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H Kumon

Publications and source records attributed to H Kumon.

At least 19 recordsLinked to original sources
PubMed2006

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model.

We developed a preclinical prostate cancer model to study the feasibility of adoptive immunotherapy for residual tumor following neo-adjuvant in situ adenoviral-vector-mediated interleukin 12 (AdIL-12) gene therapy. Splenocytes were obtained from mice with orthotopic 178-2 BMA metastatic mouse prostate cancers treated previously with AdIL-12, or a vector with the IL-12 genes plus the costimulatory gene B7-1 (AdIL-12/B7), or a control gene (Adbetagal). The splenocytes were subsequently injected intravenously into syngeneic mice bearing orthotopic 178-2 BMA tumors generated 3 days previously. Significant orthotopic tumor growth suppression was achieved with splenocytes derived from mice whose tumors had been injected with AdIL-12 compared to splenocytes from control Adbetagal mice (P = 0.0005) and splenocytes from AdIL-12/B7-treated mice significantly suppressed spontaneous lung metastases compared to splenocytes from control mice (P = 0.0356). Adoptive transfer of splenocytes from either AdIL-12 (P = 0.004) or AdIL-12/B7 (P = 0.009)-treated mice significantly prolonged survival relative to controls. Transfer of NK and tumor-specific CTL activities was detected and depletion of CD4+ and CD8+ T cells by in vitro antibody-mediated complement lysis of the splenocytes prior to injection abrogated the effects. Systemic IL-12 administration delivered by intramuscular AdIL-12 injection enhanced the antitumor effects of adoptive splenocyte transfer and boosted the CTL response. Our data provide evidence that this form of adoptive immunotherapy can enhance the effectiveness of neo-adjuvant in situ IL-12 gene therapy in cases of persistent malignancy.

Adoptive Transfer↗
PubMed2005

Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis.

Testicular germ cell-induced autoimmune orchitis is characterized by inflammatory cell infiltration followed by disturbance of spermatogenesis. Experimental autoimmune orchitis (EAO) is an animal model for human immunological male infertility; delayed-type hypersensitivity (DTH) response plays a key role in its induction. Interleukin-10 (IL-10) is a regulatory cytokine that is critical in preventing organ-specific autoimmune inflammation. To determine the effects on EAO of human IL-10 (hIL-10) gene transfer, C3H/He mice immunized by unilateral testicular injury were administered intramuscular (i.m.) injections of adeno-associated viral (AAV) vector-encoding hIL-10 on the day of immunization. Serum hIL-10 was detected beginning at 1 week postinjection, and peaked at 3 weeks. Histological examinations showed a significantly low incidence of orchitis and disturbance of spermatogenesis in AAV hIL-10-treated mice, and the DTH response to autologous testicular cells was significantly suppressed. Immunohistochemical analysis of IFN- and IL-2, T-cell-associated cytokines, in the spleen and testes revealed significantly fewer cytokine-expressing cells after treatment. We conclude that a single i.m. administration of AAV hIL-10 significantly suppresses EAO and hypospermatogenesis by regulating cell-mediated immunity in the testes.

Adenoviridae↗
PubMed2004

Analysis of retrograde ejaculation using color Doppler ultrasonography before and after transurethral collagen injection.

Transurethral bladder neck collagen injection therapy was performed in a patient with retrograde ejaculation. The phenomenon of retrograde ejaculation and its correction after the therapy were clearly demonstrated by color Doppler ultrasonography. To our knowledge this is the first report showing successful observation of retrograde ejaculation using color Doppler ultrasonography.

Adult↗
PubMed2002

Gene therapy for prostate cancer: toxicological profile of four HSV-tk transducing adenoviral vectors regulated by different promoters.

