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)

Recently we reported that human dermal fibroblasts, or conditioned media obtained from such cells, affect the growth of human melanoma cells as a direct function of tumor progression: melanoma cells obtained from early-stage (metastatically incompetent) primary lesions were growth inhibited, whereas cells obtained from more advanced (metastatically competent) primary lesions, or metastases, were growth stimulated. Ion-exchange and gel-filtration chromatography of fibroblast conditioned medium revealed the inhibitor to be a protein of molecular mass between 20 and 30 kDa and distinct from the stimulator. This is the approximate molecular mass of interleukin 6 (IL-6), a ubiquitous multifunctional cytokine known to affect in particular many kinds of hemopoietic and lymphoid cells. Since this cytokine is known to be made by fibroblasts, we attempted to determine if the human fibroblast-derived growth inhibitor (hFDGI) was identical to IL-6. Neutralizing antibodies specific for IL-6 completely eliminated the inhibitory activity of hFDGI. Moreover, exposure to human recombinant IL-6 was found to inhibit the growth of early-stage melanoma cells obtained from radial growth phase (RGP) or early vertical growth phase (VGP) primary lesions in three of four cases. In contrast, melanoma cells from a number of more advanced VGP primary lesions, or from distant metastases, were completely resistant to this IL-6-mediated growth inhibition. Acquisition of an "IL-6-resistant" phenotype by metastatically competent melanoma cell variants may provide such cells with a proliferative advantage within the dermal mesenchyme (a hallmark of melanoma cells that are malignant), helping them eventually to dominate advanced primary lesions and to establish secondary growths elsewhere.
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PMID:Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression. 140 27

p53 is a tumor suppressor gene that commonly undergoes mutations in human tumors, including lymphomas. Because p53 mutations are not restricted to a single locus, immunohistochemistry is useful to detect p53 expression and correlate this finding with lymphoma phenotype. Cryostat sections from 125 cases of lymphoma were analyzed for p53 expression using three different monoclonal antibodies (pAb 421, 1801, 240) which react with human cellular p53 and a common conformational epitope on mutant p53. A control antibody (pAb 246) reacts only with wild type p53 of murine origin and was negative in all cases. Tissue from 29 cases of lymphoid hyperplasia, including six from human immunodeficiency virus-positive (HIV+) patients, were negative for p53. p53 was predominantly localized in nuclei of high-grade lymphomas, including 14 of 46 cases of B cell immunoblastic lymphomas and two of five T cell immunoblastic lymphomas. p53 expression was relatively common in lymphomas from HIV+ patients, and unusual in intermediate and low-grade lymphomas of follicular center cell type. Low-grade lymphoma of small lymphocytic type disclosed p53+ large cells (paraimmunoblasts) that may play a role in tumor progression in this lymphoma subtype. p53 was also strongly expressed in the nuclei of Reed Sternberg cells from 19 of 37 cases of Hodgkin's disease, including six cases of mixed cellularity, and 13 cases of nodular sclerosing type. Immunohistochemical staining is a rapid method to identify p53 expression in lymphomas.
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PMID:Immunohistochemical analysis of p53 expression in malignant lymphomas. 146 98

Tonsils seem to be the ideal source of lymphocytes seeding to the mucosa of the respiratory tract. The distribution and engraftment of human lymphocytes injected into mice with severe combined immunodeficiency (SCID) are not well understood. C.B-17 SCID mice were injected intraperitoneally with human tonsillar mononuclear cells (hu-TMC). The hu-TMC-SCID mouse chimeras were subsequently tested for the appearance and distribution of human lymphocytes tagged with H33342 and immunoglobulin-secreting cells in various systemic and mucosal immunocompetent tissues. This was done by fluorescence microscopy of tissue sections for cells supravitally stained before transfer and by an enzyme-linked immunospot assay using cells isolated from murine organs. Most importantly, engraftment of hu-TMC proved to be dependent on the presence of anti-Epstein-Barr virus (EBV) antibody in the donor. hu-TMC engrafted, in decreasing numbers, in the following systemic organs: peritoneal cavity, liver, spleen and bone marrow. Among mucosal tissues tested, hu-TMC were seen in lungs, but not in the intestines. The engraftment of hu-TMC in the lung was more extensive than that in the spleen. These studies demonstrate that hu-TMC engraft in a variety of murine tissues. The striking preference of hu-TMC for the lungs when compared to intestines suggests selective engraftment among distinct mucosal tissues. The hu-TMC-SCID mouse chimera promises to be a unique animal model to study human-mucosa-associated lymphoid cells and EBV-related lymphomagenesis and B cell tumor progression.
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PMID:Distribution and engraftment patterns of human tonsillar mononuclear cells and immunoglobulin-secreting cells in mice with severe combined immunodeficiency: role of the Epstein-Barr virus. 166 36

