BETINA STIFELMAN KATZ
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
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- MicroRNAs 143 and 145 may be involved in benign prostatic hyperplasia pathogenesis through regulation of target genes and proteins(2014) VIANA, Nayara I.; REIS, Sabrina T.; DIP, Nelson G.; MORAIS, Denis R.; MOURA, Caio M.; SILVA, Iran A.; KATZ, Betina; SROUGI, Miguel; LEITE, Katia R. M.; ANTUNES, Alberto A.Objectives: The aim of this study was to analyze the roles of miR-143 and miR-145, as well as the gene and protein expression of their targets (KRAS, ERK5, MAP3K3, and MAP4K4) in the pathogenesis of benign prostatic hyperplasia (BPH). Methods: We analyzed the specimens of 44 patients diagnosed with BPH who underwent surgical treatment. The control group consisted of prostate samples from 2 young patients who were organ donors. miRNAs and their target genes were assessed using real-time polymerase chain reaction (qRT-PCR), and protein levels were assessed by Western blotting. Results: miR-143 and miR-145 were overexpressed in, respectively, 62.5% and 73.8% of the cases. The ERK5 and MAP4K4 genes were underexpressed respectively in 59.4% and 100% of the BPH samples, whereas KRAS and MAP3K3 were overexpressed respectively in 79.4% and 61.5% of the samples. Increased protein expression was found for both KRAS (4,312.2 luminance/area) and MAP3K3 (7,461.7 luminance/area), while the ERK5 protein was more abundant in the samples from patients with prostate larger than 60 grams (p = 0.019). Conclusions: The overexpression of miR-143 and miR-145 in BPH samples suggests an association with the pathogenesis of the disease; additionally, the latter miRNA may act through the inhibition of MAP4K4. KRAS and MAP3K3 overexpression may also be associated with BPH pathogenesis. Further analyses are necessary to confirm these results.
- Comprehensive Study of Gene and microRNA Expression Related to Epithelial-Mesenchymal Transition in Prostate Cancer(2014) KATZ, Betina; REIS, Sabrina T.; VIANA, Nayara I.; MORAIS, Denis R.; MOURA, Caio M.; DIP, Nelson; SILVA, Iran A.; ISCAIFE, Alexandre; SROUGI, Miguel; LEITE, Katia R. M.Prostate cancer is the most common cancer in men, and most patients have localized disease at the time of diagnosis. However, 4% already present with metastatic disease. Epithelial-mesenchymal transition is a fundamental process in carcinogenesis that has been shown to be involved in prostate cancer progression. The main event in epithelial-mesenchymal transition is the repression of E-cadherin by transcription factors, but the process is also regulated by microRNAs. The aim of this study was to analyze gene and microRNA expression involved in epithelial-mesenchymal transition in localized prostate cancer and metastatic prostate cancer cell lines and correlate with clinicopathological findings. We studied 51 fresh frozen tissue samples from patients with localized prostate cancer (PCa) treated by radical prostatectomy and three metastatic prostate cancer cell lines (LNCaP, DU145, PC3). The expression of 10 genes and 18 miRNAs were assessed by real-time PCR. The patients were divided into groups according to Gleason score, pathological stage, preoperative PSA, biochemical recurrence, and risk group for correlation with clinicopathological findings. The majority of localized PCa cases showed an epithelial phenotype, with overexpression of E-cadherin and underexpression of the mesenchymal markers. MiRNA-200 family members and miRNAs 203, 205, 183, 373, and 21 were overexpressed, while miRNAs 9, 495, 29b, and 1 were underexpressed. Low-expression levels of miRNAs 200b, 30a, and 1 were significantly associated with pathological stage. Lower expression of miR-200b was also associated with a Gleason score >= 8 and shorter biochemical recurrence-free survival. Furthermore, low-expression levels of miR-30a and high-expression levels of Vimentin and Twist1 were observed in the high-risk group. Compared with the primary tumor, the metastatic cell lines showed significantly higher expression levels of miR-183 and Twist1. In summary, miRNAs 200b, 30a, 1, and 183 and the genes Twist1 and Vimentin might play important roles in the progression of prostate cancer and may eventually become important prognostic markers.
