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Biomedical subjects

Yoichi Arai

Publications and source records attributed to Yoichi Arai.

At least 55 records · Page 3Linked to original sources

Salvage radiotherapy for biochemical recurrence after radical prostatectomy.

OBJECTIVE: To evaluate the clinical outcome of salvage radiotherapy (RT) for biochemical recurrence after radical prostatectomy (RP) at our institution. PATIENTS AND METHODS: Between March 1999 and January 2004, 37 patients had salvage RT for prostate-specific antigen (PSA) failure after RP, including eight who had had neoadjuvant hormone therapy. After surgery, PSA was measured with ultrasensitive immunoassays. In all patients RT was delivered to the prostatic bed at a total dose of 60 Gy with a four-field box technique. RESULTS: The median (range) PSA level before salvage RT was 0.146 (0.06-3.216) ng/mL and RT was started at a PSA level of <0.5 ng/mL in 34 of the 37 patients (92%). With a median follow-up of 31.9 (0-69.8), months, 11 patients (30%) had disease progression after RT and the 3- and 5-year progression-free probability was 74% and 54%, respectively. Univariate analysis showed that clinical and pathological tumour stages and PSA level before RT (>0.15 vs < or = 0.15 ng/mL) were significant predictors of disease progression. There were no late adverse events related to RT. CONCLUSION: Salvage RT for biochemical failure after RP at a low PSA level, using ultrasensitive immunoassays for monitoring, is a reasonably effective treatment. A relatively low radiation dose (60 Gy) seems to be effective.

Adenocarcinoma↗

In situ androgen producing enzymes in human prostate cancer.

Androgens have been proposed to be actively produced in situ in human prostate cancer. These locally produced androgens have also been considered to play important roles in the pathogenesis and development of prostate cancer. Therefore, it is important to examine the status of this in situ androgen metabolism and/or synthesis in detail in order to improve the clinical response to hormonal therapy in patients diagnosed with prostate cancer. Several studies have previously demonstrated the expression of androgen-producing enzymes such as 5alpha-reductase types 1 and 2, and 17beta-hydroxysteroid dehydrogenase type 5 (17beta-HSD5), in human prostate carcinoma cells. However, their biological significance has remained largely unknown. In this study, we evaluated the immunoreactivities of these steroidogenic enzymes in human prostate cancer obtained from surgery (n = 70), and correlated the findings with clinicopathological features of the patients. 17Beta-HSD5 immunoreactivity was detected in 54 cases (77%), 5alpha-reductase type 1 in 51 cases (73%) and 5alpha-reductase type 2 in 39 cases (56%). 5Alpha-reductase type 2 immunoreactivity was significantly correlated with that of androgen receptor (AR), and 17beta-HSD5 positive cases were significantly associated with clinical stage (TNM stage pT3 vs pT2). These data all suggest that androgen-producing enzymes, such as 5alpha-reductase type 1 and type 2, and 17beta-HSD5 are expressed in a majority of prostate cancers, and are involved in the local production and actions of androgens in prostate cancers.

17-Hydroxysteroid Dehydrogenases↗

[The Japanese translation and cultural adaptation of Expanded Prostate Cancer Index Composite (EPIC)].

PURPOSE: To develop a Japanese version of the Expanded Prostate Cancer Index Composite (EPIC): originally designed to measure the Quality of Life of localized prostate cancer patients, after careful assessments of cross-cultural equivalence, face validity and practically. METHODS: We translated the original version that consisted of 50 items into a preliminary Japanese version. This multi-stage procedure included a forward-translation, back-translation and discussion with the original developer. Additionally, we tested the preliminary Japanese version on 11 localized prostate cancer patients and identified problems with its cross-cultural equivalence, practicality. Based on the findings of this pretest, we revised the Japanese version. Consensus by discussion among all researchers was obtained through out this process. RESULTS: The original developer reviewed the back-translation of the preliminary Japanese version: some wording was revised. In the pretest, the average age of patients was 68.8 years old. Four of the sexual subscale showed over 10 percent missing data. In five items, all patients chose identical answers. We conducted an in-depth qualitative investigation of these items. The average response time was 11.7 minutes. We revised the Japanese to reflect patients' opinions as much as possible. Items which were showed problems in terms of cross-cultural adaptation included questions measuring 'bother' and two items of the sexual subscale. The wordings of these items were revised so that Japanese patients could easier understand them. We ensured that the original developer's intentions remained the same. The original developed approved all revisions. CONCLUSION: We translated and adapted the original EPIC to the Japanese culture. The Japanese version of EPIC was found to be functional in the pretest.

