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Biomedical subjects

K Oba

Publications and source records attributed to K Oba.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of adjuvant chemotherapy using oral fluorinated pyrimidines for curatively resected gastric cancer: a meta-analysis of centrally randomized controlled clinical trials in Japan.

Adjuvant chemotherapy for gastric cancer has been extensively explored in Japan since the 1950s, and a combination of oral fluorinated pyrimidines (o-FP) and mitomycin C (MMC) has been mainly utilized for adjuvant chemotherapy. However, there is no sufficient evidence for the efficacy of adjuvant therapy. Therefore, we assessed the efficacy of o-FPs over surgery alone (control) by means of a meta-analysis of Japanese centrally randomized controlled clinical trials conducted between 1980 and 2005. For inclusion in this study, studies had to compare adjuvant chemotherapy for curatively resected gastric cancer with surgery alone, mainly targeting o-FP, and central randomization designed to comply with contemporary standards for clinical trials in Japan. For the 4 trials that met the eligibility criteria, the estimated hazard ratio was 0.73 (95%CI=0.60-0.89). Our findings show that in Japan adjuvant chemotherapy using o-FP for long-term maintenance therapy appears to be effective for gastric cancer patients after curative resection.

Antibiotics, Antineoplastic↗
PubMed2003

The allelic loss of chromosome 3p25 with c-myc gain is related to the development of clear-cell renal cell carcinoma.

To explore the role of allelic losses at 3p25 and genetic alterations of chromosome 8, we investigated the relationships between genetic alterations in these chromosomal regions and clinicopathologic findings (such as tumor size and grade), by employing fluorescence in situ hybridization (FISH). Fifty Japanese clear-cell renal cell carcinomas (RCCs) were examined by dual-color FISH using cosmid DNA probes for 3p25.1-25.3 combined with probes for chromosome 3 centromere, 8p12, 8p21.1, 8p21.3, 8p22 and 8q24.12-24.13 (c-myc), and chromosome 8 centromere. Deletion at 3p25.1-25.3 was detected in 38 patients (76%), while 8p12 deletion, 8p21.1 deletion, 8p21.3 deletion, 8p22 deletion and c-myc gain were detected in 23 (46%), 25 (50%), 25 (50%), 25 (50%), and 20 patients (40%), respectively. There was a significant correlation between 8p21.1 deletion, 8p21.3 deletion and 8p21.1 deletion with c-myc gain and tumor grade (p = 0.04, 0.04 and 0.02, respectively). Deletions at 8p21.1 and 8p21.3 with 3p deletion were significantly related to tumor grade; the statistical significance was identical to that of sole 8p deletion with tumor grade. The deletion at 3p25.1-25.3 with c-myc gain showed a significant correlation with tumor size, indicating an association with tumor progression. Our results suggest that the allelic loss of chromosome 3p25 with c-myc gain is related to the development of clear-cell RCC.

Carcinoma, Renal Cell↗
PubMed2003

The role of chromosome 8p22 deletion for predicting disease progression and pathological staging in prostate cancer.

The natural course of human prostate cancer is highly variable, and we still lack reliable tools to predict the patient's outcome. Recent publications suggest that the deletion of chromosome 8p22 has an important role for tumor progression in prostate cancer. Totally, 97 patients (41 Japanese and 56 Swedish) were studied to detect the status of chromosome 8p22 deletion by the fluorescence in situ hybridization (FISH) technique. Seventy-seven underwent surgery (59 radical prostatectomies or 18 lymph node dissections), and the specimens were prepared by touch biopsy. Fine-needle aspiration biopsies (FNAB) were obtained from another non-operative 20 cases. Disease progression was evaluated in 57 patients with a median follow-up of 59 months. 8p22 deletions were detected in 58 (60 %) of all cases. The frequency of 8p22 deletion did not significantly differ between different preparations of specimens (touch biopsy vs. FNAB) as well as between different races (Japanese vs. Swedish). Cases with more than pT3 tumors had a significantly higher frequency of 8p22 deletion than those with pT2 (p < 0.01). Multivariate analysis demonstrated that 8p22 deletion was the strongest parameter to predict disease progression (hazard ratio = 5.75; p = 0.0001). Studies on chromosomal deletions of 8p22 by the FISH technique may serve as a universal genetic marker to optimize the treatment strategy in patients with prostate cancer.

Aged↗
PubMed2001

Detection of early gastric cancer by a real-time autofluorescence imaging system.

