Biomedical subjects

Alissa K Greenberg

Publications and source records attributed to Alissa K Greenberg.

6 recordsLinked to original sources

PubMed2005

Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis.

BACKGROUND: Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response. METHODS: Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance. RESULTS: Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and alpha-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified. CONCLUSION: Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.

Antibodies↗

PubMed2005

Basic pathogenetic mechanisms in silicosis: current understanding.

PURPOSE OF REVIEW: Silicosis continues to be a common cause of chronic lung diseases, despite evidence that these diseases can be prevented by environmental dust control. Silicosis has been studied extensively by basic and clinical scientists, yet little is known about the crucial cellular and molecular mechanisms that initiate and propagate the process of inflammation and scarring. RECENT FINDINGS: Recent in vivo, in vitro, and human studies have focused on several main areas of investigation into the causes and processes of the development of silicosis. These areas of investigation include the variability of pathogenic potential of different varieties of silica; the role of activated alveolar macrophages products in the development and progression of silicosis; and the direct role played by the silica particle surface in triggering adverse biologic reactions, such as generating ROS and RNS. The generation of oxidants by silica particles and by silica-activated cells results in cell and lung damage; increased expression of inflammatory cytokines, including TNF-alpha, IL 1 beta, and TGF-beta; activation of cell signaling pathways, including the MAP kinase pathways; and phosphorylation and activation of specific transcription factors (e.g., NFkB). The ROS, RNS, and NO generated by the silica particles also induce apoptosis in macrophages and other cells. SUMMARY: Further research on the molecular mechanisms involved in the inflammatory processes important for progression to fibrotic diseases is needed for the development of effective treatment of silicosis. Potential therapeutic strategies include inhibition of cytokines such as IL-1, TNF alpha, the use of anti-oxidants, and the inhibition of apoptosis.

Animals↗

PubMed2002

Preneoplastic lesions of the lung.

Lung cancer is the leading cause of cancer deaths worldwide. If we can define and detect preneoplastic lesions, we might have a chance of improving survival. The World Health Organization has defined three preneoplastic lesions of the bronchial epithelium: squamous dysplasia/carcinoma in situ; atypical adenomatous hyperplasia; and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma and carcinoid tumors, respectively. In this review we summarize the data supporting the preneoplastic nature of these lesions, and delve into some of the genetic changes found in atypical adenomatous hyperplasia and squamous dysplasia/carcinoma in situ.

Animals↗

PubMed2002

Selective p38 activation in human non-small cell lung cancer.

The mitogen-activated protein kinase (MAPK) pathways transmit signals from the cell membrane to the nucleus. Activation of MAPK cascades may play a role in malignant transformation. We hypothesized that enhanced expression of one or more of these pathways would occur in human lung cancers. Using Western blot analysis of tissue homogenates from resected non- small cell lung cancers and matched non-neoplastic lung tissue, we determined that only activated p38 was consistently increased in tumor compared with normal tissue. In vitro kinase assays confirmed that the levels of activated MAPK correlated with the activity of the enzymes, and immunohistochemical analysis confirmed the cellular localization of the activated MAPKs. We incubated a lung cancer cell line in a hypoxic chamber to simulate the hypoxic environment in solid lung tumors, but found no increase in p38 activation. Contrary to our expectations, ERK and JNK, the MAPK pathways traditionally associated with cell growth and perhaps malignant transformation, were not consistently activated in the human lung tumor samples. However, p38, a MAPK usually associated with stress responses, growth arrest, and apoptosis, was activated in all of the human lung cancer samples, suggesting an additional role for this pathway in malignant cell growth or transformation.

Blotting, Western↗

PubMed2002

Glucocorticoids inhibit lung cancer cell growth through both the extracellular signal-related kinase pathway and cell cycle regulators.

Glucocorticoids inhibit the proliferation of various cell types, but the mechanism of this inhibition remains unclear. We investigated the effect of dexamethasone on non-small cell lung cancer cell growth and cell cycle progression. We showed that dexamethasone suppresses the proliferation of A549 and Calu-1 cells, with accumulation of cells in G1/G0 stage of the cell cycle, as determined by fluorescence-activated cell sorter analysis. Western blot analysis confirmed that this is associated with hypophosphorylation of retinoblastoma protein. Using Western blot analysis and in vitro kinase assays, we found that dexamethasone results in decreased activity of CDK2 and 4, decreased levels of cyclin D, E2F, and Myc, and increased levels of the CDK inhibitor p21(Cip1). In addition, we found that dexamethasone decreases activity of extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK). The kinetics of all these changes indicate that inhibition of the ERK/MAPK pathway precedes the cell cycle effects, suggesting that regulation of this MAPK-signaling pathway may be an alternative mechanism for glucocorticoid-induced cell cycle arrest and growth inhibition.

Cell Cycle↗

PubMed2002

Clinical presentation of pulmonary mycetoma in HIV-infected patients.

STUDY OBJECTIVE: s: Although pulmonary mycetoma has been well-described in immunocompetent hosts, the only description in HIV-infected patients has been of 10 patients from our institution, from 1992 to 1995. To further investigate the impact of HIV status on the presentation and course of pulmonary mycetoma, we conducted a follow-up study. DESIGN: Retrospective review of all cases of pulmonary mycetoma at Bellevue Hospital from 1992 to 1999. SETTING: Patients were evaluated on the inpatient chest service and in the outpatient chest and HIV clinics of Bellevue Hospital in New York City. PATIENTS: We identified 74 patients with pulmonary mycetoma; 20 of them were HIV-infected (27%). INTERVENTIONS: The 20 HIV-infected patients were treated with antiretroviral and/or antifungal therapy. MEASUREMENTS AND RESULTS: Predisposing diseases were pulmonary tuberculosis (TB), Pneumocystis carinii pneumonia (PCP), or both TB and PCP. Seventeen patients had a CD4+ cell count of < 100 cells/ micro L at presentation. Hemoptysis was present in 13 patients, but was massive in only 1 patient. Cough was common. Of the 18 patients for whom follow-up was available, 11 received antifungal treatment and 7 were observed without therapy. Six patients received both antiretroviral and antifungal therapy. Disease progression occurred in 50%. Only five patients exhibited radiographic or clinical improvement. All five were treated with both antiretroviral and antifungal therapy. CONCLUSIONS: PCP is a risk factor for pulmonary mycetoma in the HIV-infected individual. HIV-infected patients with mycetomas have a significant rate of disease progression, although they rarely have life-threatening hemoptysis. A combination of antifungal and antiretroviral therapy may improve the clinical outcome in HIV-infected patients with pulmonary mycetoma.

AIDS-Related Opportunistic Infections↗