Enrico Andrade

The therapeutic potential of recombinant BCG expressing the antigen S1PT in the intravesical treatment of bladder cancer

PURPOSE Bacillus Calmette-Guerin (BCG) continues to be employed as the most effective immunotherapy against superficial bladder cancer. We have developed an rBCG-S1PT strain that induces a stronger cellular immune response than BCG. This preclinical study was designed to test the potential of rBCG-S1PT as an immunotherapeutic agent for intravesical bladder cancer therapy. MATERIALS AND METHODS A tumor was induced in C57BL/6 mice after chemical cauterization of the bladder and inoculation of the tumor cell line MB49. Next, mice were treated by intravesical instillation with BCG, rBCG-S1PT, or PBS once a week for 4 weeks. After 35 days, the bladders were removed and weighed, Th1 (IL-2, IL-12, INOS, INF-gamma, TNF-alpha), and Th2 (IL-5, IL-6, IL-10, TGF-beta) cytokine mRNA responses in individual mice bladders were measured by quantitative real time PCR, and the viability of MB49 cells in 18-hour coculture with splenocytes from treated mice was assessed. In an equivalent experiment, animals were observed for 60 days to quantify their survival. RESULTS Both BCG and rBCG-S1PT immunotherapy resulted in bladder weight reduction, and rBCG-S1PT increased survival time compared with the control group. There were increases in TNF-alpha in the BCG treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group. The viability of MB49 cells cocultured with splenocytes from rBCG-S1PT-treated mice was lower than in both the BCG and control groups. CONCLUSIONS rBCG-S1PT therapy improved outcomes and lengthened survival times. These results indicate that rBCG could serve as a useful substitute for wild-type BCG.

Penile erection induced in vivo by a purified toxin from the Brazilian spider Phoneutria nigriventer

To verify the effect on erectile tissue of mice of two neuropeptides extracted from the poison of a spider, Phoneutria nigriventer, (Tx2‐5 and ‐6, termed ‘eretina’) after direct injection into the corpus cavernosum, to assess the minimum dosage necessary for effect, the time for initiation of action, the local duration of the erection, histological effects and the presence of local and systemic side‐effects.

Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model

BackgroundSince successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-α and IL-10 expression and to evaluate antitumour activity.MethodsFor Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF-〈 and IL-10 cytokine responses were measured by qPCR. Experiment II was performed in the same manner as Experiment I, except the animals were not challenged with MB49 tumor cells. Results: rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and control group. There were increases in TNF-α in the BCG-treated group, as well as increases in TNF-α and IL-10 mRNA in the rBCG-S1PT group.ConclusionThese data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-α and IL-10 cytokine productions may have therapeutic value.

Histopathological characterization of a syngeneic orthotopic murine bladder cancer model

PURPOSE We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line. MATERIALS AND METHODS Bladder tumor implantation was achieved by intravesical instillation of 5 x 105 MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3). After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7), carcinoembrionic antigen (Dako-CEA), p53 and c-erbB2 oncoprotein (Her2/neu). RESULTS Twenty-nine out of 30 animals (96.7%) developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g), 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model. CONCLUSIONS High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.

Penile prosthesis implantation in an academic institution in Latin America

PURPOSE We performed a retrospective study to analyze the effectiveness of implantable penile prostheses in the treatment of erectile dysfunction. MATERIALS AND METHODS This study included 249 patients who received implants between 2001 and 2008. A total of 139 patients who underwent penile prosthesis implantation were interviewed. RESULTS Approximately half of patients had previously used oral drugs before implantation of the prosthesis. About 45% had diabetes, 25.9% had previously undergone radical prostatectomy (RP), and 64% had hypertension. Exchange was performed in 5.7% for fracture, inadequate size, or extrusion. A total of 24.5% of men had immediate postoperative pain, 7.9% had local infection, and 8.6% had other complications. Patients who had previously undergone RP were 3.2 times more likely to experience a postoperative complication than patients who had not (p = 0.061). Eighty-nine (64%) patients returned to having sex as they had before being diagnosed with ED. Ninety-two of the men (66.2%) had sexual intercourse one to two times per week. One hundred twenty patients (86.3%) rated their level of satisfaction as good, excellent or very good, which was similar to the percentage of partners. The mean follow-up was 40 months. CONCLUSION Higher rates of postoperative infections and mechanical problems with the implant were found in this study as compared to other studies, which was probably associated with the relative lack of experience of the trainees who were performing the surgeries. Patients with a history of RP or diabetes mellitus prior to implantation were at higher risk of postoperative complications.

cDNA microarray analysis of differentially expressed genes in penile tissue after treatment with tadalafil

To evaluate differential gene expression in penile tissue after treatment with the phosphodiesterase 5 (PDE5) inhibitor tadalafil, as of the three clinically available PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) used for the treatment of erectile dysfunction (ED), tadalafil has a long half‐life and low incidence of side‐effects.

The prevalence of erectile dysfunction among Brazilian men screened for prostate cancer

To determine the prevalence of erectile dysfunction (ED) in a large cohort of Brazilian men who were screened for prostate cancer, and to determine risk factors in this population, as there are large cultural differences among countries in reporting the frequency of ED, and it is likely that the prevalence of ED among men screened for prostate cancer cannot be generally applied across countries.

Penile enlargement with methacrylate injection: is it safe?

CONTEXT Penis size is a great concern for men in many cultures. Despite the great variety of methods for penile augmentation, none has gained unanimous acceptance among experts in the field. However, in this era of minimally invasive procedure, injection therapy for penile augmentation has become more popular. Here we report a case of methacrylate injection in the penis that evolved with penile deformity and sexual dysfunction. This work also reviews the investigation and management of this pathological condition. CASE REPORT A 36-year-old male sought medical care with a complaint of penile deformity and sexual dysfunction after methacrylate injection. The treatment administered was surgical removal. Satisfactory cosmetic and functional results were reached after two months. CONCLUSIONS There is a need for better structured scientific research to evaluate the outcomes and complication rates from all penile augmentation procedures.

Preliminary findings from a new animal model for Peyronie’s disease involving extracorporeal shock waves

To develop an experimental model in rabbits to analyse the efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie’s disease.

Development of a urinary lithiasis localizer mechanism to couple ultrasound and extracorporeal lithotripsy equipment in canine model

INTRODUCTION Due to the evolution of extracorporeal lithotripsy equipment (ESWL) and presently, the fact that most part of the equipment does not present ultrasound to localize urinary calculi, a system that allows adapting ultrasound equipment to ESWL equipment was developed, disposing only of fluoroscopy. Thus, this equipment was developed and was tested in urinary stones in canine models, to check its precision in relation to fluoroscopy. METHOD Seven male dogs were utilized with the introduction, in the bladder through the ureteral route, of chalkstones, with initial localization by fluoroscopy, with a further ultrasound coincidence check localization of the vesical stones, being submitted to ESWL with a 3-hour, 21 days and 60 days follow-up after the procedure. RESULTS Success of localization in all animals was verified presenting elimination of stones in the first micturitions, after ESWL. No complications were verified in those animals for 60 days. CONCLUSION We verified that this equipment can lead to an update of the equipment that use only fluoroscopy, increasing in this way, their technical capacity in the treatment of urinary calculi, mainly in cases of non-radiopaque stones.