression-free survival (median time: 6.1 vs 2.9 months; hazard ratio (HR): 0.427; P = 0.008) and overall survival (median time: 12.1 vs 5.9 months; HR: 0.376; P = 0.004), compared to the PPV alone arm. The PPV alone arm, but not the PPV/CPA arm, showed significant increase in plasma IL-6 after vaccinations, which might be associated with inhibition of antigen-specific T cell responses. These results suggested that combined treatment with low dose CPA could provide clinical benefits in aBTC patients under PPV, possibly through prevention of IL-6-mediated immune suppression. Further clinical studies would be recommended to clarify the clinical efficacy of PPV/CPA in aBTC patients. This article is protected by copyright. All rights reserved.

  5. Uso da ciclofosfamida em modelo de imunodepressão experimental em ovinos Ovine experimental immunosuppression using cyclophosphamide

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    Maurício Garcia

    2004-09-01

    Full Text Available A ciclofosfamida (CY foi usada para avaliar o efeito no sistema imune de ovinos. Carneiros adultos castrados foram divididos em 3 grupos, com 6 animais cada. Os Grupos I (dia 0 e II (dia 1 foram tratados com a CY (40 mg/kg, dose única, IV, e o Grupo III não foi tratado, permanecendo como controle. Todos os grupos foram imunizados no dia 0 com a vacina B19 contra a brucelose. No dia 6, todos animais foram sangrados e foi realizado o teste de soro-aglutinação para detecção de anticorpos anti-brucella. Foram também realizadas, diariamente durante 7 dias, contagens de linfócitos sangüíneos e dosagens de gamaglobulinas séricas por eletroforese. Os resultados encontrados mostraram uma diminuição estatística da resposta imune. Foram encontrados, nos Grupos I e II, baixos títulos de anticorpos anti-brucella, além de linfopenia e hipogamaglo-bulinemia. Uma alta mortalidade (40% foi encontrada nos animais tratados.Cyclophosphamide (CY was used to evaluate the effect on the immune system of sheep. Castred adult rams were divided into 3 groups, with 6 animals each one. Group I (day 0 and Group II (day 1 were treated with CY (40 mg/kg, single dose, IV, and Group III was not treated and remained as control. All groups were immunized on day 0 with B19 brucellosis vaccine. On day 6, all animals were bled and serum agglutination test for brucellosis antibodies detection was performed. During 7 days blood lymphocyte counts and electrophoresis gammaglobulin dosage were daily performed. The results showed statistical decrease of immune response. Low serum titers of brucellosis antibodies were found in Groups I and II, and lymphopenia and hypogammaglobulinemia were also found in these groups. A high mortality rate (40% occurred in the treated animals.

  6. Lactobacillus plantarum NCU116 Attenuates Cyclophosphamide-Induced Immunosuppression and Regulates Th17/Treg Cell Immune Responses in Mice.

    Science.gov (United States)

    Xie, Junhua; Nie, Shaoping; Yu, Qiang; Yin, Junyi; Xiong, Tao; Gong, Deming; Xie, Mingyong

    2016-02-17

    The balance of T helper cells 17 (Th17)/regulatory T cells (Treg) plays a key role in maintaining a normal immune response. It is well-known that cyclophosphamide (CTX) applied at high dose often damages the immune system by inhibiting immune cell proliferation. In this study, the immunomodulating effects of Lactobacillus plantarum NCU116 in CTX-induced immunosuppression mice were investigated. Results showed that the levels of cytokines interleukin (IL)-17 and IL-21 were significantly increased after 10 days of treatment with a high dose of NCU116 (46.92 ± 4.28 and 119.92 ± 10.89, respectively) compared with the model group (36.20 ± 2.63, 61.00 ± 6.92, respectively), and the levels of cytokines IL-23 and TGF-β3 of the three NCU116 treatment groups were significantly higher than that of the model group (90.48 ± 6.33 and 140.45 ± 14.30, respectively) (p < 0.05) and close to 62 and 69% of the normal group's level (140.98 ± 14.74 and 266.95 ± 23.11, respectively) at 10 days. The bacterium was also found to increase the expression levels of Th17 immune response and Treg immune response specific transcription factors RORγt and Foxp3. In addition, the bacterium significantly increased the number of CD4(+)T cells and dendrtic cells (DCs) and up-regulated mRNA expression of Toll-like receptors (TLRs). These findings demonstrated that NCU116 has the potential ability to enhance intestinal mucosa immunity and regulate the Th17/Treg balance, which may be attributed to the TLR pathway in DCs.

