Downregulation of protein tyrosine phosphatase PTPL1 alters cell cycle and upregulates invasion-related genes in prostate cancer cells.

PTPL1, a non-receptor type protein tyrosine phosphatase, has been involved in the regulation of apoptosis and invasiveness of various tumour cell types, but its role in prostate cancer remained to be investigated. We report here that downregulation of PTPL1 by small interfering RNA in PC3 cells decreases cell proliferation and concomitantly reduces the expression of cell cycle-related proteins such as cyclins E and B1, PCNA, PTTG1 and phospho-histone H3. PTPL1 downregulation also increases the invasion ability of PC3 cells through Matrigel coated membranes. cDNA array of PTPL1-silenced PC3 cells versus control cells showed an upregulation of invasion-related genes such as uPA, uPAR, tPA, PAI-1, integrin α6 and osteopontin. This increased expression was also confirmed in PTPL1-silenced DU145 prostate cancer cells by quantitative real time PCR and western blot. These findings suggest that PTPL1 is an important mediator of central cellular processes such as proliferation and invasion.

Immunohistochemical expression of Hsp60 correlates with tumor progression and hormone resistance in prostate cancer.

OBJECTIVES: To investigate the expression of Hsp60 protein in prostate cancer biopsy samples, and its association with prognostic clinical parameters and hormone resistance and survival. Molecular chaperones are involved in protein folding, protein degradation, and protein trafficking among subcellular compartments. METHODS: We selected 107 patients with localized and locally advanced prostate cancer at our hospital from 1999 through 2004. We performed an analysis by western blot and immunohistochemistry on paraffin-embedded tissue sections. Clinical data were used to determine associations between immunohistochemical expression of Hsp60 and tumor behavior. RESULTS: The expression level of Hsp60 was significantly increased in tumors with high Gleason score (P < .001). Hsp60 expression was also significantly associated with initial serum PSA levels (P < .01) and with the presence of lymph node metastasis (P < .003). In 50 locally advanced cancers treated by androgen ablation we found an association between high Hsp60-expressing tumors and an early onset of hormone refractory disease (P < .02) and reduced cancer-specific survival (P < .05). CONCLUSIONS: Hsp60 protein is overexpressed in poorly differentiated prostate cancers. Hsp60 expression is strongly associated with prognostic clinical parameters, such as Gleason score, initial serum PSA levels, and lymph node metastasis and with the onset of hormone-refractory disease and reduced cancer-specific survival. Identification of such markers could be of relevance in the clinical management of prostate cancer.

[Infectious complications in 159 consecutive kidney transplant recipients]. / Complicaciones infecciosas en 159 receptores de trasplante renal consecutivos.

INTRODUCTION: The incidence of infections has decreased in kidney transplant (KT) recipients owing to advances in the surgical techniques and clinical management of this population. Nevertheless, these complications continue to occur and the causes seem to be changing, in part because of the prophylactic strategies used. METHOD: Prospective, observational study investigating infections occurring during the first 2 years post-transplantation in KT recipients who underwent surgery between July 2003 and December 2005 at Hospital Universitario Virgen del Rocío. Univariate and multivariate regression analysis was performed to determine risk factors associated with the development of infection. RESULTS: The incidence of infection was 1.11 episodes per patient over 510+/-234 days. The most common infections were urinary tract infection (UTI) (46.6%), cytomegalovirus (CMV) infection (22.7%), and surgical site infection (8%). The causes were bacterial (50.4%), viral (45.9%), and fungal (3.6%) agents. The most frequent pathogens were CMV (36%), Escherichia coli (28%), extended-spectrum beta-lactamase (ESBL)-producers (26%), and coagulase-negative staphylococci (6.3%). Seventy-nine percent of infection episodes occurred in the 4 months following KT. One recipient died 30 days after the infection episode. In the infection group, patient and graft survival at the end of follow-up was 98% and 89%, respectively. CONCLUSIONS: The most frequent syndromes were UTI, CMV infection and surgical site infection. The infections were mainly produced by bacteria, in particular gram-negative rods, and there was a high rate of ESBL E. coli.

Complicaciones infecciosas en 159 receptores de trasplante renal consecutivos / Infectious diseases in 159 consecutive kidney transplant recipients

Introducción gracias a los avances en la técnica quirúrgica y en el manejo clínico de los receptores de trasplante renal (TR), las infecciones han disminuido su incidencia. Sin embargo, continúan siendo frecuentes y cambiantes en función, en parte, de la profilaxis y la etiología local. Método estudio prospectivo y observacional de las infecciones en pacientes con TR realizado entre julio de 2003 y diciembre de 2005, durante los 2 primeros años postrasplante. Se ha realizado un análisis univariado y multivariado de los factores de riesgo asociados al desarrollo de infecciones. Resultados la incidencia de infección fue de 1,1 episodios/paciente (..) (AU)

Introduction: The incidence of infections has decreased in kidney transplant (KT) recipients owing to advances in the surgical techniques and clinical management of this population. Nevertheless, these complications continue to occur and the causes seem to be changing, in part because of the prophylactic strategies used. Method: Prospective, observational study investigating infections occurring during the first 2 years post-transplantation in KT recipients who underwent surgery between July 2003 and December 2005 at (..) (AU)

Prospective study of infectious complications in a cohort of pediatric renal transplant recipients.

