Potential therapeutic effects of adjuvant chemotherapy after neoadjuvant chemotherapy for locally advanced muscle-invasive bladder cancer.

BACKGROUND: Although the administration of neoadjuvant chemotherapy has been associated with improved prognosis in patients with muscle-invasive bladder cancer, the therapeutic effects of adjuvant chemotherapy remain unknown in real-world settings. Therefore, we herein evaluated the clinical outcomes of adjuvant chemotherapy in pT3/4 muscle-invasive bladder cancer patients. MATERIALS AND METHODS: Among 587 bladder cancer patients who underwent radical cystectomy, 200 with a pathological T3 or higher muscle-invasive bladder cancer were included in the present analysis. Recurrence-free survival and cancer-specific survival were assessed by multivariate Cox regression analysis. RESULTS: Median age was 73 years, and the median follow-up duration was 17 months. The 5-year cancer-specific survival rate was 53.6% in 66 patients treated with adjuvant chemotherapy, which was significantly higher than that in those without adjuvant chemotherapy (34.0%, P = 0.025). The absence of adjuvant chemotherapy (hazard ratio = 2.114, P = 0.004) and lymphovascular invasion (hazard ratio = 2.203, P = 0.011) was identified as independent prognostic indicators for cancer-specific death. In patients treated without neoadjuvant chemotherapy (n = 143), the absence of adjuvant chemotherapy (hazard ratio:1.887, P = 0.030) remained an independent indicator for cancer-specific death. For those treated with adjuvant chemotherapy without neoadjuvant chemotherapy, three or more adjuvant chemotherapy cycles were independently associated with favourable outcome (hazard ratio = 0.240, P = 0.009). In contrast, for neoadjuvant chemotherapy-treated patients (N = 57), adjuvant chemotherapy was not independently associated with disease recurrence or cancer-specific death. CONCLUSION: Adjuvant chemotherapy was associated with improvements in the prognosis of patients, even in those with pT3 or higher muscle-invasive bladder cancer. Although three or more cycles of adjuvant chemotherapy were effective for muscle-invasive bladder cancer patients treated without neoadjuvant chemotherapy, no therapeutic advantages were observed with additional adjuvant chemotherapy in patients treated with neoadjuvant chemotherapy.

Individualized prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men.

OBJECTIVE: To individualize prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men. METHODS: A total of 406 men aged over 70 years old with prostate-specific antigen levels between 4.0 and 20.0 ng/ml, normal digital rectal examination results and diagnosed by transrectal needle biopsy were retrospectively analyzed. The patients were divided into a no/favorable-risk cancer group or an unfavorable-risk cancer group based on their Gleason score and the number of positive cores. Prostate-specific antigen levels, percent free prostate-specific antigen level, prostate transition zone volume and the number of previous biopsies were used to discriminate between the two groups. The optimal individualized prostate-specific antigen threshold values based on the other variables that gave a sensitivity of 95% for the detection of unfavorable-risk cancer were calculated using a boosting method for maximizing the area under the receiver operating characteristic curve. RESULTS: A total of 66 men had favorable-risk cancer, and 139 had unfavorable-risk cancer. The area under the receiver operating characteristic curve of the combination model determined by the boosting method for maximizing the area under the receiver operating characteristic curve was 0.852. The sensitivity and specificity of the threshold values for the detection of unfavorable-risk cancer were 95 and 36%, respectively. By using the threshold values, 100 (25%) of the subjects with no/favorable-risk cancer could have avoided undergoing biopsies, with a <5% risk of missing the detection of unfavorable-risk cancer. CONCLUSIONS: These individualized prostate-specific antigen threshold values may be useful for determining an indication of prostate biopsy for elderly men to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy.

Vitamin E succinate induced apoptosis and enhanced chemosensitivity to paclitaxel in human bladder cancer cells in vitro and in vivo.

