The impact of the distance traveled between residence and gestational trophoblastic neoplasia reference center and clinical outcomes in Brazilian women.

OBJECTIVE: To relate the distance traveled from the patient's residence to the gestational trophoblastic neoplasia (GTN) reference center (RC) and the occurrence of unfavorable clinical outcomes, as well as to estimate the possible association between this distance and the risk of metastatic disease at presentation, the need for multiagent chemotherapy to achieve remission and loss to follow-up before remission. STUDY DESIGN: Retrospective historical cohort study of patients with GTN followed at 8 Brazilian GTN-RC, from January 1st, 2000 - December 31st, 2017. RESULTS: Evaluating 1055 cases of GTN, and using a receiver operating characteristic curve, we found a distance of 56 km (km) from the residence to the GTN-RC (sensitivity = 0.57, specificity = 0.61) best predicted the occurrence of at least one of the following outcomes: occurrence of metastatic disease, need for multiagent chemotherapy to achieve remission, or loss to follow-up during chemotherapy. Multivariate logistic regression adjusted by age, ethnicity, marital status and the reference center location showed that when the distance between residence and GTN-RC was ≥56 km, there was an increase in the occurrence of metastatic disease (relative risk - RR:3.27; 95%CI:2.20-4.85), need for multiagent chemotherapy (RR:1.36; 95%CI:1.05-1.76), loss to follow-up during chemotherapy (RR:4.52; 95CI:1.93-10.63), occurrence of chemoresistance (RR:4.61; 95%CI:3.07-6.93), relapse (RR:10.27; 95%CI:3.08-34.28) and death due to GTN (RR:3.62; 95%CI:1.51-8.67). CONCLUSIONS: The distance between the patient's residence and the GTN-RC is a risk factor for unfavorable outcomes, including death from this disease. It is crucial to guarantee these patients get prompt access to the GTN-RC and receive follow-up support.

Presentation, medical complications and development of gestational trophoblastic neoplasia of hydatidiform mole after intracytoplasmic sperm injection as compared to hydatidiform mole after spontaneous conception - a retrospective cohort study and literature review.

OBJECTIVE: To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC). STUDY DESIGN: Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020. RESULTS: Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC. CONCLUSIONS: Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC.

Influence of COVID-19 pandemic on molar pregnancy and postmolar gestational trophoblastic neoplasia: An observational study.

OBJECTIVE: To assess whether the incidence and aggressiveness of molar pregnancy (MP) and postmolar gestational trophoblastic neoplasia (GTN) changed during the COVID-19 pandemic. DESIGN: Observational study with two separate designs: retrospective multicentre cohort of patients with MP/postmolar GTN and a cross-sectional analysis, with application of a questionnaire. SETTING: Six Brazilian Reference Centres on gestational trophoblastic disease. POPULATION: 2662 patients with MP/postmolar GTN treated from March-December/2015-2020 were retrospectively evaluated and 528 of these patients answered a questionnaire. METHODS: Longitudinal retrospective multicentre study of patients diagnosed with MP/ postmolar GTN at presentation and a cross-sectional analysis, with application of a questionnaire, exclusive to patients treated during the period of study, to assess living and health conditions during the COVID-19 pandemic compared with previous years. MAIN OUTCOME MEASURES: The incidence of MP/postmolar GTN. RESULTS: Compared with the last 5 pre-pandemic years, MP/postmolar GTN incidence remained stable during 2020 (COVID-19 pandemic). Multivariable logistic regression, adjusted for the patient age, showed that during 2020, presentation with MP was more likely to be >10 weeks of gestation (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.90-3.29, P < 0.001), have a pre-evacuation hCG level ≥100 000 iu/l (aOR 1.77, 95% CI 1.38-2.28, P < 0.001) and time to the initiation of chemotherapy ≥7 months (aOR 1.86, 95% CI 1.01-3.43, P = 0.047) when compared with 2015-2019. CONCLUSIONS: Although the incidence of MP/postmolar GTN remained stable during the COVID-19 pandemic in Brazil, the pandemic was associated with greater gestational age at MP diagnosis and more protracted delays in initiation of chemotherapy for postmolar GTN.

Importance of Carbohydrate Quality: What Does It Mean and How to Measure It?

