Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis, the hallmark of cancer propagation is attributed by the modification of phenotypic/functional behavior of cells to break attachment and migrate to distant body parts. Cancer cell-secreted microvesicles (MVs) contribute immensely in disease propagation. These nano-vesicles, generated from plasma membrane outward budding are taken up by nearby healthy cells thereby inducing phenotypic alterations in those recipient cells. Protease activated receptor 2 (PAR2), activated by trypsin, also contributes to cancer progression by increasing metastasis, angiogenesis etc. Here, we report that PAR2 activation promotes pro-metastatic MVs generation from human breast cancer cell line, MDA-MB-231. Rab5a, located at the plasma membrane plays vital roles in MVs biogenesis. We show that PAR2 stimulation promotes AKT phosphorylation which activates Rab5a by converting inactive Rab5a-GDP to active Rab5a-GTP. Active Rab5a polymerizes actin which critically regulates MVs shedding. Not only MVs generation, has this Rab5a activation also promoted cell migration and invasion. We reveal that Rab5a is over-expressed in human breast tumor specimen and contributes MVs generation in those patients. The involvement of p38 MAPK in MVs-induced cell metastasis has also been highlighted in the present study. Blockade of Rab5a activation can be a potential therapeutic approach to restrict MVs shedding and associated breast cancer metastasis.
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PMID:The Protease Activated Receptor2 Promotes Rab5a Mediated Generation of Pro-metastatic Microvesicles. 2974 47

The current status and time trends in breast cancer incidence and survival in the 28 European Union countries (EU-28) is presented here. Rates reported are age adjusted and standardized (ASR). A high incidence and high survival rates were observed in the Northern and Western European countries, with the exception of the Baltic countries. The higher incidence is partly attributed to the higher prevalence of lifestyle risk factors, while the higher survival is attributed to better access to beneficial treatments and general health care. Most of the countries in Southern Europe or the former Eastern Bloc have not yet reached the high GDP per capita status (2017 purchasing power parity; PPP) of the earlier established Western democracies. The breast cancer incidence and survival are associated with the PPP level (both higher for the higher PPP category; 2017 PPP above USD 40,000). Overall, a trend toward higher survival rates was observed throughout this first period of the 21st century, with the incidence for most countries either stabilizing at the 2010 levels or decreasing further.
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PMID:Breast Cancer Statistics in the European Union: Incidence and Survival across European Countries. 3193 79

The NF1 gene encodes neurofibromin, which is one of the primary negative regulatory factors of the Ras protein. Neurofibromin stimulates the GTPase activity of Ras to convert it from an active GTP-bound form to its inactive GDP-bound form through its GTPase activating protein-related domain (GRD). Therefore, neurofibromin serves as a shutdown signal for all vertebrate RAS GTPases. NF1 mutations cause a resultant decrease in neurofibromin expression, which has been detected in many human malignancies, including NSCLC, breast cancer and so on. NF1 mutations are associated with the underlying mechanisms of treatment resistance discovered in multiple malignancies. This paper reviews the possible mechanisms of NF1 mutation-induced therapeutic resistance to chemotherapy, endocrine therapy and targeted therapy in malignancies. Then, we further discuss advancements in targeted therapy for NF1-mutated malignant tumors. In addition, therapies targeting the downstream molecules of NF1 might be potential novel strategies for the treatment of advanced malignancies.
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PMID:Advancement in research and therapy of NF1 mutant malignant tumors. 3306 44


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