Abstract:
:It had been thought that the central molecular event in the malignant transformation of a cell is the mutation of certain oncogenes-and the resultant dysregulated activation of their encoded proteins. During the past decade, however, it has become clear that alteration of the activity of the protein products of tumor suppressor genes, through mutation or at the posttranslational level, is an equally basic and universal process in tumorigenesis. These proteins normally modulate cellular proliferation in the developing and adult organism, functioning as tumor suppressors by inhibiting inappropriate cell division. Therefore, inactivation of the normal function of tumor suppressor proteins removes important regulatory constraints on the cell, permitting the accelerated growth of cancerous tissue. The genesis of lung cancer is though to involve between 10 and 20 mutations. Of these, several are now known to involve tumor suppressor genes. In this review I will discuss the mechanism of tumor suppression by the protein encoded by one of these, the retinoblastoma gene, to illustrate precisely why the inactivation of tumor suppressors is a requisite step in cellular progression to lung and other carcinomas.
journal_name
Am J Respir Cell Mol Biolauthors
Weintraub SJdoi
10.1165/ajrcmb.15.2.8703470subject
Has Abstractpub_date
1996-08-01 00:00:00pages
150-5issue
2eissn
1044-1549issn
1535-4989journal_volume
15pub_type
杂志文章,评审abstract::In surgically excised nasal polyps, most epithelial mast cells were formalin sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus, this represents a population of mast cells not identified by staining for CAE. On the other hand, most stromal mast cells were formalin resistant and CAE positive, ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/6.1.37
更新日期:1992-01-01 00:00:00
abstract::Previous studies by our group as well as others have shown that acute adenosine exposure enhances lung vascular endothelial barrier integrity and protects against increased permeability lung edema. In contrast, there is growing evidence that sustained adenosine exposure has detrimental effects on the lungs, including ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0012OC
更新日期:2012-11-01 00:00:00
abstract::Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a mod...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0404OC
更新日期:2017-08-01 00:00:00
abstract::β(2)-Adrenoceptor (β2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent β2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the β2AR, epinephrine. In this study, ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0364OC
更新日期:2013-02-01 00:00:00
abstract::Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). Recent reports of increased matrix metalloproteinase-2 (MMP-2) in lungs of patients with emphysema support the paradigm of proteinase/antiproteinase imbalance in the pathogenesis of COPD. We sought to define the signaling pathwa...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0106OC
更新日期:2007-04-01 00:00:00
abstract::IL-27 is involved in inflammatory reactions. CXCL10 is an important chemokine contributing to airway inflammatory disease. In this study, we investigated whether IL-27 modulated the synthesis of CXCL10 in primary human lung fibroblasts (HLFs). HLFs were activated by IL-27 alone, or in combination with other cytokines....
journal_title:American journal of respiratory cell and molecular biology
pub_type: 临床试验,杂志文章
doi:10.1165/rcmb.2012-0340OC
更新日期:2013-04-01 00:00:00
abstract::Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apica...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.3.4098
更新日期:2000-09-01 00:00:00
abstract::Neutrophils were found to demonstrate chemotactic responses to pepsinized human placental type IV collagen and its purified aminoterminal 7S domain. The maximal chemotactic responses occur at approximately 400 ng/ml and approximately 30 ng/ml of type IV collagen and 7S collagen, respectively, and are similar in magnit...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/1.6.479
更新日期:1989-12-01 00:00:00
abstract::The effects of repeated ozone exposures on the development of immune responses toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone exposures (180 to 500 microg/m(3); 4 h, three times/wk for 4 wk) were combined with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous hypersensitivity...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.2.3898
更新日期:2000-08-01 00:00:00
abstract::Protein kinase C (PKC) is known to regulate ryanodine receptor (RyR)-mediated local Ca(2+) signaling (Ca(2+) spark) in airway and vascular smooth muscle cells (SMCs), but its specific molecular mechanisms and functions still remain elusive. In this study, we reveal that, in airway SMCs, specific PKCepsilon peptide inh...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0323OC
更新日期:2009-06-01 00:00:00
abstract::In bronchial asthma, eosinophils found in the airways have an enhanced inflammatory capacity. We hypothesized that, at least in part, changes in functional phenotype are due to the effect of transendothelial migration. To model in vivo eosinophil trafficking to the lung, we cultured human pulmonary microvascular endot...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.3.3707
更新日期:2000-09-01 00:00:00
abstract::Cyclooxygenase-2 (COX-2) expression and PGE2 secretion from human airway smooth muscle cells (hASMCs) may contribute to β2-adrenoceptor hyporesponsiveness, a clinical feature observed in some patients with asthma. hASMCs from patients with asthma exhibit elevated expression of cytokine-responsive genes, and in some in...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0129OC
更新日期:2015-04-01 00:00:00
abstract::The time course and nature of the cellular response to left pneumonectomy, with or without prior adrenalectomy, were evaluated in the right lungs of male Sprague-Dawley rats using morphometric techniques. Animals were studied at days 2, 5, and 14 following pneumonectomy, intervals prior to, during the course of, and f...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/5.4.351
更新日期:1991-10-01 00:00:00
abstract::Gene therapy is the treatment of any disorder or pathophysiologic state based upon the transfer of genetic information. The lung represents a major target of gene therapy for the treatment of genetic disorders such as cystic fibrosis and alpha 1-antitrypsin deficiency. Other diseases are also being targeted, including...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/ajrcmb.14.1.8534480
