Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic progression of cancer is a complex and clinically daunting process. We previously identified a set of human microRNAs (miRNAs) that robustly suppress breast cancer metastasis to lung and bone and which display expression levels that predict human metastasis. Although these findings revealed miRNAs as suppressors of cell-autonomous metastatic phenotypes, the roles of non-coding RNAs in non-cell-autonomous cancer progression processes remain unknown. Here we reveal that endogenous miR-126, an miRNA silenced in a variety of common human cancers, non-cell-autonomously regulates endothelial cell recruitment to metastatic breast cancer cells, in vitro and in vivo. It suppresses metastatic endothelial recruitment, metastatic angiogenesis and metastatic colonization through coordinate targeting of IGFBP2, PITPNC1 and MERTK--novel pro-angiogenic genes and biomarkers of human metastasis. Insulin-like growth factor binding protein 2 (IGFBP2) secreted by metastatic cells recruits endothelia by modulating IGF1-mediated activation of the IGF type-I receptor on endothelial cells; whereas c-Mer tyrosine kinase (MERTK) receptor cleaved from metastatic cells promotes endothelial recruitment by competitively antagonizing the binding of its ligand GAS6 to endothelial MERTK receptors. Co-injection of endothelial cells with breast cancer cells non-cell-autonomously rescues their miR-126-induced metastatic defect, revealing a novel and important role for endothelial interactions in metastatic initiation. Through loss-of-function and epistasis experiments, we delineate an miRNA regulatory network's individual components as novel and cell-extrinsic regulators of endothelial recruitment, angiogenesis and metastatic colonization. We also identify the IGFBP2/IGF1/IGF1R and GAS6/MERTK signalling pathways as regulators of cancer-mediated endothelial recruitment. Our work further reveals endothelial recruitment and endothelial interactions in the tumour microenvironment to be critical features of metastatic breast cancer.
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PMID:A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. 2217 Jun 10

Breast cancer is the most common cancer and the leading cause of cancer death among women. Despite all efforts, about 11,939 deaths and 50,000 new diagnoses for breast cancer were estimated among Italian women in 2016. Therefore new approaches are needed to improve the survival and higher remission rates. We present a case of a woman with carcinoma of the breast and multiple metastases after right mastectomy, axillary dissection, repeated cycles of chemo and radiotherapy, and estrogen block. Biological method formulated by Prof. L. Di Bella (DBM) produced a complete and stable objective response without toxicity. The DBM includes antiproliferative molecules, such as somatostatin, prolactin and estrogen inhibitors together with differentiating and apoptotic molecules such as melatonin (MLT), Retinoids, Vitamin E, D3, Vit. C, Calcium, Amino sugars, associated with metronomic microdoses of chemotherapy drugs. The blood tests did not show any damage but a progressive reduction of Prolactin, Estradiol, and IGF1, and continuing low levels of GH. The objective result of this case, in the absence of toxicity, demonstrates the efficacy of the treatment and is in agreement with the positive results already published on the use of the DBM. Not requiring hospital or day hospital admission, and with no significant toxicity, the DBM avoided the significant side effects of chemo- and radiotherapy. We believe that this case can encourage more interest and more in-depth studies on the possibilities that have been opened up in oncology by the DBM treatment of the metastatic breast cancer.
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PMID:Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast. 2929 80