Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within the cohort of patients suffering from idiopathic pulmonary arterial hypertension (IPAH) is a group that responds dramatically (VR-PAH) to an acute vasodilator challenge and that has excellent long-term hemodynamic improvement and prognosis on high dose calcium channel blockers compared with vasodilator non-responders (VN-PAH). For the purposes of diagnosing VR-PAH, there is to date no test to replace the acute vasodilator challenge. However, recent studies have identified markers that may aid in the identification of VR-PAH, including peripheral blood lymphocyte RNA expression levels of desmogelin-2 and Ras homolog gene family member Q, and plasma levels of provirus integration site for Moloney murine leukemia virus. Genome wide-array studies of peripheral blood DNA have demonstrated differences in disease specific genetic variants between VR-PAH and NR-PAH, with particular convergence on cytoskeletal function pathways and Wnt signaling pathways. These studies offer hope for future non-invasive identification of VR-PAH, and insights into pathogenesis that may lead to novel therapies. Examination of the degree of pulmonary microvascular perfusion in PAH has offered additional insights. During the acute vasodilator challenge, VR-PAH patients demonstrate true vasodilation with recruitment and increased perfusion of the capillary bed, while VN-PAH patients are unable to recruit vasculature. In the very few reports of lung histology, VR-PAH has more medial thickening in the precapillary arterioles, while VN-PAH has the classic histology of PAH, including intimal thickening. VR-PAH is a disorder with a phenotype distinct from VN-PAH and other types of PAH, and should be considered separately in the classification of PAH.
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PMID:Vasodilator responsiveness in idiopathic pulmonary arterial hypertension: identifying a distinct phenotype with distinct physiology and distinct prognosis. 2863 1

Upconversion nanoparticles (UCNPs) have gained increased attention due to their various medical applications such as drug delivery, detection, imaging, and photodynamic therapy. But little is known about their direct biological activity. In the present study, we synthesized NaYF4:Yb,Er UCNPs coated with poly-(allylamine hydrochloride) (PAH) or poly(acrylic acid) (PAA) and investigated their effects in human myeloma and leukemia cells. When these cells were incubated with both types of UCNPs, we found that PAH-UCNPs but not PAA-UCNPs increased the expression of LC3-II, a hallmark of autophagy. This effect was confirmed by the accumulation of LC3 puncta as analyzed by immunofluorescence microscopy. Induction of LC3-II could be blocked by 3-methyl adenosine (3-MA), an autophagy inhibitor. Consistent with this observation, PAH-UCNPs also inhibited both AKT and mTOR activation, the key step in autophagy activation. Further studies demonstrated that PAH-UCNPs also decreased Bcl-2 but increased Beclin1 and Atg14 expression, suggesting that PAH-UCNPs-induced autophagy was associated with increased PI3KC3-Beclin1 activity. Moreover, PAH-UCNPs induced apoptosis in myeloma cells and enhanced apoptosis induced by bortezomib and doxorubicin, two major anti-myeloma drugs. Therefore, our study suggested that PAH-UCNPs alone can induce both apoptosis and autophagy in human blood cancer cells by modulating the AKT-mTOR and PI3KC3-Beclin1-Atg14 signaling pathways. This study implies the potential application of PAH-UCNPs in blood cancer-cell killing.
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PMID:Poly-(allylamine hydrochloride)-coated but not poly(acrylic acid)-coated upconversion nanoparticles induce autophagy and apoptosis in human blood cancer cells. 3226 73