Adenoviral vector delivery of the Herpes simplex virus thymidine kinase (HSV-tk) gene in combination with the prodrug ganciclovir (GCV) has been tested in phase I clinical trials for prostate cancer and found to exhibit a satisfactory toxicity profile. We have developed additional adenoviral vectors with differing promoters to optimize the expression profile and in the present study evaluate the potential systemic toxicity of these vectors. Four recombinant adenoviral vectors that express the HSV-tk gene were generated using three different promoters: CMV (leftward orientation); RSV (both rightward and leftward orientation); and the mouse caveolin-1 (cav-1) promoter (leftward orientation). Efficacy was determined in vitro by cytotoxicity assays in a mouse prostate cancer cell line, RM-9, and in vivo by treating orthotopic tumors. Potential toxicity was evaluated from liver histology and apoptotic cell counts and enzyme levels in the serum following intravenous adenoviral vector injection. Although there were differences in HSV-tk expression at the protein level among the four vectors there were no significant differences in in-vitro cytotoxicity studies with GCV or in vivo in tumor growth suppression of an orthotopic mouse prostate cancer model in GCV treated mice. Intravenous delivery of high doses of all adenoviral vectors lead to abnormalities in liver function as measured by specific serum markers and histological evaluation of liver tissue and increased levels of apoptosis in the liver. These abnormalities were most prevalent with the vector containing the CMV promoter and the rightward oriented RSV promoter. They were least prevalent in the vector regulated by the cav-1 promoter. Upregulation of specific chemokines, MIP-2 and MIP-1beta was correlated with apoptotic counts. Our results demonstrate that comprehensive toxicological analysis of adenoviral vectors provides internally consistent information that can differentiate vectors with comparable efficacy based on toxicity. In these studies vectors with the cav-1 promoter-driven and leftward RSV-driven HSV-tk gene demonstrated minimal toxicities with cytotoxic effectiveness comparable to more toxic vectors. Our studies further suggest that promoter selection can influence the toxic effects of an adenoviral gene therapy vector.

Adenocarcinoma↗
PubMed2001

Expression of amphiphysin I in Sertoli cells and its implication in spermatogenesis.

Amphiphysin I is a protein concentrated in nerve terminals and involved in the endocytosis of synaptic vesicle membrane. We show here that amphiphysin I is expressed in the rat testis, localized exclusively in the Sertoli cells. In the postnatal testicular development, expression of amphiphysin I was not evident at birth, but became significant at postnatal day 15 (P15), coinciding with the onset of spermatogenesis. The expression level of amphiphysin I increased 10-fold between P15 and P25 to reach the adult level. In adult testes reversibly damaged by ethane dimethane sulphonate administration, expression of amphiphysin I did not change following the damage, whereas the protein was transiently converted into its phosphorylated form. The increase in levels of phosphorylated amphiphysin I was closely associated with the severe histological damage to germ cells. The present findings suggest that amphiphysin I in Sertoli cells is involved in spermatogenesis, probably through endocytic processes.

Animals↗
PubMed2001

Ny-ESO-1 expression and immunogenicity associated with transitional cell carcinoma: correlation with tumor grade.

NY-ESO-1 mRNA expression in transitional cell carcinoma was investigated by reverse transcription-PCR and immunohistochemistry. NY-ESO-1 mRNA was detected in 20 of 62 (32%) tumor specimens. There was a correlation between NY-ESO-1 expression and tumor grade: 0 of 4 (0%) grade 1 (G1), 6 of 26 (23%) grade 2 (G2), and 14 of 32 (44%) grade 3 (G3) tumors were NY-ESO-1 mRNA positive. Immunohistochemical analysis using NY-ESO-1-specific monoclonal antibody ES121 showed that 2 of 14 NY-ESO-1 mRNA-expressing G3 tumors were positive for NY-ESO-1. No NY-ESO-1 staining was observed in the panel of 30 G1 or G2 tumor specimens, including 6 NY-ESO-1 mRNA-positive cases. Sera from an expanded panel of 124 patients with transitional cell carcinoma were tested for the presence of NY-ESO-1 antibody. Seropositivity was observed in 9 of 72 (12.5%) patients with G3 tumors, whereas none of 52 patients with G1 or G2 tumors produced antibody against NY-ESO-1. In the 9 positive patients with NY-ESO-1 antibody, 4 had muscular invasive tumors, and 5 had carcinoma in situ.

Adult↗
PubMed2001

Transrectal ultrasound for monitoring murine orthotopic prostate tumor.

BACKGROUND: The mouse orthotopic prostate tumor model has been recognized as an ideal preclinical animal model simulating the anatomical and biological milieu of the prostate. In comparison with the subcutaneous tumor model, the only disadvantage of this model is the difficulty of chronological tumor growth monitoring. We have applied recent endoluminal ultrasound technology, transrectal ultrasonography (TRUS), to the monitoring of mouse orthotopic prostate tumors. METHODS: A 6 Fr. 20 MHz catheter-based radial scan probe was used and TRUS was performed without any prior preparation including anesthesia. Orthotopic tumors were initiated by inoculation of 5000 RM-9 cells into the dorsal prostate of 12-week-old C57BL/6 male mice. The tumor growth was monitored by TRUS from day 3 to day 21. In addition, TRUS was performed to detect tumor growth suppression after intraperitoneal administration of cis-diamminedichloroplatinum (CDDP). RESULTS: By ultrasound, tumors became detectable 7 days after tumor cell inoculation. TRUS images were clear and parallel to actual tumor growth. The tumor volume (X) calculated by TRUS correlated significantly with the actual tumor weight (Y) measured at autopsy; Y = 101.653 + 1.174X (R = 0.930, P < 0.001). Similarly, tumor growth suppression induced by CDDP was clearly detected by TRUS with reasonable accuracy. CONCLUSIONS: A high resolution TRUS allows simple and reliable monitoring of in situ tumor growth and growth suppression, making the mouse orthotopic prostate tumor model more efficient.