- The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior(2015) LEITE, Katia R. M.; MORAIS, Denis Reis; FLOREZ, Manuel Garcia; REIS, Sabrina T.; ISCAIFE, Alexandre; VIANA, Nayara; MOURA, Caio M.; SILVA, Iran A.; KATZ, Betina S.; PONTES JR., Jose; NESRALLAH, Adriano; SROUGI, MiguelBackground: The molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. Methods: The expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. Results: MiR-371 underexpression correlated with non-organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5 alpha-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5 alpha-dihydrotestosterone. Conclusion: Our data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.
- Micro RNA Expression and Prognosis in Low-grade Non-invasive Urothelial Carcinoma(2014) DIP, Nelson; REIS, Sabrina T.; ABE, Daniel K.; VIANA, Nayara I.; MORAIS, Denis R.; MOURA, Caio M.; KATZ, Betina; SILVA, Iran A.; SROUGI, Miguel; LEITE, Katia R. M.Purpose: To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence. Materials and Methods: Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles. Results: There was a marginal correlation between multiplicity and miR-let7c over- expression. For all others miRNA no correlation between their expression and prognostic factors was found. Conclusion: We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except miR-10a, over-expressed in most of cases, seeming to have increased levels in tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice.
- Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer(2015) LEITE, Katia R. M.; REIS, Sabrina T.; VIANA, Nayara; MORAIS, Denis R.; MOURA, Caio M.; SILVA, Iran A.; PONTES JR., Jose; KATZ, Betina; SROUGI, MiguelThe search for biomarkers to characterize prostate cancer aggressiveness has been the objective for the majority of researchers involved with the most prevalent tumor in men. MiRNAs are important for the control of many cellular functions and their deregulation is involved with tumor development and progression. To find miRNAs differentially expressed in prostate cancer and their relation to prognostic factors and biochemical recurrence we studied 53 surgical specimens from men who underwent radical prostatectomy, through a microarray analysis using the microarray platform (GeneChip (R) miRNA Array - Affymetrix) with more than 46,000 probes and 847 mature human miRNAs and transcripts. We defined different as an expression level greater or less than 1.1 with p<0.05. The validation study using qRT-PCR had confirmed miR21 as overexpressed in tumor that have recurred with a risk of 2.5. Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9. Invasion assay with Matrigel showed increase in tumor cell invasion after miR-21 transfection. We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer. And the negative control of RECK results in overexpression of MMP9 promotes increasing tumor cell invasion supporting miR-21 as an oncomiR related to aggressiveness in prostate cancer.
- The accuracy of pathological data for the prediction of insignificant prostate cancer(2012) KATZ, Betina; SROUGI, Miguel; CAMARA-LOPES, Luiz H.; ANTUNES, Alberto A.; NESRALLAH, Luciano; NESRALLAH, Adriano; DALL'OGLIO, Marcos; LEITE, Katia R. M.Introduction: The widespread screening programs prompted a decrease in prostate cancer stage at diagnosis, and active surveillance is an option for patients who may harbor clinically insignificant prostate cancer (IPC). Pathologists include the possibility of an IPC in their reports based on the Gleason score and tumor volume. This study determined the accuracy of pathological data in the identification of IPC in radical prostatectomy (RP) specimens. Materials and Methods: Of 592 radical prostatectomy specimens examined in our laboratory from 2001 to 2010, 20 patients harbored IPC and exhibited biopsy findings suggestive of IPC. These biopsy features served as the criteria to define patients with potentially insignificant tumor in this population. The results of the prostate biopsies and surgical specimens of the 592 patients were compared. Results: The twenty patients who had IPC in both biopsy and RP were considered real positive cases. All patients were divided into groups based on their diagnoses following RP: true positives (n = 20), false positives (n = 149), true negatives (n = 421), false negatives (n = 2). The accuracy of the pathological data alone for the prediction of IPC was 91.4%, the sensitivity was 91% and the specificity was 74%. Conclusion: The identification of IPC using pathological data exclusively is accurate, and pathologists should suggest this in their reports to aid surgeons, urologists and radiotherapists to decide the best treatment for their patients.
