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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 307 records · Page 17Linked to original sources

Potentiation of the antitumor activity by a novel quinoline compound, MS-209, in multidrug-resistant solid tumor cell lines.

A novel quinoline compound, MS-209, was examined for its ability to reverse multidrug resistance (MDR) in several murine and human MDR solid tumor cell lines both in vitro and in vivo. MS-209 strongly reversed drug resistance to adriamycin (ADM) and vincristine (VCR) in acquired MDR tumor cell lines, 2780AD and KB-C1. In addition, MS-209 enhanced the cytotoxic effect of ADM and VCR on various human and murine cell lines. Particularly in 4-1St cells, which are extremely resistant to ADM and VCR, MS-209 at a concentration of 3 microM enhanced the cytotoxicity of ADM and VCR, 88- and 350-fold, respectively. MS-209 administered orally, together with ADM, enhanced the antitumor activity of ADM on Colon 26 and 4-1St tumors implanted subcutaneously (SC) in mice; the antitumor effect of ADM plus MS-209 was higher than that of ADM alone at the maximum tolerated dose (MTD). Furthermore, the coadministration schedules of MS-209 to attain the highest potentiation of ADM activity were examined using Colon 26 tumors. The maximum antitumor activity was obtained when MS-209 was administered on the same day as ADM. MS-209 administered a day before the ADM injection exhibited no potentiation effect, whereas MS-209 administered a day after the ADM injection showed a moderate effect. The effect of MS-209 was weaker when administered in a fractionated manner than when administered as a single dose. The results presented in this article suggest that MS-209 is an effective agent to overcome MDR in cancer chemotherapy.

Adenocarcinoma↗

[Treatment of thoracic esophageal carcinoma which invades adjacent structure--significance of resection and combined therapy].

From January 1980 to December 1994, a total of 64 cases of thoracic esophageal carcinoma which invaded adjacent structure (A3) were resected and 35 cases were unresected in Kagoshima University Hospital. Adjacent structures were mainly trachea/bronchus, aorta or pulmonary vein. Combined resections were performed in 22 cases (34.4%), and no tumors remained in 12 cases (18.8%). One year survival rates and 50% survival time of the no residual tumor group were 25.7% and 8.5 months, while the rates of the residual tumor group were 15.7% and 5.1 months. But, there was no significant difference of survival rates according to the amount of residual tumor. On the other hand, 1-year survival rates and 50% survival time of unresected group were 3.1% and 4.5 months. As a postoperative adjuvant therapy, radiation was the most effective modality. As a result, operations should be done at first for the A3 carcinoma in which a complete combined resection is expected. On the other hand, radiation or chemotherapy should be selected for the cases in which the tumor may remain, even though combined resection is done.

Adult↗

[Analysis of DNA ploidy pattern and overexpression of p53 protein in cases of early gastric carcinoma with lymph node metastasis].

Twenty-one cases of surgically resected early gastric carcinoma with lymph nodal involvement (4 mucosal and 17 submucosal carcinomas) and 37 cases of that with no lymph nodal involvement (14 mucosal and 23 submucosal) were investigated by means of flow cytometry and immunohistochemical staining in order to clarify the correlation between lymph node metastasis and DNA ploidy pattern as well as overexpression of p53 protein. DNA aneuploidy was found to show a significantly higher frequency in submucosal carcinomas (60.0%) than in mucosal ones (22.2%), and also a significantly higher frequency in node positive cases (76.2%) than in node negative ones (32.4%). Meanwhile, the overexpression of p53 protein showed higher frequency in submucosal carcinomas (52.5%) than in mucosal ones (22.2%), and also higher frequency in node positive cases (47.6%) compared with that in node negative ones (40.5%). However there was no significant difference either in relation to the depth of tumor invasion or the lymph node metastasis. Thus, DNA aneuploidy showed a significant correlation to the depth of cancer invasion as well as lymph node metastasis, which was regarded as a useful indicator for the preoperative estimation of the depth of tumor invasion as well as lymph node metastasis.

Aneuploidy↗

[Super selective bronchial artery embolization using metallic coils in the management of hemoptysis].