Dietary carbohydrates are our main source of energy. Traditionally, they are classified based on the polymer length between simple and complex carbohydrates, which does not necessarily reflect their impact on health. Simple sugars, such as fructose, glucose, and lactose, despite having a similar energy efficiency and caloric content, have very distinct metabolic effects, leading to increased risk for various chronic diseases when consumed in excess. In addition, beyond the absolute amount of carbohydrate consumed, recent data point out that the food form or processing level can modulate both the energy efficiency and the cardiometabolic risk associated with specific carbohydrates. To account for both of these aspects-the quality of carbohydrates as well as its food form-several metrics can be proposed to help identifying carbohydrate-rich food sources and distinguish between those that would favor the development of chronic diseases and those that may contribute to prevent these. This review summarizes the findings presented during the American Society of Nutrition Satellite symposium on carbohydrate quality, in which these different aspects were presented.

Interprofessional education in healthcare and health workforce (HRH) planning in Brazil: experiences and good practices.

We report a review of interprofessional education (IPE) for health in Brazil with the objective of identifying experiences and good practices related to the different contexts of changing education and health systems. Our approach is an integrative bibliographic review using surveys and analysis of documents related to IPE in the Virtual Health Library scientific data base. The Brazilian scenario on IPE is still rudimentary, lacking clarity in its definition and scientific progress. Records of successful experiences of IPE and collaborative practices show some growth, with a tendency toward great adherence of professionals, students and teachers in the training model reshuffle. Collaborative practices are strategically used as innovative pedagogical approaches to foster the establishment of integrated teaching-service-community curricula, which coexist with traditional ones. IPE initiatives and collaborative practices have existed in Brazil since the mid-twentieth century. However, the dynamics of training models have not been accompanied by the same pace of change in health services, even under pressure to expand the primary health care (PHC) network and international influence for changes in educational models. The main challenge in this context is to make changes in the three components of training programmes: theoretical orientation, pedagogical approach and scenarios of practices, responding to population health needs and improving people's quality of life.

Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma?

OBJECTIVE: To evaluate expectant management versus immediate chemotherapy following pathological diagnosis of gestational choriocarcinoma (GCC) in patients with nonmetastatic disease. METHODS: Multicenter retrospective cohort that included patients with histological diagnosis of GCC with nonmetastatic disease followed at one of thirteen Brazilian referral centers for gestational trophoblastic disease from January 2000 to December 2016. RESULTS: Among 3191 patients with gestational trophoblastic neoplasia, 199 patients with nonmetastatic GCC were identified. Chemotherapy was initiated immediately in 152 (76.4%) patients per FIGO 2000 guideline, while 47 (23.6%) were managed expectantly. Both groups presented with similar characteristics and outcomes. All patients (n=12) who had normal human chorionic gonadotropin (hCG) in the first 2-3weeks of expectant management achieved complete sustained remission with no chemotherapy. Only 44.7% (21 patients) of patients who were expectantly managed needed to receive chemotherapy due to plateauing or rising hCG level in the first 2-3weeks of follow up. The outcome of patients receiving chemotherapy after initial expectant management was similar to those who received chemotherapy immediately after the diagnosis in terms of need for multi-agent chemotherapy or number of cycles of chemotherapy. There was no case of relapse or death in either group. Logistic regression analysis showed that age≥40years and hCG≥92,428IU/L at GCC diagnosis were risk factors for needing chemotherapy after initial expectant management of nonmetastatic GCC. CONCLUSION: In order to avoid exposing patients unnecessarily to chemotherapy, close surveillance of women with pathological diagnosis of nonmetastatic GCC seems to be a safe practice, particularly for those who have a normal hCG at the time of diagnosis. If confirmed by other studies, the FIGO guidelines may need to be revised.

The impact of replacing sugar- by artificially-sweetened beverages on brain and behavioral responses to food viewing - An exploratory study.

