Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS) stimulated normal spleen cells of DBA/2J, CBA/J, and BALB/c mice about equally in the presence of either isologous or homologous serum. This system revealed that sera from mice with five different methylcholanthrene-induced rhabdomyosarcomas inhibited mitogen stimulation of normal spleen cells. Sera from mice with a mammaryadenocarcinoma and spontaneous rhabdomyosarcoma were similarly suppressive. In contrast, sera from mice with melanoma were not inhibitory and often enhanced stimulation. Sera from tumor-bearing animals had the same effects both qualitatively and quantitatively on cells from the strain carrying the tumor and on cells from the other two strains. The mixed lymphocyte response of CBA/J times BALB/c spleen cells was affected exactly as were the responses to mitogen by the various sera. Stimulation by mitogen of mouse lymph-node cells and spleen cells with macrophages removed, as well as that of guinea pig spleen cells, was also inhibited by sera from mice with rhabdomyosarcoma and mammary adenocarcinoma.
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PMID:Effects of sera from tumor-bearing mice on mitogen and allogeneic cell stimulation of normal lymphoid cells. 12 99

Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthrene-induced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the alpha and beta globulins and albumin (molecular weight less than 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2-5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immuno-adsorbents containing goat anti-mouse immuno-globulin, and could be recovered by acid elution from the absorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin.
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PMID:Characterization of a T-lymphocyte inhibitor in the serum of tumour-bearing mice. 13 82

Benzoporphyrin derivative, monoacid ring A (BPD-MA), currently in clinical trials as a photosensitizer for photodynamic therapy for cancer, consists of two regioisomers (A1 and A2) present in equal proportions. The contribution of the regioisomers to the overall photosensitizing potency of BPD-MA was tested in vitro and in vivo. The in vitro photosensitizing potencies of BPD-MA-A1 and -A2 were tested in a standard cytotoxicity assay using M1 (rhabdomyosarcoma of DBA/2 mice) tumor cells and were found to be equivalent. The in vivo photosensitizing efficacies of the regioisomers were tested in the M1 tumor model in DBA/2 mice and were also found to be equivalent. Biodistribution of the regioisomers in mouse plasma, tumor and liver was studied in M1 tumor-bearing DBA/2 mice at 15 min and 3 hr post intravenous injection of [14C]BPD-MA-A1/A2 at 4 mg/kg body weight. Plasma and extracts from tumor and liver were analysed by HPLC and tested for radioactivity. The two regioisomers were eliminated from plasma and liver at different rates, which resulted in A1:A2 ratios of 1:0.28 in plasma and 1:0.75 in liver at 3 hr post injection. The differential elimination was not observed to any significant degree in the tumor, where even at 3 hr post injection the A1:A2 ratio was 1:1.15. Therefore, we concluded that in tumor tissue, at 3 hr post injection, the time at which laser photodynamic therapy is carried out, both regioisomers were present in about equal proportions. Further, both regioisomers were fully active as determined by an in vitro cytotoxicity assay following extraction.
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PMID:Photosensitizing efficiency of two regioisomers of the benzoporphyrin derivative monoacid ring A (BPD-MA). 161 Apr

The in vivo characteristics of four analogues of benzoporphyrin derivative (BPD) have been investigated. Biodistribution data obtained in DBA/2J mice with BPD-MA (monoacid ring A analogue) which had been tritiated or internally labelled with 14C showed that both labelled materials acted in an essentially identical manner during the period of study. Biodistribution and clearance studies showed that relative distribution in a variety of mouse tissues was similar for all BPD analogues. M1 tumour cells (rhabdomyosarcoma in DBA/2J mice) taken from tumours excised from animals treated 3 h earlier with BPD, and tested in vitro for photosensitivity provided evidence that significant levels of photosensitiser detected in tumour was both active and associated with tumour cells. The monoacid forms of BPD were found to be much more photodynamically active in this test than were the diacid analogues. The ability of the analogues to ablate tumours in mice by photodynamic therapy was also tested. Again, BPD-MA and BPD-MB proved to be measurably better than the diacid analogues. These findings are discussed in reference to structural and physical differences between the analogues.
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PMID:Photosensitising potency of structural analogues of benzoporphyrin derivative (BPD) in a mouse tumour model. 198 69

