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1.
Exp Cell Res ; 439(1): 114077, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38735620

ABSTRACT

The extracellular matrix surrounding the tumor undergoes changes in its organization during the metastasis process. The present study aims to quantify total collagen, collagen I (Col I) and collagen III (Col III), analyze the alignment of collagen fibers and assess the basement membrane integrity in samples from patients with metastatic and non-metastatic prostate cancer. Tissue samples from 60 patients were classified into groups based on prognostic parameters: better prognosis (n = 20), worse prognosis without metastasis (n = 23) and metastatic (n = 17). Picrosirius red with further analysis under polarizing microscope was used to quantify (with validation using immunohistochemistry) and analyze collagen alignment, and Periodic Acid Schiff staining was used to analyze the basement membrane integrity. The Col I/Col III ratio was found to be higher in the metastatic group than in the groups with better prognosis (p = 0.012) and worse prognosis without metastasis (p = 0.018). Basement membrane integrity constitution in malignant tumor tissue differed from that of adjacent non-tumor tissue (p < 0.001). Moreover, the worsening in the tumor tissue integrity was positively correlated with worse prognostic parameters. All in all, absence of Col III and basement membrane integrity might be indicators of poor prognosis in prostate cancer.

2.
Gene ; 907: 148252, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38350514

ABSTRACT

Epidemiological studies have shown the association of genetic variants with risks of occupational and environmentally induced cancers, including bladder (BC). The current review summarizes the effects of variants in genes encoding phase I and II enzymes in well-designed studies to highlight their contribution to BC susceptibility and prognosis. Polymorphisms in genes codifying drug-metabolizing proteins are of particular interest because of their involvement in the metabolism of exogenous genotoxic compounds, such as tobacco and agrochemicals. The prognosis between muscle-invasive and non-muscle-invasive diseases is very different, and it is difficult to predict which will progress worse. Web of Science, PubMed, and Medline were searched to identify studies published between January 1, 2010, and February 2023. We included 73 eligible studies, more than 300 polymorphisms, and 46 genes/loci. The most studied candidate genes/loci of phase I metabolism were CYP1B1, CYP1A1, CYP1A2, CYP3A4, CYP2D6, CYP2A6, CYP3E1, and ALDH2, and those in phase II were GSTM1, GSTT1, NAT2, GSTP1, GSTA1, GSTO1, and UGT1A1. We used the 46 genes to construct a network of proteins and to evaluate their biological functions based on the Reactome and KEGG databases. Lastly, we assessed their expression in different tissues, including normal bladder and BC samples. The drug-metabolizing pathway plays a relevant role in BC, and our review discusses a list of genes that could provide clues for further exploration of susceptibility and prognostic biomarkers.


Subject(s)
Arylamine N-Acetyltransferase , Urinary Bladder Neoplasms , Humans , Glutathione Transferase/genetics , Polymorphism, Genetic , Cytochrome P-450 CYP1A1/genetics , Urinary Bladder Neoplasms/genetics , Cytochrome P-450 CYP2D6/genetics , Genetic Predisposition to Disease , Genotype , Case-Control Studies , Risk Factors , Arylamine N-Acetyltransferase/genetics , Aldehyde Dehydrogenase, Mitochondrial/genetics
3.
Pathol Res Pract ; 253: 155024, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38113764

ABSTRACT

Metastasis is the main problem in the treatment of prostate cancer (PCa), and for it to occur, proteolytic enzymes must remodel the extracellular matrix (ECM) surrounding the tumor. The most important group of enzymes with this action include the matrix metalloproteinases (MMPs), which act on various substrates cleaving ECM components. The present study aimed to evaluate the protein immunostaining profiles of matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) in PCa Brazilian patients using the indirect immunohistochemical methodology. The tissue samples (n = 178), 60 from malignant tumor, 58 from adjacent non-tumor, and 60 from ECM, were evaluated according to the immunostaining intensity. The malignant tumor cytoplasmic MMP-2 immunostaining was more intense than in ECM (p = 0.001), but it did not correlate with any clinical-pathological parameter. The MMP-9 staining was similar in tumor cytoplasm, adjacent non-tumor cytoplasm and ECM, but showed significant positive correlations with ISUP grade (p = 0.044; Tau=0.249), extraprostatic extension (p = 0.025; Tau=0.309), and biochemical recurrence (p = 0.048; Tau=0.306). A significant positive correlation was also observed between MMP-2 and MMP-9 in all cell compartments analyzed. Although further research is warranted to elucidate the precise mechanisms underlying these observations, our findings suggest MMP-9 as a promising candidate marker for tissue invasion that could be used in predicting the progression and prognosis of PCa.


