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Biomedical subjects

Makoto Satoh

Publications and source records attributed to Makoto Satoh.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnoea syndrome.

Patients with OSAS (obstructive sleep apnoea syndrome) demonstrate renal signs such as proteinuria, glomerular hypertrophy and focal glomerular sclerosis. We performed a clinical study to investigate the glomerular function in OSAS patients and the short-term effect of CPAP (continuous positive airway pressure) on it. OSAS patients underwent a sodium thiosulphate and p-aminohippurate double clearance test, polysomnography and ambulatory blood pressure monitoring before and a week after the induction of CPAP. Twenty-seven consecutive patients (24 males) with moderate-to-severe OSAS admitted to our hospital for the induction of CPAP, and 32 healthy donors for renal transplantation as controls participated in the study. Before treatment, the glomerular filtration rate, estimated by the sodium thiosulphate clearance test, was within normal range, and the renal plasma flow was significantly lower than normal in the OSAS patients, thus the FF (filtration fraction) value was much higher than normal. FF before CPAP was not significantly correlated with age, body mass index or blood pressure; however, indices of increased hypoxaemia correlated with increased FF values. Polysomnographic variables after CPAP showed significant improvements in all patients, and only the nocturnal blood pressures were slightly lower than before CPAP. In 21 patients who underwent the clearance test after CPAP, FF significantly decreased from 0.26 +/- 0.04 to 0.23 +/- 0.03 (P < 0.001). OSAS patients were generally in a glomerular-hyperfiltrating condition that appeared to cause the renal findings associated with OSAS. CPAP might prevent nephropathy by ameliorating the glomerular hyperfiltration in OSAS patients.

Aged↗

Ipsilateral seminal emission generated by electrostimulation of the lumbar sympathetic nerve during nerve sparing laparoscopic retroperitoneal lymph node dissection for testicular cancer.

PURPOSE: To confirm nerve preservation during laparoscopic retroperitoneal lymph node dissection we perform electrostimulation of the lumbar sympathetic nerves relevant to ejaculation. In recent cases we monitored seminal emission using endoscopy of the posterior urethra to observe the response to stimulation. MATERIALS AND METHODS: Six patients with testicular tumors underwent intraoperative stimulation of the lumbar sympathetic nerves during laparoscopic retroperitoneal lymph node dissection with a unilateral modified template. A long handled pair of bipolar electrodes was inserted through a laparoscopic port, and ipsilateral and contralateral lumbar sympathetic nerves were individually electrostimulated. Ipsilateral stimulation was performed at the preserved lumbar splanchnic nerves and contralateral stimulation was performed at the union of nerve fibers derived from the lumbar splanchnic nerve just above the superior hypogastric plexus. The side of generated seminal emission was monitored simultaneously by endoscopy of the posterior urethra. RESULTS: In all patients each electrostimulation generated unilateral seminal emission. Each stimulation of a lumbar splanchnic nerve, whether ipsilateral or contralateral, caused seminal emission only from the ejaculatory orifice of the stimulated side. CONCLUSIONS: Intraoperative electrostimulation of the lumbar sympathetic nerves generated only ipsilateral seminal emission. This suggests that some efferent sympathetic signals for emission might run ipsilaterally in humans.

Adult↗

Risk factors in past histories and familial episodes related to development of testicular germ cell tumor.

BACKGROUND: A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus. METHODS: The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia. RESULTS: Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives. CONCLUSIONS: The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.

Adolescent↗

Health related quality of life in Japanese men after radical prostatectomy or radiation therapy for localized prostate cancer.

