Detection of C-erb B2 gene amplification in bilharzial associated bladder cancer using fluorescence in situ hybridization

BACKGROUND: Gene amplifications are common events in different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Fluorescence in situ hybridization (FISH) represents a standard methodologic approach for testing for this genetic alteration, as it is rapid, reproducible and extremely reliable in detecting presence of C-erb-B2 gene amplification for clinical utility. PATIENTS AND METHODS: In this study, FISH is used in a series of archival human bilharzial bladder cancer specimens to evaluate for the presence of cerbB-2 gene alterations in the most common malignant tumor in bilharzial endemic areas, e.g., Egypt and some other countries. The study included 40 cases, 30 males and 10 females. Their ages ranged between 30 years and 76 years (median: 51 years). Twenty-one cases had squamous cell carcinoma, 16 had transitional cell carcinoma, two had adenocarcinoma, and one case had undifferentiated carcinoma. RESULTS: Thirteen out of 40 tumor samples (32.5%) show evidence of true C-erb-B2 gene amplification. Of the remaining samples, 24 (60%) show no gene amplification and three (7.5%) fall into the borderline category with a ratio between one and two C-erb-B2 genes/cell relative to chromosome 17 centromeres. No evidence of chromosome 17 polysomy was found in any cases scored as single copy with the C-erb-B2 probe. CONCLUSION: No significant association was found between gene amplification and any of the tested clinicopathologic parameters or tumor recurrence except for tumor grade where higher tumor grades tended to be associated with more C-erb-B2 gene amplification (P = 0.01) thus reflecting more tumor aggressiveness. So, the amplification of C-erb-B2 in bilharzial associated bladder cancer is probably not independently related to clinical outcome of patients.     

Buffalo metropolitan area and Erie County stroke study: rationale, design, and methods

OBJECTIVES: The primary objective of this study was to define the incidence, disability, and death associated with stroke in the Buffalo metropolitan area and Erie County. This area has the highest stroke rate in New York State and therefore represents an ideal site to develop a successful model for prevention and management of stroke. DESIGN: A cross-sectional design to study all new and recurrent strokes that occurred in the calendar year 2000 in the geographical location of Buffalo metropolitan area and Erie County. PATIENTS AND DATA COLLECTED: A retrospective review of an estimated 5,000 patients with new stroke will be performed at regional hospitals and the coroner's office to determine the stroke subtypes, cerebrovascular risk factors, diagnostic investigations, treatment provided, and outcome. The total population residing in Buffalo in the year 2000 is available through the recent census. The study will also evaluate the quality of care provided for stroke patients including effectiveness of primary and secondary stroke prevention measures within this geographical region. CONCLUSIONS: We believe that this information will assist in allocation of resources and implementation of steps to improve stroke prevention and treatment.     

Echinococcosis of the rib with epidural extension: a rare cause of paraplegia

Skeletal echinococcosis is a relatively rare entity and that of the rib is exceptional. Less than 50 cases of costal echinococcosis have been reported in the literature so far. Accurate pre-operative diagnosis aids in appropriate management and helps to eradicate the disease. This also prevents the dissemination of parasite and further complications. We report a case of echinococcosis of the rib with epidural extension in a young adult who presented with paraparesis and back pain. His laboratory investigations were within normal limits. Plain radiographs of the dorsal spine, CT scan of thorax and MRI of dorsal spine were performed. The imaging features were suggestive of echinococcosis involving the rib with epidural extension. The cyst was completely resected. Histopathology of the resected specimen confirmed the diagnosis of echinococcosis.     

Bladder neck resection with preservation of antegrade ejaculation: Basir technique

PURPOSE: To evaluate a new method of bladder neck resection and to determine if antegrade ejaculation is preserved thereafter. PATIENTS AND METHODS: Two groups of patients were treated for their bladder neck obstruction. Group A, composed of 20 patients, was treated by bladder neck resection with preservation of more than 1 cm proximal to the verumontanum. Group B, also consisting of 20 patients, was treated by the old technique. Patients were evaluated before and after resection by semen volume, sperm count, symptoms, and urodynamic testing. RESULTS: In group A, antegrade ejaculation was maintained in 17 of the 20 patients (85%), while in 2 patients, only a small amount of semen was ejaculated and in 1 patient, complete retrograde ejaculation was reported. In group B, only 4 patients (20%) preserved antegrade ejaculation, and retrograde ejaculation occurred in 16 patients (80%). CONCLUSION: With preservation of >1 cm of the supramontanal part of the urethra during bladder neck resection, we could avoid the complication of retrograde ejaculation in those young patients who wish to preserve fertility.     

Apoptotic susceptibility of cancer cells selected for camptothecin resistance: gene expression profiling,functional analysis,and molecular interaction mapping

To study the molecular mechanisms by which drug resistance develops, we compared DU145 humanprostate cancer cells with a subline selected for resistance to camptothecin.Differences in gene expression level were assessed by hybridizing the two cell types against each other using quadruplicate "Oncochip" cDNA microarrays that included 1648 cancer-related genes. Expression levels differing by a factor of >1.5 were detected for 181 of the genes. These differences were judged statistically reliable on the basis of a stratum-adjusted Kruskal-Wallis test, after taking into account a dye-dependent variable. The 181 expression-altered genes included a larger than expected number of the "apoptosis-related" genes (P = 0.04). To assess whether this observation reflected a generalized resistance of RCO.1 to apoptosis, we exposed the cells to a range of stresses (cisplatin, staurosporine, UV, ionizing radiation, and serum starvation) and found greatly reduced apoptotic responses for RC0.1 (relative to DU145) using flow cytometric Annexin V and terminal deoxynucleotidyl transferase-mediated nick end labeling assays. We next examined the apoptosis-related genes in the context of a molecular interaction map and found expression differences in the direction "expected" on the basis of the apoptosis-resistance of RC0.1 for BAD, caspase-6, and genes that signal via the Akt pathway. Exposure of the cells to wortmannin, an inhibitor of the Akt effector phosphatidylinositol 3-kinase, provided functional support for involvement of the Akt pathway. However, closer examination of the molecular interaction map revealed a paradox: many of the expression differences observed for apoptosis-related genes were in the direction "contrary" to that expected given the resistance of RC0.1. The map indicated that most of these unexpected expression differences were associated with genes involved in the nuclear factor kappa B and transforming growth factor beta pathways. Overall, the patterns that emerged suggested a two-step model for the selection process that led to resistance in RC0.1 cells. The first hypothesized step would involve a decrease in apoptotic susceptibility through changes in the apoptosis-control machinery associated with the Bcl-2 and caspase gene families, and also in antiapoptotic pathways operating through Akt/PKB. The second step would involve changes in multifunctional upstream genes (including some genes in the nuclear factor kappa B and transforming growth factor beta pathways) that can facilitate apoptosis but that would also tend to contribute to cell proliferation in the presence of drug. Thus, we propose that a downstream blockade of apoptosis was "permissive" for the selection of upstream pathway changes that would otherwise have induced apoptosis. This model is analogous to one suggested previously for the relationship between oncogene function and apoptosis in carcinogenesis.