Subject(s)
Matrix Metalloproteinase 2 , Prostatic Neoplasms , Male , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9 , Matrix Metalloproteinases/metabolism , Prognosis
4.
Pathol Res Pract ; 250: 154806, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37738928

ABSTRACT

Prostate cancer (PCa) is the malignant neoplasm that most commonly affects men and is an important cause of death. It can be detected by changes in serum levels of Prostate Specific Antigen (PSA) and digital rectal examination, but often symptoms do not appear until advanced stages and metastases. The C-X-C Motif Chemokine Ligand 12/C-X-C Motif Chemokine Receptor 4 (CXCL12/CXCR4) axis acts in cell migration and may be involved in the metastatic process. In this context, the aim of this study was to evaluate the allelic variants rs1801157 (CXCL12) and rs2228014 (CXCR4) and the immunostaining of CXCR4 protein as candidates for prognostic markers in PCa. Samples (n = 60) were divided according to prognostic parameters (with and without metastasis at diagnosis) in tree groups: better prognosis, worse prognosis with metastasis at diagnosis and worse prognosis without metastasis at diagnosis, and immunostaining was evaluated by indirect immunohistochemistry, considering tumoral and adjacent tissues from the same patient (n = 120). A significant association was found between the C allele of rs2228014 (CXCR4) and the extraprostatic extension. For CXCR4 immunostaining a weak labeling and a cytoplasmic localization predominated, as well as a significant difference between malignant versus adjacent tissue, with higher protein expression in the malignant tissue. A significant association was found between CXCR4 tumor immunostaining with TNM staging (T2b-T2c) and PSA level (> 20 ng/mL). None of the allelic variants affected CXCR4 immunostaining. Prognostic groups did not differ in allelic variant frequency or immunostaining profile. Findings suggest that CXCR4 receptor may be one of the ways to worsen the prognosis of prostatic cancer.

5.
Anticancer Res ; 43(1): 369-379, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36585213

ABSTRACT

BACKGROUND/AIM: Prostate cancer (PCa) is one of the most frequent neoplasms in men around the world. In recent years, the search for new biomarkers with greater prognostic potential for PCa has intensified. This study aimed to evaluate single nucleotide polymorphisms (SNPs) and a combined panel of these polymorphisms in relation to biochemical recurrence in patients who were through prostatectomy, with an average of 7 years of follow-up. MATERIALS AND METHODS: Patients diagnosed with PCa (n=197) participated in this cohort study. Thirteen SNPs were analyzed: rs2279115 (BCL-2), rs26677604 (CASP3), rs1052571 (CASP9), rs11781886 (NKX3-1), rs2735343 (PTEN), rs2494750 (AKT1), rs2699887 (PI3KCA), rs3195676 (AMACR), rs17302090 (AR), rs2536 (mTOR), rs1695 (GSTP1), rs2308321 (MGMT) and rs1544410 (VDR). Variants were combined and four main panels were defined: cell death, cell survival, growth receptors, and metabolism. Genotyping was performed by real-time PCR. RESULTS: We did not observe any significant relation between the panels of variants analyzed, apart from the rare allele (G) of rs2308321 (MGMT) that was associated with a higher risk of recurrence (p=0.036) when compared to the prevalent (A) in the allelic model. CONCLUSION: This MGMT variant occurs in an exon, and it could potentially affect DNA repair and, therefore, the biochemical relapse of PCa patients.


Subject(s)
DNA Modification Methylases , Prostatic Neoplasms , Humans , Male , Alleles , Cohort Studies , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Polymorphism, Single Nucleotide , Prognosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Recurrence , Tumor Suppressor Proteins/genetics
6.
J Cancer Res Clin Oncol ; 149(2): 567-577, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36008689

