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Masato Fujisawa

Publications and source records attributed to Masato Fujisawa.

117 records · Page 7Linked to original sources
PubMed2002

Distribution of intracellular and extracellular expression of transforming growth factor-beta1 (TGF-beta1) in human testis and their association with spermatogenesis.

AIM: Spermatogenic dysfunction may result from thickening of seminiferous tubular basement membrane (BM) with tubular sclerosis. Transforming growth factor beta1 (TGF-beta1) plays an important role in fibrogenesis. The intracellular and extracellular expression of TGF-beta1 in the testis were immunohistochemically determined, using LC antibody (LC) for intracellular TGF-beta1 and CC antibody (CC) for extracellular TGF-beta1. METHODS: Twenty-three testicular biopsy specimens were obtained from varicocele and five from Sertoli-cell-only (SCO) patients, and five from normal volunteers. The relative area involved by the expression of TGF-beta1 for CC or LC (TGF-beta1 index for CC or LC) was examined, and semen parameters and serum hormonal levels and TGF-beta1 were analyzed. The Johnson score (JS), the BM thickness, and the tubular diameter were also determined. RESULTS: Immunoreactivity for CC was hardly detected. That for LC was detected in the Sertoli and germ cells. The TGF-beta1 index for LC was significantly higher in the varicoceles than in the normal testes. Interestingly, that for LC was significantly higher in the varicoceles than in the SCO. The level of serum TGF-beta1 was significantly higher in varicoceles than in the normal testes. CONCLUSION: The distribution of the intracellular and extracellular expression of TGF-beta1 in human testis was demonstrated. It suggests that TGF-beta1 is related to fibrosis of seminiferous tubules and may lead to spermatogenic disruption.

Adult↗
PubMed2002

[Gene therapy for prostate cancer].

The substantial advances made in recent years in the molecular biology of malignant urological tumors and the associated progressive analysis of these conditions at a molecular level have spurred research aimed at gene-based treatment. In the field of prostate cancer, while there have been many ground-breaking studies particularly in the United States, none has yet led to a revolutionary treatment for recurrent prostate cancer. Gene-based treatment is being applied seriously in clinical settings, especially in the United States, but so far without significant effect. Many researchers worldwide are devoting energy to the development of effective vectors. By adjusting the promoter, which has the function of directing the vector, we have developed organ-specific vectors for the treatment of prostate cancer. In the present study, which targeted prostate cancer with bone metastasis, we developed a suicide-gene therapy using an adenovirus vector with an organ-specific osteocalcin promoter. Clinical trials of this vector have already been conducted at the University of Virginia in the United States and have so far confirmed the safety of the therapy. In the present paper we present the results of this gene-therapy research from the basic to the clinical phase alongside an outline of related research at our institution. Gene therapy for cancer is now being targeted not only against the primary tumor but systemic cancers including distant metastases; systemic administration of adenovirus vectors with organ-specific promoters may become one of the most promising systemic anti-tumor therapies of the next-generation.

Genetic Therapy↗
PubMedDate not supplied

Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism.

Surgical induction of cryptorchidism in experimental animals causes testicular germ cell apoptosis and infertility. The mechanisms of germ cell apoptosis have been associated with oxidative stress or testicular exposure to elevated temperature. Nitric oxide (NO) has been associated with apoptosis in a number of cell types. The objective of this study was to investigate whether overexpression of endothelial NO synthase (eNOS) could accelerate apoptosis of germ cells in the testes of transgenic mice. There are 3 NOS isoforms, and we restricted the analysis to eNOS at this time. For the colocalization of eNOS, staining in degenerating germ cells that were apoptotic cells suggested that eNOS may be related to germ cell apoptosis. eNOS overexpression in the testes of eNOS transgenic (eNOS-Tg) mice was examined using Western blot analysis. Unilateral cryptorchidism was surgically induced in both eNOS-Tg and wild-type (WT) adult mice. The testes were evaluated 1, 3, 5, 7, and 14 days after the operation by weighing the testes and examining histopathologic features and cell apoptosis using in situ microscopic analysis of DNA fragmentation. Immunoblotting for eNOS protein demonstrated increases in eNOS protein expression in testes, as well as the lung and aorta. In eNOS-Tg mice, weight reduction of cryptorchid testis was significantly increased on days 3, 5, and 7 (P = .02, .02, and .04, respectively). The numbers of spermatocytes and spermatids of eNOS-Tg cryptorchid testis significantly decreased compared with those of WT cryptorchid testis from day 3 (spermatocytes: P = .04; spermatids: P = .02). Moreover, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling demonstrated that eNOS-Tg mice significantly accelerate germ cell apoptotic changes induced by experimental cryptorchidism compared with WT mice from day 3 (P = .03). We have provided evidence that eNOS plays a functional role in mouse spermatogenesis in cryptorchidism-induced apoptosis.

Animals↗
PubMedDate not supplied

Expression and regulation of gp130 messenger ribonucleic acid in cultured immature rat Sertoli cells.

The expression of glycoprotein 130 (gp130) was studied in rat primary Sertoli cells by Northern blot analysis. Gp130 mRNA of 9.0 and 7.5 kb were detected in a variety of rat tissues including the testis. Gp130 mRNAs were detected in isolated, immature Sertoli cells. The levels of gp130 were significantly stimulated by the addition of interleukin-1-beta (IL-1-beta) or interleukin-6 (IL-6) but not by the addition of follicle-stimulating hormone (FSH). IL-6 activates intracellular signaling by binding with a receptor consisting of an 80-kDa ligand-binding protein, IL-6 receptor (IL-6R), and a second 130-kDa protein, gp130. As previously reported, expression of IL-6R mRNA in rat Sertoli cells was stimulated not only by IL-1-beta and IL-6 but also by FSH. In contrast, gp130 mRNA expression was not stimulated by FSH in our analysis. These data suggest that gp130 expression may be regulated by more than 1 mechanism and that production of gp130 and IL-6R, the 2 components of the IL-6 receptor system, may be regulated, at least in part, by a different pathway.

