Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. Currently it is known that mTOR functions as two complexes, mTOR complex 1/2 (mTORC1/2). Rapamycin and its analogs (all termed rapalogs) first form a complex with the intracellular receptor FK506 binding protein 12 (FKBP12) and then bind a domain separated from the catalytic site of mTOR, blocking mTOR function. Rapalogs are selective for mTORC1 and effective as anticancer agents in various preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain types of cancer. Recently, a new generation of mTOR inhibitors, which compete with ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have been developed. Besides, some natural products, such as epigallocatechin gallate (EGCG), caffeine, curcumin and resveratrol, have been found to inhibit mTOR as well. Here, we summarize the current findings regarding mTOR signaling pathway and review the updated data about mTOR inhibitors as anticancer agents.
Due to their low‐symmetry lattice characteristics and intrinsic in‐plane anisotropy, 2D pentagonal materials, a new class of 2D materials composed entirely of pentagonal atomic rings, are attracting increasing research attention. However, the existence of these 2D materials has not been proven experimentally until the recent discovery of PdSe2. Herein, penta‐PdPSe, a new 2D pentagonal material with a novel low‐symmetry puckered pentagonal structure, is introduced to the 2D family. Interestingly, a peculiar polyanion of [SePPSe]4− is discovered in this material, which is the biggest polyanion in 2D materials yet discovered. Strong intrinsic in‐plane anisotropic behavior endows penta‐PdPSe with highly anisotropic optical, electronic, and optoelectronic properties. Impressively, few‐layer penta‐PdPSe‐based phototransistor not only achieves excellent electronic performances, a moderate electron mobility of 21.37 cm2 V−1 s−1 and a high on/off ratio of up to 108, but it also has a high photoresponsivity of ≈5.07 × 103 A W−1 at 635 nm, which is ascribed to the photogating effect. More importantly, penta‐PdPSe also exhibits a large anisotropic conductance (σmax/σmax = 3.85) and responsivity (Rmax/Rmin = 6.17 at 808 nm), superior to most 2D anisotropic materials. These findings make penta‐PdPSe an ideal material for the design of next‐generation anisotropic devices.
We have examined 17 primary undifferentiated nasopharyngeal carcinoma biopsies for allelic loss on 3p, comparing the findings in tumors with those in normal lymphocyte DNA from the same patients. Ten polymorphic microsatellite markers were used between 3p13 and 3p26. Allelic loss was observed in 12 samples (70%). Two loci were most frequently affected: D3S1067 (3p21.1-14.3) in 60% and D3S1217 (3p14.2-14.1) in 58%. One tumor seemed to have a homozygous deletion at 3p26, detected by the D3S1297 marker. Analysis of the clinical data showed that an increased number of aberrations in 3p was correlated with more advanced tumor stages.
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