Asian People↗

[Radical prostatectomy for localized prostate cancer].

With widespread use of PSA screening, radical prostatectomy has gained popularity among Japanese urologists over the last decade. Recent understanding of pelvic anatomy and improvement in surgical technique have substantially reduced its morbidity. Early recovery of urinary continence is possible and improvement of sexual function after surgery may be enhanced by use of sildenafil and nerve reconstructive surgery. As prostate cancer is increasingly diagnosed at early stages and therefore with more favorable survival outcomes, the basis on which patients select primary therapy has shifted toward considerations of health-related quality of life. Accordingly, QOL assessment has become an important form of outcomes based research that may weigh heavily on the treatment selection by patients.

Erectile Dysfunction↗

[A randomized study of prophylactic intravesical instillation of pirarubicin (THP) prior to transurethral resection of superficial bladder cancer].

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of pirarubicin (THP) prior to transurethral resection (TUR) of superficial bladder cancer. A total of 63 patients were randomized into two groups, the THP group and the control group. In the THP group, 30 mg of THP dissolved in 50 ml saline was administered 4 times intravesically for 4 consecutive days before TUR. In the control group, no instillation was performed before TUR. The patients were followed by cystoscopy and urinary cytology every 3 months. The non-recurrence rates in the THP group and control group were 54.1% versus 37.6% at 1 year and 40.4% versus 26.8% at 2 years, respectively (P = 0.086). Time to recurrence for tumors larger than 1 cm was significantly longer in the THP group (P = 0.0137). Time to recurrence for single and grade 1+2 tumors tended to be longer in the THP group (P = 0.09, P = 0.079). No significant adverse effects were observed in any patient. Our findings suggest that intravesical THP instillation prior to TUR would be effective for patients with single, low grade lesions larger than 1 cm of superficial bladder cancer.

Administration, Intravesical↗

Gene expression profiling identifies a set of transcripts that are up-regulated inhuman testicular seminoma.

Seminoma constitutes one subtype of human testicular germ cell tumors and is uniformly composed of cells that are morphologically similar to the primordial germ cells and/or the cells in the carcinoma in situ. We performed a genome-wide exploration of the genes that are specifically up-regulated in seminoma by oligonucleotide-based microarray analysis. This revealed 106 genes that are significantly and consistently up-regulated in the seminomas compared to the adjacent normal tissues of the testes. The microarray data were validated by semi-quantitative RT-PCR analysis. Of the 106 genes, 42 mapped to a small number of specific chromosomal regions, namely, 1q21, 2p23, 6p21-22, 7p14-15, 12pll, 12p13, 12q13-14 and 22q12-13. This list of up-regulated genes may be useful in identifying the causative oncogene(s) and/or the origin of seminoma. Furthermore, immunohistochemical analysis revealed that the seminoma cells specifically expressed the six gene products that were selected randomly from the list. These proteins include CCND2 and DNMT3A and may be useful as molecular pathological markers of seminoma.

Animals↗

Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor.

