Cytotoxicity Activity of Some meso-Dihydroguaiaretic Acid Derivatives and Mode of Action of the Most Active Compound.

The aim of this study was to screen sixteen meso-1 semi-synthetic derivatives bearing ether, esther, carbamate, phosphate or aminoether functional groups against five cancer cell lines: MCF-7 (breast), A549 (lung), HepG2 (liver), HeLa (cervix), and DU145 (prostate) at 25 µM using the MTT assay. Results from the screening showed that two derivatives had the lowest percentage of cell viability at 25 µM, the aminoether derivative meso-11 and the esther derivative meso-20 against A549 (44.15±0.78 %) and MCF-7 (41.60±0.92 %), respectively. Then, it was determined the IC50 value of each compound against their most sensitive cancer cell line. Results showed that aminoether derivative meso-11 showed potent cytotoxicity against A549 (IC50 =17.11±2.11 µM), whereas it resulted more cytotoxic against the LL-47 lung normal cell line (IC50 =9.49±1.19 µM) having a Selective Index (SI) of 0.55. On the other hand, the esther derivative meso-20 exhibited potent activity against MCF-7 (IC50 =18.20±1.98 µM), whereas it displayed moderate cytotoxicity against the MCF-10 breast normal cell line (IC50 =41.22±2.17 µM) with a SI of 2.2. Finally, studies on the mechanism of action of meso-20 indicated disruption of MCF-7 plasma membrane in vitro and the AMPK activation in silico.

Zika Virus Disease in Colombia - Preliminary Report.

BACKGROUND: Colombia began official surveillance for Zika virus disease (ZVD) in August 2015. In October 2015, an outbreak of ZVD was declared after laboratory-confirmed disease was identified in nine patients. METHODS: Using the national population-based surveillance system, we assessed patients with clinical symptoms of ZVD from August 9, 2015, to April 2, 2016. Laboratory test results and pregnancy outcomes were evaluated for a subgroup of pregnant women. Concurrently, we investigated reports of microcephaly for evidence of congenital ZVD. RESULTS: By April 2, 2016, there were 65,726 cases of ZVD reported in Colombia, of which 2485 (4%) were confirmed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay. The overall reported incidence of ZVD among female patients was twice that in male patients. A total of 11,944 pregnant women with ZVD were reported in Colombia, with 1484 (12%) of these cases confirmed on RT-PCR assay. In a subgroup of 1850 pregnant women, more than 90% of women who were reportedly infected during the third trimester had given birth, and no infants with apparent abnormalities, including microcephaly, have been identified. A majority of the women who contracted ZVD in the first or second trimester were still pregnant at the time of this report. Among the cases of microcephaly investigated from January 2016 through April 2016, four patients had laboratory evidence of congenital ZVD; all were born to asymptomatic mothers who were not included in the ZVD surveillance system. CONCLUSIONS: Preliminary surveillance data in Colombia suggest that maternal infection with the Zika virus during the third trimester of pregnancy is not linked to structural abnormalities in the fetus. However, the monitoring of the effect of ZVD on pregnant women in Colombia is ongoing. (Funded by Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

Airborne particulate matter (PM10) induces cell invasion through Aryl Hydrocarbon Receptor and Activator Protein 1 (AP-1) pathway deregulation in A549 lung epithelial cells.

