Inoculated cell density as a determinant factor of the growth dynamics and metastatic efficiency of a breast cancer murine model

Copyright: © 2016 Gregório et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large number of cells, gives rise to fast growing tumors, as well as to a surprisingly low metastatic take rate. The present work aimed at establishing the conditions enabling high metastatic take rate of the triple-negative murine 4T1 syngeneic breast cancer model. An 87% 4T1 tumor incidence was observed when as few as 500 cancer cells were implanted. 4T1 cancer cells colonized primarily the lungs with 100% efficiency, and distant lesions were also commonly identified in the mesentery and pancreas. The drastic reduction of the number of inoculated cells resulted in increased tumor doubling times and decreased specific growth rates, following a Gompertzian tumor expansion. The established conditions for the 4T1 mouse model were further validated in a therapeutic study with peguilated liposomal doxorubicin, in clinical used in the setting of metastatic breast cancer. Inoculated cell density was proven to be a key methodological aspect towards the reproducible development of macrometastases in the 4T1 mouse model and a more reliable pre-clinical assessment of antimetastatic therapies.Ana Cristina Gregório is a student of the international PhD program in Experimental Biology and Biomedicine (PDBEB) from the Institute for Interdisciplinary Research, University of Coimbra and recipient of the fellowship SFRH/BD/51190/2010 from the Portuguese Foundation for Science and Technology (FCT). The work was supported by the grants PTDC/SAU-BMA/121028/2010 (FCT) and UID/NEU/04539/2013 (FEDER/COMPETE 2020/FCT).info:eu-repo/semantics/publishedVersio

Food Insecurity Is Associated with Low Adherence to the Mediterranean Diet and Adverse Health Conditions in Portuguese Adults

Background: Food insecurity is a limited or uncertain access to the adequate food and is a significant public health problem. We aimed to assess determinants of food insecurity and the corresponding health impact in Portugal, a southern European country that faced a severe economic crisis. Methods: Data were derived from the Epidemiology of Chronic Diseases Cohort Study (EpiDoC), a population-based cohort of 10,661 individuals that were representative of the Portuguese adult population and followed since 2011. A cross-sectional analysis of the third wave of evaluation (EpiDoC 3) was performed between 2015 and 2016. Food insecurity was assessed with the household food insecurity psychometric scale. Socioeconomic, demographic, lifestyle, adherence to Mediterranean diet (MD), self-reported non-communicable disease, health-related quality of life (HRQoL) (EQ-5D-3L), physical function (HAQ score), and health resource consumption information was also collected. Results: The estimated proportion of food insecurity was 19.3% among a total of 5,653 participants. Food insecure households had low adherence to the MD (OR = 0.44; 95% IC 0.31-0.62). In addition, diabetes (OR = 1.69; 95% IC 1.20-2.40), rheumatic disease (OR = 1.67; 95% IC 1.07-2.60), and depression symptoms (OR = 1.50; 95% IC 1.09-2.06) were independently associated with food insecurity. On average, food insecure households had a lower HRQoL (OR = 0.18; 95% IC 0.11-0.31) and a higher disability (OR = 2.59; 95% IC 2.04-3.29). A significantly higher proportion of food insecure households reported being hospitalized (OR = 1.57; 95% IC 1.18-2.07) and had more public hospital medical appointments (OR = 1.48; 95% IC 1.12-1.94) in the previous 12 months. Conclusion: We found that food insecurity is highly prevalent in Portugal. Food insecurity was associated with low adherence to the MD, non-communicable chronic diseases, lower quality of life, and higher health resource consumption. Therefore, this study provides valuable insight into the relationship between food security and the diet and health of the population during an economic crisis.publishersversionpublishe

Dietary Patterns Characterized by High Meat Consumption Are Associated with Other Unhealthy Life Styles and Depression Symptoms

