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H Sone

Publications and source records attributed to H Sone.

At least 127 records · Page 7Linked to original sources

[Synergistic effects of human recombinant TNF and hyperthermia on in vitro cytotoxicity and artificial metastases].

Synergistic effects of hyperthermia on the cytotoxicity of TNF were examined, using L-M cells (mouse tumorigenic fibroblasts) and HEL cells (human embryonic lung cells) as targets. The sensitivity of L-M cells to TNF apparently increased when the culture temperature was raised from 37 degrees C to 38.5 degrees C or 40 degrees C, probably reflecting the increased turnover rate of the TNF-receptor complex. The anti-metastatic effects of a combined regimen of TNF (300U) and whole-body hyperthermia (40 degrees C, 30 min) was also examined in Balb/c mice injected with 1 X 10(6) Meth A F15 cells into a tail vein. No effects of TNF or hyperthermia alone were observed on artificial metastasis, while the combination of TNF and hyperthermia remarkably enhanced the inhibition of metastasis. These studies clearly suggest that combination of TNF with hyperthermia provides a significant synergistic effect against tumor.

Animals↗

[The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs].

The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs was examined in vitro. In vitro treatment of L-M cells with TNF and mitomycin C (MMC), adriamycin (ADM), cytosine arabinoside (Ara-C), actinomycin D (ACD), daunorubicin (DM), cisplatin (CDDP), vincristine (VCR), or 5-fluorouracil (5-FU) revealed a synergistic cytotoxicity. However, the combination of TNF with bleomycin (BLM) failed to show such a synergistic effect.

Animals↗

[Needle aspiration cytology of malignant lymphoma of the thyroid].

We have reviewed our experiences with needle aspiration cytology in five cases of malignant lymphoma of the thyroid. From the original cytologic reports, one case was correctly diagnosed as malignant lymphoma. Three were misdiagnosed as anaplastic carcinoma of the small-cell type, and two of these three were subsequently revised to malignant lymphoma at the second aspiration. Another patient was misdiagnosed as chronic thyroiditis at the first and second aspirations. Following the third aspiration, the condition was correctly diagnosed as malignant lymphoma. In the smears correctly diagnosed as malignant lymphoma, many malignant cells were distributed as isolated cells and showed monotonous features. Sometimes, cleaved cells or prominent nucleoli were visible.

Aged↗

Revised assignment for the Bacillus subtilis spo0F gene and its homology with spo0A and with two Escherichia coli genes.

The nucleotide sequences of spo0F mutant genes which block the early sporulation process of Bacillus subtilis were determined. The mutation sites together with the results of complementation tests suggested that an open reading frame for a polypeptide of Mr = 14,229 is the spo0F gene. The deduced amino acid sequence shows striking homology with that of the spo0A gene. In addition, the upstream region involving the rib some binding site of the spo0F coding region is also similar to those of spo0A and spo0B. These homologies suggest that all three genes have a similar function in regulating the initiation of sporulation, and that their expression is controlled by a common mechanism. Clear homology is also seen between the spo0 gene products and the transcriptional control proteins, OmpR and Dye, of Escherichia coli suggesting that the spo0 gene products also are involved in the control of transcription.

Alleles↗

[Pharmacological studies on ginger. IV. Effect of (6)-shogaol on the arachidonic cascade].

(6)-Shogaol, a pungent component of ginger, which is contained in semi-dried ginger but is rarely found in fresh ginger inhibited carrageenin-induced swelling of hind paw in rats and arachidonic acid (AA)-induced platelet aggregation in rabbits. Moreover, (6)-shogaol prevented prostaglandin I2 (PGI2) release from the aorta of rats when tested as an inhibitor of platelet aggregation. These results suggest that (6)-shogaol may have an inhibitory action on the cyclo-oxygenases in both platelets and aorta. Examination of the effects of (6)-shogaol on cyclo-oxygenases in rabbit platelets and microsome fractions of rat aorta indicated that (6)-shogaol inhibited cyclo-oxygenase activities of both tissues in a concentration-dependent manner. Furthermore, when we examined the effect of (6)-shogaol on 5-lipoxygenase from RBL-1 cells, (6)-shogaol exhibited an inhibitory action on 5-lipoxygenase activity. Therefore, it seems that the inhibitory effects of (6)-shogaol on the carrageenin-induced paw edema, AA-induced platelet aggregation and PGI2 production of aorta may be caused by the inhibition of cyclo-oxygenase activity.

