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 role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors.
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PMID:Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation. 283 Mar 39

It was shown previously that combination therapy of tumor-bearing mice resulted in amplification of antitumor responses at the site of tumor rejection and involved some of the classical components of the immunological network. As a continuation of this work, we now show that amplification of immune responses involves an increase in class II-MHC antigen (Ia) expression both at the tumor site and peripherally in the peritoneal cavity. Of further interest, however, was the observation that there was also an increase in Ia expression by tumor-associated macrophages (TAM) and peritoneal macrophages (PMs) in mice bearing progressing tumors. In these experiments, Ia expression by TAM and PMs was assessed in C57BL/6J mice bearing the progressing syngeneic MCA/76-9 sarcoma as well as in mice that had received combination therapy consisting of an intraperitoneal injection of cyclophosphamide (CY) and an intravenous injection of tumor-sensitized T lymphocytes (immune cells). When progressing tumors were analyzed, it was seen that by the fourth day after tumor cell implantation, 45-60% TAM expressed Ia, a level that was sustained throughout the course of tumor growth. The treatment of tumor-bearers with CY had no effect on Ia expression by TAM. However, the number of Ia-expressing TAM increased significantly after combination therapy and, as the tumors regressed, reached a peak of up to 100% in the second week after therapy. TAM were shown by Northern blot hybridization to contain mRNA encoding for the Ia beta chain. When Ia expression by PMs was assessed, it was seen that during tumor progression there was an increased expression of Ia over background (from less than 10 to about 40%), beginning 9-12 days after tumor cell implantation and continuing for the duration of the experiments. This was not influenced by CY injection. Combination therapy significantly increased the number of PMs expressing Ia (up to 80%). Ia expression by PMs could be induced rapidly in vivo by injecting normal B6 mice intraperitoneally (ip) with T cells isolated from tumors induced to regress by combination therapy. PMs isolated up to 15 days after injection were shown to express Ia. Moreover, the ip injection of a mixture of specific MCA/76-9 tumor cells and these tumor-associated lymphocytes resulted in a more rapid rate and a higher level of Ia expression by PMs compared with the level induced by either treatment alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Expression of class II-MHC antigens by tumor-associated and peritoneal macrophages: systemic induction during tumor growth and tumor rejection. 346 72

Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) during malignant tumor progression were performed by using Kirsten murine sarcoma virus-transformed BALB/c 3T3 cells that harbor a replication-defective provirus. After injection into athymic nude mice by four different routes, primary tumors and secondary lung metastases were isolated, adapted to in vitro growth, and analyzed for DNA levels and mRNA expression of both genes for comparison with the originally injected transformed cells and untransformed 3T3 cells. For all tumors (primary or secondary), the v-Ki-ras gene was amplified and v-Ki-ras mRNA expression was highly elevated above that observed in the original transformed cell population. In two of five lung metastases from the i.v. and footpad injection routes, rearranged Ki-ras DNA sequences were observed. Micrometastases from the s.c. route of injection did not display these alterations. Injection of footpad lung tumor cells with rearrangements into a second group of animals led to multiple lung metastases with even further rearrangements correlating with more effective lung colonization/growth ability (overt lung tumors in five of eight animals less than 20 days after injection). However, reinjection of an i.v. lung tumor with rearranged Ki-ras led to no further rearrangements in the lung microfoci tumors isolated greater than 40 days after injection. These data suggest (i) the significance of amplification and elevated expression of v-Ki-ras in tumor formation, (ii) correlation of this amplification with more effective tumor progression, and (iii) the selective advantage that cells with Ki-ras DNA sequence additions have in the formation of overt lung tumors.
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PMID:Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression. 347 46

Plasma levels of growth hormone (GH) and the effect of GH treatment have been evaluated in adult nongrowing sarcoma-bearing mice (C57BL/6J). Prepubertal tumor-bearing mice, tumor-bearing hypophysectomized Sprague-Dawley rats, and malnourished non-tumor-bearing animals served as additional groups of study and control animals. Adult sarcoma-bearing mice showed an increase in plasma levels of GH early following tumor implantation. GH levels increased further with tumor progression. The anorexia and the state of malnutrition in sarcoma-bearing mice were the major factors behind increased GH levels. Muscle wasting and body composition in the tumor-bearing host were not improved by GH treatment at doses that increased growth rate in normal growing mice with intact pituitaries or partially normalized growth rate in hypophysectomized rats. Exogenous GH supported tumor growth and host body growth to the same extent in hypophysectomized rats. Exogenous GH in excess of endogenous GH did not stimulate tumor growth further. It is suggested that increased GH production in a tumor-bearing host acts in concert with other hormones to stimulate endogenous substrate mobilization and in tumor-bearing animals to prevent substrate deficiency and hypoglycemia. On the basis of this conclusion, it is unlikely that GH supplementation to a freely eating tumor-bearing host will support replenishment of host tissues.
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PMID:Growth hormone and experimental cancer cachexia. 348 Mar 85

