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 effects of specific immunotherapy with allogeneic cells transformed by Schmidt-Ruppin Rous sarcoma virus (SR-RSV), of treatment with BCG, and of surgery on the growth of SR-RSV-induced sarcomas in white-lipped marmosets were studied. Tumor incidence, tumor progression, and survival did not differ between control and treated animals. Animals immunized with BCG developed lymphocyte reactivity to tuberculin, which remained until the animals died. BCG was isolated from the spleen of one tumor-bearing animal.
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PMID:Immunization of Rous sarcoma virus-inoculated marmosets with BCG and transformed allogeneic cells. 16 12

Avian-leukosis-free females from Regional Poultry Research Laboratory (RPRL) inbred lines 6(1) and 7(2) were inseminated with pooled semen from RPRL line 15I5 males. The progeny resulting from the two crosses 15I5 X 6(1) and 15I5 X 7(2) were of the B2/B15 major histocompatibility complex (MHC) genotype, the B2 haplotypes from lines 6(1) and 7(2) being indistinguishable. When challenged with Rous sarcoma virus (RSV) at 6 weeks of age, 30 out of 31 progeny of cross 15I5 X 6(1) developed tumors that rapidly regressed, whereas 26 of 29 progeny of cross 15I5 X 7(2) died with progressive tumor growth. On the other hand, 15 of 18 B2/B15 segregants from the three-way cross (15I5 X 6(3]F1 X 7(2), identical in source to the MHC of the (15I5 X 7(2]F1 progressors, were characterized by tumor regression. Thus influences associated with non-MHC background genes from lines 6(1), 6(3), and 7(2) appeared to be critical to host response to RSV-induced sarcomas. Similar findings suggesting a strong non-MHC influence on anti-sarcoma response were obtained using 107 F2 and 77 backcross progeny of RPRL line 100 and noninbred University of New Hampshire (UNH) line 105. The B2 haplotype of line 100 was associated with tumor regression when combined with the line 105 background and with tumor progression when expressed on the line 100 background. Suppression of the anti-tumor response associated with line 100 appeared to be fairly generalized, since a poor response to tumor was observed regardless of which of three subgroups of RSV was used to induce tumor.
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PMID:A non-MHC genetic influence on response to Rous sarcoma virus-induced tumors in chickens. 609 53

Macrophage functional competence was studied in two congenic chicken lines 6.6-2 (B2B2) and 6.15-5 (B5B5) which are regressors and progressors, respectively, of Rous sarcoma-induced tumors. Sephadex-elicited abdominal exudate cells (AEC) were harvested from 4-week-old chickens to determine their total number, glass adherence potential, percentage of adherent macrophages and phagocytosis of antibody coated (ops) and uncoated (unops) sheep red blood cells (SRBC). Tumoricidal abilities of culture medium conditioned with lipopolysaccharide treated macrophages and of macrophages cocultured with target cells were assessed against 51Cr-labelled tumor cell targets. The congenic lines did not differ in total AEC or percent macrophages. However, AEC from B5B5 birds exhibited significantly lower (P < 0.05) glass-adherence potential than AEC from B2B2 birds exhibited significantly lower (P < 0.05) glass-adherence potential than AEC from B2B2 birds. The percentage of phagocytic macrophages did not differ between lines for unop-SRBC, whereas a higher percentage of B5B5 compared with B2B2 birds (P < 0.05) macrophages phagocytized ops-SRBC. Macrophages from B5B5 birds had significantly (P < 0.05) lower activity in both tumoricidal tests. These results imply that the tumor progression in B5B5 birds is associated with reduced activation of macrophages towards a tumoricidal pathway.
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PMID:Analysis of macrophage functions in Rous sarcoma-induced tumor regressor and progressor 6.B congenic chickens. 823 4