Animals↗

[Pharmacological studies on ginger. V. Pharmacological comparison between (6)-shogaol and capsaicin].

Pharmacological actions of (6)-shogaol and capsaicin were studied. Both (6)-shogaol (0.5 mg/kg, i.v.) and capsaicin (0.1 mg/kg, i.v.) caused a triad such as a rapid fall in blood pressure, bradycardia and aponea in rats. Both drugs-induced marked pressor responses in blood pressure, which occurred after the rapid fall, were markedly reduced by a spinal destruction. In pithed rats, both drugs-induced peripheral pressor responses were markedly reduced with the combined treatment of [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (0.5 mg/kg, i.v.), phentolamine (10 mg/kg, i.v.) and the section of sciatic nerves. In isolated guinea-pig trachea, (6)-shogaol (100 microM) and capsaicin (10 microM) induced contractile responses which were slightly inhibited by substance P antagonist (10 microM), but exhibited also a tachyphylaxis. Furthermore, although (6)-shogaol (3.6 microM) showed positive inotropic and chronotropic actions on isolated atria in rats, this effect of (6)-shogaol disappeared by repeated injections or pretreatment (100 mg/kg, s.c.) of (6)-shogaol. These results suggest that (6)-shogaol and capsaicin have similar actions, and that both drugs may cause a peripheral action by releasing an unknown active substance from nerve ends.

Animals↗

Therapeutic effect of endogenous tumor necrosis factor on ascites Meth A sarcoma.

The therapeutic effect of endogenous tumor necrosis factor (TNF) on Meth A ascites fibrosarcoma in mice was investigated. Serum and peritoneal fluid from tumor bearing mice treated with OK-432 and LPS were cytotoxic to tumor cells in vitro. The peak of cytotoxicity in both the serum and peritoneal fluid was found in the fraction corresponding to a molecular weight of approximately 54,000-56,000 on HPLC and the pI was found to be 4.9-5.1 by isoelectric focusing. These results are consistent with previously reported findings on TNF, and indicate that endogenous TNF has a satisfactory life-prolonging effect. The tumor necrosis factor (TNF) is considered to be one of the clinically most promising anti-cancer cytokines because of its potent and very specific antitumor effect on target cells (Carswell, Old, Kassel, Green, Fiore & Williamson, 1975; Matthews & Watkins, 1978; Niitsu, Watanabe & Urushizaki, 1984). TNF as an anti-cancer cytokine for the treatment of cancer may be applied in one of the two following ways: by administration of purified TNF or by endogenously inducing TNF in cancer bearing individuals. The antitumor effects of TNF administered exogenously have been examined using crude preparations or serum containing TNF (tumor necrosis serum, TNS) (Carswell et al., 1975; Watanabe, Niitsu, Sone, Neda, Ishigaki & Urushizaki, 1984). In a previous paper we reported that mice primed with OK-432 and challenged with endotoxin produced a soluble cytotoxic factor in peritoneal fluids (Yamamoto, Nagamuta, Usami, Sugawara, Watanabe, Niitsu & Urushizaki, 1985; Nagamuta, Yamamoto, Usami, Sugawara, Watanabe, Niitsu & Urushizaki, 1985). Ths peritoneal cytotoxic factor (PCF) had cytostatic and/or cytotoxic effect not only on mouse tumor cell lines but also on human tumor cell lines without species specificity. Normal cell lines were not affected. Here we report the endogenous production of TNF in tumor bearing mice and its antitumor effects.

Animals↗

[Analysis of the TNF receptor in KYM cells by affinity cross-linking].

We investigated the identity of the TNF receptor on the KYM cell membrane by cross-linking 125I-TNF and the presumed receptor site with DSS, and subjecting the TNF-receptor complex to electrophoresis. Four specific bands were observed at 145 K, 50 K, 35 K, and 17 K, and those at 50 K, 35 K and 17 K being consistent with trimers, dimers and monomers of TNF, respectively. The 145 K band disappeared after addition of excess unlabelled TNF or anti-human recombinant TNF monoclonal antibody (IV3-E), which quenched the cytotoxic activity of TNF and inhibited the TNF binding to the receptor. The molecular weight of native TNF as estimated by gel filtration was 45 K and this observation showed that native TNF existed only as the TNF trimer. These results confirmed that 95K, i.e., the difference between 145 K and 50 K, is the molecular size of the TNF receptor.