- Expression profile of standard and variants forms of CD44 related to prostate cancer behavior(2015) MOURA, Caio M.; PONTES JR., Jose; REIS, Sabrina T.; VIANA, Nayara I.; MORAIS, Denis R.; DIP, Nelson; KATZ, Betina; SROUGI, Miguel; LEITE, Katia R. M.CD44 is a transmembrane glycoprotein and is regarded as a potential marker in various tumors. The aim of our study was to analyze the expression of the standard form of CD44 (CD44s) and its isoforms in localized prostate cancer (PCa), and to correlate these data with the classical prognostic factors and biochemical recurrence. Ninety-four surgical specimens were analyzed in this study. The expression levels of CD44s and all its 9 variants were analyzed by quantitative real time PCR (qRT-PCR). The control group consisted of 14 specimens from patients with benign prostatic hyperplasia. We correlated all the expression profiles with biochemical recurrence, as defined by a PSA > 0.4 ng/mL in a mean follow-up period of 53.3 months. In PCa, CD44s was underexpressed and all the other isoforms were overexpressed. The mean expression level of most variants was higher in patients who had not recurred, and a higher expression of CD44v2 independently correlated with a better recurrence-free survival rate (p=0.045). This variant was also underexpressed in metastatic PCa cell lines. There was no correlation between the expression levels of any of the CD44 isoforms and the classical prognostic factors. We here demonstrated that PCa cases are characterized by a change in the expression of CD44, with a loss of CD44s and an overexpression of all the other CD44 variants. However, during cancer progression we found a loss of expression of all CD44 variants, and a correlation between higher expression of CD44v2 and a better recurrence-free survival rate. The understanding of the CD44 expression patterns in PCa could contribute to its use as a new prognostic marker.
- Perineural invasion detection in prostate biopsy is related to recurrence-free survival in patients submitted to radical prostatectomy(2013) KATZ, Betina; SROUGI, Miguel; DALL'OGLIO, Marcos; NESRALLAH, Adrian J.; SANT'ANNA, Alexandre C.; PONTES JR., Jose; ANTUNES, Alberto A.; REIS, Sabritia T.; VIANA, Nayara; SANUDO, Adriana; CAMARA-LOPES, Luiz H.; LEITE, Katia R. M.Objective: Perineural invasion (PNI) is detected in almost 20% of prostate biopsies and has been related to worse prognostic factors in radical prostatectomy (RP) specimens and lower disease-free survival rates. The aim of this study was to evaluate the importance of PNI during periods of extended prostate biopsies and to determine the value of this preoperative parameter as a predictor of pathologic findings in surgical specimens and in biochemical recurrence. Materials and methods: Between 2001 and 2009, 599 prostate biopsies and their respective RP specimens were examined in our laboratory. The RP specimens were always examined completely. The mean age of the patients was 61 years, and the mean PSA was 6.4 ng/mL. The mean and median number of biopsy cores obtained was 14.4 and 14, respectively. PNI was identified in 105 biopsies (17.5%). We studied the ability of PNI in prostate biopsies to determine the tumor stage in surgical specimens and the relationship of PNI with biochemical recurrence during a mean follow-up time of 51.4 months. Results: The presence of PNI in prostate biopsies was observed in older patients (63 vs. 61 years old, P = 0.008). All of the prognostic factors determined for the RP specimens were significantly worse in patients with PNI compared with those without PNI. PNI was strongly associated with a higher pathologic stage (87% specificity, 40% sensitivity, odds ratio 4.8). Stage pT3 prostatic cancer was determined in 46 (43.8%) of 105 patients with PNI on biopsy compared to 69 (14%) of 494 patients without PNI (P = 0.01). Fifty-six (19.6%) patients had a biochemical recurrence, and PNI correlated significantly with PSA recurrence. A Kaplan-Meier analysis revealed a significant difference in recurrence-free survival between patients with and without PNI (45% vs. 53%, respectively, P = 0.021, log-rank test = 0.19). Conclusion: PNI is an important morphologic preoperative predictor of the pathologic stage as well as biochemical recurrence and must always be mentioned when adenocarcinoma is diagnosed on prostate biopsies.