We have investigated Langerhans cell (LC) distribution in 38 prostatic carcinomas, of various degrees of differentiation, by immunohistochemistry with a polyclonal anti-S-100 serum, furthermore evaluating the expression of HLA class II-DR by neoplastic cells using a monoclonal antibody (MoAb) that reacts with a monomorphic determinant in formalin-fixed paraffin-embedded tissue. Antiserum to S-100 protein identified LCs mostly in carcinomas ranging from grade 1 to grade 2, while LCs were inconspicuous in grade 4 and virtually absent in grade 5 cancers. Moreover, sections stained with the anti -HLA-DR MoAb displayed an immunoreactivity, both cytoplasmic and apical, especially confined to neoplastic glands of low grade (1-2) carcinomas. Although we did not find a direct correlation between the two parameters under investigation and lymphoid infiltrate, we were able to document an increased number of HLA class II-positive interstitial cells in low-grade carcinomas, corresponding mostly to macrophages. Our results indicate that LC number is inversely correlated to the histopathological grade and directly to the expression of HLA class II-DR molecules by tumor cells; we believe that this might be important in understanding the more favorable biological behavior of low-grade prostate carcinomas as opposed to the higher grades, since LCs and HLA class II molecules may provide a means of eliciting the immune response, both LCs and epithelial cells expressing HLA class II molecules being capable of direct antigen presentation to immune cells. In this context macrophages might play a primary role in controlling tumor progression. To the best of our knowledge this is the first time that an attempt is made to correlate LCs and HLA class II expression to histopathological grading of prostatic carcinomas. We would also suggest that the presence of LCs and HLA class II molecules, either singly or in combination, in carcinoma of the prostate represents a good prognostic indicator, being constantly associated with the clinically less aggressive low-grade tumors. The evaluation of these two parameters might prove useful in the assessment of intermediate grades where no valid histologic criteria have been found to predict the clinical course of the disease.
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PMID:Distribution of Langerhans cells and HLA class II molecules in prostatic carcinomas of different histopathological grade. 187 38

Low grade lymphomas which derive from either the B or T lineage commonly progress to a more aggressive form of lymphoma. Among follicular lymphomas this progression usually manifests pathologically by a change to a diffuse pattern of infiltration as well as by a change to a proliferation dominated by large lymphoid cells. A similar progression to a proliferation of large lymphoid cells may be seen in small lymphocytic lymphomas and in mycosis fungoides or other T cell lymphomas. To investigate whether certain tumor cell or host cell features may be associated with tumor progression, we and other investigators have applied various cell markers to lymphoma subtypes. Clinical correlations with tumor cell features such as lineage derivation, histocompatibility antigen expression, lymphocyte function-associated antigen (LFA-1) expression, and proliferation-associated marker expression are described. The clinical significance of large numbers of CD4+ cells in small cell B lineage lymphomas is also presented.
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PMID:Tumor progression in malignant lymphomas. 203 89

We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direct sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsies; 17/27 cell lines) and its leukemic counterpart L3-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia.
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PMID:p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. 205 20

The lymphoid cells of embryonic bursal follicles are engaged in rapid growth and preimmune diversification of immunoglobulin genes. Disruption of follicular architecture by mechanical dispersion of these cells in short-term tissue culture was accompanied by continued cell division and extensive cell death by apoptosis. Apoptosis was suppressed in parallel cultures of intact follicles. gamma Radiation also triggered extensive apoptosis in embryonic bursal follicles within a few hours. Preneoplastic bursal stem cell populations induced by a v-myc oncogene were hypersensitive to induction of apoptosis by follicular dispersion and radiation. In contrast, tumor progression in v-myc- and v-rel-initiated bursal neoplasms was accompanied by development of resistance to induction of apoptosis. A programmed cell death pathway can be activated during normal B-cell development in the bursa, and alterations in the expression of this pathway accompany neoplastic change in this system.
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PMID:Induction of apoptosis during normal and neoplastic B-cell development in the bursa of Fabricius. 206 63

