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Biomedical subjects

I Hara

Publications and source records attributed to I Hara.

At least 109 records · Page 6Linked to original sources

Interaction between CD44 and hyaluronic acid regulates human prostate cancer development.

PURPOSE: This study was designed to investigate the significance of the interaction between CD44 and hyaluronic acid in the development of human prostate cancer. MATERIALS AND METHODS: We transfected the standard CD44 isoform (CD44s) cDNA into PC3, a human prostate cancer cell line that barely expresses CD44s protein. The effects of the reintroduction of CD44s into PC3 cells on the ability to bind hyaluronic acid (HA) were analyzed by the cell adhesion assay and by the cell migration assay. The in vitro growth rate of CD44s transfected PC3 was measured by using the MTT assay. We then evaluated the in vivo tumor development of CD44s transfected PC3 cells by subcutaneous, intravenous, and intraperitoneal injection models in athymic nude mice. RESULTS: The introduction of CD44s in PC3 cells markedly enhanced the binding and migration of these cells to HA, but not to other extracellular matrix molecules. In vitro growth of CD44s-transfected PC3 was found to be significantly decreased. In addition, the CD44s-transfected PC3 cells also demonstrated reduced tumorigenicity and metastatic potential in in vivo experimental models. CONCLUSIONS: These findings suggest that the CD44s downregulation plays an important role in the development of human prostate cancer, in part through reduction of the ability to bind HA.

Down-Regulation↗

Multifocal renal cell carcinoma: evidence for a common clonal origin.

The reported incidence of satellite tumor lesions in kidneys resected by radical nephrectomy for renal cell carcinoma (RCC) is 7-25%; however, genetic analyses of satellite tumors in comparison with those of main tumor lesions have not been performed well. In the present study, we investigated the incidence of loss of heterozygosity (LOH) at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q using 18 microsatellite markers in 10 nonpapillary RCCs of 50 mm or less in diameter and the accompanying satellite tumor lesions to evaluate the genetic alterations in main and satellite tumors. LOH was detected in 10, 3, 5, 3, 2, and 3 cases at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q, respectively. In addition, primary and satellite tumor lesions in 8 of 10 cases exhibited identical patterns of LOH on the 18 loci examined. In the remaining two cases, both main and satellite tumors demonstrated LOH on the common seven and three loci, respectively, whereas for another locus, LOH was observed only in the satellite tumor lesions. The similarity of LOH patterns detected in main and satellite tumor lesions indicates that the presence of satellite tumors might be the result of intrarenal metastasis from the main tumor lesion. These findings strongly suggest that even in case of small nonpapillary RCC, nephron-sparing surgery might carry the risk of failing to prevent postoperative local recurrence due to the incomplete resection of unrecognized satellite tumors with genetic alterations similar to those of the main tumor.

Adult↗

Recovery of leukocyte function after super-high-dose chemotherapy with peripheral blood stem cell transplantation in testicular cancer patients.

Leukocyte functions (superoxide production and phagocytosis) were evaluated in patients with testicular cancer who had undergone super-high-dose chemotherapy (SHDT) with peripheral blood stem cell transplantation (PBSCT). In 5 patients with advanced or relapsed testicular cancer who received 8 cycles of SHDT with PBSCT, we measured superoxide production activity by phorbol myristate acetate (PMA) stimulation, as well as phagocytic activity using latex particles before and after PBSCT. The median time to reach a leukocyte count of > or = 1,000/microl was 9 days after PBSCT. Superoxide production activity was significantly decreased on day 7 compared with the pre-chemotherapy level. However, it recovered by day 12 and sustained such a level thereafter. Phagocytic activity was within the normal range on day 7 but declined slightly on days 12 and 21 compared with the pre-chemotherapy level. Our results indicate that leukocyte function and leukocyte count recover promptly following PBSCT and that PBSCT is a safe and convenient adjunctive therapy after SHDT for patients with advanced testicular cancer.

Adult↗

Pitfalls of measuring residual urine volume in orthotopic neobladders.

OBJECTIVE: To investigate the pitfalls of measuring postvoid residual urine volume (PVR) in patients with orthotopic neobladders, in an out-patient clinic. PATIENTS AND METHODS: Fifteen patients with orthotopic neobladders were enrolled in the study; five patients had a colonic neobladder, five an ileocolic neobladder and five a sigmoid neobladder. The PVR was compared after measuring by catheterization under fluoroscopic monitoring after normal or forced voiding. RESULTS: The PVR after forced voiding was always less than that after natural voiding, regardless of the type of neobladder. CONCLUSIONS: Patients with orthotopic neobladders may have a higher PVR after voiding naturally at home than when the PVR measured in hospital.

Aged↗

Percutaneous treatment of transitional cell carcinoma of the upper urinary tract.

