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

Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p < 0.05) with one virus injection, but the tumor size continued to increase after a lag period and none of the treated animals survived. Three virus injections or T-cell suppression with dexamethasone did not significantly improve treatment efficacy. It appeared that the local virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested.
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PMID:Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models. 1744 93

The proteinase-activated receptor PAR(2) has been demonstrated to modulate tumor growth, invasion and metastasis in various tissues. However, the role of PAR(2) in cutaneous cancerogenesis is still unknown. Here we could show a protective role of PAR(2) in the development of epidermal skin tumors: we established a mouse skin tumor model using chemically induced carcinogenesis. Tumors started to appear after eight weeks. After 13 weeks, PAR(2)-deficient mice showed a significantly increased number of skin tumors (14 per animal on the average) in contrast to the wild type (eight tumors per mouse). Analysis of possible signal transduction pathways activated upon PAR(2) stimulation in HaCaT keratinocytes showed an involvement of extracellular signal-regulated kinase 1/2 and profound epidermal growth factor receptor transactivation, leading to secretion of the tumor-suppressing factor transforming growth factor-beta1. Thus, our results provide early experimental evidence for a tumor-protective role of PAR(2).
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PMID:Proteinase-activated receptor-2 (PAR2): a tumor suppressor in skin carcinogenesis. 1747 97

The cancer stem cell hypothesis postulates that tumor growth is driven by a rare subpopulation of tumor cells. Much of the supporting evidence for this intriguing idea is derived from xenotransplantation experiments in which human leukemia cells are grown in immunocompromised mice. We show that, when lymphomas and leukemias of mouse origin are transplanted into histocompatible mice, a very high frequency (at least 1 in 10) of the tumor cells can seed tumor growth. We suggest that the low frequency of tumor-sustaining cells observed in xenotransplantation studies may reflect the limited ability of human tumor cells to adapt to growth in a foreign (mouse) milieu.
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PMID:Tumor growth need not be driven by rare cancer stem cells. 1807 85

Effective strategies are lacking for the management of urinary bladder cancer for which smoking is a potential risk factor. Herein, we evaluated chemoprevention of urinary bladder cancer by natural chemopreventive agents, silymarin and silibinin, in a preclinical animal (ICR mouse) model of bladder cancer induced by tobacco smoke carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN). Mice were fed p.o. with saline or OH-BBN (0.05%, w/v) in drinking water for 6 weeks or with silymarin or silibinin (200 mg/kg body weight for both) starting 1 week before OH-BBN exposure for 51 weeks. Silymarin and silibinin strongly arrested OH-BBN-induced tumor progression at the stage of mucosal dysplasia with a striking reduction in papillary nodular dysplasia as well as invasive carcinoma. Some silymarin- or silibinin-treated mice developed no urothelial lesions in spite of OH-BBN exposure. Immunohistochemical analyses at study conclusion revealed that silymarin and silibinin decreased cell proliferation by 42% (P < 0.001) and 44% (P < 0.001) and increased apoptosis by 4-fold (P < 0.05) and 6-fold (P < 0.05) in OH-BBN-induced urothelium, respectively. Antiproliferative and apoptotic effects of silymarin and silibinin were associated with decreases in (a) cyclin D1 protein level and extracellular signal-regulated kinase-1/2 phosphorylation and in (b) protein levels of survivin and nuclear phospho-p65 (Ser(276) and Ser(536)), respectively. Together, these results suggest that silymarin and silibinin inhibit chemically induced urinary bladder tumor growth and progression possibly by inhibiting cell proliferation and enhancing apoptosis.
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PMID:Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in male ICR mice. 1808 18

Tumor cells can stimulate matrix metalloproteinase (MMP) production by stromal cells through cell-cell interactions mediated by cell adhesion molecules such as extracellular matrix metalloproteinase inducer (human CD147/EMMPRIN, mouse CD147/Basigin). This study sought to characterize whether specific tumor-stromal cell interactions mediated by CD147 promote colon cancer growth by utilizing small interfering (si)RNAs directed against human CD147/EMMPRIN or mouse CD147/Basigin in co-cultures of cancer cells with macrophages and fibroblasts and established human SW620 colon cancer xenograft models in immune deficient mice. We show that blockade of host (mouse) CD147/Basigin expression, but not cancer cell-derived CD147/EMMPRIN, suppresses tumor growth in human colon cancer xenografts. Experiments in vitro indicated that colon cancer cell-stromal cell interactions mediated by CD147 lead to increased MMP-2 expression in fibroblasts but not macrophages. Furthermore, expression of host VEGF-A in both fibroblasts and macrophages is independent of CD147 in vitro and in vivo. Interestingly, inhibition of cancer cell-derived EMMPRIN leads to increased MMP-9 levels in vivo. Our findings provide new insights into CD147-mediated tumor-host interactions mediating colon cancer growth.
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PMID:Host CD147 blockade by small interfering RNAs suppresses growth of human colon cancer xenografts. 1850 6

