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1.
Genistein reduces proliferation of EP3-expressing melanoma cells through inhibition of PGE2-induced IL-8 expression.
Venza, I, Visalli, M, Oteri, R, Beninati, C, Teti, D, Venza, M
International immunopharmacology. 2018;:86-95
Abstract
Genistein, a natural isoflavone found in soybean products, is considered as a powerful anti-cancer agent, although the involved mechanisms are not fully understood. There is a growing body of evidence that, among the genes inhibited by genistein and responsible for cell cycle progression, invasion, metastasis, and angiogenesis, IL-8 occupies a relevant place. On the other hand, it is equally well documented that IL-8 is upregulated by prostaglandin E2 (PGE2) in different pathological conditions, particularly in neoplastic disease. Here we investigated whether genistein could affect cell growth in a panel of oral, uveal and cutaneous melanoma cell lines by interfering with basal or PGE2-induced IL-8 production. To this end, experiments were performed to evaluate the effect of PGE2 treatment on IL-8 levels, the expression and the role of PGE2 receptors and whether genistein could be able to interfere with these events. Finally, it was evaluated whether the inhibition of oral, uveal and cutaneous melanoma cell proliferation in the presence of genistein could be related to a reduction of IL-8 levels. We show that PGE2 enhances IL-8 synthesis via the EP3 receptor and that genistein is able to down-regulate the latter, as well as to decrease IL-8 mRNA and protein expression, thereby inhibiting oral, uveal and cutaneous melanoma cell proliferation. Taken together, our data provide new insights into the anti-cancer properties of genistein by showing that this flavonoid may affect the development and growth of melanoma at oral, uveal and cutaneous sites. Moreover, these results provide evidence that genistein may exert its therapeutic activity through its ability to prevent PGE2-mediated IL-8 induction.
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2.
Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use.
Mujtaba, S, Bostick, RM
European journal of gastroenterology & hepatology. 2018;(11):1318-1326
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Abstract
OBJECTIVE Because multiple observational studies and large, randomized controlled trials indicate that NSAIDs strongly reduce the risk of colorectal neoplasms, we investigated whether NSAID use masks associations of various other risk factors with colorectal neoplasms. MATERIALS AND METHODS Using pooled data from three case-control studies of incident, sporadic colorectal adenoma (pooled n=789 cases, 2035 polyp-free controls), using multivariable logistic regression, we investigated various risk factor-colorectal adenoma associations stratified by NSAID use. RESULTS Example multivariable-adjusted odds ratios [95% confidence intervals (CI)] for those in the highest relative to the lowest quartiles of exposure, by regular nonaspirin NSAID nonuse/use, respectively, were 1.57 (95% CI: 0.96-2.55) versus 1.14 (95% CI: 0.37, 3.49) for total fat, 1.37 (95% CI: 0.86-2.18) versus 0.70 (95% CI: 0.23-2.25) for saturated fat, 0.93 (95% CI: 0.68-1.28) versus 1.30 (95% CI: 0.61-2.75) for calcium, 0.89 (95% CI: 0.64-1.23) versus 1.38 (95% CI: 0.65-2.94) for total fruits and vegetables, and 0.85 (95% CI: 0.65-1.11) versus 0.94 (95% CI: 0.52-1.71) for physical activity. For current versus never smokers, the odds ratios (95% CIs) among regular non-NSAID users/nonusers were 2.91 (95% CI: 2.22-3.82) versus 1.75 (95% CI: 0.90-3.41), respectively, and for those who were obese versus those who were normal weight, they were 1.67 (95% CI: 1.28-2.17) versus 1.19 (95% CI: 0.69-2.04), respectively. CONCLUSION Our findings suggest that regular nonaspirin NSAID use may mask, beyond simple confounding, associations of major risk factors with colorectal adenoma, and support routinely assessing such associations stratified by regular nonaspirin NSAID use.
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[Efficacy of lycopene intake in primary prevention of prostate cancer: a systematic review of the literature and meta-analysis.].
