Alzheimer's Disease & Dementia: The Journal of the Alzheimer's Association
, researchers at the University of Chicago and Boston University School of Medicine have identified agenome-wide association study for Alzheimer's in two independent datasets using different methods. One approach focused on dementia in a large extended family of Hutterites, a founder population of central European ancestry who settled in the mid-west region of the country. Hutterites are often studied for genetic determinants of disease because they have a relatively small gene pool due to their isolated, insular culture. In this study, the individuals with Alzheimer's were all women.
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Ceritinib is a novel triple negative breast cancer therapeutic agent - Molecular CancerBackground Triple-negative breast cancers (TNBCs) are clinically aggressive subtypes of breast cancer. TNBC is difficult to treat with targeted agents due to the lack of commonly targeted therapies within this subtype. Androgen receptor (AR) has been detected in 12–55% of TNBCs. AR stimulates breast tumor growth in the absence of estrogen receptor (ER), and it has become an emerging molecular target in TNBC treatment. Methods Ceritinib is a small molecule inhibitor of tyrosine kinase and it is used in the therapy of non-small lung cancer patients. Enzalutamide is a small molecule compound targeting the androgen receptor and it is used to treat prostate cancer. Combination therapy of these drugs were investigated using AR positive breast cancer mouse xenograft models. Also, combination treatment of ceritinib and paclitaxel investigated using AR− and AR low mouse xenograft and patient derived xenograft models. Results We screened 133 FDA approved drugs that have a therapeutic effect of AR+ TNBC cells. From the screen, we identified two drugs, ceritinib and crizotinib. Since ceritinib has a well- defined role in androgen independent AR signaling pathways, we further investigated the effect of ceritinib. Ceritinib treatment inhibited RTK/ACK/AR pathway and other downstream pathways in AR+ TNBC cells. The combination of ceritinib and enzalutamide showed a robust inhibitory effect on cell growth of AR+ TNBC cells in vitro and in vivo. Interestingly Ceritinib inhibits FAK-YB-1 signaling pathway that leads to paclitaxel resistance in all types of TNBC cells. The combination of paclitaxel and ceritinib showed drastic inhibition of tumor growth compared to a single drug alone. Conclusions To improve the response of AR antagonist in AR positive TNBC, we designed a novel combinational strategy comprised of enzalutamide and ceritinib to treat AR+ TNBC tumors through the dual blockade of androgen-dependent and androgen-independent AR signaling pathways. Furthermore, we introduced LSU TNBC circadian rhythm healthequity breastcancer The risk of triple negative breast cancer (TNBC) is reduced by preventive healthcare that measures the diurnal cortisol rhythm and nocturnal melatonin amplitude and volume. .
Source: medical_xpress - 🏆 101. / 51 Read more »
Machine Learning Based Multimodal Neuroimaging Genomics Dementia Score for Predicting Future Conversion to Alzheimer’s Disease - IOS PressBackground: The increasing availability of databases containing both magnetic resonance imaging (MRI) and genetic data allows researchers to utilize multimodal data to better understand the characteristics of dementia of Alzheimer’s type (DAT). Objec
Source: medical_xpress - 🏆 101. / 51 Read more »
Addressing the routine failure to clinically identify monogenic cases of common disease - Genome MedicineChanges in medical practice are needed to improve the diagnosis of monogenic forms of selected common diseases. This article seeks to focus attention on the need for universal genetic testing in common diseases for which the recommended clinical management of patients with specific monogenic forms of disease diverges from standard management and has evidence for improved outcomes.We review evidence from genomic screening of large patient cohorts, which has confirmed that important monogenic case identification failures are commonplace in routine clinical care. These case identification failures constitute diagnostic misattributions, where the care of individuals with monogenic disease defaults to the treatment plan offered to those with polygenic or non-genetic forms of the disease.The number of identifiable and actionable monogenic forms of common diseases is increasing with time. Here, we provide six examples of common diseases for which universal genetic test implementation would drive improved care. We examine the evidence to support genetic testing for common diseases, and discuss barriers to widespread implementation. Finally, we propose recommendations for changes to genetic testing and care delivery aimed at reducing diagnostic misattributions, to serve as a starting point for further evaluation and development of evidence-based guidelines for implementation.
Source: BioMedCentral - 🏆 22. / 71 Read more »
CTE Is Diagnosed in a Major League Soccer Player for the First TimeResearchers say former Sporting Kansas City defender Scott Vermillion suffered from the degenerative brain disease I hope he is ok. Wonder if he took the vax?
Source: TIME - 🏆 93. / 53 Read more »
Thousands join stem cell register as search for match for sick NI teen continuesYoung Daniel's only chance of beating the disease is through a bone marrow transplant Blood donations & platelets are massively important for this young man too. Anyone can donate either.
Source: BelfastLive - 🏆 16. / 77 Read more »