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1.
Actas Urol Esp (Engl Ed) ; 46(8): 464-472, 2022 10.
Article in English, Spanish | MEDLINE | ID: mdl-36089504

ABSTRACT

INTRODUCTION AND OBJECTIVES: To evaluate whether there is any difference between immediate postoperative instillation of intravesical chemotherapy (IPOIC) and continuous saline bladder irrigation (CSBI) in terms of bladder cancer (BC) recurrence in patients with primary low- or intermediate-risk non-muscle-invasive BC (NMIBC). MATERIALS AND METHODS: Medical records of 1482 patients who underwent transurethral resection of bladder tumor between March 1994 and August 2020 were reviewed retrospectively. Patients were divided into two groups according to IPOIC and/or CSBI administration status [Group-1 = CSBI alone; Group-2 = CSBI following IPOIC]. Low- and intermediate-risk NMIBC patients were also divided into subgroups according to IPOIC and/or CSBI administration status. RESULTS: A total of 594 patients with primary NMIBC were included. Of the patients, 86 (14.5%) were female and 508 (85.5%) were male with a median age of 69 (60-78) years. The frequency of patients in Group-1 and Group-2 were 361 (60.8%) and 233 (39.2%), respectively. Recurrent disease was observed in 213 (35.9%) patients. There was no difference between the groups when they were compared for recurrent disease frequency, median time to first recurrence and frequency of recurrence within first 12 months (P = .064, P = .671, and P = .145, respectively). Disease recurrence rates in low-risk NMIBC patients was lower when they were treated with "CSBI following IPOIC" when compared to "CSBI alone" (P = .042). However, no difference was observed in low-risk NMIBC subgroups when they were compared for pathological features of recurrent tumors such as number, size, grade, stage, and presence of carcinoma in situ (P > .05, for each). CONCLUSIONS: "CSBI following IPOIC" combination was not superior to "CSBI alone" for preventing adverse pathological outcomes in recurrent low- and intermediate-risk NMIBC.


Subject(s)
Neoplasm Recurrence, Local , Urinary Bladder Neoplasms , Administration, Intravesical , Aged , Female , Humans , Male , Neoplasm Recurrence, Local/prevention & control , Retrospective Studies , Urinary Bladder , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery
2.
Transplant Proc ; 51(4): 1058-1063, 2019 May.
Article in English | MEDLINE | ID: mdl-31101171

ABSTRACT

Although cardiovascular (CV) assessment is recommended to minimize perioperative risk in all potential kidney transplant recipients, the utility and reliability of various assessment methods are not well established. In this study, we investigated the CV evaluations and outcomes of standardized CV assessment protocols (Lisbon and American Society of Transplantation [AST]) in potential kidney transplant recipients. Data were analyzed for 266 end-stage renal disease patients (mean age 45.4 ± 13 years, female-to-male ratio 126:140) accepted for kidney transplantation wait-listing. Patients were classified as low and high cardiac risk according to their first cardiac evaluation. Major cardiovascular events (CVEs) and deaths were recorded. At the end of follow-up (median 639 days), 72 (27.1%) patients underwent kidney transplantation. A total of 49 patients (18.4%) had CVEs and 42 (15.8%) patients died. Being over 45 years of age and having dialysis vintage over 1 year were found to be independent risk factors for CVEs. Forty-eight out of 60 high-risk patients evaluated with noninvasive tests had negative results. Twelve out of these 48 patients had a CVE in due course. Among 10 patients who underwent coronary angiography, 1 had a CVE and 1 died. The sensitivity and specificity of the AST guidelines (area under the curve = 0.647, P = .005, sensitivity 83%, specificity 54%) were higher than Lisbon. In conclusion, the predictive risk factors for CVEs were age over 45 years and dialysis vintage over a year. Our results also suggest that exercise electrocardiography and myocardial perfusion scintigraphy for cardiac evaluation are less sensitive in CVE prediction. We recommend clinicians to use the AST guidelines and to prioritize coronary angiography in pretransplant CV assessment.


Subject(s)
Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Kidney Transplantation/adverse effects , Practice Guidelines as Topic/standards , Adult , Female , Humans , Incidence , Male , Middle Aged , Reproducibility of Results , Risk Assessment , Risk Factors , Transplant Recipients
3.
Oncogene ; 35(36): 4807-15, 2016 09 08.
Article in English | MEDLINE | ID: mdl-26876202

ABSTRACT

Androgen receptor (AR)-mediated gene expression continues to have a critical role in promoting castration-resistant prostate cancer (CRPC) survival and growth even after androgen deprivation therapy. AR cistrome analyses in CRPC cells have identified a large number of AR target genes involved in proliferative and cell cycle-related functions, and hold promise for development of novel therapeutic approaches for CRPC. However, there is little understanding of how these genes function in vivo and what the clinical implications are. We previously reported that secretory leukocyte peptidase inhibitor (SLPI) is regulated by the AR in a ligand-independent manner in CRPC cells and required for CRPC cell proliferation under androgen-deprived conditions. SLPI is a secreted serine protease inhibitor, which is overexpressed in a number of cancers, including lung, breast and ovarian cancer, and involved in tumor progression. However, the oncogenic potential of SLPI in prostate cancer remains unknown. Here we provide the first evidence that SLPI is upregulated in a subset of CRPC cell lines and CRPC patient tumors. In addition, serum SLPI levels are significantly elevated in metastatic CRPC patients compared with hormone naive patients, raising the possibility that this could serve as a biomarker. We demonstrated that SLPI expression has functional significance, as it promotes CRPC cell survival and growth after androgen withdrawal in vivo and in vitro. Last, we demonstrated that the oncogenic effect of SLPI may be due to protection of growth factor progranulin from enzymatic cleavage or suppression of CRPC cell apoptosis independent of anti-protease activity of SLPI. These findings implicate SLPI as a potential biomarker of resistance to AR inhibition and therapeutic target for CRPC treatment.