To study the possible role of the host macrophages in the selection of tumor cells and tumor progression, a series of Syrian hamster tumor cell lines all originating from a single spontaneously transformed Syrian hamster embryo cell line (STHE strain) have been established. These STHE tumor cell variants, selected either in vitro with resident and lipopolysaccharide-activated macrophages or in vivo, differ in tumorigenic and metastatic activity. The selected malignant STHE cells become resistant to cytotoxic activity of activated peritoneal macrophages and of exogenous hydrogen peroxide (H2O2). Since activated macrophages are a known source for both cytotoxic agents H2O2 and tumor necrosis factor (TNF), the purpose of the present study was to define the sensitivity of the STHE tumor cell lines to a direct cytotoxic activity mediated by recombinant TNF-alpha in an attempt to understand the role of the cytokine in in vitro selection of a malignant STHE cells by activated macrophages. The spontaneously transformed STHE cells (selected in vivo and in vitro) as well as the hamster embryo cells transformed in vitro by a tumorigenic Rous sarcoma virus (Schmidt-Ruppin strain) were used as targets. TNF-alpha-sensitive mouse L929 cells were included in the study as a positive control. Sensitivity of actinomycin D-pretreated target cells studied for cytotoxic activity of a recombinant TNF-alpha was examined over 21 h with a crystal violet dye assay. It was found that, in contrast to L929 cells, the spontaneously transformed STHE cells as well as tumorigenic Rous sarcoma virus hamster embryo transformants, were all significantly resistant to the TNF-alpha-mediated cytolysis. This indicates that TNF-alpha is not the single factor responsible in in vitro selection of malignant STHE cell variants by activated macrophages. It appears that H2O2 is involved in the selection of the hamster macrophage-resistant STHE tumor cells.
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PMID:Resistance of spontaneously transformed Syrian hamster embryo cells and their malignant variants to cytotoxic activity of recombinant tumor necrosis factor-alpha. 954 39

Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.
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PMID:Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. 1093 31

Hamster tumor cell lines obtained with the Rous sarcoma virus and characterized by a high metastatic activity in vitro were transfected with the gene for C2+/calmodulin-dependent serine-threonine death-associated protein kinase (DAPk). Expression of DAPk in tumor cells dramatically reduced their survival in the blood of syngenic animals and their ability to produce metastases, but did not affect their tumorigenicity or the primary tumor growth. The DAPk-induced change in the metastatic phenotype was not accompanied by substantial changes in production and phosphorylation of v-Src or focal adhesion proteins (focal adhesion kinase and paxilline). The resulting system of transfected cells with a modulated metastatic potential provide a convenient model to study the molecular mechanisms of tumor progression at various steps.
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PMID:[Suppression of the metastatic potential of oncogene v-src-transformed cells as a result of activity of the exogenous DAP kinase]. 1206 33

To identify phosphotyrosine-containing proteins essential for maintaining the transformed state, we studied the tyrosine phosphorylation profile of temperature-sensitive mutant of Rous sarcoma virus, tsNY68, infected cells (68N7). Shifting the temperature from 39 degrees C (nonpermissive) to 32 degrees C (permissive) markedly increased the expression of phosphotyrosine-containing cell membrane proteins of approximately 40kDa, as assessed by SDS-PAGE. Membrane and nuclear proteins were separated by two-dimensional gel electrophoresis and immunoblotted with anti-phosphotyrosine antibody. Proteins showing temperature-dependent changes in phosphorylation profile were subjected to in-gel digestion with trypsin and analyzed by mass spectrometry. Five proteins were identified: heterogeneous nuclear ribonucleoprotein (hnRNP) A3, hnRNP A2, annexin II, phosphoglycerate mutase 1, and triosephosphate isomerase 1. hnRNP A3 was phosphorylated at serine residues and had both serine and tyrosine phosphorylated sites. These results suggest an important complementary role for proteomics in identifying molecular abnormalities associated with tumor progression that may be attractive candidates for tumor diagnosis.
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PMID:Identification of phosphoproteins associated with maintenance of transformed state in temperature-sensitive Rous sarcoma-virus infected cells by proteomic analysis. 1671 53

v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active variant of c-Src. Activation of Src is observed frequently in colorectal and breast cancers, and is critical in tumor progression through multiple processes. However, in some experimental conditions, v-Src causes growth suppression and apoptosis. In this review, we highlight recent progress in our understanding of cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src-expressing cells. v-Src induces cell cycle changes-such as the accumulation of the 4N cell population-and increases the number of binucleated cells, which is accompanied by an excess number of centrosomes. Time-lapse analysis of v-Src-expressing cells showed that cytokinesis failure is caused by cleavage furrow regression. Microscopic analysis revealed that v-Src induces delocalization of cytokinesis regulators including Aurora B and Mklp1. Tetraploid cell formation is one of the causes of chromosome instability; however, tetraploid cells can be eliminated at the tetraploidy checkpoint. Interestingly, v-Src weakens the tetraploidy checkpoint by inhibiting the nuclear exclusion of the transcription coactivator YAP, which is downstream of the Hippo pathway and its nuclear exclusion is critical in the tetraploidy checkpoint. We also discuss the relationship between v-Src-induced chromosome instability and growth suppression in v-Src-induced oncogenesis.
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PMID:Cytokinesis Failure Leading to Chromosome Instability in v-Src-Induced Oncogenesis. 2841 8