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Jin X, Shang B, Wang J, Sun J, Li J, Liang B, Wang X, Su L, You W, Jiang S. Farnesoid X receptor promotes non-small cell lung cancer metastasis by activating Jak2/STAT3 signaling via transactivation of IL-6ST and IL-6 genes. Cell Death Dis 2024; 15:148. [PMID: 38360812 PMCID: PMC10869786 DOI: 10.1038/s41419-024-06495-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/17/2024]
Abstract
Metastasis accounts for the majority of cases of cancer recurrence and death in patients with advanced non-small cell lung cancer (NSCLC). Farnesoid X Receptor (FXR) is a bile acid nuclear receptor that was recently found to be upregulated in NSCLC tissues. However, whether and how FXR regulates NSCLC metastasis remains unclear. In the present study, it was found that FXR promoted the migration, invasion, and angiogenic ability of NSCLC cells in vitro, and increased NSCLC metastasis in a mouse model in vivo. Mechanistic investigation demonstrated that FXR specifically bound to the promoters of IL-6ST and IL-6 genes to upregulate their transcription, thereby leading to activation of the Jak2/STAT3 signaling pathway, which facilitated tumor migration, invasion, and angiogenesis in NSCLC. Notably, Z-guggulsterone, a natural FXR inhibitor, significantly reduced FXRhigh NSCLC metastasis, and decreased the expression of FXR, IL-6, IL-6ST, and p-STAT3 in the mouse model. Clinical analysis verified that FXR was positively correlated with IL-6, IL-6ST and p-STAT3 expression in NSCLC patients, and was indicative of a poor prognosis. Collectively, these results highlight a novel FXR-induced IL-6/IL-6ST/Jak2/STAT3 axis in NSCLC metastasis, and a promising therapeutic means for treating FXRhigh metastatic NSCLC.
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Affiliation(s)
- Xiuye Jin
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China
- Department of Respiratory and Critical Care Medicine, Xi'an Chest Hospital, Shanxi, 710100, China
| | - Bin Shang
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China
- Department of Thoracic Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
| | - Junren Wang
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China
| | - Jian Sun
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China
| | - Jing Li
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Public Health Clinical Center, Jinan, Shandong, 250013, China
| | - Bin Liang
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China
| | - Xingguang Wang
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China
| | - Lili Su
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China
| | - Wenjie You
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China.
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China.
- Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
| | - Shujuan Jiang
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
- Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China.
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, 250021, China.
- Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, China.
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Hashimoto S, Hashimoto A, Muromoto R, Kitai Y, Oritani K, Matsuda T. Central Roles of STAT3-Mediated Signals in Onset and Development of Cancers: Tumorigenesis and Immunosurveillance. Cells 2022; 11:cells11162618. [PMID: 36010693 PMCID: PMC9406645 DOI: 10.3390/cells11162618] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/12/2022] [Accepted: 08/20/2022] [Indexed: 02/07/2023] Open
Abstract
Since the time of Rudolf Virchow in the 19th century, it has been well-known that cancer-associated inflammation contributes to tumor initiation and progression. However, it remains unclear whether a collapse of the balance between the antitumor immune response via the immunological surveillance system and protumor immunity due to cancer-related inflammation is responsible for cancer malignancy. The majority of inflammatory signals affect tumorigenesis by activating signal transducer and activation of transcription 3 (STAT3) and nuclear factor-κB. Persistent STAT3 activation in malignant cancer cells mediates extremely widespread functions, including cell growth, survival, angiogenesis, and invasion and contributes to an increase in inflammation-associated tumorigenesis. In addition, intracellular STAT3 activation in immune cells causes suppressive effects on antitumor immunity and leads to the differentiation and mobilization of immature myeloid-derived cells and tumor-associated macrophages. In many cancer types, STAT3 does not directly rely on its activation by oncogenic mutations but has important oncogenic and malignant transformation-associated functions in both cancer and stromal cells in the tumor microenvironment (TME). We have reported a series of studies aiming towards understanding the molecular mechanisms underlying the proliferation of various types of tumors involving signal-transducing adaptor protein-2 as an adaptor molecule that modulates STAT3 activity, and we recently found that AT-rich interactive domain-containing protein 5a functions as an mRNA stabilizer that orchestrates an immunosuppressive TME in malignant mesenchymal tumors. In this review, we summarize recent advances in our understanding of the functional role of STAT3 in tumor progression and introduce novel molecular mechanisms of cancer development and malignant transformation involving STAT3 activation that we have identified to date. Finally, we discuss potential therapeutic strategies for cancer that target the signaling pathway to augment STAT3 activity.
