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BACKGROUND: Bladder cancer is a type of cancer with a high incidence in men. Plasma electrosurgery (PES) is often used in the treatment of bladder cancer. Postoperative complications often cause depression and anxiety in patients after surgery. AIM: To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them. METHODS: A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups. Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer. RESULTS: Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery, economic status, educational level, and marital status. A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer, and the results showed that whether the risk factors were whether or not it was the first surgery, monthly income between 3000 and 3000-6000, secondary or junior high school education level, single, divorced, and widowed statuses. CONCLUSION: The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries, economic status, level of education, and marital status. This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.
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OBJECTIVE: To investigate the influence of varicocele on the volume discrepancy of bilateral testes, and the relationship between testicular volume discrepancy and semen parameters. METHODS: This study included 181 varicocele patients and 102 normal fertile men without varicocele. We retrospectively analyzed their clinical data, including the grades and locations of varicocele, testis volume and semen parameters. RESULTS: Bilateral testicular volume discrepancy was found in 132 (72.9%) of the varicocele patients (including 117 cases of left testicular hypotrophy [88.6%]), and 35 (34.3%) of the non-varicocele fertile men. The rates of bilateral testicular volume discrepancy were 61.3%, 3.5%, 20.9% and 14.3% in the grade-III, grade-II, grade-I and non-varicocele groups, respectively (P < 0.05), with statistically significant differences among different age groups (P < 0.05). The percentage of morphologically normal sperm and sperm motility were reduced differently with different degrees of testicular volume discrepancy (P <0.05). CONCLUSION: Testicular volume discrepancy is more common in men with left varicocele, and its prevalence and degree are correlated with the grade of varicocele. Semen quality decreases with the increase of testicular volume discrepancy.
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Análise do Sêmen , Testículo/patologia , Varicocele/patologia , Varicocele/fisiopatologia , Adulto , Humanos , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Adulto JovemRESUMO
OBJECTIVE: To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. METHODS: The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. RESULTS: Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (P<0.01). Immunohistochemically, we found that the rats treated with Ad-hHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. CONCLUSION: Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.
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Heme Oxigenase-1/genética , Rim/patologia , Traumatismo por Reperfusão/terapia , Transfecção , Animais , Expressão Gênica , Vetores Genéticos , Humanos , Transplante de Rim , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the growth of prostate cancer in vitro or in vivo by inhibiting the expression of EGFR and its intracellular effective proteins with small RNA interference ( SiRNA). METHODS: The hormone independence prostate cancer (HIPC) cell line PC-3 was transfected by EGFR SiRNA synthesized and cloned into a recombinant lentivirus vector. The growth rate of transfected PC-3 cell was measured by MTT. The expression of EGFR and the expression and phosphorylation of its intracellular proteins, such as Akt and MAPK, were detected by fluorescent Real-Time PCR and Western blot respectively. Meanwhile nude mice were transplanted with PC-3 cell to establish the tumor model and the tumor growth was observed. RESULTS: The transfection efficiency was stable over 75% in PC-3 cell transfected with the recombinant lentivirus vector carrying EGFR SiRNA and the survival rate of PC-3 cell was only 40%-50%. Such depressant effects might be obtained by inhibiting the expression of EGFR mRNA and protein to only 10% as compared with their untreated levels (P < 0.01); meanwhile, the expression level and phosphorylation of Akt and MAPK also obviously decreased to 76.49% and 47.15% respectively (P < 0.05). Compared with the control group, the proliferation activity of tumors in nude mice was inhibited significantly by 34.83% (P < 0.05). CONCLUSION: Lentivirus-mediated EGFR SiRNA can inhibit the growth of HIPC in vivo and in vitro by effectively suppressing the expression of EGFR and its intracellular proteins. The latter may be a potential candidate for future targeted therapy.
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Receptores ErbB/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Interferente Pequeno/genética , Animais , Linhagem Celular Tumoral , Receptores ErbB/genética , Vetores Genéticos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos , Camundongos NusRESUMO
OBJECTIVE: To investigate the enhancing effect of all-trans retinoic acid (ATRA) on the bystander effect of the herpes simplex virus thymidine kinase(HSV-TK)/ganciclovir (GCV) against androgen unresponsive prostate cancer. METHODS: The bystander effect of the HSV-TK/GCV system was measured by methyl thiazolyl tetrazolium (MTT) assay on PC-3 cells before and after ATRA treatment. The growth and the histopathology of transplant tumors were observed in 4 groups of nude mice with prostate cancer. RESULTS: ATRA augmented significantly the bystander effect of the HSV-TK/GCV system by reducing TK positive PC-3 cells from 50% to 30% (P < 0.05). HSV-TK showed an inhibiting effect, while ATRA with the HSV-TK/GCV system produced significant effect on prostate cancer 1 week earlier than the former (P < 0.05). CONCLUSION: ATRA can argument the in vivo and in vitro bystander effect of the HSV-TK/GCV system in the treatment of androgen unresponsive prostate cancer.
