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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) promotes angiogenesis in a number of tumor model systems. We reported previously that estrogen supports the growth of CCL-51 cell-based mammary tumors in mice, which could be blocked with specific chemokines. We investigated whether promotion of tumor growth by estrogen, and suppression of tumor growth by chemokines, was associated with VEGF protein expression. Female C3H mice were treated with vehicle, estradiol, or with one of several chemokines for 72 h. The presence of VEGF in mammary tissue samples was detected and quantified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting using antimurine VEGF antibodies. Estrogen significantly increased mammary VEGF expression. Cotreatment with tamoxifen or the chemokine interferon-inducible protein-10 (IP-10) suppressed the action estrogen on VEGF expression. CCL-51 tumor cells were placed into mammary tissue of C3H mice. Mice were treated every 72-h with either vehicle or estradiol, in the presence or absence of IP-10 for 21 days. Estrogen supported CCL-51 tumor growth, with an average of 2.3 tumors present/animal. Cotreatment of mice with estrogen and IP-10 resulted in significantly lower numbers of tumors in mammary tissue in comparison to animals treated with estrogen alone. VEGF levels in mammary tissue and tumors of IP-10 and estrogen cotreated mice were 40-50% less than those detected in mammary tissue of estrogen-treated mice. Our results suggest that estrogenic support of CCL-51 mammary tumor growth is related to increased VEGF expression, and that the inhibitory action of IP-10 may be related to suppressing VEGF levels in mammary tissue.
J Interferon Cytokine Res 2009 Feb
PMID:Antitumor/antiestrogenic effect of the chemokine interferon inducible protein 10 (IP-10) involves suppression of VEGF expression in mammary tissue. 1901 40

The interferon-inducible p200 family comprises a group of homologous mouse and human proteins. Most of these have an N-terminal DAPIN domain and one or two partially conserved, 200 amino acid long C-terminal domains (designated as 200X domain). These proteins play important roles in the regulation of cell proliferation, tissue differentiation, apoptosis and senescence. p200 family proteins are involved also in autoimmunity and the control of tumor growth. These proteins function by binding to various target proteins (e.g. transcription factors, signaling proteins, oncoproteins and tumor suppressor proteins) and modulating target activity. This review concentrates on p204, a murine member of the family and its roles in regulating cell proliferation, cell and tissue differentiation (e.g. of skeletal muscle myotubes, beating cardiac myocytes, osteoblasts, chondrocytes and macrophages) and signaling by Ras proteins. The expression of p204 in various tissues as promoted by tissue-specific transcription factors, its distribution among subcellular compartments, and the controls of these features are also discussed.
Cytokine Growth Factor Rev
PMID:p204, a p200 family protein, as a multifunctional regulator of cell proliferation and differentiation. 1902 46

The phosphoinositol phosphatase SHIP2 is an important regulator of energy metabolism. SHIP2 dephosphorylates phosphatidylinositol 3,4,5 trisphosphates which are critical second messengers in signaling pathways induced by various extracellular stimuli including insulin. SHIP2 also regulates cytoskeleton remodeling, cell adhesion and spreading. In addition, endogenous SHIP2 in HeLa cells regulates receptor endocytosis and ligand-induced EGFR degradation. Further, SHIP2 in MDA-MB-231 breast cancer cells regulates EGFR levels and supports in vitro cell proliferation and in vivo tumor growth and spontaneous metastasis. Here we examine the role of SHIP2 in EGF signaling in breast cancer cells using RNA interference. Our results show that suppression of SHIP2 in MDA-MB-231 breast cancer cells alters EGF and EGFR internalization. Upon SHIP2 silencing, EGF-induced Akt activation was reduced causing decreased nuclear levels of activated Akt. Cytokine receptor CXCR4, a downstream element of EGFR-Akt pathway that plays an important role in metastasis, is down-regulated upon SHIP2 knockdown. Finally, cell adhesion and EGF-induced cell migration were suppressed in SHIP2 silenced cells. These results demonstrate a positive role of SHIP2 in EGF-induced Akt activation, CXCR4 expression, and cell migration in breast cancer cells.
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PMID:SHIP2 phosphoinositol phosphatase positively regulates EGFR-Akt pathway, CXCR4 expression, and cell migration in MDA-MB-231 breast cancer cells. 1908 82

