Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laminin is a basement membrane glycoprotein that has diverse biological activities. A sequence on the A chain containing IKVAV (Ile-Lys-Val-Ala-Val) has been shown to promote neurite outgrowth, cell adhesion, and tumor growth and metastasis. Here we have determined the structural requirements of this synthetic peptide for biological activity. Twelve-amino acid-long all-L- (LAM-L) and all-D-peptide (LAM-D) segments as well as an alternating D- and L-amino acid-containing peptide (LAM-DL), which included the IKVAV sequence (residues 2097-2108), were synthesized. Circular dichroism spectral analysis revealed a mirror image conformation of LAM-D and LAM-L with mainly beta-sheet and to a minor extent alpha-helical structure. LAM-DL did not exhibit any significant ordered conformational features. LAM-D and LAM-L showed similar cell attachment activities for rat pheochromocytoma cells (PC12), whereas LAM-DL was inactive. A peptide analog with randomized IKVAV sequence (LAM-RM) was also inactive. A similar trend was observed in competition experiments of the four peptides with laminin in analogous cell attachment assays. In in vivo experiments, both LAM-D and LAM-L were capable of increasing tumor growth when subcutaneously injected into mice with murine melanoma cells B16F10. Results indicate that the conformational status of the IKVAV domain is a contributing factor in determining the biological activity but that there is no strict requirement for a specific chirality. There is a likely sequence specificity to the IKVAV region.
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PMID:The all-D-configuration segment containing the IKVAV sequence of laminin A chain has similar activities to the all-L-peptide in vitro and in vivo. 162 12

To further understand the molecular mechanisms and the biological indicators of colonic tumorigenesis, the authors examined tyrosine kinase activity in the cytosol and in the particulate fraction of the homogenates of specimens from 20 human colonic carcinomas and compared them with the adjacent normal mucosal tissues. Total protein tyrosine kinase activity could be precisely detected using miniphosphocellulose column purification and a synthetic peptide, Glu-asparagine (Asp)-alanine (Ala)-Glu-tyrosine (Tyr)-Ala-Ala-arginine (Arg)-Arg-Arg-glycine (Gly) (E11-G1), as an artificial substrate. Tyrosine kinase activity of colonic carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity in the particulate fraction was elevated with respect to protein concentration. The average specific activity ratios were 1.95 +/- 0.27 (normal cytosolic/carcinoma cytosolic) and 0.57 +/- 0.01 (normal particulate/carcinoma particulate) for tyrosine kinase activity. Cellular distribution (% cytosol) of tyrosine kinase activity in normal mucosa and in carcinoma varied from 21.0% to 91.2% and from 7.0% to 61.4%, respectively. In nearly all cases the percentage of cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal tissues. There was no difference due to histologic type or the presence of adenomatous components. A significant decrease of cytosolic tyrosine kinases was correlated with Dukes' Stage A. With advancing Dukes' stage, the average specific activity ratios (normal cytosol/carcinoma cytosol) were decreased. This study indicates that colonic carcinogenesis might be associated with alterations in cellular levels of tyrosine kinase activity and that the average specific activity ratio (normal cytosol/carcinoma cytosol) had a possible correlation with colonic tumor growth.
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PMID:Altered protein tyrosine kinase levels in human colon carcinoma. 198 53

If proton nuclear magnetic resonance (1H NMR) spectroscopy is to provide a clinically useful modality for monitoring tumor growth and treatment, the technique must be able to unambiguously detect steady-state metabolite concentrations in human tumors and differentiate these from normal tissue levels. To address this problem, a two-dimensional double quantum coherence transfer spectroscopy (2DDQCT) method was developed and tested in a series of tumor cell lines implanted in mice. Lactate-edited proton NMR spectra were determined from a roughly 1-cm3 region of interest in EMT6, RIF-1, and fibroma. In two-dimensional data matrix representations of the 2DDQCT experiments (double quantum frequency on the vertical axis and chemical shift on the horizontal axis) the lactate signal (330 Hz with the transmitter set at the water resonance) was well-resolved from lipid (480 Hz, 600 Hz). The resolution in the double quantum dimension was also sufficient to conclude that a detectable level of alanine, which would reside at 358 Hz, was not present in the three tumor types. Following the NMR experiment, tumors were chemically assayed for lactate giving 8.17, 9.1, and 6.73 mumols/g wet wt for RIF-1, EMT6, and fibroma, respectively. This technique is likely to provide a noninvasive method for monitoring the steady-state lactic acid levels in small tumors before and after therapy, as well as in tissues with impaired oxygen delivery using clinical and research NMR systems.
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PMID:A double quantum coherence transfer proton NMR spectroscopy technique for monitoring steady-state tumor lactic acid levels in vivo. 234 12

