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Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 91 records · Page 5Linked to original sources
PubMed2001

Evaluation of the epidermal growth factor receptor (EGFR) and c-erbB-2 in superspreading-type and penetrating-type gastric carcinoma.

The expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), transforming growth factor alpha (TGF alpha), and of c-erbB-2 was immunohistochemically investigated in resected gastric carcinoma (in 39 cases of superspreading type and in 11 cases of penetrating type), to understand the differential biological features of these two types of gastric carcinoma. EGF, EGFR and c-erbB-2 positive cases were preferentially found in penetrating type rather than in superspreading type (p < 0.05, p < 0.01, and p < 0.05, respectively). The positive rates of EGFR and c-erbB-2 were significantly higher in submucosal gastric carcinoma than in intramucosal gastric carcinoma (p < 0.01, p < 0.05, respectively). These results suggested that the autocrine mechanism of the growth factors and the expression of c-erbB-2 were correlated to the degree of gastric wall invasion.

Adult↗
PubMed2001

Advanced gastric cancer effectively treated by neoadjuvant continuous low-dosage 5-fluorouracil and cisplatin (FP regimen): a case report.

We have experienced a case of advanced gastric cancer with para-aortic lymph node metastasis effectively treated by neoadjuvant continuous low dosage 5-fluorouracil and cisplatin (FP regimen). The patient was a 67-year-old man diagnosed as having advanced gastric cancer type 4 with para-aortic lymph node metastasis. This patient was treated by continuous infusion of 5-fluorouracil (5-FU) 500 mg/day, for 28 days, and infusion of cisplatin 10 mg/day over 1 hr on days 1-5, 8-12, 15-19, and 22-26. At 4 weeks later, a CT revealed that swelling in the para-aortic lymph node had disappeared, and the thickening in the stomach wall had diminished. This patient underwent a curative operation, and both the serum level of carcinoembryonal antigen (CEA) and carbohydrate antigen (CA 19-9) decreased to normal. These results suggested that the FP regimen was an effective neoadjuvant treatment for advanced gastric cancer with para-aortic lymph node metastasis.

Aged↗
PubMed2001

Long-term survival after gastric cancer with liver metastasis: a report of two cases.

We have experienced two cases of long-term survival after surgery for gastric cancer case with liver metastasis. One case was of a 66-year-old male patient diagnosed as having type 1 advanced gastric cancer located in the posterior wall of the lower body with liver metastasis. The stage of this case was P0H1N1T2M0 stage IV. This patient underwent distal gastrectomy with D2 lymph node resection, partial hepatectomy of the S3 region including the metastatic liver tumor and coagulation of metastatic liver tumors in the S6 and S7 regions. This patient was treated by intra-hepatic arterial infusion of 5-FU, CDDP and peroral administration of UFT after surgery. This patient has died at 3 years and 7 months after surgery. The other case was of a 55-year-old male patient diagnosed as having type 2 advanced gastric cancer located in the lesser curvature of the cardia with liver metastasis. The stage of this case was P0H1N1T3 M0 stage IV. This patient underwent total gastrectomy with D2 lymph node dissection, wedge resection of the S8 region including the metastatic liver tumor and coagulation of a metastatic liver tumor in the S4 region. This patient was treated by obstruction of the hepatic artery using coils, peroral administration of UFT, lentinan, MMC, and continuous low-dosage 5-FU and CDDP after surgery. This patient has died at 3 years and 6 months after surgery. These results suggest that for long-term survival in cases of gastric cancer with liver metastasis, hepatectomy or coagulation of the metastatic tumor with postoperative chemotherapy are indicated in cases that have no non-curative factors and only a few metastatic tumors.

Aged↗
PubMed2001

Demethylation by 5-aza-2'-deoxycytidine (5-azadC) of p16INK4A gene results in downregulation of vascular endothelial growth factor expression in human lung cancer cell lines.

Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor progression via angiogenesis. Recently, gene transduction of wild-type p16INK4A, tumor suppressor gene, has been shown to result in downregulation of VEGF expression in p16INK4A-deleted glioma cells. Because expression of p16INK4A is regulated by methylation of the p16INK4A gene, we examined whether demethylation of the p16INK4A gene by 5-aza-2'-deoxycytidine (5-azadC) could cause the protein expression of VEGF as well as of p16INK4A in human lung cancer cells. For this, five different lung cancer cell lines with or without loss of p16 activity were used. H841 and Ma-10 cells had the methylated p16INK4A gene without expression of p16INK4A protein, whereas Ma-1 and H209 cells had the unmethylated p16INK4A gene with constitutive expression of p16INK4A protein. Neither the p16INK4A gene nor p16INK4A protein was detected in A549 cells. Treatment with 5-azadC caused demethylation of the p16INK4A gene with reexpression of p16INK4A protein in H841 and Ma-10 (methylated p16INK4A gene dominant) cell, but not in other cell lines such as Ma-1, H209 (unmethylated p16INK4A gene dominant), or A549 (p16INK4A gene deleted). In a parallel experiment, 5-azadC inhibited production of VEGF protein by H841 and Ma-10 cells, especially in the later hypermethylated cells, but not Ma-1, H209, or A549 cells. RT-PCR analysis showed that Ma-10 cells expressed VEGF isoforms 121, 165, and 189, all of which were inhibited by 5-azadC. These findings indicate that the methylation status of the p16INK4A gene plays an important role in the regulation of angiogenesis associated with progression of lung cancer, through regulation of VEGF expression.

Antimetabolites, Antineoplastic↗
PubMed2001

Corticosteroid therapy in patients with IgA nephropathy and impaired renal function.

AIM: IgA nephropathy (IgAN) is a common type of primary glomerulonephritis that constitutes a major cause of end-stage renal disease. Oral and/or intravenous glucocorticoid therapy can protect against progression of IgAN in patients with preserved renal function. We evaluated steroid therapy in IgAN with established renal dysfunction. PATIENTS AND METHODS: We retrospectively analyzed the effect of methylprednisolone (MP) pulse therapy in 8 IgAN patients with serum creatinine concentrations (sCr) 2.76 +/- 1.32 mg/dl (mean +/- SD). In each patient renal function had progressively deteriorated in the 12 months preceding treatment, as indicated by negative slopes of 1/sCr plotted against time (regression coefficients). RESULTS: Regression coefficients during the 12 months following therapy improved significantly from -0.02333 +/- 0.00732 to -0.00036 +/- 0.00423 dl/mg/month, respectively. The mean difference in slope was 0.0230 +/- 0.0076 dl/mg/month (95% confidence interval, 0.0165 to 0.0295, p < 0.001). Proteinuria also significantly decreased from a mean urine protein/creatinine ratio of 2.57 +/- 1.12 before therapy to 1.12 +/- 0.84 6 months after therapy (p < 0.005). Other factors that might affect progression of renal dysfunction remained unchanged during the observation periods. CONCLUSION: Corticosteroids may attenuate progression of renal failure and delay the need for dialysis in this patient population, although a large randomized trial is necessary.

Administration, Oral↗
PubMed2001

[Clinical evaluation of patients with pulmonary tuberculosis during the past 10 years in our hospital].

The background of patients who died of active pulmonary tuberculosis during 10 year's period (1989 to 1998). Of 973 tuberculosis patients, 76 patients died, of which 56 died of non-tuberculosis, and 20 died of tuberculosis. A total of 12 patients died within 3 months after being hospitalized. The period from hospitalization to death was significantly shorter in tuberculosis patients with independent gait failure, original treatment, without tuberculosis medical history, and no drug resistance. We considered that in tuberculosis death, severe tuberculosis itself is the cause of early death, and recurrence and drug resistance patients are the most serious problems in later deaths.