Animals↗
PubMed2001

Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.

Serological expression cloning of antigens eliciting a humoral immune response to a syngeneic mouse sarcoma identified pem (mouse placenta and embryonic expression gene) as a new member of the cancer/testis family. To identify the human homologue of pem, mouse pem sequences and pem-related expressed sequence tags from human testis were used as PCR primers for amplification using human testis cDNA. However, rather than pem, another gene, designated OY-TES-1, was isolated and found to be the human homologue of proacrosin binding protein sp32 precursor originally identified in mouse, guinea pig, and pig. OY-TES-1 maps to chromosome 12p12-p13 and contains 10 exons. Southern blot analysis suggests the presence of two OY-TES-1-related genes in the human genome. In normal tissues, OY-TES-1 mRNA was expressed only in testis, whereas in malignant tissues, a variable proportion of a wide array of cancers, including bladder, breast, lung, liver, and colon cancers, expressed OY-TES-1. Serological survey of 362 cancer patients with a range of different cancers showed antibody to OY-TES-1 in 25 patients. No OY-TES-1 sera reactivity was found in 20 normal individuals. These findings indicate that OY-TES-1 is an additional member of the cancer/testis family of antigens and that OY-TES-1 is immunogenic in humans.

Amino Acid Sequence↗
PubMed2001

Muscle-derived cell transplantation and differentiation into lower urinary tract smooth muscle.

OBJECTIVES: To explore the feasibility of primary skeletal muscle-derived cell (MDC)-based tissue engineering and gene transfer into the lower urinary tract and to explore whether the injected primary skeletal MDCs can persist and differentiate into myotubes and myofibers in the bladder wall. METHODS: Primary MDCs isolated from normal mice were first transduced with adenovirus encoding the expression of the beta-galactosidase reporter gene. Adult severe combined immunodeficiency mice (n = 12) were used in this study. The MDCs were injected into the right and left lateral bladder walls with a 10-microL Hamilton microsyringe. The amount of injected MDCs ranged from 1 to 1.5 x 10(6) cells. The tissue was harvested after 5, 35, and 70 days, sectioned, stained for fast myosin heavy chain, and assayed for beta-galactosidase expression. RESULTS: We observed a large number of cells expressing beta-galactosidase in the bladder wall at each time point. Many myotubes and myofibers expressing beta-galactosidase and positively stained for fast myosin heavy chain were also seen in the bladder wall at 35 and 70 days after injection. Additionally, the size of the injected MDCs significantly increased during the course of the study (P <0.05). CONCLUSIONS: We have demonstrated the long-term survival and beta-galactosidase expression of MDCs injected into the bladder wall. Moreover, our results suggest that some injected MDCs can differentiate into myofibers. These results suggest that MDCs can be a desirable substance for tissue engineering and an ex vivo method for gene transfer into the lower urinary tract.

Animals↗
PubMed2001

Anticlastogenic activity of cacao: inhibitory effect of cacao liquor polyphenols against mitomycin C-induced DNA damage.

Oxidative DNA damage has been implicated as a factor playing a role in mutagenesis and carcinogenesis. We investigated the anticlastogenic activity of cacao: the inhibitory effect of cacao liquor polyphenols on DNA strand cleavage induced by mitomycin C (MMC) in vitro and the anticlastogenic effect of cacao liquor extract against formation of micronuclei induced by MMC in bone marrow cells and peripheral blood cells of mice. In the DNA strand cleavage test, cacao liquor polyphenols inhibited cleavage of RFI DNA. In the micronuclei test, the frequency of occurrence of micronucleated cells among bone marrow cells and peripheral blood cells were reduced significantly when cacao liquor extract was administered orally to mice 6 h before intraperitoneal injection of MMC. These findings suggest that cacao liquor polyphenols are effective in preventing DNA damage, and one of the mechanisms of action might involve scavenging of active oxygen radicals generated in reactions initiated by MMC.

Animals↗
PubMed2001

Catheter-associated urinary tract infections: impact of catheter materials on their management.