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Affiliation(s)
- Shigeru Hashimoto
- Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
- Correspondence: (S.H.); (T.M.)
| | - Ari Hashimoto
- Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Ryuta Muromoto
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
| | - Yuichi Kitai
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
| | - Kenji Oritani
- Department of Hematology, International University of Health and Welfare, Narita 286-8686, Japan
| | - Tadashi Matsuda
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
- Correspondence: (S.H.); (T.M.)
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Wu M, Ye P, Zhang W, Zhu H, Yu H. Prognostic role of an inflammation scoring system in radical resection of oral squamous cell carcinoma. BMC Oral Health 2022; 22:226. [PMID: 35676658 PMCID: PMC9178867 DOI: 10.1186/s12903-022-02261-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/26/2022] [Indexed: 11/12/2022] Open
Abstract
Background Inflammatory markers can influence the postoperative prognosis and outcome of malignant tumors. However, the role of inflammatory factors in oral squamous cell carcinoma (OSCC) are still debatable. The primary objective of this investigation was to detect the preoperative blood fibrinogen and neutrophil–lymphocyte ratio (NLR) in OSCC patients and to determine the predictive validity of F-NLR (combined fibrinogen and NLR score). Methods A total of 365 patients with oral cancer after surgery were separated into three classes: F-NLR of 2, with hyperfibrinogenemia (> 250 mg/dL) and high NLR (> 3.2); F-NLR of 1, with only one higher index; and F-NLR of 0, with no higher indices. Univariate and multivariate analyses were used to identify risk factors for the demographic and clinical characteristics of patients in the three F-NLR groups. Kaplan–Meier survival analysis was used to assess the prognosis. Results Preoperative F-NLR showed a relatively better predictive role in oral cancer prognosis than fibrinogen and NLR alone. Multivariate analysis revealed that F-NLR has the potential to be an independent predictor for OSCC cancer-specific survival (P < 0.001). Patients with high scores had a relatively poorer prognosis than those with low scores (P < 0.001). Conclusions Our findings indicate that blood F-NLR may serve as an independent prognostic factor in OSCC patients.
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Affiliation(s)
- Meng Wu
- Department of Oral and Maxillofacial Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, No. 1, Huanghe West Road, Huaian, 223300, Jiangsu Province, China
| | - Pu Ye
- Department of Oral and Maxillofacial Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, No. 1, Huanghe West Road, Huaian, 223300, Jiangsu Province, China
| | - Wei Zhang
- Department of Oral and Maxillofacial Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, No. 1, Huanghe West Road, Huaian, 223300, Jiangsu Province, China
| | - Hong Zhu
- Department of Pharmacy, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, 223300, Jiangsu Province, China
| | - Huiming Yu
- Department of Oral and Maxillofacial Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, No. 1, Huanghe West Road, Huaian, 223300, Jiangsu Province, China.
