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Biomedical subjects

Hideaki Miyake

Publications and source records attributed to Hideaki Miyake.

At least 73 records · Page 4Linked to original sources

Over expression of CD44V8-10 in human bladder cancer cells decreases their interaction with hyaluronic acid and potentiates their malignant progression.

PURPOSE: We evaluated the effects of the over expression of CD44v8-10, one of the high molecular form of CD44, on the malignant potential of UM-UC-3 human bladder cancer cells in vitro and in vivo. MATERIALS AND METHODS: We introduced CD44v8-10 complementary DNA into UM-UC-3 cells, which do not express detectable level of CD44v8-10 protein, and generated the CD44v8-10 over expressing cell line UM-UC-3/v8-10 and the vector only transfected cell line UM-UC-3/C. The effects of the introduction of CD44v8-10 into UM-UC-3 cells on the ability to bind hyaluronic acid (HA) were analyzed by the cell adhesion assay and the cell migration assay. We then evaluated tumor progression of UM-UC-3 sublines after subcutaneous and orthotopic injection into athymic nude mice. RESULTS: There were no significant differences in in vitro growth rates. UM-UC-3/v8-10 cells showed significantly decreased binding and migration ability to HA but not to other extracellular matrix proteins. Furthermore, UM-UC-3/v8-10 cells demonstrated significantly increased tumor growth after subcutaneous as well as orthotopic injection into athymic nude mice and enhanced lymph node metastasis after orthotopic injection compared with UM-UC-3/C cells. CONCLUSIONS: These findings suggest that CD44v8-10 over expression in human bladder cancer cells decreases their interaction with HA and potentiates their malignant progression.

Cell Line, Tumor↗

Oxidative DNA damage in patients with prostate cancer and its response to treatment.

PURPOSE: We evaluated the significance of oxidative DNA damage in patients with prostate cancer based on the measurement of urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and analyzed changes in urinary 8-OHdG before and after initial treatment. MATERIALS AND METHODS: A total of 82 patients with prostate cancer were included in this study. Of these 82 patients 42 underwent radical prostatectomy and the remaining 40 received hormonal therapy as initial treatment. Urinary 8-OHdG and creatinine (Cr), and serum prostate specific antigen (PSA) in these 82 patients were assessed before and 2 months after the initiation of treatment. RESULTS: The ratio of urinary 8-OHdG-to-Cr (8-OHdG/Cr) in patients with prostate cancer was significantly higher than in age matched healthy controls. Only age was significantly associated with 8-OHdG/Cr in prostate cancer cases among several clinicopathological factors, including serum PSA clinical T stage, metastasis and Gleason score. There was no significant difference in urinary 8-OHdG/Cr in 42 patients before and after radical prostatectomy, while urinary 8-OHdG/Cr in 40 patients after hormonal therapy was significantly lower than before hormonal therapy. In addition, changes in PSA after initial treatment were not related to changes in urinary 8-OHdG/Cr in either treatment group. CONCLUSIONS: These findings suggest that oxidative stress may be involved in an early event in prostate cancer development and androgen suppression is capable of decreasing oxidative stress. Accordingly androgen withdrawal therapy combined with antioxidative agents may inhibit the progression of prostate cancer.

8-Hydroxy-2'-Deoxyguanosine↗

Synergistic antitumor activity by combined treatment with gemcitabine and antisense oligodeoxynucleotide targeting clusterin gene in an intravesical administration model against human bladder cancer kotcc-1 cells.