Cataño, JG, Trujillo, CG, Caicedo, JI, Bravo-Balado, A, Robledo, D, Mariño-Alvarez, AM, Pedraza, A, Arcila, MJ, Plata, M
Archivos espanoles de urologia. 2018;(2):187-197
Abstract
OBJECTIVE To evaluate the efficacy of lycopene intake in primary prevention of prostate cancer (PCa). METHODS A systematic search of the literature was conducted in March 2015 and the articles published between the years 1990-2015 were reviewed. The following search terms were used: prostate cancer, prostatic neoplasm, lycopene, prevention, effectiveness and efficacy (MeSH). Publications including research in humans, written in English and whose texts were accessible were reviewed. The types of studies included were: clinical trials, cohort and case-control studies. We found 343 articles; of these, 27 were included in the systematic review. After the latter were rigorously analyzed, 23 were included in the meta-analysis using the pooled odds ratios (OR) and risk ratios (RR) of case-control and cohort studies, respectively, and their confidence intervals (95% CI), using random-effects models with Review Manager 5.2. RESULTS Out of the 27 articles included in the systematic review, 22 were case-control and 5 were cohort studies. For the case-control studies, the total number of patients with PCa was 13,999 and the total number of controls 22,028. Cohort studies included 187,417 patients and PCa was diagnosed in 8,619 of these. The metaanalysis determined an OR = 0.94 (IC 95% 0.89-1.00) and RR = 0.9 (IC 95% 0.85-0.95) of PCa related with lycopene and/or raw or cooked tomatoes intake. CONCLUSIONS Although our study found that there is a statistically significant inverse association between lycopene intake and PCa, the magnitude of this association is weak and comes solely from observational studies, which do not allow recommending its use as a standard of practice. High-quality randomized clinical trials are required to clarify current evidence.
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Anticarcinogenic activities of sulforaphane are influenced by Nerve Growth Factor in human melanoma A375 cells.
Arcidiacono, P, Stabile, AM, Ragonese, F, Pistilli, A, Calvieri, S, Bottoni, U, Crisanti, A, Spaccapelo, R, Rende, M
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2018;:154-161
Abstract
Melanoma is a severe form of cancer, resistant to conventional therapies. According to in vitro studies, sulforaphane, a dietary component, has been considered a promising antineoplastic candidate. The present study analyzes the in vitro biological effects of sulforaphane in A375 melanoma cell line with or without the addition of Nerve Growth Factor. For the first time, our results show that a supplementation of Nerve Growth Factor partially reverses the sulforaphane-induced: i) inhibition of cell migration, ii) pro apoptotic changes in cell cycle and iii) modulation of active caspase-3. Furthermore, we report the sulforaphane-induced modulation in the expression of Nerve Growth Factor receptors TrKA and p75NTR, shifting their ratio from pro survival to pro apoptotic. In conclusion, the present study evidences that in vivo the antineoplastic effects of sulforaphane may be reduced by the contemporaneous presence of other biological elements such as Nerve Growth Factor and it contributes to a better definition of the real in vivo potentiality of sulforaphane as antineoplastic candidate.
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[Aspirin and colorectal cancer].
Grancher, A, Michel, P, Di Fiore, F, Sefrioui, D
Bulletin du cancer. 2018;(2):171-180
Abstract
Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation.
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Chemoprevention of Skin Carcinomas in High-Risk Transplant Recipients.
Savoia, P, Zavattaro, E, Cremona, O
Current medicinal chemistry. 2018;(6):687-697
Abstract
BACKGROUND Long-term immunosuppressive therapy, as provided to solid organ transplant recipients, inevitably results in a significant inhibition of immune defenses; this leads to frequent skin infections and malignancies, which represent an important cause of morbidity and mortality for transplanted patients. The incidence and risk of skin carcinomas are elevated in solid organ transplant recipients in comparison with the general population, with a 10-fold increased risk for basal cell carcinoma and a 50-100-fold for squamous cell carcinoma. The schedule of immunosuppressive drugs influences the type and timing of skin malignancies, but a crucial role is also played by endogenous and exogenous risk factors. METHODS & RESULTS Here, we will review the state-of-the-art in chemoprevention of epidermal carcinomas in order to provide useful information for clinicians involved in the management of transplant recipients. One-hundred and forteen paper, published on peerreviewed journals, has been included. CONCLUSION Chemoprevention would be key in controlling skin carcinogenesis in high-risk patients.
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Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis.
Applegate, CC, Rowles, JL, Ranard, KM, Jeon, S, Erdman, JW
Nutrients. 2018;(1)
Abstract
Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, accounting for 15% of all cancers in men worldwide. Asian populations consume soy foods as part of a regular diet, which may contribute to the lower PCa incidence observed in these countries. This meta-analysis provides a comprehensive updated analysis that builds on previously published meta-analyses, demonstrating that soy foods and their isoflavones (genistein and daidzein) are associated with a lower risk of prostate carcinogenesis. Thirty articles were included for analysis of the potential impacts of soy food intake, isoflavone intake, and circulating isoflavone levels, on both primary and advanced PCa. Total soy food (p < 0.001), genistein (p = 0.008), daidzein (p = 0.018), and unfermented soy food (p < 0.001) intakes were significantly associated with a reduced risk of PCa. Fermented soy food intake, total isoflavone intake, and circulating isoflavones were not associated with PCa risk. Neither soy food intake nor circulating isoflavones were associated with advanced PCa risk, although very few studies currently exist to examine potential associations. Combined, this evidence from observational studies shows a statistically significant association between soy consumption and decreased PCa risk. Further studies are required to support soy consumption as a prophylactic dietary approach to reduce PCa carcinogenesis.