  7. Effects on quality of life, anti-cancer responses, breast conserving surgery and survival with neoadjuvant docetaxel: a randomised study of sequential weekly versus three-weekly docetaxel following neoadjuvant doxorubicin and cyclophosphamide in women with primary breast cancer

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    Wiseman Janice

    2011-05-01

    Full Text Available Abstract Background Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS, Disease Free Survival (DFS and Overall Survival (OS. Methods Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m2 or four cycles of 3-weekly docetaxel (100 mg/m2. The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed. Results At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%, pathological complete response (20% vs. 27%, and breast-conserving surgery (BCS rates (49% vs. 42%. Disease-free survival and overall survival were similar between treatment groups. Conclusions Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS or survival outcomes in the neoadjuvant setting. Trial registration ISRCTN: ISRCTN09184069

  8. Inmunomodulación y antiangiogénesis en la terapéutica oncológica: De la investigación básica a la clínica Immunomodulation and antiangiogenesis in cancer therapy: From basic to clinical research

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    O. Graciela Scharovsky

    2012-02-01

    Full Text Available La investigación básica y pre-clínica en oncología celular y molecular son pilares fundamentales en los que se apoyan la mayoría de los adelantos en la terapéutica del cáncer. Los hallazgos obtenidos y su aplicación en la práctica clínica constituyen la causa del avance sostenido en el tratamiento de la enfermedad neoplásica. El objetivo de este trabajo es resumir y discutir los resultados pre-clínicos en inmunomodulación y anti-angiogénesis para el tratamiento de diversos tipos de tumores, obtenidos en nuestro Instituto durante los últimos 15 años, y la posterior traslación y aplicación del conocimiento experimental en un Ensayo Clínico Fase I/II. Se describen los resultados que contribuyeron a descifrar los mecanismos de acción de la inmunomodulación antimetastásica con ciclofosfamida, la quimioterapia metronómica con diferentes drogas únicas o combinaciones, y finalmente el diseño y resultados preliminares de un ensayo clínico de quimioterapia metronómica para pacientes con cáncer de mama avanzado.Basic and pre-clinic research in cellular and molecular oncology are the main supports accounting for the advancement in cancer therapeutics. The findings achieved, and their implementation in clinical practice are responsible for the permanent improvement in the treatment of the neoplastic disease. Our present objective is to summarize and discuss the pre-clinical findings in immunomodulation and anti-angiogenesis for the treatment of several types of tumors obtained in our Institute during the last 15 years, and the subsequent translation and application of the acquired experimental knowledge in a Phase I/II Clinical Trial. We present the results and mechanisms of action of antimetastatic immunomodulation with cyclophosphamide, the metronomic chemotherapy with different single drugs and their combinations, and finally the design and preliminary results of a clinical trial with metronomic chemotherapy for patients with

  9. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Vogel Ulla

    2010-08-01

    Full Text Available Abstract Background The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion, *6, and CYP2D6 gene duplication. Results In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.

  10. TP53 mutations are associated with higher rates of pathologic complete response to anthracycline/cyclophosphamide-based neoadjuvant chemotherapy in operable primary breast cancer.

