Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interferons (IFNs), in addition to their well-known antiviral activities, have important roles in the control of cell proliferation and are effective agents for the treatment of a limited number of malignant diseases. IFNs not only regulate cell growth and division but also influence cell survival through their effects on apoptosis. This review describes the current state of knowledge about the mechanisms of action of these cytokines on the apoptotic machinery, with particular emphasis on the synergism that exists between the IFNs and other proapoptotic agents, such as members of the tumor necrosis factor (TNF) family. The review also discusses the physiologic and clinical implications of the effects of the IFNs on apoptosis for regulation of viral infection and tumor growth.
J Interferon Cytokine Res 2003 Jun
PMID:Interferons and apoptosis. 1285 54

There is a strong graft-versus-leukemia (GVL) effect of allogeneic stem cell transplantation (SCT) due to elimination of tumor cells by alloimmune effector lymphocytes. When leukemia relapses after allogeneic SCT, donor lymphocyte transfusions (DLTs) can induce sustained remissions in some patients. This review summarizes the current status on clinical use of DLT, the basis of GVL reactions, problems associated with this therapy, and new strategies to improve DLT. Several multicenter surveys demonstrated that the GVL effect of DLT is most effective in chronic myelogenous leukemia (CML), whereas it is less pronounced in acute leukemia and myeloma. Cytokine stimulation to induce differentiation of myeloid progenitor cells or to up-regulate costimulatory molecules on tumor cells may improve the efficacy of DLT. Infections and graft-versus-host disease (GVHD) are major complications of DLT. Control of GVHD may be improved using suicide gene-modified T cells for DLT, allowing T-cell elimination if severe GVHD develops. Hopefully, in the future, GVL effect can be separated from GVHD through adoptive transfer of selected T cells that recognize leukemia-specific antigens or minor histocompatibility antigens, which are expressed predominantly on hematopoietic cells, thereby precluding attack of normal tissues. In patients with leukemia and lymphomas with fast progression, tumor growth may outpace development of effector T cells. Here it may be preferable to select stem cell transplant donors with HLA-mismatches that allow alloreactive natural killer cells, which appear early after transplantation, to retain their cytolytic function. New approaches for adoptive immune therapy of leukemia, which promise a better prognosis for these patients, are being developed.
 ...
PMID:Graft-versus-leukemia reactions in allogeneic chimeras. 1295 64

Inhibition of the neovascularization of tumors has proven efficacious in reducing tumor growth and metastases. Attaining antiangiogenesis through cationic lipid-based systemic gene therapy presents an attractive approach to the treatment of disseminated and primary cancers. Intravenous administration of an endostatin plasmid, complexed with a cationic lipid system, produced significant levels of endostatin in the lung and the circulation. The expressed endostatin blocked systemic angiogenesis and inhibited tumor growth in murine models. Cytokine induction by cationic lipid/DNA complex increased the anti-tumor activities of endostatin. These results demonstrate the possibility of using cationic lipid delivery of an antiangiogenic gene for cancer treatment.
 ...
PMID:Intravenous delivery of an endostatin gene complexed in cationic lipid inhibits systemic angiogenesis and tumor growth in murine models. 1451 19

Dendritic cells (DCs) were adenovirally engineered to constitutively and durably secrete the potent Th1-biasing cytokines interleukin (IL)-12 (AdIL12DC) and/or IL-18 (AdIL18DC) and evaluated for their ability to promote therapeutic antitumor immunity in murine sarcoma models. Injection of either AdIL12DC or AdIL18DC into day 7 CMS4 or MethA tumors resulted in tumor rejection or slowed tumor growth when compared with control cohorts. Importantly, intratumoral injection with DCs engineered to secrete both IL-12 and IL-18 (AdIL12/IL18DC) resulted in complete and the most acute rejection of any treatment group analyzed. This strategy was also effective in promoting the regression of contralateral, untreated tumors. Both CD4+ and CD8+ T cells were required for tumor rejection. CD8+ splenic T cells from mice treated with AdIL12/IL18DC produced the highest levels of IFN-gamma in response to tumor rechallenge in vitro and displayed the broadest repertoire of Tc1-type reactivity to acid-eluted, tumor-derived peptides among all treatment cohorts. This apparent enhancement in cross-presentation of tumor-associated epitopes in vivo may result from the increased capacity of engineered DCs to kill tumor cells, survive tumor-induced apoptosis, and present immunogenic MHC/tumor peptide complexes to T cells after intratumoral injection. In support of this hypothesis, cytokine gene-engineered DCs expressed higher levels of MHC and costimulatory molecules, as well as Fas ligand and membrane-bound tumor necrosis factor alpha, with the latter markers associated with elevated tumoricidal activity in vitro. Cytokine gene-engineered DCs appeared to have a survival advantage in situ when injected into tumor lesions, to be found in approximation with regions of tumor apoptosis, and to have the capacity to ingest apoptotic tumor bodies. These results support the ability of combined cytokine gene transfer to enhance multiple effector functions mediated by intralesionally injected DCs that may concertedly promote cross-priming and the accelerated immune-mediated rejection of tumors.
 ...
PMID:Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity. 1455 27