A light-induced fluorescence endoscopy in the gastrointestinal tract system was used in 52 patients with 54 lesions (33 early gastric cancers, 21 benign lesions) to assess its ability to detect early gastric cancer. Comparing the images with the histological findings, 21 of the 33 carcinomas appeared dark red, ten had a mixed pattern of dark red and white, and two could not be detected. Of the 21 benign lesions, 18 appeared light blue, as do normal mucosa, with this system. In 85% of the cancer lesions (28/33), cancer extension was correctly detected. The sensitivity and specificity were 94 and 86%, respectively. Real-time autofluorescence endoscopy is a useful adjunct to conventional white-light endoscopy for detecting early gastric cancer.

Carcinoma↗
PubMed2001

Two putative tumor suppressor genes on chromosome arm 8p may play different roles in prostate cancer.

Although loss of heterozygosity (LOH) on the short arm of chromosome 8 has been frequently observed in human prostate cancer, the relationship between LOH and clinical background is poorly understood. Fluorescence in situ hybridization (FISH) was employed to evaluate the chromosomal deletion on 8p in 42 prostate cancers using a centromeric probe for chromosome 8, in combination with 4 cosmid probes spanning 8p12 to 8p22. Deletions for at least one locus on the 8p were observed in 29 (69.0%) tumors. The most frequently deleted regions were 8p22 (54.8%) and 8p21.3 (52.4%), in almost the same frequency. The second most frequently deleted region was 8p21.1-p21.2 (38.1%). Deletions of 8p22 and 8p21.3 significantly correlated with tumor grade (P=0.0034, Fisher's exact probability test). A significantly higher frequency of the deletion on 8p21.1-p21.2 was observed in advanced prostate cancer (beyond capsular penetration or positive nodal metastases) than in localized prostate cancer (P=0.0033). In particular, deletion of 8p21.1-p21.2 was more frequently observed in the cases with lymph node metastases than without them (P=0.0029). No clinicopathological parameters had significant relation to deletions on 8p12. These results suggest that deletions on 8p22-p21.3 play an important role in tumor differentiation, while an 8p21.1-p21.2 deletion plays a role in the progression of prostate cancer.

Aged↗
PubMed2001

Oral etoposide following combination chemotherapy and radiation therapy in a patient with advanced adult neuroblastoma led to long survival.

Although neuroblastoma is a common tumor of early childhood, it is rare in adults. In spite of the poor prognosis of advanced neuroblastoma in adults, there is still no effective treatment for this condition in adults. Here we report that oral etoposide salvage chemotherapy was able to prolong the survival of an adult patient with advanced neuroblastoma. A 26-year-old man had advanced neuroblastoma that was resistant to combination intravenous chemotherapy and radiation therapy. He was then treated with oral etoposide, at a dose of 50 mg daily for 5 days in a 21-day course. Toxicity was very mild and he was followed as an outpatient while he received 76 courses of this oral etoposide salvage chemotherapy. Seventy months after diagnosis, this patient is still alive and has no new distant metastases.

Administration, Oral↗
PubMed2001

Generation and properties of ascorbic acid-deficient transgenic tobacco cells expressing antisense RNA for L-galactono-1,4-lactone dehydrogenase.

In higher plants, the terminal step of L-ascorbic acid (AsA) biosynthesis is catalyzed by the enzyme L-galactono-1,4-lactone dehydrogenase (EC 1.3.2.3, GalLDH). We generated AsA-deficient transgenic tobacco BY-2 cell lines by antisense expression of the GalLDH cDNA that was amplified from BY-2 cells using PCR. Two transgenic cell-lines, AS1-1 and AS2-2, having a marked expression of antisense RNA were analyzed. Antisense suppression of GalLDH mRNA led to a significant decline in the GalLDH activity. The AsA levels in the transgenic cell lines were found to be 30% lower than the wild-type BY-2 cells. In synchronous cultures, division of AS1-1 and AS2-2 cells was restrained with a concomitant decrease in mitotic index that was probably due to a decline in AsA levels. The rate of cell growth was also found to be less than that of the wild-type cells. Interestingly, there was a significant phenotypic difference between the transgenic and wild-type cells. The calli of AS1-1 and AS2-2 appeared to be sticky and soft. Back extrusion method also showed that AsA-deficient BY-2 callus was rheologically soft. Furthermore, microscopic analysis revealed that AS1-1 and AS2-2 cells were abnormally slender, suggesting a potential for a significant and a uni-axial elongation. Thus, we observed that decline in the AsA levels has an adverse effect on the division, growth and structure of a plant cell.

Ascorbic Acid↗
PubMed2001

Applying secondary ion mass spectrometry to the analysis of elements in goblet cells of conjunctiva.