Hemoptysis is one of the most important clinical problems of cardiopulmonary disease with high mortality rate. Its management is routinely performed with Bronchial Artery Embolization (BAE). However, it was reported that BAE had some disadvantages such as spinal injury and recurrent bleeding. In order to prevent spinal injury, we tried the super selective bronchial artery embolization (ss-BAE). This technique is especially available in the occlusion of the bronchial artery forming the common trunk with the spinal artery. Besides, BAE, considered to be only a palliative treatment, might cause recanalization due to reabsorption of the occlusive agent. So we used metallic coils to prevent this drawback. The ss-BAE with metallic coils was performed in 2 cases who had refractory hemoptysis against conservative therapy. Hemoptysis disappeared in both cases. The ss-BAE with metallic coils was shown to be safer and more effective than ordinary BAE.

Aged↗

[Rational lymphadenectomy in patients with cervical nodes metastasis for carcinoma of the lower third esophagus].

Prognostic value of removing cervical nodes in patients with carcinoma of the lower third esophagus is extremely controversial. Of 93 patients with curative esophagectomy via trans-thoracic approach, cervical nodes were involved in five patients (13%), upper mediastinal nodes in 12 patients (30%), and para-aortic nodes in only one patients (3%) for 40 patients whose proximal part of the tumor invading the mid-esophagus from below. Of the remaining 53 patients with tumor extent confined to the lower third esophagus, cervical nodes were involved in only one patients (2%), upper mediastinal nodes in five patients (9%), and paraaortic nodes in six patients (11%). Three of the five patients with cervical metastasis whose proximal part of the tumor invading the mid-esophagus survived for at least 22 months or more following three-field lymphadenectomy. Removing the cervical nodes in patients with carcinoma of the lower third esophagus may have some role to improve the survival if the tumor invades the mid-esophagus from below.

Carcinoma, Squamous Cell↗

[A case of liver metastasis of gastric leiomyosarcoma successfully treated by transarterial hepatic chemo-embolization and intra hepato-arterial chemotherapy repeated with infusion-a-port].

The patient was a 68-year-old male, who underwent total gastrectomy for giant leiomyosarcoma of the stomach and then had multiple hepatic metastases one year and six months later. Thus, transarterial hepatic chemo-embolization therapy with Lipiodol, adriamycin and gelfoam was given. Moreover, using a reservoir catheter and infusion arterial port, intermittent arterial infusion therapy with adriamycin, cyclophosphamide, and vincristine was attempted. In the metastasis lesion where there were rich blood vessels, Lipiodol was accumulated and the tumor was reduced on abdominal CT. The result indicated the efficacy of this treatment.

Aged↗

MTT-hybrid assay incorporates the advantages of both clonogenic and MTT assay radiosensitivity testing for fresh tumor samples.

After devising a 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-Hybrid assay that incorporates the advantages of both the clonogenic and standard MTT assays, we evaluated the validity of this system using a malignant fibrous histiocytoma (MFH) cell and four xenografted tumors. In the MFH cells the surviving fractions were correlated with radiation dose at three assays. In xenografted tumor cells, the surviving fractions determined by the MTT assay did not show a similar dose response, possibly because of contamination by normal cells. Changes in the surviving fraction of the xenografted cells were correlated to the radiation dose as determined by the clonogenic assays, but this assay took longer performance times and was not useful for evaluating tumors with a low planting efficiency. With the MTT-hybrid assay, changes in fractions of the four xenografted tumor cells were correlated to radiation dose. The MTT-hybrid assay required a smaller optimal number seeding cells and shorter assay time than those of the clonogenic assay. Therefore, the MTT-Hybrid assay can be used successfully to assess the radiosensitivity of both established tumor cell lines and fresh tumor samples.

Animals↗

[Surgical treatment for endocardial cushion defect in an elderly patient with pulmonary hypertension].

We performed surgery for a partial endocardial cushion defect (ECD) in a 67-year-old female patient with pulmonary hypertension. The patient had grade 2 tricuspid regurgitation and pulmonary hypertension (Pp/Ps = 0.58, Rp = 8.4 Um2). The operative procedure involved patch closure of the ostium primum and tricuspid annuloplasty with a Carpentier ring. The postoperative course was uneventful and the pulmonary hypertension improved (Pp/Ps = 0.33). Surgery for partial ECD should be recommended even for elderly patients.

