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)

It was shown previously that invasive human transitional cell carcinoma cell line EJ, but not the noninvasive RT4 cells, can degrade basement membrane laminin and that the degradation of basement membrane laminin was a result of a redistribution of activated cysteine proteinase cathepsin B to the plasma membrane of the invasive EJ cells. Using a modified Boyden chamber and an artificial basement membrane, it was found first that cysteine proteinase inhibitor E-64 can abolish the ability of the EJ cells to invade through the artificial basement membrane to the underside of the filter. Second, E-64 can prevent the degradation of purified human basement membrane laminin by the plasma membrane fraction of invasive EJ cells. Third, E-64 does not affect the ability of the EJ cells to attach to the extracellular matrix nor is the inhibitory dose toxic to the cells when assayed with trypan-blue dye exclusion. However, E-64 does affect the ability of the EJ cells to respond to autocrine motility factor-induced motility. Finally, in an in vivo model, E-64 was not toxic to the animals tested and may have limited the blood-borne metastatic ability of invasive EJ cells in the treated animals. It was concluded that proteinase cathepsin B may be involved in human bladder tumor invasion, in both extracellular matrix degradation and factor-induced cellular motility, and the authors suggested that the use of inhibitor(s) to cysteine proteinases may limit the invasive potential of human bladder cancer cells.
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PMID:Abrogation of the invasion of human bladder tumor cells by using protease inhibitor(s). 173 20

A heparan sulfate proteoglycan is a component of all basement membranes. This molecule consists of three heparan sulfate side chains linked to a large core protein of approximately 400 kDa. We have isolated seven overlapping murine cDNA clones that encode the entire mRNA sequence of 12.685 kilobases of this molecule. This sequence has a single open reading frame of 3,707 amino acids that encodes for a protein of 396 kDa. Identical or near identical matchups with nine peptide sequences derived from the core protein of the molecule isolated from the Engelbreth-Holm-Swarm tumor were found with the deduced sequence. Sequence analysis and data base comparison of the deduced sequence show the protein to consist of five different domains, most of which contain internal repeats. Domain I contains a start methionine followed by a typical signal transfer sequence and a unique segment of 172 amino acids that contains the three probable sites of heparan sulfate attachment, SGD. Domain II contains four cysteine- and acidic amino acid-rich repeats that are very similar to those found in the LDL receptor and proteins such as GP330. Domain III consists of cysteine-rich and globular regions, both of which show similarity to those in the short arm of the laminin A chain. Domain IV contains 14 repeats of the immunoglobulin superfamily that are most highly similar to the immunoglobulin-like repeats in the neural cell adhesion molecule. Domain V contains three repeats with similarity to the laminin A chain G domain that are separated by epidermal growth factor-like regions not found in the laminin A chain. As the primary structural data agree with the appearance of the molecule in the electron microscope as a series of globules separated by rods, or "beads on a string," we have adopted the name perlecan for this molecule. The variety of domains in perlecan suggest multiple interactions with other molecules.
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PMID:The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule. 174 87

RibCys, a thiazolidine prodrug of L-cysteine synthesized by the condensation of the sulfhydryl-containing amino acid with the aldose monosaccharide D-ribose, successfully elevated glutathione (GSH) levels in numerous organs of tumor-bearing CDF1 mice. GSH content was assayed 1,2,4,8 and 16 h after RibCys administration (8 mmol/kg, i.p.); various organs achieved maximal GSH content at different time points. GSH in the liver was elevated 1.5-fold compared to untreated controls at the 16-h time point. Kidney GSH also was maximal at 16 h and achieved 1.6-times control values. GSH in muscle achieved 2.5 times the levels in control animals, while the bladder was elevated 2.1-fold, and the heart 1.8-fold. Other tissues tested (spleen, pancreas, lung) showed a 1.1- to 1.2-fold increase in GSH content. GSH in implanted L1210 tumors was also elevated only 1.2-fold. These data suggest the possibility of protecting organs other than the liver from toxic insults that require the intervention of GSH for detoxication and may allow such protection without compromising the utility of chemotherapy.
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PMID:Time course for the elevation of glutathione in numerous organs of L1210-bearing CDF1 mice given the L-cysteine prodrug, RibCys. 175 32

