Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 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

The cell-mediated immune response against a transplantable syngeneic metastatic solid tumor in mice was studied. The immune reactivity of spleen cells from tumor-bearing mice was found to vary during development of the tumor. For about a week after tumor transplantation, the spleen cells were able to protect recipient mice against challenge with tumor cells. Subsequently, the protective activity was replaced by an enhancing activity. Recipient mice that received tumor cells together with spleen cells from mice bearing tumors for about two or three weeks had a higher incidence of tumor takes and larger tumors than controls. This enhancement of tumor development was correlated with the size of the local tumor or metastases in the donors. The enhancing activity was found to be mediated by T lymphocytes and appeared to suppress the protective immune response of the recipients. We devised a system to strengthen the immune response of the host against the development of tumor metastases. In the tumor model used, removal of the local tumor after s.c. transplantation failed to prevent the development of lung metastases and death in most of the mice. However, syngeneic spleen cells which had been sensitized in vitro against tumor cells were found to serve as immunotherapeutic agents. Injection of such spleen cells into mice from which primary tumor implants had been removed surgically led to a markedly increased survival. Spleen cells from both normal and tumor-sensitized donors were effective, but splenocytes from mice bearing large tumors did not reduce metastatic development after sensitization in vitro. Thus, protection against the development of lethal metastases can be achieved with certain types of lymphocytes sensitized in vitro.
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PMID:A syngeneic metastatic tumor model in mice: the natural immune response of the host and its manipulation. 108 80

A rapid method for determining labeling indices in solid tumor specimens, tumor-induced effusions, and tumor-bearing bone marrows was utilized in 116 patients. Of these, 48 patients were studied pre- and postchemotherapy. The magnitude of a significant change in labeling index (LI percent) was determined statistically. Of the 48 patients studied serially, 42 were studied 17 days or less following completion of their chemotherapy. In 26 patients without a significant change in tumor LI percent, there was no subsequent clinical response to chemotherapy. Three additional patients in this group are inevaluable at present. In 11 patients, there was a significant fall in tumor LI percent following chemotherapy. Seven of these had a 50 percent or greater regression of demonstrable disease, one patient had definite tumor effect but the effect was not a partial response and three patients were not evaluable for clinical response. In two patients there was a significant increase in tumor LI percent and the patients had rapid tumor progression and death. Predictions derived from serial study of the LI percent by this method correlate significantly with subsequent behavior of the tumors tested following chemotherapy and may prove clinically useful in making decisions about when or whether to change therapy.
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PMID:Serial labeling index determination as a predictor of response in human solid tumors. 109 72

A lipopolysaccharide (serratigen) and a polysaccharide (serratimannan) were isolated from Serratia marcescens, red strain No. 51. They were different from any other polysaccharides previously reported. The antitumor activity of these polysaccharides was determined. Serratimannan showed 63% tumor inhibition and serratigen 38%, at a dose of 150 mg/kg, against solid tumor of sarcoma-180 using ICR mice. The fraction obtained by removal of proteins from the crude extract by the Sevag method showed a high antitumor activity against solid tumor of sarcoma-180 using Swiss albino mice, but did not show so high an activity using ICR mice. In total packed cell volume method, these polysaccharides exhibited a high rate of antitumor activity against ascites tumor of sarcoma-180.
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PMID:Antitumor activity of polysaccharides from Serratia marcescens. 110 78

Studies were performed to determine the role of macrophages in inhibition of growth of the same tumor cell type both in vitro and in vivo. Bladder transitional epithelium tumor cells were injected s.c. into Toxoplasma-infected mice, previously shown to contain activated macrophages, and into uninfected controls. The subsequent growth of a solid tumor was significantly less in the Toxoplasma-infected animals. Bladder tumor cells from the same cell line were grown in vitro either alone or in the presence of peritoneal lymphocytes and/or macrophages from oxoplasma-infected and control, uninfected mice. [3H]Thymidine incorporation by the tumor cells was inhibited only in the presence of macrophages from the Toxoplasma-infected animals. Lymphocytes alone did not appear to be cytotoxic under the conditions used. Moreover, lymphocytes from Toxoplasma-infected mice did not convey cytotoxicity to macrophages from control animals under the experimental conditions used.
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PMID:A role for the macrophage in in vivo and in vitro resistance to murine bladder tumor cell growth. 110 96