Aged↗

[Hyperglycemia and symmetrical proximal neuropathy in diabetes].

A 60-year-old woman, diagnosed as having a diabetic symmetrical proximal motor neuropathy, is presented. In March 1995, she was referred to us because of untreated diabetes mellitus since 1990. Insulin treatment during one month decreased her postprandial plasma glucose level from more than 400mg/dl to about 200mg/dl. Soon after the treatment, she noticed lower proximal limb weakness bilaterally. In several months, her weakness progressed as the fasting plasma glucose level was increased. Her muscle power gradually recovered when the plasma glucose level was normalized. We therefore suggest that metabolic changes related to hyperglycemia, rather than ischemic vascular changes, play an important role in the pathogenesis of a diabetic symmetrical proximal motor neuropathy.

Diabetic Neuropathies↗

[Flutropium bromide was effective in relieving symptoms of lymphangioleiomyomatosis--a case report].

A 32-year-old woman was admitted with persistent dyspnea. Chest roentgenogram showed hyperinflation of the lungs, and diffuse reticular shadows in both lung fields. Chest CT showed diffuse cystic lesions and thickened vasculature. Examinations revealed severe hypoxemia, restrictive and obstructive ventilatory impairments, increased residual volume, and decreased carbon monoxide diffusing capacity. Lymphagioleiomyomatosis was strongly suspected, and a diagnosis confirmed histopathologically by lung biopsies. Inhalation of flutropium bromide was remarkably effective in relieving dyspnea and impaired pulmonary functions. It is suggested that flutropium bromide is beneficial for symptomatic improvement in patients with lymphangioleiomyomatosis.

Administration, Inhalation↗

Enhancement by neurotensin of hepatocarcinogenesis by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of neurotensin on hepatocarcinogenesis by N-nitrosomorpholine (NNM) was investigated in Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and alternate-day injections of neurotensin from the beginning until the end of the experiment. Preneoplastic and neoplastic lesions stained for placental type glutathione-S-transferase (GST-P) were examined histochemically. Administration of neurotensin significantly increased the percentage area and the number of GST-P-positive lesions, and the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that neurotensin enhances hepatocarcinogenesis and that this effect may be related to its effect in increasing cell proliferation in preneoplastic lesions.

Animals↗

Inhibition by the calmodulin antagonist trifluoperazine of experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of the calmodulin antagonist trifluoperazine on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) and on the ornithine decarboxylase (ODC) activity and labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks, and from the beginning of the experiment, received s.c. injections of 15 or 30 mg/kg body weight of trifluoperazine in depot form every other day until the end of the experiment. Preneoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P) were examined histochemically. In week 16, quantitative histological analysis showed that prolonged administration of 30 mg but not 15 mg/kg body weight of trifluoperazine resulted in significant reductions in the number and percentage area of GST-P-positive hepatic lesions. Trifluoperazine also caused significant decreases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and their adjacent hepatocytes. These findings indicate that trifluoperazine inhibits carcinogenesis and suggest that this effect may be closely related to its effect in inhibiting ODC activity and cell proliferation in the enzyme-altered lesions and their adjacent liver.

Animals↗

Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants.

