Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The formation and propagation of several subpopulations of human melanoma cells from a heterogeneous parental population was accomplished with the use of the Membrane Invasion Culture System (MICS) in vitro under sterile conditions. Five sequentially selected subpopulations of melanoma cells showed an increasing ability to do the following: a) invade reconstituted basement membranes in vitro; b) form experimental lung metastases in vivo; and c) express steady-state levels of human type IV collagenase, a marker for metastatic potential. In addition, the morphology and expression of 35S-methionine-labeled cell surface proteins changed with sequential selection. The adaptation of the MICS assay for studying tumor cell subpopulations allows the morphological, biochemical and molecular characterization of events associated with tumor progression in an in vitro model.
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PMID:Selection of invasive and metastatic subpopulations from a heterogeneous human melanoma cell line. 222 75

Laminin biosynthesis was compared in four pairs of human squamous cell carcinoma cultures derived from primary and recurrent or metastatic tumors in four patients with cancer of the larynx and hypopharynx to determine if changes in laminin production accompany tumor progression. Laminin profiles of the malignant cells were compared with laminin biosynthesized by nonmalignant human keratinocytes. Pulse-chase biosynthetic labeling of the cultures with [35S]methionine established that all of the squamous carcinoma cell lines synthesize immunoreactive A (Mr 400,000), B1 (Mr 205,000), and B2 (Mr 200,000) laminin subunits; assemble them to form the intact laminin molecule (Mr 950,000); and secrete a portion of the laminin they produce into the culture media. One aspect of laminin expression unique to keratinocytes, both malignant and nonmalignant, was the occurrence of three additional glycoprotein forms (Mr 195,000, 170,000, and 160,000) in the laminin immunoprecipitates. In contrast to the laminin subunits, these glycoproteins were not immunoreactive with the anti-laminin antiserum on Western blots. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis without and with reduction of disulfide bonds revealed that the laminin immunoprecipitates contained a family of oligomeric molecules. These ranged in apparent molecular weight from 370,000 to 950,000 and were composed of laminin subunits and the glycoprotein forms linked by interchain disulfide bonds. The malignant keratinocyte cell lines from different patients were distinguishable in terms of the array of laminin and glycoprotein forms displayed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the rate of [35S]methionine incorporation into laminin during the pulse-labeling, the fraction of [35S]methionine-labeled laminin secreted into the medium during the chase incubation, and the absolute amount of laminin secreted into the culture medium as determined by enzyme-linked immunosorbent assay. However, cell lines established from primary and metastatic or recurrent cancer in the same patient were indistinguishable in their profile of laminin biosynthesis and secretion. In comparison to primary cultures of nonmalignant foreskin basal keratinocytes, the malignant cells secreted into the culture medium a larger fraction of the laminin that they produce. This is an indication that the malignant keratinocytes in culture deposited a less stable basal lamina-like extracellular matrix than their malignant counterparts. The diminished integrity of the basal lamina matrix may be an important factor in the invasive growth of human epithelial cancer.
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PMID:Biosynthesis and secretion of laminin and laminin-associated glycoproteins by nonmalignant and malignant human keratinocytes: comparison of cell lines from primary and secondary tumors in the same patient. 245 36

We have studied changes in the (11C-methyl)-L-methionine (C-11 Met) uptake index in six glioma cases subsequent to radiotherapy, using positron emission tomography (PET) to evaluate the effects of radiotherapy on the amino acid metabolism of the tumor. The uptake index of the tumor represented as a percentage of the total count in the atrial blood recorded during a period of 45 min, showed an average of 0.037% and 0.039% prior to and within two months after the therapy, respectively. Out of three cases where a fall in the index was seen, two cases showed tumor regression in the size of the contrast enhanced lesion measured by CT; all three cases had a relatively long period of clinical and neurological amelioration. However, following a short period of clinical improvement, the other three patients with a rise in the index showed no change or tumor progression on CT. These findings indicate that changes in the C-11 Met uptake index can be a sensitive and precise indicator for evaluating the effect of radiotherapy on gliomas.
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PMID:[Changes in the (11C-methyl)-L-methionine uptake index in gliomas following radiotherapy]. 278 98

