Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-(Phosphonacetyl)-L-aspartate (PALA) is an analog of the transition state for the aspartate transcarbamylase reaction and has been reported previously to be a potent and specific inhibitor of de novo pyrimidine nucleotide biosynthesis. It is now shown that PALA has considerable antitumor activity against certain transplantable tumors in mice. PALA, unlike other antimetabolites, was less effective against ascitic leukemias than against two solid tumors, B16 melanoma and Lewis lung carcinoma. Another solid tumor, Ridgway osteogenic sarcoma, which is sensitivie to many established chemotherapeutic agents, did not respond to PALA. Daily or intermittent treatment with PALA did not significantly increase the life-span of mice bearing i.p. leukemia L1210. The survival time of mice bearing i.p. P388 leukemia was prolonged by PALA treatment by up to 64%. In a number of experiments mice bearing i.p. B16 melanoma survived 77 to 86% longer than did controls when treated with PALA (490 mg/kg) on Days 1, 5, and 9. Lewis lung carcinoma, a tumor refractory to most established antineoplastic agents, was highly sensitive to PALA. Treatment on Days 1, 5, and 9 following s.c. implantation of Lewis lung carcinoma was curative to 50% of the mice. If treatment was delayed until s.c. Lewis lung tumors had reached about 500 mg, PALA neither cured the mice nor produced significant tumor regression. However, extensive delay of tumor growth and prolongation of survival were still observed.
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PMID:Antitumor activity of N-(phosphonacetyl)-L-aspartic acid, a transition-state inhibitor of aspartate transcarbamylase. 106 66

During studies that showed the presence of fetal antigens on the surface of human malignant melanoma tumor cells, polyvalent antisera specific for human fetal tissues of varying ages were developed. These reagents demonstrated varying patterns of expression of fetal antigens at different ages in various tissues of the human fetus. The possibility that nonneoplastic adult cells showing either maturation arrest or excessive proliferation also might express fetal antigens led to studies of human bone marrow. Although normal bone marrow cells expressed low levels of fetal antigens, large amounts were seen on bone marrow cells of patients with anemias due to iron, B12, or folic acid deficiencies, as well as on those with leukemia. Moreover, normal adult tissues adapted to long-term culture also expressed fetal antigens. After 3 weeks in organ culture adult human skin showed morphological changes similar to those seen in fetal periderm and strongly expressed fetal antigens. In addition, lymphoblasts in long-term cultured human lymphoid cell lines established from normal donors also carried surface fetal antigens. These latter antigens were shared with neoplastic B-cells (chronic lymphocytic leukemia) but not with T-cells. Their expression varied with the cell cycle. The reexpression of fetal antigens on malignant cells is thought to signal a basic derangement in the control of differentiation which is considered to be peculiar to neoplasia. However, these studies indicate that normal adult cells also may reexpress fetal antigens under circumstances unrelated to neoplasia but associated with either maturation arrest or rapid and excessive proliferation.
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PMID:Fetal antigens in nonneoplastic conditions. 108 33

Renal localization of 67Ga citrate has been observed in 1.7% of 2,000 whole-body gallium scans in three major diseases: lymphoreticular neoplasms, leukemia, and malignant melanoma. Correlation of this finding with autopsy data in 13 cases revealed 9 with tumor and 2 with an inflammatory process. Findings in two cases were normal. In the remaining patients, correlation with abnormal urograms and laboratory data was poor. Nevertheless, gallium localization in the kidneys may be the first indicator of renal involvement with either tumor or inflammation.
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PMID:Renal localization of gallium-67 citrate. 108 59

While pure methyl 5-(2-chloroethylamino)-5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranoside hydrochloride has no L-1210 leukemia activity, a decomposed sample was found to be very active. One of several approaches taken to determine the nature of the active component involved a study of how sugar structure affects antitumor activity. A number of aminoribose derivatives were prepared and tested against the murine L-1210 and P-388 leukemia and the B-16 melanoma tumor systems. Compounds were tested as pure materials and as synthetically degraded mixtures. Both the beta-haloethyl group and a secondary amine were required for highest activity.
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PMID:Active antitumor components in a decomposed amino sugar I: Effect of sugar structure on activity. 112 86

The two-drug combination of cyclophosphamide plus adriamycin was found to be therapeutically potentiating against four different C3H mammary tumor lines, the B16 melanoma, the Ridgway osteogenic sarcoma, and the P388 leukemia. The potentiation was not schedule dependent.
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PMID:Cyclophosphamide-adriamycin combination chemotherapy of transplantable murine tumors. 113 24

