Tomatoes, lycopene-containing foods and cancer risk

Tomatoes, lycopene-containing foods and cancer ris

Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent of HER-2/neu Expression

Double transgenic mice overespressing the transforming rat HER-2/neu oncogene and the mutated p53, with both deminant-negative and a gain-of-function properties, display early aggressive and metastasizing parotid tumors. Multiple acinar and ductal hyperplasia foci overexpressing the HER-2/neu gene product are evident at wk 5 and progress to poorly differentiated carcinoma by wk 7. Mice die before wk 18 with invasive carcinomas and multiple metastases that no longer express HER-2/neu. A combination of repeated electroporations of plasmids coding for the extracellular and transmembrane domains of the rat HER-2/neu receptor with systemic IL-12 administrations started when the parotids that present diffuse hyperplasia protected all female and 50% of the male mice until the close of the experiment at wk 40. This combined treatment began when multifocal in situ - carcinomas that were already present cured 33% of the females and 25 % of the males. The most prominent immunologic features associated with the antitumor protection were the production of high titers of anti-HER-2/neu Abs and the nonappearance of cell-mediated cytotoxic reactivity. In conclusion, anti-HER-2/neu vaccination combined with systemic IL-12 control parotid carcinomas as far as p53 mutation makes their growth independent of HER-2/neu expression

Inflammation and breast cancer. Inflammatory component of mammary carcinogenesis in ErbB2 transgenic mice

This review addresses genes differentially expressed in the mammary gland transcriptome during the progression of mammary carcinogenesis in BALB/c mice that are transgenic for the rat neu (ERBB2, or HER-2/neu) oncogene (BALB-neuT664V-E mice). The Ingenuity knowledge database was used to characterize four functional association networks whose hub genes are directly linked to inflammation (specifically, the genes encoding IL-1β, tumour necrosis factor, interferon-γ, and monocyte chemoattractant protein-1/CC chemokine ligand-2) and are increasingly expressed during such progression. In silico meta-analysis in a human breast cancer dataset suggests that proinflammatory activation in the mammary glands of these mice reflects a general pattern of human breast cancer

The Mutyh Base Excision Repair Gene Influences the Inflammatory Response in a Mouse Model of Ulcerative Colitis

BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/-) mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS). The Mutyh(-/-) phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/-) mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/-) mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+) regulatory T cells were observed only in Mutyh(-/-) mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response

Cancer immunoprevention

Immunoprevention is a fresh approach to cancer prevention based on the stimulation of the immune system before tumor onset. Immunoprevention was effective in various models of carcinogen-induced or autochthonous tumor progression. Vaccines made of cells or DNA plasmids combined with appropriate adjuvants completely blocked mammary carcinogenesis in HER-2/neu transgenic mice. At variance with cancer immunotherapy, the mediators of immunoprevention are antibodies and T-cell-derived cytokines, rather than cytotoxic T-cells. Immunopreventive approaches and chemoprevention with tamoxifen or cyclooxygenase-2 inhibitors can be combined advantageously. The success obtained in preclinical studies suggests that cancer immunoprevention should progress to clinical testing

Effects of castration on the development of prostate adenocarcinoma from its precursor HGPIN and on the occurrence of androgen-independent, poorly differentiated carcinoma in TRAMP mice

Androgen ablation is thought to exert selective pressure for the development of androgen-independent forms of prostate cancer. This study was set up to investigate the effects of surgical castration on the development of prostate adenocarcinoma (ADC) from its precursor (high-grade prostate intraepithelial neoplasia (HGPIN)) and on the occurrence of androgen-independent, poorly differentiated carcinoma (PDC) in (C57Bl/6 transgenic adenocarcinoma of mouse prostate) TRAMP mice. It was found that castration cures HGPIN and ADC and prevents their further occurrence and growth, but has no effect on PDC. This indicates that in this model, PDC is not the progression of ADC favoured by androgen ablation and that its initiating cells are different from those of HGPIN and ADC

Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNF-a pathway

© 2018 by The American Society of Hematology. Hemophilic arthropathy (HA) is a debilitating degenerative joint disease that is a major manifestation of the bleeding disorder hemophilia A. HA typically begins with hemophilic synovitis that resembles inflammatory arthritides, such as rheumatoid arthritis, and frequently results in bone loss in patients. A major cause of rheumatoid arthritis is inappropriate release of the proinflammatory cytokine tumor necrosis factor-a (TNF-a) by the TNF-a convertase (TACE; also referred to as ADAM17) and its regulator, iRhom2. Therefore, we hypothesized that iRhom2/ADAM17-dependent shedding of TNF-a also has a pivotal role in mediating HA. Here, we show that addition of blood or its components to macrophages activates iRhom2/ADAM17-dependent TNF-a shedding, providing the premise to study the activation of this pathway by blood in the joint in vivo. For this, we turned to hemophilic FVIII-deficient mice (F82/2mice), which develop a hemarthrosis following needle puncture injury with synovial inflammation and significant osteopenia adjacent to the affected joint. We found that needle puncture–induced bleeding leads to increased TNF-a levels in the affected joint of F82/2 mice. Moreover, inactivation of TNF-a or iRhom2 in F82/2 mice reduced the osteopenia and synovial inflammation that develops in this mouse model for HA. Taken together, our results suggest that blood entering the joint activates the iRhom2/ ADAM17/TNF-a pathway, thereby contributing to osteopenia and synovitis in mice. Therefore, this proinflammatory signaling pathway could emerge as an attractive new target to prevent osteoporosis and joint damage in HA patients

Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study

The role of tissue transglutaminase (TG-2, TGase-2) in cancer development is still a fascinating field of research. The available reports do not elucidate fully its mechanism of action, due to the limitations of in vitro approaches. Therefore, to understand TG-2 role in cancer, we carried out an in vivo study with a more direct approach. TG-2 was in vivo overexpressed in a murine model of melanoma (intravenous injection of B16 melanoma cells in C57BL/6N mice) by means of a plasmid carrying the TG-2 cDNA. The evaluation of the frequency and size of the metastases indicated that the number of melanoma lung foci was more markedly reduced by TG-2 overexpression than the metastatic size. Then, TG-2 overexpressing mice showed a prolonged survival with respect to control mice. Further analyses were carried by means of proteomic analysis of melanoma cell lysates and meta-analysis of published transcriptomic datasets. Proteomic analysis of cell lysates from a human melanoma cell line compared to human keratinocytes showed significant differences in the expression of TG-2 substrates known to be involved in proliferation/differentiation and cancer progression. Taken together, these findings indicate a protective role of TG-2 enzymatic activity in melanoma progression in vivo

A dietary tomato supplement prevents prostate cancer in tramp mice

Transgenic adenocarcinoma of the mouse prostate (TRAMP) is a model for progressive prostate cancer that mirrors the stages of the human form. In this study, the effects of a diet enriched with processed whole tomatoes on survival, tumorigenesis, and progression of prostate cancer, and the antioxidant and inflammatory status of TRAMP mice were investigated. Tomato diet significantly increased overall survival (P < 0.01), delayed progression from prostatic intraepithelial neoplasia to adenocarcinoma, and decreased the incidence of poorly differentiated carcinoma. Biochemical data disclosed an increase in serum antioxidant activity and a reduction of serum inflammation/angiogenesis biomarkers of particular importance in prostate carcinogenesis