ABSTRACT

PURPOSE: Prostate cancer (PCa) lacks specific markers capable of distinguishing aggressive tumors from those with indolent behavior. Therefore, the aim of this study was to evaluate the immunostaining of candidate proteins (PTEN, AKT, TRPM8, and NKX3.1) through the immunohistochemistry technique (IHC) on patients with metastatic and non-metastatic PCa. METHODS: Tissues from 60 patients were divided into three groups categorized according to prognostic parameters: better prognosis (n = 20), worse prognosis (n = 23), and metastatic (n = 17). Immunostaining was analyzed by a pathologist and staining classifications were considered according to signal intensity: (0) no staining, (+) weak, and (++ and +++) intermediate to strong. RESULTS: AKT protein was associated (p = 0.012) and correlated (p = 0.014; Tau = - 0.288) with the prognostic groups. The immunostaining for TRPM8 (p = 0.010) and NKX3.1 (p = 0.003) proteins differed between malignant tumor and non-tumoral adjacent tissue as well as for proteins in cellular locations (nucleus and cytoplasm). TRPM8 was independently associated with the ISUP grade ≥ 4 (p = 0.024; OR = 8.373; 95% CI = 1.319-53.164). The NKX3.1 showed positive and predominantly strong immunostaining in all patients in both tumoral and non-tumoral adjacent tissues. All metastatic samples had positive immunostaining, with strong intensity for NKX3.1 (p = 0.021; Tau = - 0.302). In the non-metastatic group, this strong protein staining was not observed in any patients. CONCLUSION: This study confirmed that NKX3.1 is highly specific for prostate tissue and indicated that NKX3.1, AKT, and TRPM8 may be candidate markers for prostate cancer prognosis.


Subject(s)
Homeodomain Proteins , Prostatic Neoplasms , Male , Humans , Homeodomain Proteins/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , Prostatic Neoplasms/pathology , Transcription Factors/metabolism
7.
Mol Biol Rep ; 49(9): 9079-9087, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35708863

ABSTRACT

BACKGROUND: There is an ongoing search for molecular markers that are specific, sensitive, and able to predict the stage of prostate cancer (PCa), which is the second most prevalent type of cancer in men worldwide. This study examined whether different single nucleotide polymorphisms (SNPs) were reliable markers of susceptibility to and prognosis of PCa in a sample of Brazilian patients. METHODS AND RESULTS: DNA samples were extracted from peripheral blood cells of 283 PCa patients and matched with samples from healthy controls. Single nucleotide polymorphisms (SNPs in four genes (BCL-2-rs2279115, CASP3-rs4647603, CASP9-rs1052571, and NKX3-1-rs11781886) were genotyped by real-time PCR using the TaqMan® probe. Odds Ratios with 95% confidence intervals were calculated for allelic and genotypic frequencies. The association between polymorphic variants, risk of developing PCa, and clinicopathological characteristics was analyzed by univariate and multivariate logistic regression analysis. SNPs in CASP3, CASP9, and NKX3-1 genes, either alone or in combination (BCL-2+NKX3-1 and CASP3+NKX3-1) were associated with the risk of developing PCa. Genotypes and tumor histopathological data indicated that the BCL-2, NKX3-1, and CASP3 allelic variants, either alone or combined in pairs, were associated with a poor prognosis of PCa. CONCLUSIONS: Genetic polymorphisms in CASP3, NKX3-1, and BCL-2 genes were associated with susceptibility to PCa. The SNPs in the three genes alone and the SNP in the BCL-2 gene combined with the other two genes were strongly associated with adverse outcomes in PCa patients and are promising candidates for molecular markers for PCa prognosis.


Subject(s)
Genes, bcl-2 , Prostatic Neoplasms , Case-Control Studies , Caspase 3/genetics , Caspase 9/genetics , Genetic Predisposition to Disease , Homeodomain Proteins/genetics , Humans , Male , Polymorphism, Single Nucleotide/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/genetics , Transcription Factors/genetics
8.
Genet Mol Biol ; 43(3): e20180329, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32484847

ABSTRACT

Polymorphic variants in the PTEN (rs2735343), PI3K (rs2699887), AKT1 (rs2494750), AR (rs17302090), and AMACR (rs3195676) genes were evaluated as possible molecular markers of susceptibility, prognosis, and progression of prostate cancer (PCa), in a case-control study. Samples consisted of 277 patients with PCa and 277 controls from Londrina, PR, Brazil. SNPs were analyzed by real-time PCR. A family history of cancer, including PCa, as well as level of schooling were risk factors for PCa. The data were obtained via logistic regression, using odds ratios with a CI 95%. The genotypes of AKT1 and AKT1+AR demonstrated an association with protection for the disease. The combination of SNPs with the histopathological tumor data between allele variants of AMACR, AKT1+AR, and AKT1+AMACR indicated an association with protection against seminal vesicle invasion. The polymorphisms AKT1+AR and PI3K+AR were associated with protection against tumor bilaterality. The genotype combinations PTEN+AMACR and PTEN+AR were associated with the risk of extracapsular extension. Of the five genes studied, two were associated with protection for PCa, four were associated with protection for some prognostic variables, and only one was associated with risk. Thus, these SNPs are candidates for markers to discriminate men with better or worse prognosis for PCa.