Antibodies, Monoclonal↗

[Analysis of TNF receptor by binding assay].

The existence of a TNF receptor on TNF-sensitive tumor cells and on certain normal cells was elucidated by specific binding assay. A close correspondence (r = 0.855) was shown between the receptor number and the sensitivity of the tumor cells. However, for normal cells, despite the existence of TNF receptors, no cytotoxic effect was observed. Furthermore, certain normal diploid cells underwent proliferation as a result of TNF stimulation. It was therefore concluded that the existence of TNF receptor is essential but not sufficient in itself for TNF-induced cytotoxicity.

Animals↗

[TNF induction in the serum and ascites of a gastric cancer patient treated with OK-432].

A 73-year-old female was diagnosed as having gastric cancer (undifferentiated adenocarcinoma), and received gastrojejunal anastomosis as an initial treatment. One year after the operation, she was readmitted to our hospital with the complaint of fullness in her stomach. Physical examination revealed a palpable mass in the epigastric region and ascites. An attempt to induce endogenous TNF was made using OK-432. Four doses of OK-432 (10 KE) were administered intraperitoneally every other day. Seven days after the last administration of OK-432 (10 KE), OK-432 (50 KE) was given at the same site to induce TNF. At 1.5h after the injection of OK-432 (50 KE), 20.8 U/ml and 8.1 U/ml of TNF activity could be detected respectively in the serum and ascites. This is the first report describing the induction of TNF in a cancer patient.

Adenocarcinoma↗

Mechanism of the cytotoxic effect of tumor necrosis factor.

The mechanism of murine tumor necrosis factor (TNF) cytotoxicity against tumor cell lines (L929, HeLa, K562) was investigated. Electron microscopic observation revealed that most of the organellas of L929 cells incubated with partially purified murine TNF underwent almost complete lysis with no drastic disruption of the cytoplasmic membrane, while injection of the TNF into the cytoplasm or nuclei of L929 cells caused no apparent morphological change or growth inhibition. Preincubation of the TNF with tumor cells (L929, HeLa, K562) resulted in a decrease in cytotoxic activity which was proportional to their susceptibility to TNF, thus indicating their absorption of TNF. The susceptibility of L929 tumor cells to TNF was apparently suppressed by treatment with proteases, suggesting the existence of protease-sensitive recognition sites for TNF on the tumor cell.

Absorption↗

T cell involvement in production of tumor necrosis factor: reconstitution experiments with nude mice.

In order to investigate the role of T cells in the production of tumor necrosis factor (TNF), a reconstitution experiment was performed with nude mice (Balb/c, nu/nu). The results obtained were as follows: 1) The cytotoxic activity of tumor necrosis serum (TNS) from Balb/c, nu/nu mice treated with Propionibacterium acnes-LPS was 1/22 of that from Balb/c, nu/+ mice. 2) TNF activity increased 14 times in reconstituted nude mice as compared to Balb/c, nu/nu mice. 3) The production of the cytotoxic activity per cell was investigated using T cell and macrophage fractions separated from the spleens of both Balb/c, nu/nu and Balb/c, nu/+ mice treated with P. acnes as a priming agent. Elicitation with LPS was done in vitro. Release of cytotoxic activity into the culture medium was observed in the macrophage fraction, but not in the T cell fraction. However, no significant species difference was found. 4) With P. acnes treatment, the population of macrophages in the spleens from Balb/c, nu/+ mice increased 25.5 times, whereas that from Balb/c, nu/nu mice only increased 6.8 times. The above results suggest that the mechanism of the incremental effect of T cells on TNF production was due to the promotion of macrophage proliferation during the priming period after injection of P. acnes.

Animals↗

Inhibitory effect of tumor necrosis serum on the metastasis of B-16 mouse melanoma cells.