Several studies indicate that the outcome of nutritional and lifestyle interventions can be linked to brain 'signatures' in terms of neural reactivity to food cues. However, 'dieting' is often considered in a rather broad sense, and no study so far investigated modulations in brain responses to food cues occurring over an intervention specifically aiming to reduce sugar intake. We studied neural activity and liking in response to visual food cues in 14 intensive consumers of sugar-sweetened beverages before and after a 3-month replacement period by artificially-sweetened equivalents. Each time, participants were presented with images of solid foods differing in fat content and taste quality while high-density electroencephalography was recorded. Contrary to our hypotheses, there was no significant weight loss over the intervention period and no changes were observed in food liking or in neural activity in regions subserving salience and reward attribution. However, neural activity in response to high-fat, sweet foods was significantly reduced from pre-to post-intervention in prefrontal regions often linked to impulse control. This decrease in activity was associated with weight loss failure, suggesting an impairment in individuals' ability to exert control and adjust their solid food intake over the intervention period. Our findings highlight the need to implement multidisciplinary approaches when aiming to help individuals lose body weight.

Brazilian special olympics athletes: Oral health problems.

AIMS: The people with intellectual disabilities have been reported to be a vulnerable population in terms of oral health. This study was carried out to determine the oral health condition and treatment needs of Special Olympics athletes in Brazil. METHODS: This study is a retrospective review of oral health data collected from athletes participating in Healthy Athletes Program Special Olympics in Brazil, between the years 2015 and 2019. About 1241 athletes from the Brazil Special Olympics program were screened in the cities of São Paulo, Jundiai and Belo Horizonte (located in southeastern Brazil) and Recife (in northeastern Brazil). At each of these events, volunteer dental professionals performed an oral health screening for each athlete, All oral health assessments were done visually; and extra lighting were available if needed. The examinations were performed with the aid of a wooden spatula of the tongue depressor type and under natural light. The following parameters were recorded: mouth pain, untreated tooth decay, missing teeth, gingival signs, urgency and mouth hygiene habits. Data was analyzed using the STATA 14.0 program. Frequency tables were used for descriptive analyses. Categorical variables were compared between the different years of the event using the Chi-Square or Fisher's Exact test. Continuous variables were compared between different event years using the Kruskal-Wallis test followed by Dunn's post-hoc analyses. Simple logistic regression was used to assess the effect of age on dental assessment results. For all tests, a p-value was considered significant when less than or equal to .05. RESULTS: No statistically significant differences were observed in the frequencies of Mouth Pain and Missing Teeth over the years (p > .05). In relation to Untreated Tooth Decay, there is a higher frequency in the years 2016 and 2018 and a lower frequency in the year 2015 (p = .048). Regarding Gingival Signs of inflammation, there is a higher frequency in the years 2016 and 2018 and a lower frequency in the year 2017 (p < .001). In relation to cases of urgency (in need of treatment (Urgent treatment need, Non-Urgent or Maintenance)), there was a higher frequency (no urgency) in 2016 (p = .007). Finally, in relation to mouth hygiene habits, there is a higher frequency of participants with irregular habits in the years 2017 and 2019 (p < .001). CONCLUSION: The dental condition of Brazilian athletes Special Olympycs Brazil reported in this study from 2015 to 2019 showed us that athletes have a high prevalence of dental diseases and these needs could contribute to health damage. The athletes have many unmet dental treatment needs and these needs are similar in different regions of the country and in the years reported.

Estimation of Free Sugars in the Filipino Food Composition Table and Evaluation of Population-Level Intake.

Recommendations to reduce intake of free sugars are included in some national dietary guidelines. However, as the content of free sugars is absent from most of the food composition tables, the adherence to such recommendations is hard to monitor. We developed a novel method to estimate the free sugar content in the Philippines food composition table, based on a data-driven algorithm that enabled automated annotation. We then used these estimates to analyze the free sugar intake of 66,016 Filipinos aged 4 years and over. The average free sugar consumption was 19 g/day, accounting for an average of 3% of the total caloric intake. Snacks and breakfast were the meals with the highest content of free sugars. Intake of free sugars, in grams per day and as % of energy, was positively associated with wealth status. The same pattern was observed for the consumption of sugar-sweetened beverages.

EFSA Health Claims-Based Virgin Olive Oil Shelf-Life.