In F344 rats bearing transplantable 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, plasma concentrations of immunoreactive insulin were decreased following the development of mild or severe anorexia. Plasma levels of immunoreactive glucagon and lactate were elevated in severely anorectic tumor-bearing (TB) rats, while plasma glucose concentrations remained normal. Both groups of TB rats exhibited decreased plasma levels of serine, glutamine, citrulline, and tryptophan and increased concentrations of alanine. Plasma levels of proline and phenylalanine were also elevated in the severely anorectic TB rats. In a second experiment, 7 daily treatments with insulin corrected the anorexia for 6 days and increased body weights of TB rats. Plasma concentrations of lactate and immunoreactive glucagon were decreased, and the abnormal plasma concentrations of glutamine, proline, analine, and phenylalanine were altered toward normal following the insulin treatments. Therefore, these data are consistent with insulin treatments benefiting the TB host by increasing feeding, increasing body weight, reducing tumor glycolysis and metabolism, reducing gluconeogenesis, and reducing host catabolism, while not stimulating tumor growth. Thus insulin therapy may have potential benefits in cancer treatment by shifting glucose metabolism toward the host and away from the tumor.
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PMID:Reversal of tumor-induced biochemical abnormalities by insulin treatment in rats. 352 58

Proteolytic enzymes may facilitate tumor invasion by histolysis of the surrounding tissue and inhibit tumor growth in the course of host defense reactions. Using chromogenic peptide substrates, we looked for proteolytic activities related to carcinogenesis in serum and tumor extracts of rats with benzopyrene sarcomas. The enzymatic hydrolysis of two substrates (Boc-(Ala)2-p-nitroanilide and Bz-Lys-p-nitroanilide) was significantly decreased in the sera of tumor-bearing animals (P less than 0.01). This loss of proteolytic activity was highly correlated to tumor growth, so these enzymes might become useful as new tumor markers. In the tumor extracts, we found the Boc-(Ala)2-p-nitroanilide cleaving activity increased with tumor weight, whereas the Bz-Lys-p-nitroanilide cleaving activity did not exhibit any correlation to tumor growth. Studies on the potential use of these results for cancer patients are indicated.
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PMID:Proteolytic enzymes as new tumor markers in rats with benzopyrene sarcoma. 356 7

Within the physiological range of other known releasing factors, human pancreatic tumor growth hormone releasing factor (hpGRF) is specific for GH release. Data concerning hpGRF action on cAMP and GH are consistent with the concept of cAMP acting as a second messenger for this releasing factor. hpGRF-stimulated GH release is Ca++ dependent. Exogenous hpGRF40 does not alter the interdigestive gastric motility or secretion of gastrin and motilin in dogs, while large doses of hpGRF stimulate somatostatin release into the hepatic portal blood of the rat. Significant GRF activity as determined by a rat pituitary perifusion system is confined within the median eminence and the arcuate nucleus, though detectable but insignificant GRF activity is present in other area of the hypothalamus and cortex in the rat. GRF activity is present in the ovine brain as well as in the gut. Both tissues contain large (between 4000-5000 daltons) and small (but possibly larger than 1000 daltons) m.w. GRF materials. GRF appears to be structurally different between species and more than one GRF may be present within the same species. One of the ovine brain peptides with GH-releasing activity was partially characterized as His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr- Lys-Arg-Try-Asn-Lys-Glu-Met- Ala-Lys--which is similar to rat GRF and porcine VIP having His at the N-terminus. Another peptide with GRF activity which eluted earlier on reverse phase HPLC and later on cation exchange chromatography has also been obtained in a pure form.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone releasing factors in the brain and the gut: chemistry, actions, and localization. 620 12

Two experiments were conducted with male rats weighing 170 to 190 grams. In experiment 1, some nutritional parameters were determined in tumor-bearing (TB) (Walker 256 carcinosarcoma) rats fed a 23.6% casein diet for 4 weeks after the tumor inoculation. Cumulative weight gain and food intake were less in TB rats than in nontumor-bearing (NTB) rats. At 3 and 4 weeks after the tumor inoculation, plasma histidine, alanine, and glycine levels were higher in TB rats than in NTB animals. The arginine level was lower in the plasma of TB rats at 4 weeks after the inoculation. The significance of decrease in plasma arginine with regard to tumor growth is discussed. In experiment 2, the effects of total parenteral nutrition (TPN) on TB rats were evaluated as compared with those of 5% glucose (Glc) solution. Body weights of TPN rats were maintained and their nitrogen (N) balances were positive during a 7-day experimental period, while 5% Glc animals showed severe body weight loss and apparent negative N balance. After the end of infusion, the plasma urea level of the TPN group was within normal range, whereas that of 5% Glc group showed a markedly high value. The plasma albumin level was higher in the TPN group. Liver and spleen weights were increased in TPN rats. Absolute tumor weight was somewhat greater in TPN rats than in 5% Glc rats, but the difference in tumor weight:body weight ratios became more slight. These results indicate that TPN was effective for maintaining the nutritional status of TB host without significant acceleration in tumor growth.
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PMID:Nutritional responses of tumor-bearing rats to oral or intravenous feeding. 681 15