Cytokines and vitamins play a central role in controlling neoplastic cell growth. The interferon (IFN) family of cytokines regulates antiviral, anti-tumor, antimicrobial, differentiation, and immune responses in mammals. Significant advances have been made with respect to IFN-induced signal transduction pathways and antiviral responses. However, the IFN-induced anti-tumor actions are poorly defined. Although IFNs themselves inhibit tumor growth, combination of IFNs with retinoids (a class of Vitamin A related compounds) strongly potentiates the IFN-regulated anti-tumor action in a number of cell types. To define the molecular mechanisms involved in IFN/retinoid (RA)-induced apoptosis we have employed a genetic approach and identified several critical genes. In this review, I provide the current picture of IFN- RA- and IFN/RA-regulated growth suppressive pathways. In particular, I focus on a novel set of genes, the genes-associated with retinoid-interferon induced mortality (GRIM). GRIMs may be novel types of tumor suppressors, useful as biological response markers and potentially novel targets for drug development.
Cytokine Growth Factor Rev
PMID:The GRIMs: a new interface between cell death regulation and interferon/retinoid induced growth suppression. 1511 Aug

T cell immunotherapy is a potential strategy for the treatment of brain tumors because it offers a high degree of specificity, the ability to extravasate into solid tumors, and the potential for eliciting a long-term protective immune response. Various approaches have been developed to overcome T cell immune tolerance to cancer, including the use of cytokines and bispecific antibodies. T cell stimulation with the proinflammatory cytokine IL-12 can elicit antitumor immunity. T cell activation can be increased using bispecific antibodies against activating molecules on the surface of T cells and a tumor antigen. We studied the effects of systemic IL-12 administration in combination with a conjugate of an anti-CD28 antibody and a ligand for the folate receptor. The high affinity folate receptor is expressed on endogenously arising choroid plexus tumors of SV11 mice, which are transgenic for large T antigen under the control of the SV40 promoter. SV11 mice are immunocompetent, yet immunologically tolerant to large T antigen expressed by choroid plexus tumors. MRI analysis showed that the administration of IL-12 and anti-CD28 Fab/folate significantly slowed tumor growth. Proliferating CD8(+) T cells were found in choroid plexus tumors of treated animals. Treatment of animals with IL-12 + anti-CD28 Fab/folate prolonged survival compared to IL-12 alone. Cytokine treatment combined with tumor-targeted costimulation may be a useful adjunct treatment.
 ...
PMID:A conjugate of a tumor-targeting ligand and a T cell costimulatory antibody to treat brain tumors. 1536 70

CD4(+)CD25+ T regulatory (Treg) cells have been shown to critically regulate self and allograft tolerance in mice. Studies of human Treg cells have been hindered by low numbers present in peripheral blood and difficult purification. We found that cord blood was a superior source for Treg-cell isolation and cell line generation compared with adult blood. Cord blood CD4(+)CD25+ cells were readily purified and generated cell lines that consistently exhibited potent suppressor activity, with more than 95% suppression of allogeneic mixed lymphocyte reactions (MLRs) (29 of 30 donors). Cultured Treg cells blocked cytokine accumulation in MLRs, with a less robust inhibition of chemokine production. These cell lines uniformly expressed CD25, CD62L, CCR7, CD27, and intracellular cytotoxic T-lymphocyte antigen-4 (CTLA4). FoxP3 protein, but not mRNA, was specifically expressed. Upon restimulation with anti-CD3/CD28 beads, the cultured Treg cells produced minimal cytokines (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], and IL-10) and preferentially expressed tumor growth factor-beta (TGF-beta) latency associated protein. Cytokine production, however, was restored to normal levels by restimulation with phorbol myristate acetate (PMA)/ionomycin. Cord blood-derived cultured suppressor cell function was predominantly independent of IL-10 and TGF-beta. These results demonstrate cord blood contains a significant number of Treg precursor cells capable of potent suppressor function after culture activation. Banked cord blood specimens may serve as a readily available source of Treg cells for immunotherapy.
 ...
PMID:Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function. 1537 87

