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Cisplatin
Kinds of Cisplatin Terms modified by Cisplatin Selected AbstractsSynthesis of Novel gluco - and galacto -Functionalized Platinum Complexes,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2009Janina Möker Abstract Cisplatin, carboplatin, oxaliplatin and further derivatives are worldwide established cytostatics for the treatment of a vast range of tumours. These drugs showed extraordinary success; however, side effects and primary or developed secondary resistance of tumour cells represent severe problems, which prompt the development of novel functionalized platinum complexes. Selectively protected monohydroxy derivatives of glucose and galactose could be etherified by ,-halo ethers. Further, Finkelstein reaction and malonate synthesis gave precursor glycoconjugates which were easily transformed into their (diammine)platinum complexes. First tests with different tumour cell lines show biological activity of the gluco -functionalized platinum complex.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2008Cristina P. Rodriguez MD Abstract Background. Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success. Methods. Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure. Results. The 5-year Kaplan,Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control. Conclusion. Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: Results of single-center study of 45 patientsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2005Ozden Altundag MD Abstract Background. Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. Methods. We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. Results. The mean age was 56.6 years (range, 34,75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. Conclusion. Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival. © 2004 Wiley Periodicals, Inc. Head Neck27: 15,21, 2005 [source] Effect of cancer therapy on pituitary,testicular axis,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2002S. J. Howell Summary Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men. Alkylating agents, such as cyclophosphamide and procarbazine, are the most common agents implicated. The vast majority of men receiving procarbazine-containing regimens for the treatment of lymphomas are rendered permanently infertile. Treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) appears to have a significant advantage in terms of testicular function, with a return to normal fertility in the vast majority of patients. Cisplatin-based chemotherapy for testicular cancer results in temporary azoospermia in most men with a recovery of spermatogenesis in about 50% after 2 years and 80% after 5 years. There is also evidence of chemotherapy-induced Leydig cell impairment in a proportion of these men, although this appears to be of no clinical significance in the majority of patients. The germinal epithelium is very sensitive to radiation-induced damage with changes to spermatogonia following as little as 0.1 Gy, and permanent infertility after fractionated doses of 2 Gy and above, whereas clinically significant Leydig cell impairment occurs rarely with doses of less than 20 Gy. [source] Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells?INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2010Fang-Zhen Shen Summary Low-dose chemotherapy drugs can suppress tumours by restraining tumour vessel growth and preventing the repair of damaged vascular endothelial cells. Cisplatin is a broad-spectrum, cell cycle-non-specific drug, but has serious side effects if used at high doses. There have been few reports on the anti-angiogenic effects of low-dose cisplatin and hence the effect of low-dose metronomic (LDM) chemotherapy on the proliferation and neovascularization of H22 hepatocarcinoma cells is discussed in this research. The influence of LDM chemotherapy with cisplatin on human umbilical vascular endothelial cells (HUVECs) and proliferation of the HepG2 human hepatocarcinoma cell line were measured using MTT assays. The LDM group was treated with cisplatin 0.6 mg/kg/day; the control group with saline 0.2 ml; the maximum tolerated dose (MTD) group with cisplatin 9 mg/kg/day. Vascular endothelial growth factor (VEGF) and matrix metallopeptidase 2 (MMP-2) were detected using immunohistochemical staining. A chicken chorio-allantoic membrane (CAM) model was used to check the inhibitory effect of LDM chemotherapy with cisplatin on neovascularization in vivo. Low-dose cisplatin inhibited HUVEC proliferation in a dose- and time-dependent manner, but was ineffective in inhibiting HepG2 cell proliferation. Tumour growth was delayed in mice receiving LDM cisplatin, without apparent body weight loss, compared with mice that received MTD cisplatin. Microvessel density and expression of VEGF and MMP-2 were much lower in mice receiving LDM cisplatin than in the control and MTD groups. Continuous low-dose cisplatin suppressed CAM angiogenesis in vivo. LDM chemotherapy with cisplatin can inhibit the growth of blood vessel endothelial cells in vitro and shows anti-angiogenic ability in vivo. [source] Metastatic