Clinical evaluation using magnetic resonance imaging for patients with stage III cervical carcinoma treated by radiation alone in multicenter analysis: its usefulness and limitations in clinical practice

To evaluate the ability of magnetic resonance imaging (MRI) to predict the clinical outcome, we perform retrospective multicenter analysis of patients with stage III disease treated with radiation alone. From three institutions, 80 patients with stage III disease diagnosed with MRI were entered in the study. Seventy-eight patients received intracavitary brachytherapy with external beam radiotherapy. Univariate and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). The 5-year OAS, DFS, PC, and DMFS rates were 59.5%, 48.7, 74.2%, and 62.5%, respectively. Bilateral pelvic fixation to the pelvis (p = 0.001) and patient age 50 years or less (p < 0.0001) were significant adverse factors for OAS. As a function of DFS, these were positive lymph nodes (p = 0.02), bilateral fixation to the pelvis (p = 0.03), and younger patient age (p < 0.0001), respectively. Patient age 50 years or less proved to be the only significantly unfavorable factor for PC (p < 0.0001). Larger size/volume (p < 0.05), positive lymph nodes (p = 0.03), bilateral pelvic disease (p = 0.02), and younger patient age (p = 0.004) were significantly adverse factors for DMFS. Using multivariate analysis, patient age 50 years or less, disease with bilateral fixation, and calculated volume more than 100 ml proved to be significantly adverse factors for OAS and DFS. In the analysis of PC, only patient age 50 years or less was a significantly adverse factor (p = 0.0014, relative risk [RR] = 14.93). Bilateral fixation to the pelvis (p = 0.0055, RR = 4.032), positive lymph nodes (p = 0.0494, RR = 2.637), and large calculated volume (>100 ml; p = 0.0057, RR = 4.831) proved to be significantly adverse factors for DMFS. For patients with stage III disease, size/volume and lymph node status derived from MRI showed a significant correlation with the development of distant metastasis, but failed to predict locoregional control. In addition, size/volume analysis showed no apparent relationship with disease-free survival. For patients with stage III disease, MRI may provide beneficial information predicting distant metastasis, but not for local control.     

Comparison of prognostic value of MRI and FIGO stage among patients with cervical carcinoma treated with radiotherapy

PURPOSE: To compare the efficacy of MRI and FIGO stage, we performed retrospective multicenter analysis of patients with Stage II-III disease treated with radiation alone. METHODS AND MATERIALS: From three institutions, 164 patients diagnosed with cervical carcinoma were entered into the study. The majority of this cohort received intracavitary brachytherapy combined with external beam radiotherapy (n = 161). Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). RESULTS: The 5-year OAS, DFS, PC, and DMFS rates were 68.8%, 60.4%, 77.4%, and 71.7%, respectively. Using uni- and multivariate analyses, both large tumor size/volume and positive lymph node enlargement (LN) showed a significantly unfavorable influence on survival and local and/or distant failure (p < 0.05). Using these two prognostic factors, patients were divided into three subgroups; the 5-year DFS rates of patients with risk 0 (volume 50 cc or positive LN), and 2 (volume >50 cc and positive LN) were 72.9%, 53.3%, and 26.1%, respectively (p < 0.0001). Among patients with volume 0.05). CONCLUSION: MRI will provide more useful and practical information than will FIGO stage classification for patients with bulky disease, although this will remain a prognostic factor for patients with nonbulky disease (volume 相似文献   

Adenovirus-mediated gene therapy specific for small cell lung cancer cells using a Myc-Max binding motif

Recent clinical trials of gene therapy for patients with thoracic cancers have shown that these treatments were well tolerated with minimal side effects and that we need to further enhance specificity as well as efficiency of gene transfer to target cancer cells. We previously reported that myc-overexpressing SCLC cell lines became selectively sensitive to ganciclovir (GCV) by transducing the herpes simplex virus thymidine kinase (HSV-TK) gene under the control of the Myc-Max response elements (a core nucleotide sequence, CACGTG) and that this construct (MycTK) could be utilized to develop a novel treatment against chemo-radio-resistant SCLC. We report here in vivo antitumor effects and safety of a replication-deficient adenoviral vector containing the Myc-Max binding motif (AdMycTK) on SCLC cells. In vitro infection with AdMycTK selectively rendered myc-overexpressing SCLC cell lines 63- to 307-fold more sensitive to GCV. In vivo injections with AdMycTK followed by GCV administration markedly suppressed the growth of myc-overexpressing tumors established in the subcutis or in the peritoneal cavity of athymic mice. On the other hand, infection with AdMycTK did not significantly affect either in vitro GCV sensitivity of the cells expressing very low levels of the myc genes or the growth of their subcutaneous tumors. Moreover, we observed no apparent side effects of this treatment including body weight loss or biochemical abnormalities in contrast to the treatment with AdCATK that conferred strong but nonspecific expression of the HSV-TK gene. These results suggested that AdMycTK/GCV therapy is effective on SCLC patients whose tumors overexpress myc family oncogenes.     