Mice and rats of various ages (3, 10-12, and 18-19 months) were inoculated with the transplantation tumours murine melanoma B16 (B16), mammary adenocarcinoma 755 (Ca-755), leukemia P388 (P388), and rat rhabdomyosarcoma RA-2 (RA-2). Subcutaneous (sc) growth of B16 was not markedly affected by the age of the syngeneic host whereas intravenously (iv) inoculated 12 months old C57BL/6 mice developed more pulmonary metastases than animals 3 months of age. Median survival time (MST) of 18 months old mice bearing Ca-755 was significantly shorter than that of younger individuals. In contrast, old rats that had been injected RA-2 iv survived longer than controls. Survival of DBA/2 mice inoculated intraperitoneally (ip) with P388 cells was not influenced by the age of the host. The antineoplastic activity of ambazone and, to a less extent, of 5-fluorouracil against P388 was drastically lower in 12 months old mice than in 3 months old tumour bearers. Likewise a graduate loss of antineoplastic activity of ambazone against Ca-755 was observed with increasing age of the mice, whereas the effect of ambazone and 5-fluorouracil against RA-2 did not depend on the age of the rats. It is suggested that tumour-host interactions as well as pharmacokinetics of a given drug may underlie age-related changes.
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PMID:Carcinogenesis and aging. VIII. Effect of host age on tumour growth, metastatic potential, and chemotherapeutic sensitivity to 1.4-benzoquinone-guanylhydrazonethiosemicarbazone (ambazone) and 5-fluorouracil in mice and rats. 322 59

The antineoplastic activity of N-maleamide homocysteine thiolactone amide (MHTA) encapsulated within liposomes was studied in mice with transplanted tumors. Tumor weight was decreased by 4-5 biweekly intraperitoneal injections of MHTA in liposomes in DBA/2N females with MTG mammary adenocarcinoma (35% of control value, P less than 0.005) and in C57B1/6N males with MUO4 rhabdomyosarcoma (11% of control value, P less than 0.0000001). Tumor incidence was reduced from 84 to 63% (P less than 0.05) and from 100 to 32% (P less than 0.001) in the two systems, respectively. When the compound was administered in dimethyl sulfoxide to A/HeJ females with A10 mammary adenocarcinoma by daily intraperitoneal injection, tumor weight was reduced to 70% of control value (P less than 0.05), and there was no decrease in tumor incidence (100%). No toxicity was observed at the therapeutic dose utilized, 10 mg/kg/day. N-Maleamide homocysteine thiolactone amide is a derivative of the normal biochemical constituents, maleic acid and homocysteine thiolactone. The results show that the N-substituted maleamide derivative of homocysteine thiolactone decreases the growth of murine tumors of two different histological types, when administered encapsulated within liposomes.
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PMID:Antineoplastic activity of N-maleamide homocysteine thiolactone amide encapsulated within liposomes. 403 35

We have studied the induction of a granulocyte-associated leukocytosis (leukemoid reaction) in C3HA, C57B1/6, and DBA/2 mice by a number of transplantable tumors of different origin. Leukemia L1210, Hepatoma 22, a transplantable mammary carcinoma of spontaneous C3HA origin, and a L929 culture fibroblasts-derived rhabdomyosarcoma, all induced a leukemoid reaction in their specific mouse strain. Melanoma B16 and Lewis lung carcinoma gave no reaction; Adenocarcinoma 755 and Harding-Passey melanoma evoked a leukocytosis but not due to an increase in neutrophils. Some extratumoral factors can influence the hematological response; the intensity of final leukemoid reaction was higher in female mice than in males bearing the same tumor. On the other hand, Ehrlich ascites tumor transplanted in all three inbred mouse strains rendered different levels of leukemoid reaction; response was higher in DBA/2, intermediate in C3HA and lower in C57B1/6.
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PMID:Leukemoid reaction induced by different transplantable tumors in three inbred mouse strains. 707 May 57

Photosensitizing and biodistribution characteristics of a photosensitizer (benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight = 10,000) were tested in vitro and in vivo. Modified PVA was loaded with BPD at molar ratios 1:12, 1:25, 1:50, 1:75 and 1:100. Most of the work was carried out with a conjugate having a 1:25 molar ratio. In vitro photosensitization was tested using A549 (human lung carcinoma), A432 (human epidermoid carcinoma) and P815 (mastocytoma of DBA/2 mice) cell lines. Photosensitization of M1 (rhabdomyosarcoma of DBA/2 mice) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated 3H-BPD and 3 h later light activation of tumor cells was carried out in vitro. Biodistribution studies were carried out using M1 tumor-bearing DBA/2 mice and 3H-BPD either free or conjugated to M-PVA. The results of these studies showed that the conjugation of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing activity of the photosensitizer molecules and at the same time gained new characteristics, advantageous for photodynamic treatment, especially in vivo. In vitro M-PVA-BPD conjugates were at least as efficient in photosensitization of tumor cells as an equivalent number of free BPD molecules, both in the presence and in the absence of serum. Although the biodistribution was in general comparable to free BPD, the conjugate (1:25) reached slightly higher levels in the blood, kidney, lung and spleen, and lower levels in the liver, brain, skin and muscle in comparison with free BPD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modified polyvinyl alcohol-benzoporphyrin derivative conjugates as phototoxic agents. 850 92