The honeybee product propolis and its extracts are known to have biological effects such as antibiotic, anti-viral, anti-inflammatory and anti-tumor activities. This study was designed to investigate whether water-soluble propolis (WSP) inhibits tumor growth. The tumor cell line used was mouse sarcoma 180 (S-180), and its growth was determined in vitro and in vivo with exposure to different concentrations of WSP. The effects of WSP on tumor cells in vitro were evaluated by measuring the intracellular uptake of 3H-thymidine. 3H-thymidine uptake was inhibited in accordance with the concentration of WSP. The minimum concentration of WSP necessary for 3H-thymidine uptake inhibition was 1.0 microg/ml and uptake was suppressed to 88% of the level in non-treated cells at this concentration. In an experiment using tumor-bearing mice, oral administration of WSP was begun 24 hours after transplantation of S-180 cells. WSP was administered to the mice 5 times, every other day for 10 days. The doses were 320 mg/kg (10 mg/mouse) or 960 mg/kg (30 mg/mouse) of body weight. All mice were sacrificed 10 days after transplantation, and tumor growth was evaluated. The orally administered WSP significantly inhibited the growth of transplanted tumors (p < 0.05). Furthermore, histological findings revealed a significant reduction in mitotic cells and tumor invasion of the muscular tissue at both dose-levels of WSP.
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PMID:Anti-tumor effects of water-soluble propolis on a mouse sarcoma cell line in vivo and in vitro. 1854 94

Guggulsterone (GUG), a resin of the Commiphora mukul tree, has been used in ayurvedic medicine for centuries to treat a variety of ailments. Recent studies have suggested that GUG may also possess anticancer effects. In the present study, we show that GUG possesses antitumor-promoting effects in SENCAR mouse skin tumorigenesis model. We first determined the effect of topical application of GUG to mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of GUG (1.6 micromol per mouse) 30 min prior to TPA (3.2 nmol per mouse) application onto the skin of mice afforded significant inhibition against TPA-mediated increase in skin edema and hyperplasia. Topical application of GUG was also found to result in substantial inhibition against TPA-induced epidermal (i) ornithine decarboxylase (ODC) activity; (ii) ODC, cyclooxygenase-2 and inducible nitric oxide synthase protein expressions; (iii) phosphorylation of extracellular signal-regulated kinase 1/2, c-jun N-terminal kinases and p38; (iv) activation of NF-kappaB/p65 and IKK alpha/beta and (v) phosphorylation and degradation of I kappaB alpha. We next assessed the effect of topically applied GUG on TPA-induced skin tumor promotion in 7,12-dimethyl benz[a]anthracene-initiated mice. Compared with non-GUG-pretreated mice, animals pretreated with GUG showed significantly reduced tumor incidence, lower tumor body burden and a significant delay in the latency period for tumor appearance from 5 to 11 weeks. These results provide the first evidence that GUG possesses anti-skin tumor-promoting effects in SENCAR mice and inhibits conventional as well as novel biomarkers of tumor promotion. In summary, GUG could be useful for delaying tumor growth in humans.
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PMID:Guggulsterone modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in SENCAR mice. 1868 29

Lung cancer is the most common form of cancer in the world, and 90% of patients die from their disease. The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. Accordingly, we investigated the anticancer activity of the ACE inhibitor, captopril, in athymic mice injected with highly tumorigenic LNM35 human lung cells as xenografts. Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P= 0.088). There were no undesirable effects of captopril treatment on animal behavior and body weight. In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31). Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer.
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PMID:Captopril as a potential inhibitor of lung tumor growth and metastasis. 1883 85

