Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.
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PMID:Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion. 133 2

The potential of seven tracers for the metabolic imaging of tumors by positron emission tomography was studied using five experimental tumor models. The tracers examined were 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), 2-deoxy-2-[18F]fluoro-D-galactose (2-[18F]FdGal) and 2-deoxy-2-[18F]fluoro-L-fucose (2-[18F]FdFuc) for investigating energy metabolism. L-[methyl-11C]Methionine ([11C]Met) and 6-[18F]fluoro-L-fucose (6-[18F]FFuc) were used for assessing protein and glycoprotein synthesis, while [3H]thymidine ([3H]Thd) and 2-deoxy-5'-[18F]fluorouridine ([18F]FdUrd) were used to investigate nucleic acid metabolism. The highest mean uptake by the five different tumors was found for [3H]Thd, followed in order by [18F]FDG, [11C]Met, 2-[18F]FdGal, [18F]FdUrd, 2-[18F]FdFuc and 6-[18F]FFuc. The tumor-to-tissue uptake ratios indicated that the nucleosides, [11C]Met and 6-[18F]FFuc were better tracers in the brain region. All the tracers except for the fucose analogs were suitable for the thoracic region, while [11C]Thd and [18F]FDG were superior in the abdominal region. In comparison with the primary tumor model of Lewis lung carcinoma (3LL), [3H]Thd uptake in the artificial metastatic 3LL model showed the maximum enhancement, followed by [18F]FDG, [11C]Met and the other tracers. The [18F]FDG uptake correlated with the [3H]Thd uptake. [18F]FdUrd, 6-[18F]FFuc and 2-[18F]FdGal could be used for distinguishing different types of tumors. The combined use of these radiotracers can possibly allow the assessment of tumor metabolism, and this indicates the viability of tumors.
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PMID:Tumor diagnosis by PET: potential of seven tracers examined in five experimental tumors including an artificial metastasis model. 138 72

Methionine-depleting total parenteral nutrition (methionine-depleting TPN), which infuses an amino acid solution devoid of L-methionine and L-cysteine as the sole protein source, showed enhancement of the effect of several anti-cancer agents. In this study, the combined effect of the methionine-depleting TPN with the administration of doxorubicin was examined in Yoshida sarcoma (YS)-bearing rats with regard to effects on the primary tumor growth, the extension of metastasis, and the host animal's life span. In the first experiment, immediately after receiving methionine-depleting TPN for 8 days, the animals were killed. Pathologic findings evaluated tumor growth in the implanted site and extension of the metastasis. In the second experiment, the survival period was determined after animals received methionine-depleting TPN for 10 days, with subsequent oral feeding until they died naturally. Proliferation of YS was markedly suppressed. In particular, hematogenous metastasis, which is a characteristic of YS, was suppressed, and a longer survival period (42.7 +/- 15.6 days, mean +/- SD) was attained in rats in the group treated with the methionine-depleting TPN combined with the administration of doxorubicin.
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PMID:Antitumor effect of methionine-depleting total parenteral nutrition with doxorubicin administration on Yoshida sarcoma-bearing rats. 155 Oct 70

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

We have used 5'-deoxy-5'-S isobutyl-thioadenosine (SIBA), an analog of S-adenosylhomocysteine, alone or in association with a methionine-depleted diet in order to obtain an antitumoral effect in two different tumor models: a transplantable rat rhabdomyosarcoma (RMS-J1) induced by i.m. injection of nickel and the well-known Lewis lung carcinoma (3LL) of C57BL/6 mice. Since SIBA has been reported to inhibit the methyl group transfer from methionine to S-adenosylhomocysteine, among other activities, its association with a reduction of methyl donors, achieved by methionine depletion of the diet (in vivo) or the culture medium (in vitro), should logically lead to an additive effect. In vitro, 3LL and RMS-J1 were sensitive to the cytotoxic effect of SIBA and were methionine-dependent for their proliferation. Fibroblast proliferation was not affected by these two treatments alone or in association. In vivo, either SIBA treatment or a low methionine diet led to a significant decrease in the metastatic character of these two tumors; however, local tumor growth was not significantly affected. The median number of 3LL metastases counted in the lungs was reduced from 100 to 18 by SIBA treatment, and to 27 by the low methionine diet. No additive effect could be detected when the treatments were given simultaneously. RMS-J1-bearing rats treated with SIBA and fed a low Met diet underwent primary tumor excision. The median numbers of lung metastatic nodules were 27, 26, 14 and 8 for the control, SIBA-treated rats, methionine-deprived rats and rats receiving the combined therapy. Expressed as percentages 20 per cent were cured, 23 per cent showed a low number of lung metastases (P less than 10), whereas all the rats in the control group developed more than 10 pulmonary nodules. No cytotoxic effect could be observed on the treated rats. The role of SIBA and methionine depletion, as agents interfering with transmethylation processes, in regard to the control of tumor development, namely metastatic invasiveness, is discussed.
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PMID:Association of SIBA treatment and a Met-depleted diet inhibits in vitro growth and in vivo metastatic spread of experimental tumor cell lines. 325 80

