Antitumor Effect of the New Rhodium(II) Complex: Rh2 (Form)2 (02 CCF3)2 (H20)2 (Form = N,N’-di-p-tolylformamidinate)

Summary

The new rhodium(II) complex Rh₂(Form) (0₂CCF₃)₂(H₂0)₂ (Form = N, N’ — di-p-tolyl formamidinate) was evaluated for its toxicity on the rat and for its efficacy against two tumors of this animal: the Yoshida ascites sarcoma and the T8 sarcoma of Guérin.

The rhodium(II) formamidinate shows very low toxicity: in fact 150 mg/kg (the highest quantity of drug soluble in 4 ml of dimenthyl sulfoxide) is not toxic for rats. We were unable to establish the lethal dose or the highest nontoxic dose since larger mounts of complex require a dose of dimethyl sulfoxide (DMSO) that is itself toxic and the compound is insoluble in other solvents such as water or Tween.

Doses of rhodium(II) formamidinate, varying from 3 to 30 mg/kg, were administered once by i.p., i.v., i.m. and intratumor (i.t.) route from 1 to 7 days after i.p. injection of 10⁶ Yoshida ascites sarcoma cells and subcutaneous (s.c.) implantation of ? 300 mg (corresponding to 2-3 × 10⁷ living tumor cells) of T8 sarcoma of Guérin. The compound is active when administered i.p. 24 hours after Yoshida ascites sarcoma at the smallest dose tested (3 mg/Kg), increasing the average life span of 62.3% and allowing the survival of 50% of the rats. It is also active when administered i.p. at the highest dose tested (30 mg/Kg) 7 days after tumor cell challenge, increasing the average life span in 43.8% and allowing survival in 20% of the rats; it is not active after i.v. or i.m administration. The title complex exhibits anticancer activity against T8 sarcoma of Guérin, increasing significantly the average life span of 17% and 25.9% of rats if administered by i.v. and i.m. routes respectively at the dose of 30 mg/Kg the day following implantation of the neoplasia, and of 12.2% of rats by i.t. route at the dose of 10 mg/Kg five days after tumor challenge.

A comparison between the therapeutic properties of the title complex with those of the complexes Rh₂(O₂CCH₃)₄ and cis-Pt(NH₃)₂Cl₂(CDDP) reveals that the rhodium(II) formamidinate derivative exhibits the same antitumor activity associated with considerably reduced toxicity.     

难治性急性髓系白血病(M2a)的基因表达谱

背景与目的:复发是急性髓系白血病(acutemyeloidleukemia,AML)治疗失败的主要原因,部分AML复发时其免疫表型和细胞遗传学已发生了改变。耐药是AML难治的主要原因,AML耐药与基因的异常表达有关,目前对AML复发/难治或耐药相关基因及其表达所知甚少。本研究检测AML初诊与复发/难治之间的基因表达差异,为阐明AML复发/难治的可能机制提供依据。方法:应用基因芯片技术,对5例自身配对初诊与复发/难治AML鄄M2a患者之间骨髓单个核细胞的基因表达差异进行了检测。结果:在检测的925个基因中,14个基因在初诊与复发/难治AML鄄M2a之间差异表达,其中12个基因(涉及细胞信号转导、DNA复制、转录调节和RNA加工以及细胞循环等相关基因)在复发时明显上调,参与DNA复制过程的RRM1基因上调最显著。结论:在AML鄄M2a复发/难治的发生过程中有多个基因共同参与,这些基因的高表达提示复发/难治AML细胞增殖能力可能更强。     

Solid phase synthesis, radiolabeling and biological evaluation of a (99m) Tc-labeled α(V)β(3) tripeptide (RGD) conjugated to DOTA as a tumor imaging agent

Solid phase synthesis of peptides-radiometal chelator can facilitate the creation of radioactive peptide libraries to be utilized in high throughput in in vivo screening of targeted molecular imaging agents. An α(V)β(3) tripeptide derivative DOTA-NH-Arg-Gly-Asp was synthesized by Fmoc solid phase peptide synthesis and analyzed by spectroscopic techniques. In order to radiolabel this RGD peptide with (99m)Tc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was incorporated as a chelator. The DOTA-peptide conjugate binds to (99m)Tc with high efficiency at ambient temperature. The resulting conjugate is stable under physiological conditions for at least 24 h after radiocomplexation. The receptor binding studies of (99m)Tc-DOTA- α(V)β(3)-tripeptide in established human tumor cell lines U-87MG and BMG revealed K(d) values in the nM and μM range respectively. U-87MG tumors in athymic mice were accumulated in the γ-images and major accumulation of the radiotracer was observed in kidneys followed by liver and lungs. High tumor uptake was shown in the U-87MG tumor bearing athymic mice; tumor to muscle ratios reached 8.13 ± 2.18 and 35.09 ± 4.78 at 1 and 4 h after post injection respectively.     

(2″-R)-4′-o-Tetrahydropyranyladriamycin,a new anthracycline derivative; its effectiveness in lymphoid malignancies

Summary Thirty-eight patients with adult acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) were treated intravenously with (2-R)-4-o-Tetrahydropyranyladriamycin (THP) at a dose of 10 mg/m² for 5 consecutive days. Seven complete and 15 partial responses were observed in 35 evaluable patients (overall response rate, 62.8%). Both antitumor activity and antitumor spectrum were similar to those for doxorubicin. Since the patients who had had chemotherapy previously, including other kinds of anthracycline, responded rather poorly to THP, cross-resistance between THP and other anthracyclines may be present. Leukopenia and thrombocytopenia were dose-limiting factors. Nausea and vomiting episodes were mild, and epilation was also minimal. Although the observation period was short and a cumulative dose was not large enough to evaluate cardiotoxicity, there were no abnormal EKG changes or clinical signs of cardiotoxicity in this study. THP is a potent antitumor agent in the treatment of lymphoid malignancies.     

