High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.
High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.
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DOI：
10.1371/journal.pone.0033069
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Oberyszyn TM
中科院分区：
文献类型：
--
作者：
Dhabhar FS;Saul AN;Holmes TH;Daugherty C;Neri E;Tillie JM;Kusewitt D;Oberyszyn TM
尽管有广泛的轶事和科学证据，但关于心理因素和癌症易感性之间长期被怀疑的联系，仍有许多有待理解。皮肤是最常见的癌症部位，占美国所有癌症的近一半，全球每年约有200-300万例非黑色素瘤癌症发生。我们假设，高度焦虑、易应激的行为表型会导致更高的慢性应激负担、更低的保护性免疫力，以及免疫反应性皮肤癌--鳞状细胞癌的加速进展。SKH1小鼠在基线时表现为高焦虑或低焦虑，然后暴露于紫外线-B光(1次最小红斑剂量(MED)，3次/周，10周)。这种癌症模型的显著优点是，它使用了一种正常的、免疫活性的、远缘繁殖的菌株，无需手术/注射外源肿瘤细胞/细胞系，并产生类似于人类肿瘤的病变。每周清点肿瘤(主要结果)，并收集肿瘤发展早期和晚期的组织。用聚合酶链式反应检测趋化因子/细胞因子基因的表达，用免疫组织化学方法检测肿瘤浸润性辅助性细胞(Th)、细胞毒性T细胞(CTL)和调节性T细胞(Treg)的表达，用流式细胞仪检测T细胞和B细胞，用ELISA法检测肾上腺和血浆皮质酮和组织血管内皮生长因子(VEGF)的表达。高度焦虑的小鼠在肿瘤发展的所有阶段都表现出更高的肿瘤负担。他们还显示：较高的皮质酮水平(表明更大的慢性应激负荷)，CCL22表达增加和Treg浸润(增加肿瘤招募免疫抑制)，较低的CTACK/CCL27，IL-12和干扰素-γ基因表达，较低的肿瘤浸润性Th和CTL数量(受抑制的保护性免疫)，以及较高的血管内皮生长因子浓度(增加肿瘤血管生成/侵袭/转移)。这些结果表明，高特质焦虑的有害影响可能是：生活应激源加剧，癌症诊断/治疗压力加剧，并促进肿瘤进展和/或转移。因此，在癌症诊断后立即和在癌症治疗/生存期间研究化疗相容的抗焦虑治疗的使用可能是有益的。
In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2–3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED), 3 times/week, 10-weeks). The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome), and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th), cytolytic (CTL), and regulatory (Treg) T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF) by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden), increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression), lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity), and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis). These results suggest that the deleterious effects of high trait anxiety could be: exacerbated by life-stressors, accentuated by the stress of cancer diagnosis/treatment, and mediate increased tumor progression and/or metastasis. Therefore, it may be beneficial to investigate the use of chemotherapy-compatible anxiolytic treatments immediately following cancer diagnosis, and during cancer treatment/survivorship.
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影响因子：
1.6
作者：
Brigman, Jonathan L.;Mathur, Poonam;Holmes, Andrew
通讯作者：
Holmes, Andrew
影响因子：
2.4
作者：
Ben-Eliyahu, S;Shakhar, G;Shakhar, K
通讯作者：
Shakhar, K
影响因子：
4.5
作者：
CANFIELD, PJ;XU, FN;WILKINSON, F
通讯作者：
WILKINSON, F
DOI：
10.1016/s1011-1344(01)00198-1
发表时间：
2001-10-01
影响因子：
5.4
作者：
Armstrong, BK;Kricker, A
通讯作者：
Kricker, A
DOI：
10.1016/0960-0760(91)90286-e
发表时间：
1991-01-01
影响因子：
4.1
作者：
BERKENBOSCH, F;WOLVERS, DAW;DERIJK, R
通讯作者：
DERIJK, R