urothelial cancer showing an efficacy by low-dose cisplatinINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2002Hideyasu Matsuyama Abstract A 69-year-old man who had developed multiple distant metastases on retrocaval lymph nodes after four courses of Methotraxate, Vinblastine, Adriamycin, Cisplatin (MVAC) chemotherapy was successfully treated by intravenous infusion of low-dose cisplatin (CDDP) (10 mg/time, once per week) and oral administration of 600 mg/day 5,-deoxy-5-fluorouridine (5,-DFUR), a pro-drug of 5-FU, in an outpatient setting. A partial response (62% reduction rate) was confirmed by abdominal computed tomography (CT) scan after 7 months. Although the CDDP dosage had been reduced to 5 mg/week 1 year previously, the tumor was still reducing in size in November 2000. Combination therapy of 5,-DFUR with low-dose CDDP could become an option for advanced bladder cancer that compromises the patient's quality of life, especially when used in an outpatient setting. [source] Increase of lipid peroxidation by cisplatin in WI38 cells but not in SV40-transformed WI38 cellsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2003Hsiu-Chuan Yen Abstract Cisplatin (CPT) is an effective anticancer drug that causes cumulative toxicity to normal tissues. It has been suggested that CPT damages normal cells by causing oxidative stress, but it is not known whether it can induce similar oxidative damage to tumor cells. In this study, by using normal human lung fibroblast (W138) cells and SV40-transformed WI38 (VA13) cells as a model, we compared the effect of CPT on cytotoxicity, apoptosis, lipid peroxidation, and mitochondrial gene expression, which could be regulated by oxidative stress, between normal and tumor cells. CPT induced greater growth inhibition and percentage of apoptotic cells in VA13 cells. However, levels of esterified F2 -isoprostanes and 4-hydroxy-2-nonenal, two specific products of lipid peroxidation, were increased by CPT in WI38 cells, but not in VA13 cells. Furthermore, the transcript level of mitochondrial 12S rRNA was augmented by CPT in both cells, but to a higher degree in WI38 cells. The data suggest a correlation between lipid peroxidation and cytotoxicity or increased mitochondrial transcript levels in WI38 cells but not in VA13 cells. The results also indicate an altered response of oxidative damage and mitochondrial gene regulation to CPT in the transformed phenotype of WI38 cells. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:39,46, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10059 [source] Trafficking and localization of platinum complexes in cisplatin-resistant cell lines monitored by fluorescence-labeled platinum,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005Xing-Jie Liang Cisplatin is a chemotherapeutic agent commonly used in the treatment of a wide variety of malignant tumors. Resistance to cisplatin represents a major obstacle to effective cancer therapy because clinically significant levels of resistance quickly emerge after treatment. Based on previous studies indicating abnormal plasma membrane protein trafficking in cisplatin-resistant (CP-r) cells, Fluorescence (Alexa Fluor)-labeled cisplatin was used to determine whether this defect altered the trafficking and localization of cisplatin by comparing drug sensitive KB-3-1 and KB-CP-r cells. Alexa Fluor,cisplatin was readily internalized and localized throughout the KB-3-1 cells, but overall fluorescence decreased in KB-CP-r cells, as detected by flow cytometry (FACS) and confocal microscopy. Only punctate cytoplasmic staining was observed in KB-CP-r cells with less fluorescence observed in the nucleus. Colocalization experiments with a Golgi-selective stain indicate the involvement of Golgi-like vesicles in initial intracellular processing of Alexa Fluor conjugated cisplatin complexes. As detected using an antibody to Alexa Fluor,cisplatin, cisplatin complex-binding proteins (CCBPs) were reduced in membrane fractions of single-step cisplatin-resistant KB-CP.5 cells, and increased in the cytoplasm of KB-CP.5 cells compared to KB-3-1 cells. CCBPs localized to lower density fractions in KB-CP.5 cells than in KB-3-1 cells as determined by iodixanol gradient centrifugation. In summary, inappropriate trafficking of CCBPs might explain resistance to cisplatin in cultured cancer cells, presumably because membrane binding proteins for cisplatin are not properly located on the cell surface in these cells, but are instead trapped in low density vesicles within the cytoplasm. © 2004 Wiley-Liss, Inc. [source] Chemotherapy: the effect of oral cryotherapy on the development of mucositisJOURNAL OF CLINICAL NURSING, Issue 6 2005erife Karagözo, lu MSc Aims and objective., The aim of this study is to investigate the effect of oral cryotherapy on the development of chemotherapy-induced mucositis in patients administered combined chemotherapy. Background., Mucositis has been of interest to scientists for more than 20 years. Unfortunately, this has not resulted in the development of standard procedures for prevention and management. To cope with this side-effect and to