We investigated the location of elements in the goblet cells of rat conjunctiva by analyzing ion images produced by secondary ion mass spectrometry (SIMS) and comparing them with those produced by energy dispersive X-ray analyser (EDX). Conjunctivas of normal Spraque-Dawley rats were quenched in propane prechilled liquid nitrogen. Semi-thin sections were made with a cryo-ultramicrotome, freeze-dried, carbon-coated and observed under a light microscope, SIMS and scanning electron microscope (SEM). In the element analysis by SIMS, images of positive ions were examined with an O2+ primary ion source and images of negative ions with a Ga+ ion source. The same sections were observed and analysed with SEM-EDX. Morphological features and images of elements with SIMS and EDX were compared. Na, Mg, K, and Ca were detected as positive ions and OH, CN, P, S, and Cl as negative ions with SIMS, but C, N, O, Na, Mg, P, S, Cl, K, and Ca were detected with EDX. The spatial resolution of SIMS in element location was higher than that of EDX. Many elements were clearly located in the goblet cells on ion images by SIMS. Element ion images were demonstrated more densely in goblet cells than in other parts within conjunctiva and by SIMS compared to EDX. SIMS is a useful method for the detection of elements and their locations in ocular tissues and cells.

Animals↗
PubMed2001

Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer.

Several synthetic inhibitors of matrix metalloproteinases (MMPs) show antitumor, antimetastasis and antiangiogenesis effects in various models. Synergistic effects of combinations with conventional cytotoxic agents were reported previously. In this study, we examined the effects of a new selective MMP inhibitor, MMI-166, on tumor growth, angiogenesis and metastasis in a liver metastatic model of human xenotransplanted colon cancer (TK-4). We also investigated the synergistic effects of MMI-166 and a conventional cytotoxic agent, mitomycin C (MMC), in this model. Mice transplanted orthotopically with TK-4 were divided into 4 groups; a control group (treated with vehicle solution), an MMI-166 group in which MMI-166 was orally administered (p.o.) at a dose of 200 mg / kg, 6 days / week for 5 weeks, an MMC group in which MMC was administered intraperitoneally (i.p.) at a dose of 2 mg / kg / week for 5 weeks, and a combination group (treated with MMI-166 and MMC). MMI-166 did not inhibit transplanted tumor growth, but significantly inhibited liver metastasis compared with the control group and MMC group (P < 0.01). Significant antitumor and antimetastatic effects of the combination therapy were demonstrated. The microvessel density (MVD) detected by immunohistochemical staining with ER-MP12 antibody tended to be lower in the MMI-166 and the combination groups. These results suggest that MMI-166 has potential antimetastatic ability and a synergistic effect with MMC.

Animals↗
PubMed2001

Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.

We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17alpha-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)(2)cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.

Apoptosis↗
PubMed2001

An elderly patient with gastric carcinoma developing multiple metastasis in skeletal muscle.

We present a 70-year-old man with gastric carcinoma developing multiple metastasis in skeletal muscle. He had a right supraclavicular lymph node swelling. Brain, chest and abdomen CT scans revealed metastatic lesions in the brain, lung, liver and bilateral adrenal glands. Further, CT showed a ring enhanced soft-tissue mass in the left lumbar muscle. Needle aspirate of the mass in both the left lumbar muscle and the right enlarged supraclavicular lymph node revealed cells suggestive of poorly differentiated adenocarcinoma. Upper gastrointestinal endoscopic evaluation demonstrated an advanced gastric carcinoma. Two months after admission, the tumor in the left lumbar muscle had grown and some new lesions in the left iliopsoas muscles appeared. Intramuscular metastasis from gastric carcinoma is an extremely rare phenomenon.

Adenocarcinoma↗
PubMed2001

Asymptomatic pyuria in diabetic women.