BACKGROUND: We evaluated the long-term effect of percutaneous resection in 2 Japanese patients with transitional cell carcinoma of the renal pelvis, and reviewed the medical literature on similar patients, to determine the appropriate indications for percutaneous treatment of transitional cell carcinoma in the upper urinary tract. RESULTS: Indications for endoscopic resection in the 2 patients were renal insufficiency and unsuitability for major open surgery. The patients had no recurrence during follow-up. Seven previous reports described percutaneous resection of upper urinary tract transitional cell carcinoma in 82 patients. Although 72.6% of the patients were successfully treated by percutaneous resection, half of the patients with grade 3 carcinoma developed recurrence. CONCLUSION: These results, together with those of the 7 published reports, suggest that percutaneous resection should be limited to selected patients with low-grade transitional cell carcinoma.

Aged↗

Treatment of crush syndrome patients following the great Hanshin earthquake.

Five of 8 patients with rhabdomyolysis treated at our hospital following the Great Hanshin Earthquake were diagnosed with crush syndrome. One patient with crush syndrome and 3 patients with rhabdomyolysis and no renal dysfunction recovered with conservative therapy, while 1 crush syndrome patient recovered with peritoneal dialysis (PD). Of the 3 patients who died, 2 had undergone continuous arterio-venous hemofiltration (CAVH). We examined the laboratory data to identify any factors that may be prognostic for crush syndrome. The serum amylase levels were significantly higher and the levels of aspartate transaminase (AST) and lactic dehydrogenase (LDH) tended to be higher from the patients who died. Examination of the serum amylase, AST and LDH levels may be useful for assessing the prognosis in patients with crush syndrome.

Aged↗

[Interaction between neurons and astrocytes involved in brain regulatory function as assessed by in vitro brain ischemia models].

In the recent decade of brain research, one of the most interesting findings is the significance of the active neuronal-glial interaction. It is no exaggeration to say that astrocytes in the central nervous system have an important role, participating in the regulation of neuronal functions. For instance, the fate of brain neurotransmitters, especially amino acids, following their release by neurons, is to be mainly inactivated by uptake via specific high-affinity transport systems into not only neuronal cells but also astrocytes, rather than by extracellular enzymatic degradation. These uptake mechanisms in astrocytes are very important for maintaining brain neuronal function under the low energy condition. In our research using the in vitro brain ischemia model, it was demonstrated that the neuronal death induced by excessive amounts of glutamate (Glu) under low energy conditions (hypoglycemia, hypoxia, particularly acidosis) is caused by dysfunctions of astrocyte Glu uptake and glutamine (Gln) output systems, and neural death can be modulated by the number of surrounding astrocytes in the cultured brain cells. Moreover, the neuronal dysfunction induced by excessive amounts of Glu was enhanced by a blocker of Glu uptake into astrocytes rather than an antagonist of Gln synthetase, which mainly exists in the astrocytes. During dysfunctions of astrocytes induced by acidosis, sustained increases of NO metabolites, ammonia and cytokines were produced. These biological substances may regulate the functions of neuronal cells and astrocytes. Thus, the balance of astrocyte-neuronal cells can maintain the brain neuronal homeostasis.

Amino Acids↗

Basic fibroblast growth factor regulates matrix metalloproteinases production and in vitro invasiveness in human bladder cancer cell lines.

PURPOSE: This study was designed to investigate the effect of endogenous basic fibroblast growth factor (FGF-2) on matrix metalloproteinases (MMPs) production and in vitro invasive potential of human bladder cancer cell lines. MATERIALS AND METHODS: The human bladder cancer cell lines, HT1376 and KoTCC-1, were used in this study. The mRNA for FGF receptor has been shown to be expressed in both cell lines; the mRNA for FGF-2 is expressed in only KoTCC-1. The effects of FGF-2 expression on HT1376 by gene transfection and those of FGF-2 antisense oligonucleotides treatment on KoTCC-1 were analyzed by zymography and in vitro tumor cell invasion assay. RESULTS: The introduction of human FGF-2 gene into HT1376 cells markedly enhanced both the MMP-2 and MMP-9 production, and the in vitro invasive potential was also increased. In contrast, the exposure of KoTCC-1 cells to FGF-2 specific antisense oligonucleotides decreased the MMP-2 production and in vitro invasive potential, but the exposure to FGF-2 sense oligonucleotides did not. CONCLUSIONS: These findings suggest that FGF-2 plays an important role in the invasive process of human bladder cancer in part through the regulation of MMPs production.

Cell Division↗

[A case of amyopathic dermatomyositis associated with interstitial pneumonitis].