更新日期:1996-01-01 00:00:00
abstract::Lung elastin synthesis is normally confined to periods of development, is maximal during alveolarization, and declines to low levels in mature lung. We have previously described an elastogenic response in the adult rat lung associated with experimental granulomatous disease induced by silica instillation. Reinitiated ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.21.2.3641
更新日期:1999-08-01 00:00:00
abstract::Although neutrophil migration from the systemic circulation involves the beta2- (or CD18) integrin family, the existence of an alternative, CD18-independent route of neutrophil extravasation to tissues has been demonstrated in animal models. The molecular interactions involved in this alternative migratory route have ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.2.3853
更新日期:2000-08-01 00:00:00
abstract::The genetic basis for the underlying individual susceptibility to chlorine-induced acute lung injury is unknown. To uncover the genetic basis and pathophysiological processes that could provide additional homeostatic capacities during lung injury, 40 inbred murine strains were exposed to chlorine, and haplotype associ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0026OC
更新日期:2012-08-01 00:00:00
abstract::Na(+) absorption and Cl(-) secretion are in equilibrium to maintain an appropriate airway surface fluid volume and ensure appropriate mucociliary clearance. In cystic fibrosis, this equilibrium is disrupted by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in the absence of ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0456OC
更新日期:2009-02-01 00:00:00
abstract::It is generally important to elucidate airway epithelial cell lineages and to identify multipotent progenitors as targets for gene therapy. Stem (S) cells are typically present in specialized compartments spatially proximal to their differentiated progeny, but an equivalent paradigm has not been demonstrated in the ai...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.24.6.4217
更新日期:2001-06-01 00:00:00
abstract::The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-H...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0111OC
更新日期:2017-01-01 00:00:00
abstract::The mammalian alveolar epithelium is composed of alveolar type I (AT1) and alveolar type II (AT2) cells that together coordinate tissue function. We used a heterocellular culture model of AT1 and AT2 cells to determine pathways for intercellular signaling between these two phenotypes. Gap junction protein (connexin) p...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0281OC
更新日期:2003-11-01 00:00:00
abstract::The lung is richly supplied with peptidergic nerves that store and secrete substance P (SP), vasoactive intestinal peptide (VIP), and other neuropeptides known to potently modulate leukocyte function in vitro and airway inflammation in vivo. To investigate and characterize neuromodulation of immune responses compartme...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.16.2.9032120
更新日期:1997-02-01 00:00:00
abstract::A greater understanding of the regulatory processes contributing to lung development could help ameliorate morbidity and mortality in premature infants and identify individuals at risk for congenital and/or chronic lung diseases. Genomics technologies have provided rich gene expression datasets for the developing lung...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0048OC
更新日期:2009-01-01 00:00:00
abstract::We have previously identified two integrins, alpha 9 beta 1 and alpha v beta 6, from guinea pig airway epithelium. The extracellular matrix protein tenascin is a ligand for both of these receptors, and fibronectin is also a ligand for alpha v beta 6. In the present study, we used immunohistochemistry to examine the ex...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.12.5.7537970
更新日期:1995-05-01 00:00:00
abstract::IL-15 has recently been shown to induce the differentiation of functional dendritic cells (DCs) from human peripheral blood monocytes. Since DCs lay in close proximity to epithelial cells in the airway mucosa, we investigated whether airway epithelial cells release IL-15 in response to inflammatory stimuli and thereby...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0235OC
更新日期:2007-07-01 00:00:00
abstract::Pulmonary artery hypertension (PAH) is a rare and fatal disorder that involves extensive remodeling of the pulmonary arteries mediated by hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Aberrant platelet-derived growth factor (PDGF) activity can lead to hyperproliferation of PASMCs; however, littl...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2017-0111OC
更新日期:2018-02-01 00:00:00
abstract::Isoprostanes are prostaglandin-like molecules that accumulate in oxidative stress and also exert powerful biological effects on a wide variety of tissues. We investigated the effects of several different isoprostanes on contractions evoked by electrical field stimulation (EFS) in bovine trachealis, finding only 15-E2t...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0022OC
更新日期:2007-12-01 00:00:00
abstract::Chloride (Cl(-)) movement across fetal lung epithelia is thought to be mediated by the sodium-potassium-2-Cl(-) cotransporter NKCC1. We studied the role of NKCC1 in Cl(-) and liquid secretion in late-gestation NKCC-null (-/-) and littermate control fetal mouse lung. NKCC -/- mice had decreased lung water compared with...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.25.1.4500
更新日期:2001-07-01 00:00:00
abstract::Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in bleomycin (BLM)-induced lung injury and subsequent fibrotic changes remains to be determined. We evaluated the role of IL-6 in the lung inflammatory changes induced by BLM using wild-type (WT) and IL-6-de...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0299OC
更新日期:2008-05-01 00:00:00
abstract::Bleomycin-induced lung injury causes increased fibroblast numbers in the lung and pulmonary fibrosis. Studies of fibroblasts isolated from such injured lungs have revealed evidence of increased intrinsic proliferative capacity, but the mechanism is unknown. Telomerase catalyzes the addition of telomeric DNA repeats on...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.4.3958
更新日期:2000-10-01 00:00:00