Who are we missing? Language exclusivity of patient-reported outcomes in atrial fibrillation clinical trials.

INTRODUCTION: Patient-reported outcomes (PROs) are increasingly used to evaluate quality of life (QoL) in Atrial Fibrillation (AF) patients, providing crucial insights in clinical trials. This study examines the frequency of PRO use in AF trials and the linguistic accessibility of AF-specific PROs. BACKGROUND: As the United States becomes more multilingual, ensuring PROs are available in various languages is vital. The number of people speaking a language other than English at home has tripled from 23.1 million in 1980 to 67.8 million in 2019. This diversity necessitates the availability of PROs in multiple languages for inclusive clinical assessments. METHODS: We queried ClinicalTrials.gov for all US interventional AF trials up to November 28, 2023, reviewing each for PRO usage as primary or secondary outcomes. We identified the five most common AF-specific and generic PROs, extracting their available translations and original languages from published sources. RESULTS: Of 233 identified trials, 191 had associated publications, with 180 (94.2%) conducted solely in English. Only one trial (0.4%) used an AF-specific PRO as a primary outcome, compared to four (1.7%) with a generic PRO. Ten trials (4.3%) used AF-specific PROs as secondary endpoints, versus 22 (9.4%) using generic PROs. AF-specific PROs had significantly fewer translations than generic PROs (11.2 vs. 148.8; p < .001). The AF Effect on Quality-of-Life (AFEQT) was available in 24 languages, with limited translations in commonly spoken US languages like Arabic and Asian languages. CONCLUSION: The limited availability of AF-specific PRO translations highlights a barrier to inclusive AF clinical trials. Expanding translations for AF-specific PROs is crucial for equitable QoL assessments.

A novel role of IGFBP5 in the migration, invasion and spheroids formation induced by IGF-I and insulin in MCF-7 breast cancer cells.

PURPOSE: The insulin-like growth factor (IGF) system includes IGF-I, IGF-II insulin and their membrane receptors. IGF system also includes a family of proteins namely insulin-like growth factor-binding proteins (IGFBPs) composed for six major members (IGFBP-1 to IGFBP6), which capture, transport and prolonging half-life of IGFs. However, it has been described that IGFBPs can also have other functions. METHODS: IGFBP5 expression was inhibited by shRNAs, migration was analyzed by scratch-wound assays, invasion assays were performed by the Boyden chamber method, spheroids formation assays were performed on ultra-low attachment surfaces, expression and phosphorylation of proteins were analyzed by Western blot. RESULTS: IGFBP5 is a repressor of IGF-IR expression, but it is not a repressor of IR in MCF-7 breast cancer cells. In addition, IGFBP5 is a suppressor of migration and MMP-9 secretion induced by IGF-I and insulin, but it does not regulate invasion in MCF-7 cells. IGFBP5 also is a repressor of MCF-7 spheroids formation. However treatment with 340 nM rescues the inhibitory effect of IGFBP in the MCF-7 spheroids formation. CONCLUSION: IGFBP5 regulates IGF-IR expression, migration and MMP-9 secretion induced by IGF-I and/or insulin, and the spheroids formation in MCF-7 breast cancer cells.

Benzo[a]pyrene promotes an epithelial-to-mesenchymal transition process in MCF10A cells and mammary tumor growth and brain metastasis in female mice.

Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA-MB-231 and MCF-7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.

Caveolae Microdomains Mediate STAT5 Signaling Induced by Insulin in MCF-7 Breast Cancer Cells.