BACKGROUND: We performed a retrospective survey of general and disease specific health-related quality of life (HRQOL) after radical prostatectomy (RP) and external beam radiotherapy (XRT) in Japanese men. METHODS: A total of 186 patients underwent RP and 78 underwent XRT for clinically localized prostate cancer between 2000 and 2002. We measured the general and disease specific HRQOL with the MOS 36-Item Health Survey and the University of California, Los Angeles Prostate Cancer Index, respectively. Each treatment group was further divided into four subgroups according to the time scale. RESULTS: Patients from the RP group were significantly younger than those from the XRT group. The tumor characteristics differed significantly in their distributions among the treatment groups. Patients undergoing XRT had low scores in most of the general measures of HRQOL just after treatment, but after 6 months there were no differences between the treatment groups, except for the physical domains. The RP group was associated with worse urinary function, whereas the XRT group had worse bowel function and bother during the first 6 months after treatment. Thereafter, however, urinary and bowel domain did not differ between the groups. Both groups reported poor sexual function, although the RP group scored lower sexual bother. CONCLUSION: The patients who underwent RP had significantly worse urinary and better bowel function than those treated with XRT. Both treatment groups had decrements in sexual function throughout the post-treatment period; careful attention should be paid to this side-effect in preoperative counselling, especially in younger patients, regardless of the primary treatments.

Aged↗

Recovery of health related quality of life after radical prostatectomy in japanese men: a longitudinal study.

BACKGROUND: We performed a longitudinal survey of health related quality of life (HRQOL) after radical retropubic prostatectomy (RP) in Japanese men with localized prostate cancer. METHODS: The present study started with self-reported HRQOL assessments provided by 72 patients who received only RP. The RAND 36-Item Health Survey and the University of California, Los Angeles Prostate Cancer Index were administered before and 3, 6 and 12 months after RP. RESULTS: Patients who underwent RP showed problems in some domains of general HRQOL, but these problems diminished over time. Urinary function declined substantially at 3 months and continued to recover at 6 and 12 months, but scored lower than the baseline. Urinary bother at 3 months had a significant decrease, but at six months it turned out to be the same as the baseline. The data of sexual function and bother showed a substantially lower score after RP. The sexual bother score of the younger men was significantly worse than that of the older men. Those who underwent nerve sparing procedures experienced significantly better recovery of urinary and sexual functions than the non-nerve sparing group. CONCLUSION: Despite reports of problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Deterioration of the sexual domain was remarkable throughout the postoperative period. Therefore, careful attention should be given to preoperative counseling, especially for younger patients.

Aged↗

Clinical features of testicular tumors in children.

AIM: Testicular tumors are not common pediatric solid tumors, especially in Asian children. There have been few reviews of cases in Japan to date. We present the clinical features of 14 pediatric testicular tumor patients. METHODS: Clinical features of 14 testicular tumor patients, such as chief complaints, age at diagnosis, pathology, stages, treatments and prognosis, were examined from medical records. Two patients had their semen tested at adolescence. RESULTS: Of the 14 prepubescent patients, 12 (85.7%) patients were diagnosed before 3 years of age. Ten cases (71.4%) were diagnosed as yolk sac tumors, three (21.4%) as mature teratomas and one case as an epidermoid cyst. Nine cases (90.0%) among the 10 cases of yolk sac tumor were diagnosed as stage I and one case was stage IV. One stage I yolk sac tumor patient developed lung metastasis later. Eventually, two yolk sac tumor patients died, despite chemotherapy. While all the cases with a diagnosis before 2 years of age survived, 67% (2/3) of cases with a diagnosis after the age of 2 died of tumors. Semen analysis in two patients showed normospermia. CONCLUSION: In the present study, the most common testicular tumors were yolk sac tumors and the patients diagnosed before 2 years of age showed favorable results. Age could be a relapse risk factor in yolk sac tumors. Guidelines for handling testicular tumors in children is not yet well established in Japan. An organized system seems necessary to gather and accumulate the results of the cases in Japan in order to develop better guidelines for treatment.

Child↗

[The perioperative charge equivalence of radical prostatectomy with 1-year follow up since the diagnosis of prostate cancer].

