The treatment of nonseminomatous testicular tumors: 15 years experience

Thirty-two patients with nonseminomatous germ cell tumors of the testis were treated at the Northern Israel Oncology Center during the years 1968-1983. The patients were divided into two groups. Group I included 18 patients treated from 1968 to 1976; in group II there were 14 patients treated with combination therapy containing cis-platinum in the years 1977 to 1983. The actuarial survival rate at 38 months from diagnosis is 47% in group I patients and 86% in group II patients. The development of modern radiological techniques, biochemical markers for accurate staging, and the use of cis-platinum-containing combination chemotherapy made this disease curable. New treatment modalities are needed for patients with bulky disease at presentation.     

利多卡因对抗肿瘤药物的增敏作用研究

目的 :研究利多卡因对 3种化疗药物的增敏作用。方法 :微量细胞培养四氮唑 ( MTT)法检测肝癌细胞系 SSMC 772 1对 3种抗癌药物 5-氟脲嘧啶 ( 5- FU)、丝裂霉素 ( MMC)和顺铂 ( CDDP)的敏感性。结果 :SSMC 772 1对 3种化疗药物 ( 5- FU、MMC及 CDDP)均敏感。结论 :利多卡因对这 3种化疗药物均有明显增敏作用。     

Tongkat Ali as a Potential Herbal Supplement for Physically Active Male and Female Seniors—A Pilot Study

Tongkat Ali (Eurycoma longifolia; TA) is known to increase testosterone levels and alleviate aging males' symptoms. This study aimed at investigating TA as an ergogenic supplement for elderly people. Thirteen physically active male and 12 physically active female seniors (57–72 years) were supplemented with 400‐mg TA extract daily for 5 weeks. Standard hematological parameters were taken. In addition, the concentrations of total and free testosterone, dihydroepiandrosterone, cortisol, insulin‐like growth factor‐1, and sex hormone‐binding globulin were analyzed. As additional biochemical parameters, blood urea nitrogen and creatine kinase as parameters of kidney function and muscle damage, respectively, as well as the muscle strength by a simple handgrip test were determined. After treatment, hemoglobin, testosterone, and dihydroepiandrosterone concentrations, and the ratio of total testosterone/cortisol and muscle force remained significantly lower in female seniors than in male seniors. Hematocrit and erythrocyte count in male seniors increased slightly but were significantly higher than in female seniors. Treatment resulted in significant increases in total and free testosterone concentrations and muscular force in men and women. The increase in free testosterone in women is thought to be due to the significant decline in sex hormone‐binding globulin concentrations. The study affirms the ergogenic benefit of TA through enhanced muscle strength. Copyright © 2013 John Wiley & Sons, Ltd.     

Clock gene mutation modulates the cellular sensitivity to genotoxic stress through altering the expression of N-methylpurine DNA glycosylase gene

Although Clock gene product, a component of the circadian pacemaker, has been suggested to participate in the regulation of cellular sensitivity to genotoxic stress, the underlying mechanism remains to be fully understood. In this study, we showed that Clock gene mutation modulates the sensitivity of hepatocytes to alkylating agent-induced genotoxic stress through altering the expression of N-methylpurine DNA glycosylase (MPG), the first enzyme in the base excision repair pathway. Neither wild-type nor Clock mutant (Clock/Clock) mice showed a significant 24-h variation in the hepatic expression of MPG. However, the mRNA and protein levels of MPG in the liver of Clock/Clock mice were significantly lower than those in wild-type liver. The cytotoxic effect of methyl methanesulfonate (MMS), a methylating agent, on primary cultured hepatocytes prepared from Clock/Clock mice was more potent than on wild-type hepatocytes, while overexpression of MPG in Clock/Clock hepatocytes restored their MMS sensitivity to the wild-type level. These findings suggest that the product of the Clock gene controls the sensitivity of cells to genotoxic stress through regulating the expression of the MPG gene. Our present findings would provide a molecular link between the circadian clock and DNA repair pathway.     

Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide, at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10

Vitilevuamide, a bicyclic 13 amino acid peptide, was isolated from two marine ascidians, Didemnum cuculiferum and Polysyncranton lithostrotum. Vitilevuamide was cytotoxic in several human tumor cell lines, with LC(50) values ranging from 6 to 311nM, and analysis in a 25-cell line panel revealed a weak correlation with several taxol analogs. Vitilevuamide was strongly positive in a cell-based screen for inhibitors of tubulin polymerization. Vitilevuamide at 9 microg/mL (5.6 microM) had an effect equivalent to the maximal effect of colchicine at 25 microg/mL (62.5 microM). Vitilevuamide was active in vivo against P388 lymphocytic leukemia, increasing the lifespan of leukemic mice 70% at 30 microg/kg. We hypothesized that at least part of the cytotoxic mechanism of vitilevuamide was due to its inhibition of tubulin polymerization. Vitilevuamide was found to inhibit polymerization of purified tubulin in vitro, with an IC(50) value of approximately 2 microM. Cell cycle analysis showed that vitilevuamide arrested cells in the G(2)/M phase with 78% of treated cells tetraploid after 16hr. Therefore, vitilevuamide was tested for its ability to inhibit binding of known tubulin ligands. Vitilevuamide exhibited non-competitive inhibition of vinblastine binding to tubulin. Colchicine binding to tubulin was stabilized in the presence of vitilevuamide in a fashion similar to vinblastine. Dolastatin 10 binding was unaffected by vitilevuamide at low concentrations, but inhibited at higher ones. GTP binding was also found to be weakly affected by the presence of vitilevuamide. These results suggest the possibility that vitilevuamide inhibits tubulin polymerization via an interaction at a unique site.     

Anisocoria and mydriasis after scalp nerve block: a case report

Strategies for the assessment of abnormal neurological findings during general anesthesia are limited. However, pupil abnormalities may represent serious neurological complications. We herein present a case of new-onset anisocoria and mydriasis that developed after scalp nerve block. The patient’s signs were possibly related to increased intracranial pressure with resulting brain shift that ultimately affected the oculomotor nerves. A 45-year-old man was scheduled for left cerebellar tumor resection and ventricular drainage surgery; however, anisocoria and left pupillary mydriasis were observed after induction of general anesthesia and performance of scalp nerve block. After reducing the intracranial pressure, the right pupil showed constriction (1 mm) but the left pupil was dilated (5 mm). The pupils were of similar size postoperatively. Although pupillary dilation during general anesthesia has been previously described, this is the first case in which the mydriasis was considered to have been caused by brain shift due to increased intracranial pressure after scalp nerve block. Thus, we propose this phenomenon as a new possible cause of pupillary changes. Actively monitoring this presentation intraoperatively could enable early detection of and intervention for complications, therefore improving the prognosis.     

伴IgG4阳性浆细胞数量增多的脑膜Rosai-Dorfman病临床病理特点分析

目的 探讨脑膜Rosai-Dorfman病临床病理特点.方法 选取大连医科大学附属第二医院神经外科脑膜原发性伴IgG4阳性浆细胞增多的Rosai-Dorfman病1例,手术治疗,切除病变组织,分析其病理学特点.结果 脑膜局限性增厚、纤维化,肿瘤组织呈“明暗相间”的病理特点,较多淋巴细胞及多量浆细胞浸润,局部淋巴滤泡形成,并见组织细胞吞噬完整的淋巴细胞及浆细胞(即淋巴细胞伸入现象),未见席纹状纤维化、闭塞性静脉炎及嗜酸性粒细胞浸润.肿瘤组织边缘呈推挤性生长,压迫周边脑组织,周边脑组织血管周围见淋巴细胞及组织细胞套袖.应用免疫组化染色显示:组织细胞CD68及S-100阳性;IgG4阳性浆细胞数量为30个/HPF,IgG4阳性浆细胞/IgG阳性浆细胞为60％.MRI示右侧额部异常信号影,呈宽基底与邻近脑膜相连,可见硬膜尾征,邻近脑实质呈受压推挤状态,周围可见少量脑水肿影,病变范围14 mm×23 mm×16 mm,T1WI呈低信号,其内混杂高信号,T2WI呈中高信号,其内混杂少许低信号,增强扫描呈均匀强化.结论 脑膜的Rosai-Dorfman病是少见病变,需要与多种疾病鉴别,其诊断具有挑战性,并且此例伴随IgG4阳性浆细胞增多及IgG4阳性浆细胞/IgG阳性浆细胞为60％,具有IgG4相关性疾病的一个组织学特征(即致密淋巴细胞及浆细胞浸润),需要结合组织病理、临床及血清学特点综合判断,笔者认为诊断为脑膜Rosai-Dorfman病可能伴有IgG4相关性疾病较为恰当.