Effect of dietary conjugated linoleic acid on the in vivo growth of rat hepatoma dRLh-84

We examined the effect of dietary conjugated linoleic acid (CLA) on the growth of injected hepatoma dRLh-84 in Donryu rats. After experimental diets containing 0% or 2% CLA were given to male Donryu rats for 3 wk, dRLh-84 cells were injected into the left lobe of the hepatic capsule, and the experimental diet was continued. The cells formed a solid tumor > or = 1 wk after the injection, and thereafter the tumor grew with feeding duration. In a morphological study, this tumor appeared to be a low-differentiated hepatoma, and there was no remarkable difference in the morphology of the tumor between 0% and 2% CLA groups. Tumor weight was significantly higher in the 2% CLA group than in the 0% CLA group throughout the feeding period after the injection. Serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities were significantly higher in 2% CLA-injected rats than in 0% CLA-injected rats at 3 wk after the injection. CLA upregulated acyl-CoA oxidase activity, especially 1 wk after the injection. However, dietary CLA did not activate carnitine palmitoyl transferase II, which is a rate-limiting enzyme in the mitochondrial beta-oxidation pathway. Natural killer cell activity in the spleen tended to be higher in injected rats, but a significant effect of dietary CLA was not recognized. Serum interferon-gamma and tumor necrosis factor-alpha levels were higher in injected than in sham rats. Moreover, these levels were higher in 2% CLA groups than in the respective 0% CLA groups.     

Molecular analysis for p53 and mdm2 in intracranial germ cell tumors

Intracranial germ cell tumors (ICGTs) are uncommon neoplasms. The histological appearance of ICGTs is indistinguishable from that of the usual testicular germ cell tumors (TGTs). Recently, several reports have associated molecular abnormalities of p53 and mdm2 in TGTs with their malignancies. However, whether ICGTs are associated with molecular abnormalities is still unknown. We analyzed a series of 16 ICGTs for mutations in the TP53 gene by single-strand conformation polymorphisms, and for amplification of the MDM2 gene using differential PCR. In addition, the same 16 tumors were examined for p53 and mdm2 protein overexpression using antibodies directed against p53 [monoclonal antibodies (mAb) 1801 and DO7] and mdm2 (IF2), respectively. Twelve (75%) and 2 (13%) of the 16 ICGTs reacted with DO7 and PAb1801, respectively, and 1 (6%) carried a TP53 gene mutation. Thirteen (81%) of the 16 ICGTs reacted with IF2, and 3 (19%) carried MDM2 gene amplification. The less frequent TP53 gene mutation compared with MDM2 gene amplification, and the frequently expressed p53 and mdm2 protein, are similar to the case for TGTs. It is tempting to speculate that ICGTs might have the same cellular origins as TGTs with abnormalities in p53 and mdm2, which could play an important role of tumorigenesis. Received: 9 March 1999 / Revised, accepted: 10 May 1999     

Survey for Trypanosoma cruzi infection in a municipality in northeast Brazil

An epidemiological survey of Trypanosoma cruzi infection was carried out in Bodocó, located in the western part of the State of Pernambuco, Brazil. Two hundred and forty-one individuals were parasitologically and immunologically screened. Although hemoculture did not reveal the presence of parasites in the blood, the sera of 5 individuals were scored as positive by the indirect fluorescence antibody test and the enzyme-linked immunosorbent assay. Seropositivity in individuals above and below the age of 40 was 14.8 and 0.5%, respectively. These results indicate that recent infections with T. cruzi are rare in this area. However, since a T. cruzi-infected triatomid (Triatoma brasiliensis) was captured in a school classroom, this area must be considered endemic. When triatomid feces containing parasites were inoculated into a jird (mongolian gerbil), parasitemia appeared 10 days later. Immunohistochemical staining, using monoclonal antibody specific for T. cruzi, labeled organisms in jird tissues. These observations demonstrate that the jird is a suitable host for experimental T. cruzi infections and that monoclonal antibody is effective for detection of the parasite in host tissues.     

青光眼视网膜神经纤维层厚度的光学相干断层扫描纵向评估

目的：纵向评估光学相干断层扫描（OCT）视盘周围神经纤维层厚度测量，并将这些检查与临床状态和自动视野计检查作横向比较。 方法：对参与前瞻性纵向研究的青光眼或疑似青光眼患者64只眼（37例）作回顾性评估。所有参与者每6个月作一次全面的临床评估、视野检查和OCT。视野进展按可重复性测量的视野平均偏差至少比基线降低2dB，OCT进展按可重复性测量视网膜神经纤维层平均厚度至少变薄20pro。 结果：每个患者在中位值为4．7年的随访中有5个可使用的OCT扫描。青光眼和疑似青光眼患者之间视网膜神经纤维层厚度线性回归斜度的差异对所有变量均不显著；然而，Kaplan-Meier生存曲线分析显示视野比OCT测量有较高的进展率。在随访期间66％的眼是稳定的。22％只有OCT进展，9％单有视野平均偏差进展。3％视野和OCT都有进展。 结论：OCT比全自动视野计对辨别青光眼进展有更大的可能性。这可能反映OCT的敏感性或在常规方法发现之前其真实损害就能被OCT发现。     

肿瘤坏死因子α与鼠疟贫血

疟疾性贫血的原因复杂,主要是红细胞的破坏增加和生成减少,但机制不明。本文研究了疟原虫感染时巨噬细胞产生的肿瘤坏死因子(TNF-α)对原始红细胞系和红细胞生成的影响,结果认为TNF-α起着抑制红细胞生成的作用。作者选择2～3月龄的雌性BALB/c小鼠,接种伯氏疟原虫后分析骨髓、脾脏等组织中的红细胞系和多能干细胞系的变化。结果显示,感染后2天骨髓和脾脏低成熟的红系祖细胞爆发群(BFU-E)仍正常,接种后的7天,骨髓和脾脏中的BFU-E明显减少,但更成熟的红系祖细胞(CFU-E)接种后第2天即减少。CFU-E在因感染而下降9天后,有一个暂时性的上升。重组人