Target Therapy in Cancer Treatment: mPGES-1 and PARP

Target therapy is an approach focusing on specific protein or signaling pathways. This therapy is directly aimed to a molecular target such as a receptor, growth factor or enzyme in cancer cells. These targets are used by the tumor cells themselves to obtain uncontrolled proliferation, resistance to traditional therapies and to increase the number of blood vessels in the tissue of origin (neoangiogenesis). A purpose of target therapy may be to counteract the growth and proliferation of cancer cells through the use of drugs or monoclonal antibodies capable of inhibiting the receptor for the epidermal growth factor (EGFR), that is crucial in the process of neo-angiogenesis, protein kinases (PKs), as regulators of cell growth signals and human epidermal growth factor type 2 (HER2), which is essential in stimulating growth and proliferation of cancer cells. Among anticancer drugs, Bevacizumab, a humanised monoclonal antibody produced by recombinant DNA technique, is used for the first-line treatment of metastatic breast cancer, as it inhibits EGFR and the vascular endothelial cell growth factor (VEGF). Abemaciclib, a protein kinase inhibitor drug, is also used for the treatment of the same cancer. In 20-30% of primary breast tumors, the excessive expression of HER2 is observed; thus, HER2 inhibitors may represent another plausible therapy. A potent HER2 inhibitor is the recombinant humanized igG1 monoclonal antibody Trastuzumab, which was first tested in 1992 and is currently used for the treatment of HER2 positive breast cancer. Unfortunately, despite the numerous advances in finding new therapies, patients treated with these drugs often suffer from severe undesirable side effects. Therefore, the search for new therapeutic targets may be desirable. In this paper we analyse particularly two targets studied quite recently: the microsomal prostaglandin E2 synthase type 1 (mPGES-1) and poly (ADP-ribose) polymerase (PARP) proteins

Target Therapy in Cancer Treatment: mPGES-1 and PARP

Target therapy is an approach focusing on specific protein or signaling pathways. This therapy is directly aimed to a molecular target such as a receptor, growth factor or enzyme in cancer cells. These targets are used by the tumor cells themselves to obtain uncontrolled proliferation, resistance to traditional therapies and to increase the number of blood vessels in the tissue of origin (neoangiogenesis). A purpose of target therapy may be to counteract the growth and proliferation of cancer cells through the use of drugs or monoclonal antibodies capable of inhibiting the receptor for the epidermal growth factor (EGFR), that is crucial in the process of neo-angiogenesis, protein kinases (PKs), as regulators of cell growth signals and human epidermal growth factor type 2 (HER2), which is essential in stimulating growth and proliferation of cancer cells. Among anticancer drugs, Bevacizumab, a humanised monoclonal antibody produced by recombinant DNA technique, is used for the first-line treatment of metastatic breast cancer, as it inhibits EGFR and the vascular endothelial cell growth factor (VEGF). Abemaciclib, a protein kinase inhibitor drug, is also used for the treatment of the same cancer. In 20-30% of primary breast tumors, the excessive expression of HER2 is observed; thus, HER2 inhibitors may represent another plausible therapy. A potent HER2 inhibitor is the recombinant humanized igG1 monoclonal antibody Trastuzumab, which was first tested in 1992 and is currently used for the treatment of HER2 positive breast cancer. Unfortunately, despite the numerous advances in finding new therapies, patients treated with these drugs often suffer from severe undesirable side effects. Therefore, the search for new therapeutic targets may be desirable. In this paper we analyse particularly two targets studied quite recently: the microsomal prostaglandin E2 synthase type 1 (mPGES-1) and poly (ADP-ribose) polymerase (PARP) proteins

Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies

Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance

NUTRACEUTICAL FUNCTIONS OF GREEN TEA

Today, the diffusion of neoplastic diseases is a widespread phenomenon. Thus, it is always necessary to identify new molecules able to fight them. In this paper, we will deal with the interesting antineoplastic properties of green tea. We will describe the different and plausible anticancer mechanisms of epigallocatechin gallate (EGCG), the major polyphenol found in green tea, and in particular the biochemical and computational discovery of a new target for the treatment of this disease will be discussed. The bio-active substances present in tea are essentially represented by methylxanthines, as well as by the antioxidant phenolic fraction (flavonoids). Among the other active substances contained in lower concentrations there are vitamins (B, C and K), amino acids (L-theanine) and minerals (aluminium and manganese). Tea extracts, particularly EGCG, could represent the starting point for the potential emergence of new drugs for the treatment of neoplastic diseases. Other activities of tea, as the involvement in neurodegenerative diseases prevention, as well as the antioxidant, antibacterial, antifungal and antiviral effects, will be also briefly described