PURPOSE: We investigated whether antisense (AS) oligodeoxynucleotide (ODN) targeting the clusterin gene enhances the cytotoxic effect of gemcitabine in human bladder cancer KoTCC-1 cells in vitro and in vivo, and evaluated the usefulness of the combined administration of AS clusterin ODN and gemcitabine using an intraperitoneal tumor cell injection model. MATERIALS AND METHODS: The cytotoxic effect of combined treatment with AS clusterin ODN and gemcitabine on in vitro KoTCC-1 growth was examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The in vivo growth inhibitory effects of combined AS clusterin ODN and gemcitabine therapy on subcutaneous KoTCC-1 tumor was also examined. The intraperitoneal tumor cell injection model, which mimics intravesical administration therapy against bladder cancer, was used to evaluate the efficacy of combined AS clusterin ODN and gemcitabine therapy. RESULTS: AS clusterin ODN treatment of KoTCC-1 cells significantly enhanced gemcitabine chemosensitivity in a dose dependent manner, decreasing gemcitabine IC50 by approximately 90%. In vivo systemic administration of AS clusterin ODN and gemcitabine significantly decreased subcutaneous KoTCC-1 tumor volume compared with scramble control ODN plus gemcitabine. Furthermore, combined administration of AS clusterin ODN plus gemcitabine resulted in significantly delayed formation of hemorrhagic ascites compared with scramble control ODN plus gemcitabine in an intraperitoneal tumor cell injection model. CONCLUSIONS: These findings suggest that AS clusterin ODN may be useful for enhancing the cytotoxicity of gemcitabine in patients with bladder cancer, particularly as a novel therapeutic strategy for intravesical instillation therapy.

Administration, Intravesical↗

Multifocal transitional cell carcinoma of the bladder and upper urinary tract: molecular screening of clonal origin by characterizing CD44 alternative splicing patterns.

PURPOSE: CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism during cancer initiation. We assessed whether multifocal transitional cell carcinoma of the urothelium is due to field change and/or intraluminal seeding and implantation. MATERIALS AND METHODS: In a series of 24 patients with synchronous and/or metachronous multiple urothelial cancers we performed reverse transcription-polymerase chain reaction analysis using a set of primers capable of amplifying all CD44 splice variant isoforms. After polymerase chain reaction products were electrophoresed band intensities with areas corresponding to the major isoforms (that is CD44s, CD44v10 and CD44v8-10) were quantified, and CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios were calculated. Moreover, p53 gene mutations in exons 4 to 11 were screened by direct DNA sequencing. RESULTS: Of these 24 cases 18 showed similar CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios in among multiple urothelial cancers in each case. However, in the remaining 6 cases these ratios were quite different among multiple cancer lesions. Furthermore, different types of p53 mutation were detected among multiple cancer lesions in only 2 of 24 cases, which also indicated different patterns of CD44 alternative splicing. CONCLUSIONS: These findings suggest that at least some multiple transitional cell carcinomas of the urothelium seem to be of independent origin based on the analysis of alternative RNA splicing of CD44. Moreover, this hypothesis was further supported by the evaluation of p53 gene mutation.

Alternative Splicing↗

Synergistic inhibition of tumor growth and metastasis by combined treatment with TNP-470 and gemcitabine in a human bladder cancer KoTCC-1 model.

PURPOSE: TNP-470 (O-(chloroacetylcarbamoyl)fumagillol) is a potent inhibitor of angiogenesis that was reported to enhance synergistically the antitumor effects of cytotoxic agents. We evaluated the effectiveness of combined treatment with TNP-470 and gemcitabine in vitro and in vivo using highly metastatic human bladder cancer KoTCC-1 cells. MATERIALS AND METHODS: The in vitro growth inhibitory and apoptotic effects of gemcitabine and/or TNP-470 on KoTCC-1 cells were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and TUNEL staining, respectively. We then evaluated the combined effect of gemcitabine and TNP-470 therapy after subcutaneous and orthotopic injection of KoTCC-1 cells into athymic nude mice. Established tumors were analyzed by TUNEL staining and immunohistochemical staining of CD31 to quantify microvessel density. RESULTS: In vitro TNP-470 enhanced the cytotoxic effect of gemcitabine on KoTCC-1 cells, decreasing its IC50 by more than 50%. This combined treatment significantly induced apoptosis compared with treatment with either agent alone. In vivo combined treatment with TNP-470 and gemcitabine significantly decreased tumor growth after subcutaneous and orthotopic injection into athymic nude mice and significantly decreased the incidence of lymph node metastasis after arthotopic injection compared with either agent alone. Immunohistochemical analysis of the subcutaneous tumor after each treatment demonstrated that gemcitabine administration significantly induced apoptotic cell death. In contrast, a significant decrease in microvessel density was observed after TNP-470 treatment. CONCLUSIONS: These findings demonstrate that TNP-470 and gemcitabine act synergistically to inhibit tumor growth and metastasis by enhancing apoptosis and suppressing angiogenesis.

Angiogenesis Inhibitors↗

Introduction of 65 kDa antigen of Mycobacterium tuberculosis to cancer cells enhances anti-tumor effect of BCG therapy.

Bacillus Calmette Guerin (BCG) immunotherapy has anti-tumorigenic effects against bladder cancer. To improve the efficacy of BCG therapy, we introduced the gene encoding the 65 kDa heat shock protein (hsp) of Mycobacterium tuberculosis into a mouse malignant melanoma cell line (B16). An expression vector harboring the 65 kDa antigen gene was transfected into B16 using Lipofectamine, then expression of the antigen was confirmed by RT-PCR and Western blotting. Several cell lines expressing 65 kDa antigen were established (B16/65 kDa). We also established a control cell line transfected with the vector alone (B16/con). All cell lines (B16, B16/con, B16/65 kDa) were injected intraperitoneally into syngeneic mice with or without BCG prior immunization and the development of tumor ascites was examined. To analyze the mechanism of the anti-tumor effect, CD4 T cells or CD8 T cells were depleted in vivo by administering the corresponding monoclonal antibody. B16/65k Da expressed the 65 kDa hsp of M. tuberculosis. The tumor growth of B16/65 kDa was slightly retarded in naive mice, but significantly inhibited by BCG. The anti-tumor effect was totally abrogated in mice deficient in CD4 T cells, suggesting that CD4 T cells are involved in this process. The 65 kDa hsp of M. tuberculosis was expressed after gene transduction in a malignant melanoma cell line and significantly enhanced the anti-tumor effect of BCG immunotherapy. CD4 T cells play an important role in this anti-tumor effect.

Animals↗

Significance of renal function in changes in acid-base metabolism after orthotopic bladder replacement: colon neobladder compared with ileal neobladder.

BACKGROUND: The objective of this study was to determine whether renal function influences the acid-base metabolism in patients undergoing orthotopic bladder replacement using intestinal segment. METHODS: Acid-base balance, serum electrolytes and renal function were studied in 30 patients with colon neobladder and 18 patients with ileal neobladder. Mean follow up was 51 months. Effects of renal function on acid-base metabolism in both types of bladder replacement were compared. Therapeutic efficacy of the sodium bicarbonate administration was also evaluated in cases with hyperchloremic acidosis. RESULTS: No significant differences were observed in any of the variables examined between the colon and ileal neobladder groups, except for potassium concentration. Although metabolic acidosis was detected using the Siggard-Anderson acid-base nomogram in eight (26.7%) and seven (38.9%) patients in the colon and ileal neobladder groups, respectively, this difference was not significant. In both the colon and ileal neobladder groups, the serum creatinine concentrations in patients diagnosed with metabolic acidosis were significantly higher than in those diagnosed with a normal metabolic status. Furthermore, as a result of severe metabolic acidosis, three (10.0%) and three (16.7%) patients in the colon and ileal neobladder groups, respectively, were administered sodium bicarbonate and their metabolic status was fully normalized. CONCLUSIONS: Despite there being no statistical difference, patients with ileal neobladder may more easily develop metabolic acidosis compared with those with colon neobladder. In addition, a close association between the serum creatinine level and the degree of metabolic acidosis was observed in both groups. However, even if severe metabolic acidosis occurs, it is relatively easy to correct using sodium bicarbonate. These findings suggest that it might be safe to use a colon segment for orthotopic bladder reconstruction in patients with higher serum creatinine levels, despite no significant difference in acid-base metabolism and detection rates of metabolic acidosis between the colon and ileal neobladder groups.

Acid-Base Imbalance↗

Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence after radical surgery.

BACKGROUND: The objective of the present study was to investigate the significance of microscopic venous invasion (MVI) as a prognostic factor for patients with renal cell carcinoma (RCC) who underwent radical surgery. METHODS: The study included a total of 157 consecutive patients with non-metastatic RCC who underwent radical surgery between January 1986 and December 2002. The median follow-up period was 45 months (range 6-162 months). Microscopic venous invasion was defined by the presence of a cancer cell in blood vessels based on the examination of hematoxylin-eosin stained specimens. Other prognostic variables were assessed by multivariate analysis to determine whether there was a significant impact on cancer-specific and recurrence-free survivals. RESULTS: Microscopic venous invasion was found in 70 patients, and of this number, 17 (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression, while only six (6.9%) of the remaining 87 patients without MVI presented with disease-recurrence and three (3.5%) died of cancer. Among the factors examined, the presence of MVI was significantly associated with age, mode of detection, tumor size, pathological stage and tumor grade; however, only pathological stage was an independent predictor for disease-recurrence, and none of these factors were available to predict cancer-specific survival in multivariate analyses. In 120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this subgroup, recurrence-free survival rates in patients with MVI were significantly lower than those in patients without MVI, and MVI was the only independent prognostic predictor for disease-recurrence in a multivariate analysis. CONCLUSION: Microscopic venous invasion is not an independent prognostic factor in patients with non-metastatic RCC who underwent radical surgery; however, it could be the only independent predictor of disease-recurrence after radical surgery for patients with pT1 or pT2 disease.

Adult↗

Long-term results of adjuvant hormonal therapy plus radiotherapy following radical prostatectomy for patients with pT3N0 or pT3N1 prostate cancer.

BACKGROUND: The objective of the present study was to evaluate the efficacy of adjuvant androgen suppression in conjunction with external beam irradiation after radical prostatectomy in patients with pathologically confirmed extraprostatic disease. METHODS: Between July 1988 and October 1999, 38 patients with pT3N0 or pT3N1 prostate cancer received adjuvant hormonal therapy and external beam irradiation following radical retropubic prostatectomy and pelvic lymphadenectomy. Administration of luteinizing hormone-releasing hormone analog or castration were initiated as an adjuvant androgen suppression within 4 weeks after surgery, whereas pelvic irradiation was performed at a median dose of 50 G within 3 months after surgery. The prognostic advantage of this combined adjuvant therapy was analyzed. RESULTS: During the median observation period of 92 months, biochemical recurrence occurred in four of the 38 patients and five patients died. Of these five patients, only one died of prostate cancer progression. The 10-year biochemical recurrence-free, cancer-specific and overall survival rates of the 38 patients were 86.7%, 90.9% and 78.7%, respectively. Among several factors examined, only tumor grade was significantly associated with biochemical recurrence-free survival in these patients; however, there were no factors that were independent predictors for biochemical recurrence, based on multivariate analysis. Furthermore, biochemical recurrence-free survival in the 38 patients was significantly superior to that in 54 patients with locally advanced disease who did not receive any postoperative therapies until biochemical recurrence; however, there was no significant difference in cancer-specific and overall survival between these two groups. CONCLUSION: Despite retrospective analysis with a relatively small number of patients, results of the present study suggest favorable effects of the combined adjuvant treatments with androgen ablation and pelvic irradiation on cancer control for patients with pT3N0 or pT3N1 disease. However, considering the absence of a significant difference in cancer-specific and overall survival between patients with and without adjuvant treatments, it might not be necessary to routinely perform combined hormonal and radiation therapies in an adjuvant setting for pT3N0 or pT3N1 prostate cancer.

Aged↗

Increased detection of clinically significant prostate cancer by additional sampling from the anterior lateral horns of the peripheral zone in combination with the standard sextant biopsy.

