Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.      

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.      

Perspectives on colorectal cancer screening: a focus group study

Objective To assess attitudes and acceptability of Ontario consumers and doctors towards colorectal screening with faecal occult blood testing (FOBT) and colonoscopy. Design, setting and participants Focus groups with gender‐specific samples of the population, high‐risk gastroenterology patients and family doctors. Method Semi‐structured interview guides used by facilitator to lead groups through knowledge of risk factors and prevention of colorectal cancer, the screening modalities, requirements for implementing screening programmes, barriers to screening and preferences towards screening. Main findings There were low levels of knowledge about colorectal cancer and its prevention in the general population. FOBT was an acceptable screening modality, but considerable education about its use and benefits would be necessary to implement a screening programme. Colonoscopy was not perceived to be a good choice for a primary screen in the general population. The high‐risk group supported use of FOBT in the general population and emphasized the need for education. The doctors were more reluctant about screening, requesting clear guidelines. They also identified the time and resources that would be required if a screening programme were initiated. Conclusion While colorectal screening is acceptable in this sample, information and decision aids are required to enable consumers and providers to make effective decisions. Implementation of colorectal screening programmes requires substantial educational efforts for both consumers and doctors.     

氯地滴眼液的含量测定

目的：采用ＨＰＬＣ法测定氯地滴眼液中氯霉素和地塞米松磷酸钠的含量。方法：色谱分析条件：ＯＤＳ柱作分析柱,流动相为甲醇／水体系,０￣８ｍｉｎ使用４０％甲醇,８￣１６ｍｉｎ使用６０％甲醇,流速１ｍｌ／ｍｉｎ,０￣９ｍｉｎ２４０ｎｍ紫外检测,：二组分分离良好。各组各组性关系良好,平均回收率氯霉素９９．８％（ＲＳＤ＝１．２％,ｎ＝５）,地塞米松磷酸钠９９．４％（ＲＳＤ＝０．７％,ｎ＝５）,结论：该法用于氯     

Specificity of action of the novel antihypertensive agent, BRL 34915, as a potassium channel activator. Comparison with nicorandil

Experiments have been performed to investigate the specificity of the mechanism of action of the novel antihypertensive agent, BRL 34915. BRL 34915 (0.5-100 microM) and nicorandil (10-500 microM) stimulated the efflux of rubidium from preloaded rabbit isolated mesenteric arteries. BRL 34915 also caused an increase in the rubidium efflux rate constant in other vascular smooth muscles. Tetraethylammonium (0.1-30 mM) inhibited BRL 34915 (10 microM), nicorandil (100 microM) and potassium (30 mM) induced stimulations of rubidium efflux, but had no effect on noradrenaline (30 microM) induced efflux. Only noradrenaline induced efflux was inhibited by apamin (3-100 nM). Examination of other second messenger systems demonstrated that BRL 34915 (at concentrations up to 100 microM) did not have any appreciable effect on cGMP accumulation in rabbit mesenteric artery, cAMP or cGMP phosphodiesterase in rat heart, or cAMP and inositol phosphate accumulation in rat brain slices. Nicorandil (100 microM) caused a small increase in cGMP accumulation in rabbit mesenteric artery. Radioligand binding studies showed that BRL 34915 did not interact with dihydropyridine, 5-hydroxytryptamine, dopamine, alpha 1, alpha 2 or beta adrenoceptor binding sites. [3H]-BRL 34915 did not bind specifically to any site in any tissue studied, either in vitro or ex vivo. Thus we have been unable to demonstrate an effect of BRL 34915 other than of increasing potassium efflux in rabbit vascular smooth muscle. This lends support to other evidence suggesting that BRL 34915 relaxes vascular smooth muscle (and hence lowers blood pressure) by a novel, and specific, mechanism involving hyperpolarisation of the smooth muscle cell membrane.     

胚胎干细胞与胚胎生殖细胞的生物学特性及应用前景

目的:分析胚胎干细胞和胚胎生殖细胞的生物学特性、体外培养条件、周围微环境对其增殖分化的影响,了解胚胎干细胞和胚胎生殖细胞的关系和应用前景。方法:应用计算机检索万方数据库2000/2007有关生殖细胞、胚胎干细胞、胚胎生殖细胞的相关研究文章,检索词:生殖细胞,胚胎干细胞,胚胎生殖细胞,并限定文章语言种类为中文;同时应用计算机检索PUBMED2000/2006相关文章,检索词:Germ Cells,Primordial germ cells,Embryonic stem cells,Embryonic Germ Cells,限定文章语言种类为“English”。对资料进行初审,纳入标准为有关生殖细胞、胚胎干细胞、胚胎生殖细胞的生物学特性、体外培养及生长抑制因子的作用等相关文章,并查找全文。主要选择基础研究类文章,无论有无对照组均纳入。结果:共检索到相关文章59篇,排除比较陈旧的文章,最后纳入38篇进行总结分析。胚胎干细胞与胚胎生殖细胞分别从附置前早期胚胎内细胞团和早期胎儿生殖嵴原始生殖细胞分离克隆出来,均具有自我更新、无限增殖能力及多向分化潜能,在体外培养条件下可保持稳定的二倍体核型,诱导分化后可形成3种胚胎生殖层。饲养层细胞是人胚胎生殖细胞体外培养的必要条件,常用饲养层细胞有鼠STO细胞系、鼠胚胎成纤维细胞,体外生长所需主要细胞因子包括干细胞生长因子、碱性成纤维细胞生长因子和白血病抑制因子,然而只要在培养基中加入鼠成纤维细胞的上清液和碱性成纤维细胞生长因子,胚胎干细胞可在无饲养层的条件下进行体外培养。结论:胚胎干细胞和胚胎生殖细胞具有相似的增殖特性,一定条件下可以分化为包括生殖细胞在内的所有功能细胞,并可相互转变,在胚胎发育、基因治疗、药物筛选、新药开发、生殖医学及人类疾病的移植治疗中具有广泛的应用前景。