Six soft-tissue sarcomas with two separate and juxtaposed histologic patterns were selected for immunohistochemical analysis. The first pattern was represented by five phenotypes (schwannian-skeletal muscle [Triton], cartilagenous, synovial, adipocytic, and smooth muscle). In each case the second histologic pattern resembled the fibrohistiocytic phenotype, ie, malignant fibrous histiocytoma (MFH). No other histologic patterns were identified. Appropriate cell markers were demonstrated in each of the first patterns; these were not detected in the second patterns. In contrast, the second pattern in all cases expressed alpha 1-antichymotrypsin, a marker commonly found in fibrohistiocytic lesions; this was not identified in any of the first patterns. This loss of one cell-specific marker and gain of another is termed the "antigenic shift" phenomenon and appeared to foretell the emergence of a true second phenotype (the same in each of these cases, which could be termed "dedifferentiated" sarcomas). Therefore, it is hypothesized that MFH is a final common pathway for some types of sarcomas and is the result of tumor progression or "dedifferentiation." The practical implications of this hypothesis concern the approach to sarcoma differential diagnosis and the meaning of an MFH pattern in both metastatic and primary sites. On a theoretic level, this hypothesis and the antigenic shift phenomenon force a reconsideration of the pathways of soft-tissue differentiation. A new model of mesenchymal differentiation incorporating these concepts is described and supported. It provides an explanation for a number of facts in soft-tissue pathology, and its predictions can be tested.
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PMID:The significance of double phenotypic patterns and markers in human sarcomas. A new model of mesenchymal differentiation. 349 Jul 90

Previous work identified certain components of the immunological network that had been activated following the adoptive immunotherapy of tumor-bearing mice. The present report shows that part of the activation process involves the IL-1 pathway. Tumor-associated macrophages (TAM) from C57BL/6J mice bearing the immunogenic sarcoma, MCA/76-9, and tumor-bearers injected with cyclophosphamide (CY) or CY plus the intravenous transfer of tumor-sensitized lymphocytes showed relatively high levels of intracellular (IC) IL-1, as demonstrated in the mitogenic and comitogenic assays. Gel chromatography of IC IL-1 and extracellular (EC) IL-1 from TAM induced to secrete IL-1 by stimulation with lipopolysaccharide indicated a single peak of activity of similar molecular size. The active fractions of the EC IL-1 were found to increase in activity as they were diluted to a maximum of 1/64, beyond which IL-1 activity declined. Fractions of the IC IL-1 showed no increased activity on dilution. Filtrates (less than 10 kDa) obtained on concentration of the IC and EC IL-1 samples prior to fractionation were shown to contain an activity (3-5 kDa) that inhibited the uptake of [3H]TdR by thymocytes in the mitogenic and comitogenic assays. Membrane-bound IL-1 activity also was expressed by TAM and this coincided with the previously reported peak Ia expression by these cells. TAM were also shown to induce strong proliferative responses by allogeneic lymphocyte. Systemic amplification of antitumor responses was detected in mice bearing progressing tumors and in those that had received combination therapy as measured both by increases in free IL-1 in the peritoneal cavity and IL-1 within the peritoneal macrophages. These observations indicate that in addition to enhancement of Ia expression, the IL-1 pathway also is activated and amplified systemically in this model system of tumor progression and rejection.
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PMID:Activation of the IL-1 pathway during amplification of immune responses in tumor-bearing mice. 349 84

Twelve cases of epithelioid sarcoma have been reviewed, illustrating the diagnostic problems for which this rare tumor has become notorious and demonstrating varied rates of tumor progression. The histological features most helpful to the distinction of epithelioid sarcoma from other nodular skin lesions, including benign conditions such as rheumatoid nodule and granuloma annulare, are discussed. The ultrastructural appearances of two cases were similar to immature mesenchymal tissue.
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PMID:Epithelioid sarcoma. A diagnostic problem. 371 28

We have isolated clonal cell lines from a transplanted adenocarcinoma induced by the RIII strain of mouse mammary tumor virus in a BALB/c mouse. Three major morphological cell types of these lines are developmentally linked; polygonal cells give rise to cuboidal and then to elongated cells. All cell lines expressed markers that are characteristic of mammary basal cells. In addition, the polygonal lines contained cells that have cell markers and ultrastructural features of epithelial cells; in these lines an occasional cell was found with myoepithelial features. The cuboidal and elongated lines lacked many epithelial differentiation characteristics and showed no myoepithelial differentiation. The cell lines contained variable numbers of acquired mouse mammary tumor virus and ecotropic murine leukemia virus proviruses. The various subclones derived from the original cell lines contained, in addition to the acquired proviruses of the parental line, one or more unique proviruses of either mouse mammary tumor virus or ecotropic murine leukemia virus origin. These unique insertions were used as genotypic markers to demonstrate the clonal relationship of the cell lines. Both polygonal and elongated cells are tumorigenic and give rise to adenocarcinomas and sarcoma-like tumors, respectively. In contrast, the cuboidal cells are poorly tumorigenic. Since cuboidal cells are derived from the polygonal cells, this suggests that tumor progression in this system proceeds via intermediates that are either poorly or nontumorigenic.
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PMID:In vitro differentiation and progression of mouse mammary tumor cells. 375 29

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

Inbred Balb/c mice bearing 2- or 4-week-old transplantable syngeneic sarcoma L-1, when injected intravenously with the cells of the same tumor, displayed a low or high number of tumor nodules in the lungs, two weeks after the injection. In order to test whether this phenomenon is dependent on changes in host immunity associated with tumor progression, the immunocompetence of spleen cells from tumor-bearing mice was measured in a lymphocyte-induced angiogenesis assay, performed on (C57Bl/Sn X Balb/c)F1 recipients. Splenocytes from mice bearing tumors of different age, whether treated or not with cyclophosphamide, showed, however, the same angiogeneic potency.
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PMID:Immunocompetence of splenocytes from mice bearing different-aged tumors assessed in lymphocyte-induced angiogenesis assay. 616 15


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