Caveolae are small plasma membrane invaginations constituted for membrane proteins namely caveolins and cytosolic proteins termed cavins, which can occupy up to 50% of the surface of mammalian cells. The caveolae have been involved with a variety of cellular processes including regulation of cellular signaling. Insulin is a hormone that mediates a variety of physiological processes through activation of insulin receptor (IR), which is a tyrosine kinase receptor expressed in all mammalian tissues. Insulin induces activation of signal transducers and activators of transcription (STAT) family members including STAT5. In this study, we demonstrate, for the first time, that insulin induces phosphorylation of STAT5 at tyrosine-694 (STAT5-Tyr(P)694), STAT5 nuclear accumulation and an increase in STAT5-DNA complex formation in MCF-7 breast cancer cells. Insulin also induces nuclear accumulation of STAT5-Tyr(P)694, caveolin-1, and IR in MCF-7 cells. STAT5 nuclear accumulation and the increase of STAT5-DNA complex formation require the integrity of caveolae and microtubule network. Moreover, insulin induces an increase and nuclear accumulation of STAT5-Tyr(P)694 in MDA-MB-231 breast cancer cells. In conclusion, results demonstrate that caveolae and microtubule network play an important role in STAT5-Tyr(P)694, STAT5 nuclear accumulation and STAT5-DNA complex formation induced by insulin in breast cancer cells.

Bovine holo-lactoferrin inhibits migration and invasion in MDA-MB-231 breast cancer cells.

PURPOSE: Breast cancer is the most common malignancy in developed countries and the main cause of deaths in women worldwide. Lactoferrin (Lf) is an iron-binding protein constituted for a single polypeptide chain that is folded into two symmetrical lobes that bind Fe2+ or Fe3+. Lf has the ability to reversibly bind Fe3+ and is found free of Fe3+ (Apo-Lf) or associated with Fe3+ (Holo-Lf) with a different three-dimensional conformation. However, the role of bovine Apo-Lf (Apo-BLf) and bovine Holo-Lf (Holo-BLf) in the migration and invasion induced by linoleic acid (LA) and fetal bovine serum (FBS), as well as in the expression of mesenchymal and epithelial proteins in breast cancer cells has not been studied. METHODS AND RESULTS: Scratch wound assays demonstrated that Holo-BLf and Apo-BLf do not induce migration, however they differentially inhibit the migration induced by FBS and LA in breast cancer cells MDA-MB-231. Western blot, invasion, zymography and immunofluorescence confocal microscopy assays demonstrated that Holo-BLf partly inhibit the invasion, FAK phosphorylation at tyrosine (Tyr)-397 and MMP-9 secretion, whereas it increased the number and size of focal adhesions induced by FBS in MDA-MB-231 cells. Moreover, Holo-BLf induced a slight increase of E-cadherin expression in MCF-7 cells, and inhibited vimentin expression in MCF-7 and MDA-MB-231 breast cancer cells. CONCLUSION: Holo-BLf inhibits cellular processes that mediate the invasion process in breast cancer cells.

Influence of preventive sex education programmes in compulsory secondary education students: a descriptive observational study.

BACKGROUND: Sex education programmes conducted by health professionals and educators are essential for young people to adopt healthy habits and attitudes towards their sexuality. The Forma Joven Program, promoted by the Andalusian Regional Government's Ministry of Health and Families and Education, is a good example of this. The aim of the study is to determine if different "degrees of intervention" in the informative consultancies of the Forma Joven Program imply differences in knowledge and attitudes towards sexuality. METHODS: This descriptive observational study analysed 27 Compulsory Secondary Education high schools in Huelva. These were included in the Program and belonged to a Primary Care Health District. Out of the 17 institutes initially selected because they met the inclusion criteria (4.256 students), finally 14 (3.596 students) participated. During the 2018/2019 school year, students from 3rd, 4th year of Secondary Compulsory Education (ESO), 1st, and 2nd Baccalaureate of the selected centres were asked to fill in a questionnaire of knowledge and attitudes towards sexuality. It collected variables such as age, sex, school year, institute, educational level and employment status of the father or mother and profile of the professional who delivers the counselling. RESULTS: A total of 1.237 students completed the questionnaire, which represents a participation rate of 34.4%. The average age was 15.59 years (SD 1.26) and 39.9% were girls. In some evaluated questions, we found statistically significant differences between the groups with different levels of exposure to counselling and the acquisition of knowledge and attitudes towards students' sexuality, although in most of them no such differences were found. The results of this study suggest the importance of the quality of counselling over quantity. Some classic myths persist in relation to sexuality and in some situations, they can be decisive when adopting preventive measures to avoid risks related to pregnancy and contagion of STIs. CONCLUSIONS: A greater number of counselling sessions does not imply acquiring a higher level of knowledge or better attitudes towards sexuality. Perhaps the quality of the education is more important than the quantity of counselling sessions.