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Parakh S, Ernst M, Poh AR. Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities. Cancers (Basel) 2021; 13:6228. [PMID: 34944848 PMCID: PMC8699548 DOI: 10.3390/cancers13246228] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/09/2021] [Accepted: 12/10/2021] [Indexed: 12/12/2022] Open
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 85% of lung cancer cases. Aberrant activation of the Signal Transducer and Activator of Transcription 3 (STAT3) is frequently observed in NSCLC and is associated with a poor prognosis. Pre-clinical studies have revealed an unequivocal role for tumor cell-intrinsic and extrinsic STAT3 signaling in NSCLC by promoting angiogenesis, cell survival, cancer cell stemness, drug resistance, and evasion of anti-tumor immunity. Several STAT3-targeting strategies have also been investigated in pre-clinical models, and include preventing upstream receptor/ligand interactions, promoting the degradation of STAT3 mRNA, and interfering with STAT3 DNA binding. In this review, we discuss the molecular and immunological mechanisms by which persistent STAT3 activation promotes NSCLC development, and the utility of STAT3 as a prognostic and predictive biomarker in NSCLC. We also provide a comprehensive update of STAT3-targeting therapies that are currently undergoing clinical evaluation, and discuss the challenges associated with these treatment modalities in human patients.
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Affiliation(s)
- Sagun Parakh
- Department of Medical Oncology, The Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, VIC 3084, Australia;
- Tumor Targeting Laboratory, The Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia
- School of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia;
| | - Matthias Ernst
- School of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia;
- Cancer and Inflammation Laboratory, The Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia
| | - Ashleigh R. Poh
- School of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia;
- Cancer and Inflammation Laboratory, The Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia
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Li X, Weber NC, Cohn DM, Hollmann MW, DeVries JH, Hermanides J, Preckel B. Effects of Hyperglycemia and Diabetes Mellitus on Coagulation and Hemostasis. J Clin Med 2021; 10:jcm10112419. [PMID: 34072487 PMCID: PMC8199251 DOI: 10.3390/jcm10112419] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 12/21/2022] Open
Abstract
In patients with diabetes, metabolic disorders disturb the physiological balance of coagulation and fibrinolysis, leading to a prothrombotic state characterized by platelet hypersensitivity, coagulation disorders and hypofibrinolysis. Hyperglycemia and insulin resistance cause changes in platelet number and activation, as well as qualitative and/or quantitative modifications of coagulatory and fibrinolytic factors, resulting in the formation of fibrinolysis-resistant clots in patients with diabetes. Other coexisting factors like hypoglycemia, obesity and dyslipidemia also contribute to coagulation disorders in patients with diabetes. Management of the prothrombotic state includes antiplatelet and anticoagulation therapies for diabetes patients with either a history of cardiovascular disease or prone to a higher risk of thrombus generation, but current guidelines lack recommendations on the optimal antithrombotic treatment for these patients. Metabolic optimizations like glucose control, lipid-lowering, and weight loss also improve coagulation disorders of diabetes patients. Intriguing, glucose-lowering drugs, especially cardiovascular beneficial agents, such as glucagon-like peptide-1 receptor agonists and sodium glucose co-transporter inhibitors, have been shown to exert direct anticoagulation effects in patients with diabetes. This review focuses on the most recent progress in the development and management of diabetes related prothrombotic state.
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Affiliation(s)
- Xiaoling Li
- Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (X.L.); (N.C.W.); (M.W.H.); (J.H.)
| | - Nina C. Weber
- Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (X.L.); (N.C.W.); (M.W.H.); (J.H.)
| | - Danny M. Cohn
- Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
| | - Markus W. Hollmann
- Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (X.L.); (N.C.W.); (M.W.H.); (J.H.)
| | - J. Hans DeVries
- Department of International Medicine, Amsterdam UMC location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
| | - Jeroen Hermanides
- Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (X.L.); (N.C.W.); (M.W.H.); (J.H.)
| | - Benedikt Preckel
- Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (X.L.); (N.C.W.); (M.W.H.); (J.H.)