Subject(s)
Androgens/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Receptors, Androgen/genetics , Secretory Leukocyte Peptidase Inhibitor/genetics , Androgens/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Survival , Gene Expression Regulation, Neoplastic , Humans , Intercellular Signaling Peptides and Proteins/genetics , Male , Progranulins , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/pathology , Secretory Leukocyte Peptidase Inhibitor/blood , Signal Transduction , Transcriptional Activation/genetics
4.
Transplant Proc ; 47(5): 1421-4, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26093733

ABSTRACT

OBJECTIVES: Regular screening for the BK virus (BKV) is recommended for early intervention in renal transplant patients. Identification of predictors for the development of BK viremia would improve their monitoring. We performed a retrospective study investigating whether the lymphocyte count may be a predictor of BKV development in renal transplant patients. PATIENTS AND METHODS: We retrospectively analyzed 268 renal transplant patients who were followed in our clinic from January 2011 to August 2014. The viral loads of BKV in blood detected by quantitative real-time polymerase chain reaction test were performed according to relevant guidelines. We also retrospectively monitored lymphocyte count, creatinine, immunosuppressive drug doses, and tacrolimus/cyclosporine/mTor inhibitors levels during the same time as BKV screening. Demographic and other clinical data were extracted from patients' files. The calculation of correlation coefficients and receiver operating characteristics (ROC) curve analysis were performed. RESULTS: Overall, 16 patients (5.9%) who experienced BKV-DNA positivity were included the study. Mean age of patients was 38.2 ± 12.8 years. All patients received steroid and calcineurin inhibitors (CNIs). Mycophenolate mofetil/mycophenolic acid (MMF/MPA) was administered to 14 patients. BKV-DNA was found in 64 of the 88 (72.7%) plasma samples. The lymphocyte count on the first day of positive BKV-DNA test was significantly lower than in those with negative BKV-DNA results (1700/µl vs 2400/µl, respectively; P = .009). Its AUC of the ROC curve was 0.77 (P = .012). The optimal cutoff point for lymphocyte count was 1900/µl, and sensitivity and specificity for predict BKV positivity were 75% and 78.57%, respectively. We also found that lymphocyte count negatively correlated with the first detectable BKV titers (r = -0.438; P = .015). However, there is no relation between CNI/mTOR inhibitor levels, MMF/MPA doses, lymphocyte count, and all BKV-titers. CONCLUSIONS: Decreased lymphocyte count may be a predictor for preceding BKV viremia. Clinicians should be more careful in terms of the decreased lymphocyte count in case of BKV replication in renal transplant patients.


Subject(s)
BK Virus/physiology , Kidney Transplantation/adverse effects , Polyomavirus Infections/blood , Tumor Virus Infections/blood , Viral Load , Adult , Aged , Calcineurin Inhibitors/therapeutic use , Cyclosporine/administration & dosage , Female , Humans , Immunosuppressive Agents/administration & dosage , Lymphocyte Count , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Polyomavirus Infections/virology , Real-Time Polymerase Chain Reaction , Retrospective Studies , Steroids/therapeutic use , Tacrolimus/administration & dosage , Tumor Virus Infections/virology , Viremia/virology , Virus Replication , Young Adult
5.
Free Radic Res ; 47(9): 683-91, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23758074

ABSTRACT

Reactive oxygen metabolites play an important role in the ischemia/reperfusion (I/R)-induced tissue injury. This study was designed to investigate the possible protective effects of quercetin against I/R injury of the rat corpus cavernosum tissue. To induce I/R injury, abdominal aorta was clamped for 30 min and reperfused for 60 min. Quercetin (20 mg/kg) or vehicle was given before ischemia and just after reperfusion in the I/R group and in the sham-operated control group in which clamping was not performed. After decapitation, corpus cavernosum tissues were removed and either placed in organ baths or stored for evaluating biochemical parameters. Oxidative injury was examined by measuring lucigenin chemiluminescence (CL), nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities and caspase-3 protein levels. In the I/R group, contractile responses to phenylephrine and relaxation responses to carbachol were impaired significantly compared with those in the control groups, while quercetin treatment in I/R group reversed both of the responses. On the other hand, increase in lucigenin CL, NO, MDA levels and MPO and caspase-3 activities and decrease in GSH levels and SOD activity in the cavernosal tissues of the I/R group were also significantly reversed by quercetin treatment. Furthermore, observed distorted morphology with ruptured endothelial cells and vacuolization in the cytoplasm of cavernosal tissues of I/R no longer persisted in the quercetin-treated I/R group. Thus, our results suggested that treatment with quercetin may have some benefits in controlling I/R-induced tissue injury through its anti-inflammatory, anti-apoptotic, and antioxidant effects.


Subject(s)
Antioxidants/metabolism , Oxidative Stress/drug effects , Quercetin/administration & dosage , Reperfusion Injury/metabolism , Animals , Apoptosis/drug effects , Glutathione/metabolism , Lipid Peroxidation/drug effects , Male , Nitric Oxide/metabolism , Penis/drug effects , Rats , Reperfusion Injury/drug therapy , Reperfusion Injury/pathology
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