Gene expression of human immunodeficiency virus (HIV) depends on a host cellular transcription factors including nuclear factor-kappaB (NF-kappaB). The involvement of reactive oxygen intermediates (ROI) has been implicated as intracellular messengers in the inducible activation of NF-kappaB. In this study, we compared the efficacy of two antioxidants, alpha-lipoic acid (LA) and N-acetylcysteine (NAC), which are widely recognized NF-kappaB inhibitors. Here, we demonstrate that LA has a more potent activity in inhibiting NF-KappaB-mediated gene expression in THP-1 cells that have been stably transfected with a plasmid bearing a hygromycin B resistance gene under the control of HIV-1 long terminal repeat (LTR) promoter. The spontaneous activation of NF-kappaB in this cell culture system leads to expression of the hygromycin phosphotransferase gene hence rendering the cells resistance to hygromycin B. In this study, the effect of the test compounds against transcriptional activity of HIV-1 LTR was evaluated based on the degree of cellular toxicity due to the inhibitory activity on the expression of hygromycin B resistance gene in the presence of hygromycin B. We also found that 0.2 mM LA could cause 40% reduction in the HIV-1 expression from the TNF-alpha-stimulated OM 10.1, a cell line latently infected with HIV-1. On the other hand, 10 mM NAC was required to elicit the same effect. Furthermore, the initiation of HIV-1 induction by TNF-alpha was completely abolished by 1 mM LA. These findings confirm the involvement of ROI in NF-kappaB-mediated HIV gene expression as well as the efficacy of LA as a therapeutic regimen for HIV infection and acquired immunodeficiency syndrome (AIDS). Moreover, this study validates the applicability of our present assay system which we primarily designed for the screening of candidate drugs against HIV-1 gene expression.

Acetylcysteine↗

Molecular cloning of a novel T cell-directed CC chemokine expressed in thymus by signal sequence trap using Epstein-Barr virus vector.

Precursors of most secreted and cell surface molecules carry signal sequences at their amino termini. Here we describe an efficient signal sequence trap method and isolation of a novel CC chemokine. An expression library was constructed by inserting 5' portion-enriched cDNAs from phytohemagglutinin-stimulated peripheral blood mononuclear cells into upstream of signal sequence-deleted CD4 cDNA in an Epstein-Barr virus shuttle vector. After electroporation into Raji cells, CD4 antigen-positive cells were enriched by repeated cell sorting and plasmids were recovered in Escherichia coli. Out of 100 plasmid clones examined, 42 clones directed expression of CD4 antigen on the cell surface. Among them were signal sequences of CD6, beta2-microglobulin, MGC-24, and T cell receptor epsilon-chain, and at least four novel potential signal sequences. A cDNA clone encoding a novel CC chemokine was isolated by using one of the trapped fragments. The gene designated as TARC from Thymus and Activation-Regulated Chemokine was expressed transiently in phytohemagglutinin-stimulated peripheral blood mononuclear cells and constitutively in thymus. Radiolabeled recombinant TARC specifically bound to T cell lines and peripheral T cells but not to monocytes or granulocytes. The binding of radiolabeled TARC to the high-affinity receptor (Kd, 2.1 nM) on Jurkat was displaced by TARC but not by interleukin-8, MIP-1alpha, RANTES, or MCP-1. TARC also bound to the promiscuous chemokine receptor on erythrocytes (Kd, 17 nM). TARC induced chemotaxis in T cell lines Hut78 and Hut102. Pretreatment of Hut78 with pertussis toxin abolished the TARC-induced cell migration. Collectively, T cells express a highly selective receptor for TARC that is coupled to pertussis toxin-sensitive G-protein. TARC may a factor playing important roles in T cell development in thymus as well as in trafficking and activation of mature T cells.

Amino Acid Sequence↗

Inhibition by amiloride of experimental carcinogenesis induced by azaserine in rat pancreas.

The effects of prolonged administration of the diuretic amiloride on pancreatic carcinogenesis induced by azaserine and on the labeling index of carcinogen-induced pancreatic lesions were investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight azaserine and also 5 mg/kg body weight amiloride every other day until the end of the experiment at week 62. Carcinogen-induced pancreatic lesions were examined by histochemical techniques and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histologic analysis showed that prolonged administration of amiloride significantly reduced the number and size (as percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely correlated with the subsequent development of pancreatic cancer. Amiloride also significantly decreased the labeling index of carcinogen-induced pancreatic lesions, but not of the surrounding acinar cells. In contrast, amiloride has no significant influence on the number and size of ATPase-negative pancreatic lesions. These findings indicate that amiloride inhibits pancreatic carcinogenesis, and that this effect may be related to the reduction of ATPase-positive lesions and to amiloride's inhibition of cell proliferation in neoplastic lesions of the pancreas.

Adenosine Triphosphatases↗