Abstract:
:CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 antibodies of varying formulations have been evaluated in the clinic and found to be tolerable and feasible. Administration is associated with mild to moderate (but transient) cytokine release syndrome, readily managed in the outpatient setting. Antitumor activity with or without anti-CTLA4 monoclonal antibody (mAb) therapy has been observed in patients with melanoma, and major tumor regressions have been observed in patients with pancreatic cancer, mesothelioma, and other tumors in combination with chemotherapy. In a recent study of chemotherapy plus CD40 mAb, with or without PD-1 mAb, the objective response rate in patients with untreated, metastatic pancreatic cancer was >50%. Mechanistically, the combination of chemotherapy followed by CD40 mAb functions as an in situ vaccine; in addition, destruction of stroma by CD40-activated macrophages may enhance chemotherapy delivery. Evidence to date suggests that CD40 activation is a critical and nonredundant mechanism to convert so-called cold tumors to hot ones (with prominent tumor infiltration of T cells), sensitizing them to checkpoint inhibition.
journal_name
Annu Rev Medjournal_title
Annual review of medicineauthors
Vonderheide RHdoi
10.1146/annurev-med-062518-045435subject
Has Abstractpub_date
2020-01-27 00:00:00pages
47-58eissn
0066-4219issn
1545-326Xjournal_volume
71pub_type
杂志文章,评审abstract::The most significant complication of elevated parathyroid hormone (PTH) levels in uremia is the development of osteitis fibrosa cystica. The hormone also appears to play a role in soft-tissue and organ calcification, metabolic abnormalities (glucose, lipids), and electroencephalographic changes seen in uremic patients...
journal_title:Annual review of medicine
pub_type: 杂志文章
doi:10.1146/annurev.me.37.020186.000443
更新日期:1986-01-01 00:00:00
abstract::Precision medicine was conceptualized on the strength of genomic sequence analysis. High-throughput functional metrics have enhanced sequence interpretation and clinical precision. These technologies include metabolomics, magnetic resonance imaging, and I rhythm (cardiac monitoring), among others. These technologies a...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-041316-090905
更新日期:2018-01-29 00:00:00
abstract::Antipsychotic drugs (APDs) are best classified as typical or atypical. The distinction is based solely on their ability to cause extrapyramidal side effects (EPS), including tardive dyskinesia (TD). The two classes differ in mechanism of action, with atypical APDs providing important modulation of serotonergic neurotr...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-050911-161504
更新日期:2013-01-01 00:00:00
abstract::Parallel and often unrelated developments in health care and technology have all been necessary to bring about early detection of lung cancer and the opportunity to decrease mortality from lung cancer through early detection of the disease by computed tomography. Lung cancer screening programs provide education for pa...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-020917-053556
更新日期:2018-01-29 00:00:00
abstract::GnRH and its analogues have led to exciting new avenues of therapy in virtually every subspecialty of internal medicine as well as in gynecology, pediatrics, and urology. Since their discovery in 1971, it has been demonstrated that GnRH and its analogues enable medical professionals to influence the hypothalamic-pitui...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.45.1.391
更新日期:1994-01-01 00:00:00
abstract::Paget's disease affects approximately 3% of the population over age forty. It may be genetically transmitted (autosomal-dominant), but recent evidence suggests a viral etiology. Effective agents for control of the disorder have been developed over the past decade, but all have significant drawbacks. Calcitonin tends t...
journal_title:Annual review of medicine
pub_type: 杂志文章
doi:10.1146/annurev.me.28.020177.001043
更新日期:1977-01-01 00:00:00
abstract::Remarkable progress made in the past few years has brought pancreatic islet transplantation to the threshold of human clinical trials. Islet transplants have reversed diabetes in experimental animals and prevented or reversed early diabetic complications in the recipients. Methods have been developed that prevent reje...
journal_title:Annual review of medicine
pub_type: 临床试验,杂志文章,评审
doi:10.1146/annurev.me.37.020186.000341
更新日期:1986-01-01 00:00:00
abstract::Volume reduction surgery is based on the removal of volume-occupying but nonfunctioning emphysematous lung, which is thought to improve pulmonary elastic recoil. The reduction in thoracic volume may also improve thoracic cage and inspiratory muscle function. In addition, dyspnea is lessened, exercise tolerance is incr...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.48.1.387
更新日期:1997-01-01 00:00:00
abstract::Carcinoma of the head of the pancreas can be diagnosed and staged effectively by computed tomography (CT) scan and by visceral angiography. If the tumor appears to be resectable, no further studies such as percutaneous biopsy are required. Pancreaticoduodenectomy is the only potentially curable treatment. This operati...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.46.1.361
更新日期:1995-01-01 00:00:00
abstract::In 2012, a zoonotic coronavirus was identified as the causative agent of Middle East respiratory syndrome and was named MERS coronavirus (MERS-CoV). As of August 11, 2016, the virus has infected 1,791 patients, with a mortality rate of 35.6%. Although MERS-CoV generally causes subclinical or mild disease, infection ca...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-051215-031152
更新日期:2017-01-14 00:00:00
abstract::Deregulation of gene expression is a hallmark of cancer. Although genetic lesions have been the focus of cancer research for many years, it has become increasingly recognized that aberrant epigenetic modifications also play major roles in the tumorigenic process. These modifications are imposed on chromatin, do not ch...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.59.061606.095816
更新日期:2008-01-01 00:00:00
abstract::Obesity is perhaps the most significant public health problem facing the United States today. Obese patients are at increased risk for numerous medical problems, which can adversely affect surgical outcome. However, these risks have not uniformly translated into increased or prohibitive operative morbidity and mortali...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.49.1.215
更新日期:1998-01-01 00:00:00
abstract::Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-062218-023720
更新日期:2020-01-27 00:00:00
abstract::Following the "finished," euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better unde...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-051010-162644
更新日期:2012-01-01 00:00:00
abstract::Organ preservation is the supply line for organ transplantation. Currently, the liver, pancreas, and kidney can be successfully preserved for up to two days by flushing the organs with the University of Wisconsin (UW) organ preservation solution and storing them at hypothermia (0-5 degree C). The UW solution is effect...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.46.1.235
更新日期:1995-01-01 00:00:00
abstract::The foregoing summarizes what can be learned from a carefully performed antiglobulin test using specific antisera. Clinical syndromes can be more easily considered, and mechanisms of destruction can be more certainly discerned. ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.26.020175.001555
更新日期:1975-01-01 00:00:00
abstract::Our understanding of the role of the immune system in modulating glomerular injury continues to evolve. The participation of antibody, complement, and neutrophils alone cannot completely explain many aspects of the pathways of experimental and human glomerulonephritis. The elements of the immune system that mediate ce...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.000325
更新日期:1991-01-01 00:00:00
abstract::Ketamine is the prototype for a new generation of glutamate-based antidepressants that rapidly alleviate depression within hours of treatment. Over the past decade, there has been replicated evidence demonstrating the rapid and potent antidepressant effects of ketamine in treatment-resistant depression. Moreover, prec...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-053013-062946
更新日期:2015-01-01 00:00:00
abstract::It is clear from the preceding material that bacterial infection is a significant threat to the newborn infant. The most common gram-negative organism causing meningitis in the neonate is E. coli, and the invasive capacity of this organism is correlated with its polysaccharide antigen, K1. Careful studies of supportiv...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.29.020178.001021
更新日期:1978-01-01 00:00:00
abstract::In the practice of internal medicine, the value of genetic testing in common (mono)genetic diseases such as familial hemochromatosis, hypercholesterolemia, Mediterranean fever, and thrombophilia is limited. The genotype insufficiently predicts the phenotype because of the powerful effects of other modifying genes, env...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.60.103007.132540
更新日期:2009-01-01 00:00:00
abstract::Acute myocardial infarction is caused by coronary thrombosis on an ulcerated atheroma. We now believe that the predominant cause of this intimal disruption is the rupture of the atheroma through the intimal surface, caused by enzymes released by activated macrophages. The subsequent clinical course following atheroma ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.000343
更新日期:1991-01-01 00:00:00
abstract::The neuropeptide substance P modulates the activities of a number of different leukocytes that characterize both acute and delayed inflammatory responses. Substance P may play a role in the pathogenesis of such diverse diseases as arthritis, asthma, and inflammatory bowel disease. ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.40.020189.002013
更新日期:1989-01-01 00:00:00
abstract::Eccrine sweat is produced by millions of miniscule glands buried in the skin. Eccrine sweating from the general body surface is an extremely important function in human thermoregulation; disturbances either in the control of sweating activity or in the glands themselves can result in problems ranging from minor social...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.34.020183.002241
更新日期:1983-01-01 00:00:00
abstract::The standard of care for the evaluation of axillary nodal involvement remains complete lymph node dissection. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this long-held paradigm; indeed, several leading institutions already reserve complete axillary dissection for patients with metastasis to th...
journal_title:Annual review of medicine
pub_type: 杂志文章
doi:10.1146/annurev.med.51.1.525
更新日期:2000-01-01 00:00:00
abstract::Stress and starvation, especially when complicated by sepsis, will give rise to a rapid erosion of the cellular mass, which significantly affects morbidity and mortality. The best clinical evaluation of the nutritional state is obtained from the medical history and the physical examination. In the patient who cannot e...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.003001
更新日期:1991-01-01 00:00:00
abstract::An effective host response to infection or tissue damage requires focal accumulation of leukocytes. Leukocyte adhesion to the vessel wall, a key step in this process, depends on the ordered expression of specific endothelial cell surface molecules. The endothelial molecules that support adhesion include selectins that...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.45.1.361
更新日期:1994-01-01 00:00:00
abstract::Societal expectations about drug safety and efficacy are rising while productivity in the pharmaceutical industry is falling. In 2004, the US Food and Drug Administration introduced the Critical Path Initiative with the intent of modernizing drug development by incorporating recent scientific advances, such as genomic...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.59.090506.155819
更新日期:2008-01-01 00:00:00
abstract::Physiologic thrombolysis is efficient, while pathologic aberrations in the fibrinolytic system may result in either thrombotic or hemorrhagic disease. This review considers the molecular interactions involved in fibrinolysis, discusses the normal control mechanisms that provide for localized activation without systemi...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.37.020186.001155
更新日期:1986-01-01 00:00:00
abstract::In vitro coculture studies of normal T lymphocytes, natural killer (NK) cells, or monocytes with human hematopoietic progenitor cells (HPC) suggest a potential role for immune cells in the regulation of hematopoiesis. In some patients with severe aplastic anemia or selective pure red cell, white cell, or megakaryocyte...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.38.020187.000425
更新日期:1987-01-01 00:00:00
abstract::Airway hyperresponsiveness to a large number of stimuli is a characteristic of asthma in humans. Various components of the tracheobronchial tree might contribute to this characteristic, such as smooth muscle, the bronchial epithelium, various neurohumoral mechanisms, and the mechanical linkages between the lung parenc...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.001035
更新日期:1991-01-01 00:00:00