The Scatter Factors are two homologous proteins, named Scatter Factor/Hepatocyte Growth Factor and Macrophage Stimulating Protein. Their receptors are the products of two oncogenes, Met and Ron, respectively. The Scatter Factors induce movement, stimulate proliferation, regulate apoptosis and are morphogenic, i.e. operate an integrated program that seems tailored to drive organ development and to regenerate injured tissues. On the other hand, Scatter Factors may be responsible for pathologic tissue remodeling, infiltration of inflammatory cells, and tumor growth and diffusion. The review describes the involvement of Scatter Factors in renal disease, including acute renal failure, glomerulonephritis, chronic fibrosing nephropathies, dialysis, renal transplantation and renal tumors, and discusses the double-faced role of Scatter Factors, that play either a protective or a pathogenic role.
Cytokine Growth Factor Rev 2009 Feb
PMID:Scatter Factors in renal disease: Dr. Jeckyll and Mr. Hyde? 1920 Dec 50

Sodium stibogluconate (SSG), an inhibitor of SHP-1 that negatively regulates cytokine signaling and immunity, suppressed growth of murine Renca tumors in combination with interleukin-2 (IL-2) via a T-cell-dependent mechanism. The ability of SSG to interact with IL-2 in activating primary human immune cells was evaluated herein by assessing its induction of interferon (IFN)-gamma(+) TH1 cells in human peripheral blood in vitro. The significance of IFN-gamma(+) cells was also investigated by assessing SSG/IL-2 antitumor activity in wild-type and IFN-gamma(-/-) mice. IFN-gamma(+) cells but not IL-5(+) cells were induced markedly (9.1x) in healthy peripheral blood by SSG/IL-2 in contrast to the modest induction by SSG alone (2.1x) at its clinically achievable dose (20 microg/mL) or by IL-2 (3.1x) at its C(max) of low-dose schedule (30 IU/mL). SSG at a higher dose (100 microg/mL) was less effective alone (1.5x) or in combination with IL-2 (7.8x). Peripheral IFN-gamma(+) cells were induced after 4 or 16 h treatment with SSG/IL-2 within CD4(+) and CD8(+) lymphocytes coincided with heightened CD69 expression (approximately 3-4x). SSG/IL-2 was also more effective than the single agents in inducing IFN-gamma(+) cells in the peripheral blood of melanoma patients, whose basal IFN-gamma(+) cell levels were approximately 5% of healthy controls. Renca tumor growth was inhibited by SSG/IL-2 in wild-type but not IFN-gamma(-/-) mice. These results demonstrate SSG interactions with IL-2 in vitro to activate key antitumor immune cells in peripheral blood of healthy and melanoma donors, providing further evidence for proof of concept clinical trials for effecting augmentation of IL-2 through inhibiting negative regulatory protein tyrosine phosphatases.
J Interferon Cytokine Res 2009 Aug
PMID:Interferon-gamma is induced in human peripheral blood immune cells in vitro by sodium stibogluconate/interleukin-2 and mediates its antitumor activity in vivo. 1951 39

Cervical cancer is the most common malignant disease responsible for the deaths of a large number of women in the developing world. Although certain strains of human papillomavirus (HPV) have been identified as the cause of this disease, events that lead to formation of malignant tumors are not fully clear. STAT3 is a major oncogenic transcription factor involved in the development and progression of a number of human tumors. However, the mechanisms that result in loss of control over STAT3 activity are not understood. Gene associated with Retinoid-Interferon-induced Mortality-19 (GRIM-19) is a tumor-suppressive protein identified using a genetic technique in the interferon/retinoid-induced cell death pathway. Here, we show that reduction in GRIM-19 protein levels occur in a number of primary human cervical cancers. Consequently, these tumors tend to express a high basal level of STAT3 and its downstream target genes. More importantly, using a surrogate model, we show that restoration of GRIM-19 levels reestablishes the control over STAT3-dependent gene expression and tumor growth in vivo. GRIM-19 suppressed the expression of tumor invasion- and angiogenesis-associated factors to limit tumor growth. This study identifies another major novel molecular pathway inactivated during the development of human cervical cancer.
J Interferon Cytokine Res 2009 Oct
PMID:Down-regulation of GRIM-19 expression is associated with hyperactivation of STAT3-induced gene expression and tumor growth in human cervical cancers. 1964 6