During Lewis lung carcinoma (3LL) growth, red blood cell (RBC) spermidine (Spd) level evolution was proportional to the increase in tumor volume and inversely correlated with the decrease in tumor Spd concentration. Similarly, in cancer mice i.p. injected with [14C] Spd, the increasing amount of erythrocyte [14C] Spd was in proportion with tumor volume enhancement and linked to decrease in tumor tissue [14C] Spd concentration. After i.p. injection of [14C] Spd putrescine or [14C] spermine, contrary to normal mice, cancer mice provided [14C] Spd in their erythrocytes. When injected with [14C] methionine, [14C] polyamines were never found in normal or cancer mice erythrocytes. As previously noted in vitro, increasing amounts of polyamines produced by tumor tissue and excreted into blood would modify erythrocyte stroma proteins involved in the RBC [14C] Spd uptake process. These data obtained in vivo demonstrate the tumor origin of polyamines carried by erythrocytes. Since RBC polyamine levels are directly correlated with tumor progression, these experimental results reinforce the clinical use of this index of cell proliferation in malignant diseases with a short doubling time.
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PMID:Spermidine uptake by erythrocytes from normal and Lewis lung carcinoma (3LL) grafted mice: II. In vivo study. 281 87

Methionine has been successfully used to control tumor progression in vivo and to induce reversions of transformed cells in vitro. In the present study, we measured mutations at the HGPRT locus of RSV-transformed cells serially propagated in methionine-supplemented medium and assayed at each passage for thioguanine resistance. The frequency of spontaneous mutants at this locus was 7.2 X 10(-5); this value gradually increased during the methionine treatment to as much as 9.2 X 10(-4), and returned to initial values when the methionine treatment was withdrawn. It is proposed that the mutants were induced by the methionine derivative, S-adenosylmethionine, and the resulting mutant frequency determined by equilibrium between mutagenic action of this metabolite and DNA repair.
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PMID:Mutagenicity of methionine or its metabolic products in RSV-transformed Chinese hamster fibroblasts. 283 94

Analysis of a number of B16 melanoma clones has revealed a high correlation between metastatic activity and the quantitative expression of a 72,000 dalton glycoprotein, Met 72. In the present study, metastatic tumor cell variants have been directly isolated from a heterogeneous, poorly metastatic melanoma (B16-F1) by anti-Met 72 monclonal antibodies and cell sorting procedures. These studies provide direct proof that Met-72 antigens are in fact surface markers of B16 melanoma metastatic variants and may provide the means of monitoring their presence, influence and autonomy during tumor progression.
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PMID:Isolation of metastatic B16 melanoma variants using anti-Met 72 monoclonal antibodies and flow cytometry. 382 95

We investigated the expression of alpha v-integrins in different stages of human cutaneous melanocytic tumor progression. We observed that alpha v beta 5 was the alpha v-integrin expressed in all common nevocellular nevi, in 78% of dysplastic nevi, in 63% of early primary melanomas, in 43% of advanced primary melanomas, and in 33% of melanoma metastases. Hence, loss of alpha v beta 5 expression was related to melanocytic tumor progression. In line with earlier reports, alpha v beta 3 was exclusively detected in advanced primary melanomas and metastases (24% and 50% respectively). Staining with anti-alpha v monoclonal antibodies (MAbs) in lesions where both alpha v beta 3 and alpha v beta 5 were absent showed that alternative alpha v-integrins were expressed in advanced primary melanomas and metastases. By FACS analysis, we determined expression of alpha v beta 5 and alpha v beta 3 in 4 human melanoma cell lines with different metastatic capacities after s.c. inoculation into nude mice. One of the non-metastatic and both highly metastatic cell lines expressed alpha v beta 5 at their surface. Surprisingly, alpha v beta 3 was detected exclusively in the non-metastatic cell lines. Absence of alpha v beta 3 in the highly metastatic cell lines was confirmed by lack of immunoprecipitation from 35S-methionine-labeled cells and by absence of immunohistochemical staining on primary and metastatic xenograft lesions. Our findings indicate that alpha v beta 5 expression is often lost in advanced stages of melanocytic tumor progression in situ, while alpha v beta 3 is acquired, but that a decrease in alpha v beta 5 and an increase in alpha v beta 3 expression are not necessarily related to the metastatic behavior of human melanoma cells in nude mice.
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PMID:Alpha v-integrins in human melanoma: gain of alpha v beta 3 and loss of alpha v beta 5 are related to tumor progression in situ but not to metastatic capacity of cell lines in nude mice. 753 77

Although human breast tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumor suppressor genes, the identity of the genetic alterations that are critical in the early stages of the breast tumorigenic process remains obscure. A high frequency (27-41%) of loss of heterozygosity (LOH) occurrence has been shown at the MET locus on chromosome band 7q31 and this specific alteration is associated with poorer survival. Here, we report that restriction fragment length polymorphism (RFLP) analysis on 221 informative (heterozygous) primary breast tumors and 57 informative relapses (13 local recurrences and 44 distant metastases) revealed a similar frequency of 7q31 LOH as tumors progress from primary cancer to relapse, in marked contrast to other changes such as 11p15.5 LOH. This finding suggests that inactivation of a putative tumor suppressor gene located in 7q31 is a very early event in breast tumorigenesis. Our results also show that metastatic potential is an induced phenomenon that occurs at a relatively early stage, rather than a marker of tumor progression.
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PMID:Loss of heterozygosity on 7q31 occurs early during breast tumorigenesis. 753 86

Dietary folate/methyl deficiency provides a unique model of endogenous hepatocarcinogenesis in which to study progressive alterations in DNA methylation patterns during tumor progression in vivo. Weanling male F344 rats were given a semi-purified diet deficient in the methyl donors choline, methionine and folic acid for a period of 9 weeks. Using a genomic sequencing procedure based on the PCR amplification of bisulfite-modified DNA, the methylation status of individual CpG sites within exons 6 and 7 of the p53 gene in liver samples from control and deficient rats was determined. Treatment of denatured nuclear DNA with sodium bisulfite quantitatively converts all cytosine residues to uracil which are then amplified as thymine in the PCR reaction. In contrast, 5-methylcytosine is resistant to bisulfite deamination under the reaction conditions and is amplified as cytosine. Automated sequencing of bisulfite-modified DNA will then elucidate the methylation status of each cytosine residue within a defined gene sequence. In addition to evaluation of the methylation status of the p53 gene, the relative activity of the DNA methyltransferase was also quantified in nuclear extracts from control and folate/methyl deficient rats. The results indicate that specific 5-methyl cytosines within the hepatic p53 gene from methyl deficient rats are resistant to demethylation despite the diet-induced decrease in S-adenosylmethionine and the increase in cell proliferation associated with this dietary intervention. Progressive demethylation was observed at other methylated cytosine residues in folate/methyl deficient rats after 9 weeks despite a paradoxical increase in DNA methyltransferase activity. The application of this sequence-specific technology will allow the definition of the methylation status of every CpG site within a coding sequence or promoter region and should provide new insights into mechanisms and consequences of methylation dysregulation during progressive multistage carcinogenesis.
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PMID:Differential sensitivity to loss of cytosine methyl groups within the hepatic p53 gene of folate/methyl deficient rats. 758 11

Hepatocyte growth factor (scatter factor) and its receptor, the c-met proto-oncogene product (c-MET), have been implicated in embryogenesis, tissue reorganization, and tumor progression. Little is known, however, of the expression and functional significance of these molecules in prostatic cells and tissue. In this investigation, we assessed the expression of hepatocyte growth factor (HGF) and c-MET in prostatic tissues and cell lines and also determined the effect of purified recombinant HGF on cell proliferation and scattering of prostatic carcinoma cell lines. HGF was expressed by human prostatic stromal myofibroblasts in primary culture but not by three human prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3) as assessed by Northern blot analysis. HGF was also detected by reverse transcriptase-polymerase chain reaction in both benign and malignant tissues from radical prostatectomy specimens. c-MET transcripts were identified by Northern blot in two androgen-insensitive human prostatic carcinoma cell lines (DU 145 and PC-3) but not the androgen-sensitive LNCaP cell line. Additional evidence of linkage of androgen responsiveness and c-MET was provided by experiments in which androgen deprivation of normal rat prostates via castration produced a marked up-regulation of c-MET expression as determined by Northern blot and immunohistochemistry. c-MET protein was detected by immunohistochemical analysis in a substantial percentage (58 of 128 or 45%) of prostatic carcinomas and was found more often in metastatic growths of human prostatic carcinoma (15 of 20 patients) compared with primary tumors (43 of 108 patients; P < 0.005). Moreover, in Dunning R-3327 rat prostatic carcinoma cell lines, c-MET expression was highest in the androgen-insensitive subline with the highest metastatic capacity. Purified recombinant human HGF induced dose-dependent cellular proliferation and scattering in the DU 145 carcinoma cell line. These data indicate that HGF may function in the prostate gland as a paracrine growth factor, with synthesis by stromal cells and with biological target cells being the epithelial cells. Expression of the HGF receptor, c-MET, is up-regulated by androgen deprivation and c-MET appears to be preferentially expressed on androgen-insensitive, metastatic cells, suggesting a possible linkage of c-MET expression with prostatic carcinoma progression.
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PMID:Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. 763 32


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