Infection associated with an indwelling catheter is a representative type of biofilm infection occurring in the urinary tract. Since the most effective way to control this intractable infection is the prevention of bacterial attachment and subsequent biofilm formation on the catheter, the importance of catheter materials and anti-bacterial coating cannot be underestimated. The difference in the degree of bacterial attachment among standard catheter materials, the efficacy of silver-coating of catheters in preventing infection and the potency and effectiveness of a new lecithin/silver coating are discussed.

Anti-Infective Agents, Urinary↗
PubMed2001

Treatment of androgen-independent prostate cancer with dexamethasone: a prospective study in stage D2 patients.

PURPOSE: In order to evaluate the efficacy of dexamethasone in the treatment of Japanese men with androgen-independent prostate cancer, a prospective study was conducted using prostate-specific antigen (PSA) as a primary end-point. METHODS: Nineteen Japanese men with stage D2 androgen-independent prostate cancer were registered and treatment was started. After ruling out anti-androgen withdrawal syndrome, they were treated with dexamethasone (1.5 mg daily). Patients were monitored for PSA, symptoms, radiologic response, survival rate, time to disease progression, time to treatment failure and complications. RESULTS: Prostate-specific antigen levels decreased in nine patients (50.0%); five (27.8%) showed a 50% or greater decrease and two (11.1%) showed an 80% or greater decrease. For the nine patients, the mean duration of PSA response was 7.3 months and the median duration was 2.1 months (range, 1.2-27.5+). Bone pain, which was noted in 13 patients at study entry, improved in seven patients (53.8%). Of nine patients who had serial radiographic examinations with bone scan, three (33%) showed partial response, two (22%) were stable and four (44%) showed disease progression. Treatment was well tolerated, except for one patient who suffered a severe pulmonary infection. CONCLUSION: Dexamethasone decreased PSA levels and produced subjective symptomatic improvement in the patients with stage D2 androgen-independent prostate cancer.

Aged↗
PubMed2001

Orthotopic neobladder reconstruction in elderly bladder cancer patients.

BACKGROUND: We compared the clinical results of orthotopic neobladder reconstruction in elderly patients and those in younger patients retrospectively in order to verify whether age is a critical factor in selecting a method of urinary diversion. METHODS: Following radical cystectomy for bladder cancer, 12 patients aged 75 or older and 17 patients under 75 who underwent orthotopic neobladder reconstruction between January 1992 and May 1999 were investigated in this study. The authors TS and BS were among the surgeons who performed operations for all cases. Of the 12 elderly patients, orthotopic neobladders were constructed according to Hautmann's method in nine cases, Studer's method in one case and Reddy's method in two cases. Of the 17 younger patients, these methods were employed in 12, one and four cases, respectively. Operative procedure, early and late complications, prognosis, continence and voiding pattern were investigated in these patients. RESULTS: The follow-up periods for elderly and younger groups ranged from 21.3 to 82.7 months and from 8.8 to 94.2 months, respectively. No difference in operation time, amount of bleeding or postoperative length of hospitalization was observed between elderly and younger patients. The rates of early complications in elderly and younger patients were 41.7% and 35.3%, respectively. Late complication rates were 33.3% and 47.1%, respectively. The difference in these complication rates was not statistically significant. One of the elderly and two of the younger patients had local recurrence and metastasis postoperatively. Those three patients had died of their bladder cancer. No statistically significant difference between groups was recognized in either cause-specific survival or overall survival, nor was there such a difference in relation to micturition/continence. CONCLUSION: Based on these results, we believe that because age is not a critical factor in the selection of urinary diversion method, neobladder reconstruction following cystectomy for bladder cancer is indicated in elderly patients. As stoma management is difficult for the patients, we consider orthotopic neobladder reconstruction to be the method of choice if the patients' general physical condition allows.

Age Factors↗
PubMed2001

Gene therapy and tissue engineering for urologic dysfunction: status and prospects.

This article reviews the recent advances in gene therapy and tissue engineering for urologic dysfunction. Although the number of gene therapy-based clinical trials has increased dramatically in the field of urologic oncology, such trials are still few within the neurourologic field. Recently, new biologic approaches employing growth factors have been utilized to treat various pathological conditions. Among them, transfer of genes such as those encoding growth factors represents a promising way to deliver therapeutic proteins to malfunctioning tissues, which leads to the improvement of organ function. Tissue engineering, which may eventually be combined with gene therapy, also offers the potential to create new functional genitourinary tissue for regeneration and replacement of tissue lost as a consequence of disease. Thus, both tissue engineering and gene therapy may hold promising new solutions in the urologic field.