The consumption of extra virgin olive oil (EVOO) has been linked to various health benefits, including a reduced risk of cardiovascular disease. EVOO contains triglycerides and unsaturated fatty acids, as well as minor compounds, such as polar phenols and tocopherols, which play a crucial nutritional and biological role. The composition of these minor compounds is affected by various factors that distinguish EVOOs from lower-quality olive oils. The European Parliament approved Regulation 1924/2006 that governs the use of health claims on food products based on EFSA reports. Currently, there are several authorized health claims related to unsaturated fatty acids, vitamin E, and polyphenol content that can be used for commercial reasons on EVOO labels. Consumers can easily take enough grams of EVOO per day to receive the beneficial effects of the nutrient in question; nevertheless, the use of these health claims is subject to a required concentration of specific nutrients throughout the shelf life of olive oil. Few studies have examined the evolution of these compounds along the shelf life of EVOO to meet health claims. This work aims to evaluate the nutritional profile of several EVOOs with potential health claims and the evolution of related nutrients during storage in darkness at different temperatures. This study proposes an accelerated method to determine the end of the EVOO shelf life based on the loss of its nutraceutical capacity and the inability to comply with the stated health claims.

Low bioavailability of dietary iron among Brazilian children: Study in a representative sample from the Northeast, Southeast, and South regions.

Background: Despite all efforts, iron deficiency anemia remains a serious public health problem among Brazilian children. Objective: To evaluate dietary iron intake and dietary practices that interfere with the absorption of this nutrient from three regions of Brazil. Methods: Brazil Kids Nutrition and Health Study is a cross-sectional dietary intake study in children aged 4-13.9 years old designed to investigate nutrient intakes and gaps of Brazilian children in a representative sample of households from Northeast, Southeast and South regions. Nutrient intake was assessed based on multiple-pass 24-h dietary recall and U.S. National Cancer Institute method was used to estimate usual micronutrients intakes and compliance with Dietary Reference Intakes. Results: Five hundred sixteen individuals participated in the study (52.3% male). The top three most consumed food sources of iron were products of plant origin. Food sources of animal origin contributed with <20% of the total iron intake. Vitamin C intake was adequate, but the concomitant consumption of food sources of vitamin C with plant food sources of iron was not common. On the other hand, the concomitant intake of plant food sources of iron with food sources of iron chelators (e.g., coffee and teas) was frequent. Conclusions: Adequate iron intake was observed in all three regions in Brazil. Children's diet showed low iron bioavailability and insufficient consumption of food sources of iron absorption stimulants. Frequent presence of iron chelators and inhibitors of iron absorption might help to explain the high prevalence of iron deficiency in the country.

Characteristics of pediatric patients hospitalized with COVID-19 during the third wave (omicron variant) at a referral hospital in Peru. / Características de los pacientes pediátricos hospitalizados con COVID-19 durante la tercera ola (variante ómicron) en un hospital de referencia del Perú.

OBJECTIVES.: Motivation for the study. There are few reports on the clinical experience of the population infected with the omicron variant of COVID-19 in Latin America, particularly in pediatric population. Main findings. There was a rapid increase in the number of hospitalizations compared to previous waves, mainly due to respiratory conditions; most patients progressed favorably. Antibiotics and corticosteroids were the most used drugs. Implications. Studying the characteristics of children hospitalized during the third wave of COVID-19 in Peru may increase the knowledge of how the omicron variant affects this population group, which will allow comparisons with possible new waves or diseases.

Longitudinal and cross-sectional changes in active commuting to school among Brazilian schoolchildren.

OBJECTIVE: The objective of the study is to evaluate cross-sectional and longitudinal changes in children's commuting to school in a representative sample of a Brazilian city. METHODS: Two school-based studies were carried out in 2002 (n=2936; 7-10 years old) and 2007 (n=1232; 7-15 years old) in Florianopolis, Brazil. Cross-sectional data were collected from children aged 7 to 10 years in 2002 and 2007. Longitudinal analyses were performed with data from 733 children participating in both surveys. Children self-reported their mode of transportation to school using a validated illustrated questionnaire. Changes were tested with chi square statistics and McNemar's test. RESULTS: Cross-sectional data showed a 17% decline in active commuting; a decrease from 49% in 2002 to 41% in 2007. On the other hand, active commuting among the 733 children increased as they entered adolescence 5 years later, rising from 40% to 49%. CONCLUSION: Active commuting to school decreased in Brazilian children aged 7-10 years over a five year period; whereas, it increased among children entering adolescence. Policies should focus on safety and environmental determinants to increase active commuting.

