Overexpression of platelet-derived endothelial cell growth factor (PD-ECGF) factor/thymidine phosphorylase (TP) in interstitial cystitis.
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Adult↗
Biomedical subjects
O Ogawa
Publications and source records attributed to O Ogawa.
Usefulness of stable HbA(1c) for supportive marker to diagnose diabetes mellitus in Japanese subjects.
To evaluate the adequacy and usefulness of the stable glycated hemoglobin (HbA(1c)) value of 6.5% suggested by the Japan Diabetic Society in 1999 for supportive diagnostic marker of diabetes, we assessed the sensitivity and specificity of an HbA(1c) value of 6.5% in patients who were newly diagnosed by the 75 g oral glucose tolerance test (75g-OGTT). A total of 866 Japanese subjects underwent the 75g-OGTT and HbA(1c) measurement (normal range: 4.3-5.8%). They were divided into three groups [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM)], using the WHO criteria, since no subject with impaired fasting glycemia (IFG) was observed. The cut-off value of HbA(1c) separating DM from NGT or DM from IGT on cumulative distribution curve analysis was 5.9% (sensitivity 0.76 and specificity 0.86) and 5.9% (sensitivity 0.76 and specificity 0.77), respectively. The sensitivity of an HbA(1c) of 6.5% for separation of DM from NGT or IGT by the same analysis was 0.49 and 0.49, respectively. Similarly, the specificity for separation of DM from NGT or IGT was 0.98 and 0.98, respectively. These results mean that 49% of diabetic subjects show an HbA(1c)> or =6.5%, and 51% have an HbA(1c) less than 6.5%, while only 2% of NGT and IGT subjects have an HbA(1c)> or =6.5%, and 98% have a value less than 6.5%. Therefore, the sensitivity of an HbA(1c) value of 6.5% in separating DM from NGT or IGT is low, and thus 6.5% is too high value to use when screening for diabetes. However, the specificity is very high, so an HbA(1c) of 6.5% is a useful supportive marker to diagnose diabetes.
Adult↗
Expression of Apg-1, a member of the Hsp110 family, in the human testis and sperm.
BACKGROUND: Apg-1 encodes a heat shock protein belonging to the Hsp110 family and is inducible by a 32 degrees C to 39 degrees C heat shock in somatic cells. In mouse testicular germ cells Apg-1 mRNA is constitutively expressed depending on the developmental stage. As human Apg-1 has recently been identified, the expression of Apg-1 in the human testis and sperm was investigated. METHODS: Expression and heat-inducibility of Apg-1 in the human testicular germ cell tumor cell line, NEC8, was analyzed. Using an antimouse Apg-1 antibody, expression of Apg-1 in the human testis and sperm was examined by western blotting after confirmation of the specificity of the antibody. The cells expressing Apg-1 in the testis were further determined by immunohistochemistry. RESULTS: Slight induction of Apg-1 mRNA was detected in NEC8 cells after 32 degrees C to 39 degrees C temperature shift. In the human testis, the antibody specifically recognized Apg-1, which was absent in the testis without germ cells (Sertoli-cell-only syndrome) or arrested at spermatogonia. Spermatocytes and spermatids, but not testicular somatic cells, were positively stained with the anti-Apg-1 antibody. By western blot analysis, Apg-1 was detected in the preparation enriched for sperm from normal volunteers and infertile patients, but not from azoospermia patients. CONCLUSION: Apg-1 is developmentally expressed in human testicular germ cells and sperm, suggesting its role in spermatogenesis and fertilization. Identification of substrates for Apg-1 chaperone activity will help elucidate its function.
Adult↗
Enhanced sensitivity of bladder cancer cells to tumor necrosis factor related apoptosis inducing ligand mediated apoptosis by cisplatin and carboplatin.