Animals↗
PubMed2001

Retroperitoneoscopic pyelotomy combined with the transposition of crossing vessels for ureteropelvic junction obstruction.

PURPOSE: We developed a new approach of retroperitoneoscopic pyelotomy combined with the transposition of crossing vessels for ureteropelvic junction obstruction as an alternative to conventional antegrade or retrograde endopyelotomy. MATERIALS AND METHODS: From February 1997 to August 1999 we treated 5 cases of ureteropelvic junction obstruction due to crossing vessels that were diagnosed by helical computerized tomography. Ureterovascular hydronephrosis characterized by a malrotated renal pelvis with anterior crossing vessels was observed in 4 cases and ureteropelvic junction obstruction with a posterior crossing artery was present in 1. After endoureterotomy stent insertion under cystoscopic guidance we performed retroperitoneoscopic endopyelotomy with the kidney in standard position. Crossing vessels were transposed to a higher position to remove obstruction and fixed with peripelvic tissue via retroperitoneoscopy. In all cases a longitudinal incision approximately 1.5 cm. long was made with a potassium titanyl phosphate laser. RESULTS: Convalescence was uneventful in all patients and the endoureterotomy stent was removed 4 to 8 weeks after surgery. Postoperatively helical computerized tomography showed the successful transposition of crossing vessels and significant hydronephrosis resolution in all cases. All patients were asymptomatic during followup of 17 to 28 months. CONCLUSIONS: Despite our small number of patients our results are sufficient to conclude that retroperitoneoscopic pyelotomy combined with the transposition of crossing vessels is a simple and reliable method for treating ureterovascular hydronephrosis and associated conditions.

Adult↗
PubMed2001

Persistence and survival of autologous muscle derived cells versus bovine collagen as potential treatment of stress urinary incontinence.

PURPOSE: We explored the use of autologous muscle derived cells as a method of treating stress urinary incontinence. We determined whether urethral muscle derived cell injection is feasible and compared it with bovine collagen injection. MATERIALS AND METHODS: Muscle derived cells isolated from female Sprague-Dawley rats were first transduced with retrovirus carrying the transgene for beta-galactosidase. We injected approximately 1 to 1.5 x 106 cells into the bladder wall and proximal urethra of 6 autologous animals. Tissue was harvested after 3 and 30 days, sectioned, stained for fast myosin heavy chain and assayed for beta-galactosidase. To compare muscle derived cell and bovine collagen injections 100 microl. of commercially available bovine collagen were also injected in Sprague-Dawley female rats. Tissue was harvested in 3 animals each after 3 and 30 days, sectioned and stained for trichrome. Subsequently, 3 adult SCID mice were used to compare the level of transgene expression at each time point after injecting 1.5 x 106 cells per injection, which were transduced with adenovirus carrying the transgene for beta-galactosidase. RESULTS: A large number of cells expressing beta-galactosidase were observed in the bladder and urethral wall 3 and 30 days after autologous cell injection in Sprague-Dawley rats. The persistence of primary muscle derived cells at 3 days was similar to that of collagen. However, at 30 days there was significant cell persistence while only a minimal amount of injected bovine collagen was detectable. Approximately 88% of the beta-galactosidase expression at day 3 remained at day 30 in SCID mice. CONCLUSIONS: We present 2 new findings important for the emerging field of urological tissue engineering, including the feasibility of injecting autologous skeletal muscle derived cells into the lower urinary tract and the greater persistence of such injected cells versus injected bovine collagen. Therefore, autologous muscle derived cell injection may be an attractive alternative treatment option for stress urinary incontinence.

Animals↗
PubMed2001

A non-surgical rat model of foreign body-associated urinary tract infection with Pseudomonas aeruginosa.

This study established a rat model of foreign body-associated urinary tract infection. A spiral polyethylene tube (PT) was placed transurethrally into the bladder without surgical manipulation, followed by transurethral inoculation with Pseudomonas aeruginosa. The persistence of P. aeruginosa in the kidneys and bladder was significantly enhanced by placement of the PT, whereas the bacteria were eliminated rapidly from the urinary tract in the animals without the PT. Scanning electron microscopy revealed a thick biofilm on the surface of the PT from the early stage of infection. Histopathologically, acute pyelonephritis was followed by chronic renal inflammation as well as continuous and sporadic polymorphonuclear leukocyte accumulation and hemorrhage in the pelvis and adjacent tissues, suggesting continuous ascending introduction of the bacteria from the biofilm adhering to the PT. We believe our model simulates the pathophysiology of foreign body-associated urinary tract infection characterized by biofilm formation on the surface of a foreign body.

Animals↗