BACKGROUND: Particulate matter with an aerodynamic size ≤ 10 µm (PM10) is a risk factor for lung cancer development, mainly because some components are highly toxic. Polycyclic aromatic hydrocarbons (PAHs) are present in PM10, such as benzo[a]pyrene (BaP), which is a well-known genotoxic and carcinogenic compound to humans, capable of activating AP-1 transcription factor family genes through the Aryl Hydrocarbon Receptor (AhR). Because effects of BaP include metalloprotease 9 (MMP-9) activation, cell invasion, and other pathways related to carcinogenesis, we aimed to demonstrate that PM10 (10 µg/cm2) exposure induces the activation of AP-1 family members as well as cell invasion in lung epithelial cells, through AhR pathway. METHODS AND RESULTS: The role of the AhR gene in cells exposed to PM10 (10 µg/cm2) and BaP (1µM) for 48 h was evaluated using AhR-targeted interference siRNA. Then, the AP-1 family members (c-Jun, Jun B, Jun D, Fos B, C-Fos, and Fra-1), the levels/activity of MMP-9, and cell invasion were analyzed. We found that PM10 increased AhR levels and promoted its nuclear localization in A549 treated cells. Also, PM10 and BaP deregulated the activity of AP-1 family members. Moreover, PM10 upregulated the secretion and activity of MMP-9 through AhR, while BaP had no effect. Finally, we found that cell invasion in A549 cells exposed to PM10 and BaP is modulated by AhR. CONCLUSION: Our results demonstrated that PM10 exposure induces upregulation of the c-Jun, Jun B, and Fra-1 activity, the expression/activity of MMP-9, and the cell invasion in lung epithelial cells, effects mediated through the AhR. Also, the Fos B and C-Fos activity were downregulated. In addition, the effects induced by PM10 exposure were like those induced by BaP, which highlights the potentially toxic effects of the PM10 mixture in lung epithelial cells.

Gait speed according to cognitive status in older adults: a cross-sectional study in a resource-limited country.

OBJECTIVE: We aimed to investigate the association between gait speed and cognitive status in outpatient older adults from a resource-limited setting in Peru. METHODS: We performed a cross-sectional study including older adults aged ≥60 years attending a geriatrics outpatient clinic between July 2017 and February 2020. Gait speed was measured over a 10-meters distance without considering the first and last meter traveled. Cognitive status was assessed through the Short Portable Mental Status Questionnaire (SPMSQ) and the Mini-Mental State Examination (MMSE). We used a multivariate binomial logistic regression to conduct both an epidemiological and fully adjusted models. RESULTS: We included 519 older adults (mean age: 75 years; IQR = 10), of whom 95 (18.3%) and 151 (31.5%) were cognitively impaired according to the SPMSQ and MMSE, respectively. Gait speed was slower among patients with poorer cognitive status as assessed by both tools (p < 0.001). Malnutrition (PR: 1.74; CI: 1.45-2.08) and functional dependency (PR: 4.35; CI: 2.68-7.08) were associated with a greater prevalence of cognitive impairment according to the SPMSQ, whereas a faster gait speed (PR: 0.27, CI: 0.14-0.52) and longer years of education (PR: 0.83, CI: 0.77-0.88) were associated with a less prevalence. CONCLUSIONS: Slower gait speed was associated with poorer cognitive status in outpatient older adults. Gait speed may be a complementary tool in the cognitive assessment of older adults from resource-limited settings.

High level of infection prevention and control in surveyed hospitals in Colombia, 2021.

Objective: This study aimed to determine the performance of infection prevention and control (IPC) programs in eight core components in level 2 and level 3 hospitals across all provinces in Colombia. Methods: This cross-sectional study used self-assessed IPC performance data voluntarily reported by hospitals to the Ministry of Health and Social Protection during 2021. Each of the eight core components of the World Health Organization's checklist in the Infection Prevention and Control Assessment Framework contributes a maximum score of 100, and the overall IPC performance score is the sum of these component scores. IPC performance is graded according to the overall score as inadequate (0-200), basic (201-400), intermediate (401-600) or advanced (601-800). Results: Of the 441 level 2 and level 3 hospitals, 267 (61%) reported their IPC performance. The median (interquartile range [IQR]) overall IPC score was 672 (IQR: 578-715). Of the 267 hospitals reporting, 187 (70%) achieved an advanced level of IPC. The median overall IPC score was significantly higher in private hospitals (690, IQR: 598-725) than in public hospitals (629, IQR: 538-683) (P < 0.001). Among the core components, scores were highest for the category assessing IPC guidelines (median score: 97.5) and lowest for the category assessing workload, staffing and bed occupancy (median score: 70). Median overall IPC scores varied across the provinces (P < 0.001). Conclusions: This countrywide assessment showed that 70% of surveyed hospitals achieved a self-reported advanced level of IPC performance, which reflects progress in building health system resilience. Since only 61% of eligible hospitals participated, an important next step is to ensure the participation of all hospitals in future assessments.