A patient (47-year old female) who had erythema similar to Gottron's sign on bilateral finger joints since two years ago, started to have polyarthralgia on bilateral knee and shoulder on the spring of 1993. Polyarthralgia was extended to both wrist and hand joints on Oct. of 1995. On the middle of Dec. 1995, she began to have exertional dyspnea and was referred and admitted in our hospital on 18th, Dec., 1995. Chest X-ray and CT scan showed the shadow for active interstitial pneumonitis on bilateral lower lung fields. Blood gas analysis indicated hypoxia (PaO2: 62.8 mmHg) and low % DLCO (64.7%). Skin eruption of face (heliotrope-like erythema) and hands (Gottron's sign) and skin biopsy (right hand) findings were compatible with that in dermatomyositis. The analysis in blood biochemistry showed no elevation for muscle enzymes. The diagnosis for amyopathic dermatomyositis (ADM) was made according to the criteria proposed by Euwer & Sontheimer (1993). The steroid pulse therapy and 50 mg per day of cyclophosphamide were immediately administered. The dyspnea and dermatitis were improved within two weeks after therapy. She is presently in remission until Jan. 1997 with the maintenance dosis of 10 mg per day of oral prednisolone.

Anti-Inflammatory Agents↗

Immune response to a differentiation antigen induced by altered antigen: a study of tumor rejection and autoimmunity.

Recognition of self is emerging as a theme for the immune recognition of human cancer. One question is whether the immune system can actively respond to normal tissue autoantigens expressed by cancer cells. A second but related question is whether immune recognition of tissue autoantigens can actually induce tumor rejection. To address these issues, a mouse model was developed to investigate immune responses to a melanocyte differentiation antigen, tyrosinase-related protein 1 (or gp75), which is the product of the brown locus. In mice, immunization with purified syngeneic gp75 or syngeneic cells expressing gp75 failed to elicit antibody or cytotoxic T-cell responses to gp75, even when different immune adjuvants and cytokines were included. However, immunization with altered sources of gp75 antigen, in the form of either syngeneic gp75 expressed in insect cells or human gp75, elicited autoantibodies to gp75. Immunized mice rejected metastatic melanomas and developed patchy depigmentation in their coats. These studies support a model of tolerance maintained to a melanocyte differentiation antigen where tolerance can be broken by presenting sources of altered antigen (e.g., homologous xenogeneic protein or protein expressed in insect cells). Immune responses induced with these sources of altered antigen reacted with various processed forms of native, syngeneic protein and could induce both tumor rejection and autoimmunity.

Animals↗

Messenger ribonucleic acids for fibroblast growth factors and their receptor in bladder and renal cell carcinoma cell lines.

FGF-like growth factors have been detected in the urine of patients with bladder or renal cell carcinoma. FGF-1-like and FGF-2-like proteins have been detected in the urine of patients with bladder carcinoma. However, the expression of FGFs and their receptor in bladder and renal cell carcinoma cells remains limited. We measured the mRNA levels of FGFs and their receptor in these carcinoma cell lines by means of RT-PCR. We detected FGF-8 mRNA expression in murine cell lines of bladder and renal cell carcinomas but not in those of the normal bladder and kidney. Furthermore, FGF-8 mRNA expression was detected in all human bladder and renal cell carcinoma cell lines tested. We also frequently detected FGF-1, FGF-2 and FGF-5 mRNA expression in human bladder and renal cell carcinoma cell lines. These results indicate that FGF-8 is also candidate for marker of these types of carcinoma as well as FGF-1 and FGF-2.

Animals↗

Introduction of basic fibroblast growth factor gene into mouse renal cell carcinoma cell line enhances its metastatic potential.

To clarify the role of basic fibroblast growth factor (FGF-2) in the malignant progression of renal cell carcinoma, we transfected the FGF-2 gene, which lacks the typical signal sequence, into RenCa, a mouse renal cell carcinoma cell line that does not express FGF-2 mRNA. In an in vitro tumor cell invasion assay, the FGF-2-transfected cell lines (RenCa/F) exhibited 3- to 4-fold higher invasive potential than either the parental RenCa (RenCa/P) or the vector-only transfected cell line (RenCa/C). Zymography showed a marked increase in matrix metalloproteinase 2 (MMP-2) production in the culture supernatants of RenCa/F. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa/F formed more than 10 times as many metastatic nodules in the lung as did RenCa/P and RenCa/C. Metastases to the liver and mesenteric lymph nodes were observed only after the injection of RenCa/F into the renal subcapsule. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among RenCa sublines. These results suggest that if it is overexpressed, endogenous native FGF-2 plays an important role in the invasion and metastasis of renal cell carcinoma, probably through the production of MMP-2.

Animals↗

Rejection of mouse renal cell carcinoma elicited by local secretion of interleukin-2.

