In carcinomas such as those of breast, pancreas, stomach, and colon, cancer cells support the expansion of molecular and cellular stroma in a phenomenon termed desmoplasia, which is characterized by a strong fibrotic response. In the case of breast tissue, in which stroma is mainly a fatty tissue, this response presumably occurs at the expense of the adipose cells, the most abundant stromal phenotype, generating a tumoral fibrous structure rich in fibroblast-like cells. In this study, we aimed to determine the cellular mechanisms by which factors present in the media conditioned by MDA-MB-231 and MCF-7 human breast cancer cell lines induce a reversion of adipose cells to a fibroblastic phenotype. We demonstrated that soluble factors generated by these cell lines stimulated the reversion of mammary adipose phenotype evaluated as intracellular lipid content and expression of C/EBP alpha and PPAR gamma. We also demonstrated that exogenous TGF-beta 1 and TNF-alpha exerts a similar function. The participation of both growth factors, components of media conditioned by tumoral mammary cells, on the expression and nuclear translocation of C/EBP alpha and PPAR gamma was tested in 3T3-L1 cells by interfering with the inhibitory effects of media with agents that block the TGF-beta 1 and TNF-alpha activity. These results allow us to postulate that TGF-beta 1 and TNF-alpha present in this media are in part responsible for this phenotypic reversion.
Patients who undergo breast reduction surgery have a low risk of being found to have breast cancer, but they need to be made aware of it—and doctors need to debate whether routine histological examination of tissue specimens is a good idea. We sought the views of Tom Treasure, a surgeon (doi:), Jeremy Sugarman, an ethicist (doi:), and Tessa Boase, a lay person ()
Introduction: The COVID-19 pandemic has changed health systems across the world, both in general hospitals and in oncology institutes or centres. For cancer specialists, particularly breast cancer (BC), the COVID-19 pandemic represents a combination of challenges since the hospital resources and staff have become more limited; this has obliged oncology specialists to seek a consensus and establish which patients with BC require more urgent attention and which patients can wait until there is a better control of this pandemic. The health system in Latin America has some special characteristics; in some of the countries, there are shortages which limit access to several specialities (surgery, clinical oncology and radiotherapy) in some regions. Objective: After a systematic review of the most recent literature regarding the management of BC during the COVID-19 pandemic, the main objective is to understand the position of the different Latin American Societies of Mastology in terms of available alternatives for the treatment of BC. Methods: After carrying out a comprehensive and exhaustive search of the most recent guides on the management of BC during the COVID-19 pandemic, the board members of the Latin American Federation of Mastology invited, via email, different specialists, all experts in BC care, to complete an anonymous survey online. The survey was distributed between 30 and 10 May 2020. The survey included 27 questions on four topics: demographic information, consultations, imaging and treatment of BC. The questionnaire was sent and then distributed to various health specialists including breast surgeons, clinical oncologists, radiation oncologists and radiologists via the Presidents of the different Latin American Societies of Mastology in 18 countries. The results are summarised as tallies based on the number of responses to each question. Results: A total of 499 responses were received. The majority of the respondents were males (275 (55.11%)); 290 participants were over 45 years (58.11%). The questionnaire presented those surveyed with three possible answers (agree, disagree and neither agree nor disagree). The results reflect that there was consensus in the majority of situations presented. Only seven questions revealed disagreement among those responding. The results are presented as recommendations. Conclusion: The management of patients with BC presents unique challenges during the current world health situation produced by COVID-19 pandemic. Breast care specialists (surgical oncologists, breast care clinicians, clinical oncologists, radiation oncologists and radiologists) from 18 countries in Central and South America submitted through their responses and recommendations for the treatment of BC during the COVID-19 pandemic.
Through the production of cytokines and growth factors the endothelium of secondary lymphoid organs plays a crucial role in controlling lymphocyte migration to the lymphoid microenvironment, an essential step in the initiation of the immune response. Here we demonstrate that direct contact of B cell lines with tonsil-derived human endothelial cells resulted in changes in the phosphorylation state of endothelial cells, causing their functional activation. We found a rapid (<15-s) and transient dephosphorylation, followed by a rapid rephosphorylation of tyrosine residues of the focal adhesion kinase, paxillin, and ERK2. Maximal rephosphorylation occurred after 15–30 min of B cell contact. Preincubation of lymphoid B cells with an adhesion-blocking Ab directed against α4β1 integrin abrogated adhesion-mediated changes of endothelial cell tyrosine phosphorylation, suggesting that cell contact was essential. Similar patterns of tyrosine phosphorylation, but with slightly different kinetics were induced after cross-linking of β1 integrin or CD40 on endothelial cells. Functional activation of endothelial cells by B cell adhesion was confirmed by the production of IL-6, IL-8, monocyte chemoattractant protein-1, M-CSF, and macrophage inflammatory protein-1β mRNA. However, direct cross-linking of β1 integrin and CD40 failed to accomplish the same functional activation. These data indicate that direct contact of lymphoid B cells with the endothelium from lymphoid tissue induce endothelial cell signaling, resulting in chemokine and cytokine production. This phenomenon may provide a mechanism for the remodeling of the endothelium from lymphoid tissues, thus contributing to the free migration of lymphocytes and other cells into the lymphoid organs.
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