- Correspondence: ; Tel.: +31-20-5669111
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Schrepf A, Lutgendorf SK, Pyter LM. Pre-treatment effects of peripheral tumors on brain and behavior: neuroinflammatory mechanisms in humans and rodents. Brain Behav Immun 2015; 49:1-17. [PMID: 25958011 PMCID: PMC4567396 DOI: 10.1016/j.bbi.2015.04.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 04/14/2015] [Accepted: 04/17/2015] [Indexed: 12/12/2022] Open
Abstract
Cancer patients suffer high levels of affective and cognitive disturbances, which have been attributed to diagnosis-related distress, impairment of quality of life, and side effects of primary treatment. An inflammatory microenvironment is also a feature of the vast majority of solid tumors. However, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and cognitive disturbances. In this review, we summarize the burgeoning evidence from rodent cancer models that solid tumors alter neurobiological pathways and subsequent behavioral processes with relevance to affective and cognitive disturbances reported in human cancer populations. We consider, in parallel, the evidence from human clinical cancer research demonstrating that affective and cognitive disturbances are common in some malignancies prior to diagnosis and treatment. We further consider the underlying neurobiological pathways, including altered neuroinflammation, tryptophan metabolism, prostaglandin synthesis and associated neuroanatomical changes, that are most strongly implicated in the rodent literature and supported by analogous evidence from human cancer populations. We focus on the implications of these findings for behavioral researchers and clinicians, with particular emphasis on methodological issues and areas of future research.
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Affiliation(s)
- Andrew Schrepf
- Department of Psychology, University of Iowa, Iowa City, IA 52242, USA
| | - Susan K Lutgendorf
- Department of Psychology, University of Iowa, Iowa City, IA 52242, USA; Departments of Urology and Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
| | - Leah M Pyter
- Institute for Behavioral Medicine Research, Departments of Psychiatry and Behavioral Health and Neuroscience, Ohio State University, Columbus, OH 43210, USA.
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El Sayed R, Okab A, El-Mahdy M, Kasb I, Ismail Y. Role of interleukin-6 (IL-6) in diagnosis of malignant pleural mesothelioma. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2015. [DOI: 10.1016/j.ejcdt.2014.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Cheng D, Kong H, Li Y. Prognostic values of VEGF and IL-8 in malignant pleural effusion in patients with lung cancer. Biomarkers 2013; 18:386-90. [DOI: 10.3109/1354750x.2013.797499] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Elevated levels of plasma fibrinogen in patients with pancreatic cancer: possible role of a distant metastasis predictor. Pancreas 2009; 38:e75-9. [PMID: 19276866 DOI: 10.1097/mpa.0b013e3181987d86] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Although changes of plasma fibrinogen have been documented in limited pancreatic malignant tumors, a relationship between plasma fibrinogen and pancreatic cancer in a large-scale clinical study has not been shown. METHODS Preoperative plasma levels of fibrinogen were retrospectively analyzed in 133 pancreatic cancer and 38 pancreatic benign tumor patients. RESULTS Plasma fibrinogen in pancreatic cancer patients were significantly higher than those with benign pancreatic tumor (3.99 +/- 1.01 vs 2.62 +/- 0.65; P < 0.001). The percentage of hyperfibrinogenemia (>4.20 g/L) in pancreatic cancer was 41.1%, and no positive results were obtained in benign pancreatic disease. Plasma fibrinogen levels were increased in pancreatic cancer with advanced tumor stage. Accompanied with the progression of tumor stage, there was an increase in the percentage of positivity of hyperfibrinogenemia in pancreatic cancer. There were markedly higher levels of plasma fibrinogen in the distant-metastasis group than in the no-distant-metastasis group (4.41 +/- 0.84 vs 3.76 +/- 1.04; P < 0.01). Univariate and multivariate analysis revealed that high plasma fibrinogen levels (>4.20 g/L) were positively associated with distant metastasis of pancreatic cancer. CONCLUSIONS Plasma fibrinogen levels had a positive relationship with tumor stage of pancreatic cancer. Increased preoperative plasma fibrinogen levels might be a useful predictor for distant metastasis in human pancreatic cancer.
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Gam LH, Leow CH, Man CN, Gooi BH, Singh M. Analysis of differentially expressed proteins in cancerous and normal colonic tissues. World J Gastroenterol 2006; 12:4973-80. [PMID: 16937492 PMCID: PMC4087399 DOI: 10.3748/wjg.v12.i31.4973] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.
METHODS: Colon tissues (normal and cancerous) were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.
RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.
CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.
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Affiliation(s)
- Lay-Harn Gam
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
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Yeh HH, Lai WW, Chen HHW, Liu HS, Su WC. Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion. Oncogene 2006; 25:4300-9. [PMID: 16518408 DOI: 10.1038/sj.onc.1209464] [Citation(s) in RCA: 180] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Malignant pleural effusion (MPE) is a poor prognostic sign for patients with non-small-cell lung cancer (NSCLC). The generation of MPE is largely regulated by vascular endothelial growth factor (VEGF), and upregulation of VEGF by Stat3 has been observed in several types of tumor cells. In this study, we demonstrate constitutively activated Stat3 in several human lung cancer cell lines and in tumor cells infiltrated in the pleurae of patients with adenocarcinoma cell lung cancer (ADCLC) and MPE. The observations suggest that activated Stat3 plays a role in the pathogenesis of ADCLC. In PC14PE6/AS2 cells, a Stat3-positive human ADCLC cell line, autocrine IL-6 activated Stat3 via JAKs, not via Src kinase. PC14PE6/AS2 cells express higher VEGF mRNA and protein than do Stat3-negative PC14PE6/AS2/dnStat3 cells. In an animal model, PC14P6/AS2/dnStat3 cells produced no MPE and less lung metastasis than did PC14P6/AS2 cells. PC14PE6/AS2 cells also expressed higher VEGF protein, microvessel density, and vascular permeability in tumors than did PC14P6/AS2/dnStat3 cells. Therefore, we hypothesize that autocrine IL-6 activation of Stat3 in ADCLC may be involved in the formation of malignant pleural effusion by upregulating VEGF. Higher levels of IL-6 and VEGF were also found in the pleural fluids of patients with ADCLC than in patients with congestive heart failure. The autocrine IL-6/Stat3/VEGF signaling pathway may also be activated in patients with ADCLC and MPE. These findings provide novel targets for the management of MPE.
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Affiliation(s)
- H-H Yeh
- Institute of Basic Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Hata N, Tanaka K, Imaizumi T, Ohara T, Ohba T, Shinada T, Takano T. Clinical significance of pleural effusion in acute aortic dissection. Chest 2002; 121:825-30. [PMID: 11888967 DOI: 10.1378/chest.121.3.825] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
STUDY OBJECTIVE To clarify the clinical significance of pleural effusion in the clinical course of acute aortic dissection (AAD). DESIGN Retrospective clinical series. SETTING A university hospital. PATIENTS Fifty-five patients strongly suspected of having AAD because of severe chest or back pain. Patients with obvious ischemic heart disease, lung disease, and pleural disease were excluded. INTERVENTIONS An additional diagnosis of pleural effusion was made when evident by CT. MEASUREMENTS AND RESULTS Pleural effusion was detected in 42 of 48 patients (88%) with AAD (mean plus minus SD age, 65 plus minus 12 years; 35 men and 13 women), but in only 1 of 7 patients (14%) who proved not to have AAD (mean age, 74 +/- 10 years; 6 men and 1 woman). Effusion appeared at a mean of 4.5 days after onset of dissection. Thoracentesis performed in six patients showed a bloody effusion in three patients and an exudative effusion in three patients. In the six AAD patients without pleural effusion, four patients underwent surgery within 3 days after onset of dissection. In patients with AAD, effusion was demonstrated on the first CT after hospital admission in 18 patients, and was bilateral in 32 patients. WBC count in blood, serum C-reactive protein concentration, and body temperature were higher in patients with effusion (13,400 +/- 3,600/microL, 18.4 +/- 11.5 mg/dL, and 38.2 +/- 0.7 degrees C) than in those without effusion (10,300 +/- 2,900/microL, 4.5 +/- 4.2 mg/dL, and 37.0 +/- 1.0 degrees C, respectively). CONCLUSIONS Pleural effusion occurs frequently in patients with AAD, often in association with inflammatory reactions.
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Affiliation(s)
- Noritake Hata
- Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan.
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