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8.
Oleocanthal and oleacein contribute to the in vitro therapeutic potential of extra virgin oil-derived extracts in non-melanoma skin cancer.
Polini, B, Digiacomo, M, Carpi, S, Bertini, S, Gado, F, Saccomanni, G, Macchia, M, Nieri, P, Manera, C, Fogli, S
Toxicology in vitro : an international journal published in association with BIBRA. 2018;:243-250
Abstract
Although the anticancer properties of extra virgin olive oil (EVOO) extracts have been recognized, the role of single compounds in non-melanoma skin cancer is still unknown. The in vitro chemopreventive and anticancer action of EVOO extracts and oil-derived compounds in non-melanoma skin cancer models were evaluated on cutaneous squamous cell carcinoma cells and on immortalized human keratinocytes stimulated with epidermal growth factor. Preparation of EVOO extracts and isolation of single compounds was carried out by chromatographic methods. Antitumor activity was assessed by cell-based assays (cell viability, migration, clonogenicity, and spheroid formation) and apoptosis documented by internucleosomal DNA fragmentation. Finally, inhibition of key oncogenic signaling nodes involved in the progression from actinic keratosis to cutaneous squamous cell carcinoma was studied by western blot. EVOO extracts reduced non-melanoma skin cancer cell viability and migration, prevented colony and spheroid formation, and inhibited proliferation of atypical keratinocytes stimulated with epidermal growth factor. Such a pharmacological activity was promoted by oleocanthal and oleacein through the inhibition of Erk and Akt phosphorylation and the suppression of B-Raf expression, whereas tyrosol and hydroxytyrosol did not have effect. The current study provides in vitro evidence for new potential clinical applications of EVOO extracts and/or single oil-derived compounds in the prevention and treatment of non-melanoma skin cancers.
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Colorectal Cancer: Causes and Evidence of Chemopreventive Treatments.
Pérez-Escalante, E, Cariño-Cortés, R, Fernández-Martínez, E, Ortiz, MI, Muñoz-Pérez, VM, Sánchez-Crisóstomo, I, Jiménez-Ángeles, L
Current pharmaceutical biotechnology. 2018;(14):1135-1155
Abstract
Colorectal cancer (CRC) is the second and third most frequent cancer in women and men, respectively; indeed, CRC is placed as the fourth world's most deadly cancer (after lung, liver, and stomach cancer). The incidence of CRC is strongly influenced by nutrition and the high fat/high carbohydrate Western-style diet. CRC is one of the most intensively studied cancer types, partly because of its high prevalence, but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently serrated adenomas. The morphological steps in the adenomacarcinoma sequence have been elucidated at a molecular level, which allow the identification of the genes responsible for CRC. Review and Conclusions: The main aim of this review is to provide data regarding the pathophysiological characteristics, molecular mechanisms as well as carcinogenic and chemopreventive agents for CRC, with emphasis on evidence supporting their efficacy. These compounds may modulate multiple signaling pathways involved in cell proliferation and apoptosis in transformed cells, they also enhance the host immune system and favor an effective treatment. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials. The mechanistic spectrum and specificity of the action of phytochemicals represent a complex and evolving field of research.
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The association between green tea consumption and breast cancer risk: A systematic review and meta-analysis.
Najaf Najafi, M, Salehi, M, Ghazanfarpour, M, Hoseini, ZS, Khadem-Rezaiyan, M
Phytotherapy research : PTR. 2018;(10):1855-1864
Abstract
This systematic review and meta-analysis aimed to critically evaluate the relation between green tea (GT) consumption and the risk of breast cancer. Popular electronic databases were systematically searched for papers in English language. All case-control and cohort studies in addition to randomized clinical trials were included if they assessed the chemopreventive effects of GT on breast cancer. The quality of included studies was assessed using the Newcastle-Ottawa and Jadad scale. This systematic review comprised 14 studies: 9 case-control studies, 4 cohort studies, and 1 clinical trial. Odds ratio (OR) in case-control studies suggested that women in the group receiving the highest level of GT had 19% reduction in breast cancer risk compared with those who received the lowest level of GT (summary OR = 0.81, p = .031; 95% CI [0.66, 0.981]; heterogeneity, I2 = 71.53, p < .001, random effect model; 9 studies). OR in cohort studies also showed no significant difference (OR = 0.99, p = .94; 95% CI [0.81, 1.138]; heterogeneity, I2 = 19.06, p = .29; fixed-effect model; 4 studies). According to the only clinical trial, treatment with GT could not alter the mammographic density compared with placebo (26% vs. 25%). It cannot be concluded that GT consumption may decrease the risk of breast cancer. Due to high heterogeneity, a pooled analysis of case-control and cohort studies was not performed.