Adult↗
PubMed2001

[A case of advanced non-small-cell lung cancer responding remarkably to weekly chemotherapy with paclitaxel].

We report a case of advanced non-small-cell lung cancer showing remarkable response to weekly administration of paclitaxel. The patient was a 63-year-old man who had IIIB advanced lung adenocarcinoma. Though he received one course of cisplatin and etoposide, the tumor was not reduced. In addition, because of his nauseous response, he no longer wanted to receive that chemotherapy. The chemotherapy regimen was therefore changed to weekly administration of vinorelbine, but this was not effective. Next, after changing the regimen to the weekly administration of paclitaxel, the tumor was remarkably reduced following 3 courses. This case shows that weekly administration of paclitaxel may be an effective chemotherapy for non-small cell lung cancer not responsive to first-line chemotherapy.

Adenocarcinoma↗
PubMed2001

[The usefulness of two-step tuberculin skin testing in nosocomial infection cases].

The usefulness of the two-step tuberculin skin test in the preceding year for the contact investigation was reported, when a pulmonary tuberculosis patient was discovered in our hospital. Four persons showed stronger reaction than the results in two-step tuberculin skin test in the preceding year after nosocomial infection. One of them was diagnosed as pulmonary tuberculosis by chest radiograph, and antituberculosis chemotherapy was started. Other three started chemoprophylaxis. The chemoprophylaxis subjects might increase 4, if basic value of tuberculin reaction had not been available by two-step tuberculin skin test in the previous year. We could identify persons in whom tuberculin reaction became stronger by comparing the test results after exposure with the result of two-step tuberculin skin test in the preceding year. It is considered that two-step tuberculin skin test is very useful to efficiently execute the protective measure.

Adult↗
PubMed2001

[The effectiveness of steroid as adjunctive therapy in the management of two patients with febrile reaction due to antituberculous drugs].

Antituberculous treatment could be continued by using steroid as adjunctive therapy in two patients showing febrile reaction to antituberculous drugs in spite of desensitization therapy. Case 1 (39-year-old man) was admitted to our hospital with positive sputum-smear and bilateral cavitary tuberculosis (b II 2) on chest X-ray. He showed fever of 38-39 degrees C after 8 days of HREZ treatment. Desensitization therapy of RFP with the combined use of prednisolone was enforced, since the exothermic reaction continued in spite of stopping the 4 medicines, and the treatment became possible. Case 2 (40-year-old woman) was admitted with positive sputum-smear and bilateral cavitary tuberculosis (b II 2) on chest X-ray. The administration of drugs was stopped as temperature rose to 38-39 degrees C after 12 days of HREZ treatment. Though the DLST of INH was positive, the treatment with INH became possible by the combined use of PSL.

Adult↗
PubMed2001

[Angioplasty with stenting for intracranial vertebral and basilar artery stenosis: three technical case reports and literature review].

Patients with intracranial vertebral artery (VA) or basilar artery (BA) stenosis have been mainly treated with medication. However, it has been reported that about 10% of patients experience restroke in the VBA territory, with a high rate of morbidity and mortality. Percutaneous transluminal angioplasty (PTA) is regarded as one of the treatments although it carries the risk of restenosis, recoil or dissection. Stent placement is, therefore, considered to be a further option for the treatment of intracranial artery stenosis since it can prevent the restenosis. We report three medical refractory cases of intracranial VA (2 cases) or BA stenosis (1 case) treated with stenting, none of which had complications and their symptoms disappeared or diminished. Angioplasty with the use of a stent device is regarded as a useful treatment for intracranial artery stenosis, but its risk and long-term result need to be investigated further.

Aged↗
PubMed2001

Analysis of gene expression of lymphocytes in microgravity.

