Raman microspectroscopic discrimination of TCam-2 cultures reveals the presence of two sub-populations of cells.

TCam-2 cells are the main in vitro model for investigations into seminomatous tumors. However, despite their widespread use, questions remain regarding the cells' homogeneity and consequently how representative they are of seminomas. We assess the TCam-2 cell line using routine and novel authentication methods to determine its homogeneity, identify any cellular sub-populations and resolve whether any changes could be due to generational differentiation. TCam-2, embryonal carcinoma cells (2102EP) and breast cancer cell (MCF7) lines were assessed using qRT-PCR, immunocytochemistry, flow cytometry and short tandem repeat analyses. Raman maps of individual cells (minimum of 10) and single scan spectra from 200 cells per culture were obtained. TCam-2s displayed the characteristic marker gene expression pattern for seminoma, were uniform in size and granularity and short tandem repeat analysis showed no contamination. However, based only on physical parameters, flowcytometry was unable to differentiate between TCam-2 and 2102EPs. Raman maps of TCam-2s comprised three equally distributed, distinct spectral patterns displaying large intercellular single spectral variation. All other cells showed little variation. Principal component, cluster and local spectral angle analyses indicated that the TCam-2s contained two different types of cells, one of which comprised two subgroups and was similar to some 2102EP cells. Protein expression corroborated the presence of different cells and generational differences. The detailed characterization provided by the Raman spectra, augmented by the routine methods, provide substantiation to the long-held suspicion that TCam-2 are not homogeneous but comprise differing cell populations, one of which may be embryonal carcinoma in origin.

A kidney tumor in an adolescent with severe hypertension and hypokalemia: an uncommon case--case report and review of the literature on reninoma.

This report presents a case of a 16-year-old hypertensive boy who presented to our clinic. Laboratory findings showed severe hypokalemia and markedly increased plasma renin activity. Abdominal ultrasonography and contrast-enhanced computed tomography of the abdomen revealed a well-circumscribed, solid, hypoenhancing cortical lesion (2 cm) in the lower pole of the left kidney. The patient underwent nephron-sparing surgery. Histopathologic examination gave a diagnosis of juxtaglomerular cell tumor. Reninoma is an uncommon cause of hypertension in a young adult and should be included in the differential diagnosis as a potential life-threatening and curable condition. The conservative surgical management is the gold standard for small, circumscribed lesions.

Prevention of urinary bladder cancer in the FHIT knock-out mouse with Rofecoxib, a Cox-2 inhibitor.

OBJECTIVES: Aberrant or increased expression of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of many diseases, including cancer. However, the exact mechanism by which COX-2 may influence tumorigenesis has yet to be described. To investigate the chemopreventive role of a COX-2 inhibitor, rofecoxib, in the development of urinary bladder cancer, we studied the effect of this drug in heterozygous and nullizygous fragile histidine triad (FHIT) gene-deficient mice in a chemically induced carcinogenesis model. MATERIALS AND METHODS: Two-hundred eight mice consisting of 50 FHIT +/+, 63 FHIT +/- and 95 FHIT -/-, were divided into five treatment groups and followed up for 15 weeks. Mice were treated with freshly prepared solution of 0.1% or 0.01% N-butyl-N-(-4-hydroxybutyl)-nitrosamine (BBN) in their drinking water and rofecoxib was administered in mouse chow at 150 parts per million concentration. Mice were sacrificed, and accurate histological analysis of the bladder was performed. RESULTS: Rofecoxib treatment significantly reduced the incidence of preneoplastic lesions/bladder tumors (P = 0.016). Comparing the incidence of neoplastic lesions in mice treated with rofecoxib and BBN (22/56, 39.3%) and mice treated only with BBN (32/57, 56.1%), a protective role of rofecoxib on the BBN tumor induction has been observed (P = 0.024). A similar result (P = 0.002) has been reached observing the incidence of mild and moderate dysplasia in mice treated with a lower concentration of BBN (8/16, 50.0% vs. 20/24, 83.3%).Moreover, as previously observed, a significant increase in neoplastic lesions in the FHIT +/- and FHIT -/- vs. FHIT +/+ mice after BBN treatment has been observed (P = 0.003). CONCLUSIONS: These findings suggest that rofecoxib provides a therapeutic defense against bladder carcinogenesis in our model and confirmed that the FHIT knock-out mouse is a suitable system to study in vivo bladder carcinogenesis.

Cardiac metastasis from renal cell carcinoma without inferior vena involvement: a review of the literature based on a case report. Two different patterns of spread?

We report the case of a 59-year-old man with advanced renal cell carcinoma (RCC), without inferior vena cava (IVC) involvement, treated with radical nephrectomy, palliative radiotherapy for bone metastasis, and medical therapy for bone and lung metastases. The patient died of cardiac arrest after evidence of massive malignant pericardial effusion. At autopsy, massive myocardial and pericardial neoplastic invasion was found. Heart involvement via the IVC is a well-known phenomenon during RCC progression, while in the absence of IVC involvement, clinically evident cardiac involvement is exceptional, with few cases reported in the worldwide literature. Analysis of prior reports and of the present case provides evidence on how the cardiac metastasis may have two distinct origins and clinical features. The first is hematogenous, via the IVC, even in the absence of renal vein involvement; it is generally circumscribed and has a good prognosis after surgery. The second is through the intrathoracic lymphatic system, in the presence of disseminated disease, especially pulmonary metastasis, and this type has a very poor prognosis.

Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract.

