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Leukoplakia and Immunology: New Chemoprevention Landscapes?
Grigolato, R, Bizzoca, ME, Calabrese, L, Leuci, S, Mignogna, MD, Lo Muzio, L
International journal of molecular sciences. 2020;(18)
Abstract
Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological derangements upon histological analysis. Among them, oral leukoplakia is the most common type of these disorders. This work aims to analyze the possible use of drugs such as immunochemopreventive agents for OPMDs. Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to malignant form. Experimental and in vivo data offer us the promise of molecular prevention through immunomodulation; however, currently, there is no evidence for the efficacy of these drugs in the chemoprevention action. Alternative ways to deliver drugs, combined use of molecules with complementary antitumor activities, diet influence, and better definition of individual risk factors must also be considered to reduce toxicity, improve compliance to the protocol treatment and offer a better individualized prevention. In addition, we must carefully reconsider the mode of action of many traditional cancer chemoprevention agents on the immune system, such as enhancing immunosurveillance and reversing the immune evasion. Several studies emphasize the concept of green chemoprevention as an alternative approach to accent healthy lifestyle changes in order to decrease the incidence of HNSCC.
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Mechanisms of action of vitamin D in colon cancer.
Ferrer-Mayorga, G, Larriba, MJ, Crespo, P, Muñoz, A
The Journal of steroid biochemistry and molecular biology. 2019;:1-6
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Abstract
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.
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Molecular Mechanisms Underlying Cancer Preventive and Therapeutic Potential of Algal Polysaccharides.
Sajadimajd, S, Momtaz, S, Haratipour, P, El-Senduny, FF, Panah, AI, Navabi, J, Soheilikhah, Z, Farzaei, MH, Rahimi, R
Current pharmaceutical design. 2019;(11):1210-1235
Abstract
BACKGROUND Algal polysaccharide and oligosaccharide derivatives have been shown to possess a variety of therapeutic potentials and drug delivery applications. Algal polysaccharides contain sulfated sugar monomers derived from seaweed including brown, red, and green microalgae. Here, in this review, the recent progress of algal polysaccharides' therapeutic applications as anticancer agents, as well as underlying cellular and molecular mechanisms was investigated. Moreover, recent progress in the structural chemistry of important polysaccharides with anticancer activities were illustrated. METHODS Electronic databases including "Scopus", "PubMed", and "Cochrane library" were searched using the keywords "cancer", or "tumor", or "malignancy" in title/abstract, along with "algae", or "algal" in the whole text until July 2018. Only English language papers were included. RESULTS The most common polysaccharides involved in cancer management were sulfated polysaccharides, Fucoidans, Carageenans, and Ulvan from different species of algae that have been recognized in vitro and in vivo. The underlying anticancer mechanisms of algal polysaccharides included induction of apoptosis, cell cycle arrest, modulation of transduction signaling pathways, suppression of migration and angiogenesis, as well as activation of immune responses and antioxidant system. VEGF/VEGFR2, TGFR/Smad/Snail, TLR4/ROS/ER, CXCL12/ CXCR4, TGFR/Smad7/Smurf2, PI3K/AKT/mTOR, PBK/TOPK, and β-catenin/Wnt are among the main cellular signaling pathways which have a key role in the preventive and therapeutic effects of algal polysaccharides against oncogenesis. CONCLUSION Algal polysaccharides play a crucial role in the management of cancer and may be considered the next frontier in pharmaceutical research. Further well-designed clinical trials are mandatory to evaluate the efficacy and safety of algal polysaccharides in patients with cancer.
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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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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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[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.