9.
Carcinogenesis ; 41(2): 139-145, 2020 04 22.
Article in English | MEDLINE | ID: mdl-31305891

ABSTRACT

Prostate cancer (PCa) is the second most common cancer in men. The indolent course of the disease makes the treatment choice a challenge for physicians and patients. In this study, a minimally invasive method was used to evaluate the potential of molecular markers in identifying patients with aggressive disease. Cell-free plasma samples from 60 PCa patients collected before radical prostatectomy were used to evaluate the levels of expression of eight genes (AMACR, BCL2, NKX3-1, GOLM1, OR51E2, PCA3, SIM2 and TRPM8) by quantitative real-time PCR. Overexpression of AMACR, GOLM1, TRPM8 and NKX3-1 genes was significantly associated with aggressive disease characteristics, including extracapsular extension, tumor stage and vesicular seminal invasion. A trio of genes (GOLM1, NKX3-1 and TRPM8) was able to identify high-risk PCa cases (85% of sensitivity and 58% of specificity), yielding a better overall performance compared with the biopsy Gleason score and prostate-specific antigen, routinely used in the clinical practice. Although more studies are required, these circulating markers have the potential to be used as an additional test to improve the diagnosis and treatment decision of high-risk PCa patients.


Subject(s)
Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , Prostatic Neoplasms/diagnosis , RNA, Messenger/blood , Aged , Biomarkers, Tumor/genetics , Brazil , Cell-Free Nucleic Acids/genetics , Clinical Decision-Making/methods , Gene Expression Regulation, Neoplastic , Humans , Kallikreins/blood , Liquid Biopsy , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness/genetics , Patient Selection , Prostate/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , RNA, Messenger/genetics , Risk Assessment/methods
10.
PLoS One ; 12(9): e0184094, 2017.
Article in English | MEDLINE | ID: mdl-28910345

ABSTRACT

Circulating nucleic acids are found in free form in body fluids and may serve as minimally invasive tools for cancer diagnosis and prognosis. Only a few studies have investigated the potential application of circulating mRNAs and microRNAs (miRNAs) in prostate cancer (PCa). The Cancer Genome Atlas (TCGA) database was used for an in silico analysis to identify circulating mRNA and miRNA as potential markers of PCa. A total of 2,267 genes and 49 miRNAs were differentially expressed between normal and tumor samples. The prediction analyses of target genes and integrative analysis of mRNA and miRNA expression revealed eleven genes and eight miRNAs which were validated by RT-qPCR in plasma samples from 102 untreated PCa patients and 50 cancer-free individuals. Two genes, OR51E2 and SIM2, and two miRNAs, miR-200c and miR-200b, showed significant association with PCa. Expression levels of these transcripts distinguished PCa patients from controls (67% sensitivity and 75% specificity). PCa patients and controls with prostate-specific antigen (PSA) ≤ 4.0 ng/mL were discriminated based on OR51E2 and SIM2 expression levels. The miR-200c expression showed association with Gleason score and miR-200b, with bone metastasis, bilateral tumor, and PSA > 10.0 ng/mL. The combination of circulating mRNA and miRNA was useful for the diagnosis and prognosis of PCa.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Biomarkers, Tumor/blood , Bone Neoplasms/blood , MicroRNAs/blood , Neoplasm Proteins , Prostatic Neoplasms/blood , RNA, Messenger/blood , RNA, Neoplasm/blood , Receptors, Odorant , Aged , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Humans , Kallikreins/blood , Male , Middle Aged , Neoplasm Metastasis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/therapy , Reverse Transcriptase Polymerase Chain Reaction
11.
Obes Surg ; 23(10): 1575-80, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23519632