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Efeito Espectador/efeitos dos fármacos , Genes Transgênicos Suicidas/genética , Terapia Genética/métodos , Neoplasias da Próstata/terapia , Tretinoína/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ganciclovir/farmacologia , Humanos , Masculino , Camundongos , Camundongos Nus , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Simplexvirus/enzimologia , Timidina Quinase/genética , Timidina Quinase/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVE: To investigate the expressions of endothelial nitric oxide synthase (eNOS) and connexin 43 (Cx43) in the penile tissue of rats with diabetes mellitus induced erectile dysfunction (DMED) and their correlation with DMED. METHODS: SD rat models of DM were established by intraperitoneal injection of alloxan, and 8 weeks later, apomorphine was administered to induce ED in the DM models. The expressions of eNOS and Cx43 were measured by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. RESULTS: Alloxan did not influence the expressions of eNOS mRNA and Cx43 mRNA in the penile tissue. Compared with the DM models, the expression of eNOS mRNA significantly decreased in the DMED group (0.155 +/- 0.157 vs 0.508 +/- 0.242, P < 0.01), while that of Cx43 mRNA markedly increased (0.993 +/- 0.157 vs 0.545 +/- 0.138, P < 0.01), with a negative correlation between the two expressions (r = -0.987). The same results were shown by immunohistochemistry in the penile smooth muscle cells of the DMED rats. CONCLUSION: The decrease of eNOS expression in the penile tissue might play a key role in the development of ED in diabetic patients, while the accompanying compensative elevation of the Cx43 level has yet to be further studied.
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Conexina 43/biossíntese , Disfunção Erétil/fisiopatologia , Óxido Nítrico Sintase Tipo III/biossíntese , Pênis/metabolismo , Animais , Conexina 43/genética , Diabetes Mellitus Experimental/complicações , Disfunção Erétil/etiologia , Imuno-Histoquímica , Masculino , Óxido Nítrico Sintase Tipo III/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Chronic prostatitis was the most common type of prostatitis and oxidative stress was reported to be highly elevated in prostatitis patients. In this study, we determined the effect of N-acetylcysteine (NAC) on prostatitis and the molecular mechanism involved in it. Male Sprague-Dawley rats were divided into three groups: control group (group A, n = 20), carrageenan-induced chronic nonbacterial prostatitis (CNP) model group (group B, n = 20), and carrageenan-induced CNP model group with NAC injection (group C, n = 20). Eye score, locomotion score, inflammatory cell count, cyclooxygenase 2 (COX2) expression, and Evans blue were compared in these three groups. The expression of miR-141 was determined by quantitative real-time PCR (qRT-PCR). Moreover, protein expressions of Kelch-like ECH-associated protein-1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) and its target genes were examined by Western blot. Luciferase reporter assay was performed in RWPE-1 cells transfected miR-141 mimic or inhibitor and the plasmid carrying 3'-UTR of Keap1. The value of eye score, locomotion score, inflammatory cell count, and Evans blue were significantly decreased in group C, as well as the expression of COX2, when comparing to that of group B. These results indicated that NAC relieved the carrageenan-induced CNP. Further, we found that NAC increased the expression of miR-141 and activated the Keap1/Nrf2 signaling. Luciferase reporter assay revealed that miR-141 mimic could suppress the activity of Keap1 and stimulate the downstream target genes of Nrf2. In addition, miR-141 inhibitor could reduce the effect of NAC on prostatitis. NAC ameliorates the carrageenan-induced prostatitis and prostate inflammation pain through miR-141 regulating Keap1/Nrf2 signaling.
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Acetilcisteína/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/metabolismo , Prostatite/tratamento farmacológico , Animais , Carragenina , Ciclo-Oxigenase 2/biossíntese , Modelos Animais de Doenças , Masculino , Estresse Oxidativo/efeitos dos fármacos , Prostatite/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy. METHODS: Data from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density (PSAD), free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection. RESULTS: PCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group (8.39 µg/L vs. 7.16 µg/L, 0.20 vs. 0.16, 14.15% vs. -1.36%, respectively). PSADVR had the largest area under the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR >10% than PSADVR ≤10% (28.6% vs. 6.5%, P< 0.001). In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa (r = 0.63, P = 0.03). CONCLUSIONS: Our results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment.