    Science.gov (United States)

    Wang, Yuxia; Xu, Ye; Chen, Jiuan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2016-01-15

    The role of TP53 mutations in predicting response to neoadjuvant chemotherapy in breast cancer remains controversial. The aims of this study were to investigate whether TP53 mutations were associated with response and survival in breast cancer patients who received neoadjuvant chemotherapy. Therefore, we identified TP53 mutations in the core-needle biopsy tumor samples obtained before the neoadjuvant chemotherapy from 351 operable primary breast cancer patients who either received anthracycline/cyclophosphamide-based (n = 252) or paclitaxel (n = 99) neoadjuvant chemotherapy. We found that 41.0% (144 of 351) of patients harbored TP53 mutations, and 14.8% of patients achieved a pCR (pathologic complete response) after neoadjuvant chemotherapy. Among patients treated with anthracycline/cyclophosphamide (n = 252), patients with TP53 mutations had a significantly higher pCR rate than those with wild-type (28.6 vs.7.1%; p TP53 mutation was an independent favorable predictor of pCR [odds ratio (OR) = 3.41; 95% confidence interval (CI) 1.50-7.77; p = 0.003] in this group; moreover, patients with TP53 mutation had a better distant recurrence-free survival (DRFS) than those with wild-type [unadjusted hazard ratio (HR) = 0.43; 95% CI 0.20-0.94; p = 0.030] in this group. Among patients treated with paclitaxel (n = 99), no significant difference in pCR rates was observed between patients with or without TP53 mutations (15.2 vs. 11.3%; p = 0.57). Our results suggested that patients with TP53 mutations are more likely to respond to anthracycline/ cyclophosphamide-based neoadjuvant chemotherapy and have a favorable survival.

  11. Involvement of interleukin-6-regulated nitric oxide synthase in hemorrhagic cystitis and impaired bladder contractions in young rats induced by acrolein, a urinary metabolite of cyclophosphamide.

    Science.gov (United States)

    Wang, Ching-Chia; Weng, Te-I; Wu, En-Ting; Wu, Mei-Hwan; Yang, Rong-Sen; Liu, Shing-Hwa

    2013-01-01

    Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, a chemotherapeutic alkylating agent. Acrolein is a urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis. Here, we investigated the effects and mechanisms of acrolein by intravesical instillation on urinary bladder muscle contractions and pathological alterations in rats. Acrolein instillation significantly increased the muscle contractions of rat bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions after 24 h. Acrolein increased phosphorylated protein kinase C (pan-PKC) expressions in bladders after 1 and 6 h but inhibited it after 24 h. Inducible nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in bladders 24 h after acrolein treatment. Twenty-four-hour acrolein instillation increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary bladder. The iNOS inhibitors significantly inhibited the acrolein-increased nitrite/nitrate levels, but not IL-6 levels. IL-6-neutralizing antibodies effectively inhibited the acrolein-increased NOx levels. The increased detrusor contractions by 1-h acrolein treatment were significantly reversed by the PKC inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing antibody. Both the iNOS inhibitor and IL-6-neutralizing antibody effectively reversed the increased iNOS expression, decreased PKC phosphorylation, increased bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment. Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates in the acrolein-triggered detrusor contraction inhibition and hemorrhagic cystitis. These findings may help us to find a new strategy to treat cyclophosphamide-induced hemorrhagic cystitis.

  12. Inhibition of cyclophosphamide-induced oxidative stress in brain by dietary inclusion of red dye extracts from sorghum (Sorghum bicolor) stem.

    Science.gov (United States)

    Oboh, Ganiya; Akomolafe, Toyin L; Adetuyi, Abayomi O

    2010-10-01

    The stem of sorghum is used as color additives in cooking meals and taken as beverages when steeped or boiled in water as folklore for the management of anemia and some other diseases. This study sought to assess the antioxidant and neuroprotective potentials of red dye extract from sorghum stem on cyclophosphamide-induced oxidative stress in rat brain. Wistar strain albino rats were fed diet supplemented with the red dye (0.5% and 1.0% inclusion) for 14 days. There was no significant difference (P > .05) in average feed intake and weight gain of rats fed the basal diet and the red dye-supplemented diet. However, intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight) 24 hours prior the termination of the experiment caused a significant (P brain malondialdehyde (MDA) content and serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in those rats fed diet without the dye supplement, whereas there was a significant decrease (P brain MDA content and serum enzyme activities in rats fed diet with the dye in a concentration-dependent manner. The protective effect of the red dye against cyclophosphamide-induced oxidative stress could be attributed to the high phenolic content (56.2%) and antioxidant activities of the red dye as typified by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging ability, reducing properties, and Fe(2+) chelating ability. Therefore, dietary inclusion of the red dye from sorghum stem could be harnessed in the management of neurodegenerative diseases associated with oxidative stress.

