Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer), including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of several diseases, but further investigation is needed to evaluate the real efficacy of these therapeutic interventions. The purpose of this paper is to provide a review of literature on this complex topic of ever increasing interest.

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Oxidative stress, aging, and diseases.

Nrf2 signaling pathway: Pivotal roles in inflammation.

Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress and xenobiotic damage. Activation of Nrf2 signaling induces the transcriptional regulation of ARE-dependent expression of various detoxifying and antioxidant defense enzymes and proteins. Keap1-Nrf2-ARE signaling has become an attractive target for the prevention and treatment of oxidative stress-related diseases and conditions including cancer, neurodegenerative, cardiovascular, metabolic and inflammatory diseases. Over the last few decades, numerous Nrf2 inducers have been developed and some of them are currently undergoing clinical trials. Recently, over-activation of Nrf2 has been implicated in cancer progression as well as in drug resistance to cancer chemotherapy. Thus, Nrf2 inhibitors could potentially be used to improve the effectiveness of cancer therapy. Herein, we review the signaling mechanism of Keap1-Nrf2-ARE pathway, its disease relevance, and currently known classes of small molecule modulators. We also discuss several aspects of Keap1-Nrf2 interaction, Nrf2-based peptide inhibitor design, and the screening assays currently used for the discovery of direct inhibitors of Keap1-Nrf2 interaction.

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Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents.

http://publicationslist.org/data/torsten-bohn/ref-63/Kaulmann_NutrRes_2014.pdf

Carotenoids, inflammation, and oxidative stress—implications of cellular signaling pathways and relation to chronic disease prevention

Natural product compounds have recently attracted significant attention from the scientific community for their potent effects against inflammation-driven diseases, including cancer. A significant amount of research, including preclinical, clinical, and epidemiological studies, has indicated that dietary consumption of polyphenols, found at high levels in cereals, pulses, vegetables, and fruits, may prevent the evolution of an array of diseases, including cancer. Cancer development is a carefully orchestrated progression where normal cells acquires mutations in their genetic makeup, which cause the cells to continuously grow, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Compounds that modulate these oncogenic processes can be considered as potential anti-cancer agents that may ultimately make it to clinical application. Resveratrol, a natural stilbene and a non-flavonoid polyphenol, is a phytoestrogen that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has been reported that resveratrol can reverse multidrug resistance in cancer cells, and, when used in combination with clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic agents. Several novel analogs of resveratrol have been developed with improved anti-cancer activity, bioavailability, and pharmacokinetic profile. The current focus of this review is resveratrol's in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol. This is also accompanied by a comprehensive update of the various clinical trials that have demonstrated it to be a promising therapeutic and chemopreventive agent.

The Role of Resveratrol in Cancer Therapy

Chronic inflammation is a pathological condition characterized by continued active inflammation response and tissue destruction. Many of the immune cells including macrophages, neutrophils and eosinophils are involved directly or by production of inflammatory cytokine production in pathology of chronic inflammation. From literatures, it is appear that there is a general concept that chronic inflammation can be a major cause of cancers and express aging processes. Moreover, many studies suggest that chronic inflammation could have serious role in wide variety of age-related diseases including diabetes, cardiovascular and autoimmune diseases. Inflammatory process induces oxidative stress and reduces cellular antioxidant capacity. Overproduced free radicals react with cell membrane fatty acids and proteins impairing their function permanently. In addition, free radicals can lead to mutation and DNA damage that can be a predisposing factor for cancer and age-related disorders. This article reviews the antioxidant defense systems, free radicals production and their role in cancer and age related diseases and also some of the recent patent relevant to the field. Study of the role of free radicals in human diseases can help the investigators to consider the antioxidants as proper agents in preventive medicine, especially for cancer and aging processes.

Chronic Inflammation and Oxidative Stress as a Major Cause of Age- Related Diseases and Cancer

Reduced efficacy of multiple doses of CpG-matured dendritic cell tumor vaccine in an experimental model.

/pdf/anticancer-dendritic-cell-vaccines-producing-effective-1xtsrtm0qk.pdf

Anticancer Dendritic Cell Vaccines Producing Effective Antitumor T Cell Responses

Immunotherapy in Breast Cancer

During past 50 years many new treatment approaches have been developed. Most of the new modalities are based immunotherapy by either potentiating system nonspecifically or by potentiating specific cytotoxic lymphocytes to destroy tumor cells. Among many therapeutic vaccines tried, dendritic cell-based cancer vaccines have gotten more attention since last decade [1]. Even though there has been some success in a few cancer cases but total remission in a lot of cases have not been achieved [2]. In 1964, Wheelock and Dingle reported that repeated injection of Newcastle Disease Virus (NDV) to a patient suffering from acute lymphoblastic leukemia cured patient [3]. Later on, Csatary reported regression od metastatic colon cancer in a farmer patient following NVD outbreak in chicken farms [4].

https://crimsonpublishers.com/sbb/pdf/SBB.000516.pdf

Nemat Khansari

Papers

Chronic Inflammation and Oxidative Stress as a Major Cause of Age- Related Diseases and Cancer

Reduced efficacy of multiple doses of CpG-matured dendritic cell tumor vaccine in an experimental model.

Anticancer Dendritic Cell Vaccines Producing Effective Antitumor T Cell Responses

Immunotherapy in Breast Cancer

New Hope for Cancer Immunotherapy: Viral Based Cancer Vaccines