Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell-rich B-cell lymphomas (TCRBCLs) are diffuse lymphomas that contain a minority of large neoplastic B cells amidst a majority of non-neoplastic T cells and numerous histiocytes, an unusually pronounced reactive component not seen in most diffuse large B-cell lymphomas (DLBCLs). This reaction may be influenced by various cytokines secreted by lymphoma or reactive cells; therefore, expression of interleukin (IL)-1 beta, IL-2, IL-4, IL-6, and IL-9 was evaluated immunohistochemically on paraffin-embedded sections of 18 TCRBCLs and was compared with that of 15 DLBCLs containing a minority of reactive T cells and to that of seven reactive lymph nodes. Moderate to intense expression of IL-4 was detected in variable numbers of tumor cells and in numerous histiocytes in 16 TCRBCLs. In contrast, intense IL-4 expression in numerous histiocytes was observed in only one of 15 DLBCLs with few T cells. In four other DLBCLs and three reactive nodes, moderate to intense staining for IL-4 was noted only in rare large transformed cells or in occasional histiocytes. Except for one IL-1 beta positive and another IL-9 positive TCRBCL, there was no marking or weak staining only with other cytokine antibodies in the neoplastic and reactive cases studied. The expression of IL-4 in most TCRBCLs, but not in other DLBCLs or in reactive nodes, suggests that this cytokine is one factor involved in the pathobiology of the abundant T-cell reaction and, perhaps, contributes to the paucity of neoplastic B cells in TCRBCLs.
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PMID:Interleukin-4 may contribute to the abundant T-cell reaction and paucity of neoplastic B cells in T-cell-rich B-cell lymphomas. 144 42

We have established that melanomas express shared tumor antigens (Ags) that can be recognized by T cells if presented in the context of self-MHC molecules. Tumor-infiltrating lymphocytes (TILs) from six melanoma patients were tested for lysis of large panels of HLA-matched or unmatched targets representing a variety of tissue types. Lysis was specific for allogeneic melanomas sharing at least one HLA-A, -B, or -C Ag with TILs, and demonstrated commonly expressed tumor Ags. Similar findings were obtained when cytokine secretion by TILs was used to indicate specific Ag recognition. Transfection of the HLA-A2.1 gene into HLA-A2- melanoma lines conferred susceptibility to lysis by HLA-A2 restricted melanoma TILs, demonstrating expression of common tumor Ags among patients of diverse HLA types. These findings have important implications for developing broadly applicable cancer immunotherapies such as vaccines.
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PMID:Recognition of shared melanoma antigens by human tumor-infiltrating lymphocytes. 144 13

Cytokines are important modulators of host antitumor responses. Two of these cytokines, interleukin-2 (IL-2) and interferon gamma (IFN-gamma), are produced after antigen-induced activation of helper lymphocytes. The cytokines are released into the immediate vicinity where they either interact with the appropriate receptors on effector cell populations or are rapidly degraded. To mimic this physiologic release of cytokines at the effector-target site, we used retroviral vectors to transduce melanoma cells with the IL-2 or IFN-gamma cDNA. Five melanoma cell lines were transduced with IL-2- or IFN-gamma-containing vectors and secreted IL-2 at 1 to 40 U/mL/10(6) cells/24 h or IFN-gamma 1 to 8 U/mL/10(6) cells/24 h, respectively. After gamma irradiation, these cells continued to secrete cytokines for about 3 to 4 weeks. Secretion of IFN-gamma induced upregulation of major histocompatibility complex class I molecules in a subset of melanoma cell lines. IL-2 production by human melanoma xenografts induced tumor rejection in BALB/c nu/nu mice, showing the in vivo effect of this cytokine. This study shows that (1) human melanoma cells can be stably transduced with cytokine-containing retroviral vectors; (2) cytokines are secreted constitutively by the transduced tumor cells and have the expected biologic effects in vitro and in vivo; and (3) after gamma irradiation, cytokines continue to be secreted for several weeks. These data suggest that irradiated cytokine-secreting allogenic or autologous tumor cells can be used in vaccination protocols for cancer patients.
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PMID:Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-gamma in irradiated human melanoma cells. 145 Apr 8

The ultrastructural features and the gene expression pattern of Kaposi's sarcoma (KS) spindle cells in vivo suggest that KS is a tumor of the mixed cell type. The expression pattern of cytokines and cytokine receptors in the tumor lesion, together with the results obtained from in vitro characterization of KS-derived cells, provide evidence that paracrine mechanisms of growth factor action are important for the maintenance of KS. The reports on virus infection of KS cells suggest an indirect role of virus infection in the induction of KS, most likely mediated by immunostimulation and subsequent production of cytokines.
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PMID:Kaposi's sarcoma: a review of gene expression and ultrastructure of KS spindle cells in vivo. 145 89

Radiation oncology is a dynamic discipline. The radiobiologic basis for understanding and anticipating treatment effects continues to grow. Improved understanding is permitting study of altered fractionation regimens and safer integration into the clinic of high-dose-rate brachytherapy. A new agent, SR 4233, may completely revise clinical approaches to tumor hypoxia, especially intermittent (or "dynamic") hypoxia. The availability of computer technology that permits three-dimensional treatment planning with unusual beam and treatment table orientations should result in isodose lines that conform very tightly to desired treatment volumes, permitting higher doses of treatment with acceptable normal-tissue risk. The biology of cytotoxic drug and irradiation interactions and of cytokine and irradiation interactions is an area of growing promise. Combined chemotherapy and radiotherapy treatments have, in the past year, suggested major improvements in the management of esophageal and laryngeal cancer. The importance of local and regional tumor control in contributing to clinical disease course is being understood with increasing clarity, validating the development of technically demanding new approaches to administering irradiation and the use of adjunctive radiotherapy following chemotherapy for selected neoplastic diseases.
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PMID:Recent developments in radiotherapy. 145 24

