Suppression of human ovarian carcinoma metastasis by the metastasis-suppressor gene, BRMS1

Metastasis-suppressor genes, by definition, suppress metastasis without affecting tumorigenicity and, hence, present attractive targets as prognostic or therapeutic markers. BRMS1 (breast cancer metastasis suppressor) has recently been identified as a metastasis-suppressor gene for human breast cancer and melanoma. Expression of BRMS1 messenger RNA (mRNA) in multitissue including normal prostate, ovarian, testis, and colon has been detected by northern blot analysis. We hypothesize that the role of BRMS1 in tumor progression may not be limited to breast cancer and melanoma. We previously found that BRMS1 mRNA levels in primary ovarian epithelial carcinomas were significantly lower than that in normal ovarian and benign tumors (P < 0.05), and statistical analysis of BRMS1 mRNA levels revealed that BRMS1 mRNA levels were significantly higher in early tumor stages (I, II) compared with advanced tumor stages (III, IV) in which lymph node or distant metastases were present (P < 0.01). Our data showed that reduced BRMS1 mRNA seems to influence ovarian carcinoma metastatic ability. Therefore, we transfected BRMS1 plasmid into highly malignant ovarian carcinoma cell line, HO-8910PM, and examined cell biologic behaviors including proliferation, adhesion, invasion, and metastasis in vitro and in vivo. BRMS1 expression did not alter the proliferation of HO-8910PM cells in vitro and primary tumor formation in vivo. But, BRMS1 expression significantly suppressed the cell adhesion to extracellular matrix components and in vitro cell invasion in BRMS1-transfected HO-8910PM cells compared to parental HO-8910PM and vector-only transfectants (HO-8910PM-vect). Furthermore, motility of BRMS1 transfectants was inhibited. lung colony formation of intravenously injected BRMS1 transfectants in nude mice was significantly reduced. Also, BRMS1 transfectants form significantly less metastatic to organs of peritoneal cavity in orthotopically implanted ovarian tumor nude models. We further discovered that BRMS1 expression did downregulate expression of an actin-bundling protein associated with cell motility -fascin, which perhaps is the mechanism underlying BRMS1 suppression of metastasis. These data suggested that in addition to its already described role in breast cancer and melanoma, BRMS1 functions as a metastasis-suppressor gene in ovarian carcinoma by modifying several metastatic-associated phenotypes, offering a new target for therapeutic intervention.     

The need for future surgical low rectal cancer studies

Optimal surgery remains the mainstay of best outcome for rectal cancer. The demonstration, during the 3rd Annual Pelican Surgical Workshop Symposium, of an abdomino‐perineal excision (APE) performed in the ‘Berlin position’, further added to the debate on optimal surgical technique. Much interest was created at the 1st Pelican symposium with the demonstration, by the Swedish surgeon Dr Torbjorn Holm, of a prone APE and the delivery of a ‘cylindrical’ specimen and the potential to reduce local recurrence using this approach. The high rates of local recurrence following APE and the discussions as to optimal technique have led to the development of a proposed MERCURY Study Group study to assess the benefit of a radical APE, with careful assessment of the impact that this operation may have on morbidity. A German study has also been proposed adopting the UK's multidisciplinary team approach. It aims at targeting preoperative chemoradiotherapy at those patients in whom a radical APE or total mesorectal excision is likely to result in an involved surgical resection margin. In this article we review the evidence for improving the surgical technique for low rectal cancer. We believe improvements may be best achieved through continued European prospective, multi‐centre, multidisciplinary studies.     

