Biobehavioral-Cytokine Interactions in Ovarian Cancer

卵巢癌的生物行为-细胞因子相互作用

• 批准号: 7257219
• 负责人: SUSAN K LUTGENDORF
• 金额: $ 25.74万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7257219
• 关键词: Adrenergic Agents; Adrenergic beta-Agonists; Angiogenesis Inhibition; Ascites; Behavioral; Blood Vessels; Cancer Control; Cancer Patient; Cancer Prognosis; Cell Line; Cells; Clinical; Clinical Course of Disease; Clinical Research; Coupled; Data; Diagnosis; Disease; Disease Progression; Distant; Distress; Epinephrine; Epithelial ovarian cancer; Exploratory/Developmental Grant; Face; Feeling; Fibrinogen; Future; Goals; Growth; Health; Hormonal; Hormones; Hydrocortisone; IL8 gene; Immune; Immune response; Immunity; Immunologics; In Vitro; Interleukin-12; Interleukin-6; Interleukin-8; Intervention; Investigation; Isoproterenol; Life Stress; Liquid substance; Localized Disease; Longitudinal Studies; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Measurement; Mediating; Mediator of activation protein; Mental Depression; Neurosecretory Systems; Norepinephrine; Numbers; Operative Surgical Procedures; Outcome; Ovarian; Pathway interactions; Patients; Personality Traits; Plasma; Platelet Factor 4; Process; Production; Psychosocial Factor; Recurrence; Relapse; Reporting; Research; Research Personnel; Resources; Risk Factors; Role; Salivary; Sampling; Serum; Signal Transduction; Social support; Solid Neoplasm; Staging; Stress; Survival Rate; Time; Tumor Angiogenesis; Tumor Cell Line; Tumor Promoters; Variant; Vascular Endothelial Growth Factors; Woman; Work; adrenergic; angiogenesis; beta-adrenergic receptor; biobehavior; cancer diagnosis; coping; cytokine; depressive symptoms; emotional distress; in vitro Model; innovation; multidisciplinary; neoplastic cell; novel; optimism; ovarian neoplasm; peripheral blood; prospective; psychosocial; resilience; trend; tumor; tumor growth; tumor progression

DESCRIPTION (provided by applicant): Ovarian cancer is the second most common gynecologic cancer. Because of low rates of survival for the majority of ovarian cancer patients, identification of factors contributing to tumor growth and progression is of paramount importance. Although relationships between psychosocial factors and immunity have been extensively documented, there has been little investigation of relationships between psychosocial factors and cytokines involved in angiogenesis, the formation of new blood vessels that enhance tumor growth. These cytokines include Interleukin-8 (IL-8), Interleukin-12 (IL-12), Interleukin-6 (IL-6), and Vascular Endothelial Growth Factor (VEGF). VEGF, one of the key promoters of tumor angiogenesis, is associated with poorer ovarian cancer survival. VEGF is influenced by a variety of cytokines, hormones including cortisol, and by sympathetic activation. We have reported that ovarian cancer patients reporting greater social support had significantly lower serum VEGF pre-surgery, whereas those reporting greater feelings of distress had higher VEGF. Additionally, in an in vitro model, we have observed that stress hormones, such as norepinephrine, induce production of VEGF from an ovarian tumor cell line and that these tumor cells also express beta-adrenergic receptors. These effects are further augmented by cortisol. These novel findings, coupled with known hormonal modulation of other angiogenic cytokines, highlight the possibility that psychosocial factors may directly influence angiogenesis, and thus tumor progression in ovarian cancer. This 5-year prospective longitudinal study will investigate relationships among psychosocial factors and 4 angiogenic cytokines: VEGF, IL-6, IL-8, and IL-12, among 154 ovarian cancer patients in a clinical setting. We have selected these cytokines because of their critical role in ovarian cancer growth and progression. Measurements of cytokines and psychosocial factors will be taken pre-surgery and at intervals up to 9 months post-surgery; disease progression will be assessed until 18 months post-surgery. The significance of these findings is that they will investigate a novel mechanism by which biobehavioral factors in ovarian cancer patients may contribute to tumor growth and disease progression. Findings will have implications for innovative behavioral and pharmacological intervention strategies for ovarian cancer patients.