Effects of Dietary Carbohydrate Profile on Nocturnal Metabolism, Sleep, and Wellbeing: A Review.

Sleep is a crucial biological function and a well-established driver of health and wellbeing across the lifespan. In this review, we describe how sleep in humans is associated with specific circadian metabolic and physiological changes, and how the organization of sleep-wake states is related to regulation of nocturnal metabolism during fasting. Among the modifiable factors that can contribute to sleep-related benefits, emerging evidence suggests that diet and nocturnal changes in glucose regulation are strong determinants of sleep quality. Here, we review studies that have explored the importance of quantity and quality of dietary carbohydrates and proteins in modulation of sleep and sleep-related health benefits. Future research may guide the creation of nutritional solutions to improve sleep, which could lead to positive changes in health, wellbeing, and overall quality of life.

Modelling Virgin Olive Oil Potential Shelf-Life from Antioxidants and Lipid Oxidation Progress.

The development of effective shelf-life prediction models is extremely important for the olive oil industry. This research is the continuation of a previous accelerated shelf-life test at mild temperature (40-60 °C), applied in this case to evaluate the oxidation effect of temperature on minor components (phenols, tocopherol, pigments) to properly complete a shelf-life predictive model. The kinetic behaviour of phenolic compounds, α-tocopherol and pigments during storage of different virgin olive oil samples at different temperatures (25-60 °C) is reported. Hydroxytyrosol, tyrosol and α-tocopherol fitted to pseudo-zero-order kinetics, whereas secoiridoid derivatives of hydroxytyrosol and tyrosol, o-diphenols and total phenols apparently followed pseudo-first-order kinetics. The temperature-dependent kinetic of phenolic compounds and α-tocopherol were well described by the linear Arrhenius model. The apparent activation energy was calculated. Principal component analysis was used to transform the considered compositional and degradation variables into fewer uncorrelated principal components resulting in 4: "no oxidizable substrate", "initial oxidation state and conditions", "free simple phenols", and "degradation rates". In addition, multivariate linear regression was used to yield several modelling equations for shelf-life prediction, considering initial composition and experimental variables easily determined in accelerated storage.

Nutrient Intakes among Brazilian Children Need Improvement and Show Differences by Region and Socioeconomic Level.

Brazil is the most populous country in South America. Using 24 h dietary data, we compared the nutrient intakes of 4-13-year-olds to reference values and tested for regional and socioeconomic (SES) differences. A considerable proportion reported intakes below the Estimated Average Requirements (EAR) for vitamins E (78.1%, 96.5%), D (100% for both), and calcium (80.5%, 97.7%) for 4-8 and 9-13-year-olds, respectively. Few exceeded Adequate Intakes (AI) for potassium or fiber. Older children reported greater inadequacies and, while there was regional variability, patterns of inadequacy and excess tended to be similar. For vitamin C, the percent of children below EAR in the Northeast and Southeast was lower than in the South. Most children, regardless of SES, had energy intakes within the Acceptable Macronutrient Distribution Ranges (AMDRs) for carbohydrates and protein. Over a quarter reported total energy from fat less than the AMDR, and inversely associated with SES (low 50.9%, moderate 26.0%, and high 15.0%), but also exceeding the percentage of energy recommendation for saturated fat, increasing with SES (low 18.1%, moderate 38.9%, and high 48.8%). The contrast observed between the diets of young Brazilians and recommendations underscores the need for individual and regional environmental interventions to promote healthier dietary patterns.

Balanced carbohydrate ratios are associated with improved diet quality in Australia: A nationally representative cross-sectional study.