The clinical manifestations of Gardner's syndrome were studied in 280 patients from 11 families. Forty-five per cent of the patients at risk inherited the syndrome. Forty-one patients had carcinoma of the intestine develop, with only a 27 per cent survival rate for this type cancer. Eight per cent of the patients with the syndrome showed peritoneal fibrosis and fibrous tumors. They also had carcinomas of the ampulla of Vater, liver, bldder and ovary develop as well as osteogenic sarcoma. The patients without the syndrome had carcinomas of the pancreas and breast develop as well as melanoma and leukemia. Twelve of the 16 patients having had a colectomy and ileoproctostomy showed regression of the remaining polyps of the rectum.
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PMID:Gardner's syndrome. 115 13

Hydantoin derivatives of varying lipophilic character were prepared as nitrogen mustard carriers for CNS antitumor evaluation. Activity was studied in the murine ependymoblastoma brain tumor system. Multiple cures were observed for three of the four analogs examined. The compounds were also active in the intraperitoneal leukemia L1210 and P388 systems as well as in B16 melanoma and Lewis lung carcinoma.
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PMID:Potential central nervous system antitumor agents. Hydantoin derivatives. 115 4

Levamisole and tetramisole had no antitumor effect against the following transplantable syngeneic murine tumors: L1210 leukemia, P388 leukemia, B16 melanoma, Madison 109 lung tumor, and Lewis lung carcinoma. In the Lewis lung carcinoma system there was no effect on primary tumor growth, metastasis, or survival. Tetramisole had a variable effect on the growth of rhabdomyosarcomas and the survival of BALB/c mice following intramuscular inoculation of Moloney sarcoma virus. In two experiments treatment with tetramisole either prior to or following inoculation of Moloney sarcoma virus increased the number of mice with tumor regression as opposed to progressive tumor growth, incrneased the number of long-term survivors, and prolonged the lifespan of mice that died of tumor. In two further tests neither levamisole nor tetramisole had an effect in this system. In mice immunosuppressed with cyclophosphamide prior to virus inoculation, there was not effect of treatment with levamisole or tetramisole.
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PMID:Effects of levamisole (NSC-177023) and tetramisole (NSC-102063) in experimental tumor systems. 117 64

Transplantable adenocarcinomas of the colon in mice have been developed from primary tumors induced by 1,2-dimethylhydrazine. Two such transplant lines, MAC-13 and MAC-15, have been used to assess the possible value of this type of tumor in chemotherapy screening. A protocol has been established and 11 standard drugs were tested against the two lines. Both tumors show sensitivity which is remarkably similar to that of human large bowel cancer, and MAC-13 would have correctly predicted the activity in man for ten of the 11 drugs. Quantitatively, CCNU, methyl-CCNU, and cyclophamide were the most effective drugs. A comparison of the predictive efficiencies of L1210 leukemia, B16 melanoma, and these new tumors as screening systems for colorectal cancer is made and discussed.
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PMID:Chemotherapy of transplanted adenocarcinomas of the colon in mice. 122 93

Two new murine monoclonal antibodies were prepared by hybridoma technique after immunization with the immature pluripotent leukemia cell line K562. The monoclonal antibody Bra10G (IgG2b) reacted in a non-lineage pattern with all examined hematopoietic neoplastic cell lines and peripheral blood cells (granulocytes, lymphocytes, erythrocytes) of healthy donors, with the exception of monoblastoid cell line U-937 and B lymphoma cell line Daudi. This monoclonal antibody immunoprecipitated an 18-20 kDa cell surface protein expressed also on the cell surface of examined non-hematopoietic (malignant glioma, melanoma and breast carcinoma) cell lines. These properties and the efficient inhibition of Bra10G binding to the cell surface of K562 cells by the reference CD59 monoclonal antibody (MEM-43) indicated that Bra10G belongs to the CD59 cluster of monoclonal antibodies which identify the human protectin molecule. The monoclonal antibody Bra7G (IgM) reacted with a 95 kDa cell surface protein expressed on hematopoietic cells (with the exception of erythrocytes) and was absent on the examined non-hematopoietic neoplastic cell lines. These data together with a partial inhibition of Bra7G binding by the reference CD-43 monoclonal antibody suggested the CD43 (leukosialin, sialophorin) specificity of this monoclonal antibody.
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PMID:Monoclonal antibodies to two adhesive cell surface antigens (CD43 and CD59) with different distribution on hematopoietic and non-hematopoietic tumor cell lines. 128 43


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