There have been several studies on the antitumor activities of vitamin E succinate (alpha-TOS) as complementary and alternative medicine. In the present study, we investigated the cytotoxic effect of alpha-TOS and the enhancement of chemosensitivity to paclitaxel by alpha-TOS in bladder cancer. KU-19-19 and 5637 bladder cancer cell lines were cultured in alpha-TOS and/or paclitaxel in vitro. Cell viability, flow cytometric analysis, and nuclear factor-kappa B (NF-kappaB) activity were analyzed. For in vivo therapeutic experiments, pre-established KU-19-19 tumors were treated with alpha-TOS and/or paclitaxel. In KU-19-19 and 5637 cells, the combination treatment resulted in a significantly higher level of growth inhibition, and apoptosis was significantly induced by the combination treatment. NF-kappaB was activated by paclitaxel; however, the activation of NF-kappaB was inhibited by alpha-TOS. Also, the combination treatment significantly inhibited tumor growth in mice. In the immunostaining of the tumors, apoptosis was induced and proliferation was inhibited by the combination treatment. Combination treatment of alpha-TOS and paclitaxel showed promising anticancer effects in terms of inhibiting bladder cancer cell growth and viability in vitro and in vivo. One of the potential mechanisms by which the combination therapy has synergistic cytotoxic effects against bladder cancer may be that alpha-TOS inhibits NF-kappaB induced by chemotherapeutic agents.

Docetaxel in combination with prednisolone for hormone refractory prostate cancer.

OBJECTIVE: The objective of this study was to evaluate the efficacy and toxicity of docetaxel in combination with prednisolone in Japanese patients with hormone refractory prostate cancer. METHODS: Twenty patients with hormone refractory prostate cancer (HRPC) were administered a treatment regimen consisting of docetaxel 75 mg/m(2) once every 3 or 4 weeks and prednisolone 5 mg twice daily at our institution between 2006 and 2008. RESULTS: The patients received a median of 5.5 cycles of treatment (range, 2-12 cycles). Nine of the 20 patients (45%) had a >or=50% decrease in serum prostate-specific antigen (PSA). The median duration of response was 4 months (range, 1-11 months). The number of cycles performed, the presence of bone metastasis and the extent of disease had statistically significant associations with the response. Three patients had a transient PSA rise among the patients who ultimately had a response. Grade 3/4 leukopenia and neutropenia occurred in 80.0% and 85.0% of the patients, respectively. Interstitial pneumonia occurred in only one patient; however, the patient recovered. Finally, no treatment-related deaths were seen during the observation period. CONCLUSIONS: The combination of docetaxel 75 mg/m(2) every 3 weeks and prednisolone 10 mg daily was effective and well tolerated in Japanese patients with HRPC. The results of this study suggest that a decision concerning discontinuation of this treatment should be carefully considered because a transient PSA rise was observed. Although interstitial pneumonia was rare, the potential risk of its development should be taken into consideration.

Predicting the probability of significant prostate cancer in Japanese men with serum prostate-specific antigen less than 10 ng/mL: development of a novel pre-biopsy nomogram.

OBJECTIVES: To develop and assess a new nomogram incorporating pre-biopsy clinical data to predict significant prostate cancer in Japanese men with a serum prostate-specific antigen (PSA) level of less than 10 ng/mL. METHODS: We collected pre-biopsy data from 620 men with a serum total PSA of less than 10 ng/mL. They included 491 men with a negative biopsy and 129 men who were confirmed to have histological prostate cancer and subsequently underwent radical prostatectomy. Clinically significant tumors were defined as those with a tumor volume larger than 0.5 mL and/or a Gleason score of 7 or more. RESULTS: One hundred and seven prostatectomy patients had clinically significant cancers. Stepwise multivariate logistic regression analysis showed that digital rectal examination findings, PSA adjusted for transition zone volume and free-to-total PSA ratio were the significant independent predictors of significant cancers (P < 0.0001). Using these pre-biopsy independent factors, a nomogram was developed to predict significant cancers. According to a receiver operating characteristics analysis, the nomogram showed an area under the curve of 0.831. CONCLUSION: This represents the first nomogram to predict the probability of clinically significant cancers before biopsy. This tool is most likely to be useful in the management of patients with moderate to elevated PSA.

Ureterosciatic Hernia Treated with Laparoscopic Intraperitonization of the Ureter.

