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)

These studies were designed to look for a correlation of intrathymic survival of virus-infected thymocytes with lymphomagenesis. Cells from the normal-appearing prelymphoma thymus of SL3-3 virus-treated AKR mice were studied. Also, phenotypic properties of the malignant cells from the virus-induced lymphomas are described. In this model system, 100% of mice inoculated with virus at three days of age develop thymic lymphoma between 60 and 90 days of age. The experiments show that cells with malignant potential do not appear in the thymus until 36 days after virus inoculation. These cells are initially thymus-dependent (TD) in that they produce lymphoma of donor-type in recipients after intrathymic inoculation with long latency. They do not produce lymphoma after subcutaneous inoculation in syngeneic hosts. At 39 days after virus inoculation, the first thymus independent (TI) lymphoma cells appear. These cells, like the cells isolated from thymi with overt tumors, produce lymphoma of donor-type after a short latency when inoculated by the intrathymic or subcutaneous route. Thymocytes from normal-appearing thymi of mice at 42 days after virus inoculation, which could be expected to include TD, TI or no lymphoma cells, were evaluated for their ability to survive in a recipient thymus for three weeks after intrathymic inoculation. They were compared to thymocytes from age-matched control mice. Thymi receiving the virus-infected thymocytes showed 15% to 80% donor cells at three weeks. The highest numbers of donor cells were from thymi which were shown to contain TI lymphoma cells. However, cells from thymi with TD and no lymphoma cells could also be detected in significant numbers at three weeks after intrathymic inoculation. Less than 2% of donor-type thymocytes could be found after inoculation of thymocytes from normal control AKR mice. These data provide evidence that virus infection of thymocytes, even before the appearance of cells with lymphomagenic potential, endows them with a capacity for prolonged intrathymic survival. This appears to be a necessary step for tumor progression in this model. A remarkable phenotypic diversity of the virus-induced lymphomas was shown. The effect of various growth environments, intrathymic, subcutaneous, and in vitro on lymphoma cell phenotypic expression revealed individual differences in each tumor and in each environment.
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PMID:Observations on lymphomagenesis and lymphoma in AKR mice. A description of prelymphoma changes in the thymus and phenotypic diversity of lymphomas induced by SL3-3 virus. 138 66

A chronological study of the individual thymic lobes of young AKR mice after neonatal inoculation of the oncogenic AKR retrovirus SL 3-3 was performed. 100% of mice treated in this manner develop lymphoma between 60 and 100 days of age. A search for early lymphoma cells in individual thymi was carried out by inoculating the thymocytes subcutaneously in syngeneic and intrathymically in syngeneic and semisyngeneic recipients. Tumor progression was observed in animals between 48 and 60 days of age. These animals have: (a) normal weight lobes, in which no lymphoma cells could be detected, (b) thymus-dependent lymphoma cells, in one or both normal weight lobes; (c) thymus-independent lymphoma cells, found in lobes of normal weight as well as in thymi enlarged by lymphoma cells. Thymocyte characteristics of virus-treated animals of 21 to 63 days of age were compared with those of age-matched controls. Beginning at 28 days a concordant, progressive with time, increase of thymocyte surface staining for the viral envelope glycoprotein gp70 was seen in all lobes from virus-treated animals. Evaluation of cell surface markers by two-color fluorescence with antibodies to CD4 and CD8 showed that after 50 days of age, thymic lobes with and without lymphomas had nonspecific, but marked, alterations of the typical thymocyte surface marker pattern. No characteristic CD4, CD8 surface phenotype was found in primary lymphomas. Using probes for the T-cell receptor J beta 2 gene segments and the Akv ecotropic virus gp70 envelope genes, oligoclonality in J beta 2 rearrangements and clonality using the Akv env genes was demonstrated in thymi with the thymus-dependent phenotype. In lymphomas T-cell receptor beta gene probes showed either oligoclonality or clonality. Clonal virus integrations were found in these lymphomas. These experiments suggest the following series of events in virus-accelerated AKR lymphomagenesis. First, lymphoma cells arise which are initially thymus-dependent and can appear in one or simultaneously in both thymic lobes. These progress to become thymus-independent, fully autonomous, tumor cells. Thymocytes close to or at the time of the initial transformation event show a marked disorder of differentiation defined by the alterations in the CD4, CD8 surface phenotype distribution.
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PMID:Development of lymphoma in the thymus of AKR mice treated with the lymphomagenic virus SL 3-3. 254 38

