Intrapleural mitoxantrone for the palliative treatment of malignant pleural effusions

A group of 21 patients with malignant pleural effusions were treated with the instillation of 40 mg mitoxantrone intrapleurally, after complete fluid drainage. There was a 100% complete response rate with no toxic effects (0%). The mean survival of the patients was 57.1 weeks.     

In vitro and in vivo responses of a murine transitional cell carcinoma to doxorubicin,mitoxantrone and aclacinomycin-A

Summary In vitro and in vivo effects of mitoxantrone, aclacinomycin-A and doxorubicin were examined in a transplantable murine transitional bladder carcinoma, FCB. The in vitro parameters used included monolayer growth kinetics, tumor stem-cell colony formation and autoradiographic analysis of thymidine labeling. Monolayer growth kinetics revealed that both mitoxantrone and aclacinomycin-A resulted in reductions in FCB cell growth, which were significantly higher (41% and 65%, respectively) than those seen with doxorubicin treatment (22%). Similarly, by the stem-cell assay, an increased reduction in colony formation was seen in aclacinomycin-A (98%) and mitoxantrone (91%) treated cultures when compared with doxorubicin (51%) treated cultures. Autoradiographic data revealed that 24-h exposure with both aclacinomycin-A and mitoxantrone significantly inhibited thymidine incorporation (98% and 80% respectively), which was an increase over doxorubicin (19%). In vivo studies revealed that aclacinomycin-A treatment increased the mean life span of C57BL mice by 60.6% when compared with a 33.6% increase in doxorubicin-treated animals and a 19.7% increase in mitoxantrone-treated animals. Both the in vitro and in vivo data suggest that aclacinomycin-A is a superior drug when used against this specific murine bladder tumor cell and that further testing of this agent for its efficacy in other urologic tumors is justified.     

肝靶向米托蒽醌白蛋白微球的研究

用乳化—热固化法制备了米托蒽醌白蛋白微球,并对其形态、大小及其分布、微粉学性质、载药性能、体外释药、稳定性和体内分布进行了研究。结果表明,该载药微球的平均算术径为0.99μm,平均表面径为1.24μm,平均容积径为1.44μm;表观载药量为2.558%±0.101%;有效载药量为1.503%±0.127%;包封率为92.82%±4.60%;体外释药符合双相动力学规律,释药方程为1-Q=0.6428e^-0.2132t+0.3988e^-000150t(γ₁=-0.9951,γ₂=-0.9982);T_1/2α=3.250h,T_1/2β=461.7h;室温放置3个月,微球形态、药物含量等均无明显变化。HPLC测定表明,小鼠尾iv该微球20min内即有77.6%±1.38%的药物浓集于肝脏,具有明显的肝靶向性。提示米托蒽醌白蛋白微球有可能提高米托蒽醌的抗肝癌效果和降低其全身毒副作用。     

A multicenter phase I study of cabazitaxel,mitoxantrone, and prednisone for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer: A department of defense prostate cancer clinical trials consortium study

Background

Cabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile.

Effectiveness of mitoxantrone on the proliferation of cell cultures derived from malignant mesenchymal tumors of human origin

Summary The antiproliferative potency of mitoxantrone (MITOX) has predominatly been established for epithelial and hematologic neoplasias. In this study the effectiveness of MITOX was investigated in vitro for 6 sarcomatous human cell lines derived from 2 synovial sarcomas, a malignant schwannoma, a malignant histiocytoma, a leiomyosarcoma, and a chondrosarcoma. The examination was performed using a proliferation assay with monolayer cell cultures. The effect of MITOX was compared with that of adriamycin (ADR) and cisplatin (CDDP). For each drug at least 3 concentrations were tested which covered the therapeutically achievable range, i.e., for MITOX 0.2–0.002 g/ml, for ADR 0.5–0.005 g/ml, and for CDDP 5.0–0.05 g/ml. Test incubations were performed for 3 days. Antiproliferative potency of the cytostatic drugs was assessed by counting the number of cells at the start and the end of the test period with and without drug addition. Furthermore the dose inhibiting cell growth to 50% of controls (ID₅₀) was determined for MITOX. For comparison 4 cell lines from carcinomatous lesions were included in the study. MITOX inhibited proliferation rates of 4 sarcomatous tumor cell lines more intensively than ADR, and was less effective in 2 cell lines. However, these differences were not significant. In all mesenchymal cell lines tested the antiproliferative potency of MITOX was more pronounced than that of CDDP. In carcinomatous cell lines the MITOX-induced growth inhibition was similar to that found in response to administration of ADR and CDDP confirming the described effect on epithelial tumors. The study suggests that MITOX possesses a growth inhibitory potency for malignant soft tissue tumors in vitro. From these data it may be worthwhile to initiate clinical trials testing the treatment of sarcomatous lesions with MITOX.This work was supported by the Hamburger Stiftung zur Förderung der Krebsbekämpfung, the Hamburger Landesverband zur Krebsbekämpfung und Krebsforschung and the E. und G. Roggenbruck-Stiftung     

肝靶向抗癌药NGA—DHAQ中DHAQ含量的测定方法

目的 测定肝靶向抗癌药ＮＧＡ－ＤＨＡＱ中ＤＨＡＱ的含量。方法 通过均匀设计和正产都是靶向化学偶联物ＮＧＡ－ＤＨＡＱ发生水解而游离出ＤＨＡＱ的最佳条件：０．５ｍｌＮＧＡ－ＤＨＡＱ液透析中，加入４３０μｌ水和７０μｌ浓ＨＣｌ，水浴９０℃恒温４０分钟。并在此条件下初步考察了ＤＨＡＱ的稳定性。结果 建立了ＮＧＡ－ＨＤＡＱ中ＤＨＡＱ含量的测定方法。结论 说明此方法可行。     

