Impact of TNF-α and IL-6 Levels on Development of Cachexia in Newly Diagnosed NSCLC Patients

Kayacan, Oya; Karnak, Demet; Beder, Sumru; Güllü, Emine; Tutkak, Hüseyin; Şenler, Filiz Çay; Köksal, Deniz

doi:10.1097/01.coc.0000221300.72657.e0

Cited by 65 publications

(53 citation statements)

References 28 publications

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“…Another major finding of the present study was the positive association between the expression of the two cytokines. Our finding is consistent with the reports which demonstrate that IL-6 and TNF-a were interdependent cytokines [48][49][50]. Ben-Baruch [51], in a review of breast cancer development and progression, indicated the fact that the IL-6 and TNF-a are interrelated and may act in an additive manner, suggesting that these cytokines, together with IL-1, form a network of related factors that may affect tumor cell progression in a cooperative manner.…”

Section: Discussionsupporting

confidence: 92%

Coexpression of IL-6 and TNF-α: prognostic significance on breast cancer outcome

Tripsianis¹,

Papadopoulou²,

Αναγνωστόπουλος³

et al. 2014

neo

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Presented study was conducted to investigate the prognostic significance of the coexpression of serum interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in breast cancer, by correlating their presence with clinicopathological characteristics indicative of tumor progression and the overall survival of breast cancer patients. One hundred twelve consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of IL-6 and TNF-a were measured by quantitative sandwich enzyme immunoassay (ELISA). Median split was used to subdivide patients with low or high IL-6 and TNF-a levels. A positive association between the expression of the two cytokines was found. The coexpression of high IL-6 and TNF-α was independently associated with extended lymph node (>3) involvement (aOR, 7.8) and lymphovascular invasion (aOR, 14.1), increasing the prognostic significance of each cytokine separately; it also provided additional prognostic information regarding survival, defining a high-risk subgroup of patients with significantly shorter survival and higher risk of death compared to patients with both cytokines low (aHR, 4.45) and patients with only one cytokine high (aHR, 3.63). Our findings suggest that the coexpression of these two cytokines could be used clinically as a useful tumor marker for the extension and the outcome of the disease.

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Section: Discussionsupporting

confidence: 92%

Coexpression of IL-6 and TNF-α: prognostic significance on breast cancer outcome

Tripsianis¹,

Papadopoulou²,

Αναγνωστόπουλος³

et al. 2014

neo

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“…Cancer cachexia and paraneoplastic syndrome are the primary causes of mortality in cancer patients. Although a few cytokines including TNF-␣ and IL-6 contribute to CASS, its underlying molecular mechanisms remain unknown (8,9). Our present study provides a novel mechanistic insight into the role of tumor-derived VEGF in the development of CASS.…”

Section: Discussionmentioning

confidence: 81%

Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome

Xue

Religa

Cao

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

107

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The underlying mechanism by which anti-VEGF agents prolong cancer patient survival is poorly understood. We show that in a mouse tumor model, VEGF systemically impairs functions of multiple organs including those in the hematopoietic and endocrine systems, leading to early death. Anti-VEGF antibody, bevacizumab, and anti-VEGF receptor 2 (VEGFR-2), but not anti-VEGFR-1, reversed VEGF-induced cancer-associated systemic syndrome (CASS) and prevented death in tumor-bearing mice. Surprisingly, VEGFR2 blockage improved survival by rescuing mice from CASS without significantly compromising tumor growth, suggesting that “off-tumor” VEGF targets are more sensitive than the tumor vasculature to anti-VEGF drugs. Similarly, VEGF-induced CASS occurred in a spontaneous breast cancer mouse model overexpressing neu . Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs.

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“…Grotzinger et al 11 proposed that this is the active form of the IL-6R complex. juvenile idiopathic arthritis, 26 systemic lupus erythematosus, 27 Crohn disease, 28 inflammatory bowel disease, 29 cardiovascular disease, 30 sepsis, 31 fever, 32 cachexia, 21 insulin resistance, 22 osteoporosis, 33 and, most notably in the current review, many types of cancer (Table 3 and Table 4). IL-6 also is observed at higher levels in the elderly, and it is believed that IL-6 contributes to some of the changes associated with advanced age, such as decreased lean body mass, low-grade anemia, lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer disease.…”

Section: Biologic Activities Of Il-6mentioning

confidence: 86%

“…Human diseases that involve prolonged inflammation frequently exhibit cachexia and loss of muscle mass, and IL-6 appears to be the mediator of these processes as well. 21 IL-6 may mediate loss of adipose tissue in part by enhancing endogenous corticosteroid secretion. It is noteworthy that high circulating levels of IL-6 also have been linked to insulin resistance, high body mass index, and obesity.…”

Section: Biologic Activities Of Il-6mentioning

confidence: 99%

Interleukin‐6 and its receptor in cancer

Hong

Angelo

Kurzrock

2007

Cancer

336

127

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Interleukin-6 (IL-6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL-6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL-6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL-6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL-6 are observed in almost every type of tumor studied and predict a poor outcome.

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Impact of TNF-α and IL-6 Levels on Development of Cachexia in Newly Diagnosed NSCLC Patients

Cited by 65 publications

References 28 publications

Coexpression of IL-6 and TNF-α: prognostic significance on breast cancer outcome

Coexpression of IL-6 and TNF-α: prognostic significance on breast cancer outcome

Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome

Interleukin‐6 and its receptor in cancer

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