Neurokinin-1 Receptor (NK-1R) Antagonists as a New Strategy to Overcome Cancer Resistance

Nowadays, the identification of new therapeutic targets that allow for the development of treatments, which as monotherapy, or in combination with other existing treatments can contribute to improve response rates, prognosis and survival of oncologic patients, is a priority to optimize healthcare within sustainable health systems. Recent studies have demonstrated the role of Substance P (SP) and its preferred receptor, Neurokinin 1 Receptor (NK-1R), in human cancer and the potential antitumor activity of NK-1R antagonists as an anticancer treatment. In this review, we outline the relevant studies published to date regarding the SP/NK-1R complex as a key player in human cancer and also evaluate if the repurposing of already marketed NK-1R antagonists may be useful in the development of new treatment strategies to overcome cancer resistanceThe researcher Marilina García-Aranda is the benefactor of a postdoctoral contract financed by the European Social Fund—Operational Program of Andalusia 2014–2020 for the “Incorporation of Research Personnel with a PhD degree in the field of Health Sciences and Technologies in R&D and Innovation Centers of the Public Health System of Andalusia” (RH-0055-2020). This work was partially supported by grant from the University of Malaga—Consejería de Transformación Económica, Industria, Conocimiento y Universidades—Junta de Andalucia (UMA20-FEDERJA-161). Partial funding for open access charge: Universidad de Málag

Calcium Homeostasis in the Development of Resistant Breast Tumors.

Cancer is one of the main health problems worldwide. Only in 2020, this disease caused more than 19 million new cases and almost 10 million deaths, with breast cancer being the most diagnosed worldwide. Today, despite recent advances in breast cancer treatment, a significant percentage of patients will either not respond to therapy or will eventually experience lethal progressive disease. Recent studies highlighted the involvement of calcium in the proliferation or evasion of apoptosis in breast carcinoma cells. In this review, we provide an overview of intracellular calcium signaling and breast cancer biology. We also discuss the existing knowledge on how altered calcium homeostasis is implicated in breast cancer development, highlighting the potential utility of Ca2+ as a predictive and prognostic biomarker, as well as its potential for the development of new pharmacological treatments to treat the disease.Partial funding for open access charge: Universidad de Málaga

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an adaptive antioxidant and anti-inflammatory response, which could be potentially useful in the management of CIPN. (2) Methods: The aims of this works are: (a) to summarize the potential mechanisms that could induce CIPN by the most relevant drugs (platinum, taxanes, vinca alkaloids, and bortezomib), with particular focus on the role of oxidative stress; (b) to summarize the current situation of prophylactic and treatment approaches; (c) to describe the action mechanisms of ozone therapy to modify oxidative stress and inflammation with its potential repercussions for CIPN; (d) to describe related experimental and clinical reports with ozone therapy in chemo-induced neurologic symptoms and CIPN; and (e) to show the main details about an ongoing focused clinical trial. (3) Results: A wide background relating to the mechanisms of action and a small number of experimental and clinical reports suggest that ozone therapy could be useful to prevent or improve CIPN. (4) Conclusions: Currently, there are no clinically relevant approaches for the prevention and treatment of stablished CIPN. The potential role of ozone therapy in this syndrome merits further research. Randomized controlled trials are ongoing

Validation and comparison of instruments to identify frail patientes in primary care settings: Study protocol

International audienceBACKGROUND:In the last few years several indices and tools, aimed at identifying frail subjects in various care settings have been developed. However, to date none of them has been incorporated into usual practice in the primary care setting. The purposes of this study are: 1) to evaluate the predictive capacity of the Tilburg Frailty Indicator (TFI), the Gérontopôle Frailty Screening Tool (GFST) and the KoS model together with two biomarker levels (SOX2 and p16INK4a) for adverse events related to frailty; 2) to determine differences in the use of healthcare services according to frailty.METHODS/DESIGN:Prospective multicentre cohort study with a 2-year follow-up. The study will be performed in primary care centres of Gipuzkoa and Costa del Sol, both located in Spain. Autonomous, non-institutionalized individuals aged 70 and over that agree to participate in this study will constitute the study population. A total of 900 individuals will be randomly selected from the healthcare administrative data bases of the participating health services. Data will be collected at baseline and at 1 and 2 years. The main independent variables assessed at baseline will be TFI outcomes, GFST and the KoS model, together with the expression of SOX2 and p16INK4a levels. During follow-up, loss of autonomy, the occurrence of death and consumption of healthcare resources will be assessed.DISCUSSION:The main focus of this work is the identification and evaluation of several instruments constructed under different rationales to identify frail subjects in primary care settings. The resulting outcomes have potential for direct application to the primary care practice. Early identification of the onset of functional impairment of elderly is an essential, still unresolved aspect in the prevention of dependence in the scope of primary care