Animals↗
PubMedDate not supplied

Correlation between endothelin expression in early post-transplant biopsy specimens and long-term allograft function in living-related renal transplantation.

OBJECTIVE: We investigated whether degree of immunohistochemically evident endothelin (ET) expression in early post-transplant biopsy specimens could predict long-term allograft function in living-related renal transplantation. METHODS: Allograft biopsy specimens obtained from 40 patients with living-related transplants were studied. Cases with episodes of acute rejection or calcineurin inhibitor toxicity were excluded. We immunostained graft biopsy specimens obtained at pre-transplantation (PRE) and at 3 months (3M) afterward with anti-ET antibody. The number of stained tubular epithelial cells per 1000 tubular cells was defined as the staining index (SI). In the 21 patients whom we could assess at 3 yr (3Y) after transplantation, the correlation between ET expression and long-term graft function was examined. RESULTS: Anti-ET antibody staining was appreciable in tubular epithelium but not in glomeruli. Tubular SI at PRE and at 3M were 10.6 +/- 15.3 and 32.0 +/- 35.6 (mean +/- SD) respectively (p < 0.01). When patients were classified according to SI (group A, SI < 25; group B, SI > 25), declining ratio in creatinine clearance at 3Y after transplantation for groups A and B with respect was 21.8% +/- 15.4% and 41.9% +/- 21.6% (p < 0.05). CONCLUSION: High ET expression in early post-transplantation, biopsy specimens was related to poor long-term allograft function following living-related renal transplantation.

Adolescent↗
PubMedDate not supplied

Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model.

BACKGROUND: Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model. MATERIALS AND METHODS: In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days. RESULTS: The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated > 20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 microM of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model. CONCLUSION: The systemic administration of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.

Acyclovir↗
PubMedDate not supplied

Enhanced expression of heat shock protein 27 following neoadjuvant hormonal therapy is associated with poor clinical outcome in patients undergoing radical prostatectomy for prostate cancer.

BACKGROUND: The objectives of this study were to characterize changes in the expression of heat shock protein 27 (HSP27) in prostate cancer before and after androgen withdrawal therapy and to assess the prognostic significance of HSP27 expression in patients undergoing radical prostatectomy (RP) following neoadjuvant hormonal therapy (NHT). MATERIALS AND METHODS: This study included 97 patients with clinically localized prostate cancer who received NHT followed by RP. Paired needle biopsy and corresponding RP specimens obtained from these patients were analyzed for expression of the HSP27 protein by immunohistochemical staining. These findings were evaluated with respect to several clinicopathological factors. RESULTS: HSP27 expression in the RP specimens following NHT was significantly up-regulated compared with that in the corresponding needle biopsy specimens. The expression level of HSP27 in the biopsy specimens was significantly associated with the biopsy Gleason score, but not with other factors available before RP. HSP27 expression in the RP specimens was significantly correlated with the pre-operative value of serum prostate-specific antigen and pathological stage, but not with other pathological factors. Biochemical recurrence-free survival in patients with strong HSP27 expression in the RP specimens was significantly lower than that in those with weak HSP27 expression; however, the expression level of HSP27 was not an independent predictor of biochemical recurrence. CONCLUSION: Despite the lack of independent significance, the expression level of HSP27 in prostate cancer tissue after NHT, which may inversely reflect the therapeutic effect of NHT, could be a useful parameter predicting biochemical recurrence in patients undergoing RP.

Aged↗
PubMedDate not supplied

Stable hematopoietic recovery after peripheral blood stem cell transplantation in patients receiving high-dose chemotherapy for advanced germ cell tumors.

AIM: The objective of this study was to evaluate the utility of CD34-positive peripheral blood stem cell transplantation (PBSCT) in the hematopoietic recovery, in patients receiving high-dose chemotherapy (HDCT), for advanced germ cell tumor (GCT). MATERIALS AND METHODS: This study included 41 patients with advanced GCT, who were treated with HTCT combined with PBSCT. PBSCs were harvested after conditioning chemotherapy followed by the administration of granulocyte colony-stimulating factor. A retrospective analysis of a total of 86 PBSCTs was carried out focusing on the effects of several factors, including age (<35 years versus > or = 35 years), CD34-positive cell dose (<5.0 x10(6)/kg versus > or =5.0 x10(6)/kg), indication of HDCT (first-line versus salvage) and previous history of HDCT before PBSCT (with versus without), on hematopoietic recovery after PBSCT. RESULTS: The median number of CD34-positive PBSCs collected during a single apheresis and the median cumulative number of CD34-positive PBSCs from each patient were 8.3x10(6)/kg and 23.2x10(6)/kg, respectively. The median number of PBSCT performed in each patient was two and the median number of CD34-positive cells transplanted during a single course was 5.7x10(6)/kg. The median recovery times to white blood cells (WBC) greater than 500/microl, 1000/microl and 2000/microl were 8, 9 and 10 days, respectively, following PBSCT, while that to neutrophils greater than 500/microl and that to platelets greater than 50000/microl were 9 and 13 days, respectively, following PBSCT Only the recovery time to platelet count greater than 50000/microl was significantly affected by age; however, there were no significant differences in the recovery of WBC, neutrophils and platelets in relation to several parameters examined. CONCLUSION: These findings suggest that CD34-positive PBSCT may facilitate stable hematopoietic recovery after HDCT in patients with advanced GCT, and that HDCT, if combined with PBSCT, could be performed with comparative safety in such patients, irrespective of their individual characteristics.

Adolescent↗