The tolerance of BALB/c mice to different doses of blank and cisplatin-loaded PLGA-mPEG nanoparticles and the in vivo anticancer activity of these nanoparticles on SCID mice xenografted with colorectal adenocarcinoma HT 29 cells were investigated. Nanoparticles with an average size of 150-160 nm and approximately 2% w/w cisplatin content were prepared by a modified emulsification and solvent evaporation method. Normal BALB/c mice tolerated three weekly intravenous injections of a relatively high dose of blank PLGA-mPEG nanoparticles (500 mg/kg, equivalent to about 10mg nanoparticles/mouse) and three weekly intravenous injections of a high dose of nanoparticle-entrapped cisplatin (10 mg/kg). Also, histopathology examination indicated that there were no differences in the kidneys or spleens from animals treated with cisplatin-loaded nanoparticles or blank nanoparticles compared to the untreated control group. A moderate granulation of protoplasm of hepatic cells was observed in the livers from mice treated with cisplatin-loaded nanoparticles and blank nanoparticles, however, both the hepatic lobe and the portal hepatis maintained their normal architecture. The cisplatin-loaded PLGA-mPEG nanoparticles appeared to be effective at delaying tumor growth in HT 29 tumor-bearing SCID mice. The group of mice treated with cisplatin-loaded nanoparticles exhibited higher survival rate compared to the free cisplatin group. The results justify further evaluation of the in vivo antitumor efficacy of the PLGA-mPEG/cisplatin nanoparticles.
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PMID:In vivo investigation of tolerance and antitumor activity of cisplatin-loaded PLGA-mPEG nanoparticles. 1892 49

Exosomes (EXOs) derived from tumor cells have been used to stimulate antitumor immune responses. It has been demonstrated that EXO released by tumor cells engineered to express cytokines are of enhanced stimulatory effect on CD8(+) cytotoxic T-lymphocyte (CTL) responses and antitumor immunity. J558 is a mouse myeloma cell line expressing tumor antigen P1A. In this study, we purified EXO(TNF-a), EXO(IL-2), and EXO(IFN-gamma) released by three cytokine-gene (TNF-alpha, IL-2 and IFN-gamma)-engineered J558 (J558(TNF-a), J558(IL-2) and J558(IFN-gamma)) tumor cell lines from their culture supernatants, respectively, by differential ultracentrifugation. These EXOs showed a "saucer" or round shape with a diameter between 50 and 90 nm by electron microscopy and contained EXO-associated proteins, such as LAMP-1 and AIP1, but not lysate-associated protein galectin, by Western blot analysis. EXO displayed expression of molecules (H-2K(d), CD54, and P1A) similarly to, but to a lesser extent to, J558 tumor cells. We then compared the stimulatory effect of these EXOs on P1A-specific CD8(+) CTL responses and antitumor immunity 6 days subsequent to intravenous (i.v.) EXO immunization (30 microg/each BALB/c mouse). We demonstrated that EXO(TNF-alpha) immunization was able to induce more efficient P1A-specific CD8(+) T-cell response accounting for 0.62% of the total CD8(+) T-cell population, using PE-H-2K(d)/P1A peptide and FITC-CD8 staining by flow cytometric analysis then EXO(IL-2) (0.31%) and EXO(IFN-gamma) (0.22%) immunization (P < 0.05), respectively, at day 6 after immunization. EXO(IL-2) and EXO(IFN-gamma) vaccine (i.v. 30 microg/each mouse) only protected 3 of 8 (38%) and 2 of 8 (25%) mice from tumor growth after subcutaneous (s.c.) challenging of immunized mice with J558 tumor cells (0.5 x 10(6) cells/each mouse), whereas EXO(TNF-alpha) immunization protected all 8 of 8 (100%) mice from tumor growth (P < 0.05). Taken together, we demonstrate that EXO(TNF-a) released by engineered J558(TNF-a) tumor cells more efficiently stimulate tumor antigen P1A-specific CD8(+) CTL responses and antitumor immunity than EXO(IL-2) and EXO(IFN-gamma) released by engineered J558(IL-2) and J558(IFN-gamma) tumor cells. Therefore, TNF-alpha-expressing tumor cell-released EXO may represent a more effective EXO-based vaccine in the induction of antitumor immunity.
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PMID:Tumor necrosis factor gene-engineered J558 tumor cell-released exosomes stimulate tumor antigen P1A-specific CD8+ CTL responses and antitumor immunity. 2018 93


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