In vitro cytotoxicity of mitoxantrone-incorporated albumin microspheres on acute promyelocytic leukaemia cells

In the present study, the preparation and characterization of bovine serum albumin (BSA) microspheres and the evaluation of the in vitro cytotoxicity of these microspheres on acute promyelocytic leukaemia (HL-60) cells were described. Mitoxantrone (MTZ)-incorporated microspheres were evaluated for particle size, drug loading, release characteristics and surface morphology. The biological effect of MTZ released from BSA microspheres was determined on an in vitro cultured HL-60 cell line, showing that, after encapsulation, MTZ still retains cytotoxic activity. For this purpose, methyl-thiazol-tetrazolium (MTT) assay was used to evaluate the in vitro cytotoxicity of MTZ-loaded microspheres. Particle size of BSA microspheres was determined between 17.61–20.38?µm and they were smooth and spherical in shape. Encapsulation efficiency of the drug-loaded microspheres was between 22.26–60.50%. For MTZ-containing microspheres, the cell death ratios were greater than 80% for all formulations. This study demonstrate that BSA microspheres were well suited for the controlled release of MTZ and were promising for anti-cancer chemotherapy.     

米托蒽醌处理B16F10-ESAT-6-gpi/IL-21瘤苗特征及其诱导的抗肿瘤免疫反应初探

背景与目的:蒽环类药物处理可使肿瘤细胞免疫原性增加。本文旨在分析米托蒽醌(mitoxantrone,MIT)处理的B16F10-ESAT-6-gpi/IL-21瘤苗特征,初步探讨该瘤苗诱导的抗肿瘤免疫反应。方法:MIT处理B16F10-ESAT-6-gpi/IL-21瘤苗后,用吖啶橙/嗅化乙啶(AO/EB)染色法观察瘤苗细胞形态,流式细胞仪(FCM)检测其粒度及凋亡比例,荧光显微镜观察瘤苗凋亡后细胞膜表面结核杆菌早期分泌靶抗原6KD(ESAT-6)的表达情况,蛋白质印迹法(Western blot)检测瘤苗经MIT处理后IL-21的表达。瘤苗免疫小鼠后,FCM检测了补体依赖的细胞毒性(complement dependent cytotoxicity,CDC)及细胞毒T细胞(cytotoxicT lymphocyte,CTL)活性。结果:经MIT处理后,瘤苗停止分裂,细胞逐渐增大,数日内可保持生物活力,并表达IL-21。瘤苗细胞凋亡后,ESAT-6成点簇状分布于胞膜表面。MIT处理的瘤苗能诱导小鼠产生抗肿瘤免疫应答,免疫鼠血清和CD8+T细胞可分别通过CDC和CTL杀伤野生型B16F10细胞。结论:MIT处理的B16F10-ESAT-6-gpi/IL-21瘤苗失去增殖能力,但仍能表达IL-21且具有免疫原性,能诱导小鼠产生抗肿瘤免疫反应。     

Overlapping and distinct mechanisms of action of multiple sclerosis therapies

In the last two decades MS has changed from an idiopathic condition with only symptomatic treatments to a disease with better characterized pathophysiologic underpinnings and several treatments that modify its long-term course based on specific mechanisms of action. There are now several FDA approved options for therapy at the onset of disease, and discussions have begun on choosing the best treatment in individual patients and what option to choose next in patients who are failing their current treatment. Numerous studies have begun to highlight that the underlying pathology of CNS damage may be different in subsets of patients, raising the possibility that some may respond to a treatment with a mechanism of action that is targeted to ‘their’ MS. Trials are ongoing of numerous new agents with different mechanisms of action and some combination therapies. A better understanding of how each therapy works may guide decisions on initiating, combining or changing therapy in a more rational way to improve patient outcomes. Further knowledge of underlying mechanisms of disease in different patients with ‘the same’ disease may lead to more targeted therapies, as will biomarkers that predict clinical response to therapy. Studies of the effects of various agents used in MS reveal both overlapping and distinct mechanisms of actions that may be relevant to their efficacy and side effects in individual patients. However, it is important to remember that most agents are approved based on their reduction of MRI lesions and relapse rates over a short time frame. These measures only partially correlate with long-term disability, which may be the most relevant clinical outcome for people with MS. Fixed disability requires years to become apparent, and there is a lack of large studies of biomarkers for chronic outcomes. In addition, few large studies correlate response to therapy with cognitive outcomes, which are a major cause of chronic disability.     

环磷酰胺、米托蒽醌及顺铂联合治疗晚期乳腺癌的临床疗效

目的　评价环磷酰胺、米托蒽醌及顺铂（ＣＭＰ方案）联合治疗晚期乳腺癌３９例的疗效。方法环磷酰胺６００ｍｇ／ｍ２，静冲，ｄ１；米托蒽醌１０ｍｇ／ｍ２；静滴，ｄ１；顺铂３０ｍｇ／ｍ２，静滴，ｄ１、２、３。 ２１天为１周期。结果总有效率５９％（２３／３９），完全缓解率１０．３％（４／３９），中位缓解期６．８月，中位生存期１３．４月。对软组织转移的有效率６７．９％（１９／２８），肺、胸膜、骨、肝转移有效率分别为５／１０、３／６、２／６、１／４。初治有效率６３．６％（２１／３３），复治者２／６。本组病人有不同程度胃肠道反应、脱发及骨髓抑制；未发现肾毒性及心脏毒性。结论ＣＭＰ方案是治疗晚期乳腺癌的有效方案。