prevent opportunistic infections that may emerge during treatment, attempts are taken to provide preventative and comfort measures. In this context, cryotherapy (oral cooling) has become popular as a cheap and readily applicable method in preventing the developing due the rapid infusion of chemotherapy agents, or decreasing its severity. Design and method., Study involved 60 patients, 30 of whom were in the study group and 30 in the control group. Ice cubes at a size that can be moved easily in the mouth and whose corners have been smoothed in order that they will not cause irritation in the mouth has been used in oral cryotherapy in the study group. Oral chemotherapy was initiated five minutes before chemotherapy and maintained during venous infusions of etoposide (Vepesid®), platinol (Cisplatin®), mitomycin (Mitomycin-C®) and vinblastin (Velbe®) depending on the chemotherapy course. Results., According to Patient-Judged Mucositis Grading, the rate of mucositis is 36.7% in study group and 90.0% in control group, the difference between two groups being statistically significant (P < 0.05). According to Physician-Judged Mucositis Grading, the rate of mucositis is 10.0% in the study group and 50.0% in the control group, the difference between two groups being statistically significant (P < 0.05). Oral pH values decreased in 90% of the subjects in study group, i.e. mucositis risk was reduced whereas oral pH values remained unchanged or decreased in 86.7% of the subjects in the control group, namely mucositis risk increased. The difference between study and control groups in terms of the change in pH values after chemotherapy was found to be statistically significant (P < 0.05). Conclusion., Our findings have demonstrated that oral cryotherapy makes an important contribution to the protection of oral health by reducing the mucositis score according to patient- and physician-judged mucositis score and by increasing oral pH values. Relevance to clinical practice., Aggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae have often become overlooked as priorities of the treatment team. Effective approaches for the prevention or treatment of oral mucositis have not been standardized, and vary considerably among institutions. Prophylactic measures begin with an increased emphasis on improved oral status. Oral cryotherapy, the therapeutic administration of cold, is a prophylactic measure for oral inflammation. The relevance for clinical practice will be to understand the content of mucositis; comprehensive care should focus on the prevention of this complication in the clinical practice. [source] Ovarian endodermal sinus tumor in a 76-year-old womanJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2003Gülaydan Filiz Abstract A 76-year-old woman underwent surgery for pelvic mass, during which a 13 × 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later. [source] Influence of dosing schedules on toxicity and antitumour effects of combined cisplatin and docetaxel treatment in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Ayumi Kodama Abstract Objectives The combination of cisplatin and docetaxel shows a better cure rate against non-small-cell lung cancer than other drug combinations in clinical studies; however, severe myelosuppression and nephrotoxicity are dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule to reduce adverse effects and improve the antitumour effects. Methods Cisplatin and docetaxel were administered i.p. to male ICR mice simultaneously, or sequentially with either cisplatin or docetaxel first followed by the second drug 12 h later (docetaxel,cisplatin and cisplatin,docetaxel groups). Antitumour effects of these schedules were also tested in C57BL/6N mice bearing Lewis lung carcinomas. Key findings The simultaneous docetaxel/cisplatin group showed the lowest survival rate and the highest blood urea nitrogen (BUN) concentration. Cisplatin concentrations in the plasma and kidney were higher in the simultaneous dosing group than the sequential dosing groups. Antitumour effect was the greatest in the docetaxel,cisplatin group. Conclusions The docetaxel,cisplatin regimen inhibited tumour growth the best and reduced mortality and nephrotoxicity. [source] Antitumour Activity and Side Effects of Combined Treatment with Chitosan and Cisplatin in Sarcoma 180-Bearing MiceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2000YOSHIYUKI KIMURA We examined the possible modulation by chitosan of the antitumour effects and side effects of cisplatin (cis-diaminedichloroplatinum, CDDP). The study showed that CDDP had potent antitumour activity when administered orally as well as intraperitoneally. We also compared the antitumour activity and side effects of orally administered CDDP plus orally administered chitosan versus intraperitoneally administered CDDP plus orally administered chitosan in sarcoma 180-bearing mice. When CDDP (1.25 mg kg,1 × 2 day,1) was intraperitoneally administered to sarcoma 180-bearing mice, myelotoxicity (the reduction of leucocyte and platelet numbers), nephrotoxicity (the increase of blood nitrogen urea level), immunotoxicity (the reduction of spleen and thymus weight) and a reduction in body weight resulted. These intraperitoneally administered CDDP-induced side effects were not prevented by oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1) for 14 consecutive days. On the other hand, the side effects such as the reductions of body and spleen weights induced by orally administered CDDP (1.25 mg kg,1 × 2 day,1) were prevented by the oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1). From these results, we conclude that the orally administered chitosan plus CDDP might be useful for the prevention of body weight reduction and immunotoxicity (the reduction of spleen weight) induced by the orally administered CDDP without diminishing antitumour activity. [source] Investigation of interaction between human hemoglobin A0 and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detectionJOURNAL OF SEPARATION SCIENCE, JSS, Issue 10 2008Tibebe Lemma Abstract CIEF with whole column imaging detection (WCID) was used to investigate the interaction of platinum-based anticancer drugs, cis -platinum(II) diamine dichloride (cisplatin) and [SP-4-2-{1R-trans)]-(1,2-cyclohexanediamine- N,N,)[ethanedioata(2,)- O,O,]platinum (oxaliplatin), with human hemoglobin A0 (Hb). This technique facilitates the investigation and characterization of the formation of adducts between drugs and proteins. Cisplatin and oxaliplatin were mixed with the target protein at different concentrations (0:1, 1:1, 1:10, 1:50, and 1:100), and the reaction mixtures were incubated for 0, 0.5, 1, 12, 24, 48, and 72 h at 37°C in a water-bath. The focused Hb,drug adduct profiles were imaged by WCID. At higher drug to protein molar ratios (for both oxaliplatin and cisplatin), the results exhibit significant changes in the peak shapes and heights, which may indicate the destabilization of the protein. However, the conformational change was less evident at lower molar ratios. In addition, a major pI shift was observed for the oxaliplatin reaction mixtures (for 1:10, 1:50, and 1:100 ratios). In comparison with previously reported findings obtained by other analytical methods, conclusions were drawn about the validity of CIEF as a simple and convenient method for the investigation of protein,drug interactions. These results may provide useful information for further understanding the activity and toxicity of these chemotherapeutic drugs and improving their clinical performance. [source] Chemoradiotherapy in gallbladder cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 8 2006FACS, Xabier de Aretxabala MD Abstract Gallbladder cancer (GC) is considered a rare disease associated with a poor prognosis. Unfortunately, the low number of cases makes the performance of trials addressing the role of adjuvant, neoadjuvant, and/or palliative therapy difficult. For a long time, the majority of trials were 5-fluorouracil (5 FU)-based, and results were uniformly poor. Since the introduction of Gemcitabine, response rates of approximately 30% have been observed through the use of this drug and new approaches have been tested. In this sense, drugs such as Cisplatin and Capecitabine have been employed concurrently with gemcitabine and/or radiation. Since a recurrence pattern is both distant and local, chernoradiation seems a logical option to deal with the disease. However, at the present time, the lack of valid and scientific evidence means that most of the recommendations originate from trials dealing with other tumors, such as pancreas cancer and biliary tract cancer (BTC). The aforementioned treatment alternatives warrant further evaluation focusing on GC. J. Surg. Oncol. 2006;93:699,704. © 2006 Wiley-Liss, Inc. [source] Evaluation of serum cystatin C levels and 99mTechnetium-mercaptoacetyltriglycine-3 renal scintigraphy for the early detection of cisplatin-induced renal toxicity in cancer patientsNEPHROLOGY, Issue 2 2002Nazan GÜNEL SUMMARY: Cisplatin has a broad-spectrum antineoplastic activity. Nephrotoxicity is a prominent component of the toxicity profile of cisplatin-based chemotherapy. In recent years, several reports have confirmed that cystatin C (cys-C) demonstrates a better correlation with the glomerular filtration rate than with serum creatinine. Scintigraphic techniques are also widely used in evaluating renal function. In the present study, serum cys-C, serum creatinine concentrations and 99mTechnetium-mercaptoacetyltriglycine-3 (99mTc-MAG-3) scintigraphy were studied in 22 cisplatin-naive cancer patients, 3 days before and 24 h after the first cycle of cisplatin-based chemotherapy. Serum cystatin C and creatinine levels increased in cancer patients after chemotherapy (creatinine: from 68 ± 12 to 72 ± 17 nmol/L; cystatin-C: from 0.064 ± 0.025 to 0.072 ± 0.033 jimol/L), but these differences were not statistically significant (P>0.05). Semiquantitative variables of 99mTc-MAG-S scintigraphy significantly elevated after chemotherapy (T½*: from 10.27 ± 5.00to 16.17 ± 9.40 min, R20/max*: from 0.40 ± 0.12 to 0.67+0.45, Tmax**: from 5.40 ± 4.01 to 7.59 ± 5.30 min; *P<0.001, **P<0.01, respectively). These results suggest that MAG-3 