Posttransplant lymphoproliferative disorders (PTLD) are abnormal growths of lymphoid cells that occur in immunosuppressed organ transplant recipients. Most cases are of B-lymphocyte origin and are associated with Epstein-Barr virus infection. Twelve of 72 allograft recipients with PTLD in our series have had disease predominantly involving the gastrointestinal tract. The lesions are most often multiple and preferentially involve the distal small bowel. The appearance of the lymphoid cells ranges from nonuniform (polymorphic) to uniform (monomorphic). Most tumors contain a clonal component of B-lymphocytes, with or without a nonclonal background. Appropriate primary treatment includes surgical resection and reduction of immunosuppression. Occasional PTLD of the gastrointestinal tract do not respond to this regimen, these represent a more advanced state of tumor progression. Currently, 11 of 12 patients are alive 10-13 months after diagnosis. The surgical pathologist must be aware of the appropriate setting in which to consider a diagnosis of PTLD and be able to distinguish this condition from other lymphoproliferative disorders of the gastrointestinal tract.
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PMID:Involvement of the gastrointestinal tract by Epstein-Barr virus--associated posttransplant lymphoproliferative disorders. 215 45

We have previously shown that spleen cells from BALB/c mice that are in the process of eradicating a large MOPC-315 tumor following low-dose (2.5 mg/kg) melphalan (L-phenylalanine mustard) therapy are effective in preventing tumor progression upon adoptive transfer into BALB/c mice bearing a barely palpable tumor that had been treated with a subcurative dose of melphalan [Mokyr et al. (1989) Cancer Res 49:4597]. Here we show that such spleen cells in conjunction with a subcurative dose of drug (adoptive chemoimmunotherapy, ACIT) can cause the complete regression of a large (15-20 mm) s.c. MOPC-315 tumor in a large percentage of T-cell-deficient (athymic nude) tumor-bearing mice. Spleen cells that were effective in ACIT of athymic nude mice displayed in vitro a substantial direct lytic activity against MOPC-315 tumor cells, and the lytic activity was greatly enhanced when the spleen cells were cultured for 5 days with or without mitomycin-C-treated MOPC-315 stimulator tumor cells. The cells responsible for the therapeutic effectiveness of the spleen cells in ACIT of athymic nude mice, as well as the cells responsible for the direct in vitro anti-MOPC-315 lytic activity of the spleen cells, were of the Lyt 2 and not the L3T4 phenotype. Most of the athymic nude mice that completely eradicated a large MOPC-315 tumor as a consequence of ACIT were capable of rejecting a challenge with 30-100 times the minimal lethal tumor dose for 100% of normal BALB/c mice administered more than 1 month after the ACIT. The ability of these athymic nude mice to resist the tumor challenge was associated with the presence of a greatly elevated percentage of cells expressing T cell surface markers in their spleens. Thus, it is conceivable that splenic Lyt 2+T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor mediate their therapeutic effectiveness in ACIT of athymic nude mice bearing a large MOPC-315 tumor, at least in part, through direct cytotoxicity for MOPC-315 tumor cells. In addition, eradication of a large MOPC-315 tumor through cooperation between antitumor immunity and melphalan toxicity endues the athymic nude mice with an elevated percentage of T cells in their secondary lymphoid organs, and these T cells are probably responsible for the long-lasting protective antitumor immunity exhibited by these mice.
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PMID:Eradication of a large MOPC-315 tumor in athymic nude mice by chemoimmunotherapy with Lyt2+ splenic T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor. 233 2

A rapid, simple, convenient method for extracting DNA from fine needle aspiration (FNA) samples of human solid tumors for Southern blot hybridization studies is described. After the preparation of an air-dried cytologic smear, the remaining sample in the needle was rinsed directly into a test tube for DNA extraction. The extraction procedure, in which manipulation of the sample is minimized, produced sufficient DNA for Southern blot analysis within 24 hours of the FNA biopsy in the ten consecutive cases studied. The DNA bound to the nylon membranes can be washed and reexamined with a variety of probes, allowing studies of lymphoid cell lineage, oncogene amplification or tumor progression. The assessment of cellularity on the cytologic specimen at the time of FNA provided a reliable guide to the need for further passes to obtain sufficient cells for DNA hybridization; the cytologic diagnosis could also be made on the smears.
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PMID:Method of extracting DNA from fine needle aspirates of human solid tumors for Southern blot analysis. 255 50


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