Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.
 ...
PMID:BRM activities of low-toxic Bordetella pertussis lipopolysaccharides. 141 7

Intratumoral induction of tumour necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as compared with that by the agent OK-432 was investigated in mice. Two hours after such administration tumour tissues tested were resected from the mice, homogenised, and the TNF activities in the homogenate were assayed using a L-929 fibroblast assay. Intravenous injection of BPV into mice bearing the MM46 carcinoma resulted in a greater concentration of TNF in the tumour homogenate than in the serum. With OK-432, however, there was a greater concentration of TNF in the serum than in the tumour homogenates. A high level of intratumoral TNF induction by BPV was also observed in mice bearing Meth A fibrosarcoma or Lewis lung carcinoma. The therapeutic effect against the Meth A fibrosarcoma was in parallel with the intratumoral TNF activity. Intratumoral TNF activity is therefore believed to be a good index of therapeutic effect.
 ...
PMID:Intratumoral induction of tumour necrosis factor by systemic administration of Bordetella pertussis vaccine. 220 45

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.
 ...
PMID:Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis. 819 67

We studied the mechanism of anti-tumour action of sulphydryl glycoprotein (SAGP) purified from an extract of Streptococcus pyogenes in vitro. SAGP rapidly inhibited the incorporation of nucleic acid precursors into murine fibrosarcoma (Meth A) cells before it inhibited the cell growth. SAGP-induced cell growth inhibition was diminished by incubating the cells with pertussis toxin (IAP), whereas the SAGP activity was augmented by incubating the cells with cholera toxin (CTX). Meth A cells exposed to SAGP underwent an increase in labelling of the alpha-subunit of an inhibitory guanine nucleotide-binding (Gi) protein in a subsequent IAP-catalysed [32P]ADP ribosylation of the cell membrane fraction. Gi alpha labelling was not increased either in the membrane from the Meth A cells exposed to heat-inactivated SAGP or in the membrane from L929 cells exposed to SAGP, in which growth was also unaffected. By contrast, SAGP caused no alteration in labelling the alpha-subunit of stimulatory guanine nucleotide-binding (Gs) protein in a subsequent CTX-catalysed ADP ribosylation of membrane fractions of Meth A and L929 cells. The amount of intracellular cAMP was decreased slightly in Meth A cells incubated with SAGP. Although the precise roles of Gs protein and adenylate cyclase in the cell growth inhibition induced by SAGP are not clear, these findings suggested that the modulation of Gi protein is involved in such SAGP-induced cellular events as the inhibition of nucleic acid synthesis and cell growth inhibition.
 ...
PMID:Streptococcal glycoprotein-induced tumour cell growth inhibition involves the modulation of a pertussis toxin-sensitive G protein. 861 26

An acidic antitumor glycoprotein (SAGP) was purified from a crude extract of Streptococcus pyogenes, Su strain. Intraperitoneal injection with SAGP (20 mg protein/kg/day for 4 consecutive days) prolonged the life span of mice inoculated i.p. with Ehrlich ascite carcinoma cells and methylcholanthrene-induced fibrosarcoma cells (Meth A) up to 244% and 169% of that of the control mice, respectively. These in vivo antitumor effects were reduced in immunosuppressed mice. The effector spleen cells from the Meth A-inoculated and SAGP-injected mice showed a considerable cytostatic activity on Meth A cells in vitro, and immunosuppression studies suggested that carrageenan-sensitive and/or asialo-GM1 positive spleen cells are responsible for the in vivo antitumor effect of SAGP. SAGP inhibited the cell growth of cultured cell lines including transformed hamster embryonic lung cells, murine leukemia L 1210, Meth A and human promyelocytic leukemia HL60 cells. The IC50s for the cell growth of these cells were all below 0.1 microg protein/ml. SAGP inhibited the incorporation of nucleic acid precursors into Meth A cells. It seems that sulfhydryl groups of the SAGP molecule are essential for the expression of the antitumor action of SAGP. The cell growth-inhibitory activity of SAGP was diminished in Meth A cells preincubated with pertussis toxin (IAP), whereas it was augmented in the cells preincubated with cholera toxin (CTX), suggesting the involvement of toxin-sensitive GTP (G)-proteins in the SAGP-action. IAP and CTX-catalyzed ADP ribosylation assays confirmed that SAGP augmented the activity of IAP-sensitive G-protein. In addition, this augmentation was detected neither in Meth A cells incubated with heat-inactivated SAGP nor in SAGP-insensitive L929 cells. SAGP induced apoptosis in Meth A and HL60 cells as assessed by DNA fragmentation. A single dose injection of SAGP (100 mg protein/kg, i.v., s.c., or i.p.) into mice produced no toxic signs except occasional pain responses observed for one week after the injection. Thus, SAGP is a low toxic substance that shows in vivo antitumor activity by modulating immune responses of the host, and also exhibits in vitro cell-growth inhibition through IAP-sensitive G-protein.
 ...
PMID:Characterization of a streptococcal antitumor glycoprotein (SAGP). 951 6

An acidic glycoprotein (SAGP) purified from an extract of Streptococcus pyogenes has been shown to inhibit the growth of methylcholanthrene-induced fibrosarcoma A (Meth A) cells via pertussis toxin-sensitive GTP-binding protein. The present study revealed that SAGP has activity to induce apoptosis in Meth A cells as assessed by DNA fragmentation and cell morphology with chromatin staining. The SAGP-induced DNA fragmentation in Meth A cells was augmented by herbimycin A, an inhibitor of protein tyrosine kinase, and prevented by orthovanadate, an inhibitor of protein tyrosine phosphatase. The growth inhibitory effect of SAGP on Meth A cells was reduced by orthovanadate, whereas the effect tended to be increased by herbimycin A. Western blotting analysis using antiphosphotyrosine antibody demonstrated that tyrosine phosphorylation of 170 kDa cellular protein was diminished in the cells incubated with SAGP. The inhibition of protein tyrosine phosphorylation was neither observed in the cells incubated with SAGP and orthovanadate nor in the cells incubated with heat-inactivated SAGP. These findings indicate that inhibition of tyrosine phosphorylation by protein tyrosine phosphatase(s) may be responsible for the SAGP-induced apoptosis and inhibition of cell growth.
 ...
PMID:Antiproliferative and apoptosis-inducing effects of an antitumor glycoprotein from Streptococcus pyogenes. 1047 Jan 29