Background: Ureterosciatic hernia (USH) is a rare benign disease. We report a case of USH treated with laparoscopic intraperitonization of the ureter. Case Presentation: A 70-year-old woman was admitted to our hospital with right abdominal pain lasting for 2 months. CT showed right hydronephrosis and invagination of the right ureter into the right sciatic foramen. She underwent retrograde ureterography, which revealed abnormal tortuosity of the right lower ureter, and was found to have USH. We performed laparoscopic intraperitonization of the ureter and she presented good postoperative course. Conclusion: Laparoscopic intraperitonization of the ureter can be a useful treatment for USH.

Preoperative prognostic nomogram (probability table) for renal cell carcinoma based on TNM classification.

PURPOSE: Recently several prognostic nomograms have been developed to predict the prognosis of malignant diseases, including renal cell carcinoma. However, to our knowledge a preoperative prognostic nomogram that predicts survival in patients with renal cell carcinoma is not available. We developed a preoperative nomogram based on the TNM classification that predicts cause specific survival in patients with renal cell carcinoma. MATERIALS AND METHODS: A total of 545 patients with renal cell carcinoma, including metastatic disease, who underwent radical nephrectomy or nephron sparing surgery at our institution were included in the study. Cases were staged according to the 2002 UICC TNM system, 6th edition. T, N and M factors were used as prognostic factors and a Cox proportional hazards regression model was developed to predict cause specific survival. A nomogram to predict cause specific survival was developed by repeating the analysis on 200 bootstrap samples. To validate the nomogram a concordance index was estimated and calibration was also examined by plotting the predictions made by the nomogram. RESULTS: Overall 1, 3 and 5-year patient survival was 95.2%, 92.0% and 89.9%, respectively. T, N and M factors were significant prognostic factors in the Cox proportional hazards regression model. Using the combined TNM factors we developed a nomogram predicting 1, 3 and 5-year cause specific survival rates. The nomogram had excellent ability to discriminate, as evidenced by a concordance index of 0.81, and it was generally well calibrated. CONCLUSIONS: The preoperative information shown by this nomogram may be important for obtaining informed consent from patients with renal cell carcinoma who have indications for surgery.

Tumour length of the largest focus predicts prostate-specific antigen-based recurrence after radical prostatectomy in clinically localized prostate cancer.

OBJECTIVE: To investigate the possible significance of tumour dimensional variables, including maximum tumour diameter (MTD), maximum tumour area (MTA) and total tumour volume (TTV), with standard prognostic factors for predicting prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Serial whole sections of the prostate from 164 patients who had RP for localized prostate cancer were investigated. Cox proportional hazards regression models were used for univariate and multivariate analyses to test the relationships between biochemical failure and clinicopathological factors, including tumour dimensional variables. The results were analysed retrospectively to develop a prognostic factor-based model for risk stratification. RESULTS: In the univariate Cox proportional hazard model, pathological T stage, Gleason score, perineural invasion, microvascular invasion, positive surgical margins, MTD, MTA and TTV were significantly associated with biochemical failure. In the multivariate Cox proportional hazard model using a stepwise inclusion of these factors, Gleason score, positive surgical margins and MTD were independent indices in association with biochemical failure. Using the three statistically significant variables, the relative risk of biochemical failure could be calculated. CONCLUSION: These results imply that MTD is possibly one of the most important prognostic factors for predicting biochemical recurrence after RP. As calculating the MTD on the section a rapid, simple and objective method, it can be used instead of the TTV calculation. The prognostic factor- based risk stratification might help clinicians to predict biochemical failure after RP.

Remarkable response to abiraterone acetate in castration-resistant prostate cancer patient with aggressive liver metastasis.