ABSTRACT

BACKGROUND: The objective of this study was to assess predictors for new-onset stone formers after Roux-en-Y gastric bypass (RYGBP). METHODS: One hundred and fifty-one obese patients underwent RYGBP and were followed for 1 year. The analysis comprised two study time points: preoperative (T0) and 1 year after surgery (T1). They were analyzed for urinary stones, blood tests, and 24-h urinary evaluation. Nonparametric tests, logistic regression, and multivariate analysis were conducted using SPSS 17. RESULTS: Median BMI decreased from 44.1 to 27.0 kg/m2 (p < 0.001) in the postoperative period. Urinary oxalate (24 versus 41 mg; p < 0.001) and urinary uric acid (545 versus 645 mg; p < 0.001) increased significantly postoperatively (preoperative versus postoperative, respectively). Urinary volume (1310 versus 930 ml; p < 0.001), pH (6.3 versus 6.2; p = 0.019), citrate (268 versus 170 mg; p < 0.001), calcium (195 versus 105 mg; p < 0.001), and magnesium (130 versus 95 mg; p = 0.004) decreased significantly postoperatively (preoperative versus postoperative, respectively). Stone formers increased from 16 (10.6 %) to 27 (17.8%) patients in the postoperative analysis (p = 0.001). Predictors for new stone formers after RYGBP were postoperative urinary oxalate (p = 0.015) and uric acid (p = 0.044). CONCLUSIONS: RYGBP determined profound changes in urinary composition which predisposed to a lithogenic profile. The prevalence of urinary lithiasis increased almost 70% in the postoperative period. Postoperative urinary oxalate and uric acid were the only predictors for new stone formers.


Subject(s)
Calcium Oxalate/urine , Gastric Bypass/adverse effects , Obesity, Morbid/surgery , Uric Acid/urine , Urolithiasis/epidemiology , Urolithiasis/etiology , Adult , Brazil/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Male , Metabolic Clearance Rate , Obesity, Morbid/epidemiology , Obesity, Morbid/urine , Postoperative Period , Predictive Value of Tests , Preoperative Period , Prospective Studies , Urolithiasis/urine
12.
Int Braz J Urol ; 37(4): 528-33, 2011.
Article in English | MEDLINE | ID: mdl-21888706

ABSTRACT

PURPOSE: SUI (Stress Urinary Incontinence) results from sudden increases in intravesical peak pressures exceeding urethral resistance leading to involuntary urine loss. Obesity and smoking are well established reversible risk factors for SUI and may alter intravesical peak pressures. BMI, smoking status, and other clinical factors were studied to determine their relationship to CIPP (maximal Intravesical Peak Pressures generated by Cough) in SUI complaining women. MATERIALS AND METHODS: Three hundred nineteen women complaining of SUI were evaluated with medical history and urodynamics. Age, parity, comorbidities, previous surgery, BMI and history of smoking were obtained. The maximal intravesical peak pressures generated by cough (CIPP) and cough leak point pressure (CLPP) were acquired. Univariate and multivariate analysis were conducted. RESULTS: Current smokers and former smokers had similar CIPP (170cmH2O and 170cmH2O; p = 0.5, respectively); Those individuals who had never smoked had significantly lower CIPP (140cmH2O; p = 0.000 and p = 0.009 respectively). BMI was directly related to CIPP (r = 0.41; p = 0.000). Vaginal deliveries (r = -0.15, p = 0.08) and diabetes (r = 0.15, p = 0.016) were also directly related to CIPP on univariate analysis. Only smoking status (p = 0.000) and BMI (p = 0.000) were independently significantly related to CIPP on multivariate analysis. CONCLUSIONS: Obesity and smoking showed increased CIPP (maximal Intravesical Peak Pressures generated by Cough). While reduced BMI is related to lower CIPP, smoking cessation does not appear to diminish CIPP. These findings suggest that weight loss may reduce incontinence by CIPP modulation. However, the benefits of smoking cessation without additional lifestyle modification, may have no benefit to improve urinary incontinence.