  13. Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma.

    Science.gov (United States)

    Nijhof, Inger S; Franssen, Laurens E; Levin, Mark-David; Bos, Gerard M J; Broijl, Annemiek; Klein, Saskia K; Koene, Harry R; Bloem, Andries C; Beeker, Aart; Faber, Laura M; van der Spek, Ellen; Ypma, Paula F; Raymakers, Reinier; van Spronsen, Dick-Johan; Westerweel, Peter E; Oostvogels, Rimke; van Velzen, Jeroen; van Kessel, Berris; Mutis, Tuna; Sonneveld, Pieter; Zweegman, Sonja; Lokhorst, Henk M; van de Donk, Niels W C J

    2016-09-19

    The prognosis of multiple myeloma (MM) patients who become refractory to lenalidomide and bortezomib is very poor, indicating the need for new therapeutic strategies for these patients. Next to the development of new drugs, the strategy of combining agents with synergistic activity may also result in clinical benefit for patients with advanced myeloma. We have previously shown in a retrospective analysis that lenalidomide combined with continuous low-dose cyclophosphamide and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients. To evaluate this combination prospectively, we initiated a phase 1/2 study to determine the optimal dose and to assess its efficacy and safety in lenalidomide-refractory MM patients. The maximum tolerated dose (MTD) was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous cyclophosphamide (50 mg/day) and prednisone (20 mg/day). At the MTD (n=67 patients), the overall response rate was 67%, and at least minimal response was achieved in 83% of the patients. Median PFS and OS were 12.1 and 29.0 months, respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities, defined as t(4;14), t(14;16), del(17p), and/or ampl(1q) as assessed by FISH. Neutropenia (22%) and thrombocytopenia (22%) were the most common grade 3-4 hematologic adverse events. Infections (21%) were the most common grade 3-5 non-hematologic adverse events. In conclusion, the addition of continuous low-dose oral cyclophosphamide to lenalidomide and prednisone offers a new therapeutic perspective for multidrug refractory MM patients. This trial was registered at www.clinicaltrials.gov as #NCT01352338.

  14. Expression of phosphorylated cAMP response element binding protein (p-CREB) in bladder afferent pathways in VIP-/- mice with cyclophosphamide (CYP)-induced cystitis

    DEFF Research Database (Denmark)

    Jensen, Dorthe G; Studeny, Simon; May, Victor

    2008-01-01

    The expression of phosphorylated cAMP response element binding protein (p-CREB) in dorsal root ganglia (DRG) with and without cyclophosphamide (CYP)-induced cystitis (150 mg/kg, i.p; 48 h) was determined in VIP(-/-) and wild-type (WT) mice. p-CREB immunoreactivity (IR) was determined in bladder...... (Fast blue) afferent cells. Nerve growth factor (NGF) bladder content was determined by enzyme-linked immunosorbent assays. Basal expression of p-CREB-IR in DRG of VIP(-/-) mice was (p .... Detrusor smooth muscle thickness was significantly increased in VIP(-/-) mice. Bladder NGF expression may contribute to differences in p-CREB expression....

  15. Saddle pulmonary embolus and bronchiolitis obliterans with organizing pneumonia develop simultaneously after first cyclophosphamide, methotrexate, 5FU chemotherapy for breast cancer.

    Science.gov (United States)

    Al-Hameed, Fahad M

    2015-06-01

    A 62-year-old woman underwent a right mastectomy with axillary node dissection for a poorly differentiated ductal carcinoma. One month later, she underwent a left nephrectomy for a renal cell carcinoma. Two weeks after, she received her first cycle of cyclophosphamide, methotrexate, and 5FU (CMF) as a part of her breast cancer treatment. We describe an unusual case of non-occlusive saddle pulmonary embolus with extensive bilateral deep vein thrombosis and severe bronchiolitis obliterans with organizing pneumonia developing simultaneously after the first CMF chemotherapy for breast cancer.