The inhibitory effect of tumor necrosis serum (TNS) on the artificial metastasis of B-16 melanoma cells and the spontaneous metastasis of Lewis lung carcinoma cells was investigated. The results obtained were as follows: 1) When tumor necrosis serum (TNS) was administered either 20 min or 2 days after injection of B-16 melanoma cells, a very strong inhibitory effect (99%) relative to the control was noted. 2) TNS showed a 60% inhibitory effect on spontaneous metastasis, and the weight of the original tumor regressed by 60%. 3) No histological changes in normal tissues were observed microscopically following TNS injection. The above results confirm that TNS is extremely effective in preventing metastasis.

Animals↗

Antitumor effect of tumor necrosis factor against various primarily cultured human cancer cells.

The antitumor activity of tumor necrosis factor (TNF) against various primarily cultured human cancer cells (32 cases) was investigated by the 51Cr cytotoxic release assay and the tumor stem cell assay. Over 50% sensitivity (the ratio to the cytotoxicity in L929 cells) was noted in 4 of 14 cases of gastric cancer (28.6%), 7 of 9 cases of leukemic cells (77.8%), and 1 case each of pancreatic carcinoma and ovarian cancer. Scarcely any sensitivity, however, was observed in 1 case of acute promyelocytic leukemia or in some of the gastric cancer cases. No correlation was observed between the histological type of the cancer and TNF sensitivity. The above results seem to confirm that TNF has significant antitumor activity against human cancer cells.

Adult↗

[Antitumor effect of the tumor necrosis factor against various types of human cancer cells].

The antitumor activity of tumor necrosis factor (TNA) against various human cancer cells (32 cases) was investigated by 51Cr cytotoxic release assay and tumor stem cell assay. Over 50% sensitivity (the ratio of cytotoxicity for L929 cells) was shown by 4 of 14 cases of gastric cancer (28.6%), 7 of 9 cases of leukemic cells (77.8%), and 1 case each of pancreatic carcinoma and ovarian cancer. However, scarcely any sensitivity was shown by APL, a portion of the gastric cancer cells, normal lymphocytes or colony-forming cells tested. No correspondence was observed between the histological type of the cancer and TNF sensitivity. The above results seem to confirm the significant antitumor activity of TNF against human cancer cells.

Adenocarcinoma↗

Action of nicotine on guinea-pig isolated bronchial smooth muscle preparation.

In the isolated bronchial preparation of the guinea-pig, nicotine induced a contraction but not a relaxation. The contractile response of the bronchial preparation to nicotine was inhibited by hexamethonium and d-tubocurarine but not influenced by atropine and tetrodotoxin. In the isolated tracheal preparation of the guinea-pig where nicotine stimulated nicotinic receptor in nervous tissues, the contractile response to nicotine as considerably accelerated by the treatment of the guinea-pig with egg-albumin, while the contractile response of the bronchial preparation to nicotine was not influenced by the same treatment. These results suggest that a possible site of action of nicotine in the isolated bronchial preparation is not on the nervous cells but on the smooth muscle cells. However, we could not rule out a contribution by chemical mediators released by nicotine in the contractile mechanisms in the bronchial preparation.

Airway Resistance↗

[Mechanisms of production of tumor necrosis factor (TNF)--reconstitution experiment white nude mice].

In order to investigate the role of T cells in the production of tumor necrosis factor (TNF), a reconstitution experiment was performed with nude mice (Balb/c, nu/nu). The results obtained were as follows: The cytotoxic activity of tumor necrosis serum (TNS) from Balb/c, nu/nu mice treated with P. acnes-LPS was 1/22 against that from Balb/c, nu/+ mice. TNF activity increased 14 times in reconstituted nude mice against Balb/c, nu/nu mice. Investigation of the production of the cytotoxic activity per cell was carried out using T cell and macrophage fractions separated from the spleens of both Balb/c, nu/nu and Balb/c, nu/+ mice treated with P. acnes as a priming agent. Elicitation employing LPS was done in vitro. Cytotoxic activity released into culture medium was observed in the macrophage fraction, but not in the T cell fraction. However, no significant difference was shown in species. With P. acnes treatment, the population of macrophages in the spleens from Balb/c, nu/+ mice increased 25.5 times, whereas that from Balb/c, nu/nu mice only increased 6.8 times. The above results suggest that the mechanism of the incremental effect of T cells on TNF production was due to the promotion of macrophage proliferation during the priming period after injection of P. acnes.

Animals↗