Many Experimental and human tumor cell lines have been previously described as being dependent upon exogenous methionine for their in vitro proliferation. The rationale of the experiments described herein was to decrease the in vivo growth of malignant tumors by reducing the exogenous methionine available in diets fed to Wistar AG rats bearing the highly metastatic rhabdomyosarcoma, RMS-J1. The methionine content in the diet was reduced either by replacing casein (diet 1) with soybean protein (diet 4), or by lowering the amount of soybean protein in the diet (from 23 g/100 g to 12 g/100g) (diet 5), or by using a crystalline amino acid-defined mixture as the source of protein (diet 7). In the latter diet homocysteine replaced methionine and allowed the survival of the animals. Diet 4 significantly reduced the mean number of lung metastases without affecting the primary tumor growth. Treatment of RMS-J1 bearing rats with diet 5 led to the decrease of pulmonary invasion (78 and 21 median lung metastases, respectively, in control and treated groups). This diminished metastatic dissemination resulted from the reduced methionine consumption: the lowered casein content in diet 3 (10 g/100 g) as compared to diet 1 (23 g) did not alter primary tumor growth or the amplitude of lung invasion. Moreover, the addition of methionine to diet 5 prevented the diminution of the median number of lung metastases. Replacement of methionine with homocysteine in the crystalline amino acid-defined mixture (diet 7) fed to RMS-J1 bearing rats led to a limited retardation of primary tumor growth (less than 10%) and to a significant decrease in pulmonary invasion: the median number of pulmonary metastases was 28 and 9 for control and treated rats respectively.
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PMID:Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet. 367 75

A new strain of feline sarcoma virus, designated HZ1-FeSV, was isolated from a 4-year-old domestic cat with multicentric fibrosarcoma. A primary tumor cell line was established and virus produced from that line was found to induce foci in feline embryonic lung fibroblasts (FLF3) and mink lung fibroblasts (CCL64) in tissue culture and fibrosarcomas in inoculated 10-week-old kittens. The derivation of transformed nonproducer clones of FLF3 and CCL64 cells containing helper virus-rescuable, focus-forming activity indicated that HZ1-FeSV was defective for replication. The only discernible translation product of the HZ1-FeSV genome in cultured cells was a 100,000-Da polyprotein (P100) which contained amino-terminal sequences of the FeLV gag gene precursor protein covalently linked to a sarcoma virus-specific domain. Immunoprecipitates containing P100 exhibited a protein kinase activity capable of phosphorylating tyrosine residues of P100. Immunologically, P100 was highly cross-reactive with gag-fes polyproteins encoded by two previously characterized strains of FeSV, the GA- and the ST-FeSV. By comparison of methionine-containing tryptic peptides, the HZ1-FeSV protein was shown to be more closely related to the GA-FeSV protein than to the ST-FeSV protein, but to be distinguishable from both other proteins.
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PMID:Isolation of a new feline sarcoma virus (HZ1-FeSV): biochemical and immunological characterization of its translation product. 632 May 33

The effects of variations in the concentrations of L-cystine (Cys), L-methionine (Met), and L-glutamine (Glu) on the establishment of melanocyte cell lines obtained from a primary tumor and its metastasis in the same patient were studied. The special role of Glu was also studied in 4 lymph node metastases from other patients. Differentiation in vitro was dependent on the culture conditions, as assessed by morphologic and biochemical studies. Karyologic expression, doubling time, cloning efficiency, and tumorigenicity in nude BALB/c mice varied widely among the cell lines. Cys was an indispensable amino acid and Glu was not. Met and Glu were implicated in melanogenesis. From these observations arose the question of the accuracy of comparative results, concerning differentiation and tumorigenicity, that had been collected for cell lines obtained under different culture conditions.
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PMID:Differentiation and tumorigenicity of human malignant melanocytes in relation to their culture conditions. 642 May 97

The cytogenetic study of a nodal metastasis from a gastric carcinoma, after two passages in nude mice, revealed a large number of double minutes. Comparative genomic in situ hybridization (CGH) analysis using DNA extracted from this xenograft revealed the existence of three clear amplification units that originated from the chromosomal subregions 6q24-25, 7q31-32, and 8q24 in the xenograft DNA. Similar, though less prominent, CGH results were found with DNAs extracted from the primary tumor and its metastasis, implying that the same amplicons were also present, albeit less abundantly, in the DNAs of these neoplastic tissues. Southern analysis of the second-passage xenograft detected 18- and 10-fold amplification of MET (located at 7q31) and MYC (located at 8q24), respectively. The retrospective study of the first passage of the xenograft, as well as of the metastatic and primary tumors before xenografting, showed amplification levels of MET of, respectively, 12-, 9-, and 5-fold and MYC of, respectively, 8-, 7-, and 5-fold. Our results suggest that increased levels of co-amplification of MYC and MET correlate with enhanced growth potential in this case of gastric carcinoma.
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PMID:Increasing levels of MYC and MET co-amplification during tumor progression of a case of gastric cancer. 766 43

Allelic deletion of multiple regions on the short arm of chromosome 3 (3p) implies the presence of multiple important tumor suppressor genes in human carcinogenesis. The FHIT gene, identified recently in chromosome 3p14.2, shows frequent allelic deletion and aberrant transcripts in gastrointestinal tumors. After determining the intron sequences flanking each of the coding exons of the FHIT gene and designing intron primers to facilitate mutation analysis of genomic DNA samples, we analyzed the complete coding sequences in matched cancer and normal tissues from 40 cases with primary gastric cancer using intron primers, PCR-single-strand conformation polymorphism analysis, and direct sequencing. A somatic missense mutation in exon 6, codon 61, ACG (threonine) --> ATG (methionine) was found in a signet ring cell adenocarcinoma. We also evaluated allelic deletion in these tumors by PCR-based microsatellite analysis; allelic deletion occurred in 42.1% (16 of 38) of evaluable cases. This is the first report of a somatic missense mutation of the FHIT gene in a primary tumor. Presence of a point mutation and frequent allelic deletions are consistent with the hypothesis that FHIT gene alterations are involved in the development of primary gastric cancers.
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PMID:FHIT mutations in human primary gastric cancer. 910 41


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