Cancer-associated Fibroblasts Communicate with Breast Tumor Cells Through Extracellular Vesicles in Tumor Development.

Breast cancer is the leading cause of cancer death among women worldwide. In solid tumors, the microenvironment plays a critical role in tumor development, and it has been described a communication between the different cell types that conform the stroma, including fibroblasts, pericytes, adipocytes, immune cells and cancer-associated fibroblasts. Intercellular communication is bidirectional, complex, multifactorial and is mediated by the secretion of molecules and extracellular vesicles. The extracellular vesicles are vesicles limited by two membranes that are secreted by normal and cancer cells into the extracellular space. Extracellular vesicle cargo is complex and includes proteins, miRNAs, DNA and lipids, and their composition is specific to their parent cells. Extracellular vesicles are taken up for neighboring or distant cells. Particularly, extracellular vesicles from breast cancer cells are taken up for fibroblasts and it induces the activation of fibroblasts into cancer-associated fibroblasts. Interestingly, cancer associated fibroblasts release extracellular vesicles that are taken up for breast cancer cells and promote migration, invasion, proliferation, epithelial-mesenchymal transition, changes in metabolism, chemoresistance, evasion of immune system and remodeling of extracellular matrix. In addition, the enrichment of specific cargos in extracellular vesicles of breast cancer patients has been suggested to be used as biomarkers of the disease. Here we review the current literature about the intercommunication between tumor cells and cancer associated fibroblasts through extracellular vesicles in breast cancer.

Accuracy of machine learning algorithms for the assessment of upper-limb motor impairments in patients with post-stroke hemiparesis: A systematic review and meta-analysis.

BACKGROUND: The assessment of motor function is vital in post-stroke rehabilitation protocols, and it is imperative to obtain an objective and quantitative measurement of motor function. There are some innovative machine learning algorithms that can be applied in order to automate the assessment of upper extremity motor function. OBJECTIVES: To perform a systematic review and meta-analysis of the efficacy of machine learning algorithms for assessing upper limb motor function in post-stroke patients and compare these algorithms to clinical assessment. MATERIAL AND METHODS: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database. The review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed using 6 electronic databases. The meta-analysis was performed with the data from the correlation coefficients using a random model. RESULTS: The initial search yielded 1626 records, but only 8 studies fully met the eligibility criteria. The studies reported strong and very strong correlations between the algorithms tested and clinical assessment. The meta-analysis revealed a lack of homogeneity (I2 = 85.29%, Q = 48.15), which is attributable to the heterogeneity of the included studies. CONCLUSION: Automated systems using machine learning algorithms could support therapists in assessing upper extremity motor function in post-stroke patients. However, to draw more robust conclusions, methodological designs that minimize the risk of bias and increase the quality of the methodology of future studies are required.

Judicialization of health: profile of demands for oncological medicines in a state in the central region of Brazil.

BACKGROUND: The significant increase in access to oncological medicines through court cases suggests that constitutional guarantees of integral and universal care in the Brazilian public health system are uncertain. METHODS: A retrospective observational study was conducted to analyze data from lawsuits requesting oncological medicines from 2014 to 2020 in the State of Goiás, Brazil, in state and federal courts. Sociodemographic, medical, and legal variables were statistically examined using descriptive, association, and correlation methods. RESULTS: Women brought more than half (54%) of the 301 processes analyzed. The most frequent age group was over 55 years, with income below 3 × the minimum wage (total about USD$600/month), and their cases were promoted through the public minister and public defender's offices. The most requested medications, not on official public health system lists, were indicated for multiple myeloma and brain cancer. CONCLUSIONS: Improved quality of life, frequently used as a justification, could be conceptually confused with increased survival. Finally, judicialization itself indicates that individual health needs arise even with properly defined and adequately implemented public policies. These needs should be considered for the adequate provisioning of services by the state to ensure the right to health.

Extracellular vesicles from blood of breast cancer women induce angiogenic processes in HUVECs.