描述（由申请人提供）： 卵巢癌是第二常见的妇科癌症。由于大多数卵巢癌患者的生存率较低，因此鉴定有助于肿瘤生长和进展的因素至关重要。尽管已经广泛记录了社会心理因素与免疫力之间的关系，但是对参与血管生成的社会心理因素与细胞因子之间的关系几乎没有研究，这是增强肿瘤生长的新血管的形成。这些细胞因子包括白介素-8（IL-8），白介素12（IL-12），白介素6（IL-6）和血管内皮生长因子（VEGF）。 VEGF是肿瘤血管生成的关键启动子之一，与较差的卵巢癌存活有关。 VEGF受多种细胞因子，包括皮质醇在内的激素和交感神经激活的影响。我们报道说，报道更多社会支持的卵巢癌患者的血清VEGF前手术前较低，而报道更多痛苦感的人的VEGF则更高。此外，在体外模型中，我们观察到诸如去甲肾上腺素等应激激素会诱导卵巢肿瘤细胞系的VEGF产生，并且这些肿瘤细胞也表达β-肾上腺素能受体。皮质醇进一步增强了这些作用。这些新颖的发现，再加上其他血管生成细胞因子的已知激素调节，强调了社会心理因素可能直接影响血管生成，从而导致卵巢癌的肿瘤进展的可能性。这项为期5年的前瞻性纵向研究将研究心理社会因素和4种血管生成细胞因子之间的关系：VEGF，IL-6，IL-8和IL-12，在临床环境中的154名卵巢癌患者中。我们之所以选择这些细胞因子，是因为它们在卵巢癌的生长和进展中具有关键作用。细胞因子和社会心理因素的测量将在手术前和手术后长达9个月进行。疾病进展将评估直到手术后18个月。这些发现的重要性是，他们将研究一种新的机制，卵巢癌患者的生物行为因素可能有助于肿瘤生长和疾病进展。调查结果将对卵巢癌患者的创新行为和药理干预策略产生影响。

项目成果

Biobehavioral influences on cancer progression.

• DOI: 10.1016/j.iac.2010.09.001
• 发表时间: 2011-02
• 期刊: IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA
• 影响因子: 2.6
• 作者: Costanzo, Erin S.;Sood, Anil K.;Lutgendorf, Susan K.
• 通讯作者: Lutgendorf, Susan K.

Biobehavioral and neuroendocrine correlates of antioxidant enzyme activity in ovarian carcinoma.

• DOI: 10.1016/j.bbi.2015.04.019
• 发表时间: 2015-11
• 期刊: Brain, behavior, and immunity
• 作者: Bayer JL;Spitz DR;Christensen D;McCormick ML;Farley D;DeGeest K;Damoush L;Aust S;Sood AK;Lutgendorf SK
• 通讯作者: Lutgendorf SK

Biobehavioral approaches to cancer progression and survival: Mechanisms and interventions.

• DOI: 10.1037/a0035730
• 发表时间: 2015-02
• 期刊: The American psychologist
• 作者: Lutgendorf SK;Andersen BL
• 通讯作者: Andersen BL

Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability.

• DOI: 10.1016/j.bbi.2012.07.022
• 发表时间: 2013-03
• 期刊: BRAIN BEHAVIOR AND IMMUNITY
• 影响因子: 15.1
• 作者: Schrepf, Andrew;Clevenger, Lauren;Christensen, Desire;DeGeest, Koen;Bender, David;Ahmed, Amina;Goodheart, Michael J.;Dahmoush, Laila;Penedo, Frank;Lucci, Joseph A., III;Ganjei-Azar, Parvin;Mendez, Luis;Markon, Kristian;Lubaroff, David M.;Thaker, Premal H.;Slavich, George M.;Sood, Anil K.;Lutgendorf, Susan K.
• 通讯作者: Lutgendorf, Susan K.

Psychoneuroimmunology and cancer: a decade of discovery, paradigm shifts, and methodological innovations.

• DOI: 10.1016/j.bbi.2013.01.003
• 发表时间: 2013-03
• 期刊: BRAIN BEHAVIOR AND IMMUNITY
• 影响因子: 15.1
• 作者: McDonald, Paige Green;O'Connell, Mary;Lutgendorf, Susan K.
• 通讯作者: Lutgendorf, Susan K.