Functionally active mammalian membrane-free ribosomes were prepared from rat forebrain, a solid tumor (mouse neuroblastoma C-1300) and a human tumor cell-line in suspension culture (HeLa). Proteins were extracted from these ribosomes and were resolved by a newly developed. Two dimensional gel electrophoretic procedure. Although the ribosomal protein patterns from the three preparations were generally similar, there were four obvious differences between the forebrain ribosomes and the ribosomes from the two neoplastic cell types.
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PMID:Comparison of ribosomal proteins from neoplastic and non-neoplastic cells. Resolution by two-dimensional gel electrophoresis. 112 27

Subcutaneously transplanted 3-methylcholanthrene-induced KMT-17 tumor in WKA rats yielded not only a local solid tumor but also frequent metastases in regional lymph nodes. Neither active immunization with xenogenized identical tumor cells nor surgical excision of the solid tumor prohibited the metastases when each treatment was given 4 days after tumor transplantation. However, immunization combined with surgery significantly decreased the metastases and prolonged survival.
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PMID:Inhibition of metastasis in rats immunized with xenogenized autologous tumor cells after excision of the primary tumor. 112 31

An in vitro colony formation assay was used to determine the efficacy of in vitro therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on a rat brain tumor. The fraction of clonogenic cells surviving in vivo therapy was determined by a comparison between the in vitro colony-forming capacity of cells derived from previously treated and untreated tumors. With this intracerebral solid tumor a direct correlation was found between the surviving fraction of cells and animal survival, implying that the in vitro assay system is a reliable test of therapeutic effect. The BCNU dose-response curve was exponential up to a dose of 0.75 times the LD10 dose with little additional cell kill noted at higher drug levels. This plateau does not appear to represent a resistant subpopulation of cells, since retreatment of tumors derived from cells surviving an LD10 dose were as sensitive to BCNU as those with no prior drug exposure. Instead, it may represent, at least in part, failure of the drug to reach and/or enter cells in all parts of solid tumors. On the average BCNU doses of 0.75 times the LD10 dose or greater resulted in slightly more than a 3-log cell kill and doubled the life-span for our tumor-bearing animals. The finding that an increase in animal life-span requires at least a 1-log tumor cell kill indicates that survival studies with intracranial tumor models may be insensitive to single courses of many chemotherapeutic agents with modest but significant antitumor activity.
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PMID:In vitro evaluation of in vivo brain tumor chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. 113 13

Mycophenolic acid, a novel antibiotic of low toxicity containing no nitrogen atoms in its structure, induces tumor regression in several murine solid tumor assays. It has been reported in extensive structure-activity studies that chemical modifications on the antibiotic itself reduce or eliminate antitumor activity. With the objective of antitumor activity enhancement, nitrogen-containing analogs of mycophenolic acid were synthesized according to a program directed toward the ultimate synthesis of close bioisosteres of the antibiotic. Intial efforts reported here describe the terpenoid side-chain degradation of N-geranyl-2(1H)-pyridones and N-geranylglutarimides, where the terminal isopropylidene is replaced with a carboxyl group as it occurs in mycophenolic acid. The resulting nitrogen-containing analogs of the antitumor antibiotic were inactive in the l-1210 and Walker 256 tumor systems.
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PMID:Antitumor agents II: nitrogen analogs of mycophenolic acid. 113 12

An increase of the radiosensitivity can be obtained by means of microwave use in combination with sparsely ionizing radiation. Comparing the therapeutic effect on the model of an euoxic tumor (mice testicles) with a tumor that contains important parts of hypoxic cells (solid tumor of Ehrlich) it appears that the sensitization evidentely is seen in the hypoxic tumor first of all. No sensitization can be obtained on the euoxic profileration tissue on the testicles. The temperature enhancement ratio (equal TER) does not increase linearly with increasing temperature, but is the greatest within the scope of 41 degrees C. The mere heat effect appears in the foreground with high temperatures (43 degrees C and more). The high frequency application lets hope a solution of the oxygen problem in radiotherapy and could substitute the use of heavy particles (high LET) in the combination with sparsely ionizing radiation as far as a concentration of high frequency and heat on the tumor succeeds in.
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PMID:Microwaves in radiotherapy of tumors - alternative to heavy particles? 113


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