Ehrlich ascites tumor cells (EAT) could not proliferate in a basal medium (BM). L-Cysteine (L-CYS) added to BM in a concentration of 0.5 to 2 mM could promote the growth of EAT. At an unusual concentration of L-CYS (1 mM), the growth-rate was 233% (n = 50) at 72 hr after EAT transplantation. A similar growth-rate was obtained when EAT was transplanted 24 hr after addition of L-CYS to BM, although the free SH content in L-CYS-added BM at this time decreased to the level of that in BM. S-Methyl- and S-benzyl-L-cysteine showed no growth-promoting effect. The metabolic products of L-CYS (L-cysteine sulfinic acid, hypotaurine and taurine) showed a lower effect or none, but L-cystine showed the same activity as L-CYS. The EAT cultured in L-CYS-added BM was found to have an increased intracellular free SH and unchanged protein SH. These findings suggest that L-CYS added to BM is changed in a non-SH compound (possibly L-cystine) that is taken up into the cells and increases the intracellular free SH, resulting in the cell growth promotion.
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PMID:[Growth-promoting action of L-cysteine and its related compounds on Ehrlich ascites tumor cells in vitro]. 178 25

To examine the potential role of lipoxygenase products in the pathophysiology observed after experimental tumor implantation, we examined the generation of leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) in peritoneal macrophages. C57BL/6 mice were given subcutaneous inoculations of B16 melanoma cells, and peritoneal macrophages were isolated various days after the inoculation. Macrophages were incubated for 1 h at 37 degrees C in serum-free RPM11640 containing 10 microM calcium ionophore A23187, 10 microM exogenous arachidonic acid (AA), 5 mM cysteine hydrochloride and 1 mM reduced glutathione. LTs and HETEs were separately extracted, passed through Sep-Pak cartridges, then identified and quantitated with a HPLC system using UV absorbance. The B16 melanoma-cell-treated/untreated macrophages were found to produce substantial amounts of 15-HETE, 12-HETE and 5-HETE and LTC4 by enzymatic mechanisms. Thus, when determined under various conditions, the production of HETEs was dependent on substrate-concentration, incubation-time and cell-number. The production of LTC4 was dependent on incubation-time and cell number but not substrate-concentration, indicating utilization of endogenous AA stores. Of these products, 12-HETE and LTC4 showed a significant increase on the fourth day after the tumor cell inoculation and returned to the control level by the 11th day after the same treatment. These results suggest that in vivo tumor cell implantation may induce a transient increase of 12-HETE and LTC4 production in macrophages.
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PMID:Generation of leukotrienes and hydroxyeicosatetraenoic acids in peritoneal macrophages of tumor-bearing mice. 180 27

Identification of the G1-P120 antigen with the aid of the monoclonal antibody to its "human-specific epitope" has resulted in rapid development of information on its molecular biology. With the monoclonal antibody, it rapidly became possible to identify and subsequently sequence its cDNA and with cDNA clones to isolate and sequence its genomic DNA. It was demonstrated that the protein had 4 major domains: a basic domain, an acidic domain, a hydrophobic and methionine-rich domain and a domain rich in cysteine and proline residues. In addition to a nuclear recognition signal, the epitope region is juxtaposed to phosphorylation sites. The epitope region contains the sequence Gln-Ala-Ala-Ala-Gly-Ile-Asn-Trp which is unique to the human P120 molecule; this may be a site for drug attack either by analogs to the region or by novel constructs based on antisense oligonucleotides. When tumor cells were transfected with antisense constructs of the P120 gene, growth rates were markedly reduced. 3T3 cells transformed by transfection with the P120 gene reverted to a nontransformed state by subsequent transfection and activation of a P120 antisense construct. Opportunities for control of malignant cells with antisense oligonucleotides are currently under study.
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PMID:Nucleolar protein P120 and its targeting for cancer chemotherapy. 180 2

Selenium is an essential trace element that has been shown to have anticarcinogenic activity. One mechanism that has been proposed for this activity is a cytotoxic effect of selenium on tumor cells. As a means of assessing its cytotoxicity, we have examined the effect of selenite on tumor cell viability, using as an assay the ability of the cells to form colonies. We have found that brief exposure of HeLa cells to micromolar concentrations of selenite resulted in significant inhibition of colony formation, indicating that this is an assay for selenite cytotoxicity that is more sensitive than those that have been employed previously. In order to investigate the involvement of cellular glutathione in selenite cytotoxicity, we treated cells with buthionine sulfoximine (BSO) before selenite exposure. This treatment, which resulted in a 7-fold reduction in the level of intracellular glutathione, also caused a significant decrease in the inhibitory effect of selenite on colony formation. However, when cells were exposed to selenite that had previously been reacted with glutathione, the BSO-induced decrease in cytotoxicity was eliminated. In contrast, reaction of selenite with other sulfhydryl compounds, such as cysteine and mercaptoethylamine, did not restore its potency in BSO-treated cells. The simplest explanation for these results is that, for selenite to exert its inhibitory effect, it must react with intracellular glutathione to form the selenodiglutathione derivative.
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PMID:Inhibition of cell colony formation by selenite: involvement of glutathione. 182 39