PURPOSE: The development and acquisition of multiple drug resistance in cancer cells are a consequence of cancer chemotherapy and remain a major obstacle in treatment. Therefore, there is an obvious need for alternative approaches, such as immunotherapy and gene therapy. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is one of the tumor necrosis factor ligand families and it selectively induces apoptosis against cancer cells. Several cytotoxic anticancer drugs also mediate apoptosis and may share the common intracellular pathways leading to apoptosis. We reasoned that combination treatment of cancer cells with TRAIL and drugs may overcome this resistance. We evaluated whether bladder cancer cells are sensitive to TRAIL mediated cytotoxicity and whether TRAIL may synergize with anticancer agents in cytotoxicity and apoptosis against bladder cancer cells. MATERIALS AND METHODS: Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. RESULTS: Human T24 bladder cancer line was relatively resistant to TRAIL and TRAIL was not cytotoxic against normal bladder cells. Treatment of T24 cells with TRAIL in combination with 5-fluorouracil or mitomycin C did not overcome resistance to these agents. However, treatment of T24 cells with a combination of TRAIL and cisplatin resulted in a synergistic cytotoxic effect. Synergy was also achieved in the cisplatin resistant T24 line (T24/CDDP), 2 other bladder cancer lines and 3 freshly derived bladder cancer cells. The combination of TRAIL and carboplatin resulted in a synergistic cytotoxic effect on T24 cells. However, the combination of TRAIL and trans-diamminedichloroplatinum (II) resulted in an antagonistic cytotoxic effect. The synergy achieved in cytotoxicity with TRAIL and cisplatin was also achieved in apoptosis. Treating T24 cells with cisplatin enhanced the expression of bax but not bcl-2. Incubation of T24 cells with TRAIL increased the intracellular accumulation of cisplatin. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with TRAIL and cisplatin overcomes their resistance. The sensitization obtained with established cisplatin resistant and freshly isolated bladder cancer cells required low subtoxic concentrations of cisplatin, supporting the in vivo potential application of a combination of TRAIL and cisplatin for treating TRAIL resistant and cisplatin resistant bladder cancer.
Antineoplastic Agents↗
Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors.
PURPOSE: Although synchronous and/or metachronous tumor development is common in urothelial cancer, genetic and biological differences in upper urinary tract and bladder tumors are unclear. We compared the genetic alteration pattern in multifocal disease in patients with upper urinary tract and subsequent bladder tumors, and those with recurrent bladder tumor. MATERIALS AND METHODS: Using 21 microsatellite markers on the 8 chromosomal arms 2q, 4p, 4q, 8p, 9p, 9q, 11p and 17p we analyzed 34 tumors from 15 patients with upper urinary tract and subsequent bladder disease, and 70 tumors from 22 with recurrent bladder disease. RESULTS: Judging from the patterns of genetic alterations multifocal tumors were considered to have derived from an identical progenitor cell in 7 of 13 evaluable patients (54%) with upper urinary tract and subsequent bladder tumors, and 16 of 19 (84%) who were evaluable with recurrent bladder tumor. These data confirm the view that seeding or intraepithelial spread is a major mechanism for the multifocal development of urothelial cancer in general. However, a discordant microsatellite alteration pattern in multifocal tumors was observed in 6 of 7 patients (86%) with upper urinary tract and subsequent bladder lesions but in 2 of 16 (13%) with recurrent bladder cancer (p <0.005). CONCLUSIONS: Our results imply that upper urinary tract neoplasms may be genetically more unstable than bladder neoplasms. The implantation of tumor cells from upper urinary tract to bladder may involve additional and diverse genetic alterations. Furthermore, a considerable number of multifocal upper urinary tract and subsequent bladder lesions may arise independently via field cancerization mechanism. Our study indicates that the factors contributing to multifocal development are different in the 2 groups.
DNA, Satellite↗
Quantitative analysis of gene expressions of vascular endothelial growth factor-related factors and their receptors in renal cell carcinoma.
