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

Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse dentate gyrus

Neurogenesis persists in certain regions of the adult brain including the subgranular zone of the hippocampal dentate gyrus wherein its regulation is essential, particularly in relation to learning, stress and modulation of mood. Lysophosphatidic acid (LPA) is an extracellular signaling phospholipid with important neural regulatory properties mediated by specific G protein-coupled receptors, LPA1–5. LPA1 is highly expressed in the developing neurogenic ventricular zone wherein it is required for normal embryonic neurogenesis, and, by extension may play a role in adult neurogenesis as well. By means of the analyses of a variant of the original LPA1-null mutant mouse, termed the Malaga variant or “maLPA1-null,” which has recently been reported to have defective neurogenesis within the embryonic cerebral cortex, we report here a role for LPA1 in adult hippocampal neurogenesis. Proliferation, differentiation and survival of newly formed neurons are defective in the absence of LPA1 under normal conditions and following exposure to enriched environment and voluntary exercise. Furthermore, analysis of trophic factors in maLPA1-null mice demonstrated alterations in brain-derived neurotrophic factor and insulin growth factor 1 levels after enrichment and exercise. Morphological analyses of doublecortin positive cells revealed the anomalous prevalence of bipolar cells in the subgranular zone, supporting the operation of LPA1 signaling pathways in normal proliferation, maturation and differentiation of neuronal precursors

Influence of depression on survival of colorectal cancer patients drawn from a large prospective cohort

Objective The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis. Methods This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS-D) at 5 years of follow-up. Survival was analysed using the Kaplan–Meier method and Cox regression models. Results According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21–1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51–0.76), age (>70 years: HR = 3.78; 95% CI: 1.94–7.36), need for help (yes: HR = 1.43; 95% CI: 1.17–1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16–1.82), tumour size (T3–T4: HR = 1.56; 95% CI: 1.22–1.99), nodule staging (N1–N2: HR = 2.46; 95% CI: 2.04–2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55–0.91). Conclusions There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.Funding for open Access charge: Universidad de Málaga / CBUA. This study was supported by public grant from Instituto de Salud Carlos III (PI09/90397, PS09/00314, PS09/00746, PI09/90460, PI/0990490, PI13/01692, PI13/00013, PI18/01181, Pi18/01589) and was co-funded by the European Regional Development fund

Análisis molecular de la expresión de antígenos de histocompatibilidad en el carcinoma broncogénico : relación con parámetros de agresividad tumoral

Reducción altaNosotros hemos estudiado la expresión de antígenos de histocompatibilidad en 115 muestras de carcinomas broncogenicos y su relación con parámetros clinico - patologicos indicadores de agresividad tumoral. Así encontramos que la perdida de expresión de antígenos de histocompatibilidad de clase i, debida a la perdida simultanea de cadena pesada y b2-microglobulina, esta asociada significativamente con la escasa diferenciación celular y la presencia de alteraciones en el contenido de adn celular. Así mismo la presencia de antígenos de clase II sobre las células tumorales se asocia significativamente a los tumores bien diferenciados. Para estudiar los mecanismos de regulación implicados en las alteraciones de los antígenos de histocompatibilidad hemos contado, aparte de los tumores sólidos, con 6 líneas celulares de carcinomas broncogenicos procedentes de la atcc. Hemos encontrado que el desequilibrio de expresión entre las moléculas hla-a y hla-b presente en todas las líneas no es debido a reordenamientos o diferencias en el numero de copias genicas, haciendo posible el tratamiento con gamma interferon la recuperación de las moléculas polo expresadas, lo que apunta la existencia de factores locus- específicos reguladores como causa de las alteraciones selectivas de expresión en células tumorales. También hemos estudiado el posible papel jugado por la activación de ciertos oncogenes en la expresión de antígenos de histocompatibilidad, encontrando que en tumores no pertenecientes al grupo de carcinomas de células pequeñas la activación del oncogen c-myc es independiente de características biológicas de agresividad tumoral, no presentando relación con la expresión alterada de antígenos de histocompatibilidad. Así mismo la presencia de mutaciones en el codon 12 de k-ras no es un fenómeno prevalente en el carcinoma broncogenico, limitándose al grupo de adenocarcinomas pobremente diferenciados y no presentando relación alguna con la expresión hca.Univ. de Granad

Effect of Breast Cancer Treatment on Dietary Vitamin Intake Levels.

Breast cancer is the most common tumor among women, representing the second cause of cancer deaths in women. Treatment with chemotherapy negatively interferes with nutritional status. The intake of vitamins before, during and after treatment in a pilot cohort of women with non-invasive breast cancer (type I, II) treated at the Valencian Institute of Oncology (IVO) is evaluated. A 3-day anthropometric and nutritional assessment was performed using the DIAL program. Nutritional intake is compared with the values of Estimated Average Requirements (EAR) and Dietary Reference Intake (DRI) provided by the United States Department of Agriculture (USDA) and the European Food Safety Authority (EFSA). There is an overall decrease in vitamin intake during treatment which worsens at the end of said treatment. The decrease is significant in the case of vitamins B2 (p = 0.006), B3 (p = 0.042), B5 (p = 0.001), and B8 (p = 0.021). The relative risk during and after treatment increases with respect to the reference timeframe, before treatment. Deficit risks are statistically significant in the case of vitamins B5 (p = 0.001), B8 (p = 0.001) and B12 (p = 0.001). Decreased vitamin intake during treatment suggests a negative change in the patients' dietary behaviors during this time. Nutritional intervention and support may be beneficial to optimize overall dietary intake and maintain compliance with EAR and DRI for patients during a time in which adequate nutrition is important

First hospital contact via the Emergency Department is an independent predictor of overall survival and disease-free survival in patients with colorectal cancer.

the aim of this study was to examine the possible association between the type of hospital admission and subsequent survival of the patient, as well as the pathological features recorded in a large population of patients with colorectal cancer. the study included 1,079 patients diagnosed with colon or rectal cancer in the Hospital Costa del Sol (Marbella, Spain). The relationship between patient survival rate and type of first admission to the hospital (elective or emergency admission) was assessed. The following variables were studied: age, gender, tumor location, pathological stage, differentiation grade, chemotherapy before surgery and survival. colon tumors are more common in patients admitted to hospital for the first time via the emergency service (63.7%) and the tumors tend to be poorly differentiated (64.2%) and metastatic (70%). These patients also present a more aggressive disease and a poorer prognosis than patients with an elective admission. With regard to patients from the Emergency Department, a Cox regression analysis showed a risk-ratio (RR) of 1.36 (confidence interval [CI] 95%: 1.11-1.66) for disease-free survival and of 1.41 (95% CI: 1.14-1.76) for overall survival. hospital admission via the Emergency Department is an indicator of aggressiveness and poorer prognosis compared to patients who enter via programmed routes