Use of Gene Expression Profiles in Cells of Peripheral Blood to Identify New Molecular Markers of Acute Pancreatitis

Bluth, Martin H.; Lin, Yinyao; Zhang, Hong; Viterbo, Domenico; Zenilman, Michael E.

doi:10.1001/archsurg.2007.73

Cited by 27 publications

(21 citation statements)

References 34 publications

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“…Therefore, selective induction of PLD1 by pathogen activation might play a relevant role in the late phase of immune response and in chronic inflammation. Microarray analysis during the transcriptional profiling of peripheral blood mononuclear cells associated with acute pancreatitis demonstrated that PLD1 was the top up-regulated gene (61), suggesting that it is a suitable molecular marker of acute pancreatitis. Genetic silencing of PLD1 effectively blocked the cytokine/chemokine production, vascular permeability, and leukocyte recruitment triggered by tumor necrosis factor ␣ (TNF␣) in an in vivo peritonitis model (62).…”

Section: Selective Induction Of Pld1 By Inflammatory Cytokinesmentioning

confidence: 99%

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

Kang

Choi

Min

2014

Journal of Biological Chemistry

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Phospholipase D (PLD) regulates downstream effectors by generating phosphatidic acid. Growing links of dysregulation of PLD to human disease have spurred interest in therapeutics that target its function. Aberrant PLD expression has been identified in multiple facets of complex pathological states, including cancer and inflammatory diseases. Thus, it is important to understand how the signaling network of PLD expression is regulated and contributes to progression of these diseases. Interestingly, small molecule PLD inhibitors can suppress PLD expression as well as enzymatic activity of PLD and have been shown to be effective in pathological mice models, suggesting the potential for use of PLD inhibitors as therapeutics against cancer and inflammation. Here, we summarize recent scientific developments regarding the regulation of PLD expression and its role in cancer and inflammatory processes.Phospholipase D produces phosphatidic acid (PA) 2 via hydrolysis of phospholipids such as phosphatidylcholine and cardiolipin. As a lipid second messenger, PA has been implicated in a wide range of pathophysiological processes including proliferation, oncogenesis, inflammation, phagocytosis, membrane fusion, and spermatogenesis. Phosphatidylcholine-specific PLD1 and PLD2 are the classic mammalian isoforms of PLD (1, 2). Growth factor, mitogen, and inflammatory cytokines up-regulate expression and activity of PLD; however, aberrant dysregulation of PLD occurs in various cancers and inflammation-related diseases. Accordingly, it is important to understand how expression of PLD is regulated and contributes to these diseases.An association between inflammation and cancer has been observed (3) and supported by recent epidemiological data that indicated ϳ20% of cancer deaths are linked to chronic infections and persistent inflammation (4). The PLD signaling pathway provides a possible molecular link between inflammation and cancer; however, systematic investigation of PLD as a therapeutic target has only begun within the last few years with the development of small molecule PLD inhibitors and PLD knock-out mice (5-13). This review covers recent advances in the regulation of PLD expression and its role in cancer and inflammation.

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Section: Selective Induction Of Pld1 By Inflammatory Cytokinesmentioning

confidence: 99%

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

Kang

Choi

Min

2014

Journal of Biological Chemistry

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“…Moreover, microarray analysis in the transcriptional profiling of peripheral blood mononuclear cells during acute pancreatitis showed that PLD1 is the top upregulated gene (14). However, the functional role of PLD in a pathological lesion of chronic inflammatory diseases, such as RA, remains unknown.…”

mentioning

confidence: 99%

Phospholipase D1 Has a Pivotal Role in Interleukin-1β-Driven Chronic Autoimmune Arthritis through Regulation of NF-κB, Hypoxia-Inducible Factor 1α, and FoxO3a

Kang

Park

et al. 2013

Molecular and Cellular Biology

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“…It has been suggested that tumors could be recognized by the immune system and that cancer cells can evade the elimination of immunological surveillance [6]. Therefore, immune evasion might occur as an early event in tumorigenesis [7], [8]. Peripheral blood mononucleated cells (PBMCs) mainly consist of monocytes, T cells, B cells, granulocytes, and natural killer cells [9] and act as the first line of defense against malignancy in the immune system [9].…”

Section: Introductionmentioning

confidence: 99%

A Prediction Model Based on Biomarkers and Clinical Characteristics for Detection of Lung Cancer in Pulmonary Nodules

Guarnera

Zhou

et al. 2017

Translational Oncology

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Lung cancer early detection by low-dose computed tomography (LDCT) can reduce the mortality. However, LDCT increases the number of indeterminate pulmonary nodules (PNs), whereas 95% of the PNs are ultimately false positives. Modalities for specifically distinguishing between malignant and benign PNs are urgently needed. We previously identified a panel of peripheral blood mononucleated cell (PBMC)-miRNA (miRs-19b-3p and -29b-3p) biomarkers for lung cancer. This study aimed to evaluate efficacy of integrating biomarkers and clinical and radiological characteristics of smokers for differentiating malignant from benign PNs. We analyzed expression of 2 miRNAs (miRs-19b-3p and -29b-3p) in PBMCs of a training set of 137 individuals with PNs. We used multivariate logistic regression analysis to develop a prediction model based on the biomarkers, radiographic features of PNs, and clinical characteristics of smokers for identifying malignant PNs. The performance of the prediction model was validated in a testing set of 111 subjects with PNs. A prediction model comprising the two biomarkers, spiculation of PNs and smoking pack-year, was developed that had 0.91 area under the curve of the receiver operating characteristic for distinguishing malignant from benign PNs. The prediction model yielded higher sensitivity (80.3% vs 72.6%) and specificity (89.4% vs 81.9%) compared with the biomarkers used alone (all P < .05). The performance of the prediction model for malignant PNs was confirmed in the validation set. We have for the first time demonstrated that the integration of biomarkers and clinical and radiological characteristics could efficiently identify lung cancer among indeterminate PNs.

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Use of Gene Expression Profiles in Cells of Peripheral Blood to Identify New Molecular Markers of Acute Pancreatitis

Cited by 27 publications

References 34 publications

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

Phospholipase D1 Has a Pivotal Role in Interleukin-1β-Driven Chronic Autoimmune Arthritis through Regulation of NF-κB, Hypoxia-Inducible Factor 1α, and FoxO3a

A Prediction Model Based on Biomarkers and Clinical Characteristics for Detection of Lung Cancer in Pulmonary Nodules

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