Molecular Characterization of Cancer Associated Fibroblasts in Prostate Cancer

Background: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor–stroma interactions may yield novel therapeutic targets for prostate cancer. Methods: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity®: IPA® software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF). Results: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-β as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs. Conclusions: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells

Molecular Characterization of Cancer Associated Fibroblasts in Prostate Cancer

Background: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor-stroma interactions may yield novel therapeutic targets for prostate cancer. Methods: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity (R) : IPA (R) software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF). Results: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-beta as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs. Conclusions: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells

Metastatic Potential of Small Testicular Germ Cell Tumors: Implications for Surveillance of Small Testicular Masses.

Incidental detection of urogenital tumors has increased in recent decades owing to the greater use of ultrasonography and cross-sectional imaging. For patients with low-risk prostate cancer or small renal masses, active surveillance represents a valid treatment option. Similarly, for men with small testicular masses <10 mm, active surveillance has been discussed as an alternative to surgery, although little is known regarding the behavior of small testicular germ cell tumors (GCTs). In the Swiss Austrian German Testicular Cancer Cohort Study we identified 849 patients (546 seminoma, 303 nonseminoma) treated with radical inguinal orchiectomy for GCT with a median tumor diameter of 35 mm. A tumor diameter <10 mm was observed in 25 patients (13 seminoma, 12 nonseminoma). Of these, five patients (20%) presented with primary metastatic disease, all of whom had elevated tumor markers and nonseminomatous GCTs. Two patients (8%) with initially localized disease (1 seminoma, 1 nonseminoma) and without elevated tumor markers experienced relapse at 4 mo (nonseminoma) and 14 mo (seminoma) after orchiectomy, despite the fact that the latter had received adjuvant chemotherapy. These findings highlight the metastatic potential of small testicular GCTs and raise the question of whether active surveillance for small testicular masses is safe. Patient summary This study on testicular cancer assesses the metastatic potential of small testicular germ cell tumors. Men with small testicular masses should be counseled about the malignant potential of small testicular germ cell tumors

Antimicrobial peptides of the Cecropin-family show potent antitumor activity against bladder cancer cells

<p>Abstract</p> <p>Background</p> <p>This study evaluated the cytotoxic and antiproliferative efficacy of two well-characterized members of the Cecropin-family of antimicrobial peptides against bladder tumor cells and benign fibroblasts.</p> <p>Methods</p> <p>The antiproliferative and cytotoxic potential of the Cecropins A and B was quantified by colorimetric WST-1-, BrdU- and LDH-assays in four bladder cancer cell lines as well as in murine and human fibroblast cell lines. IC₅₀values were assessed by logarithmic extrapolation, representing the concentration at which cell viability was reduced by 50%. Scanning electron microscopy (SEM) was performed to visualize the morphological changes induced by Cecropin A and B in bladder tumor cells and fibroblasts.</p> <p>Results</p> <p>Cecropin A and B inhibit bladder cancer cell proliferation and viability in a dose-dependent fashion. The average IC₅₀values of Cecropin A and B against all bladder cancer cell lines ranged between 73.29 μg/ml and 220.05 μg/ml. In contrast, benign fibroblasts were significantly less or not at all susceptible to Cecropin A and B. Both Cecropins induced an increase in LDH release from bladder tumor cells whereas benign fibroblasts were not affected. SEM demonstrated lethal membrane disruption in bladder cancer cells as opposed to fibroblasts.</p> <p>Conclusion</p> <p>Cecropin A and B exert selective cytotoxic and antiproliferative efficacy in bladder cancer cells while sparing targets of benign murine or human fibroblast origin. Both peptides may offer novel therapeutic strategies for the treatment of bladder cancer with limited cytotoxic effects on benign cells.</p

Robotic-assisted laparoscopic radical cystectomy: surgical and oncological outcomes