Vascular endothelial growth factor (VEGF), which was originally discovered as vascular permeability factor, is critical to human cancer angiogenesis through its potent functions as a stimulator of endothelial cell survival, mitogenesis, migration, differentiation and self-assembly, as well as vascular permeability, immunosuppression and mobilization of endothelial progenitor cells from the bone marrow into the peripheral circulation. Genetic alterations and a chaotic tumor microenvironment, such as hypoxia, acidosis, free radicals, and cytokines, are clearly attributed to numerous abnormalities in the expression and signaling of VEGF and its receptors. These perturbations confer a tremendous survival and growth advantage to vascular endothelial cells as manifested by exuberant tumor angiogenesis and a consequent malignant phenotype. Understanding the regulatory mechanisms of both inducible and constitutive VEGF expression will be crucial in designing effective therapeutic strategies targeting VEGF to control tumor growth and metastasis. In this review, molecular regulation of VEGF expression in tumor cells is discussed.
Cytokine Growth Factor Rev 2004 Oct
PMID:Constitutive and inducible expression and regulation of vascular endothelial growth factor. 1545 Feb 48

Local therapy of pancreatic cancer with microencapsulated CYP2B1-producing cells and ifosfamide showed an effect both on the primary tumor and on distant metastatases. This possibly represents a consequence of the activation of immune response. Other studies have demonstrated that local tumor irradiation leads to the activation of the intratumoral lymphocyte infiltration. The aim of our study was to investigate the efficacy of the combined therapy with low-dose irradiation, ifosfamide and CYP2B1-producing cells. Syngenic pancreatic cancer was induced in 38 Lewis-rats by subcutaneous inoculation of 1 x 10(6) (DSL6A) tumor cells. Microencapsulated CYP2B1-producing cells were injected peritumorally 10--12 weeks after tumor implantation. Animals were randomized to the following groups: 1) control (NaCl, 1 ml i.p.), 2) ifosfamide (50 mg/kg, i.p., (3x/week), 3) local irradiation with 5 Gy and 4) ifosfamide plus irradiation. The tumor growth was monitored for 3 weeks. The tumor infiltration with CD4+, CD8+, NK-cells, microvessel density and proliferation rates were investigated by immunohistochemistry. Cytokine plasma level for TNF-alpha were measured by ELISA. Seven of 9 animals in the group of combined therapy showed an objective response to the therapy. The therapy with ifosfamide or radiation alone showed 5 and 3 responders, respectively. The mean tumor volume was significantly reduced after combined ifosfamide plus radiation therapy in the first week, whereas monotherapy with ifosfamide or radiation significantly decreased tumor growth earliest after 2 and 3 weeks, respectively. The high plasma level of TNF-alpha in the control group was significantly reduced after combined ifosfamide/irradiation treatment. The lymphocyte infiltration and tumor proliferation were not significantly different between the groups. Microvascular density was significantly increased after ifosfamide and ifosfamide plus irradiation therapy. The combination of ifosfamide/CYP2B1-producing cells and irradiation showed an earlier therapeutical effect on the growth of rat pancreatic cancer than the irradiation or ifosfamide alone. There was no evidence of late activation of lymphocyte infiltration and PCNA-positive tumor cells.
 ...
PMID:Combined therapy of experimental pancreatic cancer with CYP2B1 producing cells: low-dose ifosfamide and local tumor irradiation. 1545 74

Eph receptors are the largest receptor tyrosine kinase family of transmembrane proteins with an extracellular domain capable of recognizing signals from the cells' environment and influencing cell-cell interaction and cell migration. Ephrins are the ligands to Eph receptors and stimulate bi-directional signaling of the Eph/ephrin axis. Eph receptor and ephrin overexpression can result in tumorigenesis as related to tumor growth and survival and is associated with angiogenesis and metastasis in many types of human cancer. Recent data suggest that Eph/ephrin signaling could play an important role in the development of novel inhibition strategies and cancer treatments to potentially target this receptor tyrosine kinase and/or its ligand. A deeper understanding of the molecular basis for normal versus defective cell-cell interaction through the Eph/ephrin axis will enable the potential development of novel cancer treatments. This review emphasizes the biology of Eph/ephrin as well as the potential for novel targeted therapy through this pathway.
Cytokine Growth Factor Rev 2004 Dec
PMID:The role of ephrins and Eph receptors in cancer. 1556


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>