T-cell lymphomas induced in rats by Moloney murine leukemia virus acquire increasing numbers of proviruses in their genome during tumor progression in vivo and passage of tumor cells in vitro. To determine whether the proviruses progressively acquired during tumor progression play a causal role in this process, we cloned one of them from a cell line derived from the primary tumor 2772. A probe from the cellular DNA flanking the provirus was used to analyze 79 DNA samples from primary tumor tissues of 28 tumor-bearing rats and 80 DNA samples from 30 independent tumor cell lines. This analysis revealed a rearrangement in this region in the primary tumor derived from the thymus of one animal but not in a clone of the same tumor segregating in the spleen. Of the cell line DNA samples, three carried a provirus in this region. Two of these integration events had occurred independently in two clonally related sublines derived from tumor 2772, and they were followed by rapid selection in culture. On the basis of these findings this locus was named Tpl-1 (tumor progression locus 1). The Tpl-1 locus was mapped to rat chromosome 8 and to mouse chromosome 9 at a genetic distance of 1.2 +/- 0.9 centimorgans from the Ets-1 protooncogene. Although the genetic distance between Tpl-1 and Ets-1 indicates that they are different genes, analysis of Tpl-1 cDNA clones revealed that the two are closely related.
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PMID:Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. 255 46

The CT examination of 36 patients with masses in the thymus (three thymus hyperplasias, 33 thymomas) were evaluated retrospectively. Three tumours in atypical positions posed problems in differential diagnosis from bronchial carcinomas and two cases with extensive pleural metastases had to be differentiated from pleural mesotheliomas. There were no certain morphological features on CT which indicated whether the mass was malignant. Eleven patients with thymomas had metastases; in seven of these they were extra-thoracic, with preference for supraclavicular lymph nodes, adrenals and the axial skeleton. Tumour progression and distant metastases were found particularly in malignant thymomas of the epithelial type. Calcification in a thymoma tends to indicate that it is malignant.
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PMID:[Computed tomographic findings in 36 patients with space-occupying lesions of the thymus]. 284 74

An examination of the variant generation and selection hypothesis of tumor progression was undertaken using the NK-sensitive, NAb-sensitive SL2-5 lymphoma in the threshold inoculum model of tumor progression. Tumor cells obtained from the i.p. injection site expressed increased heterogeneity for sensitivity to syngeneic NAb and to NR measured in the 131IUdR-labelled tumor elimination assay. Cells retrieved from the s.c. injection site exhibited reductions in sensitivity to NR which correlated with decreases in sensitivity to syngeneic NAb and NK cells in vitro. These data confirm and extend our previous observations with the NK-resistant L5178Y-F9 lymphoma and further substantiate the evidence for the participation of NAb and NK cells in host-mediated anti-tumor resistance. Characterization of the model revealed that the selection for reduced sensitivity to NR in thymus-depleted AT x BM mice and normal animals could not be distinguished, suggesting that thymus-independent mechanisms may be major contributors to the surveillance of nascent tumors. The decreases in susceptibility to NR occurred in a stepwise and time-dependent manner in accord with the sequential multistage concept of progression. Furthermore, the selection for tumor cells which exhibited reductions in sensitivity to NR correlated with selection for increased tumorigenicity, in keeping with the idea that progression is associated with development towards an increasingly autonomous tumor.
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PMID:Characterization of tumor progression from threshold tumor inocula: evidence for natural resistance. 397 73

