Micro RNA expression and prognosis in low-grade non-invasive urothelial carcinoma

Purpose To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence. Materials and Methods Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles. Results There was a marginal correlation between multiplicity and miR-let7c over-expression. For all others miRNA no correlation between their expression and prognostic factors was found. Conclusion We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except miR-10a, over-expressed in most of cases, seeming to have increased levels in tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice. .

MicroRNA 100: a context dependent miRNA in prostate cancer

OBJECTIVE: MicroRNAs are noncoding RNA molecules involved in the development and progression of tumors. We have found that miRNA-100 is underexpressed in metastatic prostate cancer compared to localized disease. Conversely higher levels of miR-100 are related to biochemical recurrence after surgery. This suggests that miR-100 may be a context-dependent miRNA, acting as oncogene or tumor suppressor miRNA. Our aim is to demonstrate the role of miR-100 in the control of predicted target genes in prostate cancer cell lines. METHODS: Cell lines DU145 and PC3 were transfected with miR-100, antimiR-100 and after 24 h and 48 h of exposure, qRT-PCR and western blot were performed for mTOR, FGFR3, THAP2, SMARCA5 and BAZ2A. RESULTS: There was reduction in mTOR (p = 0.025), THAP2 (p = 0.038), SMARCA5 (p = 0.001) and BAZ2A (p = 0.006) mRNA expression in DU145 cells after exposure to miR-100. In PC3 cells, mTOR expression was decreased by miR-100 (p = 0.01). There was a reduction in the expression levels of proteins encoded by studied genes, ranging from 34% to 69%. CONCLUSIONS: We demonstrate that miR-100 is a context-dependent miRNA controlling BAZ2, mTOR, FGFR3, SMARCA5 and THAP2 that might be involved in PC progression. The elucidation of the roles of miRNAs in tumors is important because they can be used as therapeutic targets in the future. .

Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

OBJECTIVES: Bladder cancer represents 3% of all carcinomas in the Brazilian population and ranks second in incidence among urological tumors, after prostate cancer. The loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cancer cell death in various cancer types. Our aim was to investigate the ability of Prima-1 to induce apoptosis after DNA damage in bladder cancer cell lines. METHOD: The therapeutic effect of Prima-1 was studied in two bladder cancer cell lines: T24, which is characterized by a p53 mutation, and RT4, which is the wild-type for the p53 gene. Morphological features of apoptosis induced by p53, including mitochondrial membrane potential changes and the expression of thirteen genes involved in apoptosis, were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR). RESULTS: Prima-1 was able to reactivate p53 function in the T24 (p53 mt) bladder cancer cell line and promote apoptosis via the induction of Bax and Puma expression, activation of the caspase cascade and disruption of the mitochondrial membrane in a BAK-independent manner. CONCLUSION: Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo may be conducted to test this molecule as a new therapeutic agent for urothelial carcinomas of the bladder, which characteristically harbor p53 mutations.

Nuevo radioinmunoconjugado -dota-h-r3: Sintesis y radiomarcaje / New radioimmunoconjugate -dota-h-r3: synthesis and radiolabeling

El marcaje de anticuerpos monoclonales con metales radiactivos para diagnóstico y terapia generalmente involucra el uso de agentes quelatantes bifuncionales que contienen una función reactiva para conjugarse con las proteínas y un grupo capaz de enlazar fuertemente al metal formando complejos fisiológicamente estables. El objetivo del trabajo fue modificar el anticuerpo monoclonal humanizado (h-R3) con el ácido 1,4,7,10-tetraazaciclododecano-N,N´,N´´,N´´´-tetraacético (DOTA) en solución acuosa, realizar el marcaje de los conjugados obtenidos con y estudiar algunas de las variables que influyen en la reacción, así como la estabilidad del radioinmunoconjugado en presencia de otros agentes quelatantes.

Labelling of monoclonal antibodies with radioactive metals for cancer diagnosis and therapy has usually been accomplished by the use of bifunctional chelating agents, which contain both a reactive functionality for covalent attachment to proteins and a strong metal-binding group capable of forming a physiologically stable complex with the radionuclide. The objective of the present work was to modify the humanized monoclonal antibody (h-R3) with the 1,4,7,10-tetraaza-cyclododecane N,N´,N´´,N´´´-tetraacetic acid (DOTA) in aqueous solution, achieve the labelling of the obtained conjugates with and study some of the variables that influence in the labelling reaction, as well as the stability of the radioimmunoconjugate in presence of other chelating agents.

Valor del ECMO en el tratamiento del shock cardiogénico refractario posoperatorio / Value of ECMO in the treatment of refractory postoperative cardiogenic shock

Este estudio presenta los resultados del uso de circulación extracorpórea con oxigenador de membrana (ECMO) para el tratamiento del shock cardiogénico posoperatorio en 219 pacientes operados en el Herzzentrum Leipzig entre 1997 y 2002. Durante la hospitalización, el 61 por ciento de los pacientes fueron desconectados exitosamente y el 24 por ciento fueron dados de alta. Las variables predictoras de sobrevida hospitalaria fueron la edad, la ausencia de infarto preoperatorio, la ausencia de diabetes, el uso de balón de contrapulsación intraaórtico (BCIA) y el tipo de cirugía realizada. A pesar de que el ECMO está asociado con una morbimortalidad significativa, se ofrece a pacientes que de otra manera fallecerían.

Histology of two rice bodies isolated from the stifle of an adult draught horse stallion

In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia.

Laparoscopic cholecystectomy in Jamaica: the initial experience

This review of all laparoscopic cholecystectomies performed between 1993 and 1995 in Jamaica records the experience of local surgeons following an accelerated training programme. Special attention was paid to operating time, conversions, complications, analgesic requirements, time to discharge and cost. Comparisons were made of the local experience with the international experience. Laparoscopic cholecystectomy has been found to be a safe and viable option for Jamaican patients with gall bladder disease.

Thoracic outlet syndrome

A case of thoracic outlet syndrome (TOS) treated at the University Hospital of the West Indies, Jamaica is presented. The diagnosis, investigation and management of TOS are discussed.