INTRODUCTION: The number of treatment options for metastatic castration-resistant prostate cancer has increased in recent years. Abiraterone, which selectively inhibits CYP17 in the androgen synthesis pathway, is widely used. Liver metastasis is one of the worst prognostic factors in metastatic castration-resistant prostate cancer. Only a few case reports have shown abiraterone successfully treated the liver metastasis of metastatic castration-resistant prostate cancer. CASE PRESENTATION: A 62-year-old man with prostate-specific antigen of 16.69 ng/mL was diagnosed with Gleason 8 (3 + 5) poorly differentiated prostate adenocarcinoma. Androgen deprivation therapy and sequential anti-androgen replacement were performed; however, the disease advanced to castration-resistant prostate cancer with liver metastasis. Prior to docetaxel, abiraterone achieved marked improvements in liver metastasis and prostate-specific antigen. CONCLUSION: Metastatic castration-resistant prostate cancer patients with visceral metastasis were excluded from COU-AA-302, which is phase III trial on abiraterone prior to docetaxel. Although docetaxel is the recommended treatment for the visceral metastasis of castration-resistant prostate cancer according to the European Association of Urology guidelines, abiraterone also has potential as a treatment option.

The novel NF-kappaB activation inhibitor dehydroxymethyl-epoxyquinomicin suppresses anti-Thy1.1-induced glomerulonephritis in rats.

BACKGROUND: NF-kappaB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-kappaB in inflammatory renal diseases. Therefore, NF-kappaB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl-epoxyquinomicin (DHMEQ), a novel NF-kappaB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). METHODS: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-kappaB activation was analyzed by a fluorescent electrophoretic mobility shift assay. RESULTS: On day 7, DHMEQ treatment resulted in marked inhibition of NF-kappaB, decreased proteinuria (223.2 +/- 42.3 vs. 434.8 +/- 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 +/- 0.38 vs. 1.07 +/- 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 +/- 1.2 vs. 31.2 +/- 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. CONCLUSION: DHMEQ inhibited NF-kappaB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.

The predictors of local recurrence after radical cystectomy in patients with invasive bladder cancer.

OBJECTIVES: To examine the association between local recurrence and distant metastasis or disease-specific survival and identify independent factor predictors for local recurrence. METHODS: We identified a study population of 146 consecutive patients treated surgically for invasive bladder cancer at our institution between 1987 and 2003. We clarified the relationship among local recurrence, distant metastasis and disease-specific survival and identified significant predictors for local recurrence. RESULTS: Local recurrence developed in 26 (17.8%) of the 146 patients at a median of 10 months (range, 1-73 months) after cystectomy. It was independently associated with distant metastasis in addition to the number of retrieved lymph nodes. The 2- and 5-year metastasis-free rates were 86.7 and 76.5% in patients without local recurrence and 26.5 and 0% in those with local recurrence (P < 0.001), respectively. The presence or absence of local recurrence and tumor grade were independent predictors of disease-specific survival. The 2- and 5-year disease-specific survival rates were 93.5 and 88.3% in patients without local recurrence and 55.1 and 35.4% in those with local recurrence (P < 0.001). The presence of concomitant adenocarcinoma component, pathological nodal involvement and the number of retrieved lymph nodes were independent predictors of local recurrence. CONCLUSIONS: Local recurrence was independently associated with distant metastasis and disease-specific survival. Patients who have the predictive factors described above may benefit from integrated surgical therapies with post-operative adjuvant chemotherapy.

Simple stratification of survival using bone scan and serum C-reactive protein in prostate cancer patients with metastases.

BACKGROUND: IL-6 has been reported to be a significant prognostic factor for prostate cancer and induces synthesis of C-reactive protein (CRP) by hepatocytes. The present study was undertaken to evaluate the clinical value of serum CRP in prostate cancer patients with metastases. METHODS: The prognostic significance of serum CRP as well as tumor histology, extent of disease (EOD) on bone scan, serum levels of prostate-specific antigen (PSA) and alkaline phosphatase (ALP) and hemoglobin was assessed using Cox's proportional hazards model analyses in 126 prostate cancer patients with metastases treated with endocrine therapy. RESULTS: Serum levels of CRP, PSA and ALP significantly increased and hemoglobin significantly decreased with advancing EOD grade. Univariate analysis demonstrated that EOD, CRP, PSA, ALP, hemoglobin and tumor histology are significantly associated with disease-specific survival. Multivariate analysis demonstrated that serum CRP and EOD were significant prognostic factors. The 5-year survival rates in low-risk patients (CRP < or = 0.15 mg/dl and EOD < or = 1) and high-risk patients (CRP > 0.15 mg/dl and EOD > or = 2) were 74 and 24%, respectively. CONCLUSION: These results indicate that a combination of serum CRP and EOD can identify patients with a poor prognosis who may be candidates for innovative treatments among prostate cancer patients with metastases.