Adherence to guidelines on the use of amoxicillin for treatment of ambulatory pneumonia in children younger than 5 years, Colombia, 2017-2019.

Objectives: To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence. Methods: This was a cross-sectional study of secondary data from the Colombian Integrated Social Protection Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1-4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, direct payment, pay per case, pay for event). Results: Of 215 925 cases of community-acquired pneumonia reported during 2017-2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guidelines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion: In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity.

In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential.

Multivariate Prognostic Models for Patients with Stages I and Ii Colon Carcinoma: a Strobe-Compliant Retrospective Cohort Study.

Background: Colorectal cancer is the most frequent gastrointestinal malignancy worldwide. The value of adjuvant treatment is controversial in Stages I and II. Objective: The aim of this study was to construct post-operative prognostic models applicable to patients with stages I-II colon carcinoma (CC). Methods: This is a retrospective cohort study of patients with Stage I-II CC treated over a 25-year period. Exposure was defined as clinical, histopathological, and immunohistochemical factors (including CDX2 and MUC2 expression). Patients were randomly allocated to either a "modeling set" or a "validation set". Factors associated with recurrence, disease-free survival (DFS), and overall survival (OS) were defined in the "modeling set". Their performances were tested in the "validation set". Results: From a total of 556 recruited patients, 339 (61%) were allocated to the "modeling set" and 217 (39%) to the "validation set". Three models explaining recurrence, DFS, and OS were described. Tumor location in the left colon (Hazards ratio [HR] = 1.57; 95% Confidence interval [CI] 0.99-2.48), lymphocyte (HR = 0.46; 96% CI 0.27-0.88) and monocyte (HR = 0.99; 95% CI 0.99-1) counts, neutrophil/platelet ratio (HR = 1.3; 95% CI 0.74-2.3, and HR = 2.3; 95% CI 1.3-4.1; for second and third category, respectively), albumin/monocyte ratio (HR = 0.43; 95% CI 0.21-0.87), and microscopic residual disease after surgery (HR = 8.7; 95% CI 3.1-24) were independently associated with OS. T classification and expression of CDX2 and/or MUC2 were not independently associated with recurrence or prognosis. Conclusion: These models are simple and readily available, and distinguish the risk and prognosis in patients with CC stages I and II; these models require cheaper processes than the use of more sophisticated molecular biology techniques. They may guide either the need for adjuvant therapy versus post-operative surveillance only, as well as aid in the design of clinical trials.

Non-alcoholic fatty liver disease prevalence in Latin America: A systematic review and meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) produces high morbidity and mortality rates. Its worldwide prevalence is 25%, but evidence from Latin America (LA) is lacking. We aimed to estimate the prevalence of NAFLD in the adult population of LA. We conducted a systematic review and meta-analysis. Data were collected from OVID, Cochrane Library and LILACS search engines. We used terms related to NAFLD and LA countries. Observational studies in adults who were born and live in LA were included. Two reviewers evaluated the articles, extracted data and assessed the risk of bias. Discrepancies were resolved by consensus or by a third reviewer. A validated tool was used to assess risk of bias. We found and analyzed 19 articles (n=5625). The prevalence in the general and captive population found was 24%. Populations with type 2 diabetes mellitus or obesity had a higher mean prevalence that reached 68%. We concluded that the average prevalence of NAFLD in LA is around 24%. Among high-risk groups, this value increases to 68%. Further studies in the general population using appropriate designs are required for an accurate estimate of the prevalence of NAFLD in LA.

Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PM10) through XPA Deregulation in Lung Epithelial Cells.