ObjectiveWe aimed to identify dietary patterns (DPs) of Portuguese adults, to assess their socioeconomic, demographic, lifestyle determinants, and to identify their impact on health.DesignEpiDoC 2 study included 10,153 Portuguese adults from the EpiDoC Cohort, a population-based study. In this study, trained research assistants using computer-assisted telephone interview collected socioeconomic, demographic, dietary, lifestyles, and health information from March 2013 to July 2015. Cluster analysis was performed, based on questions regarding the number of meals, weekly frequency of soup consumption, vegetables, fruit, meat, fish, dairy products, and daily water intake. Factors associated with DP were identified through logistic regression models.ResultsTwo DPs were identified: the “meat dietary pattern” and the “fruit & vegetables dietary pattern.” After multivariable adjustment, women (OR = 0.52; p < 0.001), older adults (OR = 0.97; p < 0.001), and individuals with more years of education (OR = 0.96; p = 0.025) were less likely to adopt the “meat dietary pattern,” while individuals in a situation of job insecurity/unemployment (OR = 1.49; p = 0.013), Azores island residents (OR = 1.40; p = 0.026), current smoking (OR = 1.58; p = 0.001), daily alcohol intake (OR = 1.46; p = 0.023), and physically inactive (OR = 1.86; p < 0.001) were positively and significantly associated with “meat dietary pattern.” Moreover, individuals with depression symptoms (OR = 1.50; p = 0.018) and the ones who did lower number of medical appointments in the previous year (OR = 0.98; p = 0.025) were less likely to report this DP.ConclusionOur results suggest that unhealthy DPs (meat DP) are part of a lifestyle behavior that includes physical inactivity, smoking habits, and alcohol consumption. Moreover, depression symptoms are also associated with unhealthy DPs

Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint)

This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications

An intriguing shift occurs in the novel protein phosphatase 1 binding partner, TCTEX1D4: evidence of positive selection in a pika model

T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) contains the canonical phosphoprotein phosphatase 1 (PPP1) binding motif, composed by the amino acid sequence RVSF. We identified and validated the binding of TCTEX1D4 to PPP1 and demonstrated that indeed this protein is a novel PPP1 interacting protein. Analyses of twenty-one mammalian species available in public databases and seven Lagomorpha sequences obtained in this work showed that the PPP1 binding motif 90RVSF93 is present in all of them and is flanked by a palindromic sequence, PLGS, except in three species of pikas (Ochotona princeps, O. dauurica and O. pusilla). Furthermore, for the Ochotona species an extra glycosylation site, motif 96NLS98, and the loss of the palindromic sequence were observed. Comparison with other lagomorphs suggests that this event happened before the Ochotona radiation. The dN/dS for the sequence region comprising the PPP1 binding motif and the flanking palindrome highly supports the hypothesis that for Ochotona species this region has been evolving under positive selection. In addition, mutational screening shows that the ability of pikas TCTEX1D4 to bind to PPP1 is maintained, although the PPP1 binding motif is disrupted, and the N- and C-terminal surrounding residues are also abrogated. These observations suggest pika as an ideal model to study novel PPP1 complexes regulatory mechanisms

Reactividad del sistema bifásico tricloroacetonitrilo-CH2Cl2/H2O2 en la epoxidación del aceite de soja

In this work we report on the epoxidation of soybean oil by the trichloroacetonitrile -CH2Cl2/H2O2 byphasic system. The reaction was carried out at room temperature and, most importantly, in non acid conditions which prevent the opening of the oxirane ring. The epoxidized soybean oil was characterized by infrared, 1H and 13C NMR. A maximum conversion of 81 % was achieved in two hours with 86% of selectivity in epoxy groupsEn el presente trabajo informamos sobre la epoxidación de aceite de soja mediante el sistema bifásico tricloroacetonitrilo-CH2Cl2/H2O2. La reacción fue realizada bajo condiciones de temperatura ambiente y, lo más importante, en condición no ácida, lo que evita la apertura del anillo oxirano. El aceite de soja fue caracterizado por infrarrojo y RMN de 1H and 13C. En dos horas se alcanzó una conversión máxima del 81 % obteniéndose una selectividad del 86 % en grupos epóxido

Validation of the Telephone-Administered Version of the Mediterranean Diet Adherence Screener (MEDAS) Questionnaire

