Release of tumor necrosis factor (TNF) into mouse peritoneal fluids by OK-432, a streptococcal preparation

Yamamoto, Akihiro; Nagamuta, Masahiro; Usami, Hatsuhiko; Sugawara, Yutaka; Watanabe, Naoki; Niitsu, Y; Urushizaki, I

doi:10.1016/0162-3109(86)90027-5

Cited by 70 publications

(25 citation statements)

References 14 publications

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“…This indicates that the LTA-induced TNF is antigenically related to LPS-induced TNF. It may also exclude the possibility that the LTAinduced TNF contains lymphotoxin (LT) in an appreciable amount, since Stone-Wolff et al (1984) reported that LT was antigenically different from TNF. We reported previously that no death of P. acnes-primed CD-1 mice was caused by LTA, even at a dose as high i mg/mouse under assay conditions in which the LDo50 of LPS was 3.13 ig/mouse (Yamamoto et al, 1985a). The extreme low toxicity of LTA was further confirmed using galactosamine-loaded mice which are known to be highly susceptible to the lethal effects of toxic bacterial products.…”

mentioning

confidence: 64%

“…In a previous paper, we reported that lipoteichoic acids (LTA) prepared from Streptococcus pyogenes induces tumour necrosis factor (TNF) in the sera of mice which had been primed with formalin-killed Propionibacterium acnes (Yamamoto et al, 1985a). Thus, serum specimens of P. acnes-primed, and LTA-elicited mice had a cytoidal effect on L-929 cells in vitro, and the i.v.…”

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confidence: 98%

“…This paper presents evidence which strongly suggests that LTA-induced TNF is distinct in toxicity from that induced by LPS, although they share some antigenic epitopes. LTA was prepared as described previously (Yamamoto et al, 1985a). The purity of the LTA preparation was assessed by gas-liquid chromatography, and by chemical and immunochemical analysis (Hamada et al, 1985).…”

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confidence: 99%

“…Thus the LTA-and LPSinduced TNFs were similar in their mode of cytotoxic action, i.e., lack of species specificity and the ability to discriminate between tumour cells and normal cells. The necrotizing effect of LTA-induced TNF on solid-type Meth A fibrosarcoma pre-established in BALB/c mice was described previously (Yamamoto et al, 1985a).…”

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confidence: 99%

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A nontoxic tumour necrosis factor induced by streptococcal lipoteichoic acids

Usami¹,

Yamamoto²,

Sugawara³

et al. 1987

Br J Cancer

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confidence: 64%

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confidence: 98%

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confidence: 99%

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confidence: 99%

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A nontoxic tumour necrosis factor induced by streptococcal lipoteichoic acids

Usami¹,

Yamamoto²,

Sugawara³

et al. 1987

Br J Cancer

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“…OK-432 is an immunomodulatory agent prepared from an avirulent human strain of Streptococcus pyogenes. It has been shown to induce various cytokines, especially Th1 cytokines (Saito et al, 1982;Yamamoto et al, 1986;Yang et al, 1992) and to upregulate both perforin (Kataoka et al, 1991) and Fas ligand expression (Toda et al, 1996;Sato et al, 1997) of immune cells. In accordance with these findings, OK-432 is also known to enhance or activate the cytotoxic activity of various effector cells (Ishii et al, 1976;Uchida and Micksha, 1983), which may be responsible for its therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients

et al. 2001

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SummaryTo investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg Ϫ1 i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day Ϫ1) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5-and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5-and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micrometastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.

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