Changes in the host T-lymphocyte subsets during the development of spontaneous mammary carcinomas in C3H/HeJ mice were analyzed on the basis of Lyt antigenic markers in retired breeder females prior to and following tumor appearance. Lymphocytes derived from various host lymphoid organs as well as from the tumor site were labeled either directly with 125I-conjugated monoclonal anti-Lyt antibodies or by a sandwich labeling technique with monoclonal anti-Lyt antibodies and 125I-conjugated anti-mouse Ig. The relative incidence of the various Lyt subsets was determined by radioautography. It was found that the overall incidence of T cells within the tumors increased during tumor progression. The incidence of the Lyt-1-, 2+ subset was very high (congruent to 20%) initially within the small, young tumors, and then this incidence declined progressively as the tumor increased in size to 0-5% in older and larger tumors, with a concomitant increase of the Lyt-1+, 2- subset. High levels of Lyt-1-, 2+ lymphocytes were also detected within the thymus (up to 41%) as well as the regional draining nodes (up to 7%) of animals bearing small newly detected tumors and could also occasionally be found in old clinically "tumor-free" control animals. These results support the earlier proposal based on functional studies with primary chemically induced tumors and in hosts bearing transplanted tumors that Lyt-1-, 2+ lymphocytes may play an immunoregulatory role in the early stages of tumor development possibly as facilitators of tumor growth.
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PMID:An analysis of host T-cell subsets based on Lyt antigenic markers during the development of spontaneous C3H mammary carcinomas. 660 12

Experimental studies on modulation of antitumor immunity by administration of levamisole (LMS) were performed using a metastasizing rat's mammary tumor (MRMT-1) which was routinely inoculated subcutaneously at one back side of the Slc-SD rat. Experiment 1: The optimal ip dose of LMS for getting antitumor effects was found to be 2.5 mg/kg/day, administered every other day for 7 times. Administration at doses between 0.5 mg/kg and 2.5 mg/kg tended to cause tumor suppression and the doses over 10 mg/kg tended to cause tumor progression. Experiment 2: Optimal timing of starting LMS administration was found to be on day 2 of tumor inoculation. Starting LMS on day 14 of inoculation caused a tendency of transient tumor progression. Experiment 3: A slight tumor suppression was observed when splenectomy was done on day 14 of inoculation. However, when LMS was, given simultaneously, the tumor suppressive effect of splenectomy was cancelled. Experiment 4: According to immunological parameters with whole lymphocyte of peripheral blood, spleen cells and thymus cells, the mechanism of modulation of antitumor immunity by LMS administration was suggested to be an increase in immunocompetency of peripheral lymphocytes and augmentation of specific cytotoxicity. Immunocompetency of NK cells was found to be reduced. LMS was found to have some effects also on spleen and thymus cell functions.
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PMID:[Experimental study on levamisole modulation of antitumor immunity--1]. 698 98

The major histocompatibility complex (MHC) class II genes encode surface molecules that are required for presentation of antigenic peptides to helper T-cells. The concentration of these proteins on the surface of effector cells (antigen-presenting cells such as B-cells and macrophage) is one of the parameters affecting the intensity of the immune response. Many studies have thus focused their attention on the mechanisms that control the expression of class II genes, particularly in B-cells. The anatomy of MHC class II promoters has been dissected in detail, and many trans-acting factors and their cognate DNA regulatory elements have been identified and characterized, thus helping to elucidate the molecular circuitry which determines tissue-specific, coordinate expression of these genes. In most cases, regulation has been investigated at the level of mRNA transcription. MHC class II gene expression has been observed as well, under physiological conditions, in many other tissues and organs such as brain, thyroid, thymus, and intestine, thus implying that class II molecules may be involved, whether directly or indirectly, in the modulation of other important biological responses in addition to the control of the immune reaction against soluble antigens. Spurious MHC class II activity is also detected in tumor cells and in other pathological conditions such as those found in autoimmune, inflammatory, and infectious diseases. In autoimmunity, cells that express class II molecules may present tissue-specific antigens, thus triggering a mechanism of self-destruction. In tumors, instead, unscheduled MHC class II expression may be part of a mechanism that prevents tumor progression. Comprehension of the regulatory functions operating in pathological conditions as compared to those active in B-cells and in macrophages is still rudimentary. Because of the possible pathogenetic importance of aberrant class II expression, knowledge of the cis- and trans-acting elements controlling gene expression at either the transcriptional or posttranscriptional level may allow the development of strategies for immunointervention against these diseases.
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PMID:Control of MHC class II gene expression in autoimmune, infectious, and neoplastic diseases. 811 Mar 78

