mesna and Weight-Loss

Mediastinal angiosarcoma is a rare intrathoracic tumour and the therapeutic approach remains poorly codified.. We report the case of a 65-year-old female patient presenting with chest pain. Further exploration revealed an anterior mediastinal mass with pericardial invasion. Transthoracic biopsy gave the diagnosis of angiosarcoma. Multimodal treatment with neoadjuvant chemotherapy (doxorubicin 20 mg/m(2), Ifosfamide 2500 mg/m(2), Uromitexan® 2500 mg/m(2)) and surgery followed by adjuvant radiotherapy has led to remission of the tumour that has persisted for 12 months.. Systematic recording of such conditions in dedicated registries could contribute to enhance the description of the clinical and pathological characteristics, thus helping define the principles of specific management.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chest Pain; Doxorubicin; Dyspnea; Female; Hemangiosarcoma; Humans; Ifosfamide; Magnetic Resonance Imaging; Mediastinal Neoplasms; Mesna; Neoadjuvant Therapy; Neoplasm Invasiveness; Positron-Emission Tomography; Radiotherapy, Adjuvant; Remission Induction; Tachycardia, Sinus; Tomography, X-Ray Computed; Weight Loss

Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present study examined the effect of mesna on bleomycin-induced lung fibrosis in rats. Animals were divided into three groups: (1) saline control group; (2) Bleomycin group in which rats were injected with bleomycin (15 mg/kg, i.p.) three times a week for four weeks; (3) Bleomycin and mesna group, in which mesna was given to rats (180 mg/kg/day, i.p.) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the treatment. Bleomycin treatment resulted in a pronounced fall in the average body weight of animals. Bleomycin-induced pulmonary injury and lung fibrosis was indicated by increased lung hydroxyproline content, and elevated nitric oxide synthase, myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration and angiotensin converting enzyme activity in lung tissues. Moreover, bleomycin-induced severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and mesna reduced bleomycin-induced weight loss and attenuated lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, and concentrations of myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. Furthermore, mesna ameliorated bleomycin-induced reduction in reduced glutathione concentration and angiotensin activity in lung tissues. Finally, histological evidence supported the ability of mesna to attenuate bleomycin-induced lung fibrosis and consolidation. Thus, the findings of the present study provide evidence that mesna may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Topics: Animals; Bleomycin; Drug Administration Schedule; Drug Screening Assays, Antitumor; Glutathione; Hydroxyproline; Injections, Intraperitoneal; Lung; Male; Mesna; Nitric Oxide Synthase; Peptidyl-Dipeptidase A; Peroxidase; Platelet Activating Factor; Pulmonary Fibrosis; Rats; Rats, Wistar; Time Factors; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss

BNP7787 (2',2'-dithio-bis-ethane sulphonate sodium), a water-soluble disulphide, is chemically and mechanistically different from other sulphur-containing chemoprotective agents. Presently, BNP7787 is under investigation for its protective properties with regard to the side-effects of platinum compounds. In this study, we evaluated BNP7787, mesna and amifostine for their effects on the antitumour activity of platinum compounds. Continuous exposure to BNP7787 did not affect the antiproliferative effects of cisplatin or carboplatin, but the efficacy of both compounds was reduced in the presence of mesna in vitro in two human ovarian cancer cell lines. BNP7787 or amifostine combined with cisplatin or carboplatin given in standard schedules for the treatment of nude mice bearing well-established OVCAR-3 xenografts did not interfere with platinum-induced inhibition of tumour growth. Of interest, BNP7787 or amifostine co-administered with carboplatin was significantly more effective than carboplatin alone (P<0.01). In the presence of amifostine, doses of cisplatin and carboplatin could be safely increased by factors of 1.6 and 1.5, respectively. Unlike in a previous study of BNP7787 in tumour-bearing rats, BNP7787 did not protect against additional weight loss following treatment with higher doses of cisplatin in OVCAR-3-bearing mice. Pharmacokinetics of (mixed) disulphides including BNP7787 and extractable mesna in deproteinised plasma revealed a rapid disappearance of BNP7787 and an AUC(5-60) value of mesna 9-fold lower than that calculated after an equivalent dose of mesna by weight. We can conclude that BNP7787 does not interfere with the antitumour activity of platinum compounds in vitro and in vivo. Clinical trials are underway to evaluate the protection of normal tissues by BNP7787 when combined with cisplatin.

Topics: Amifostine; Animals; Antineoplastic Agents; Carboplatin; Cell Division; Cisplatin; Drug Interactions; Female; Humans; Lethal Dose 50; Mesna; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Protective Agents; Radiation-Protective Agents; Transplantation, Heterologous; Weight Loss