scintigraphy is a highly sensitive method in the early detection of cisplatin-induced nephrotoxicity. Serum cystatin C doesn't seem to play a role in the early detection of cisplatin-induced nephrotoxicity. As a result, MAG-3 scintigraphy may be used in selected patients who have a predisposition for renal toxicity. [source] Initial testing of cisplatin by the pediatric preclinical testing program,PEDIATRIC BLOOD & CANCER, Issue 5 2008Mimi Tajbakhsh BS Abstract Background Cisplatin is one of the most widely used drugs for the treatment of solid tumors in adults and children. Here, we report the activity of cisplatin against the PPTP panels of childhood cancer xenografts. Procedures Cisplatin was evaluated against 23 cell lines, and 40 xenografts representing brain tumors, neuroblastoma, rhabdoid tumors, sarcoma, Wilms tumor, and acute lymphoblastic leukemia (ALL). The IC50 concentration in vitro was determined for 96 hr exposure. Solid tumors were grown subcutaneously in immune-deficient mice, and tumor dimensions measured weekly. ALL xenografts were inoculated intravenously and the percent human CD45+ cells in the peripheral blood determined weekly. The antitumor activity of cisplatin (7 mg/kg administered intraperitoneally on Days 0 and 21) was evaluated using time to event (EFS T/C), tumor growth delay (tumor volume T/C), and objective response measures. Results The median IC50 concentration in vitro was 0.87 µM (0.24,4.29 µM), and cisplatin exhibited broad range activity. Cisplatin induced significant differences in EFS distributions compared to controls in 20/28 solid tumors and 4/8 ALL models. Objective responses were observed in 7/28 solid tumor models (25%): partial responses in three rhabdomyosarcomas and one Ewing's sarcoma; complete responses in one rhabdoid tumor and the medulloblastoma; and a maintained complete response in one Wilms tumor. No objective responses were observed in the ALL panel. Conclusions Cisplatin exhibits significant antitumor activity against a broad range of solid tumor xenograft models and limited activity against ALL xenografts. This preclinical pattern of activity is generally consistent with cisplatin's clinical activity. Pediatr Blood Cancer 2008;50:992,1000. © 2007 Wiley-Liss, Inc. [source] Role of heat treatment in childhood cancers: Distinct resistance profiles of solid tumor cell lines towards combined thermochemotherapyPEDIATRIC BLOOD & CANCER, Issue 5 2005Anette Debes PhD Abstract Background Since information on the efficacy of hyperthermia in combination with chemotherapy on pediatric tumors is limited, we performed a systematic analysis on the synergistic effects of a combined application of heat and chemotherapy on 20 tumor cell lines derived from patients with neuroblastomas, Ewing tumors, germ cell tumors (GCT), and osteosarcomas. Methods Cisplatin (cDDP), a cross-linking agent, and etoposide (VP-16), a topoisomerase II inhibitor, were examined either alone or in combination with heat (42°C, 43°C) by using the XTT-assay 1. Results Our data demonstrate that heat stress at 43°C for 1 hr, but not at 42°C, leads to a notable cytotoxic effect on the different tumor cells. The comparison of mean survival fractions reveals values between 62% for neuroblastoma cells and 76% for Ewing tumor cells. Analyzing the sensitivity to chemotherapy alone, our results show that cDDP (5 ,g/ml) reduces cell growth to 47% in Ewing tumor cells, to 61% in neuroblastoma cells, to 75% in GCT cells, and to 76% in osteosarcoma cells. Treatment with VP-16 (10 ,g/ml) decreases cell survival to mean values between 58% (neuroblastomas) and 77% (osteosarcomas). Simultaneous application of heat and chemotherapy enhances synergistically cDDP cytotoxicity in all tumor types tested, whereas the efficacy of VP-16 is only slightly influenced by additional application of hyperthermia. The cytotoxicity of cDDP (5 ,g/ml) can be increased by a factor of between 1.5 and 2.5 at 42°C and from 2.6 to 14.0 at 43°C. Furthermore, the results show that the sensitivity to heat (43°C) as well as the sensitivity to chemotherapy and combined thermochemotherapy varies considerably between cell lines of the same tumor group. Conclusions Simultaneous application of hyperthermia synergistically enhances the cytotoxicity of the alkylating agent cDDP, but not of the topoisomerase II inhibitor VP-16, in a defined spectrum of cell lines from different pediatric tumor entities. © 2005 Wiley-Liss, Inc. [source] Biology, clinical characteristics, and management of adrenocortical tumors in childrenPEDIATRIC BLOOD & CANCER, Issue 3 2005Carlos Rodriguez-Galindo MD Abstract Childhood adrenocortical tumors (ACT) are very aggressive endocrine neoplasms whose incidence is quite low. Little is known about their pathogenesis, clinical presentation, and optimal treatment. In recent years, however, new information has been derived from the International Pediatric Adrenocortical Tumor Registry (IPACTR), and new clues to its pathogenesis have emerged. To provide an overview of the available data that may apply to pediatric ACT, we reviewed the epidemiology, pathogenesis, and treatment of ACT in