  16. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    DEFF Research Database (Denmark)

    Vangsted, A. J.; Soeby, K.; Klausen, T.W.

    2010-01-01

    the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods: Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected....... We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion...

  17. Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine

    Directory of Open Access Journals (Sweden)

    Mandrik O

    2015-08-01

    Full Text Available Olena Mandrik,1 Isaac Corro Ramos,2 Saskia Knies,1,3 Maiwenn Al,1,2 Johan L Severens1,2 1Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Institute of Medical Technology Assessment (iMTA, Erasmus University Rotterdam, Rotterdam, the Netherlands; 3National Health Care Institute, Diemen, the Netherlands Abstract: The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER

  18. Efficacy of Compound of Ganoderma lucidum and Astragalus Extracts on Tumor-Bearing Mice Treated by Cyclophosphamide%灵芝黄芪复配物提高环磷酰胺对荷瘤小鼠的疗效

    Institute of Scientific and Technical Information of China (English)

    张佳俊; 廖鲜艳; 翁新楚

    2012-01-01

    研究灵芝(Ganoderma lucidum)黄芪(Astragalus)复配物对环磷酰胺(cyclophosphamide,CTX)治疗的荷瘤小鼠肿瘤和免疫功能的影响.建立小鼠S180肉瘤模型,每日灌胃低、中、高剂量的灵芝黄芪复配物,并配合腹腔注射CTX.连续处理小鼠2周后,分析抑瘤效应,测定小鼠脾指数、胸腺指数、外周血白细胞(white blood cell,WBC)数和红细胞(red blood cell,RBC)数等免疫指标.同单CTX治疗组相比,中、高剂量的灵芝黄芪复配物能显著加强CTX对小鼠S180肉瘤的抑制作用(P<0.01),明显改善CTX引起的小鼠胸腺萎缩(P<0.01)和白细胞减少症状(P<0.05,P<0.01).灵芝黄芪复配物对CTX的抑瘤治疗具有明显的增效减毒作用,其效果堪比于单味中药灵芝提取物辅助CTX的抑瘤疗效,可大大降低单味灵芝提取物的治疗成本,经济价值可观.%Effects of the compound of Ganoderma lucidum and Astragalus extracts on immunity and tumor of mice treated by cyclophosphamide (CTX) were investigated. The mice were given both compounds of Ganoderma lucidum and Astragalus extracts by gavage and CTX by peritoneal injection for two weeks after the mouse model bearing SI80 tumor were produced. Then the anti-tumor effect, the thymus index, spleen index and the amount of white blood cells (WBCs) and red blood cells ( RBCs) were observed and determined. Compared with the CTX group, the middle and high dose group of Ganoderma lucidum and Astragalus extracts significantly enhanced the effect of CTX on inhibiting the growth of S180 tumor (P < 0. 01) , and prominently relieve thymic atrophy ( P < 0. 01 ) and leucopenia ( P < 0. 05 , P < 0. 01 ) caused by CTX in mice. The compound of Ganoderma lucidum and Astragalus extracts showed synergy and attenuation of CTX in tumor therapy. Its efficacy was equivalent to that of single folium Ganoderma lucidum extract, which largely reduced the cost of single folium Ganoderma lucidum extract with a great economical value.

  19. Roscovitine triggers apoptosis in B-cell chronic lymphocytic leukemia cells with similar efficiency as combinations of conventional purine analogs with cyclophosphamide.