High incidence of and risk factors for metachronous bilateral upper tract urothelial carcinoma in Taiwan

AIM: Urothelial carcinoma (UC) can occur multifocally in the whole urothelium. A higher rate of bilateral metachronous upper tract (UT) UC was noted in Taiwan. The incidence and risk factors were largely unknown and hence were explored in the study. METHODS: From January 1977 through June 2003, 462 patients with unilateral UT-UC were studied retrospectively. The cumulative incidence of contralateral recurrence was analysed with the Kaplan-Meier analysis. Potential risk factors for contralateral recurrence including age, smoking, bladder cancer, renal function, diagnostic year etc. were evaluated with the log-rank test. Independent risk factors were identified by using the Cox regression analysis. RESULTS: The median follow-up time was 34 months (6-337). Among the 462 patients, 52 (11.3%) developed metachronous contralateral UC. The 2, 5, and 10-year contralateral disease-free survivals were 93.5%, 84.0%, and 75.7%, respectively. The median time to contralateral recurrence was 31.0 months. With the univariate analysis, only poor renal function (serum creatinine < or > OR =2.0 mg/dL, P < 0.001) and late diagnostic year (before or after 1990, P < 0.001) were risk factors for contralateral recurrence. In the multivariate analysis, poor renal function (hazard ratio: 2.98; 95% confidence interval: 1.67-5.33; P < 0.001) and late diagnostic year (hazard ratio: 4.27; 95% confidence interval: 1.71-10.65; P = 0.002) remained independent risk factors. CONCLUSIONS: The incidence of metachronous UT-UC is high in Taiwan. Patients who had either chronic renal insufficiency or a disease diagnosed after 1990 had a higher risk of contralateral recurrence.     

11C-choline positron emission tomography in bladder cancer: Report of four cases

Little work has been done with positive emission tomography (PET) in bladder tumors because high urinary excretion of (18)F-FDG makes visualization of the bladder tumor difficult. (11)C-choline has recently been reported as a new tracer which lacks urinary radioactivity. We report the result of (11)C-choline PET in four patients with invasive bladder tumors. In one case, (11)C-choline PET could detect bladder tumor effectively without urinary activity and bone metastasis despite negative bone scintigraphy. On the other hand, an intense accumulation of the tracer in the bladder hampered the interpretation on PET scanning in three patients. The mechanisms of the (11)C-choline accumulation in the bladder were reported to be due to inflammatory and proliferative changes in the mucosa of the bladder from previous catheterization or other factors. Further study is necessary to prove the value of (11)C-choline PET for detecting primary bladder cancer and bone metastasis.     

Fine-needle aspiration cytology of an endometrioid-like variant of yolk sac tumor.

A 36-year-old male with a history of immature teratoma and embryonal carcinoma of the testis was admitted to the hospital for abdominal pain and fever. A CT scan revealed a large right abdominal mass. The patient's serum alpha-fetoprotein (AFP) was 46.8 ng/ml (reference < 25 ng/ml). Fine-needle aspiration (FNA) of the mass revealed malignant glandular cells. Chemotherapy was instituted, followed by resection of the large abdominal mass. The tumor was grossly encapsulated, consisting of large areas of necrotic, hemorrhagic tissue surrounded by smaller, multiloculated cysts. Microscopically, the tumor had a villoglandular pattern and variably stratified tall columnar cells. A prominent feature of the columnar cells was supranuclear and subnuclear vacuolization. Intracytoplasmic PAS-positive, diastase-resistant hyaline globules were occasionally present. AFP by immunoperoxidase was prominent within the tumor. This recurrence of the previously diagnosed testicular teratoma with embryonal carcinoma represents a yolk sac tumor with components strongly resembling endometrioid carcinoma, a variant only recently described in eight cases of ovarian origin (Clement et al.: Am J Surg Pathol 1987; 11(10):767-778). We believe this is the first reported case of an endometrioid-like variant of testicular yolk sac tumor and also the first report of the FNA cytology findings in this variant.     

Loss of constitutional heterozygosity in human astrocytomas

Summary Inactivation of tumour suppressor genes or anti-oncogenes as well as activation of dominant acting oncogenes seem to be important mechanisms in the pathogenesis of gliomas. We compared constitutional and tumoural genotypes at different restriction fragment length polymorphism loci (RFLP) on chromosomes 10 and 17 in 15 unrelated individualsLoss of heterozygosity (LOH) pointing to chromosomal loss or deletions was detected for at least one chromosme 17 marker in 11 gliomas (astrocytomas grades I–III and glioblastoma multiforme), whereas LOH for chromosome 10 loci was only detected in 3 out of 9 cases of glioblastoma multiforme and was not detected in low grade gliomas. Since LOH for chromosome 10 loci seems to be restricted only to glioblastoma multiforme, it is possible that recessive mutations on chromosome 10 are engaged in tumour progression from astrocytomas to glioblastoma multiforme. As LOH of chromosome 17 markers occurs in astrocytomas as in glioblastoma multiforme, chromosome 17 loci probably are involved in early tumour development.     