Airborne particulate matter with a diameter size of ≤10 µm (PM10) is a carcinogen that contains polycyclic aromatic hydrocarbons (PAH), which form PAH-DNA adducts. However, the way in which these adducts are managed by DNA repair pathways in cells exposed to PM10 has been partially described. We evaluated the effect of PM10 on nucleotide excision repair (NER) activity and on the levels of different proteins of this pathway that eliminate bulky DNA adducts. Our results showed that human lung epithelial cells (A549) exposed to 10 µg/cm2 of PM10 exhibited PAH-DNA adducts as well as an increase in RAD23 and XPD protein levels (first responders in NER). In addition, PM10 increased the levels of H4K20me2, a recruitment signal for XPA. However, we observed a decrease in total and phosphorylated XPA (Ser196) and an increase in phosphatase WIP1, aside from the absence of XPA-RPA complex, which participates in DNA-damage removal. Additionally, an NER activity assay demonstrated inhibition of the NER functionality in cells exposed to PM10, indicating that XPA alterations led to deficiencies in DNA repair. These results demonstrate that PM10 exposure induces an accumulation of DNA damage that is associated with NER inhibition, highlighting the role of PM10 as an important contributor to lung cancer.

Somatic Mutational Landscape in Mexican Patients: CDH1 Mutations and chr20q13.33 Amplifications Are Associated with Diffuse-Type Gastric Adenocarcinoma.

The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets.

Long-term PM2.5 exposure before diagnosis is associated with worse outcome in breast cancer.

PURPOSE: Increasingly epidemiological evidence supports that environmental factors are associated with breast cancer (BC) outcomes after a BC diagnosis. Although evidence suggests that air pollution exposure is associated with higher mortality in women with BC, studies investigating potential mechanisms have been lacking. METHODS: We evaluated women with BC (N = 151) attended at the National Cancer Institute-Mexico from 2012 to 2015. We calculated 1-year average exposures to particulate matter < 2.5 µm (PM2.5) at home address before diagnosis. We used linear and logistic regression models to determine the associations between PM2.5 exposure and BC aggressiveness (tumor size, molecular phenotype). RESULTS: Average annual PM2.5 exposure of this population was 23.0 µg/m3 [standard deviation (SD)]: 1.90 µg/m3]. PM2.5 levels were positively correlated with tumor size at diagnosis (r = 0.22; p = 0.007). Multivariable linear models had a similar inference [risk ratio (RR): 1.32; 95% confidence interval (95% CI): 1.04, 1.674]. We did not observe differences in this association by age or menopause status. Further, women with triple-negative BC (TNBC) had significantly higher PM2.5 levels compared with other phenotypes (p = 0.015). Multivariable-adjusted logistic regression models assessing the association between PM2.5 and tumor size had a similar inference (RR 1.41; 95% CI 1.05, 1.89) overall for all ages and also for women who were ≤ 50 years old at diagnosis (RR 1.63; 95% CI 1.036, 2.57). CONCLUSIONS: Our findings suggest a significant association between long-term PM2.5 exposure and BC aggressiveness based on tumor size and phenotype, as well as a worse outcome.

Nutritional Indexes as Predictors of Survival and Their Genomic Implications in Gastric Cancer Patients.

Gastric cancer is an aggressive malignancy with poor prognosis. Although obesity is a risk factor, an association between overweight and better survival has been reported. We explored the genomic implications of such association. Data from 940 patients were analyzed using Cox regression models and ROC curves to assess body mass index (BMI) and prognostic nutritional index (PNI) as predictors of survival. The exome sequencing of a random subset was analyzed to determine copy number variation (CNV) and single nucleotide variation (SNV), using Kruskal-Wallis and chi-square tests to evaluate their clinical implications. Overall survival was lower in patients with BMI ≤ 24.9 and PNI ≤ 29 (p < 0.001). BMI and survival were directly correlated (HR: 0.972, 95% CI: 0.953, 0.992; p-value < 0.007). A higher PNI correlated with improved survival (HR: 0.586, 95% CI: 0.429, 0.801; p-value <0.001). We found a PNI cutoff point of 41.00 for overall survival. Genomic analysis showed an association between lower BMI, less CNV events (p-value = 0.040) and loss of tumor suppressor genes (p-value = 0.021). BMI and PNI are independent factors for overall survival in gastric cancer, probably linked to variations in genomic intratumoral alterations.

Particulate Matter (PM10) Promotes Cell Invasion through Epithelial-Mesenchymal Transition (EMT) by TGF-ß Activation in A549 Lung Cells.

Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 µm or less in diameter (PM10) is considered an important risk factor in lung carcinogenesis. Epithelial-mesenchymal transition (EMT) is a regulatory program capable of inducing invasion and metastasis in cancer. In this study, we demonstrated that PM10 treatment induced phosphorylation of SMAD2/3 and upregulation of SMAD4. We also reported that PM10 increased the expression and protein levels of TGFB1 (TGF-ß), as well as EMT markers SNAI1 (Snail), SNAI2 (Slug), ZEB1 (ZEB1), CDH2 (N-cadherin), ACTA2 (α-SMA), and VIM (vimentin) in the lung A549 cell line. Cell exposed to PM10 also showed a decrease in the expression of CDH1 (E-cadherin). We also demonstrated that expression levels of these EMT markers were reduced when cells are transfected with small interfering RNAs (siRNAs) against TGFB1. Interestingly, phosphorylation of SMAD2/3 and upregulation of SMAD induced by PM10 were not affected by transfection of TGFB1 siRNAs. Finally, cells treated with PM10 exhibited an increase in the capacity of invasiveness because of EMT induction. Our results provide new evidence regarding the effect of PM10 in EMT and the acquisition of an invasive phenotype, a hallmark necessary for lung cancer progression.

Antitumor activity of a hydrogel loaded with lipophilic bismuth nanoparticles on cervical, prostate, and colon human cancer cells.

The objective of this study was to analyze the antitumor activity of a hydrogel loaded with lipophilic bismuth nanoparticles on human cervical, prostate, and colon cancer cell lines. The effect of lipophilic bismuth nanoparticles on the viability of cancer cell lines (HeLa, DU145, and HCT-116) and non-cancer lung fibroblasts (HLF; LL 47[MaDo]) was determined with the MTT cell viability assay and compared with known antineoplastic drugs. The biocompatibility at an organismal level was verified in a murine model by histological examination. A lipophilic bismuth nanoparticle hydrogel at 50 µM time-dependently inhibited the growth of the three cancer cell lines, in a time-dependent way. A 1-hour exposure to 250 µM lipophilic bismuth nanoparticle hydrogel, inhibited the growth of the three cancer cell lines. The in-vitro efficacy of lipophilic bismuth nanoparticle was similar to the one of docetaxel and cisplatin, but without inhibiting the growth of non-cancer control cells. Histology confirmed the biocompatibility of lipophilic bismuth nanoparticles as there were no signs of cytotoxicity or tissue damage in any of the evaluated organs (kidney, liver, brain, cerebellum, heart, and jejunum). In conclusion, a lipophilic bismuth nanoparticle hydrogel is an innovative, low-cost alternative for the topical treatment of cervicouterine, prostate, and colon human cancers.

Molecular and cellular mechanisms linking air pollution and bone damage.

Air pollution is the second most important risk factor associated with noncommunicable diseases after smoking. The effects of pollution on health are commonly attributable to particulate matter (PM), a complex mixture of particles suspended in the air. PM can penetrate the lower respiratory tract and has harmful direct and indirect effects on different organs and tissues. Direct effects are caused by the ability of PM components to cross the respiratory membrane and enter the bloodstream; indirect effects are systemic consequences of the local airway response. Recent work suggests that PM is an independent risk factor for low bone mineral density and osteoporosis-related fractures. Osteoporosis is a common age-related disease closely linked to bone fractures, with severe clinical consequences affecting quality of life, morbidity, and mortality. In this review, we discuss potential mechanisms behind the association between outdoor air pollution, especially PM, and bone damage. The discussion features four main mechanisms: 1) several different atmospheric pollutants can induce low-grade systemic inflammation, which affects bone metabolism through a specific effect of cytokines such as TNFα, IL-1ß, IL-6, and IL-17 on osteoblast and osteoclast differentiation and function; 2) some pollutants, particularly certain gas and metal compounds, can cause oxidative damage in the airway and bone cells; 3) different groups of pollutants can act as endocrine disruptors when binding to the receptors in bone cells, changing their functioning; and 4) air pollution can directly and indirectly cause vitamin D deficiency. Characterizing these mechanisms will better define the physiopathology of bone damage, and recognizing air pollution as a modifiable risk factor for osteoporosis will inform environmental policies. Such knowledge will also guide the prevention of fractures due to fragility and help reduce health-related costs.