    Science.gov (United States)

    Zolnierczyk, Jolanta D; Błoński, Jerzy Z; Robak, Tadeusz; Kiliańska, Zofia M; Wesierska-Gadek, Józefa

    2009-08-01

    B-cell chronic lymphocytic leukemia (CLL) is characterized by an accumulation in peripheral blood of many long-lived lymphocytes that do not die because of the deregulation of apoptosis. Most CLL cells are quiescent, and therefore the leukemic lymphocytes are resistant to conventional chemotherapy. The aim of this study was to evaluate in vitro the chemosensitivity of CLL cells to cladribine or fludarabine used alone or in combinations with mafosfamide (Mf; the active form of cyclophosphamide) as well as to roscovitine, a potent inhibitor of cyclin-dependent kinases with proapoptotic potential. The results of flow cytometry revealed that tested agents differentially reduced the viability of leukemic cells. Interestingly, roscovitine exerts a similar cytotoxic effect as the combinations of the used purine analogs with Mf, but with other kinetics. Roscovitine kills leukemic cells after a much shorter exposure time. Immunoblotting analysis showed that the reduction of the number of living cells coincides with marked changes of the balance between pro- and antiapoptotic factors. The latter were markedly reduced. The activation of proapoptotic proteins became evident especially after exposure of cells to roscovitine alone or to combinations of purine analogs and Mf. Furthermore, exposure of CLL cells to tested drugs degraded p27(KIP1) protein. Our findings demonstrate that roscovitine alone significantly reduces the number of viable CLL cells by inducing them to undergo apoptosis, and it acts earlier than clinically applied combinations of purine analogs with Mf/cyclophosphamide. These results confirm the high efficacy of roscovitine against CLL cells.

  20. Increase of hematopoietic responses by triple or single helical conformer of an antitumor (1-->3)-beta-D-glucan preparation, Sonifilan, in cyclophosphamide-induced leukopenic mice.

    Science.gov (United States)

    Tsuzuki, A; Tateishi, T; Ohno, N; Adachi, Y; Yadomae, T

    1999-01-01

    It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on its conformation in mice. In this study, we examined the relationship between the conformation of Sonifilan (SPG) and hematopietic responses in cyclophosphamide (Cy)-induced leukopenic mice. SPG, a high molecular weight (1-->3)-beta-D-glucan, has a triple helical conformation in water, and it was changed by treatment with aqueous sodium hydroxide to the single helical conformer (SPG-OH). The effects of SPG or SPG-OH on hematopoietic responses in cyclophosphamide induced leukopenic mice were investigated by monitoring i) gene expression of cytokines by RT-PCR, ii) protein synthesis of interleukin 6 (IL-6) by ELISA and iii) colony formation of bone marrow cells (BMC). The mice administered Cy and SPG or SPG-OH expressed and produced higher levels of IL-6 mRNA and protein than the mice administered only Cy. Gene expression of NK1.1 was also induced by Cy/SPG (or SPG-OH) treatment. Induced gene expression of stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) by SPG/SPG-OH were also found in in vitro culture of BMC from Cy treated mice. These results strongly suggested that conformation of the glucans, single and triple helix, are independent of the hematopietic response.

  1. Efficacy of immunosoppressive therapy and steroid sparing effect in interstitial lung disease associated to antisynthetase syndrome

    Directory of Open Access Journals (Sweden)

    G. De Marchi

    2011-09-01

    Full Text Available Objective: To evaluate the role of bronchoalveolar lavage (BAL in patients with interstitial lung disease associated to antisynthetase syndrome. Methods: We describe 5 patients, anti-Jo1 positive, with interstitial lung disease (lung fibrosis and/or diffusion capacity of CO <80%. Patients were monitored with lung function tests every 6 months, with high-resolution computed tomography (HRCT every 12 months, and with bronchoalveolar lavage (BAL at baseline and in the subsequent follow-up. Patients were treated as follows: a azathioprine with colchicine, or cyclosporine alone b cyclophosphamide when high neutrophil or eosinophil count on BAL was observed. Only low-dose steroids were used for mild muscular or articular involvement. Results: Pulmonary involvement remained stable in all patients at months +24. Lung function remained unchanged compared to the baseline evaluation; HRCT was stable in patients with fibrosis and no progression into fibrosis was observed in patients with ground glass areas at baseline. Bacterial pneumonia occurred in one patient treated with cyclophosphamide and resolved after antibiotic therapy. Conclusions: Clinical manifestations, instrumental tests and BAL may be of value to choice the best immunosuppressive therapy in the single case. An early less aggressive approach (azathioprine with colchicine, or cyclosporine alone may be useful. BAL could be performed when a progression of the lung involvement is demonstrated in the subsequent follow-up. Cyclophosphamide may be a valid alternative treatment in the presence of a neutrophilic or eosinophilic alveolitis. Efficacy and safety of the aforementioned immunosuppressive approach were observed in our series, avoiding prolonged high-dose steroid administration.

