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Biomedical subjects

K Iwase

Publications and source records attributed to K Iwase.

166 records · Page 10Linked to original sources

Indirect inhibitory effect of a neurotensin receptor antagonist on human colon cancer (LoVo) growth.

The effect of the nonpeptide neurotensin (NT) receptor antagonist SR48692 on NT-mediated growth of xenografted human colon cancers (LoVo) was determined. Sixty-four athymic nude mice, inoculated with LoVo cells at a single site, were randomized into four groups of 16 mice each to receive either vehicle NT (600 microg/kg), SR48692 (2 mg/kg) or NT+SR48692 administered s.c., t.i.d., for 25 days. Treatment with NT significantly stimulated LoVo tumour growth, weight, DNA and protein content; SR48692 blocked this NT-mediated effect but had no effect when administered as a single agent. In addition, normal jejunum and ileum were removed and assessed. Similar to the effects on LoVo tumours, NT stimulated jejunal and ileal growth; SR48692 blocked this NT-mediated effect. In contrast to our in vivo findings, NT had no effect on LoVo cell growth in vitro. Also, Northern blot analysis demonstrated no expression for the NT receptor in either LoVo tumour cells or xenografted tumours. Our findings suggest that the trophic effect of NT on LoVo may be through an indirect effect; one possibility is that administration of NT may stimulate the release of other trophic factors which then stimulate tumour growth. The nonpeptide NT receptor antagonist SR48692 will be a useful agent to delineate the specific effects of NT on neoplastic as well as normal gastrointestinal tissues.

Analysis of Variance↗

Changes in superoxide dismutase activities and concentrations and myeloperoxidase activities in leukocytes from patients with diabetes mellitus.

To investigate whether the two free-radical scavengers, Cu, Zn- and Mn-superoxide dismutase (SOD), are changed in leukocytes of diabetic patients, and the alteration of these enzymes correlates with the diabetic state, we measured the activity and concentration of these enzymes in leukocytes from diabetic patients. Both Cu, Zn-SOD and Mn-SOD activities in neutrophils and lymphocytes were significantly lower in patients with non-insulin-dependent diabetes mellitus than in healthy controls. The concentrations of these enzymes in leukocytes from diabetic patients, however, did not differ from those in controls. Cu, Zn-SOD and Mn-SOD activities in neutrophils inversely correlated with HbA(1c) concentrations. Myeloperoxidase activity in leukocytes was significantly reduced in NIDDM patients. These findings suggest that changes in these enzymes may affect the susceptibility to infection and immunocompetence of patients with diabetes.

Diabetes Mellitus, Type 2↗

Neonatal periventricular leukomalacia preceded by fetal periventricular echodensity.

OBJECTIVE: The purpose of this prospective study is to verify whether fetal periventricular echodensity (PVE) precedes neonatal periventricular leukomalacia (PVL). METHODS: Fetal brains were studied with transvaginal scan in 63 high-risk fetuses from 17 to 32 weeks of pregnancy, PVE echogenicity was quantified with ultrasonic histogram, and neonatal brains and clinical courses were studied after birth. RESULTS: No fetal cystic PVL was found, instead, fetal PVE was detected in 42 fetuses. The quantified echogenicity value was higher in PVE than in normal brain. Four cases developed neonatal PVL among 28 preterm and 1 among 14 term births. Neonatal PVL developed in the 23 cases of persistent fetal PVE, whereas no neonatal PVL was found when fetal PVE was negative or disappeared. Cord compression signs were common in PVL cases. CONCLUSION: Neonatal PVL was preceded by antepartum persistent fetal PVE in the present study.

Cerebral Palsy↗

JMV1155: a novel inhibitor of glycine-extended progastrin-mediated growth of a human colon cancer in vivo.

BACKGROUND: Glycine-extended progastrin (G-17-Gly), the immediate biosynthetic precursor to gastrin (G-17), stimulates growth of some gastrointestinal cancers in vitro. The purpose of this study was twofold: to evaluate the effects of G-17-Gly on a human colon cancer (DLD-1) in vivo and to determine whether the novel gastrin-receptor antagonist, JMV1155, inhibits G-17-Gly-mediated growth. METHODS: DLD-1 cells (2 x 10(6)) were injected subcutaneously (s.c.) at a single site in athymic nude mice. Mice were randomized to four groups (n = 6/group) to receive injections, s.c., tid of either saline (control), G-17-Gly, JMV1155, or G-17-Gly + JMV1155 for 28 days. Tumors were measured biweekly until sacrifice at which time tumors were weighed and analyzed for DNA and protein content. RESULTS: JMV1155 significantly inhibited G-17-Gly-stimulated growth of DLD-1 tumors by 14 days of treatment, producing a 56% decrease in tumor size by 28 days. JMV1155 also significantly decreased G-17-Gly-mediated increases in tumor weight (by 64%), DNA content (by 61%), and protein content (by 65%). CONCLUSIONS: We have demonstrated, for the first time, that the novel gastrin-receptor antagonist, JMV1155, blocks G-17-Gly-induced growth of a transplanted human colon cancer in vivo. Hormonally based therapy with JMV1155 potentially could be employed for some patients with colon carcinoma.

Animals↗