Trophinin is a membrane protein that is potentially involved in human embryo implantation by mediating homophillic cell adhesion between trophoblastic cells and endometrial cells. Trophinin expression by maternal cells may be induced by the embryo that secretes human chorionic gonadotropin (hCG). Because the process of tumor metastasis resembles that of trophoblast invasion and proliferation during embryo implantation, we hypothesized that testicular cancers that synthesize hCG express trophinin thus becoming aggressive trophoblast-like cells. We screened paraffin-embedded orchiectomy specimens of 158 patients with testicular germ cell tumor by immunohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage I, 14 of 24 (58%) in stage II, and 41 of 43 (95%) in stage III (P < 0.001). Thus, trophinin expression positively correlates with clinical stage. Remarkably, trophinin was found in all of the cases (33 of 33) with lung metastasis. The levels of serum hCG-beta were significantly higher in the patients with trophinin-positive tumors than those with trophinin-negative tumors (P = 0.004). To determine whether trophinin promotes aggressiveness of the cell, trophinin-negative human seminona cell line JKT-1 was stably transfected with a mammalian expression vector containing trophinin cDNA. In vitro assays revealed that trophinin-expressing JKT-1-Tro cells are more invasive than JKT-1-mock cells, whereas there are no differences between JKT-1-Tro and JKT-1-mock in their proliferation activity. Upon orthotopic inoculation to athymic nude mice, JKT-1-Tro cells exhibited i.p. metastases in all of the mice (n = 5), whereas JKT-1-mock produced no metastases (n = 5). These results suggest strongly that trophinin enhances invasiveness of the cells and promotes metastasis of testicular germ cell tumor.

Animals↗

Inhibition of motility and invasiveness of renal cell carcinoma induced by short interfering RNA transfection of beta 1,4GalNAc transferase.

Human renal cell carcinoma (RCC) has been characterized by remarkable changes in ganglioside composition. TOS1 cells, typical of metastatic RCC, are characterized by predominance of GM2 as monosialoganglioside, and beta 1,4GalNAc disialyl-Lc(4) (RM2 antigen) as disialoganglioside [J. Biol. Chem. 276 (2001) 16695]. In order to observe the functional role of gangliosides in RCC malignancy, TOS1 cells were transfected with short interfering RNA (siRNA) based on open reading frame sequence of beta 1,4GalNAc transferase (beta 1,4GalNAc-T), and its disordered sequence of siRNA (dsiRNA) as control. In siRNA transfectant, beta 1,4GalNAc-T mRNA level and GM2 expression were greatly reduced, whereby GM3 expression appeared. In contrast, RM2 antigen level was unchanged, even though it has the same beta 1,4GalNAc epitope at the terminus. dsiRNA transfectant showed no change of beta 1,4GalNAc-T mRNA and did not express GM3. Concomitant with reduction of GM2 and appearance of GM3, siRNA transfectant showed greatly reduced motility and invasiveness, although growth rate was unaltered. Both transfectants with siRNA and dsiRNA expressed the same level of tetraspanin CD9. Since CD9/GM3 complex is known to reduce integrin-dependent motility and invasiveness [Biochemistry 40 (2001) 6414], it is plausible that motility and invasiveness of siRNA transfectant of TOS1 cells may be reduced by enhanced formation of such complex.

Antigens↗

Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy.

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.

Carbohydrates↗

Identification by proteomic analysis of calreticulin as a marker for bladder cancer and evaluation of the diagnostic accuracy of its detection in urine.

BACKGROUND: New methods for detection of bladder cancer are needed because cystoscopy is both invasive and expensive and urine cytology has low sensitivity. We screened proteins as tumor markers for bladder cancer by proteomic analysis of cancerous and healthy tissues and investigated the diagnostic accuracy of one such marker in urine. METHODS: Three specimens of bladder cancer and healthy urothelium, respectively, were used for proteome differential display using narrow-pH-range two-dimensional electrophoresis. To evaluate the presence of calreticulin (CRT) as detected by Western blotting, we obtained 22 cancerous and 10 noncancerous surgical specimens from transurethral resection or radical cystectomy. To evaluate urinary CRT, we collected 70 and 181 urine samples from patients with and without bladder cancer, respectively. Anti-CRT COOH-terminus antibody was used to detect CRT in tissue and urine. RESULTS: Proteomic analysis revealed increased CRT (55 kDa; pI 4.3) in cancer tissue. Quantitative Western blot analysis showed that CRT was increased in cancer tissue (P = 0.0003). Urinary CRT had a sensitivity of 73% (95% confidence interval, 62-83%) at a specificity of 86% (80-91%) for bladder cancer in the samples tested. CONCLUSIONS: Proteomic analysis is useful in searching for candidate proteins as biomarkers and led to the identification of urinary CRT. The diagnostic accuracy of urinary CRT for bladder cancer appears comparable to that of Food and Drug Administration-cleared urinary markers, but further studies are needed to determine its diagnostic role.

Aged↗

Gemcitabine plus carboplatin; and gemcitabine, docetaxel, and carboplatin combined chemotherapy regimens in patients with metastatic urothelial carcinoma previously treated with a platinum-based regimen: preliminary report.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of two combined chemotherapy regimens in the treatment of previously treated metastatic urothelial carcinoma: gemcitabine plus carboplatin (GC), and gemcitabine, docetaxel, and carboplatin (GDC). METHODS: Sixteen patients with metastatic urothelial cancer, previously treated with a platinum-based regimen, were studied. GC (gemcitabine 750 mg/m(2), on days 1, 8, and 15; carboplatin 200 mg/m(2), on day 2) was administered every 28 days to 15 patients. GDC (gemcitabine 750 mg/m(2), on days 1 and 8; docetaxel 50 mg/m(2), on day 1; carboplatin 200 mg/m(2) on day 1) was administered every 21 days to 9 patients. Eight of the 9 GDC-treated patients had earlier been treated with GC and had become refractory. RESULTS: With the GC therapy, 7 of the 15 treated patients (47%; 95% confidence interval, 21%-73%) showed an objective response, with 3 achieving a clinical complete response (CR) and 4 a partial response (PR). With the GDC therapy, 6 of the 9 treated patients (67%; 95% confidence interval, 29%-92%) showed an objective response, with 1 achieving CR and 5, PR. Five of the 8 (63%) GC-refractory patients responded to GDC therapy. The median duration of response was 4 months (range, 2-10+ months) on GC therapy, and 3 months (range, 3-5 months) on GDC therapy. Toxicities associated with GC were less than those with GDC. CONCLUSION: GC was effective for refractory metastatic urothelial cancer, and GDC was effective for GC-refractory cancer. The aim of this study was to evaluate the efficacy and safety of two combined chemotherapy regimens in the treatment of previously treated metastatic urothelial carcinoma: gemcitabine plus carboplatin (GC), and gemcitabine, docetaxel, and carboplatin (GDC).

Aged↗

Post-laminectomy long-term survival of a patient with spinal cord compression secondary to metastatic prostate cancer.

Spinal cord compression is a skeletal-related event in advanced malignancies and is associated with serious morbidity and poor prognosis. Despite the palliative nature of laminectomy treatment, it is important to prevent neurological deficits and relieve pain as a means to improve quality of life. Here we report on a prostate cancer patient with spinal cord compression who became ambulant from paraparesis after he underwent a decompression laminectomy; he survived for 9.5 years with good quality of life.

Decompression, Surgical↗

A case of severe hemorrhagic cystitis following bone marrow transplantation.

Hemorrhagic cystitis (HC) is a common adverse effect caused by the preparative regimens for bone marrow transplantation. Unfortunately, an effective therapy for HC has not yet been established. Here we report a case of severe HC in which the upper as well as the lower urinary tract were severely affected, resulting in right ureteral obstruction and a contracted bladder. Hyperbaric oxygen therapy was effective in suppressing the severe HC, but the cause of HC could not be identified. Five years after the bone marrow transplantation the patient underwent augmentation ileocystoplasty with ileal ureteral replacement.