Subject(s)
Cough/complications , Obesity/complications , Smoking/adverse effects , Urinary Incontinence, Stress/etiology , Adult , Aged , Analysis of Variance , Body Mass Index , Cough/physiopathology , Female , Humans , Middle Aged , Pressure , Risk Factors , Urinary Bladder/physiopathology , Urodynamics/physiology
13.
Int. braz. j. urol ; 37(4): 528-533, July-Aug. 2011. ilus, tab
Article in English | LILACS | ID: lil-600819

ABSTRACT

PURPOSE: SUI (Stress Urinary Incontinence) results from sudden increases in intravesical peak pressures exceeding urethral resistance leading to involuntary urine loss. Obesity and smoking are well established reversible risk factors for SUI and may alter intravesical peak pressures. BMI, smoking status, and other clinical factors were studied to determine their relationship to CIPP (maximal Intravesical Peak Pressures generated by Cough) in SUI complaining women. MATERIALS AND METHODS: Three hundred nineteen women complaining of SUI were evaluated with medical history and urodynamics. Age, parity, comorbidities, previous surgery, BMI and history of smoking were obtained. The maximal intravesical peak pressures generated by cough (CIPP) and cough leak point pressure (CLPP) were acquired. Univariate and multivariate analysis were conducted. RESULTS: Current smokers and former smokers had similar CIPP (170cmH2O and 170cmH2O; p = 0.5, respectively); Those individuals who had never smoked had significantly lower CIPP (140cmH2O; p = 0.000 and p = 0.009 respectively). BMI was directly related to CIPP (r = 0.41; p = 0.000). Vaginal deliveries (r = -0.15, p = 0.08) and diabetes (r = 0.15, p = 0.016) were also directly related to CIPP on univariate analysis. Only smoking status (p = 0.000) and BMI (p = 0.000) were independently significantly related to CIPP on multivariate analysis. CONCLUSIONS: Obesity and smoking showed increased CIPP (maximal Intravesical Peak Pressures generated by Cough). While reduced BMI is related to lower CIPP, smoking cessation does not appear to diminish CIPP. These findings suggest that weight loss may reduce incontinence by CIPP modulation. However, the benefits of smoking cessation without additional lifestyle modification, may have no benefit to improve urinary incontinence.


Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Cough/complications , Obesity/complications , Smoking/adverse effects , Urinary Incontinence, Stress/etiology , Analysis of Variance , Body Mass Index , Cough/physiopathology , Pressure , Risk Factors , Urinary Bladder/physiopathology , Urodynamics/physiology
14.
Cancer Invest ; 28(9): 917-24, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20632874

ABSTRACT

The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androgen receptor (AR) genes were involved in prostate cancer risk and aggressiveness. Genotypes were determined by PCR-RFLP (PSA) or using a 377 ABI DNA Sequencer (AR). PSA(G/G) genotype (OR = 1.78, 95% CI = 1.06­2.99) and AR short CAG repeats (OR = 1.89, 95% CI = 1.21­2.96) increased risk for prostate cancer and were related with tumor aggressiveness. About 38.3% of tumors showed microsatellite instability. In conclusion, polymorphisms in these genes may be indicated as potential biomarkers for prostate cancer.


Subject(s)
Polymorphism, Genetic , Prostate-Specific Antigen/genetics , Prostatic Neoplasms/genetics , Receptors, Androgen/genetics , Aged , Alleles , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Gene Frequency , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Middle Aged , Neoplasm Invasiveness , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Prostatic Neoplasms/pathology , Sequence Analysis, DNA , Trinucleotide Repeats/genetics
15.
Clin Exp Med ; 9(1): 21-8, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18979064

ABSTRACT

Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case-control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455-->G), and GSTP1 (A313-->G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case-controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76-2.41 and OR = 0.75; 95% CI = 0.41-1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01-3.12 and OR = 1.99; 95% CI = 1.07-3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.


Subject(s)
Cytochrome P-450 CYP1A1/genetics , Glutathione S-Transferase pi/genetics , Glutathione Transferase/genetics , Urinary Bladder Neoplasms/genetics , Aged , Aged, 80 and over , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length
16.
Urology ; 72(4): 770-4, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18632141