We assessed the 1-year charges in the group of patients undergoing radical prostatectomy and the changes in hospital costs and resource use following implementation of a clinical care path. A total of 69 consecutive men treated with radical prostatectomy for clinically localized prostate cancer were enrolled in the study. Hospital and outpatient records were analyzed for each patient in regard to preoperative, operative and postoperative charges of a 12-month period. Parameters included number of encounters, diagnostic and therapeutic interventions, hospitalization and operative charges, and follow-up visits, diagnostic tests and interventions for 1 year. The mean first-year cost of treatment with radical prostatectomy for localized prostate cancer was 144 x 10(4) yen. The increases in the first-year cost with higher prostate specific antigen (PSA) level for the diagnosis level appeared to primarily be associated with increased inpatient resource use and greater use of hormonal therapy. Length of the stay in a hospital significantly influenced the first-year cost. After implementation of the radical prostatectomy care path hospital costs decreased by 30% (66 x 10(4) yen vs 46 x 10(4) yen), total costs decreased 40% (190 x 10(4) yen vs 113 x 10(4) yen) and length of hospital stay decreased by 56% (37.0 vs 16.6). The first-year costs with radical prostatectomy are influenced greatly by the hormonal therapy and the number of hospital days. By standardizing preoperative and postoperative management for patients undergoing radical prostatectomy, significant savings can be achieved toward shorter hospital stays and lower hospital costs.

Age Factors↗

Gene transfer of alpha1,3-fucosyltransferase increases tumor growth of the PC-3 human prostate cancer cell line through enhanced adhesion to prostatic stromal cells.

Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC-3 with alpha1,3-fucosyltransferase III (FTIII) to obtain stable transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X. When inoculated in the prostate of nude mice, PC-3-FTIII cells produced large prostate tumors, while mock-transfected PC-3 cells, which are negative for sialyl Lewis X antigen, produced small prostate tumors. The aggressive tumor formation by PC-3-FTIII cells was inhibited by preincubation of the tumor cells with anti-sialyl Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide but not by control peptide. PC-3-FTIII cells and mock-transfected PC-3 cells exhibited no significant difference in cell numbers when cultured in vitro. Remarkably, PC-3-FTIII adhered to prostatic stromal cells in vitro with higher affinity than mock-transfected PC-3. Such adhesion was inhibited by preincubation of PC-3-FTIII cells with antisialyl Lewis X antibody, by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide. However, anti-E-selectin, anti-P-selectin or anti-L-selectin antibodies did not inhibit the adhesion of PC-3-FTIII cells to the stromal cells. These results suggest that prostate cancer cells gain aggressiveness through adhesive interaction with prostatic stromal cells by a novel mechanism involving sialyl Lewis X.

Adenocarcinoma↗

Human alpha2,3-sialyltransferase (ST3Gal II) is a stage-specific embryonic antigen-4 synthase.

Monosialosyl globopentaosylceramide (MSGb5), originally described as stage-specific embryonic antigen-4, is expressed in testicular germ cell tumors and in aggressive cases of human renal cell carcinoma (RCC). Clarification of the molecular mechanisms regulating synthesis of MSGb5 is very important to understand testicular carcinogenesis and the malignant progression of human RCC. For this purpose, we have investigated alpha2,3-sialyltransferase involved in the synthesis of MSGb5. We used the method of expression cloning combined with polymerase chain reaction targeted to sialylmotif to isolate a cDNA clone from RCC cell line ACHN library. The cloned cDNA was found to be identical to the previously cloned ST3Gal II in sequence. A soluble recombinant form of the protein in COS-1 cells showed an enzyme activity of alpha2,3-sialyltransferase toward globopentaosylceramide (Gb5) in addition to asialo-GM1 and GM1a. Transient transfection of COS-7 and ACHN cells with this cDNA induced an increase of MSGb5, whereas stable transfection of antisense ST3Gal II cDNA suppressed expression of MSGb5 in ACHN cells. The ST3Gal II mRNA level was increased in 7 of 8 RCC cell lines and in all six RCC tissues surgically obtained, although it was not necessarily consistent with the MSGb5 level in RCC cell lines. This study indicates that ST3Gal II is a MSGb5 (stage-specific embryonic antigen-4) synthase and that its increased expression level is closely related to renal carcinogenesis.

Animals↗

Active chemotherapy for bone metastasis in sarcomatoid renal cell carcinoma.