Adult↗

Laparoscopic partial nephrectomy using microwave tissue coagulator for small renal tumors: usefulness and complications.

OBJECTIVES: We evaluated the usefulness and complications of laparoscopic partial nephrectomy for small renal tumors using a microwave tissue coagulator without renal pedicle clamping. METHODS: Between September 1999 and March 2003, 19 patients with small renal tumors 11 to 45 mm in diameter underwent laparoscopic partial nephrectomy without renal ischemia. RESULTS: Six and 13 patients were treated by the transperitoneal and retroperitoneal approaches, respectively. Excluding a case with open conversion due to dense perirenal adhesions, 18 patients successfully underwent laparoscopic procedures. The mean operative time was 240 minutes with minimal blood loss in 14 patients and 100 to 400 ml in 4. In a patient, frozen sections revealed a positive surgical margin and additional resection was performed. Postoperative complications included extended urine leakage for 14 days, arteriovenous fistula and almost total loss of renal function, respectively, in a patient. With the median follow-up of 19 months, no patients showed local recurrence or distant metastasis by CT scan. CONCLUSIONS: Laparoscopic non-ischemic partial nephrectomy using a microwave tissue coagulator may be useful for treating small renal tumors because it does not require advanced laparoscopic skill. However, the indication of this procedure should be highly selective in order to minimize serious complications secondary to unexpected collateral damage to surrounding structures.

Adult↗

High incidence of inguinal hernia after radical retropubic prostatectomy.

OBJECTIVES: To assess the incidence of, and risk factors for, inguinal hernia after retropubic radical prostatectomy compared with after pelvic lymph node dissection and total cystectomy. METHODS: A total of 155 radical prostatectomies, 35 pelvic lymph node dissections, and 56 total cystectomies were included in this study. We reviewed the charts retrospectively and evaluated the incidence of, and risk factors for, inguinal hernia after surgery using Kaplan-Meier plots and a Cox proportional hazard model. RESULTS: Of 155 patients in the radical prostatectomy group, 35 patients in the pelvic lymph node dissection group, and 56 patients in the cystectomy group, 33 (21.3%), 4 (11.4%), and 3 (5.4%), respectively, developed inguinal hernias during follow-up. In the radical prostatectomy group, 27 (81.8%) of the 33 patients developed inguinal hernia within 2 years postoperatively. Multivariate Cox proportional hazard analysis revealed that prostatectomy group, past history of inguinal hernia, and body mass index of less than 23 were significant risk factors for postoperative inguinal hernia. CONCLUSIONS: The incidence of inguinal hernia after radical prostatectomy is not low. Urologists should realize that inguinal hernia is one of the major complications of radical prostatectomy and examine the groin preoperatively and postoperatively.

Aged↗

Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients.

OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level <or=4 ng/ml) rate, the 12 week overall tumor response rate (proportion with a partial response or better) and the proportion of withdrawals due to adverse drug reactions (ADRs) at follow-up. This interim analysis was undertaken after a minimum of 6 months' follow-up (median 15 months). RESULTS: The 12 week PSA normalization rate was 79.4% for MAB and 38.6% for LHRH agonist monotherapy (P < 0.001). The 12 week overall tumor response rate was 77.5 and 65.3%, respectively (P = 0.063). The withdrawal rate due to ADRs was 8.8% and 10.9%, respectively. There were differences in favor of MAB over monotherapy with respect to time to treatment failure (TTTF) (P = 0.038) and time to progression (TTP) (P = 0.016). There have been too few deaths (n = 10) to analyze survival. The profiles of adverse events and ADRs were broadly similar in the two treatment groups. CONCLUSION: In Japanese patients with advanced prostate cancer, first-line treatment with bicalutamide 80 mg in combination with an LHRH agonist is superior to LHRH agonist monotherapy in terms of the antitumor response at 12 weeks, and also time to treatment failure and progression, and does not compromise treatment safety. The study is ongoing.

Aged↗