BACKGROUND: The objective of the present study was to investigate whether obtaining an increased number of biopsy cores by sampling additional areas, along with the standard sextant biopsy, results in a higher rate of detection of potentially insignificant prostate cancer. METHODS: We included 130 patients who underwent radical retropubic prostatectomy at our institution between January 1999 and June 2003 after being diagnosed as having prostate cancer based on systematic prostate biopsies that included the areas examined by standard sextant biopsies and the bilateral anterior lateral horns (ALHs) of the peripheral zone (PZ). Several clinicopathological factors were analyzed, focusing on the significance of additional sampling from ALHs in relation to the incidence of potentially insignificant cancer, which was defined as organ confined disease with tumor volume less than 0.5 cc and Gleason scores <7. RESULTS: According to the location of positive biopsy results, these 130 patients were divided into three groups as follows: 61 patients (46.9%) with cancer detected from the cores taken by standard sextant biopsy only (group A), 15 (11.6%) from ALHs of the PZ only (group B), and 54 (41.5%) from both sites (group C). There were no significant differences in age, incidence of abnormal digital rectal examination, prostate volume, or biopsy Gleason score among these three groups; however, pretreatment serum PSA value in group C was significantly higher than that in groups A or B. Pathological examinations of radical prostatectomy specimens demonstrated that there were no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score among the three groups; however, group C had a significantly larger tumor volume than groups A or B. Furthermore, insignificant tumor was detected in eight patients in group A (13.1%), two in group B (13.3%), and four in group C (7.4%). CONCLUSION: These findings suggest that the additional sampling of biopsy cores from ALHs does not appear to increase the detection of potentially insignificant cancer, and that biological tumor characteristics seem to be similar irrespective of cancer location on the needle biopsy.

Aged↗

Health-related quality of life after chemotherapy for advanced germ cell tumors: a comparison of standard-dose and high-dose chemotherapy.

BACKGROUND: The objective of this study was to evaluate the health-related quality of life (HRQoL) in patients with germ cell tumors who received standard-dose chemotherapy or high-dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT), and to compare the HRQoL of these patients with patients who had undergone surveillance therapy only. METHODS: Among the 102 patients included in this study, 38 underwent standard-dose cisplatin-based combination chemotherapy alone, 24 received high-dose chemotherapy with PBSCT following standard-dose chemotherapy, and 40 underwent surveillance monitoring. HRQoL was evaluated using the SF-36 survey, which contains 36 questions that assess eight quality-of-life aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. RESULTS: The follow-up period of the surveillance group was significantly longer than that of the remaining two groups receiving chemotherapy; however, scale scores were not affected by the duration of follow up in either group. No significant difference was observed in any scale scores between the patients undergoing chemotherapy and those in the surveillance group. In comparison with the general population in the USA, social functioning in both the chemotherapy and surveillance groups was significantly lower, whereas vitality in these two groups was significantly higher. Patients undergoing standard-dose chemotherapy alone had a significantly higher score for mental health than those undergoing high-dose chemotherapy. However, there were no significant differences in the remaining seven scores, irrespective of the type of chemotherapy. CONCLUSIONS: Seven of the eight scale scores of HRQoL were favorable in patients who received chemotherapy or surveillance, and no significant difference was observed between these two groups. Moreover, with the exception of the mental health score, HRQoL was not significantly affected by the type of chemotherapy. Therefore, patients who received chemotherapy, including high-dose chemotherapy with PBSCT, seem to be generally satisfied with their overall HRQoL.

Adult↗

Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model.

BACKGROUND: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system. METHODS: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody. RESULTS: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells. CONCLUSION: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms.

Animals↗

Successful treatment for squamous cell carcinoma of the female urethra with combined radio- and chemotherapy.

We report on two cases of women with locally advanced squamous cell carcinoma of the urethra. Patient 1 also displayed regional lymph node metastasis. Treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin. Complete response was obtained in both patients, including the inguinal lymph nodes of Patient 1. Patient 1 experienced recurrent inguinal lymph node metastasis on the contralateral side at 42 months after initial treatment, and the same treatment was performed followed by surgical excision. Both patients remain alive with no evidence of disease, at 12 months after recurrence in Patient 1, and at 27 months after treatment in Patient 2.