We introduced the interleukin-2 (IL-2) gene into mouse renal cell carcinoma (RenCa) in order to examine the mechanism of tumor rejection. IL-2 gene-transfected RenCa (RenCa/IL-2Hi) exhibited marked retardation of tumor growth when implanted in a syngeneic host. Growth retardation of RenCa/IL-2Hi was also observed in athymic nude mice even after depletion of natural killer (NK) cells by treatment with anti-asialo GM1 antibody. Histological analysis of RenCa/IL-2Hi tumors disclosed non-specific inflammatory changes in syngeneic hosts. Co-injection of Bacillus Calmette Guerin with RenCa/IL-2Hi considerably enhanced the anti-tumor effects. Taken together, these findings strongly suggest that in situ IL-2 production leads to tumor rejection through non-specific inflammatory responses without participation of T cells and NK cells. On the other hand, the syngeneic mice that had rejected RenCa/IL-2Hi acquired immunity against parental RenCa, suggesting possible participation of memory T cells in the second rejection of the tumor.

Animals↗

Comparison of hormonal therapy and chemohormonal therapy in patients with newly diagnosed clinical stage D prostatic cancer.

BACKGROUND: In order to examine the usefulness of chemohormonal therapy, we conducted a multicentered randomized trial comparing hormonal therapy, using a luteinizing hormone-releasing hormone (LH-RH) agonist, with chemohormonal therapy, hormonal therapy plus cyclophosphamide (CPM), in patients with newly diagnosed clinical stage D prostatic cancer. METHODS: Between January 1991 and March 1995, 41 evaluable patients with stage D prostatic cancer were randomized into 2 groups: group A (hormonal therapy alone), goserelin acetate depot 3.6 mg subcutaneously every 4 weeks: group B (chemohormonal therapy), goserelin acetate depot 3.6 mg subcutaneously and CPM 1000 mg/m2 intravenously every 4 weeks. The responses to the therapies were evaluated based on the criteria of The Japanese Urological Association. RESULTS: There were no significant differences between the 2 groups with regard to objective and subjective response rates. No advantage in chemohormonal therapy was observed in the survival rate and progression-free survival rate. However, the survival rate and progression-free survival rate of responders were significantly higher than those of nonresponders in both groups. When the results were categorized by histologic grade patients with poorly-differentiated adenocarcinoma had significantly higher response rates, survival rates, and disease-progression-free survival rates in Group B compared to similar patients in Group A. CONCLUSIONS: We conclude that chemohormonal therapy does not definitely improve the clinical response and prognosis of patients with stage D prostatic cancer; however, for patients with poorly-differentiated adenocarcinoma, chemohormonal therapy is a useful treatment.

Aged↗

[Association between dental erosion and exposure to acids in a chemical factory].

An examination of dental erosion status and a semi-quantitative assessment of exposure to acids were carried out for 134 workers in a chemical factory in Osaka Prefecture, and an association between the dental erosion and the exposure to acids was discussed. 1) Percentage of workers with dental erosion of grade + or more among the subjects was 30.6%. 2) Most of the erosion was observed in the front teeth. There were more eroded teeth in the upper jaw than in the lower jaw. 3) The workers were divided into 4 groups according to job type at the time of the examination: production, research, clerical work and others. The production workers, those routinely handling a large amount of various kinds of acids, was the highest proportion of workers with eroded teeth. Because some of the clerical workers had previously handled acids, this group of workers included a larger number of those with dental erosion than the other two groups. 4) More than half of the workers who had been engaged in production had eroded teeth including those of grade +/- 5) The intensity of exposure to acids, as a semi-quantitative index for cumulative exposure to acids, was calculated in each worker from a score for the job type and its duration. A significant association was observed between the intensity and the manifestation of dental erosion.

Acids↗

[Radical prostatectomy for localized prostate cancer].

We studied 81 patients who underwent radical prostatectomy for prostate cancer. Ten, 57 and 14 patients were clinically diagnosed with stage T1, T2 and T3, respectively. Pelvic lymph node dissection was performed prior to prostatectomy in all cases. The neurovascular bundle was preserved in 21 patients. Compared with pathological stage, the accuracy rate of clinical staging in T1, T2 and T3 was 40, 46 and 64% respectively. Approximately half of the patients clinically diagnosed with stage T2 were pT3. The positive rate of lymph node in pT2 and pT3 was 3.3 and 37% respectively, showing a marked difference between these two pathological stages. The 3-year non-recurrence rates were 89% in patients with pT2 and 79% in pT3. In the well differentiated carcinoma group, no patients had recurrence for up to 3 years. All of the patients with infiltration (INF) gamma showed recurrence within 3 years. Fifty-five patients had no problem on urination post-operatively, while the other 23 patients had a mild or moderate incontinence and the remaining 3 patients had a small urine stream. Regarding erectile potency, 4 out of 18 evaluable patients were potent.

Aged↗