二氧化氮(NO_2)

<正>1.指导值:年平均:40微克/立方米;1小时平均:200微克/立方米。目前世卫组织的指导值40微克/立方米(年平均),是为保护公众避免气体造成的健康影响而设定。2.定义和主要来源:作为一种空气污染物,二氧化氮具有几个相关联的活动:短期浓度超过200微克/立方米时,它是一种引起呼吸道严重发炎的有毒气体。二氧化氮是硝酸盐气溶胶的主要来源,构成PM2.5和在紫外线下臭氧的主要     

小鼠(Mouse)遗传命名规则(2)

表型典型的表型命名方法是用突变等位基因的全名或用能够表示突变等位基因的符号来命名,如:rex、asebia、grey-lethal、whirler。蛋白质表型用正体大写字母表示,原有的上标也改为正常的大写字母,如Es1基因的等位基因Es1a和Es1b有三种可能的表型:ES1A、ES1B(纯合体)、ES1AB(杂合     

苯丙(a)蒽的毒性研究进展

苯丙（a）蒽（BaA）是一种四环结构的多环芳烃（PAH）类物质,是化石燃料不完全燃烧的副产物,与其他的PAHs以混合物的形式存在。BaA可通过口腔、鼻腔及皮肤等多种途径暴露于人类,对人的主要危害是致癌性。国际癌症研究机构（IARC）根据其分类标准将BaA归为2B类（对人可能致癌）。目前尚无充足数据支持通过计算剂量外推斜率因子（slope factor）来完成动物致癌系数与人体致癌系数之间的推导。本文对BaA的致癌性等毒性研究进行系统文献检索与综述,以期为今后进行BaA的健康风险评估提供可靠的毒理学数据基础。     

Cohorts and consortia conference: a summary report (Banff, Canada, June 17�C19, 2009)

Epidemiologic studies have adapted to the genomics era by forming large international consortia to overcome issues of large data volume and small sample size. Whereas both cohort and well-conducted case-control studies can inform disease risk from genetic susceptibility, cohort studies offer the additional advantages of assessing lifestyle and environmental exposure-disease time sequences often over a life course. Consortium involvement poses several logistical and ethical issues to investigators, some of which are unique to cohort studies, including the challenge to harmonize prospectively collected lifestyle and environmental exposures validly across individual studies. An open forum to discuss the opportunities and challenges of large-scale cohorts and their consortia was held in June 2009 in Banff, Canada, and is summarized in this report.     

系统性红斑狼疮继发急性非淋巴细胞白血病M_(2a)1例

系统性红斑狼疮继发急性非淋巴细胞白血病Ｍ２ａ１例白月辉李幼鹏徐有光１临床资料患者，女，１７岁，因间断发热２年，右膝踝关节痛３天于１９９５年６月１日入院。１９９３年７月无明显诱因出现发热、胸痛、头晕，体温３９．８℃，中度贫血貌，未见蝴蝶斑及皮疹。胸骨左...     

Ⅲa(N2)期非小细胞肺癌是否需要手术治疗

目的 探讨Ⅲａ（Ｎ２）期非小细胞肺癌（ｎｏｎ－ｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒ，ＮＳＣＬＣ）是否需要手术治疗，材料与方法 所有病人均经临床或病理确诊为ⅢａＮ２期，手术治疗组为接受根治性手术及术后予根治性常规分割放疗无术前放疗史者，共７１例，术后放疗剂量中位值为５９（５０～７０）Ｇｙ／３１（２４～３８）次，４６（３３～６３）天，无手术组８６例，其中采用非常规放疗（超分割或加速超分割）５６例，常     

母子同患急性髓细胞白血病(M_(2a))2例

母子同患急性髓细胞白血病（Ｍ２ａ）２例钟卓衡卢素春１病例报告１．１例１女，２８岁，家庭妇女。第３次妊娠３４周，因牙龈出血，皮肤紫癜，进行性脸色苍白、头晕、四肢疼痛乏力两个月于１９９１年８月１日入院。体检：重度贫血貌，全身皮肤粘膜散在出血紫斑，腋下腹股...     

Interaction of folliculin (Birt-Hogg-Dubé gene product) with a novel Fnip1-like (FnipL/Fnip2) protein

Birt-Hogg-Dubé (BHD) syndrome is characterized by the development of pneumothorax, hair folliculomas and renal tumors and the responsible BHD gene is thought to be a tumor suppressor. The function of folliculin (Flcn), encoded by BHD, is totally unknown, although its interaction with Fnip1 has been reported. In this study, we identified a novel protein binding to Flcn, which is highly homologous to Fnip1, and which we named FnipL (recently reported in an independent study as Fnip2). The interaction between FnipL/Fnip2 and Flcn may be mediated mainly by the C-terminal domains of each protein as is the case for the Flcn-Fnip1 interaction. FnipL/Fnip2 and Flcn were located together in the cytoplasm in a reticular pattern, although solely expressed Flcn was found mainly in the nucleus. Cytoplasmic retention of Flcn was canceled with C-terminal truncation of FnipL/Fnip2, suggesting that FnipL/Fnip2 regulates Flcn distribution through their complex formation. By the employment of siRNA, we observed a decrease in S6K1 phosphorylation in the BHD-suppressed cell. We also observed a decrease in S6K1 phosphorylation in FNIP1- and, to a lesser extent, in FNIPL/FNIP2-suppressed cells. These results suggest that Flcn-FnipL/Fnip2 and Flcn-Fnip1 complexes positively regulate S6K1 phosphorylation and that FnipL/Fnip2 provides an important clue to elucidating the function of Flcn and the pathogenesis of BHD.