adults and in children. Germline TP53 mutation is almost always the predisposing factor in childhood ACT. A unique germline mutation (TP53,R337H) has been described in Southern Brazil, where the incidence of ACT is 10,15 times the general incidence. Childhood ACT typically present during the first 5 years of life and has female predominance. Hormone hyperproduction is almost universal, and most patients present with virilization. Two-thirds of patients have resectable tumors. Surgery is the definitive treatment for ACT, and a curative complete resection should always be attempted. Cisplatin-based chemotherapy with mitotane is indicated for unresectable or metastatic disease, although its impact on overall outcome is slight. In childhood ACT, age, tumor size, and tumor resectability are the most important prognostic indicators. Outcome is stage-dependent; patients with small, resectable tumors have survival rates in excess of 80%, whereas the outcome for patients with unresectable disease is dismal. Patients with large, resectable tumors have an intermediate outcome. Childhood ACT are rare, but their unique epidemiology appear to implicate novel oncogenic pathways that are unique to the pediatric population. Multi-institutional and prospective studies are necessary to further our understanding of the pathogenesis and to improve outcomes. © 2005 Wiley-Liss, Inc. [source] Adult primary extragonadal germ cell tumors: Treatment results and long-term follow-upPEDIATRIC BLOOD & CANCER, Issue 1 2003Argon Andac MD Abstract Background Primary extragonadal germ cell tumors (PEGCT) are rare neoplasms. They have a poor prognosis, different behavior, and natural course compared to their gonadal counterparts. Both primary and salvage treatment of these tumors constitute a challenge. We retrospectively evaluated the clinicopathologic status, therapeutic implications, and outcome of our patients with PEGCT. Procedure Between 1991 and 2000, 18 patients with PEGCT (median age 31 years; range 17,63), diagnosed with tru-cut biopsy and treated with cisplatin-based chemotherapy, were evaluated in respect to treatment response and outcome. Results Cisplatin-based chemotherapy achieved a complete response rate of 27.8% and a partial response rate of 55.5%. Overall response rate was 83.3%. Only three patients were unresponsive to chemotherapy; an additional six patients with residual mass underwent surgical resection and were rendered disease-free by surgery. The 5-year actuarial event-free and overall survival were 63.4 and 71.3%, respectively. Conclusions The outcomes of our patients with extragonadal primaries including mediastinal localization appear to be slightly better than those previously reported. Multimodality therapy is essential for these patients and given the relatively poor prognosis, prospective trials with large sample sizes, and new treatment approaches to improve outcome are required. Med Pediatr Oncol 2003;41:49,53. © 2003 Wiley-Liss, Inc. [source] Proanthocyanidin protects against cisplatin-induced nephrotoxicityPHYTOTHERAPY RESEARCH, Issue 12 2009Ahmed Amir Radwan Sayed Abstract Cisplatin (CP) [cis -diamminedichloroplatinum (II)] is one of the most widely therapeutic agents used for treating many types of cancer. At effective doses, CP causes nephrotoxicity which has been attributed to the induction of reactive oxygen species (ROS). In the present investigation proanthocyanidin (PA) was studied to demonstrate its therapeutic efficacy against CP-induced nephrotoxicity in mice. Cp treatment caused significant elevation of urea, creatinine and IL-6. In addition, CP enhanced malondialdehyde (MDA) levels and lowered the glutathione (GSH) content in kidney. On the other hand, superoxide dismutase (SOD) activity was decreased. These alterations were reversed by PA in a dose-dependent manner. These findings suggested a beneficial role of PA in attenuating CP-induced oxidative renal toxicity. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quality of life in patients diagnosed with primary hepatocellular carcinoma: Hepatic arterial infusion of Cisplatin versus 90-Yttrium microspheres (Therasphere®)PSYCHO-ONCOLOGY, Issue 2 2004Jennifer Steel Background. The aims of the study were to test the difference in health-related quality (HRQL) of life and survival in patients diagnosed with primary hepatocellular carcionma (HCC) and treated with either hepatic arterial infusion (HAI) of Cisplatin or 90-Yttrium microspheres (Therasphere®). Method. The design of the study was a non-randomized parallel cohort study. Twenty-eight patients participated in the present study. HRQL was assessed by administration of the Functional Assessment of Cancer Therapy-Hepatobiliary. Survival was measured using Kaplan Meier methods. Results. The results of present study suggest treatment with Therasphere® had an advantage in regard to HRQL and survival when compared to Cisplatin. At 3-month follow-up, patients who were treated with Therasphere® had a higher level of functional well-being as well as overall quality of life when compared to patients treated with Cisplatin. At 6-month follow-up patients (treated with Therasphere®) continued to have better functional well-being when compared to patients being treated with HAI of Cisplatin. At 6-month follow-up, survival was found to be similar for patients treated with Therasphere® when compared to patients being treated with Cisplatin. Conclusions. Preliminary data suggest that treatment with Therasphere® has a modest advantage in regard to HRQL when compared patients treated with HAI of Cisplatin. Future research with Therasphere®, that includes a larger sample size and longer follow-up, is necessary to make definitive conclusions regarding the efficacy and effect on HRQL. Copyright © 2003 John Wiley & Sons, Ltd. [source] Intra-arterial Effects of Cisplatin on Microvascular Anastomoses in the Rat ModelTHE LARYNGOSCOPE, Issue 8 2002Deepak Gurushanthaiah MD Abstract Objective To evaluate the patency of microvascular anastomoses in arteries exposed to intra-arterial cisplatin. Study Design Animal model. Methods The common iliac artery of 15 rats was injected with 150 mg/m2 cisplatin. Five rats were injected with the same volume of saline serving as physiological controls. The ipsilateral femoral artery was transected and anastomosed using microsurgical technique within 3 to 5 days. A Doppler probe was used before and after the anastomosis to assess blood flow. The vessel was re-examined on postoperative day 5. Pulsatile blood flow and the presence or absence of a Doppler signal was recorded at this time. Vessels were harvested to include the anastomosis site and fixed for histological evaluation. The contralateral femoral artery was also harvested for comparison. Results All femoral artery anastomoses in the experimental and control arm had good, pulsatile blood flow by microscopic evaluation. No thrombosed vessels were visualized, and Doppler signals remained strong at all vessel anastomoses. Histological analysis of the vessels revealed a trend toward increased inflammatory infiltrate in the walls of the vessels treated with cisplatin. We did not appreciate a functional decrease in lumen size. Conclusions Selective catheterization intra-arterial cisplatin chemotherapy does not affect the patency of vessels following a microvascular anastomosis in the rat model. The trend toward increased inflammatory response in the vessel walls may suggest the need for closer monitoring in patients treated with intra-arterial chemotherapy. [source] Innentitelbild: Discovery, Structure, and Anticancer Activity of an Iridium Complex of Diselenobenzoquinone (Angew. Chem.ANGEWANDTE CHEMIE, Issue 41 201041/2010) Das erste Diselenobenzochinon wurde in Form des stabilen Komplexes [Cp*Ir(,4 -C6H4Se2)] isoliert; eine Röntgenstrukturanalyse bestätigte die Struktur. H. Amouri et,al. beschreiben in ihrer Zuschrift auf S.,7692,ff. außerdem die Antitumoraktivität dieses Komplexes: Der Diselenokomplex zeigt eine ähnliche cytotoxische Aktivität wie Cisplatin. [source] Titelbild: Kristallstruktur eines Cisplatin-(1,3-GTG)-Schadens im Komplex mit DNA-Polymerase , (Angew. Chem.ANGEWANDTE CHEMIE, Issue 17 201017/2010) Cisplatin-DNA-Schäden hemmen die DNA-Transkription und führen zum Zelltod. In ihrer Zuschrift auf S.,3142,ff. beschreiben T. Carell und Mitarbeiter die Kristallstruktur eines Cisplatin-(1,3-GTG)-Schadens im Komplex mit Polymerase,,. Die Bewegung dieses Enzyms entlang des DNA-Doppelstrangs wird verhindert, indem sich das zentrale Desoxythymidin des Schaden aus dem Doppelstrang herausdreht. [source] Kristallstruktur eines Cisplatin-(1,3-GTG)-Schadens im Komplex mit DNA-Polymerase ,,ANGEWANDTE CHEMIE, Issue 17 2010Thomas Reißner Auf den richtigen Dreh kommt es an: Das Cisplatin-(1,3-GTG)-Addukt (siehe Struktur), ein stark zytotoxischer DNA-Schaden, wird durch die DNA-Polymerase,, der Y-Familie partiell überlesen. Die Kristallstruktur des DNA-Protein-Komplexes gibt Aufschluss über den Mechanismus des Überleseprozesses: Das zentrale Desoxythymidin des Schadens wird aus dem DNA-Doppelstrang herausgedreht und verhindert somit die Bewegung der Polymerase entlang der DNA. [source] A Single Slow Electron Triggers the Loss of Both Chlorine Atoms from the Anticancer Drug Cisplatin: Implications for Chemoradiation Therapy,ANGEWANDTE CHEMIE, Issue 42 2009Janina Kopyra Dr. Cisplatin wird aktiviert: Bei der dissoziierenden Elektronenaufnahme von Cisplatin (1) treten intensive Resonanzen bei sehr niedrigen Energien auf, die in einem Bruch der Pt-Cl-Bindung resultieren. Ein einziges niederenergetisches Elektron kann die Abspaltung beider Chloratome unter Bildung von [Pt(NH3)2], auslösen (siehe Schema). Dieses Komplexfragment ist eine reaktive Zwischenstufe bei der Bildung von Cisplatin-DNA-Addukten, die die DNA-Replikation hemmen. [source] Metastatic basal cell carcinoma: rapid symptomatic response to Cisplatin and PaclitaxelANZ JOURNAL OF SURGERY, Issue 8 2004Michael Jefford Background: Basal cell carcinoma (BCC) is the most common cancer in the community, although it rarely metastasizes. The literature reports less than 100 patients who have received chemotherapy for metastatic BCC. A further case of this rare disease is reported here. The pattern of