OBJECTIVE: To identify the prognostic factors predictive of metachronous bladder transitional cell carcinoma (TCC) in a multi-institutional dataset of patients who had undergone nephroureterectomy (NU) for nonmetastatic upper urinary tract (UUT) TCC. PATIENTS AND METHODS: The clinical and pathological data of 231 patients who had had NU for UUT-TCC from 1989 to 2005 in three European centres were collected retrospectively, and analysed for clinical and pathological variables. RESULTS: The median follow-up was 38 months; during the follow-up, bladder TCC was detected in 109 patients (47.2%), and was significantly more common in patients who had UUT-TCC after previous bladder TCC (P < 0.001), in those with ureteric cancer (P = 0.022), and in those with pT2 UUT-TCC (P = 0.017). On multivariate analysis, a previous history of bladder TCC was the only independent predictor of metachronous bladder TCC (hazard ratio 2.825; P < 0.001). The 5-year probability of being free from metachronous bladder TCC was 45.5%. A history of bladder TCC (P < 0.001) and UUT tumour site (P = 0.01) were significantly associated with the probability of bladder recurrence-free survival. On multivariate analyses, a previous history of bladder TCC (hazard ratio 2.226; P < 0.001) and the presence of ureteric TCC (1.562; P = 0.036) were independent predictors of the probabilities of being free from metachronous bladder TCC. CONCLUSION: In this multi-institutional study of patients who had had NU for UUT-TCC, a history of bladder TCC was the only independent predictor of metachronous bladder TCC, while both a history of bladder TCC and the presence of ureteric tumours were predictive of the probabilities of being free from metachronous bladder TCC.

Micro-RNA profiling in kidney and bladder cancers.

OBJECTIVES: Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors. METHODS AND MATERIALS: A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes. RESULTS: A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082). CONCLUSIONS: Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.

Independent predictors of cancer-specific survival in transitional cell carcinoma of the upper urinary tract: multi-institutional dataset from 3 European centers.

BACKGROUND: The objective of the current study was to identify variables that were predictive of cancer-specific survival in patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (UUT-TCC). METHODS: Clinical and pathologic data from 269 patients who underwent nephroureterectomy for UUT-TCC from 1989 to 2005 in 3 urologic European centers were collected retrospectively. Log-rank tests and Cox proportional-hazards regression models were used for univariate and multivariate analyses. RESULTS: Two hundred fifty patients underwent nephroureterectomy, and 19 patients underwent concomitant cystectomy for synchronous muscle-invasive bladder cancer. The median follow-up of the whole cohort was 34 months, and the median follow-up of the patients who remained alive and disease-free was 52 months. At follow-up, 57 cancer-related deaths (21.2%) were censored, and 169 patients (62.8%) were alive and disease-free. On univariate analysis, a history of previous bladder cancer, pathologic stage of the primary tumor and lymph nodes, tumor grade, the presence of lymphovascular invasion, tumor site, synchronous muscle-invasive bladder TCC, and tumor multifocality were associated with cancer-specific survival probabilities. On multivariate analysis, pathologic stage of the primary tumor and lymph nodes, tumor multifocality within the UUT, synchronous muscle-invasive bladder TCC, and a history of bladder TCC before the diagnosis of UUT-TCC were independent predictors of cancer-specific survival probabilities. CONCLUSIONS: In a multi-institutional dataset of patients who had undergone nephroureterectomy for UUT-TCC, the current results indicated that pathologic stage of the primary tumor and lymph nodes, a history of prior bladder TCC, the presence of synchronous muscle-invasive bladder cancer, and tumor multifocality within the UUT were independent predictors of cancer-specific survival probabilities.

Retroperitoneal fibrosis after chemotherapy.

We report the case of a patient with a non-Hodgkin lymphoma, who after a standard chemotherapy protocol, developed retroperitoneal fibrosis (RPF) in the absence of radiotherapy or other known causes. The final diagnosis was reached with the microscopic examination of tissue obtained by fine-needle aspiration and true-cut biopsy of the retroperitoneal mass. RPF can be related to chemotherapy alone.

A phase II study of gemcitabine at fixed infusion rate of 10 mg/m2/min with or without immunotherapy in advanced renal cancer.

BACKGROUND: Advanced renal cancer remains a challenge for oncologists since no treatment other than surgery has demonstrated a clear survival advantage. PATIENTS AND METHODS: Gemcitabine was given to suitable patients at a fixed infusion rate of 10 mg/m2/min. Eighteen patients received concomitant immunotherapy, mostly low doses of interleukin 2 (IL2). RESULTS: Thirty patients were enrolled. The overall response rate was 14% (22% in the subset of patients treated with both chemotherapy and immunotherapy) with a median progression-free survival time of 4.1 + months. Toxicity was not mild, mostly fatigue, nausea and anaemia, even though not life threatening. CONCLUSION: Gemcitabine at the fixed infusion rate of 10 mg/m2/min with concomitant low doses of IL2 could be useful in the palliative treatment of symptomatic patients with renal carcinoma progressing after tyrosine kinases inhibitor.

[BTA tests in the diagnosis and follow-up of superficial bladder cancer]. / BTA tests in the diagnosis and follow-up of superficial bladder cancer.

We reviewed the literature on Bladder Tumor Antigen (BTA Trak and STat) tests to evaluate the usefulness of such tests in the diagnosis and follow-up of bladder cancer and to compare these tests to routine diagnostic tools. We also report our experience on BTA tests in monitoring tumor recurrence of superficial bladder cancer in 194 patients: a correlation between an augmented risk of tumor recurrence and serial measurements of BTA Trak and positive BTA Stat have been identified. According to the available data, BTA tests can be useful in the diagnosis and follow-up of superficial bladder cancer.