Antisera raised in rabbits to three peptides corresponding to amino acid sequences found in human O6-alkylguanine-DNA alkyltransferase were used to study the fate of the alkyltransferase protein in human colon tumor cells after exposure to N-methyl-N'-nitro-N-nitrosoguanidine or to O6-benzylguanidine. Under these conditions, the alkyltransferase protein becomes inactivated, presumably by the conversion of its cysteine acceptor site to S-methylcysteine or S-benzylcysteine respectively. It was found that the protein was rapidly degraded after such inactivation both in intact cells and in cell-free extracts. It is probable that a conformational change in the protein is brought about by conversion of the alkyltransferase to the inactive form by alkylation of the cysteine acceptor site. This change may render the protein very sensitive to proteolytic degradation. The rapid degradation of the inactive form of the protein may serve as a signal for its resynthesis but in the short term ensures that its reactivation by regeneration of the cysteine acceptor site is unlikely to occur to any significant extent. The short half-life of the inactivated alkyltransferase protein makes it probable that measurement of the content of the alkyltransferase protein by immunohistochemistry, which is likely to measure the sum of the active and inactivated forms of the protein, will nevertheless yield an accurate estimation of the cellular capacity to repair O6-methylguanine provided that procedures with sufficient specificity and affinity can be developed.
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PMID:Use of antibodies to human O6-alkylguanine-DNA alkyltransferase to study the content of this protein in cells treated with O6-benzylguanine or N-methyl-N'-nitro-N-nitrosoguanidine. 189 28

L-methionine-deprived total parenteral nutrition (methionine-deprived TPN), infusing amino acid solution devoid of L-methionine and L-cysteine by the method of TPN as an only protein source, showed enhancement of the effect of several anti-cancer agents. In this study the combined effect of the methionine-deprived TPN with administration of 5-fluorouracil (5-FU) was examined in Yoshida Sarcoma (YS)-bearing rats, from aspects of effects on the tumor metastasis and the host animal's life span, in the following four groups treated with: methionine-deprived TPN with administration of 5-FU, methionine-deprived TPN without administration of 5-FU, L-methionine-contained TPN plus 5-FU, and L-methionine-contained TPN without 5-FU. In the first experiment, TPN was continued for 8 days in the four groups, and the anti-cancer effect of methionine-deprived TPN and administration of 5-FU based on both the growth of the primary tumor at the implanted site and the tumor metastasis was studied from the view point of pathologic findings of animals killed immediately after these treatments. In experiment 2 the survival period was examined after these treatments for 10 days with subsequent oral feeding until death. The results were as follows: proliferation of YS, transplanted subcutaneously, was markedly suppressed; particularly hematogenous metastasis, characteristic in YS, was prominently blunted then obtained an apparent longer survival period in rats treated with the methionine-deprived TPN with administration of 5-FU.
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PMID:Anti-tumor effect of L-methionine-deprived total parenteral nutrition with 5-fluorouracil administration on Yoshida sarcoma-bearing rats. 190 13

To elucidate a factor required for tumor-imaging 99mTc-labeled radiopharmaceuticals, in vivo behaviors of 99mTc-L-cysteine (99mTc-Cys) and 99mTc-2-mercaptoethylamine (99mTc-ME) were compared with that of 99mTc-DL-homocysteine (99mTc-Hcy) which had been found to accumulate in several experimental tumors. When these three complexes were intravenously injected into mice bearing Ehrlich solid tumor, their tumor affinity was found to depend on their binding ability to serum albumin; 99mTc-Hcy, the albumin-binding ability of which was highest of the three, was the most tumor-tropic. When the albumin-bound complexes of these three were injected, their tumor distributions were enlarged. These results suggest the importance of serum albumin in serving as a carrier for the transport of 99mTc-Hcy-related compounds to tumor tissue.
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PMID:Role of serum albumin as a carrier of 99mTc-complex to tumor tissue. 191 19


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