NUTRACEUTICAL FUNCTIONS OF GREEN TEA

Today, the diffusion of neoplastic diseases is a widespread phenomenon. Thus, it is always necessary to identify new molecules able to fight them. In this paper, we will deal with the interesting antineoplastic properties of green tea. We will describe the different and plausible anticancer mechanisms of epigallocatechin gallate (EGCG), the major polyphenol found in green tea, and in particular the biochemical and computational discovery of a new target for the treatment of this disease will be discussed. The bio-active substances present in tea are essentially represented by methylxanthines, as well as by the antioxidant phenolic fraction (flavonoids). Among the other active substances contained in lower concentrations there are vitamins (B, C and K), amino acids (L-theanine) and minerals (aluminium and manganese). Tea extracts, particularly EGCG, could represent the starting point for the potential emergence of new drugs for the treatment of neoplastic diseases. Other activities of tea, as the involvement in neurodegenerative diseases prevention, as well as the antioxidant, antibacterial, antifungal and antiviral effects, will be also briefly described

Vitamin D in the Prevention, Development and Therapy of Oncological Diseases.

Vitamin D, traditionally known as a fat-soluble essential vitamin, is a precursor of a powerful steroid hormone that regulates a broad spectrum of physiological processes. In addition to its fundamental role in bone metabolism, epidemiological, preclinical and cellular researches in recent decades have revealed that vitamin D can play a considerable role in the prevention of some pathologies, including extra-skeletal ones, such as neoplasms. Vitamin D, as a prohormone, undergoes first hepatic and subsequently renal metabolism to produce a biologically active metabolite, calcitriol or 1α,25-dihydroxyvitamin D or (1,25 (OH)2D), which binds the vitamin D receptor by regulating the expression of several genes involved in bone metabolism and other biological functions. Furthermore, recent studies have revealed that vitamin D can be also metabolized and activated through a non-canonical metabolic pathway catalyzed by CYP11A1, the gene encoding the cholesterol side chain cleavage enzyme or P450scc. The metabolites of vitamin D deriving from the CYP11A1 enzyme have shown antiproliferative and anti-inflammatory activities and are able to promote the differentiation process on neoplastic cells in comparable way or better than calcitriol, thus contributing to its tumor preventive effect. Clinical data have demonstrated that vitamin D has anticancer activity against prostate, colon, and breast cancers. Several molecular mechanisms of vitamin D involved in tumor etiopathogenesis have been proposed that have not yet been fully clarified. Vitamin D may play a key role in preventing the early stage of the neoplastic process by exerting anti-inflammatory, antioxidant defenses and inducing enzymes responsible for repairing DNA damage and could also be involved in mechanisms of inhibition of cell proliferation, induction of cell differentiation, and cell death. In addition, some studies indicate various mechanisms through which vitamin D can quantitatively and qualitatively influence the intestinal microbiota, strongly linked to chronic inflammatory bowel diseases and the development of colon cancer. However, the metabolism and functions of vitamin D are dysregulated in some neoplasms which therefore develop resistance to the antiproliferative effect of vitamin D, and this promotes tumor development and progression. In this review, studies regarding vitamin D in relation to its activity in cancer have been summarized, as long as the metabolic pathways described for vitamin D

Federica Giuzio*, Maria Grazia Bonomo, Alessia Catalano*, Vittoria Infantino, Giovanni Salzano, Magnus Monné, Athina Geronikaki, Anthi Petrou, Stefano Aquaro, Maria Stefania Sinicropi#, Carmela Saturnino#

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is the target of chronic obstructive pulmonary disease (COPD), for which many new compounds have been developed. In this study, phosphodiesterase 4 (PDE4) inhibitors are being investigated. The inhibition of PDE4 enzyme produces antiinflammatory and bronchodilator effects in the lung by inducing an increase in cAMP concentrations. Piclamilast and rolipram are known selective inhibitors of PDE4, which are unfortunately endowed with common side effects, such as nausea and emesis. The selective inhibition of the phosphodiesterase 4B (PDE4B) subtype may represent an intriguing technique for combating this highly contagious disease with fewer side effects. In this article, molecular docking studies for the selective inhibition of the PDE4B enzyme have been carried out on 21 in-house compounds. The compounds were docked into the pocket of the PDE4B catalytic site, and in most cases, they were almost completely superimposed onto piclamilast. Then, in order to enlarge our study, drug-likeness prediction studies were performed on the compounds under study

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy

Natural Products for the Prevention, Treatment and Progression of Breast Cancer

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy