Abstract：
:The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor disease outcome in some human cancers. Monoclonal antibodies (mAbs) blockading the PD-1/PD-L1 pathway have been developed for cancer immunotherapy via enhancing T cell functions. Clinical trials with mAbs to PD-1 and PD-L1 have shown impressive response rates in patients, particularly for melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and bladder cancer. Further studies are needed to dissect the mechanisms of variable response rate, to identify biomarkers for clinical response, to develop small-molecule inhibitors, and to combine these treatments with other therapies.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Ohaegbulam KC,Assal A,Lazar-Molnar E,Yao Y,Zang Xdoi
10.1016/j.molmed.2014.10.009subject
Has Abstractpub_date
2015-01-01 00:00:00pages
24-33issue
1eissn
1471-4914issn
1471-499Xpii
S1471-4914(14)00183-Xjournal_volume
21pub_type
杂志文章,评审abstract：:As gene therapy begins to produce its first clinical successes, interest in ocular gene transfer has grown owing to the favorable safety and efficacy characteristics of the eye as a target organ for drug delivery. Important advances also include the availability of viral and non-viral vectors that are able to efficien...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2008.11.003
更新日期：2009-01-01 00:00:00
abstract：:Cancer cells meet their needs for energy and biomass production by consuming high levels of nutrients and rewiring metabolism to support macromolecular biosynthesis. Mitochondrial enzymes play central roles in anabolic growth, and acetylation may provide a key layer of regulation over mitochondrial metabolic pathways....
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2012.05.004
更新日期：2012-09-01 00:00:00
abstract：:Hundreds of millions of people worldwide are affected by bone-related diseases, such as osteoporosis and rheumatoid arthritis. Understanding the molecular mechanisms of bone metabolism is crucial for developing novel drugs for treating such diseases. In particular, genetic experiments showing that the receptor activat...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2005.11.007
更新日期：2006-01-01 00:00:00
abstract：:Rheumatoid arthritis (RA) is a multifactorial immune disease exhibiting diverse clinical responses to specific therapeutic agents. Such heterogeneity reflects variable activation of signaling pathways. Consequently, RA physiopathology has been linked to many immune cells and factors, with controversial observations fo...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2018.02.001
更新日期：2018-04-01 00:00:00
abstract：:Protective autoimmunity is the body's defense mechanism against destructive self-compounds such as those commonly associated with neurodegenerative disorders. Autoimmune disease and neurodegenerative disorders can thus be viewed as two extreme manifestations of the same process. Therefore, when designing therapy, it i...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/s1471-4914(02)02373-0
更新日期：2002-07-01 00:00:00
abstract：:Ten years ago, the linkage between mutations in the gene coding for the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) and the neurodegenerative disease known as familial amyotrophic lateral sclerosis (FALS) was established. This finding has prompted a myriad of new studies in experimental models aimed at invest...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2004.06.009
更新日期：2004-08-01 00:00:00
abstract：:The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortica...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2011.07.008
更新日期：2011-12-01 00:00:00
abstract：:Transport into the endoplasmic reticulum (ER) is the crucial step in the biosynthesis of most secretory proteins and many membrane proteins. The products of the SIL1, SEC62 and SEC63 genes act in concert with the SEC61 complex and the molecular chaperones BiP and GRP170 to transport proteins into the ER. Interestingly...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2006.10.004
更新日期：2006-12-01 00:00:00
abstract：:It is now well recognized that cells traffic in both directions between fetus and mother during pregnancy. Moreover, fetal cells have been found to persist for years, probably for a lifetime, in the circulation of healthy women. Harboring of cells from another individual at low levels is called microchimerism. Women h...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/s1471-4914(01)02269-9
更新日期：2002-03-01 00:00:00
abstract：:Successful molecular targeting of nanoparticle drug carriers can enhance therapeutic specificity and reduce systemic toxicity. Typically, ligands specific for cognate receptors expressed on the intended target cell type are conjugated to the nanoparticle surface. This approach, often called active targeting, seems to ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2018.05.003
更新日期：2018-07-01 00:00:00
abstract：:Many fundamental questions about sleep remain unanswered. The presence of sleep across phyla suggests that it must serve a basic cellular and/or molecular function. Microarray studies, performed in several model systems, have identified classes of genes that are sleep-state regulated. This has led to the following con...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2008.12.002
更新日期：2009-02-01 00:00:00
abstract：:Accumulating evidence supports the important role for epigenetic changes in modulating clinical parameters of complex disorders, including neurodegenerative disease. Several conditions, including fragile X syndrome and Huntington's disease are caused by trinucleotide repeat (TNR) expansions in or near specific genes. ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2013.07.007
更新日期：2013-11-01 00:00:00
abstract：:One hypothesis for the etiology of neuropsychiatric disorders proposes that viral infection contributes to the induction of neuronal system dysfunction, resulting in a wide range of behavioral abnormalities. Recent research in molecular biology supports this hypothesis and refocuses on the role of viral infection in t...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2003.12.001
更新日期：2004-02-01 00:00:00
abstract：:Induced pluripotent stem cells (iPSCs) are cutting edge biotechnology that may revolutionize medicine, and creating iPSCs from ethnically diverse individuals would generate valuable therapeutic and drug development tools. However, challenges must be overcome in creating the infrastructure and scientific capacity neede...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2012.10.005
更新日期：2012-12-01 00:00:00
abstract：:The identification of functionally relevant polymorphisms of peptidylarginine deiminase 4, an enzyme that catalyzes the post-translational citrullination of proteins, as a rheumatoid arthritis gene is one of the most convincing success stories of complex disease gene mapping to date. In addition to an extensive single...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2003.08.007
更新日期：2003-10-01 00:00:00
abstract：:Degenerated motor neurons in the spinal cord are the pathological hallmark of spinal muscular atrophy (SMA). SMA is caused by mutations in the ubiquitously expressed survival motor neuron 1 (SMN1) gene, which lead to reduced levels of functional SMN protein. Many different functions have been assigned to SMN, includin...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2006.01.005
更新日期：2006-03-01 00:00:00
abstract：:While preclinical studies have reported improvement of behavioral deficits in the Ts65Dn mouse model of Down syndrome (DS), translation to human clinical trials to improve cognition in individuals with DS has had a poor success record. Timing of the intervention, choice of animal models, strategy for drug selection, a...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2019.10.001
更新日期：2020-02-01 00:00:00
abstract：:Long-standing difficulties in the in vitro transformation of human cells have been overcome. Using telomerase, several successful oncogene-mediated transformations of human cells have been reported and the following cellular requirements for human cell transformation have been proposed: the maintenance of telomere seq...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2004.09.001
更新日期：2004-11-01 00:00:00
abstract：:Sex differences have been clinically documented in numerous neurodegenerative diseases and yet the reasons for these differences are not well understood. Recent studies have found that microglia, the innate immune cells of the central nervous system, are a key cell type involved in neurodegenerative diseases. This cel...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2019.05.001
更新日期：2019-09-01 00:00:00
abstract：:Non-alcoholic steatohepatitis (NASH), a cause of cirrhosis and hepatocellular carcinoma, is characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. Progress has been made in understanding the molecular and cellular mechanisms implicated in the pathogenesis of this condition,...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2007.12.003
更新日期：2008-02-01 00:00:00
abstract：:Recurrent pregnancy loss (RPL), which occurs in 0.5%-1% of total pregnancies, is usually defined as three or more consecutive spontaneous abortions before 20 weeks of gestation. Although an immunology-based etiology underlying unexplained RPL has been demonstrated, the exact molecular mechanisms are still poorly under...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2007.05.005
更新日期：2007-07-01 00:00:00
abstract：:Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we review the link betwe...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2016.05.007
更新日期：2016-07-01 00:00:00
abstract：:During the past decade, successful gene therapies for immunodeficiencies were finally brought to the clinic. This was accomplished through new gene therapy vectors and improved procedures for genetic modification of autologous hematopoietic stem cells. For HIV, autologous hematopoietic stem cell (HSC) gene therapy wit...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2014.08.004
更新日期：2014-11-01 00:00:00
abstract：:Hypoxia-inducible factor 1 (HIF-1) controls oxygen delivery (via angiogenesis) and metabolic adaptation to hypoxia (via glycolysis). HIF-1 consists of a constitutively expressed HIF-1 beta subunit and an oxygen- and growth-factor-regulated HIF-1 alpha subunit. In xenografts, tumor growth and angiogenesis are correlate...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/s1471-4914(02)02317-1
更新日期：2002-01-01 00:00:00
abstract：:Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially lethal monogenic disorder, with more than 12 million cases worldwide. The two causative genes for ADPKD, PKD1 and PKD2, encode protein products polycystin-1 (PC1) and polycystin-2 (PC2 or TRPP2), respectively. Recent data have shed lig...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2014.01.004
更新日期：2014-05-01 00:00:00
abstract：:The surfaces of all vertebrate cells are decorated with a dense and complex array of sugar chains, which are mostly attached to proteins and lipids. Most soluble secreted proteins are also similarly decorated with such glycans. Sialic acids are a diverse family of sugar units with a nine-carbon backbone that are typic...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2008.06.002
更新日期：2008-08-01 00:00:00
abstract：:Despite advances in treatment for glioblastoma multiforme (GBM), patient prognosis remains poor. Although there is growing evidence that molecular targeting could translate into better survival for GBM, current clinical data show limited impact on survival. Recent progress in GBM genomics implicate several activated p...
journal_title：Trends in molecular medicine
pub_type： 临床试验,杂志文章,评审
doi：10.1016/j.molmed.2011.01.011
更新日期：2011-06-01 00:00:00
abstract：:Clustered regularly interspaced short palindromic repeats, or CRISPR, has been widely accepted as a versatile genome editing tool with significant potential for medical application. Reliable allele specificity is one of the most critical elements for successful application of this technology to develop high-precision ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2019.09.008
更新日期：2020-03-01 00:00:00
abstract：:Genetically engineered mouse models have revolutionized the study of pancreatic cancer, but have several technical and practical limitations. A new adeno-associated virus (AAV)-driven somatic genome-editing model of pancreatic ductal adenocarcinoma reported by Ideno et al. (Lab. Invest. published online February 6, 20...
journal_title：Trends in molecular medicine
pub_type： 信件
doi：10.1016/j.molmed.2019.02.012
更新日期：2019-05-01 00:00:00
abstract：:Clinical medicine of the future is poised to use an individual's genomic data to predict disease risk and guide clinical care. The treatment of cigarette smoking and tobacco use disorder represents a prime area for genomics implementation. The genes CHRNA5 and CYP2A6 are strong genomic contributors that alter the risk...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2017.12.001
更新日期：2018-02-01 00:00:00
