The ionotropic P2X7 receptor (P2X7R) is involved in bone homeostasis but its role in osteogenesis is controversial. Thus, we investigated the expression of P2X7R and the effects exerted by its modulation in mesenchymal stromal cells from human subcutaneous adipose tissue (S-ASCs), which have potential therapeutic application in bone regenerative medicine. We found that undifferentiated S-ASCs expressed P2X7R and its functional splice variants P2X7AR and P2X7BR. Cell stimulation by P2X7R agonist BzATP (100 μM) neither modified proliferation nor caused membrane pore opening while increasing intracellular Ca 2+ levels and migration. The P2X7R antagonist A438079 reversed these effects. However, 25-100 μM BzATP, administered to S-ASCs undergoing osteogenic differentiation, dosedependently decreased extracellular matrix mineralization and expression of osteogenic transcription factors Runx2, alkaline phosphatase and osteopontin. These effects were not coupled to cell proliferation reduction or to cell death increase, but were associated to decrease in P2X7AR and P2X7BR expression. In contrast, expression of P2X7R, especially P2X7BR isoform, significantly increased during the osteogenic process. Noteworthy, the antagonist A438079, administered alone, at first restrained cell differentiation, enhancing it later. Accordingly, A438079 reversed BzATP effects only in the second phase of S-ASCs osteogenic differentiation. Apyrase, a diphosphohydrolase converting ATP/ADP into AMP, showed a similar behavior. Altogether, findings related to A438079 or apyrase effects suggest an earlier and prevailing pro-osteogenic activity by endogenous ATP and a later one by adenosine derived from endogenous ATP metabolism. Conversely, P2X7R pharmacological stimulation by BzATP, mimicking the effects of high ATP levels occurring during tissue injuries, depressed receptor expression/activity impairing MSC osteogenic differentiation.
Background and Objectives: The surgical choice treatment of the breast cancer mostly depends on the stage of the disease. In the last years, breast cancer surgery has moved from being destructive to being more respectful of the anatomical and physiological integrity of the gland. The aim of the breast surgery should be finalized to obtain the best aesthetic and functional results, respecting the principles of oncologic radicality. The present study is a retrospective analysis aimed to evaluate the long-term outcomes of a conservative technique like the nipple-sparing mastectomy. Materials and Methods: We observed 894 patients with a median age of 47.5 years old, underwent nipple-sparing mastectomy between 2002–2017. The data acquired include population and tumor characteristics, patient reconstructive outcomes, including locoregional, regional, and distant metastases; other variables, among nipple–areola complex necrosis and infection were collected. Results: The complications detected were considered as “early” within 1 month later the nipple-sparing mastectomy or “late” after this time. The overall complications rate (early and late) and the overall survival and the relapses detected by this study were comparable with those reported in the literature. In order to identify factors that correlate with complications, either early or later, it has been processed an evaluation of the univariate analysis showing adjuvant chemotherapy as the only predictive factor for late complications, while we encountered no predictors for early complications. Conclusions: The present study adds to the data already present in literature, demonstrating that the nipple-sparing mastectomy is a safe procedure, providing good oncological and aesthetic results in patients carefully selected.
Chemosensory receptors play a crucial role in distinguishing the wide range of volatile/soluble molecules by binding them with high accuracy. Chemosensation is the main sensory modality in organisms lacking long-range sensory mechanisms like vision/hearing. Despite its low number of sensory neurons, the nematode Caenorhabditis elegans possesses several chemosensory receptors, allowing it to detect about as many odorants as mammals. Here, we show that C. elegans displays attraction towards urine samples of women with breast cancer, avoiding control ones. Behavioral assays on animals lacking AWC sensory neurons demonstrate the relevance of these neurons in sensing cancer odorants: calcium imaging on AWC increases the accuracy of the discrimination (97.22%). Also, chemotaxis assays on animals lacking GPCRs expressed in AWC allow to identify receptors involved in binding cancer metabolites, suggesting that an alteration of a few metabolites is sufficient for the cancer discriminating behavior of C. elegans, which may help identify a fundamental fingerprint of breast cancer.
of mass, the specimen was inserted into plastic retrieval bag and extracted via extended umbilical port. And then Jackson Pratt drain was placed around inferior vena cava. Result There was no intraoperative transfusion and complications during laparoscopic retroperitoneal excision for paraganglioma. The operation time was 190 min, and estimated blood loss was 100 ml. The patient was discharged on postoperative 5th day without complications. Final pathologic result was paraganglioma of 7.5 cm sized with PASS score 4 (pheochromocytoma of the adrenal gland scaled score). Conclusion Laparoscopic surgery for huge retroperitoneal paraganglioma behind IVC was successfully performed with the maneuver of hanging IVC. This procedure could be useful with appropriate laparoscopic technique and proper patient selection.
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