Cytokines or biologic response modifiers in combination with traditional chemotherapeutic agents can be used as therapeutics in patients with cancer. Biologic response modifiers, which are involved in the control and regulation of a wide variety of physiologic activities, have previously been used primarily to enhance or boost host immunologic function. Although immune modulatory therapeutic approaches are yet to be fully realized, biologic response modifiers have also been considered in combination with cytotoxic drugs for their effects on hematopoietic progenitor cells, tumor cells directly, and microvascular endothelial cells. Interleukin-1 is a multifunctional cytokine that not only activates the immune system but also plays a central role in regulating hematopoiesis, has potent effects on vascular function, and has shown significant antitumor activity alone or in combination with various chemotherapeutic agents. As a result, interleukin-1 is an excellent candidate for combination with conventional antineoplastic drugs toward the design of innovative therapeutic approaches to malignancy. This review examines the studies using preclinical animal tumor models as well as the recent phase I clinical trials and includes an overview of their potential for further application.
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PMID:Modulation of chemotherapy antineoplastic agents with biologic agents: enhancement of antitumor activities by interleukin-1. 145 25

Biologic therapies are playing an increasingly important role in the treatment of patients with cancer. A better understanding of immune responses to tumors now exists, and more defined reagents are now available including new recombinant cytokines, cultured lymphoid cells of defined specificity, and most recently, vectors containing specific genes that can be introduced either into tumor cells or lymphoid effectors. During this past year, we have observed the reporting of new cytokines identified and tested in humans and the advent of cytokine gene therapy. The successful application of these new reagents either singly or in combination will require significant ingenuity, resources, and intuition over the next decade.
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PMID:New biologic agents come to bat for cancer therapy. 145 26

Recently, new tumor vaccine approaches were developed in animal systems that modify tumor cells genetically to secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigens or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity. The development of high efficiency gene transfer technologies such as defective retroviral vectors allows for the translation of these preclinical studies to clinical trials. However, before large investments are made in this area of gene therapy, it will be important to demonstrate that the actual gene transfer component of the strategy significantly enhances antitumor immune responses relative to alternative nongenetic approaches.
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PMID:Immunotherapy with cytokine gene-transduced tumor cells: the next wave in gene therapy for cancer. 145 27

We analyzed several factors which could influence the immunogenicity of colon tumor cells, using a series of clones derived from a single chemically induced rat adenocarcinoma cell line. These clones display variable tumorigenic potential in syngeneic immunocompetent animals, and it has been established that in this model the tumorigenicity of the cells depends on their ability to escape immune surveillance. The results show an absence of relationship between tumorigenicity and expression of MHC-class-I antigens, cell adhesion to rat fibroblasts or fibroblast extracellular matrix. The secretion of latent and active TGF beta I appeared to be quite variable from one clone to the other, but was unrelated to tumorigenicity. Unexpectedly, some regressive clones produced elevated levels of this cytokine, suggesting that in this model, spontaneous secretion of TGF beta I is not sufficient to impair the immune system of the host. In contrast, the more tumorigenic clones were more resistant than less tumorigenic ones to cytotoxicity mediated by NK or LAK cells. They also showed arrest of cell proliferation after reaching confluence, something not observed in the less tumorigenic clones. Finally, the strongest relationship with tumorigenicity was found for expression of blood-group carbohydrate antigens. Increased expression of blood-group-H antigen and, conversely, decreased expression of beta-galactoside precursors of this antigen correlated with increased tumorigenicity.
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PMID:Analysis of factors associated with the tumorigenic potential of 12 tumor clones derived from a single rat colon adenocarcinoma. 145 34

Cytokines are known to play an important role in host defense by regulating the function, growth, and differentiation of the cells of the immune system. We hypothesize that, in the tumor microenvironment, tumor cells and resident tissue cells (e.g., fibroblasts) also produce cytokines that may regulate the local immune response to tumors. Initially, homogenates of eight head and neck squamous cell carcinomas (HNSCC) were assayed for the presence of interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) to establish the presence of these cytokines in the tumors in vivo. We detected IL-1 in all tumor homogenates and IL-4, IL-6, and GM-CSF in some homogenates. To assess the ability of HNSCC to produce these cytokines, supernatants of short-term primary cultures of HNSCC were assayed for the same cytokines. No IL-1 was detected, although baseline levels of IL-4, IL-6, and GM-CSF were present. However, the stimulation of primary tumor cultures with exogenous IL-1 induced or significantly enhanced production of IL-4 (p < 0.01), IL-6 (p < 0.001), and GM-CSF (p < 0.02). These results support our hypothesis that HNSCC secrete cytokines that may influence the response of local immune cells. Our data also suggest that IL-1 may have a central role in regulating the local immune response through the enhancement or induction of cytokine production by tumor and/or resident tissue cells.
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PMID:Cytokine expression by head and neck squamous cell carcinomas. 146 1


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