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer.

OBJECTIVE: The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated. METHODS: TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis. RESULTS: Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without (P < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers. CONCLUSIONS: Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.

Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer.

OBJECTIVES: To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer. METHODS: One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease. RESULTS: Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer (P < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters. CONCLUSIONS: The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.

Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer.

BACKGROUND: Angiotensin II (AII) type 1 receptor (AT1R) antagonists are used widely as antihypertensive agents, and long-term AT1R blockade may have a protective effect against cancer. We previously demonstrated that specific AT1R blockade with candesartan, an AT1R antagonist, inhibited vascular endothelial growth factor (VEGF) production and dramatically decreased lung metastasis of renal cancer by inhibiting tumor angiogenesis. This study was then undertaken to investigate the effects of AT1R blockade using candesartan in prostate cancer (PCa). METHODS: We first determined whether hormone-independence is associated with tumor angiogenesis and AT1R expression. Accordingly, we postulated that AT1R blockade may affect angiogenesis in androgen-independent PCa rather than in androgen-dependent PCa, and investigated the effects of AII and candesartan on PCa cell lines and a tumor xenograft model. RESULTS: A human hormone-refractory PCa (HRPC) and C4-2 androgen-independent PCa cell line showed significantly higher expression of VEGF, MVD, and AT1R than did human androgen-dependent PCa and an LNCaP androgen-dependent PCa cell line. In vitro, AII and candesartan did not directly affect the proliferation of LNCaP and C4-2 cells, but candesartan significantly suppressed VEGF production in C4-2 cells. In vivo, candesartan significantly suppressed VEGF expression, serum PSA concentration and tumor growth (1.1 +/- 0.2, 45.0 +/- 17.6 ng/ml, 235.8 +/- 37.4 mm(3)) in C4-2 xenografts in castrated mice, compared with the controls (2.4 +/- 0.6, 376.7 +/- 74.2 ng/ml, 830.8 +/- 147.6 mm(3)). CONCLUSIONS: Candesartan exerted preventive effects on HRPC, rather than on androgen-sensitive PCa, through the inhibition of tumor angiogenesis.

Ureteral Stone in the Distal Blind-ending Branch of a Bifid Ureter.

A bifid ureter with a distal blind-ending branch is a rare congenital anomaly. Most patients are asymptomatic; only patients with complications, such as infection, vesicoureteral reflux, or stone formation, present symptoms. We describe the case of a patient with urinary stone located in the distal blind-ending branch of a bifid ureter diagnosed during transurethral lithotripsy. Preoperative noncontrast-enhanced computed tomography did not reveal a stone in the distal blind-ending branch of the bifid ureter, but a rigid ureteroscope did; however, it could not reach the stone. Therefore, the stone was extracted using a basket catheter under a flexible ureteroscope.

Prevention of cancer cachexia by a novel nuclear factor {kappa}B inhibitor in prostate cancer.

PURPOSE: To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of a new nuclear factor kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer. EXPERIMENTAL DESIGN: The association between serum IL-6 levels and variables of cachexia was evaluated in 98 patients with prostate cancer. The inhibitory effects of DHMEQ on IL-6 secretion and cachexia were investigated in in vitro and in vivo studies using JCA-1 cells derived from human prostate cancer. RESULTS: Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumor-bearing mice as well as in prostate cancer patients with progressive disease. IL-6 secretion was significantly inhibited in JCA-1 cells exposed to DHMEQ. Intraperitoneal administration of DHMEQ (8 mg/kg) to tumor-bearing mice produced a significant amelioration of the reduction in body weight, epididymal fat weight, gastrocnemius muscle weight, hematocrit, and serum levels of triglyceride and albumin when compared with administration of DMSO or no treatment. DHMEQ caused a significant decrease of serum IL-6 level in JCA-1 tumor-bearing mice (all P < 0.05). CONCLUSIONS: These results suggested an association between serum IL-6 and cachexia in patients with prostate cancer and in JCA-1 tumor-bearing mice and that a new NF-kappaB inhibitor, DHMEQ, could prevent the development of cachexia in JCA-1 tumor-bearing mice presumably through the inhibition of IL-6 secretion. DHMEQ seems to show promise as a novel and unique anticachectic agent in hormone-refractory prostate cancer.

