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T Baba

Publications and source records attributed to T Baba.

At least 451 records · Page 25Linked to original sources

[New directions in research on cancer metastases: molecular biological approaches].

Cancer metastasis is a multistep process related to various factors (genes). One objective of research on cancer metastasis is to identify factors responsible for each of these steps and to evaluate the weight of each factor in the entire metastatic process. Molecular biological approaches are increasingly used in the field of research on cancer metastasis to identify and analyze each factor, at the gene level. Oncogenes, such as ras, N-myc, c-myc, sis, erb B, and fos, are reported as candidate genes related to metastasis. Other candidate genes, such as MHC, cadherin, laminin, and actin have already been cloned and sequenced. By reviewing molecular biological approaches to metastasis, present issues and directions of research on metastasis will be discussed.

Animals↗

Malignant progression of a transformed rat cell line by transfer of the v-fos oncogene.

Transfer of the v-fos oncogene into a rat cell line transformed by Rous sarcoma virus increased both the spontaneous and experimental lung-metastasis. Metastatic ability of each v-fos transferred cell line was dependent on both the manner of integration and transcriptional amount of the v-fos oncogene, but did not correlate with the growth rate in vivo. Expression of the src, myc or ras genes were not altered by transfer of the v-fos gene, except that the myc expression was enhanced in the cell line, which acquired augmentation of growth rate in vivo but not metastatic potential to the lung. Cells of the metastatic lung nodules of each cell line also possessed exogenous fos DNA and the transcripts. These results suggest that v-fos oncogene functions in the transfected cells and causes malignant progression.

Animals↗

Efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, in combination with angiotensin II in a rat limb tumor.

We combined the angiotensin II (AT-II)-induced hypertension method with "two-route chemotherapy" (TRC), using cis-diamminedichloroplatinum(II) (CDDP) and its antidote, sodium thiosulfate (STS). The efficacy of the modified TRC was evaluated in rats bearing a limb tumor (transitional cell carcinoma). Immediately after infusing CDDP (15 mg/kg) and AT-II (15 micrograms/kg) via the femoral artery for 5 min, 1580 mg/kg STS (200-fold molar ratio to 15 mg/kg of CDDP) were administered i.v. for a further 5 min. Other treatments were as follows: 5 mg/kg of CDDP mixed or not mixed with 15 micrograms/kg of AT-II were given intraarterially (i.a.); 5 mg/kg of CDDP alone were injected i.v.; CDDP (15 mg/kg, i.a.) and STS (1580 mg/kg, i.v.) were simultaneously administered, without AT-II (conventional TRC). The antitumor effects of the modified TRC, evaluated by regression of tumor growth and extended life span, were superior to the other treatments. On the other hand, nephrotoxicity, loss of body weight, and leukopenia, seen in the rats given TRC with AT-II, occurred less than or at the same rate as in rats given other treatments. Thus, the TRC with AT-II was the most effective treatment given to rats bearing a regionally confined tumor. The feasibility of clinical application of modified TRC using i.a. CDDP plus AT-II and i.v. STS is discussed.

Angiotensin II↗

Dehydrodolichyl diphosphate synthetase from rat seminiferous tubules.

Homogenates of seminiferous tubules from rat testes catalyzed the incorporation of label from [14C]isopentenyl diphosphate into a variety of polyprenyl products. Long chain polyprenyl mono- and diphosphates were formed as major products when undesirable side reactions were minimized. The long chain polyprenyl diphosphate synthetase was measured as a sum of the mono- and diphosphate derivatives formed and was dependent on the addition of t,t-farnesyl diphosphate, isopentenyl diphosphate, and divalent cation. The highest activity was associated with the membranous fractions, whereas activity was negligible in the cytosolic fraction. The products of this prenyl transferase were labile to acid and yielded petroleum ether soluble products which indicated that the alpha-isoprene unit was unsaturated. Hydrolysis of either the polyprenyl mono-or diphosphates with a testicular phosphatase in the absence of NaF yielded C75, C80, C85, and C90 polyprenols. The chain lengths of the products of the synthetase suggest that this enzyme is responsible for the de novo biosynthesis of dehydrodolichyl diphosphates which are precursors of the dolichyl derivatives found in testes.

Alkyl and Aryl Transferases↗

Ultrastructural cytochemistry of oxytalan fibres in monkey periodontal ligaments with the high iron diamine method.

Monkey periodontal ligaments have been examined at the ultrastructural level to demonstrate the nature of reactive sites in oxytalan fibres. The high iron diamine (HID) and HID-thiocarbohydrazide-silver proteinate methods specific for sulphate groups, with and without prior oxidation with monopersulphate, were used. Oxytalan fibres were composed of bundles of microfibrils with a diameter of 11.5 +/- 1.7 nm (mean +/- S.D., n = 50). In cross section the microfibrils were found to have a denser periphery, giving them a 'tubular' appearance. The oxytalan microfibrils of non-oxidized specimens showed little reactivity with either HID method, except that the extracellular matrix material in close association with collagen fibrils stained weakly; in oxidized specimens, both HID methods strongly stained oxytalan microfibrils and weakly stained the extracellular matrix material. Such reactivity of oxytalan microfibrils was not altered by digestion with testicular hyaluronidase or chondroitinase ABC, performed prior to or after persulphate oxidation. Further, the sequential thiosulphation and HID method for the demonstration of disulphide and sulphhydryl groups stained oxytalan fibres moderately. These results indicate that the oxidative generation of sulphate groups in oxytalan fibres may occur from either disulphide or sulphhydryl groups, or both, rather than the result of unmasking of sulphated glycosaminoglycans.