PURPOSE:Our first 91 consecutive cases undergoing a robotic assisted cystectomy were analyzed regarding perioperative outcomes, pathological stages and surgical complications. MATERIALS AND METHODS: Between 2007 and 2010 a total of 91 patients (76 male and 15 female), 86 with clinically localized bladder cancer and 5 with non-urothelial tumors underwent a radical robotic assisted cystectomy. We analyzed the perioperative factors, length of hospital stay, pathological outcomes and complication rates. RESULTS: Mean age was 65.6 years (range 28 to 82). Among the 91 patients, 68 were submitted to an ileal conduit and 23 to a neobladder procedure for urinary diversion. Mean operating time was 412 min (range: 243-618 min.) and mean blood loss was 294 mL (range: 50-2000 mL). In 29% of the cases with urothelial carcinoma the T-stage was pT1 or less, 38% were pT2; 26% and 7% were classified as pT3 and pT4, respectively. 14% of cases had lymph node positive disease. Mean number of lymph nodes removed was 15 (range 4 to 33). Positive surgical margins occurred in 2 cases (2.1%). Mean days to flatus were 2.13, bowel movement 2.88 and inpatient stay 18.8 (range: 10-33). There were 45 postoperative complications with 11% major (Clavien grade 3 or higher). At a mean follow-up of 15 months 10 patients had disease recurrence and 6 died of the disease. CONCLUSIONS: Our experience demonstrates that robotic assisted radical cystectomies for the treatment of bladder cancers seems to be very promising regarding surgical and oncological outcomes

Fatal Multiorgan Failure Associated with Disseminated Herpes Simplex Virus-1 Infection: A Case Report

Herpes simplex virus type 1 (HSV-1) infections cause typical dermal and mucosal lesions in children and adults. Also complications to the peripheral and central nervous system, pneumonia or hepatitis are well known. However, dissemination to viscera in adults is rare and predominantly observed in immunocompromised patients. Here we describe the case of a 70-year-old male admitted with macrohematuria and signs of acute infection and finally deceasing in a septic shock with multi organ failure 17 days after admission to intensive care unit. No bacterial or fungal infection could be detected during his stay, but only two days before death the patient showed signs of rectal, orolabial and genital herpes infection. The presence of HSV-1 was detected in swabs taken from the lesions, oropharyngeal fluid as well as in plasma. Post-mortem polymerase chain reaction analyses confirmed a disseminated infection with HSV-1 involving various organs and tissues but excluding the central nervous system. Autopsy revealed a predominantly retroperitoneal diffuse large B-cell lymphoma as the suspected origin of immunosuppression underlying herpes simplex dissemination

Silencing of the SEC62 gene inhibits migratory and invasive potential of various tumor cells

Sec62 is part of the protein translocation apparatus in the membrane of the endoplasmic reticulum (ER). In yeast, Sec62 participates in the post-translational translocation of proteins into the ER, but its function in mammals remains elusive. Previously we described the amplification and over-expression of the SEC62 gene in prostate cancer cell lines and the protein has been described as a potential target gene in prostate cancer. In the current study we show that in the tumor tissue of prostate cancer patients Sec62 protein levels are elevated compared with tumor-free tissue derived from the same patients or from prostates of control group patients and that the higher Sec62 protein content correlates with an increasing de-differentiation of the cells. Therefore, up-regulation of Sec62 protein content indeed is a phenomenon associated with prostate cancer progression. Analysis of a multi-tissue tumor array showed that in addition to prostate cancer, overproduction of Sec62 is observed in various other tumors, most significantly in tumors of the lung and the thyroid. To examine the tumor-related functions of Sec62, we silenced the SEC62 gene in the prostate cancer cell-line PC3 as well as in a set of other tumor cell-lines with two different siRNAs. In general, after silencing of SEC62 the cell migration and the invasive potential of the cells was blocked or at least dramatically reduced while cell viability was hardly affected. Thus, the SEC62 gene may indeed be considered as a target gene in the therapy of various tumors