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1.  Adhesion molecules of detrusor muscle cells are influenced by a hypercholesterolemic diet or bladder outlet obstruction in a wistar rat model 
BMC Urology  2013;13:50.
Background
Cell adhesion molecules (CAMs) are essential for maintaining tissue integrity by regulating intercellular and cell to extracellular matrix interactions. Cadherins and catenins are CAMs that are located on the cell membrane and are important for adherens junction (AJ) function. This study aims to verify if hypercholesterolemic diet (HCD) or bladder outlet obstruction (BOO) promotes structural bladder wall modifications specific to alterations in the expression of cadherins and catenins in detrusor muscle cells.
Methods
Forty-five 4-week-old female Wistar rats were divided into the following three groups: group 1 was a control group that was fed a normal diet (ND); group 2 was the BOO model and was fed a ND; and group 3 was a control group that was fed a HCD (1.25% cholesterol). Initially, serum cholesterol, LDL cholesterol and body weight were determined. Four weeks later, groups 1 and 3 underwent a sham operation; whereas group 2 underwent a partial BOO procedure that included a suture tied around the urethra. Six weeks later, all rats had their bladders removed, and previous exams were repeated. The expression levels of N-, P-, and E-cadherin, cadherin-11 and alpha-, beta- and gamma-catenins were evaluated by immunohistochemistry with a semiquantitative analysis.
Results
Wistar rats fed a HCD (group 3) exhibited a significant increase in LDL cholesterol levels (p=0.041) and body weight (p=0.017) when compared to both groups that were fed a normal diet in a ten-week period. We found higher β- and γ-catenin expression in groups 2 and 3 when compared to group 1 (p = 0.042 and p = 0.044, respectively). We also observed Cadherin-11 overexpression in group 3 when compared to groups 1 and 2 (p = 0.002).
Conclusions
A HCD in Wistar rats promoted, in addition to higher body weight gain and increased serum LDL cholesterol levels, overexpression of β- and γ-catenin in the detrusor muscle cells. Similar finding was observed in the BOO group. Higher Cadherin-11 expression was observed only in the HCD-treated rats. These findings may be associated with bladder dysfunctions that occur under such situations.
doi:10.1186/1471-2490-13-50
PMCID: PMC3817818  PMID: 24139451
Cell adhesion molecules; Bladder dysfunction; Hypercholesterolemic diet; Bladder outlet obstruction
2.  Predicting necrosis in residual mass analysis after retroperitoneal lymph node dissection: a retrospective study 
Background
Recent studies have demonstrated that pathological analysis of retroperitoneal residual masses of patients with testicular germ cell tumors revealed findings of necrotic debris or fibrosis in up to 50% of patients. We aimed at pursuing a clinical and pathological review of patients undergoing post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in order to identify variables that may help predict necrosis in the retroperitoneum.
Methods
We performed a retrospective analysis of all patients who underwent PC-RPLND at the University Hospital of the University of São Paulo and Cancer Institute of Sao Paulo between January 2005 and September 2011. Clinical and pathological data were obtained and consisted basically of: measures of retroperitoneal masses, histology of the orchiectomy specimen, serum tumor marker and retroperitoneal nodal size before and after chemotherapy.
Results
We gathered a total of 32 patients with a mean age of 29.7; pathological analysis in our series demonstrated that 15 (47%) had necrosis in residual retroperitoneal masses, 15 had teratoma (47%) and 2 (6.4%) had viable germ cell tumors (GCT). The mean size of the retroperitoneal mass was 4.94 cm in our sample, without a difference between the groups (P = 0.176). From all studied variables, relative changes in retroperitoneal lymph node size (P = 0.04), the absence of teratoma in the orchiectomy specimen (P = 0.03) and the presence of choriocarcinoma in the testicular analysis after orchiectomy (P = 0.03) were statistically significant predictors of the presence of necrosis. A reduction level of 35% was therefore suggested to be the best cutoff for predicting the absence of tumor in the retroperitoneum with a sensitivity of 73.3% and specificity of 82.4%.
Conclusions
Even though retroperitoneal lymph node dissection remains the gold standard for patients with residual masses, those without teratoma in the primary tumor and a shrinkage of 35% or more in retroperitoneal mass have a considerably smaller chance of having viable GCT or teratoma in the retroperitoneum and a surveillance program could be considered.
doi:10.1186/1477-7819-10-203
PMCID: PMC3502267  PMID: 23021209
Testicular cancer; Retroperitoneal lymph node dissection; Necrosis; Teratoma
3.  Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer 
BMC Urology  2012;12:18.
Background
Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC).
Methods
MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia.
Results
MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005).
Conclusion
We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.
doi:10.1186/1471-2490-12-18
PMCID: PMC3424138  PMID: 22695075
Bladder cancer; Matrix metalloproteinase; Prognosis; Diagnosis; Gene expression
4.  miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer 
BMC Urology  2012;12:14.
Background
Prognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line.
Materials and methods
To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR).
Results
The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025).
Conclusions
Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.
doi:10.1186/1471-2490-12-14
PMCID: PMC3431982  PMID: 22642976
Prostate cancer; Prognosis; RECK; Micro RNA; Metaloproteinases
5.  Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer 
Clinics  2011;66(7):1143-1147.
OBJECTIVE:
To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer.
PATIENTS AND METHODS:
TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of 11 patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels.
RESULTS:
In the majority of the tumor samples, TGF-β1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores ≥7 when compared to patients with Gleason scores <7 (p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3% had poor prognostic features.
CONCLUSIONS:
TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.
doi:10.1590/S1807-59322011000700004
PMCID: PMC3148455  PMID: 21876965
Prostate cancer; Prognosis; Molecular markers; TGF-β
6.  Evaluation of the expression of integrins and cell adhesion molecules through tissue microarray in lymph node metastases of prostate cancer 
Background:
Integrins and adhesion molecules are responsible for the maintenance of the epithelial phenotype. Cell culture studies have reported the correlation between adhesion molecule expression and prostate carcinoma, but their role in the metastatic process is not yet known. Our aim is to study the expression profiles of these molecules and evaluate their association with the metastatic behavior of prostate adenocarcinoma.
Materials and Methods:
A Tissue Microarray containing two samples from 19 primary tumors and one from their corresponding lymph node metastases was constructed and subjected to immunohistochemical analysis of the expression of integrins, E-cadherin and β and γ-catenins. Within each case, paired analyses were also performed to evaluate gains or losses in metastasis compared to its primary tumor.
Results:
The expression of αv, αvβ3, α2β1 and γ-catenin were abnormal in almost every case. Marked loss of E-cadherin and β4 integrin was found in primary and metastatic lesions. β-catenin was normal in all primary cases and in 94% of metastases. α6 was normal in all primary tumors and metastases. α3 and α3β1 were normal in 32% of primary cases and in 53% and 6% of metastases, respectively. In paired analyses, loss of E-cadherin, β4, αv, α3β1 and αvβ3 was found in 65%, 71%, 59%, 53% and 47% of patients, respectively. Catenins and α2β1 showed maintenance of expression in most of the cases.
Conclusions:
In this preliminary study we have shown that the loss of cell adhesion molecules can be considered a characteristic of the metastatic phenotype in prostate cancer. Larger series should be evaluated in order to confirm our findings.
doi:10.4103/1477-3163.48453
PMCID: PMC2678866  PMID: 19240373
Cell adhesion molecules; integrins; lymph nodes; metastases; prostate cancer

Results 1-6 (6)