Breast cancer is the most frequent malignancy among women in developed countries and the main cause of death related to cancer in women worldwide. Extracellular vesicles (EVs) are vesicles with a variable size enclosed within a phospholipid bilayer that contain a variety of molecules with biological activity. Cancer cells release EVs that induce proliferation, escape from apoptosis, reprogramming energy metabolism, invasion and metastasis. In this study we studied whether EV fractions deprived of platelet EVs from breast cancer women (BC EVs) can mediate cell processes related with angiogenesis in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that BC EVs enhance migration, invasion and formation of new tubules in HUVECs, compared with EV fractions deprived of platelet EVs from healthy women (Ctrl EVs). In summary, we demonstrate, for the first time, that BC EVs induce cellular processes in HUVECs that participate in angiogenesis.

Extracellular vesicles from MDA-MB-231 breast cancer cells stimulated with insulin-like growth factor 1 mediate an epithelial-mesenchymal transition process in MCF10A mammary epithelial cells.

Insulin-like growth factor-1 (IGF-1) plays an important role in function and development of the mammary gland. However, high levels of IGF-1 has been associated with an increased risk of breast cancer development. Epithelial-mesenchymal transition (EMT) is a process where epithelial cells lose their epithelial characteristics and acquire a mesenchymal phenotype, which is considered one of the most important mechanisms in cancer initiation and promotion of metastasis. Extracellular vesicles (EVs) are released into the extracellular space by different cell types, which mediate intercellular communication and play an important role in different physiological and pathological processes, such as cancer. In this study, we demonstrate that EVs from MDA-MB-231 breast cancer cells stimulated with IGF-1 (IGF-1 EVs) decrease the levels of E-cadherin, increase the expression of vimentin and N-cadherin and stimulate the secretion of metalloproteinase-9 in mammary non-tumorigenic epithelial cells MCF10A. IGF-1 EVs also induce the expression of Snail1, Twist1 and Sip1, which are transcription factors involved in EMT. Moreover, IGF-1 EVs induce activation of ERK1/2, Akt1 and Akt2, migration and invasion. In summary, we demonstrate, for the first time, that IGF-1 EVs induce an EMT process in mammary non-tumorigenic epithelial cells MCF10A.

Role of Src/FAK in migration and invasion mediated by extracellular vesicles from MDA-MB-231 cells stimulated with linoleic acid.

Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in occidental diets, which mediate a variety of processes in human breast cancer cells, including migration and invasion. Extracellular vesicles (EVs) are vesicles released from endosomes and plasma membrane that are composed of a variety of molecules, including proteins, nucleic acids and lipids. EVs from cancer cells promote processes related with cancer progression. In the present study, we demonstrate that treatment of MDA-MB-231 cells with EVs from MDA-MB-231 cells stimulated with LA (LA EVs) promote migration and invasion via Src activity. LA EVs induce activation of FAK via Src activity and of Src and Akt2. LA EVs also induce the assembly of focal adhesions and MMP-9 secretion. These findings demonstrate that LA EVs mediate an autocrine and/or paracrine Src/FAK signaling pathway to promote migration and invasion.

The influence of hydrogen ions on coagulation in traumatic brain injury, explored by molecular dynamics.

Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition.Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests.Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten "healthy control subjects", and another nine patients as "disease control subjects"; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules.Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in "disease control subjects". Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors "trap" ions.Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.

Linoleic acid induces secretion of extracellular vesicles from MDA-MB-231 breast cancer cells that mediate cellular processes involved with angiogenesis in HUVECs.

Extracellular vesicles (EVs) are vesicles secreted by normal and malignant cells that are implicated in tumor progression. Linoleic acid (LA) is an essential polyunsaturated fatty acid that induces migration, invasion and an increase in phospholipase D activity in breast cancer cells. In this study, we determined whether stimulation of MDA-MB-231 breast cancer cells with LA induces the secretion of EVs, which can mediate cell processes related with angiogenesis in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that treatment of MDA-MB-231 cells with 90 µM LA for 48 h induce an increase in the number of EVs released. Moreover, EVs from MDA-MB-231 stimulated with 90 µM LA induce FAK and Src activation and migration via FAK and Src activity, whereas the secretion of these EVs is through FFAR1 and FFAR4 activation in HUVECs. The EVs from MDA-MB-231 cells treated with LA also increase proliferation, invasion, MMP-9 secretion, an increase of MMP-2 secretion and formation of new tubules in HUVECs. In summary, we demonstrate, for the first time, that treatment with LA induces the release of EVs from MDA-MB-231 cells that induce cellular processes involved with angiogenesis in HUVECs.

Factors related to asymptomatic or severe COVID-19 infection.

The factors that may contribute to a COVID-19 patient remaining in the asymptomatic stage, or to the infection evolving into the more serious stages are examined. In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2. Also, we review other factors related to the susceptibility and pathogenicity of SARS-CoV-2.

Prevention of severe COVID-19 in the elderly by early high-titer plasma

BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression. MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate [≥]30 and/or an O2 sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible. Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%. A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed. ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives. Funded by The Bill & Melinda Gates Foundation and The Fundacion INFANT Pandemic Fund. Registered in the Direccion de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163). All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.

Bisphenol A induces focal adhesions assembly and activation of FAK, Src and ERK2 via GPER in MDA-MB-231 breast cancer cells.

Bisphenol A (BPA) is an industrial synthetic chemical used in the production of polycarbonate plastics and epoxy resins. Human exposition to BPA is primarily through eating food, and drinking liquids, because BPA can leach from polycarbonate plastic containers, beverage cans and epoxy resins. BPA induces proliferation and migration in human breast cancer cells. The G protein-coupled estrogen receptor (GPER) is a G protein-coupled receptor coupled with Gs proteins that is activated by estrogen and estrogenic compounds and it is the receptor for BPA. However, the signal transduction pathways that mediate migration via BPA/GPER in triple negative breast cancer (TNBC) cells has not been studied in detail. Here, we demonstrate that BPA induces an increase of GPER expression and activation of FAK, Src and ERK2, and an increase of focal adhesion assembly via GPER in TNBC MDA-MB-231 cells. Moreover, BPA induces FAK and ERK2 activation, focal adhesion assembly and migration via epidermal growth factor receptor (EGFR) transactivation. Collectively our data showed that BPA via GPER and/or EGFR transactivation induces activation of signal transduction pathways that mediate migration in TNBC MDA-MB-231 cells.

Obesity subtypes, related biomarkers & heterogeneity.

Obesity is a serious medical condition worldwide, which needs new approaches and recognized international consensus in treating diseases leading to morbidity. The aim of this review was to examine heterogeneous links among the various phenotypes of obesity in adults. Proteins and associated genes in each group were analysed to differentiate between biomarkers. A variety of terms for classification and characterization within this pathology are currently in use; however, there is no clear consensus in terminology. The most significant groups reviewed include metabolically healthy obese, metabolically abnormal obese, metabolically abnormal, normal weight and sarcopenic obese. These phenotypes do not define particular genotypes or epigenetic gene regulation, or proteins related to inflammation. There are many other genes linked to obesity, though the value of screening all of those for diagnosis has low predictive results, as there are no significant biomarkers. It is important to establish a consensus in the terminology used and the characteristics attributed to obesity subtypes. The identification of specific molecular biomarkers is also required for better diagnosis in subtypes of obesity.

Role of PI3K/Akt on migration and invasion of MCF10A cells treated with extracellular vesicles from MDA-MB-231 cells stimulated with linoleic acid.

In breast cancer cells, the linoleic acid (LA), an ω-6 essential polyunsaturated fatty acid, induces a variety of biological processes, including migration and invasion. Extracellular vesicles (EVs) are structures released by normal and malignant cells into extracellular space, and their function is dependent on their cargo and the cell type from which are secreted. Particularly, the EVs from MDA-MB-231 breast cancer cells treated with LA promote an epithelial-mesenchymal-transition (EMT)-like process in mammary non-tumorigenic epithelial cells MCF10A. Here, we found that EVs isolated from supernatants of MDA-MB-231 breast cancer cells stimulated with 90 µM LA induces activation of Akt2, FAK and ERK1/2 in MCF10A cells. In addition, EVs induces migration through a PI3K, Akt and ERK1/2-dependent pathway, whereas invasion is dependent on PI3K activity.