BACKGROUND: Carbohydrate quality influences major health outcomes; however, the best criteria to assess carbohydrate quality remain unknown. OBJECTIVE: The objectives were to: i) evaluate whether a diet that meets a carbohydrate ratio (simple, modified or dual ratio) is associated with higher nutrient intakes and diet quality, and ii) model the impact of substituting carbohydrate foods that meet the proposed ratios in place of foods that do not, on nutrient intakes. DESIGN: A secondary analysis of cross-sectional data from the 2011-12 Australian National Nutrition and Physical Activity Survey. PARTICIPANTS/SETTING: National data from participants aged 2 years and older (n = 12,153). MAIN OUTCOME MEASURES: Ratios were defined as (i) simple ratio, 10:1 (10g carbohydrate:≥1g dietary fiber); (ii) modified ratio, 10:1:2 (10g carbohydrate:≥1g dietary fiber:≤2g free sugars); and (iii) dual ratio, 10:1 & 1:2 (10g carbohydrate:≥1g dietary fiber & ≤2g free sugars per 1g dietary fiber). Ratios were compared to nutrient intakes obtained via automated multiple-pass 24-hour dietary recall and diet quality calculated using the Australian Healthy Eating Index. STATISTICAL ANALYSES PERFORMED: Substitution dietary modelling was performed. Data were analyzed using paired and independent sample t-tests. RESULTS: Ratio adherence was highest for simple (50.2% adults; 28.6% children), followed by dual (40.6% adults; 21.7% children), then modified (32.7% adults; 18.6% children) ratios. Participants who met any ratio reported higher nutrient intake and diet quality compared to those who failed to meet the respective ratio (P < .001 for all), with the greatest nutrient intakes found for those who met modified or dual ratios. Dietary modelling improved nutrient intakes for all ratios, with the greatest improvement found for the dual ratio. CONCLUSIONS: All carbohydrate ratios were associated with higher diet quality, with a free sugars constraint in the dual ratio providing the greatest improvements.

An Assessment of Three Carbohydrate Metrics of Nutritional Quality for Packaged Foods and Beverages in Australia and Southeast Asia.

Carbohydrate quality is an aetiological factor of diet-related disease. Indices of carbohydrate quality featuring various ratios of carbohydrates-to-dietary fibre-to-sugar have been associated with improved product and/or diet quality in westernised countries. Carbohydrate intake is especially high in Asia Pacific. Thus, this study evaluated the ability of such carbohydrate metrics to discriminate the nutritional quality of carbohydrate-rich packaged foods and beverages in Australia, Malaysia, Singapore, Thailand and the Philippines, with an additional focus on beverages. This evaluation was conducted by comparing product nutritional composition and assessing products against three national nutrient profiling models. Results showed that Australia had the highest proportion of products meeting all metrics, compared to the Southeast Asian countries. Beverages had a low adherence to all metrics compared to solid foods. Across the five countries, both processed food and beverages meeting the metrics generally contained higher dietary fibre, protein, and certain vitamins and minerals whilst having lower energy, total sugars, free sugars, trans fat and cholesterol content compared to products not meeting the metrics. The metrics were also aligned with national nutrient profiling models to identify nutritious products. In conclusion, these metrics allowed us to discriminate product nutritional quality in the countries assessed and are applicable to beverages.

Ruthenium (II) complexes with N, O-chelating proline and threonine ligands cause selective cytotoxicity by the induction of genomic instability, cell cycle arrest and apoptosis in breast and prostate tumor cells.

Ruthenium complexes are being considered as novel chemotherapeutic alternatives for cancer treatment. In our study, we assessed the antitumoral activities of novel ruthenium complexes coupled to the amino acids proline (RuPro) and threonine (RuThr) in prostate tumor cell lines (DU145) and breast (MCF7), and normal cell lines of the lung fibroblast (GM07492A). Our results revealed that the EC50 of the complexes for DU145 and MCF7 was two times lower than that GM07492A. Moreover, RuPro and RuThr were not able to induce significant genomic instability, cell cycle arrest or cell death in GM07492A, but could induce DNA damage, arrest in G2/M and apoptosis in DU145 and MCF7. Furthermore, BAX, TP53 and ATM were found to be upregulated in DU145 and MCF7 treated with RuPro and RuThr, in which, a higher ASCT2 gene expression was also observed. Using molecular docking, RuPro and RuThr interact with ASCT2, suggesting that this transporter might have a pivotal role in the execution of their activities. Hence, our results with RuPro and RuThr are capable of selectively inducing genetic damage, cell cycle arrest and apoptosis in DU145 and MCF7. We suggest that the selective action of the RuPro and RuThr complexes is related to the higher expression of ASCT2 in the tumor cells.