disease in the reported patient was similar to that described in the literature, but the patient experienced a long period with untreated metastatic disease compared with that in the literature. Method: The patient was treated with cisplatin in combination with paclitaxel. Literature review suggests this to be the first report of this combination. Results: Rapid symptomatic response was achieved though late neurotoxicity occurred. Conclusion: This regimen is an active combination for the rare patient with metastatic BCC. The combination of carboplatin and paclitaxel causes less neurotoxicity and may therefore be a superior regimen. [source] Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line,BIOELECTROMAGNETICS, Issue 8 2002M.J. Ruiz-Gómez Abstract The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1cch. The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P,<,0.01), exhibiting 6.1% of survival at 47.5 ,g/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 ,g/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P,<,0.001). Cisplatin showed a significant reduction in the % of survival (44.2,39.1%, P,<,0.05) at 25 Hz and 47.5 ,g/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1cch, with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation. Bioelectromagnetics 23:578,585, 2002. © 2002 Wiley-Liss, Inc. [source] Intra-arterial versus intravenous chemoradiation for advanced head and neck cancer: Results of a randomized phase 3 trial,CANCER, Issue 9 2010Coen R. N. Rasch MD Abstract BACKGROUND: Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra-arterial (IA) cisplatin-based chemoradiation in phase 2 studies. METHODS: Two hundred and thirty-nine patients with (functionally) unresectable head and neck cancer were included, from 2000 to 2004, in a multicenter, randomized phase 3 trial, comparing IA and intravenous chemoradiation. Intravenous chemoradiation comprised 3×100 mg/m2 cisplatin infusion on Days 1, 22, 43 combined with 70 Gy in 35 daily fractions. The IA chemoradiation treatment arm comprised 4x150 mg/m2 cisplatin administered in the tumor-feeding artery on Days 1, 8, 15, 22, immediately followed by systemic rescue with sodium thiosulfate with the same radiotherapeutic regimen. RESULTS: Two patients were excluded from analysis because of nontreatment-related death immediately after randomization (n = 1) and esophageal carcinoma (n = 1). The median follow-up was 33 months 1-104 months. Ninety percent of the patients required tube feeding during treatment. Renal toxicity >grade 2 was 9% in the intravenous compared with 1% in the IA treatment arm (P , .0001). There was no difference in locoregional control, disease-free survival (DFS) or overall survival (OS), between the treatment arms. At 3 years, local control, locoregional control, DFS, and OS was .76, .63, .44, .51 in the IA versus .70, .65, .47, .47 in the intravenous treatment arm, respectively. CONCLUSIONS: Cisplatin-based IA chemoradiation was not superior to intravenous chemoradiation for advanced stage IV head and neck cancer regarding locoregional control and survival. Cancer 2010. © 2010 American Cancer Society. [source] Survival and toxicity differences between 5-day and weekly cisplatin in patients with locally advanced cervical cancerCANCER, Issue 1 2007Mark H. Einstein MD Abstract BACKGROUND. Cisplatin (CDDP) administration concomitant with radiotherapy (RT) for the treatment of locally advanced cervical cancer has evolved from an inpatient 5-day every 21-day regimen to a weekly outpatient regimen. This study was designed to test for differences in progression-free survival (PFS) and toxicity between the 2 regimens. METHODS. In all, 77 consecutive patients at a single institution with stage IB2-IV cervical cancer were included in this analysis (using the International Federation of Gynecologists and Obstetricians staging system). All patients were treated with CDDP, external beam RT, and 2 9-Gy high-dose-rate brachytherapy treatments. Two cohorts were compared: 1) 5-day, patients treated from 1995 to 2001 with CDDP 20 mg/m2 × 5 days every 21 days concomitant with RT; 2) weekly, treated after May 2001 with CDDP 40 mg/m2 weekly concomitant with RT. RESULTS. In all, 50 patients were treated with the 5-day regimen and 27 patients with the weekly regimen. There were no significant demographic differences between the groups. Overall 3-year PFS, controlling for stage, was 90% and 76% for 5-day and weekly groups, respectively (P = .01). Adjusting for stage, age, and completion of treatment, the risk of treatment failure among the weekly group was 3.46 times higher than the 5-day group (P = .02). The weekly group had a 3.43 times higher risk of developing acute toxicities than the 5-day group (P = .02) in advanced-stage patients. CONCLUSIONS. Patients who received weekly CDDP have a shorter 3-year PFS. Patients with advanced-stage cervical cancer who received weekly CDDP had significantly more acute toxicities. These data should be confirmed in a multiinstitutional, randomized, controlled study. Cancer 2007. © 2006 American Cancer Society. [source] | |||||||||||||||||||||||||||||||||||||