ABSTRACT

OBJECTIVES: To evaluate potential preoperative predictive factors for complications in ureteroscopic treatment of ureteral stones. METHODS: One thousand two hundred thirty-five semirigid ureteroscopies for ureteral stones were prospectively inserted in our database and analyzed for complications. Preoperative variables evaluated were as follows: age, gender, length of symptoms, previous extracorporeal shock wave lithotripsy (ESWL), associated urinary tract infection (UTI), stone location, and degree of hydronephrosis. Univariate analysis and multivariate logistic regression were conducted. RESULTS: Fifty-five (4.4%) procedures had complications. There were 8 ureteral perforations, 5 paraureteral stones, 2 ureteral avulsions, 5 mucosal eversions, 1 urethral injury, and 34 mucosal tears. In univariate analysis, age (P = .000), gender (P = .002), previous ESWL (P = .047), stone size (P = .001), and location (P = .001) were predictors of complications. Gender (P = .012), previous in situ ESWL (P = .037), stone size (P = .025), and location (P = .019) remained predictors in multivariate logistic regression. CONCLUSIONS: Semirigid ureteroscopy is a safe procedure with few complications. Larger stones, proximally located (iliac vessels or above) with previous in situ ESWL in men are preoperative predictors for intraoperative complications.


Subject(s)
Intraoperative Complications/etiology , Lithotripsy/methods , Ureteral Calculi/therapy , Ureteroscopes , Ureteroscopy , Adolescent , Adult , Aged , Child , Child, Preschool , Equipment Design , Female , Humans , Intraoperative Complications/epidemiology , Male , Middle Aged , Predictive Value of Tests
17.
Rev. Col. Bras. Cir ; 34(5): 354-356, set.-out. 2007. ilus
Article in Portuguese | LILACS | ID: lil-467899

ABSTRACT

Sump Syndrome after choledochoduodenostomy is becoming rare, mainly because endoscopic procedures are replacing this surgery. We report a case of this syndrome where the only symptom was pain. The diagnosis was made after 3 years and many doctors attended the patient. The treatment was endoscopic and the result was excellent.

18.
Surg Endosc ; 20(12): 1858-61, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17031748

ABSTRACT

BACKGROUND: Surgical stress promotes impaired immunological function, which contributes to tumor growth. Natural killer activity (NKA) has a protective role in immunity to tumors. So, the aim of this experimental study was to assess tumor growth and (NKA) after pneumoperitoneum and laparotomy. METHODS; Sixty male Wistar rats were divided into three groups (anesthesia, CO2 pneumoperitoneum and laparotomy) plus ten controls. All experimental animals were inoculated subcutaneously with 8 x 105 Walker carcinosarcoma 256 cells. Animals were sacrificed on 1st(POD1) and 8th (POD8) postoperative day. Tumors were excised and weighed. RESULTS: On POD1 all animals had diminished NKA when compared to controls; NKA after pneumoperitoneum was significantly greater than after laparotomy. On POD8 all animals, except after laparotomy, reached NKA at controls levels. Tumor weight was significantly greater after laparotomy when compared to pneumoperitoneum. CONCLUSIONS: Pneumoperitoneum causes a less depressed NKA and less tumor growth when compared to laparotomy.


Subject(s)
Carcinoma 256, Walker/immunology , Cytotoxicity, Immunologic/immunology , Immunity, Cellular/immunology , Killer Cells, Natural/immunology , Laparotomy , Peritoneal Neoplasms/immunology , Pneumoperitoneum, Artificial , Animals , Carcinoma 256, Walker/pathology , Carcinoma 256, Walker/surgery , Disease Progression , Male , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Prognosis , Rats , Rats, Wistar , Stress, Mechanical
20.
RBM rev. bras. med ; 60(1/2): 39-: 43-: 46-: passim-40, 44, 46, jan.-fev. 2003. ilus, tab
Article in Portuguese | LILACS | ID: lil-357756

ABSTRACT

O câncer da próstata se tornou a malignidade mais comum em homens nos Estados Unidos. Pesquisas recentes demonstram que a dieta intima tem relação com as variações de incidência desta neoplasia ao redor do mundo. Tal conhecimento pode ser uma medida importante na prevenção do câncer da próstata. Dentre os alimentos estudados, substâncias chamadas fitoestrógenos, que são estrogênios fracos encontrados na soja, contêm propriedades capazes de reduzir o risco de câncer da próstata. Compostos ricos em gordura também têm sido associados a tumores mais avançados. Em relação às vitaminas, o calcitriol (vitamina D ativa) é considerado atualmente como hormônio regulador de crescimento e diferenciação celular, existindo relação inversa entre seus níveis e a incidência de câncer da próstata. A dieta encontrada nos países orientais, rica em vitaminas e vegetais e com baixo teor lipídico, tem papel protetor contra o câncer da próstata.


Subject(s)
Humans , Male , Prostatic Neoplasms/diet therapy , Chemoprevention/methods
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