Animals↗

Multiple oral doses of nicardipine, a calcium-entry blocker: effects on renal function, plasma renin activity, and aldosterone concentration in mild-to-moderate essential hypertension.

We studied the effects of nicardipine administered in a 4-week fixed oral maintenance dosage (20 or 40 mg t.i.d.) on renal function, plasma renin activity (PRA), and plasma aldosterone concentration in seven patients with mild-to-moderate essential hypertension. Glomerular filtration rate and renal blood flow were measured by means of sodium thiosulfate and para-aminohippurate, respectively. Nicardipine increased renal blood flow by 11.5% +/- 4.3% (mean +/- SE; P less than 0.05) and glomerular filtration rate by 16.3% +/- 6.4% (P less than 0.05) and decreased total renal vascular resistance by 30.0% +/- 2.7% (P less than 0.05), with a significant (P less than 0.05) reduction in systolic and diastolic blood pressure as compared with placebo values. Nicardipine increased PRA significantly (P less than 0.05), whereas plasma aldosterone concentration remained unchanged. Our results indicate that nicardipine given in a multiple oral dosage has some favorable renal effects with a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. Nicardipine appears to blunt the secretion of aldosterone responding to an increased PRA possibly through its calcium-antagonizing action.

Adult↗

A case of leiomyoma of the lamina muscularis mucosae of the esophagus with a complication of carcinoma in situ of the overlying mucosa.

An extremely rare case of leiomyoma originating in the lamina muscularis mucosae of the esophagus with a complication of carcinoma in situ in its overlying mucosa was reported. The patient was a 53-year-old male who complained of a feeling of abdominal fullness. A small, elevated tumor was found in the middle portion of the esophagus by esophagoscopy. Biopsy specimens showed it to be squamous cell carcinoma. The resected material revealed the tumor mass to be composed of both a leiomyoma, measuring 0.8 x 0.6 x 0.25 cm, which continued from the lamina muscularis mucosae, and carcinoma in situ and dysplasia in the overlying mucosa of the leiomyoma. The mucosa apart from that covering the leiomyoma was intact. It was speculated that chronic stimulation of the epithelium covering the leiomyoma might have induced the dysplasia and carcinoma in situ.

Biopsy↗

A new metabolite of methamphetamine; evidence for formation of N-[(1-methyl-2-phenyl)ethyl]ethanimine N-oxide.

1. N-Hydroxyamphetamine and N-hydroxymethamphetamine, metabolic intermediates of amphetamine and methamphetamine, showed no reactivity towards endogeneous protein, amino acids, nucleic acids and fatty acids. In contrast, formaldehyde, acetaldehyde and propionaldehyde reacted well with N-hydroxyamphetamine and slightly with N-hydroxymethamphetamine under mild conditions (pH 7.4, 37 degrees C). 2. Two products were isolated from the reaction mixture of acetaldehyde and N-hydroxyamphetamine. These were characterized as N-[(1-methyl-2-phenyl)ethyl]ethanimine N-oxide and N-[(1-methyl-2-phenyl)ethyl]butenimine N-oxide by mass and n.m.r. spectrometries. 3. N-[(1-Methyl-2-phenyl)ethyl]ethanimine N-oxide was formed by incubating methamphetamine with liver 9000 g supernatants of rats and guinea-pigs. The butenimine N-oxide derivative, however, could not be detected as a metabolite of methamphetamine in vitro. 4. N-[(1-Methyl-2-phenyl)ethyl]ethanimine N-oxide was also detected as a urinary metabolite of methamphetamine in rats and guinea-pigs. Thus, the ethanimine N-oxide was established as a novel metabolite of methamphetamine.

Amphetamine↗

Potentiation of cytotoxicity of zinostatin under acidic conditions in vitro and in vivo.

The cytotoxicity and antitumor effects of zinostatin (NCS) were examined under various conditions of pH using cultured HeLa cells and a transplantable tumor line of WKA rats. The cytotoxicity of NCS against HeLa cells was highly dependent on the pH at ranges of 6-8. When HeLa cells were treated with 0.075 microgram/ml of NCS, the survival rate was about 1% at pH 6.0, while it was near 90% at pH 7.4 and pH 8.0. Even at pH 6.5-6.75, the survival rate was about 50% lower than that seen with pH 7.4 and pH 8.0. The ratio of the dose of NCS for a 90% cell mortality at pH 6.0 to that at pH 7.4 was less than one-seventh. Antitumor effects were assessed by local intra-arterial infusion against tumors 4 or 9 days after inoculation of 10(6) RBT-1 tumor cells into the thigh of rats. When NCS (0.7 mg/kg) in phosphate-buffered saline (PBS) (pH 7.4) or 5 mM lactate (about pH 3.0) was administered, the ratio of average tumor weight about 2 weeks after treatment (tumor weight of the rats given NCS in PBS/tumor weight of the rats given NCS in lactate) was 3.2 or 1.7 for the rats treated 4 or 9 days after tumor inoculation, respectively. Lactate or PBS alone had no effect on the growth of tumor. After treatment there was no difference in body weight change between the group treated with NCS in lactate and the group treated with NCS in PBS. We conclude that the cytotoxicity of NCS was potentiated under acidic conditions, both in vitro and in vivo.

Animals↗