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In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m 2 ), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile’s population turns out to be the closest to BA’s, principally due to the presence of Verrucomicrobiales of the genus Akkermansia . These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.

Estrogen receptor alpha gene ( ESR1 ) mutations occur frequently in ER-positive metastatic breast cancer (MBC), and confer clinical resistance to aromatase inhibitors (AIs). Expression of the ESR1 Y537S mutation induced an epithelial-mesenchymal transition (EMT) with cells exhibiting enhanced migration and invasion potential in vitro . When small subpopulations of Y537S ESR1 mutant cells were injected along with WT parental cells, tumor growth was enhanced with mutant cells becoming the predominant population in distant metastases. Y537S mutant primary xenograft tumors were resistant to the antiestrogen tamoxifen (Tam) as well as to estrogen withdrawal. Y537S ESR1 mutant primary tumors metastasized efficiently in the absence of estrogen; however, Tam treatment significantly inhibited metastasis to distant sites. We identified a 9 gene expression signature which predicted clinical outcomes of ER-positive breast cancer patients, as well as breast cancer metastasis to the lung. Androgen receptor (AR) protein levels were increased in mutant models, and the AR agonist dihydrotestosterone (DHT) significantly inhibited estrogen-regulated gene expression, EMT, and distant metastasis in vivo, suggesting that AR may play a role in distant metastatic progression of ESR1 mutant tumors.

Mesenchymal progenitor cell characteristics that can identify progenitor populations with specific functions in immunity are actively being investigated. Progenitors from bone marrow and adipose tissue regulate the macrophage (MΦ) inflammatory response by promoting the switch from an inflammatory to an anti-inflammatory phenotype. Conversely, mesenchymal progenitors from the mouse aorta (mAo) support and contribute to the MΦ response under inflammatory conditions. We used cell lines with purported opposing immune-regulatory function, a bone marrow derived mesenchymal progenitor cell line (D1) and a mouse aorta derived mesenchymal progenitor cell line (mAo). Their interaction and regulation of the MΦ cell response to the inflammatory mediator, lipopolysaccharide (LPS), was examined by coculture. As expected, D1 cells suppressed NO, TNF-α, and IL-12p70 production but MΦ phagocytic activity remained unchanged. The mAo cells enhanced NO and TNF-α production in coculture and enhanced MΦ phagocytic activity. Using flow cytometry and PCR array, we then sought to identify sets of MSC-associated genes and markers that are expressed by these progenitor populations. We have determined that immune-supportive mesenchymal progenitors highly express chondrogenic and tenogenic transcription factors while immunosuppressive mesenchymal progenitors highly express adipogenic and osteogenic transcription factors. These data will be useful for the isolation, purification, and modification of mesenchymal progenitors to be used in the treatment of inflammatory diseases.

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Background: Research has established that mammograms reduce breast cancer mortality, and regular Pap testing reduces both incidence and mortality from cervical cancer. Despite clear recommendations and benefits, Puerto Rican women remain disproportionally under-screened. Behavioral interventions in PR are scarce, therefore Puerto Rico Cancer Control Outreach Program (PRCCOP) trained lay health workers (Promotoras) to focus on increasing breast and cervical screening practices among non-adherent women. This effort was possible through a partnership with Taller Salud, a community based organization. Objectives: To summarizes the methodology of recruitment and intervention delivery of this population-based intervention among non-adherent women living in Canóvanas, PR. Methods: A systematic random sample of 444 women (236 intervention arm; 208 control arm). Eligible women were: 40+ years old with no mammogram in the past year or 21+ years old with no Pap test in the last 3 years. According to their non-adherence status, women were assigned to either a Mammography or a Pap group, and randomly assigned to intervention or control groups. We conducted a baseline survey that included questions about history of breast and Pap test screening, knowledge, perceptions and attitudes about breast and cervical cancer screening and sociodemographic characteristics. Promotoras delivered educational sessions to women in the intervention group. Follow-up surveys were conducted four months after the baseline survey (control group) or after intervention delivery (intervention group), to assess self-reported mammogram and Pap test screening rates. Results: Study period was July 2012-July 2013 and included collaboration from 25 interviewers and 12 Promotoras. Trainings for the Promotoras lasted about 8 hours and included topics such as: role of the Promotora, reaching women, finding breast cancer early, breast cancer screening: barriers and responses, Pap Test: barriers and responses, teaching methods, practices session using program materials and resources and referrals. Participation rate for the baseline survey was 94.8%. A total of 210 interventions (88.9%) were completed. Mean age of study participants was 50 ±14.1 years. Eighteen percent of the women 40+ years old reported never having a mammography, while 12.4% of the sample reported never having had a Pap in their lifetime. Over half of the participants had not completed high school (52%) and were married (58%). Almost two thirds of the sample reported having a household gross income of less than $19,999 and 9.5% reported having no medical plan. Fifty percent of the participants reported having Mi Salud, a governmental healthcare plan of Puerto Rico. Conclusions: The experience gained in this educational intervention will help establish similar studies island-wide. It also highlights the need to reach under screened women and maintaining efforts with Community Based Organizations to promote cancer screening among Puerto Rican women. Citation Format: Maria E. Fernandez, Vivian Colon-Lopez, Edna Acosta, Camille Velez, Natalie Fernandez, Marievelisse Soto-Salgado, Erick Suarez, Alana Feldman, Alelí Ayala Marín, Angela Pattatucci. Outreach efforts for cervical and breast cancer prevention and control in Puerto Rico: Cultivando la Salud. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B69. doi:10.1158/1538-7755.DISP13-B69

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