It has been reported that lymphocyte function decreases under microgravity. Though molecular mechanism of the immunosuppression in microgravity still remains enigmatic, it is suggested that gene expression of lymphocytes may be altered in microgravity. In this study we developed automatic flash-freezing equipment which can be utilized for exposing lymphocytes to microgravity by drop shaft experiments in Japan Microgravity Center (JAMIC). Gene expression profiles were analyzed by using DNA array in ground control lymphocytes and microgravity-exposed lymphocytes.

Freezing↗
PubMed2000

Natural killer cell-dependent suppression of systemic spread of human lung adenocarcinoma cells by monocyte chemoattractant protein-1 gene transfection in severe combined immunodeficient mice.

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine with various biological activities, including augmentation of cytotoxic activity of monocytes and natural killer (NK) cells. The present study was undertaken to determine whether transfection of the MCP-1 gene into lung cancer cells affected their tumorigenicity and metastatic potential by the NK cell-mediated mechanism. The human MCP-1 gene inserted into an expression vector (BCMGSNeo) was transfected into human lung adenocarcinoma (PC-14) cells. There was no difference in in vitro proliferation between MCP-1 gene-transfected PC-14 cells and the parent cells or mock-transfected cells. The tumorigenicity and in vivo tumor growth of MCP-1 gene-transfected PC-14 cells were similar to those of the parent cells or mock-transfected cells when tumor cells were injected into the s.c. space of NK cell-intact severe combined immunodeficient (SCID) mice. Although parent cells and mock-transfected cells inoculated i.v. formed lung metastatic colonies and pleural effusion, MCP-1 gene transfectants reduced the systemic spread in NK cell-intact SCID mice. Interestingly, these modulations in a systemic spread by MCP-1 gene transfection were not observed in NK cell-depleted SCID mice. Decreased survival of MCP-1 gene transfectants in the lung was observed in NK cell-intact SCID mice but not in NK cell-depleted SCID mice. Recombinant MCP-1 or the supernatant of MCP-1 gene transfectants enhanced the cytotoxicity of human CD56+ NK cells and spleen cells of SCID mice against PC-14 cells. These findings suggest that locally produced MCP-1 suppresses tumor progression by a NK cell-mediated mechanism, depending on organ microenvironment.

Adenocarcinoma↗
PubMed2000

Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.

We investigated the molecular mechanisms of angiogenesis in experimental brain metastasis. Cells from six different human cancer cell lines (proven to produce visceral metastasis) were injected into the internal carotid artery of nude mice. Colon carcinoma (KM12SM) and lung adenocarcinoma (PC14PE6 and PC14Br) cells produced large, fast-growing parenchymal brain metastases, whereas lung squamous cell carcinoma (H226), renal cell carcinoma (SN12PM6), and melanoma (TXM13) cells produced only a few slow-growing brain metastases. Rapidly progressing brain metastases contained many enlarged blood vessels. The expression of VEGF mRNA and protein by the tumor cells directly correlated with angiogenesis and growth of brain metastasis. Causal evidence for the essential role of VEGF in this process was provided by transfecting PC14PE6 and KM12SM cells with antisense-VEGF165 gene, which significantly decreased the incidence of brain metastasis. In contrast, transfection of H226 human lung squamous carcinoma cells with sense-VEGF121 or sense-VEGF165 neither enhanced nor inhibited formation of brain metastases. Collectively, the results indicate that VEGF expression is necessary but not sufficient for the production of brain metastasis and that the inhibition of VEGF represents an important therapeutic target.

Animals↗
PubMed2000

Complete regression of xenografted human carcinomas by camptothecin analogue-carboxymethyl dextran conjugate (T-0128).