  2. The use of electroconvulsive therapy in a patient with juvenile systemic lupus erythematosus and catatonia.

    Science.gov (United States)

    Mon, T; L'ecuyer, S; Farber, N B; White, A J; Baszis, K W; Hearn, J K; Spiegel, T E; French, A R; Kitcharoensakkul, M

    2012-12-01

    Catatonia is a rare manifestation in patients with systemic lupus erythematosus (SLE). As catatonia can be associated with both psychiatric and organic conditions, this could create a diagnostic dilemma once this occurs in SLE patients. The report describes a 15-year-old female with SLE who developed catatonia three days after the diagnosis of SLE was made. Her catatonia was refractory to the treatment with immunosuppressive therapy, which included pulse methylprednisolone, intravenous cyclophosphamide, rituximab, intravenous immunoglobulin (IVIG) and plasmapheresis. Given her persistent catatonia, electroconvulsive therapy (ECT) was initiated three months after the onset of her symptoms. After the third ECT treatment, her mental status dramatically improved and returned nearly to baseline while she was continued on the immunosuppression. This is the first report of a successful ECT therapy in catatonic lupus in children.

  3. Combination immunotherapy and photodynamic therapy for cancer

    Science.gov (United States)

    Hamblin, Michael R.; Castano, Ana P.; Mroz, Pawel

    2006-02-01

    Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

  4. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage II and IV low-grade malignant non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    A. Hagenbeek; H. Eghbali; S. Monfardini; U. Viloto; P.J. Hoskin; C. de Wolf-Peeters; K. MacLennan; E. Staab-Renner; J. Kalmus; A. Schott; I. Teodorovic; A. Negrouk; M. van Glabbeke; R. Marcus

    2006-01-01

    Purpose To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. Patients and Methods Between 1993 and 1997

  5. Family Therapy

    Science.gov (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  6. Hormone Therapy

    Science.gov (United States)

    ... types of estrogen therapy relieve vaginal dryness. • Systemic estrogen protects against the bone loss that occurs early in menopause and helps prevent hip and spine fractures. • Combined estrogen and progestin therapy may reduce the risk of ...

  7. Radiation Therapy

    Science.gov (United States)

    ... the area is stitched shut. Another treatment, called proton-beam radiation therapy , focuses the radiation on the ... after radiation treatment ends. Sore mouth and tooth decay. If you received radiation therapy to the head ...

  8. Electroconvulsive therapy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007474.htm Electroconvulsive therapy To use the sharing features on this page, please enable JavaScript. Electroconvulsive therapy (ECT) uses an electric current to treat depression ...

  9. Proton Therapy

    Science.gov (United States)

    ... IMRT) Brain Tumor Treatment Brain Tumors Prostate Cancer Lung Cancer Treatment Lung Cancer Head and Neck Cancer Images related to Proton Therapy Videos related to Proton Therapy Sponsored by Please ...