Airborne Particulate Matter (PM10) Inhibits Apoptosis through PI3K/AKT/FoxO3a Pathway in Lung Epithelial Cells: The Role of a Second Oxidant Stimulus.

Outdoor particulate matter (PM10) exposure is carcinogenic to humans. The cellular mechanism by which PM10 is associated specifically with lung cancer includes oxidative stress and damage to proteins, lipids, and DNA in the absence of apoptosis, suggesting that PM10 induces cellular survival. We aimed to evaluate the PI3K/AKT/FoxO3a pathway as a mechanism of cell survival in lung epithelial A549 cells exposed to PM10 that were subsequently challenged with hydrogen peroxide (H2O2). Our results showed that pre-exposure to PM10 followed by H2O2, as a second oxidant stimulus increased the phosphorylation rate of pAKTSer473, pAKTThr308, and pFoxO3aSer253 2.5-fold, 1.8-fold, and 1.2-fold, respectively. Levels of catalase and p27kip1, which are targets of the PIK3/AKT/FoxO3a pathway, decreased 38.1% and 62.7%, respectively. None of these changes had an influence on apoptosis; however, the inhibition of PI3K using the LY294002 compound revealed that the PI3K/AKT/FoxO3a pathway was involved in apoptosis evasion. We conclude that nontoxic PM10 exposure predisposes lung epithelial cell cultures to evade apoptosis through the PI3K/AKT/FoxO3a pathway when cells are treated with a second oxidant stimulus.

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks.

Air pollution has been recognized as a global health problem, causing around 7 million deaths worldwide and representing one of the highest environmental crises that we are now facing. Close to 30% of new lung cancer cases are associated with air pollution, and the impact is more evident in major cities. In this review, we summarize and discuss the evidence regarding the effect of particulate matter (PM) and its impact in carcinogenesis, considering the "hallmarks of cancer" described by Hanahan and Weinberg in 2000 and 2011 as a guide to describing the findings that support the impact of particulate matter during the cancer continuum.

Titanium dioxide nanoparticles induce an adaptive inflammatory response and invasion and proliferation of lung epithelial cells in chorioallantoic membrane.

Titanium dioxide nanoparticles (TiO2 NPs) studies have been performed using relatively high NPs concentration under acute exposure and limited studies have compared shape effects. We hypothesized that midterm exposure to low TiO2 NPs concentration in lung epithelial cells induces carcinogenic characteristics modulated partially by NPs shape. To test our hypothesis we synthesized NPs shaped as belts (TiO2-B) using TiO2 spheres (TiO2-SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10 µg/cm(2)) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO2-B effect on agglomerates size, cell size and granularity than TiO2-SP. Agglomerates size in cell culture medium was 310 nm and 454 nm for TiO2-SP and TiO2-B, respectively; TiO2-SP and TiO2-B induced 23% and 70% cell size decrease, respectively, whilst TiO2-SP and TiO2-B induced 7 and 14-fold of granularity increase. NOx production was down-regulated (31%) by TiO2-SP and up-regulated (70%) by TiO2-B. Both NPs induced a transient cytokine release (IL-2, IL-6, IL-8, IL-4, IFN-γ, and TNF-α) after 4 days, but cytokines returned to basal levels in TiO2-SP exposed cells while TiO2-B induced a down-regulation after 7 days. Midterm exposure to both shapes of NPs induced capability to degrade cellular extracellular matrix components from chorioallantoic membrane and Ki-67 marker showed that TiO2-B had higher proliferative potential than TiO2-SP. We conclude that midterm exposure to low NPs concentration of NPs has an impact in the acquisition of new characteristics of exposed cells and NPs shape influences cellular outcome.

Predictors of Endocrine Resistance in a Cohort of Mexican Breast Cancer Patients.

Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.