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Biópsia/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Próstata/metabolismo , Próstata/patologia , Curva ROCRESUMO
OBJECTIVE: To retrospectively evaluate appropriate treatment for patients with symptomatic caliceal diverticular calculi, by comparing the therapeutic outcomes for those undergoing minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureterorenoscopy (F-URS). METHODS: From March 2009 to May 2014, 36 consecutive patients with caliceal diverticular calculi were divided into 2 groups: 21 patients underwent MPCNL, and 15 were treated by F-URS. All procedures were performed by one surgical group, which ensured relatively constant parameters. Patient characteristics, operative time, hospital stay after surgery, stone-free rate, symptomatic improvement rate, complications, diverticular obliteration, and stone composition were analyzed retrospectively in the 2 groups. RESULTS: Patient preoperative variables were comparable between the two groups, with no significant difference (P > 0.05). Mean operative time was 136.9 ± 22.8 min in the MPCNL group and 117.3 ± 24.3 min in the F-URS group (P = 0.019). Hospital stay was significantly longer in the MPCNL group than in the F-URS group (9.4 ± 3.1 vs. 6.9 ± 2.1 days, P = 0.010). The stone-free rates after MPCNL and F-URS were 90.5% (19/21) and 60.0% (9/15), respectively (P = 0.046). Additionally, 71.4% (15/21) of patients in the MPCNL group and 46.7% (7/15) of patients in the F-URS group had symptomatic improvement at the 6-month follow-up (P = 0.175); the rates of complications in the 2 groups were 19.0% (4/21) and 13.3% (2/15), respectively (P = 0.650). Complete diverticular obliteration was achieved in 16 (76.2%) cases in the MPCNL group and 5 (33.3%) cases in the F-URS group (P = 0.017). The distributions of calcium oxalate and hydroxyapatite in the stones were 66.7% (14/21) and 33.3% (7/21), respectively, in the MPCNL group; however, the distributions in the F-URS group were 46.7% (7/15) and 53.3% (8/15), respectively (P = 0.310). CONCLUSION: MPCNL is an effective method for the treatment of caliceal diverticular calculi. However, F-URS is an alternative technique in selected patients with a patent infundibulum, despite lower stone-free rates than with MPCNL. Fulguration of the diverticular lining with a high-power holmium laser and permitting the cavity to collapse are useful to increase the chance of diverticular obliteration.
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OBJECTIVE: To investigate the relationship between mRNA expression of platelet-derived endothelial cell growth factor (PD-ECGF) and invasion of bladder transitional cell carcinoma (BTCC). METHODS: The mRNA expression of PD-ECGF in BTCC was detected by RT-PCR. The target PCR bands were analyzed by NIH Image 1.62 software. RESULTS: The mRNA level of PD-ECGF in BTCC was 3.86 times as high as that of normal bladder mucosa (t = 2.36, P < 0.05). The expression level of stage Ta, T1 and T2-4 tumor was 1.33, 4.02 and 7.59 times as high as that of normal bladder mucosa, respectively. That of Grade 3 tumor was 2.27 times as high as that of Grade 1 - 2 tumor (t = 3.52, P < 0.01). CONCLUSION: The mRNA expression of PD-ECGF was positively correlated with the invasiveness and grade of BTCC. The results suggest that the mRNA level of PD-ECGF might be used as an indicator of tumor progression and a guide for clinical treatment of bladder transitional cell carcinoma.
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Carcinoma de Células de Transição/metabolismo , RNA Mensageiro/análise , Timidina Fosforilase/genética , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Carcinoma de Células de Transição/patologia , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To investigate the mRNA expression of platelet-derived endothelial cell growth factor (PD-ECGF) in superficial bladder cancer and its significance. METHODS: PD-ECGF mRNA expressions were determined by RT-PCR in 28 cases of superficial bladder cancers and 6 cases of normal bladder mucosa. The relation between PD-ECGF mRNA expression and tumor invasion to lamina propria or recurrence after transurethral resection was also analyzed. RESULTS: Some degree of PD-ECGF mRNA expression was present in all the samples. The PD-ECGF mRNA level was 3.1-fold higher in pT(1) tumors than in normal bladder mucosa (t = 2.13, P < 0.05) and 2.2-fold higher in pT(1) tumors than in pT(a) tumors (t = 2.66, P < 0.05); G(3) tumors expressed 3.3-fold higher PD-ECGF mRNA than normal bladder mucosa (t = 2.44, P < 0.05) and 2.5-fold higher than G(1 - 2) tumors (t = 3.36, P < 0.01). Eleven cases recurred during the mean follow-up period of 18 months. Three-fold higher PD-ECGF mRNA expression was showed in cases who recurred after transurethral resection than that in cases who did not recur (t = 4.49, P < 0.01). The specificity and sensitivity of predicting tumor recurrence were 82.4% and 81.8% respectively using 0.095 as a cutoff value of PD-ECGF mRNA level in this group of superficial bladder cancer. CONCLUSION: PD-ECGF mRNA expression correlates with tumor dedifferentiation and plays an important role in the early invasion in superficial bladder cancer. To analyze the PD-ECGF mRNA level contributes to the evaluations of tumor differentiation and invasion to lamina propria as well as recurrence prediction in superficial bladder cancer.