重组人肿瘤坏死因子诱导HL－60白血病细胞分化及调控原癌基因表达的作用

采用２０～２００Ｕ／ｍｌ的重组人肿瘤坏死因子（ｒｈＴＮＦ－α）处理体外液相培养的人早幼粒白血病细胞珠ＨＬ－６０，观察到５０～２００Ｕ／ｍｌ的小剂量ＴＮＦ具有诱导其向单核－巨噬细胞途径分化及抑制其增殖的效应。采用细胞总ＲＮＡ打点杂交技术检测１～１００Ｕ／ｍｌＴＮＦ诱导ＨＬ－６０细胞早期（１２小时内）对其ｃ－ｍｙｃ，ｃ－ｆｏｓ原癌基因表达的影响，发现ＴＮＦ可抑制ｃ－ｍｙｃｍＲＮＡ水平及ｃ－ｆｏｓ短暂性表达增高。结果表明此小剂量ｒｈＴＮＦ－α具有诱导白血病细胞分化的效应及调控多癌基因表达的作用。     

Is the circumferential resection margin a predictor of local recurrence after preoperative radiotherapy and optimal surgery for rectal carcinoma?

OBJECTIVE: Circumferential resection margin (CRM) involvement has been correlated with a high risk of developing local recurrence. The aim of this study was to examine the prognostic significance of the CRM involvement after curative resection of rectal cancer in patients treated with preoperative radiotherapy and postoperative chemotherapy where indicated. METHOD: All patients with rectal cancer treated in a regional central unit from 1996 to 2004 were identified. A surgical resection was performed on 257 patients, and in 229 of these this was assessed as potentially curative. The CRM was examined in all patients. A CRM of < or = 1 mm was considered positive. RESULTS: A positive margin was seen in 19 (8%) patients. At a median follow up of 40 months, only four (1.7%) patients had developed local recurrence, one of whom had a positive CRM. In the four patients the tumour was 5 cm or less from the anal verge. There were no significant differences regarding local recurrence and survival between CRM positive and negative tumours. CONCLUSION: Rectal cancer managed by combined radiochemotherapy and surgery resulted in a low positive CRM rate and a low local recurrence rate. An involved CRM was not a predictor of local recurrence.     

全肝MR灌注成像早期监测肝VX2肿瘤经皮酒精注射疗效的实验研究

目的研究全肝MR灌注成像（MRPI）早期监视兔肝VX2瘤经皮酒精注射（PEI）疗效的价值。方法新西兰大白兔10只，经开腹手术于肝内注射VX2肿瘤细胞悬液0．1ml，分别在种瘤后第2、3周进行MRT。WI、T2WI检查监视肿瘤生长情况。在种瘤后第3周时，于CT引导下，于肿瘤一侧的早期强化最明显处注射无水乙醇1.0ml，治疗1周后应用MRPI观察治疗效果。灌注参数包括：对比剂到达时间（T0）和最大上升斜率（ss），应用t检验比较治疗区与肿瘤未治疗区的灌注参数。结果10只兔肿瘤均种植成功，第3周时肿瘤直径（2．6±0．6）cm。治疗过程中3只兔死亡，PEI治疗1周后的治疗区呈无或低度强化。肿瘤未治区与治疗区的11D分别为（16．0±1．2）、（50，8±5．9）S，ss分别为38．9±2．2、6．0±1．2，差异均有统计学意义（t值分别为15．8、-39．6，P值均〈0．05）。常规T1 WI、T2 WI无法清晰显示治疗区与未治疗区的差异。结论全肝MRPI可以较敏感的早期监测PEI疗效，早期强化的消失可作为PEI治疗有效的标志。