Aged↗

Advances in the management of non-seminomatous germ cell tumors during the cisplatin era: a single-institution experience.

BACKGROUND: The objectives of the present study were to review chronological changes in the long-term survival of patients with non-seminomatous germ cell tumor (NSGCT) who were treated at a single institution after the introduction of cisplatin-based combination chemotherapy. METHODS: One hundred and twenty patients with NSGCT who were treated between January 1978 and October 2001 were enrolled in this study. To evaluate chronological changes in treatment outcome between 1978 and 2001, data were analyzed according to the timing of initial treatment in two consecutive 12-year periods. The numbers of patients who were treated during 1978-1989 and 1990-2001 were 59 and 61, respectively. Patients were classified according to criteria of both the Japanese Urological Association (JUA classification) and the International Germ Cell Cancer Collaborative Group (IGCCCG classification). RESULTS: The mean follow up of surviving patients during the periods 1978-1989 and 1990-2001 was 84 months and 63 months, respectively. The overall 5-year survival rate of patients with NSGCT significantly increased from 72.8% during the period 1978-1989 to 83.6% during the period 1990-2001 (P = 0.02, log-rank test). A significant improvement in survival was found in the patients with stage III disease, according to the JUA classification, and in the patients with poor-risk disease, according to the IGCCCG classification (P = 0.004 and 0.05, respectively). CONCLUSIONS: The overall 5-year survival rate of patients with NSGCT increased significantly from 72.8% during 1978-1989 to 83.6% during 1990-2001. This improvement resulted mainly from an increased survival of patients with metastatic poor-risk NSGCT.

Adult↗

Clinical outcome of retroperitoneal lymph node dissection after induction chemotherapy for metastatic non-seminomatous germ cell tumors.

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) following induction chemotherapy has been considered a critical component in the comprehensive management of advanced non-seminomatous germ cell tumors (NSGCT). The objectives of the present study were to review the clinical outcome of patients who underwent RPLND and to evaluate the probability of necrosis alone, based on some readily available clinical data for these patients. METHODS: Forty-seven consecutive patients with NSGCT were treated with first-line chemotherapy at our institution between January 1993 and September 2002. Twenty-four of these patients, who underwent RPLND with normal values of tumor markers after induction chemotherapy, were included in the study. The cause-specific survival rate was calculated using the Kaplan-Meier method. Various predictive factors for the histology were analyzed using multivariate analysis. RESULTS: The pathological findings at resection were necrosis alone in 62.5% of cases, teratoma in 25.0%, and viable cancer in 12.5%. The cause-specific 3-year survival rate of patients who underwent complete and incomplete resection was 100% and 50.0%, respectively. Among several clinical factors, prechemotherapy tumor size less than 50 mm was found to be an independent predictor of necrosis alone (hazard ratio = 4.45, P= 0.04). CONCLUSION: Metastatic tumor size before chemotherapy appears to be one of the most important factors for the prediction of necrosis alone in the resected specimens of RPLND. The prognosis of patients might be influenced by the degree to which resection has been completed.

Adult↗

Global analysis of gene expression profiles in ileum in a rat bladder augmentation model using cDNA microarrays.

BACKGROUND: The objective of the present study was to globally characterize the changes in the gene expression profile in the ileum after long-term urine exposure in a rat ileal augmented bladder model using cDNA microarrays. METHODS: Bladder augmentation using the ileum was performed in female 8-week-old rats. The ileal epithelia used for bladder augmentation were harvested 1 and 3 months postoperatively and changes in the gene expression in these tissues were compared with that of intact ileal epithelia from sham-operated rats using cDNA microarrays consisting of 1176 rat genes. RESULTS: Marked changes in gene expression in the ileum used for bladder augmentation were observed for 30 genes (16 up-regulated and 14 down-regulated genes). The differentially expressed genes include those associated with signal transduction, cell adhesion and stress response. Subsequent evaluation of changes in two randomly selected genes from the 30 differentially expressed genes by semiquantitative reverse transcription-polymerase chain reaction demonstrated the reliability of the present cDNA microarray analyses. CONCLUSION: The present experiments identified an extensive list of genes differentially expressed in the ileum after bladder augmentation, providing valuable information for the pathophysiological assessment of patients who undergo urinary reconstruction and representing a source of novel targets for treating complications after urinary diversion.