The aim of the present study was to determine the prevalence of and the host factors for asymptomatic pyuria (ASP) in women with type 2 diabetes. The study included 179 type 2 diabetic women and consecutive 455 non-diabetic women attending as out-patients in 1996. Patients with symptoms of a urinary tract infection were excluded. ASP was defined as the presence of more than 10 leukocytes/high-power field in a random urine sample. Diabetic women more often had ASP than non-diabetic women (27.9 vs. 15.8%, P<0.001). The prevalence of ASP was significantly increased in patients with a duration of diabetes exceeding 15 years (0 approximately 4 years; 20.3%, 5 approximately 9 years; 24.3%, 10 approximately 14 years; 23.8%, and > or =15 years; 46.3%). No differences were evident in HbA(1C) between diabetic patients without ASP and those with ASP. Diabetic women with ASP more often had diabetic retinopathy, neuropathy, nephropathy, cerebrovascular disease, ischemic heart disease, and hyperlipidemia than those without ASP. However, no statistically significant differences were evident in the prevalence of hypertension, constipation, or dementia. As the degree of neuropathy increases, it is accompanied by an increasing prevalence of ASP (none, 21.4%; blunt tendon reflexes, 24.5%; symptomatic, 50.0%; and gangrene, 66.6%). The prevalence of ASP was significantly increased in the patients with proliferative diabetic retinopathy (none, 23.2%; background, 29.4%; pre-proliferative, 18.2%; and proliferative, 50.0%). As the degree of nephropathy increases, it is accompanied by an increasing prevalence of ASP (none, 20.0%; microalbuminuria, 31.9%; macroalbuminuria, 37.0%; and renal failure, 60.0%). Thus, the prevalence of ASP is increased in women with diabetes and increased with longer duration of diabetes but was not affected by glucose control. The incidence of ASP increases significantly as diabetic microangiopathy becomes severer.

Aged↗
PubMed2001

Clinical usefulness of the common carotid artery blood flow velocity ratio as measured by an ultrasonic quantitative flow measurement system: evaluation with respect to prevalence of ischemic heart disease.

The present study evaluated the clinical usefulness of the measurement of common carotid artery blood flow velocity by an ultrasonic quantitative flow measurement system (QFM), and its correlation with the prevalence of ischemic heart disease (IHD). The subjects in this study included 287 patients (149 men and 138 women; mean age, 67.6+/-11.0 years) being treated as outpatients. Bilateral common carotid artery blood flow velocity was measured using a QFM-1100 (Hayashi Denki Co., Ltd.). The "high to low velocity ratio" (H/L ratio) was calculated by dividing the higher value by the lower value of the velocity of the common carotid artery. In 43 of 287 patients, we used an SSA-270 ACE (Toshiba Co., Ltd) to determine the presence of plaque and measure intimal-medial thickness (IMT) in the common carotid arteries. The mean H/L ratio was 1.45, with a median value of 1.25. The patients were stratified into subgroups based on H/L ratios from 1.0 and above in 0.1 increments in order to compare the prevalence rates of IHD. The prevalence rates in groups with H/L ratios of 1.3 and greater were significantly higher than those in the group with H/L ratios less than 1.3. In logistic regression analysis, the unadjusted H/L ratio was an independent risk factor for IHD at ratios from greater than 1.1 to greater than 1.6. The age-adjusted H/L ratio was an independent risk factor for IHD at ratios from greater than 1.1 to greater than 1.4. IMT was significantly higher in patients with a H/L ratio of 1.4 or greater versus patients with a ratio less than 1.4 (1.154+/-0.417 mm vs. 0.421+/-0.425 mm; p<0.05). The prevalence of carotid artery plaque was also significantly higher in patients with a H/L ratio of 1.4 or greater versus patients with a ratio of less than 1.4 (76.5% vs. 38.5%; p<0.03). Therefore, determination of the carotid artery H/L ratio by means of QFM may be clinically useful in screening patients for coronary artery lesions.

Aged↗
PubMed2001

Clinical usefulness of measuring pulse wave velocity in predicting cerebrovascular disease: evaluation from a cross-Sectional and longitudinal follow-up study.

The present study was designed both as a cross-sectional and longitudinal follow-up study to evaluate the association between pulse wave velocity (PWV) and cardiovascular disease. The subjects in this study included a total 260 patients (134 men and 126 women) ranging from 25 to 91 years (mean, 67.6+/-11.0 years). Carotid to femoral PWV was measured in all patients. The subsequent development of a cerebrovascular or coronary event was defined as a cardiovascular event. The longitudinal follow-up study was conducted with the occurrence of a cardiovascular event as the endpoint. The patients were classified into two groups: an L group with a PWV of less than 10 m/sec and an H group with a PWV of 10 m/sec or higher. Cross-sectional study at baseline: The H group patients were significantly older than the L group patients. The prevalence of hypertension, cardiovascular disease, ischemic heart disease, and cerebrovascular disease were significantly higher in the H group. Systolic blood pressure and serum uric acid were significantly higher in the H group than in the L group. However, there were no significant differences between the two groups with respect to other risk factors. Multivariate analysis using the prevalence of cardiovascular disease as the dependent variable showed "age" and "H group" to be independent variables. When the prevalence of ischemic heart disease or cerebrovascular disease was used as dependent variable, only "age" was an independent variable. Longitudinal follow-up study: The prevalence of cardiovascular event and cerebrovascular event were significantly higher in the H group than in the L group. The prevalence of coronary event in the H group tended to be higher than in the L group, but the difference was not statistically significant. Multivariate analysis using the cardiovascular event rate or coronary event rate as the dependent variable showed only "age" to be an independent variable. When the cerebrovascular event rate was used as the dependent variable, "uric acid" and "H group" were independent variables. The results of this study suggest a higher rate of cerebrovascular disease in patients with high PWV.