The effect of blocking VEGF activity in solid tumors extends beyond inhibition of angiogenesis. However, no studies have compared the effectiveness of mechanistically different anti-VEGF inhibitors with respect to changes in tumor growth and alterations in the tumor microenvironment. In this study we use three distinct breast cancer models, a MDA-MB-231 xenograft model, a 4T1 syngenic model, and a transgenic model using MMTV-PyMT mice, to explore the effects of various anti-VEGF therapies on tumor vasculature, immune cell infiltration, and cytokine levels. Tumor vasculature and immune cell infiltration were evaluated using immunohistochemistry. Cytokine levels were evaluated using ELISA and electrochemiluminescence. We found that blocking the activation of VEGF receptor resulted in changes in intra-tumoral cytokine levels, specifically IL-1beta, IL-6 and CXCL1. Modulation of the level these cytokines is important for controlling immune cell infiltration and ultimately tumor growth. Furthermore, we demonstrate that selective inhibition of VEGF binding to VEGFR2 with r84 is more effective at controlling tumor growth and inhibiting the infiltration of suppressive immune cells (MDSC, Treg, macrophages) while increasing the mature dendritic cell fraction than other anti-VEGF strategies. In addition, we found that changes in serum IL-1beta and IL-6 levels correlated with response to therapy, identifying two possible biomarkers for assessing the effectiveness of anti-VEGF therapy in breast cancer patients.
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PMID:Cytokine levels correlate with immune cell infiltration after anti-VEGF therapy in preclinical mouse models of breast cancer. 1988 52

New strategies of immunotherapy are currently being evaluated, and the combination of chemo- and immunotherapy has shown promising results. The cytokine interleukin-21 (IL-21) is known to enhance immune function, and in this study we have investigated its ability to boost the efficacy of chemoimmunotherapy-cyclophosphamide and adoptive cell transfer (ACT)-in the B16-OVA/OT-I murine model of malignant melanoma. Subcutaneous B16-OVA tumors were established in C57BL/6J mice 8 days before adoptive transfer of tumor-specific OT-I T cells. In addition to cyclophosphamide and ACT, one group of mice received daily injections of murine IL-21 (mIL-21). Mice treated with mIL-21 had more tumor-specific T cells in the circulation 4 and 7 days following ACT (P=0.004 and P=0.002, respectively). Importantly, mIL-21 and ACT controlled tumor growth instantly and more effectively than ACT alone (P=0.001, day 4)-an effect that persisted up to 5 days after the last mIL-21 injection. We conclude that mIL-21 enhances chemoimmunotherapy: it amplifies the number of tumor-specific T cells in the circulation and also stunts early tumor growth.
Cytokine 2010 Jan
PMID:Interleukin-21 restrains tumor growth and induces a substantial increase in the number of circulating tumor-specific T cells in a murine model of malignant melanoma. 1996 21

FDA approval of several inhibitors of the VEGF pathway has enabled significant advances in the therapy of cancer and neovascular age-related macular degeneration. However, similar to other therapies, inherent/acquired resistance to anti-angiogenic drugs may occur in patients, leading to disease progression. So far the lack of predictive biomarkers has precluded identification of patients most likely to respond to such treatments. Recent suggest that both tumor and non-tumor (stromal) cell types are involved in the reduced responsiveness to the treatments. The present review examines the role of tumor- as well as stromal cell-derived pathways involved in tumor growth and in refractoriness to anti-VEGF therapies.
Cytokine Growth Factor Rev 2010 Feb
PMID:Pathways mediating VEGF-independent tumor angiogenesis. 2000 48

In the last years it became clear that the tumor microenvironment plays a major role in neoplastic growth. Proteins secreted either by the malignant cells or by the tumor-associated stromal cells act as extracellular signal transductors, orchestrating tumor progression. Sentinel cells of the innate immune system patrol the different organs and have proven either to promote tumor growth or induce tumor suppression. In recent years, members of the matricellular family of extracellular proteins were shown to be involved in different aspects of the inflammatory response during tumor development, although in contradictory ways. In this review we discuss the evidence available up to date that relates matricellular proteins with the regulation of the inflammatory response and tumor progression.
Cytokine Growth Factor Rev 2010 Feb
PMID:Matricellular proteins and inflammatory cells: a task force to promote or defeat cancer? 2000 33


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