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     

A depot neuroleptic withdrawal study

A double-blind withdrawal trial in 41 chronic schizophrenic outpatients was carried out during 6 months. Depot neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were compared with placebo to evaluate clinical and neurological effects during continued therapy and during withdrawal. The drugs were significantly more effective than placebo in preventing relapse and rehospitalization. In the placebo group 62% relapsed compared to 27% in the drug group. There was a weak and nonsignificant tendency to a higher relapse frequency in the flupenthixol group compared to the fluphenazine group. After withdrawal for 6 months, plasma levels for fluphenazine were detectable. Plasma levels for flupenthixol were not detectable after 9 weeks of withdrawal. The differences in the plasma levels may possibly explain the difference in relapse rate between the two depot neuroleptics. Furthermore, it was found that the patients who relapsed during fluphenazine treatment had a significantly lower plasma level of the drug than patients who did not relapse during treatment. The results from this study provide some information on the therapeutic levels of fluphenazine and flupenthixol in schizophrenic patients.