Adult↗
PubMed2001

Ileus after administration of cold remedy in an elderly diabetic patient treated with acarbose.

A 69-year-old type 2 diabetic man was admitted due to diabetic gangrane. He had a history of subtotal gastrectomy. During hospitalization, he was treated with regular insulin and 300 mg/day of acarbose. He developed a low grade fever, cough and nasal discharge, and was given a compound "cold" remedy with anticholenergic properties. The next day, he suffered from a paralytic ileus. Oral intake and acarbose were withheld and the ileus spontaneously resolved after 2 days. These finding indicate the possibility that the ileus was triggered by drugs with anticholinergic properties in this elderly diabetic patient treated with alpha-glucosidase inhibitors.

Acarbose↗
PubMed2001

[A four-year prospective study on the influence of serum elevated lipoprotein (a) concentration on ischemic heart disease and cerebral infarction in elderly patients with type 2 diabetes].

To clarify the influence of elevated serum lipoprotein (a) (Lp(a)) concentration on ischemic heart disease (IHD) and the perforating artery occlusion type of cerebral infarction (CI) in elderly patients with type 2 diabetes, we measured the serum levels of Lp(a) of type 2 diabetic patients (n = 158, 81 men and 77 women). The group was followed up prospectively for 4 years and the incidence of IHD or CI was monitored. The diagnosis of CI was confirmed by computed tomography and that of IHD, which includes myocardial infarction and angina pectoris, was diagnosed by electrocardiogram and blood chemistry examination, Lp(a) concentrations of 20 mg/dl or more were identified as elevated Lp(a) levels and Lp(a) concentrations of less than 20 mg/dl were identified as normal Lp(a) levels. A Kaplan-Meier survival analysis (log-rank test) assessed the time to event rate stratified by an Lp(a) cutoff point of 20 mg/dl. The predictive value for CI or IHD events was assessed by multiple logistic regression analysis. The probability of IHD events was significantly higher in the elevated Lp(a) group than in the normal Lp(a) group without a history of IHD but was similar in the two groups for those patients with a history of IHD. There was no significant difference between the elevated Lp(a) group and the normal Lp(a) group with regard to CI events in patients without a history of CI and with a history of CI. On multiple logistic regression analysis, Lp(a), hyperlipidemia and a history of IHD were significant predictors of IHD and hypertension, hyperlipidemia and a history of CI were significant predictors of CI. These results show that elevated serum Lp(a) concentrations is an independent risk factor for IHD, but not for the perforating artery occlusion type of CI in type 2 elderly diabetic patients.

Aged↗
PubMed2001

Deletions on chromosome 8p22 may predict disease progression as well as pathological staging in prostate cancer.

PURPOSE: A recent report demonstrated that the deletion of chromosome 8p22 could predict disease progression in stage III (capsular penetrating) prostate cancer. We studied if the status of chromosomal deletions of 8p22 could reflect pathological stage as well as patient prognosis, thereby serving as a diagnostic tool to optimize the treatment strategy in prostate cancer. EXPERIMENTAL DESIGN: A total of 97 patients (41 Japanese and 56 Swedish) were studied by the fluorescence in situ hybridization technique. Seventy-seven patients (23 pT2, 18 pT3, and 36 pN+ tumors) underwent surgery (radical prostatectomy or lymph node dissection). The specimens were prepared by touch biopsy. From another 20 cases, fine-needle aspiration biopsies were obtained. RESULTS: 8p22 deletions were detected in 47 (61%) and 11 (55%) specimens of 77 touch biopsies and 20 fine-needle aspiration biopsies, respectively. No significant difference was found in the frequency of 8p22 deletion between different preparations of specimens, as well as between different races (Japanese versus Swedish). The frequency of 8p22 deletion was statistically higher in patients with pT3 or more than in those with pT2 (P < 0.01). Disease progression was evaluated in 57 patients. The Cox proportional hazards model revealed 8p22 deletion to be the strongest parameter to predict disease progression (hazards ratio = 5.75; P = 0.0001). CONCLUSIONS: Studies on chromosomal deletions of 8p22 by fluorescence in situ hybridization technique may serve as a genetic marker to optimize the treatment strategy in patients with prostate cancer to the optimal treatment.

Aged↗