Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles.

The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity induced by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. In vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, fibroblast-produced secreted factors stimulated treatment-independent enhancement of tumor cell proliferation. Spatial analyses indicated that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo. These observations suggested an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate this hypothesis, a spatial agent-based model of stroma impact on proliferation/death dynamics was developed that was quantitatively parameterized using inferences from histologic analyses and experimental studies. The model demonstrated that the observed enhancement of tumor cell proliferation within stroma-proximal niches could enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, this study supports the existence of an indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes. SIGNIFICANCE: Integration of experimental research with mathematical modeling reveals an indirect microenvironmental chemoresistance mechanism by which stromal cells stimulate breast cancer cell proliferation and highlights the importance of consideration of proliferation/death dynamics. See related commentary by Wall and Echeverria, p. 3667.

Paracrine enhancement of tumor cell proliferation provides indirect stroma-mediated chemoresistance via acceleration of tumor recovery between chemotherapy cycles.

The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. Our in vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, we observed treatment-independent enhancement of tumor cell proliferation by fibroblast-produced secreted factors. Using spatial statistics analyses, we found that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo . Based on these observations, we hypothesized an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate the feasibility of this hypothesis, we developed a spatial agent-based model of stroma impact on proliferation/death dynamics. The model was quantitatively parameterized using inferences from histological analyses and experimental studies. We found that the observed enhancement of tumor cell proliferation within stroma-proximal niches can enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, our study supports the existence of a novel, indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes.

Relación entre seguridad alimentaria y estado nutricional: abordaje de los niños indígenas del norte del Valle del Cauca, Colombia / Relationship between food security and nutritional status: in indigenous children in north of Valle del Cauca, Colombia

INTRODUCCIÓN: La seguridad alimentaria (SA) es el acceso físico, social y económico a los alimentos suficientes en calidad nutricional, cantidad e inocuidad, que conlleven a una vida sana y activa. La falta de SA genera malnutrición. Los grupos sociales más vulnerables son los indígenas y sus niños. El presente estudio tuvo como objetivo describir la relación entre el nivel de seguridad alimentaria y el estado nutricional de los niños de una comunidad indígena Embera Chamí del Valle del Cauca. METODOLOGÍA: Se seleccionaron hogares con niños entre 1 y 5 años y se aplicó encuesta sociodemográfica, la Escala Latinoamericana y Caribeña de Seguridad Alimentaria (ELCSA); se tomaron medidas antropométricas (peso, talla y perímetro cefálico). RESULTADOS: Todos los hogares se encontraron en algún grado de inseguridad alimentaria (IA), el 78,7% se encontraba en IA severa, el 12,7% en IA moderada y el 8,5% en IA leve. Referente al estado nutricional con retraso en talla se encontró el 68,33% de los menores, con desnutrición aguda moderada o severa el 10% de los niños. Para la relación entre IA y estado nutricional se evidenció que en los hogares con IA severa 6 niños (10%) tienen desnutrición aguda y 41 niños (68,33%) tienen retraso en talla

INTRODUCTION: Food security (FS) is defined as physical, social and economic access to sufficient food in nutritional quality, quantity and safety; If this is the first time this occurs, malnutrition especially in the most vulnerable social groups such as indigenous people and children of these communities. The objective of the study is to describe the relationship between the level of food security and the nutritional status of children from an Embera Chamí indigenous community in Valle del Cauca, Colombia. METHODOLOGY: Homes with children between 1 and 5 years were selected; to which a sociodemographic survey was applied, the Latin American and Caribbean Scale of Food Security (ELCSA) and anthropometric measures were taken (weight, height and cephalic perimeter). Data were analyzed in STATA. The results All households were enrolled in Food insecurity (FI), 78.7% were found in severe FI, 12.7% in moderate FI and 8.5% in low FI. With regard to nutritional status, weight-for-height it was found that 6.3% of homes have at least one child with severe acute malnutrition. For the relationship between FI and nutritional status, 60 children were taken into account, evidencing that: 2 of the 3 children who were in severe acute malnutrition presented severe FI (3.33%) and the other child FI low (1.66%); Of the 41 children who had severe chronic malnutrition, 32 had severe FI (53.3%), 5 moderate FI (8.33%) and 4 low FI (6.66%)

Two sisters in the same dress: Heliconius cryptic species.

BACKGROUND: Sister species divergence and reproductive isolation commonly results from ecological adaptation. In mimetic Heliconius butterflies, shifts in colour pattern contribute to pre- and post-mating reproductive isolation and are commonly correlated with speciation. Closely related mimetic species are therefore not expected, as they should lack several important sources of reproductive isolation. RESULTS: Here we present phenotypic, behavioral and genetic evidence for the coexistence of two sympatric 'cryptic' species near Florencia in the eastern Andes of Colombia that share the same orange rayed colour pattern. These represent H. melpomene malleti and a novel taxon in the H. cydno group, here designated as novel race of Heliconius timareta, Heliconius timareta florencia. No-choice mating experiments show that these sympatric forms have strong assortative mating ( approximately 96%) despite great similarity in colour pattern, implying enhanced divergence in pheromonal signals. CONCLUSION: We hypothesize that these species might have resulted from recent convergence in colour pattern, perhaps facilitated by hybrid introgression of wing pattern genes.