Mouse fibrosarcoma cells were grown in vitro and incubated with L-2,4 diaminobuturic acid, a non-metabolizable amino acid. The tumor cells were irreversibly and totally damaged by incubation with 10 mM DAB for 24 h at 37 degrees C. The cell-destructive effect by DAB was probably due to an osmotic lysis induced by the non-saturated intracellular accumulation of DAB. The harmful effect of DAB could be abolished by concomitant incubation with L-alanine and L-methionine, that compete with DAB for the same transport system, while the D-forms of the same amino acids as well as sarcosine had a weak effect. The fibrosarcoma cells were also transplanted s.c. into mice that were subsequently treated with i.p. injections of an isotonic 0.1 M DAB solution. The neoplastic cells were transplanted into totally 90 animals. The mean tumor weight of 42 treated animals was 1.16 g (+/- 0.77 g) compared with the corresponding figures of the 27 untreated mice, that were 2.05 g (+/- 1.22 g), i.e., a 43.4% reduction of tumor growth. There were, however, 17 drug-related deaths. Treatment with DAB generally resulted in weight reduction, at least partly due to loss of appetite, in animals. In addition, neurological symptoms of a specific character could develop among several of the treated animals. The side effects apparently restrict the usefulness of DAB alone as an anti-tumor agent, but since the principle of action of DAB is unique and not shared by other known chemotherapeutics it might offer new possibilities in the combined treatment of neoplastic growth.
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PMID:Antitumor activity of L-2,4 diaminobuturic acid against mouse fibrosarcoma cells in vitro and in vivo. 743 Feb 41

Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer cell line were treated with potent luteinizing hormone (LH)-releasing hormone (LH-RH) antagonist SB-75 (Cetrorelix; [Ac-D-Nal(2)1, D-Phe(4 CI)2, D-Pal(3)3, D-Cit6, D-Ala10]LH-RH in which Ac-D-Nal(2) = N-acetyl-3-(2-naphthyl)-D-alanine, D-Phe(4CI) = 4-chloro-D-phenylalanine, D-Pal(3) = 3-(3-pyridyl)-D-alanine, and D-Cit = D-Citrulline) or with the agonist [D-Trp6]LH-RH. In the first experiment, SB-75 and [D-Trp6]LH-RH were administered in the form of microcapsules releasing 60 and 25 micrograms/day, respectively. In the second study, the analogs were given by daily s.c. injections in doses of 100 micrograms/day. In both experiments, tumor growth, as measured by reduction in tumor volume, percentage change in tumor volume, tumor burden, and increase in tumor doubling time, was significantly inhibited by treatment with SB-75 but not with [D-Trp6]LH-RH. Uterine and ovarian weights were reduced and serum LH levels decreased by administration of either analog. Chronic treatment with SB-75 greatly reduced the concentration of receptors for epidermal growth factor and insulin-like growth factor I in tumor cell membranes, a phenomenon that might be related to tumor growth inhibition. It is possible that the antitumoral effects of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression of the pituitary-gonadal axis, but also directly. In view of its strong inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH-RH antagonist SB-75 might be considered for possible hormonal therapy of advanced epithelial ovarian carcinoma.
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PMID:Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75. 751 26

The administration of an acute tumor necrosis factor-alpha (TNF) dose (100 micrograms/kg BW) to 20-day pregnant rats resulted in a substantial decrease in the fetal availability of maternally administered amino acids, as measured by the accumulation of alpha-amino-[1-14C]isobutyrate ([14C]AIB) and [1-14C]cycloleucine ([14C]CLEU), nonmetabolizable analogs of the amino acids alanine and leucine, respectively. Thus, TNF treatment resulted in a decreased accumulation of the tracers in the whole fetus as well as in fetal liver. The cytokine also caused important changes on the maternal liver, where it increased both [14C]AIB and [14C]CLEU accumulation. In skeletal muscle and heart, TNF treatment resulted in decreased [14C]AIB accumulation, but increased [14C]CLEU. These changes in tissue amino acid uptake were accompanied by changes in circulating amino acids. TNF treatment promoted an increase in the concentrations of both alanine and leucine in the maternal circulation, whereas no changes in the circulating concentrations of these amino acids were observed in the fetuses. The decreased fetal accumulation of maternally derived amino acid analogs is partially explained by a decrease in fetal blood flow [as measured by the accumulation of [14C]1,1,1-trichloro-2,2- bis-(p-chlorophenyl)ethane] induced by the cytokine). It is suggested that the cytokine may be involved in fetal growth impairment during pathological states (such as tumor growth or chronic infection) by promoting a decreased transplacental passage of amino acids, essential compounds for both protein accretion and oxidation in fetal metabolism.
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PMID:Administration of tumor necrosis factor-alpha results in a decreased placental transfer of amino acids in the rat. 762 96


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