Sarcomatoid renal cell carcinoma (SRCC) is associated with an aggressive course, high incidence of bone metastasis, and an extremely poor prognosis. There are a few case reports concerning the effectiveness of chemotherapy on metastasis in SRCC. To our knowledge, however, there are no reports describing its effectiveness on bone metastasis. We report a 22-year-old woman with an 8-cm x 7-cm left renal mass. Left nephrectomy was done. The pathological diagnosis was SRCC, INF-beta, pT3aN2. Although, she received continuous infusion of interferon alpha-2a (INFalpha-2a) and interleukin-2 (IL-2) as adjuvant therapy, liver metastasis appeared 2 months later. Resection of the liver metastasis was done. After resection of the metastasis, multiple bone metastases appeared, in both humeri, the left chest wall, the left fourth rib, and the left iliac bone. The patient was treated with gemcitabine, 1000 mg/m(2) (days 1, 8), docetaxel 80 mg/m(2) (day 1), and carboplatin 300 mg/m(2) (day 1). A computed tomography (CT) scan after the first cycle revealed that the multiple osteolytic bone tumors had significantly decreased in size. Her ability of daily life (ADL) improved and this continued for almost 2 months. A second course of chemotherapy, with gemcitabine and IL-2 was given, but it was ineffective, and the patient died approximately 16 months after the initial diagnosis of SRCC. Combination chemotherapy with gemcitabine, docetaxel, and carboplatin was effective for the bone metastasis of SRCC.

Adult↗

Complete regression of bone metastases on super bone scan, by low-dose cisplatin, UFT, diethylstilbestrol diphosphate, and dexamethasone in a patient with hormone-refractory prostate cancer.

Many types of chemotherapy are now being attempted all over the world for hormone-refractory prostate cancer (HRPC) patients, and prostate-specific antigen (PSA) reduction in almost half of the treated patients has been reported. However, only a few studies have reported the response of bone metastasis. The authors report a patient with HRPC who obtained complete regression of bone metastases on super bone scan by biochemical modulation (BM), dexamethasone, and endocrine therapy.

Adenocarcinoma↗

Nasal continuous positive airway pressure improves quality of life in obesity hypoventilation syndrome.

We studied the quality of life of obesity hypoventilation syndrome (OHS) by comparing it with age- and body mass index-matched patients without hypoventilation and age-matched obstructive sleep apnea (OSA) patients with body mass index (BMI) under 30, and the efficacy of nasal continuous positive airway pressure (CPAP) therapy for 3 to 6 months on the quality of life in these patients. Prospectively recruited patients from six sleep laboratories in Japan were administered assessments of the general health status by the Short-Form 36 Health Survey (SF-36) and subjective sleepiness by the Epworth Sleepiness Scale (ESS). Compared with matched healthy subjects, OHS and OSA patients not yet treated had worse results on the ESS scores and the SF-36 subscales for physical functioning, role limitations due to physical problems, general health perception, energy/vitality, role limitations due to emotional problems, and social functioning. The ESS scores of OHS patients were worse than those of the OSA groups including the age- and BMI-matched OSA patients. In the SF-36 subscales of OHS patients, only the subscale of social functioning showed worse results compared with that of BMI-matched OSA patients. After 3 to 6 months of treatment, ESS scores and these SF-36 subscales in all three patient groups improved to the normal level. These results suggested that the quality of life of OHS before nasal CPAP was significantly impaired and that nasal CPAP for OHS improved the quality of life associated with the improvement of daytime sleepiness to the level of the other OSA patients.

Adult↗

Electrostimulation of sympathetic nerve fibers during nerve-sparing laparoscopic retroperitoneal lymph node dissection in testicular tumor.

A long-handled pair of electrodes with sufficient length to allow stimulation during laparoscopic retroperitoneal lymph node dissection (RPLND) was designed at our institute. We clinically utilized this electrode in the treatment of a 37-year-old patient with testicular tumor who underwent right orchidectomy and nerve-sparing laparoscopic RPLND. During laparoscopic RPLND, sympathetic nerve fibers relevant to ejaculation were electrically stimulated and changes in pressure at the bladder neck were observed. Nerve preservation was confirmed by increased pressure at the bladder neck and ejaculation immediately after the electrostimulation. The application of laparoscopic electrostimulation may become widespread, particularly since it meets the increasing demand for minimally invasive surgery.

Adrenergic Fibers↗