UNLABELLED: Infections are frequent and serious in pediatric RT recipients; however, the information available is scarce. The aim of this study was to determine the incidence, etiology, and risk factors for infection in these patients. This was a prospective, observational study of a consecutive pediatric RT recipient cohort. Risk factors for infection and descriptive analyses during the first two post-transplantation years were performed. Twenty-one patients (58.3%) had at least one infection (incidence 1.5 episodes/patient/first year of transplantation). There were 33 bacterial infections (73.3%), 11 viral infections (24.4%), and one protozoal infection. UTI was the most common syndrome (48.3%), followed by CMV infection (15.5%). The main microorganisms isolated were Escherichia coli (28.9%), 46.1% of which were ESBL producers, and CMV (20%). Patient and graft survival at the end of follow-up were 97.2% and 83.3%, respectively. The only risk factor for infection was cold ischemia time >800 min (OR 5.7, CI 95% 1.7-19.3). CONCLUSIONS: In pediatric RT recipients, UTI is the most frequent syndrome. Bacterial infections are the most common, with a high rate of ESBL producer strains. Despite their good prognosis, infections are a cause of morbidity that could potentially be reduced by decreasing cold ischemia times.

Mycotic pseudoaneurysm following a kidney transplant: a case report and review of the literature.

Vascular complications represent a significant cause of morbidity and mortality following a kidney transplant. Pseudoaneurysms are rare, occurring in approximately 1% of cases. We present a 15-yr-old patient who received a kidney transplant in the right iliac fossa. Thirty-six days following the transplant, the patient was admitted to the hospital because of a marked increase in serum creatinine levels, arterial hypertension, scrotal edema, and lower right limb pain. The patient did not present fever or raised inflammatory markers. A pseudoaneurysm was diagnosed by means of a Doppler echography and a CT. By a selective arteriography of the right iliac artery, we placed a 8 x 5 cm stent to isolate the pseudoaneurysm, due to the high risk of an extensive defect occurring in the arterial wall. Forty-eight h later the patient underwent transplant nephrectomy. Seven days following surgery, the patient experienced febrile syndrome and therefore another CT was carried out which showed a large abscess around the stent. So we decided to perform another intervention in order to drain this abscess. Due to the extensive loss of the arterial wall where the prosthesis was largely exposed, we ligated the common iliac and external iliac arteries, removed the prosthesis and performed a femoro-femoral bypass with the usual subcutaneous positioning of the prosthesis (separate from surgical site). The stent and mural thrombus were sent for culture analysis and Candida albicans was observed. The diagnosis of a pseudoaneurysm in these types of patients continues to be considered as a surgical emergency by the majority of authors. Transplantectomy is the most frequently used treatment technique. Positioning a stent prior to transplantectomy avoids ligature of the iliac artery in the majority of cases.

Vesicoureteral reflux after kidney transplantation in children.

We analyzed the frequency of vesicoureteral reflux and the factors that favor its appearance after kidney transplantation in pediatric patients. This retrospective analysis examined the prevalence of post-transplant vesicoureteral reflux in a total of 181 kidney transplants performed in children at our center between 1978 and 2004. In patients who required corrective surgery for this problem, we analyzed pretransplant residual diuresis, pretransplant pathology and post-transplant problems related to vesicoureteral reflux. We also analyzed form of presentation, whether reflux was to the graft or to the native kidney, degree of reflux, and surgical technique used to correct reflux. Ten patients (5.5%) needed surgery to correct reflux to the graft (nine children) or to the native kidney (one child). Reflux was manifested as urinary tract infection in six children and progressive graft failure in one. Urethrovesical disorders that favored vesicoureteral reflux were present in eight patients (non-compliance bladder, detrusor overactivity, posterior urethral valves, urethral stenosis). Lengthening the submucosal tunnel stopped urinary tract infections in all 10 patients, whereas six-month voiding cystourethrograms showed resolution in 8 patients and (only) reduction in the degree of reflux in two. The high percentage of post-transplant vesicoureteral reflux in pediatric patients were related with higher frequencies of ureterovesical pathology in children who received the transplant. Lengthening the submucosal ureteral tunnel vesicoureteral reflux was corrected in 80%. We recommend during implantation in children with pretransplant urethrovesical abnormality an initial technique, which utilizes a longer submucosal tunnel such as the Lich-Gregoir.

Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak.

Androgen-sensitive prostate cancer cells turn androgen resistant through complex mechanisms that involve dysregulation of apoptosis. We investigated the role of antiapoptotic Bcl-xL in the progression of prostate cancer as well as the interactions of Bcl-xL with proapoptotic Bax and Bak in androgen-dependent and -independent prostate cancer cells. Immunohistochemical analysis was used to study the expression of Bcl-xL in a series of 139 prostate carcinomas and its association with Gleason grade and time to hormone resistance. Expression of Bcl-xL was more abundant in prostate carcinomas of higher Gleason grades and significantly associated with the onset of hormone-refractory disease. In vivo interactions of Bcl-xL with Bax or Bak in untreated and camptothecin-treated LNCaP and PC3 cells were investigated by means of coimmunoprecipitation. In the absence of any stimuli, Bcl-xL interacts with Bax and Bak in androgen-independent PC3 cells but only with Bak in androgen-dependent LNCaP cells. Interactions of Bcl-xL with Bax and Bak were also evidenced in lysates from high-grade prostate cancer tissues. In LNCaP cells treated with camptothecin, an inhibitor of topoisomerase I, the interaction between Bcl-xL and Bak was absent after 36 h, Bcl-xL decreased gradually and Bak increased coincidentally with the progress of apoptosis. These results support a model in which Bcl-xL would exert an inhibitory effect over Bak via heterodimerization. We propose that these interactions may provide mechanisms for suppressing the activity of proapoptotic Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to androgen resistance and progression of prostate cancer.