  10. Effect of the administration time of HS6101 on hematopoietic recovery in ICR mice injured by cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Shuang XING

    2015-06-01

    Full Text Available Objective To explore the effect of the administration time of HS6101 on hematopoietic recovery in ICR mice injured by cyclophosphamide (CTX. Methods One hundred and three male ICR mice were divided into 4 groups: CTX control, HS6101 prevention, HS6101 treatment, and HS6101 prevention+treatment groups. CTX was intraperitoneally injected into the ICR mice at a dose of 100mg/(kg.d for three consecutive days to establish a chemotherapeutics-injured model. HS6101 at a dose of 27μg/mouse in 0.2ml was subcutaneously injected into the mice 1h before the first administration of CTX in HS6101-prevention group, 1h after the last administration of CTX in HS6101 treatment group, and both at 1h before the first administration and 1h after the last administration of CTX in HS6101 prevention + treatment group. Physiological saline was subcutaneously injected into the mice in CTX control group (0.2ml/mouse. 10μl peripheral blood was collected from the caudal vein for WBC, neutrophil lymphocyte, RBC and platelet counts on day -1, 3, 5, 7, 9, 11, 13, 15, 17 with the MEK-7222K cell analyzer, and the cell count was compared between HS6101 treatment mice and CTX control mice. Another 30 male ICR mice were used for bone marrow colony forming unit (CFU assay and bone marrow histopathological examination, and they were assigned into normal control, CTX control, HS6101 prevention, HS6101treatment and HS6101 prevention + treatment groups (each n=6. On the day 4 and day 9 after CTX injection, mice were sacrificed and bone marrow cells were collected from the left femur for mononuclear cell (MNC isolation. 1×104 MNCs were planted in 1.0ml mouse CFU culture medium M3434 and cultured in incubator with the temperature of 37℃, and 5% CO2 for 7 days. After that, granulocyte macrophage-colony-forming unit (GM-CFU, megakaryocyte colony forming unit (MK-CFU, mixture-colony-forming unit (Mix-CFU, burst-forming unit-erythroid (BFU-E and colony-forming unit-erythroid (CFU

  11. New and emerging therapies for diseases of the oral cavity.

    Science.gov (United States)

    Popovsky, J L; Camisa, C

    2000-01-01

    It is obvious from the review of the literature that most treatments for oral diseases such as lichen planus, pemphigoid, and pemphigus are based on case reports, anecdotes, and small uncontrolled studies. Efforts must be made to perform more controlled studies to evaluate the efficacy of new treatments. Small numbers of patients at each site and multiple-drug therapy make this task difficult. Dermatologists should familiarize themselves with the newer immunosuppressive agents available. Use of these drugs requires knowledge of their pharmacokinetics and potential side effects, so that they may be used effectively and safely. Relatively low doses of azathioprine, cyclophosphamide, and cyclosporine should then be added to the dermatologist's armamentarium for the treatment of severe or recalcitrant diseases. Old drugs are resurfacing with new (but often off-label) uses as the underlying mechanisms of disease become understood. Thalidomide and mycophenolate mofetil are two examples of promising drugs for the future of dermatology.

  12. Methanolic Extract of Curcuma caesia Roxb. prevents the toxicity caused by Cyclophosphamide to bone marrow cells, liver and kidney of mice

    Directory of Open Access Journals (Sweden)

    Heisanam Pushparani Devi

    2016-01-01

    Full Text Available Introduction: With an ever increasing cause of cancer, it has been recommended to treat with conventional drugs, however because of the side effects caused by the conventional drugs, the research on medicinal plants has been intensified due to their less adverse and toxic effects. Objectives: The primary objective of the present study was to evaluate the protective effect of the medicinal plant Curcuma caesia Roxb. against free radicals ABTS + and O2 - . Also it was aimed to evaluate the protective effect of C.caesia Roxb. against the chemotherapeutic drug Cyclophosphamide and its side effects in liver and kidney. Methods: The rhizomes of the plant was extracted with methanol through soxhlet and its antioxidant activity was tested against ABTS + and O2 - . For antigenotoxic studies, animals were divided into eight groups and micronucleus assay was employed and for biochemical analysis serum sample was collected from the blood and SGOT, SGPT analysis was performed. Also the biochemical analysis was performed from both the liver and kidney. Results: The methanolic extract of Curcuma caesia Roxb. was found to scavenge the free radicals ABTS + and O2 - . the micronuclei formation was found to be increased in the positive control group as compared to the negative control group significantly (P<0.002 however increase in the number of micronuclei was found to be decrease with the pretreatment of the extract at