Endocytoscopy: novel endoscopic imaging technology for in-situ observation of bladder cancer cells.

BACKGROUND AND PURPOSE: Recent advances in endoscopy have enabled microscopic imaging of live bladdercancer cells in situ. The newly developed Endocystoscopy system (Olympus Medical Systems Co., Tokyo, Japan) is a flexible digital endoscope that has more than a 450-fold magnifying power on a video monitor. PATIENTS AND METHODS: This supermagnifying endoscope was used to evaluate bladder carcinoma in five patients through the working channel of a rigid cystoscope. RESULTS: The cell structure and nuclear morphology were imaged adequately compared with conventional hematoxylin and eosin staining of a biopsy specimen. The tumors were graded correctly in four of five cases. CONCLUSION: This novel technology appears to be useful for histologic diagnosis during endoscopic examinations, potentially allowing us to avoid a conventional biopsy.

Suppression of hormone-refractory prostate cancer by a novel nuclear factor kappaB inhibitor in nude mice.

We have synthesized and explored the feasibility of using a novel nuclear factor (NF) kappaB inhibitor, a dehydroxymethylepoxyquinomicin designated as DHMEQ, against prostate cancer. The activity of NFkappaB, evaluated by transient transfection of a luciferase reporter DNA containing a specific binding sequence for NFkappaB, was inhibited by DHMEQ in three human hormone-refractory prostate cancer cell lines, DU145, JCA-1, and PC-3. Statistically significant growth inhibition was achieved by 20 micro g/ml of DHMEQ, and marked levels of apoptosis were induced 48 h after DHMEQ administration in vitro. Electrophoretic mobility shift assay showed that DHMEQ completely inhibited NFkappaB DNA binding activity in JCA-1 cells. Furthermore, i.p. administrations of DHMEQ significantly inhibited pre-established JCA-1 s.c. tumor growth in nude mice without any side effects. Our result indicates the possibility of using a novel NFkappaB activation inhibitor, DHMEQ, as a new treatment strategy against hormone-refractory prostate cancer.

Modulation of bcl-2 family proteins in MAPK independent apoptosis induced by a cdc25 phosphatase inhibitor Cpd 5 in renal cancer cells.

Protein phosphatases have been classified into two basic types, namely protein serine/threonine phosphatase (PP), and protein tyrosine phosphatase (PTP). Cpd 5 is a selective inhibitor of cdc25 phosphatases, which belong to members of PTPs and regulate cell proliferation by controlling cyclin-dependent kinases (cdks). The present study was undertaken to investigate the potential utility of Cpd 5 as an anti-neoplastic agent for renal cell carcinomas (RCCs). Three renal cancer cell lines, 769P, Sw839, and A498 were used. The effects of Cpd 5 on the viability of renal cancer cell lines was analyzed using an Alamar Blue assay. Apoptosis was determined by flow cytometric TUNEL analysis. Changes in the expression of cdc25 phosphatases, mitogen-activated protein kinases (MAPKs), and bcl-2 family proteins were detected using Western blot analysis. The apoptosis-inducing effect of Cpd 5 on human RCC tissue was analyzed through TUNEL staining of organ cultures from RCCs. Cpd 5 showed a strong cytotoxicity against all renal cancer cell lines with an apoptosis-inducing effect. All cell lines treated with Cpd 5 resulted in a down-regulation of cdc25A, cdc25B, and cdc25C, however, the MAPK pathways were not affected. In addition, the up-regulation of bax, and the down-regulation of bcl-2 and bcl-xL, was observed. In organ cultures from RCCs, TUNEL-positive apoptotic nuclei were observed when treated with Cpd 5. Cpd 5 was thus found to effectively inhibit the proliferation of human renal cancer cells while also inducing apoptosis by inhibiting cdc25 phosphatases and modulating bcl-2 family proteins. The administration of Cpd 5 may thus be an effective therapeutic approach for RCCs.