A 14-Item Mediterranean Diet Adherence Screener (MEDAS) questionnaire was developed and validated in face-to-face interviews, but not via telephone. The aims of this study were to evaluate the validity and reliability of a telephone-administered version of the MEDAS as well as to validate the Portuguese version of the MEDAS questionnaire. A convenience community-based sample of adults (n = 224) participated in a three-stage survey. First, trained researchers administered MEDAS via a telephone. Second, the Portuguese version of Food Frequency Questionnaire (FFQ), and MEDAS were administered in a semi-structured face-to-face interview. Finally, MEDAS was again administered via telephone. The telephone-administered MEDAS questionnaire was compared with the face-to-face-version using several metrics. The telephone-administered MEDAS was significantly correlated with the face-to-face-administered MEDAS [r = 0.805, p < 0.001; interclass correlation coefficient (ICC) = 0.803, p < 0.001] and showed strong agreement (k = 0.60). The MEDAS scores that were obtained in the first and second telephone interviews were significantly correlated (r = 0.661, p < 0.001; ICC = 0.639, p < 0.001). The overall agreement between the Portuguese version of MEDAS and the FFQ-derived Mediterranean diet adherence score had a Cohen's k = 0.39. The telephone-administered version of MEDAS is a valid tool for assessing the adherence to the Mediterranean diet and acquiring data for large population-based studies.info:eu-repo/semantics/publishedVersio

Nucleolin Overexpression Predicts Patient Prognosis While Providing a Framework for Targeted Therapeutic Intervention in Lung Cancer

Notwithstanding the advances in the treatment of lung cancer with immune checkpoint inhibitors, the high percentage of non-responders supports the development of novel anticancer treatments. Herein, the expression of the onco-target nucleolin in patient-derived pulmonary carcinomas was characterized, along with the assessment of its potential as a therapeutic target. The clinical prognostic value of nucleolin for human pulmonary carcinomas was evaluated through data mining from the Cancer Genome Atlas project and immunohistochemical detection in human samples. Cell surface expression of nucleolin was evaluated by flow cytometry and subcellular fraction Western blotting in lung cancer cell lines. Nucleolin mRNA overexpression correlated with poor overall survival of lung adenocarcinoma cancer patients and further predicted the disease progression of both lung adenocarcinoma and squamous carcinoma. Furthermore, a third of the cases presented extra-nuclear expression, contrasting with the nucleolar pattern in non-malignant tissues. A two- to twelve-fold improvement in cytotoxicity, subsequent to internalization into the lung cancer cell lines of doxorubicin-loaded liposomes functionalized by the nucleolin-binding F3 peptide, was correlated with the nucleolin cell surface levels and the corresponding extent of cell binding. Overall, the results suggested nucleolin overexpression as a poor prognosis predictor and thus a target for therapeutic intervention in lung cancer

An intriguing shift occurs in the novel protein phosphatase 1 binding partner, TCTEX1D4: evidence of positive selection in a pika model

T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) contains the canonical phosphoprotein phosphatase 1 (PPP1) binding motif, composed by the amino acid sequence RVSF. We identified and validated the binding of TCTEX1D4 to PPP1 and demonstrated that indeed this protein is a novel PPP1 interacting protein. Analyses of twenty-one mammalian species available in public databases and seven Lagomorpha sequences obtained in this work showed that the PPP1 binding motif 90RVSF93 is present in all of them and is flanked by a palindromic sequence, PLGS, except in three species of pikas (Ochotona princeps, O. dauurica and O. pusilla). Furthermore, for the Ochotona species an extra glycosylation site, motif 96NLS98, and the loss of the palindromic sequence were observed. Comparison with other lagomorphs suggests that this event happened before the Ochotona radiation. The dN/dS for the sequence region comprising the PPP1 binding motif and the flanking palindrome highly supports the hypothesis that for Ochotona species this region has been evolving under positive selection. In addition, mutational screening shows that the ability of pikas TCTEX1D4 to bind to PPP1 is maintained, although the PPP1 binding motif is disrupted, and the N- and C-terminal surrounding residues are also abrogated. These observations suggest pika as an ideal model to study novel PPP1 complexes regulatory mechanisms.publishe