A detailed analysis of the immune system response has been performed during the development and progression of dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. For this aim, a number of immune parameters (thymocyte and splenocyte proliferative response to T-dependent mitogens, antibody production, lymphocyte subset phenotyping, interleukin 2 receptor expression in resting and activated lymphocytes, thymus morphology and morphometry), were correlated with tumor appearance and growth at different (-7, 0, +15, +30, +60, +90, and +120 days) time intervals after intragastric administration of DMBA, in the absence or the presence of a concomitant treatment with the thymic pentapeptide thymopentin (TP5). A profound and time-dependent immunosuppression characterized the treatment with the carcinogen. Both cell-mediated and humoral immune responses showed a 50% inhibition 2 weeks after DMBA administration, with a peak after 30 days, followed by a plateau until 120 days of observation. The mechanism responsible for reduced ability of thymocytes and splenocytes to respond to both Con-A and PHA was explained by the significant inhibition of one of the key steps of T cell activation, namely the expression of IL-2 receptor in lymphocytes from DMBA-treated animals. The flow cytometric analysis of lymphocyte subpopulations revealed an important reduction in the overall populations of thymocytes and splenocytes. At the thymus gland level, a dramatic reduction of double positive CD4+CD8+ and a decrease of CD4+CD8- and CD4-CD8+ were observed, together with a marked atrophy of the thymic cortex, and impairment of the thymic microenvironment. One hundred and twenty days after DMBA administration, approximately 60 to 70% of the animals developed tumors with a mean tumor surface area of 2.88 +/- 0.86 cm2, and a number of 2.44 +/- 1.0. Treatment with TP5 (100 ng/animal, three times a week, starting a week before DMBA), produced specific effects on different immune compartments and tumoral growth, characterized by a significant reversal of immune depression with a stimulatory effect measured on lymphoproliferative assays, lymphocyte subset distribution, and IL-2 receptor expression. Moreover, thymic atrophy was almost completely prevented in TP5 treated animals. Of major interest, a significant delay in the appearance and growth of tumors was observed in TP5 treated rats. When DMBA-treated animals were followed for the entire observation period (0-120 days) and the immune responsiveness correlated according to tumor progression, stability, or regression, a positive correlation was calculated between the degree of immune system depression and the individual rate of tumor growth; in TP5-treated rats the majority of the tumors were static or regressing tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The immune system response during development and progression of carcinogen-induced rat mammary tumors: prevention of tumor growth and restoration of immune system responsiveness by thymopentin. 831 80

Pituitary PRL is involved in immunoregulation. Also, a PRL-like molecule is secreted by peripheral blood mononuclear cells. In this study, we examined tissues of the human immune system to evaluate if the PRL gene is expressed and to determine the location and type of cells involved in its synthesis. To evaluate the expression of PRL messenger RNA (mRNA) in normal and abnormal human lymphoid tissues, we used RT-PCR to generate a specific 276-bp product from normal human thymus, spleen, tonsil, lymph node, and lymphoid tumors. Restriction enzyme digestion confirmed that this PCR product was expressed PRL. Furthermore, we developed a specific and sensitive nonisotopic in situ hybridization technique for PRL mRNA, and cells containing PRL mRNA were found in each tissue of the human immune system. Also, PRL mRNA was widely distributed throughout neoplastic tissue from a thymoma and lymphomas where mitogenic and anti-apoptotic properties of PRL could be involved in tumor progression. PRL mRNA was localized in lymphocytes, epithelial cells, and vascular endothelial cells. The presence of PRL mRNA in vascular endothelium cells suggests other roles for PRL in these tissues in addition to immunomodulation. In conclusion, the presence of PRL mRNA in human lymphoid tissue implies that locally synthesized PRL may play a critical role in immunocompetence by providing an important regulatory signal to the microenvironment of human lymphoid organs.
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PMID:Expression and localization of prolactin messenger ribonucleic acid in the human immune system. 853 34


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