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

A Comprehensive Review on the State of the Art of Breast Cancers in Italy

: Breast cancer (BC) currently represents one of the most prevalent cancers among women worldwide and the leading cause of cancer death among women, also negatively affecting the quality of life (QoL) in patients. Over the past two decades, BC research has led to extraordinary advances in our understanding of the disease, resulting in more effective treatments. However, its occurrence is still increasing. Several new treatments are now under development worldwide, but they are not devoid of well-- known side effects, and a great number of patients develop endocrine resistance. Nevertheless, the design and synthesis of more suitable strategies and new drugs to treat breast cancers, overcome resistance and side effects, and obtain better therapeutic outcomes are needed. In this review, we summarize the therapies and the clinical studies currently ongoing in Italy for the treatment of BCs, mainly HER2+ MBC, HER2-low MBC, and TNBC, focusing on the most recent ones, also in consideration of diverse facets, including some aspects related to QoL. Finally, some studies related to the usefulness of physical activity in BC will be cited

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

Use of Antimicrobial Irrigation and Incidence of Capsular Contracture in Breast Augmentation and Immediate Implant Based Breast Reconstruction

t Capsular contracture (CC) is one of the most common complications of implant-based breast reconstruction or augmentation surgery. Common risk factors of CC include biofilm, surgical site infections, history of prior CC or fibrosis, history of radiation therapy, and implant characteristics. Though bacterial contamination of breast protheses is associated with adverse sequelae, there are not universally accepted guidelines and limited best practice recommendations for antimicrobial breast pocket irrigation. Despite advanced molecular biology, the exact mechanism of this complication is not fully understood. Interventions that decrease the rate of CC include antibiotic prophylaxis or irrigation, acellular dermal matrix, leukotriene inhibitors, surgical techniques, and others. However, there is inconsistent evidence supporting these risk factors, and the current data was based on broad heterogeneous studies. The objective of this review was to provide a summary of the current data of contributing risk factors as well as preventative and treatment measures for CC