Vascular endothelial growth factor (VEGF)-related factors are believed to regulate angiogenesis, an essential event in the growth of solid tumors. In this study, we investigated the expression of VEGF-related factor genes (VEGF, VEGF-B, and VEGF-C) and their receptor genes (VEGFR-1 and VEGFR-2) in renal cell carcinoma (RCC). There were significant differences in the expression level of VEGF, VEGFR-1 and VEGFR-2 between RCC and the corresponding normal renal tissue. The expression level of VEGF in the tumor tissue significantly correlated with those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C genes were not significantly different between RCC and normal renal tissue. A moderate to high protein expression for VEGF, VEGFR-1, and VEGFR-2 was observed in both the tumor cells and the endothelial cells, whereas the protein expression was low for VEGF-B and VEGF-C. The present results suggested that VEGF and its receptors VEGFR-1 and VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC, while VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2 proteins were expressed in the tumor cells as well as in the endothelial cells, these receptors may also be responsible for the progression of RCC.
Aged↗
Antiatherogenic mitochondrial genotype in patients with type 2 diabetes.
OBJECTIVE: To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C --> A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Mt5178 typing was done by polymerase chain reaction-restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C. RESULTS: The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mrt5178A group than in the Mt5178C group (0.906 +/- 0.018 vs. 0.995 +/- 0.021 mm, mean +/- SEM, P = 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis. CONCLUSIONS: The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals.
Adult↗
Activation of caspase-3 in renal cell carcinoma cells by anthracyclines or 5-fluorouracil.
The caspase family of proteases is speculated to have a crucial role in apoptosis. The effect of treatment with adriamycin (ADR), cisplatin (CDDP), 5-fluorouracil (5-FU), vinblastine (VLB), IFN-alpha, or IFN-gamma on the activation of caspase-3, -6, -8, and -9 in renal cell carcinoma (RCC) cells was investigated, to clarify the mechanisms of chemo- and immunotherapeutic agent-mediated apoptosis. Caspase activity was determined by a quantitative colorimetric assay. Apoptosis was monitored by acridine-orange staining assay. Treatment of ACHN cells with CDDP, VLB, IFN-alpha, or IFN-gamma did not activate caspase-3, but its activity was increased 7.2-fold (p = 0.0001) with ADR and 2.8-fold (p = 0.0385) with 5-FU in comparison with control. Furthermore, when the ADR treatment time was shortened from 24 to 8 or 2 h, the same caspase-3 activation occurred. Activation of caspase-3 was also observed in six freshly isolated human RCC cells after the treatment with ADR. Of the six freshly derived RCC cells treated with 5-FU, caspase-3 activity was increased 3.1-fold (p = 0.0051) and 2.4-fold (p = 0.0346) in two of them, respectively. Epirubicin and pirarubicin, compounds closely related to ADR, also respectively enhanced 4.2-fold (p = 0.0052) and 2.8-fold (p = 0.0147) caspase-3 activity in ACHN cells. The activation of caspase-3 observed with a colorimetric assay was confirmed with immunocytochemical analysis using the anti-active caspase-3 mAb, which specifically recognizes the active form of caspase-3. Furthermore, both active caspase-3 and apoptosis triggered by either ADR or 5-FU were inhibited significantly by the general caspase inhibitor Z-VAD-FMK, or a specific caspase-3 inhibitor DMQD-CHO. These findings provide a mechanistic explanation for anthracyclines and 5-FU induced-apoptosis.
Amino Acid Chloromethyl Ketones↗
The presence of the virulence island containing the usp gene in uropathogenic Escherichia coli is associated with urinary tract infection in an experimental mouse model.
PURPOSE: A putative virulence island commonly noted in the genome of uropathogenic Escherichia coli strains has recently been reported. We have observed that the island includes a gene consisting of a protein designated uropathogenic specific protein (usp) and 3 small open reading frames (orfU1-3). In our current study we assessed the importance of the genes located in the putative virulence island in the pathogenesis of urinary tract infection using a mouse pyelonephritis model. MATERIALS AND METHODS: A total of 427 E. coli strains isolated from the urine of 194, 76 and 107 subjects suffering from cystitis, pyelonephritis and prostatitis, respectively, and 50 isolates from the feces of healthy individuals were examined for genotypes and serotypes. In addition, several recombinant E. coli strains possessing usp and/or orfU1 to 3 were constructed for evaluating the significance of these genes using an experimental pyelonephritis mouse model. RESULTS: The usp was significantly more often associated with uropathogenic E. coli strains (79.4% from cystitis, 93.4% from pyelonephritis and 88.8% from prostatitis) than with fecal E. coli strains from healthy individuals (24%). Furthermore, usp was frequently associated with all common serotypes of uropathogenic E. coli (71.7% to 100%). In challenge experiments using the mouse urinary tract infection model the vector possessing usp significantly enhanced the infectibility of the E. coli host cell, whereas the 3 small proteins at the downstream of usp failed to show the effect. CONCLUSION: Our results indicate that usp may contribute to the causation of urinary tract infection and may be considered a major virulence determinant of uropathogenic E. coli.
Animals↗
[Diagnosis and treatment of prostate cancer--it's diversity and future prospects].
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Forecasting↗
[A case of malignant fibrous histiocytoma arising from the renal capsule].
A 62-year-old man was admitted with a chief complaint of general malaise. Computed tomography showed a large mass adjacent to the parenchyma of the left kidney. The mass was 17 x 13 x 12 cm in size. Preoperative diagnosis was left renal cell carcinoma and left radical nephrectomy was performed. Histopathologically, the tumor was diagnosed as malignant fibrous histiocytoma (MFH), and the tumor was considered to have arisen from the renal capsule. There has been no recurrence for 7 months postoperatively. We review 40 cases of MFH arising from the kidney or the renal capsule in the literature.
Diagnosis, Differential↗
Expression patterns of cancer testis antigens in testicular germ cell tumors and adjacent testicular tissue.
PURPOSE: The human cancer-testis antigens (CTAs) are a group of tumor specific antigens recognized by cytotoxic T lymphocytes whose expression occurs in human malignancies as well as in normal testicular tissue. We studied a series of CTA gene transcripts in testicular germ cell tumors of various histological types to test the hypothesis that the expression of CTA in testicular germ cell tumors reflects developmental stages of tumorigenesis rather than constitutive tumor antigens recognized by cytotoxic T lymphocytes. MATERIALS AND METHODS: Total RNA was obtained from 31 primary and 3 metastatic testicular germ cell tumors, and 11 parenchymal tissues adjacent to the testicular germ cell tumors. We performed an expression study of the CTA genes MAGE-A, MAGE-B, GAGE, PAGE-1, HOM-MEL-40 (SSX2), NY-ESO-1, LAGE-1 and SCP-1 in these samples using reverse transcriptase-polymerase chain reaction. RESULTS: The results showed that expression patterns of CTA genes depended on the histological differentiation of the testicular germ cell tumors. Overall CTA expression was more common in seminomas than in nonseminomatous germ cell tumors. Specifically all 13 seminomas (100%) demonstrated the positive expression of MAGE-B1 and MAGE-B2, while 3 of 17 nonseminomatous germ cell tumor samples (18%) showed positive expression of these genes. All 5 teratomatous elements (100%) had homogenous null expression with regard to all CTA genes examined. In addition, we detected deficiencies in CTA expression in 7 of 11 parenchymal tissues adjacent to the testicular germ cell tumors (64%). CONCLUSIONS: These data support the idea that CTA transcripts in testicular germ cell tumors serve as developmental footprints of testicular germ cell tumors rather than as constitutive tumor antigens recognized by cytotoxic T lymphocytes.
Antigens, Neoplasm↗
[Progression from adenocarcinoma to small cell carcinoma of the prostate during endocrinotherapy: a case report].
A 72-year-old man had undergone surgical castration for metastatic prostate cancer (stage D2, the PSA value was 4,300 ng/ml) in September, 1997. He was well clinically for 16 months with undetected level of PSA. However, he presented with general malaise and gross hematuria in May, 1999. After admission to our hospital his condition rapidly deteriorated and he died one week later with respiratory failure. Autopsy revealed extensive involvement of the prostate and bladder by solid tumor with multiple metastases in lungs, liver, spleen, kidneys and bone. Histological examination revealed pure small cell carcinoma of the prostate.
Adenocarcinoma↗
[Molecular epidemiology and cancer prevention].
Environmental factors act in concert with individual susceptibility to cause most human cancers. The modulation of these environmental factors by host susceptibility has rarely been evaluated. Recently, the molecular epidemiology of human cancer has been extended to a study clarifying individual variation and gene-environmental interactions by integrating molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. This article briefly reviews genetic polymorphisms frequently used in molecular epidemiological studies and shows, as an example, a possible association between the genetic polymorphisms of CYP17 genes and prostate cancer risk.
Androgens↗
[Prostate cancer incidence, mortality, and survival rates in Japan].
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Age Factors↗
Rapid detection of candidate metastatic foci in the orthotopic inoculation model of androgen-sensitive prostate cancer cells introduced with green fluorescent protein.
BACKGROUND: An in vivo spontaneous metastatic model using androgen-sensitive prostate cancer cells is needed to the better understanding of prostate cancer progression. Orthotopically inoculated LNCaP cells to SCID mice manifests metastases, but it takes no less than 12 weeks to detect them by conventional methods. METHODS: The green fluorescent protein (GFP) gene was introduced into LNCaP cells by conventional lipofection technique. Biological characteristics of a subline (LNCaP-GFP) that expressed GFP at high level were compared to those of the parental cells. LNCaP-GFP cells were orthotopically inoculated to the SCID mouse, and metastases to distant organs were chronologically examined under fluorescence microscopy. RESULTS: There was no difference in growth rates and androgen-responsiveness in vitro between LNCaP-GFP and LNCaP cells. LNCaP-GFP cells inoculated to SCID mice produced prostate specific antigen. Histopathological examination at 12 weeks after inoculation of LNCaP-GFP revealed that metastases were identified as the inoculation of LNCaP cells. Colonies consisting of a few LNCaP-GFP cells, however, were detected in the lung under fluorescence microscopy as early as 4 weeks after inoculation. CONCLUSIONS: Orthotopic inoculation of LNCaP-GFP to SCID mice may provide a useful tool to investigate the molecular mechanism of progression, in particular the early stage of metastasis, of androgen-sensitive prostate cancer cells.
Androgens↗
Inhibition of inducible nitric oxide synthase gene expression by indomethacin or ibuprofen in beta-amyloid protein-stimulated J774 cells.
Recent studies show that a mononuclear phagocyte lineage, including microglia, plays a possible role in the pathogenesis of Alzheimer's disease through nitric oxide (NO)-mediated neurotoxicity. Epidemiological studies show that nonsteroidal anti-inflammatory drugs (NSAIDs) have a protective effect against Alzheimer's disease. Based on these observations, it has been hypothesized that an anti-Alzheimer's disease effect of NSAIDs could result from the inhibition of NO synthesis. We report here that indomethacin or ibuprofen dose-dependently reduce beta-amyloid protein and interferon-gamma-induced NO production, accompanied by an inhibition of inducible nitric oxide synthase mRNA expression in J774 cells, a murine macrophage cell line. Aspirin, however, does not produce such an effect, suggesting that the cyclooxygenases pathway is not involved in the inhibitory effects of NSAIDs on beta-amyloid protein and interferon-gamma-induced NO production in J774 cells.
Alzheimer Disease↗
Plasma cortisol levels in elderly female subjects with Alzheimer's disease: a cross-sectional and longitudinal study.
We investigated the plasma cortisol levels at a fasting state in elderly female Alzheimer's disease (AD), vascular dementia (VD), and non-demented subjects (n=66, 28 and 21, respectively). Twenty-eight AD subjects were followed for 40 months. The plasma cortisol levels in AD and VD subjects were significantly higher than those of non-demented subjects at baseline. In AD subjects in relatively early stages of the disease [Mini-Mental State Examination (MMSE)], at baseline, high plasma cortisol led to rapid declines in MMSE scores over a 40-month period.
Aged↗