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Carcinoma de Células de Transição/metabolismo , Timidina Fosforilase/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Carcinoma de Células de Transição/patologia , Seguimentos , Humanos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Timidina Fosforilase/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Malignant cancer is the leading cause of death in man, exceeding cerebrovascular disease and heart disease. More than half of the total mortality due to malignant cancer is from lung, liver, intestinal and gastric cancer. Chemotherapy is one of the effective treatments for cancer. However, the great majority of Western anticancer medicines have considerable side effects. Herbal medicines offer many more advantages than synthesized compounds because they are made from purely natural compounds and have less adverse effects. However, the single administration methods used as standard in herbal medicine, and deficient drug targeting, severely limit their anticancer activity. Single-walled carbon nanotubes (SWNTs) can be used as drug carriers. They have been modified to form Chinese anticancer medicine-SWNT compounds which can specifically target tumors, thereby significantly increasing the therapeutic effectiveness of these medicines. Water-soluble SWNTs have high stability. As a drug carrier, SWNTs functional modification of the anticancer medicine may improve the targeting and killing of tumor cells. SWNTs have been attached to the Chinese antitumor medicines paclitaxel and plumbagin and have achieved excellent therapeutic effects. Furthermore, choosing the best administration methods such as internal iliac arterial infusion, intravesical infusion and embedment of a hypodermic chemotherapeutic pump, may also improve the anticancer effects of Chinese medicine.
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Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Nanotubos de Carbono/química , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Portadores de Fármacos , Estudos de Viabilidade , Humanos , Neoplasias/patologiaRESUMO
BACKGROUND: Epidemiological studies evaluating the association of two variants rs9340799 and rs2234693 on estrogen receptor 1 (ESR1) with prostate risk have generated inconsistent results. METHODS: A meta-analysis was here conducted to systematically evaluate the relationship of these two variants with prostate cancer susceptibility. RESULTS: For rs9340799, heterozygosity of T/C carriers showed a significant increased prostate cancer risk with a pooled odds ratio (OR) of 1.34 (95% CI = 1.06-1.69) while homozygote C/C carriers showed an increased but not statistically significant association with prostate cancer risk (pooled OR = 1.29, 95% CI = 0.94-1.79). Compared to the homozygous TT carriers, the allele C carriers showed a 31% increased risk for prostate cancer (pooled OR = 1.31, 95% CI = 1.06-1.63). No significant association between the rs2234693 and prostate cancer risk was found with the pooled OR of 1.15 (95% CI = 0.97-1.39, T/C and C/C vs. T/T) under the dominant genetic model. Compared to the homozygote T/T carriers, the heterozygous T/C carriers did not show any significantly different risk of prostate cancer (pooled OR = 1.13, 95% CI = 0.94-1.36) and the homozygous C/C carriers also did not show a significant change for prostate cancer risk compared to the wide-type T/T carriers (pooled OR = 1.26, 95% CI = 0.98-1.62). CONCLUSIONS: These data suggested that variant rs9340799, but not rs2234693, on ESR1 confers an elevated risk of prostate cancer.
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Receptor alfa de Estrogênio/genética , Predisposição Genética para Doença , Polimorfismo Genético/genética , Neoplasias da Próstata/etiologia , Estudos de Casos e Controles , Humanos , Masculino , Fatores de RiscoRESUMO
BACKGROUND & OBJECTIVE: Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is an essential enzyme in converting 5'-deoxy-5-fluorouridine (5'-DFUR), and 5-fluorouracil (5-FU) to their active metabolites in vivo, and can be up-regulated by some cytokines such as interleukin-1, and interferon gamma (INFgamma). This study was to observe the regulative effect of INFgamma on expression of PD-ECGF/TP, and its relation with the anti-cancer effect of 5'-DFUR, and 5-FU on RT4 bladder cancer cells. METHODS: PD-ECGF/TP mRNA, and protein expression were determined by reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot analysis, respectively. Cytotoxicity of 5'-DFUR, and 5-FU against RT4 cells was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymetho-xyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. RESULTS: Expression levels of PD-ECGF/TP mRNA and protein were elevated in RT4 cells after cultured with INFgamma. INFgamma reduced IC50s of 5'-DFUR [from (9.7+/-0.2) mmol/L to (3.7+/-0.9) mmol/L], and 5-FU [from (130.0+/-21.2) mmol/L to (49.3+/-18.4) mmol/L] in RT4 cells. CONCLUSIONS: INFgamma enhances cytotoxicity of 5'-DFUR, and 5-FU against RT4 cells through induction of PD-ECGF/TP. INFgamma/5'-DFUR or INFgamma/5-FU combination treatment may lead to better chemotherapeutic results in human bladder cancer.