Clinically available camptothecins (CPTs), such as irinotecan (CPT-11) and topotecan, represent one of the most promising classes of antitumor agents, despite their toxicity. To improve their pharmacological profiles, a new macromolecular prodrug, denoted T-0128, was synthesized. This prodrug is a novel CPT analogue (T-2513)-carboxymethyl (CM) dextran conjugate via a triglycine spacer, with a molecular weight of Mr 130,000. This study was designed to test the concept that the rational design of a CPT-polymer conjugate would increase the efficacy of the parent drug. The in vivo antitumor study against Walker-256 carcinoma demonstrated that T-0128 was 10 times as active as T-2513, supporting this concept. Additionally, comparative efficacy studies of T-0128, T-2513, CPT-11, and topotecan were performed using a panel of human tumor xenografts in nude mice, showing the advantage of T-0128 over these CPTs. The maximal tolerated doses (MTDs) of T-0128, T-2513, and CPT-11 were comparable. Even a single i.v. injection of T-0128 at 6 mg/kg (based on the amount of T-2513 bound to CM dextran) induced complete regression of MX-1 mammary carcinoma. T-0128 at 10 mg/kg weekly for 3 weeks (one-tenth of its MTD) cured LX-1 lung carcinoma. Also, T-0128 below its MTD consistently cured or regressed St-4 gastric and HT-29 colorectal tumor xenografts that are highly refractory to CPTs. These demonstrate the broad range of therapeutic doses achieved with T-0128. Pharmacokinetic studies were performed to correlate the efficacy results obtained for T-0128 with plasma and tissue drug concentrations using Walker-256 tumor-bearing rats. Results showed that after i.v. administration of T-0128, the conjugate continued to circulate at a high concentration for an extended period, resulting in tumor accumulation. In the tumor, the sustained release of T-2513 occurred. In contrast, T-2513 disappeared rapidly from the body. The significant increases in the amount and exposure time of released T-2513 in the tumor explain well the enhanced efficacy of T-0128. In conclusion, this study indicated that T-0128 improved the potency of T-2513, demonstrating the proof of the above concept.

Animals↗
PubMed2000

Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 2'-deoxyribonucleosides.

A new class of 5-halogenated pyrimidine analogs substituted at the 6-position was evaluated as competitive inhibitors of thymidine phosphorylase (TPase). The most potent member of the series was 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidine dio ne hydrochloride (TPI), which has an apparent K(i) value of 1.7 x 10(-8) M. TPI selectively inhibited the activity of TPase, but not that of uridine phosphorylase, thymidine kinase, orotate phosphoribosyltransferase, or dihydropyrimidine dehydrogenase. In vitro inhibition studies of TPI using a thymidine analogue, 5-trifluoromethyl-2'-deoxyuridine (F(3)dThd), as the substrate demonstrated that F(3)dThd phosphorolytic activity was inhibited markedly by TPI (1 x 10(-6) M) in extracts from the liver, small intestine, and tumors of humans, from the liver and small intestine of cynomolgus monkeys, and from the liver of rodents, but not from the liver or small intestine of dogs or the small intestine of rodents, suggesting that the distribution of TPase differs between humans and animal species, and that TPI could contribute to the modulation of TPase in humans. When F(3)dThd or 5-iodo-2'-deoxyuridine (IdUrd) was coadministered to mice with TPI at a molar ratio of 1:1, the blood levels of F(3)dThd (or IdUrd) were about 2-fold higher than when F(3)dThd (or IdUrd) was administered alone. In monkeys, the maximum concentration (C(max)) and the area under the concentration-time curve (AUC) after oral F(3)dThd alone were 0.23 microg/mL and 0.28 microg. hr/mL, respectively, but markedly increased to 15.18 microg/mL (approximately 70-fold) and 28.47 microg. hr/mL (approximately 100-fold), respectively, when combined with equimolar TPI. Combined oral administration of TPI significantly potentiated the antitumor activity of F(3)dThd on AZ-521 human stomach cancer xenografts in nude mice. In conclusion, TPI may contribute not only to inhibition of TPase-mediated biological functions but also to potentiation of the biological activity of various 2'-deoxyuridine and thymidine derivatives by combining with them.

Administration, Oral↗