Animals↗

Clinicopathological outcome of radical retropubic prostatectomy for 200 men with prostate cancer in a single institution in Japan.

The objective of this study was to retrospectively evaluate the clinicopathological outcome of radical retropubic prostatectomy (RRP) performed at a single institution in Japan. A consecutive series of 200 patients with prostate cancer who underwent RRP and pelvic lymphadenectomy between March 1985 and April 2003 were included in this study. The median age at RRP and the observation period were 69 years old and 43 months, respectively. Clinicopathological findings were reviewed to determine parameters providing predictive information about biochemical recurrence-free, cause-specific, and overall survivals. The pathological stage was pT0 in 7 patients (3.5%), pT2a in 43 (21.5%), pT2b in 58 (29.0%), pT3a in 42 (21.0%) pT3b in 36 (18.0%), and pT4 in 14 (7.0%). Lymph node metastasis was detected in 32 of 200 patients (16.0%). Forty-seven patients (23.5%) received neoadjuvant hormonal therapy, while 48 (24.0%) underwent hormonal therapy alone or hormonal therapy plus radiotherapy following RRP as an adjuvant treatment. During the observation period, 4 patients (2.0%) died of prostate cancer, 11 (5.5%) died of other diseases and biochemical recurrence occurred in 23 (11.5%), when biochemical recurrence was defined as prostate specific antigen (PSA) persistently greater than 0.4 ng/ml. Five-year biochemical recurrence-free, cause-specific, and overall survival rates were 83.6%, 97.7% and 91.4%, respectively. Furthermore, multivariate analyses showed that lymph node metastasis or clinical stage was an independent predictive factor for cause-specific or overall survival, respectively. These findings suggest that it would be possible to achieve a favorable cancer control for patients with localized prostate cancer, including locally advanced cases, by the RRP-based combination therapies.

Aged↗

Health-related quality of life in patients with testicular cancer: a comparative analysis according to therapeutic modalities.

Investigating health-related quality of life (HRQoL) in testicular cancer patients has become important, because of an increasing number of young survivors with recent advance of multimodal therapy. The objective of this study was to compare the HRQoL in patients with advanced testicular cancer according to the types of treatment they received. Among 130 patients included in this study, 40 underwent surveillance monitoring (group A), 64 received cisplatin-based combination chemotherapy (group B), and 26 underwent infradiaphragmatic radiotherapy (group C). HRQoL in these 3 groups were evaluated using the SF-36 survey containing 36 questions that assess 8 aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. Furthermore, HRQoL in group B were analyzed according to the experience with retroperitoneal lymph node dissection (RPLND) or high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT). The follow-up period of the chemotherapy group was significantly shorter than that of the remaining 2 groups; however, scale scores were not affected by the duration of follow-up in these 3 groups. There were no significant differences in any scale scores among the 3 groups. In comparison with the general population in the USA, social functioning in the 3 groups with testicular cancer was significantly lower, whereas vitality in these groups was significantly higher. Furthermore, in group B, there were no significant differences in any scale scores between patients with and without RPLND, while patients undergoing standard-dose chemotherapy alone had a significantly higher score for mental health than those undergoing high-dose chemotherapy following standard-dose chemotherapy despite the absence of a significant difference in the remaining 7 scores irrespective of the experience with high-dose chemotherapy. These findings suggest that 7 of the 8 scale scores of HRQoL examined by the SF-36 survey were satisfactory in patients with testicular cancer regardless of the 3 treatment modalities, and that there were no significant differences in any scale scores among these groups. Moreover, the HRQoL was not affected by experience with RPLND or high-dose chemotherapy except for mental health in patients undergoing high-dose chemotherapy. Therefore, the overall HRQoL in patients with testicular cancer may be generally favorable and not affected by differences in treatment type.

Adult↗