Characterization of Patients With Advanced Pancreatic Cancer and High Serum Interleukin-6 Levels

Miura, Tomofumi; Mitsunaga, Shuichi; Ikeda, Masafumi; Shimizu, Satoshi; Ohno, Izumi; Takahashi, Hideaki; Furuse, Junji; Inagaki, Masumi; Higashi, Sayumi; Kato, Hiroyuki; Terao, Keiji; Ochiai, Atsushi

doi:10.1097/mpa.0000000000000335

Cited by 74 publications

(64 citation statements)

References 35 publications

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“…IL-6 is linked to both pancreatic cancer 18-20 and to fatigue and depression 16,19,21 . Elevated levels of IL-6 have been found to be associated with clinical depression in patients with other cancers 15,22,23,24 . It seems possible that depression and fatigue could represent part of a paraneoplastic syndrome associated with this disease, with cytokines released by an undiagnosed tumor leading to fatigue and depression before diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Weight Loss, Diabetes, Fatigue, and Depression Preceding Pancreatic Cancer

Olson

Herzog

et al. 2016

Pancreas

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Objectives We aimed to determine the severity and co-occurrence of established and potential paraneoplastic conditions in pancreatic cancer (weight loss, new onset diabetes, fatigue, and depression) and their relation to patient characteristics. Methods Using information from personal interviews with 510 cases and 463 controls, we obtained adjusted odds ratios for weight loss, long-term and new-onset diabetes, fatigue and depression before diagnosis. Among cases, we investigated the extent to which these factors occurred together and the characteristics of those reporting them. Results The adjusted odds ratio (OR) for weight loss (>3% of usual weight) was 27.0 (95% confidence interval (CI) 17.1-42.6). Severe weight loss was common (21% of cases lost >15%), and was more common in those previously obese. Diabetes was more common in cases and was strongly associated with weight loss (P<0.0001). Diabetes in cases more often led to prescription of insulin, compared to controls. Fatigue and depression were significantly more common in cases than controls but not related to weight loss or diabetes. These conditions were not related to stage at diagnosis. Conclusions Weight loss, often severe, and new onset diabetes frequently occur together before diagnosis of pancreatic cancer. Fatigue and depression are also potential precursors of diagnosis.

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Section: Discussionmentioning

confidence: 99%

Weight Loss, Diabetes, Fatigue, and Depression Preceding Pancreatic Cancer

Olson

Herzog

et al. 2016

Pancreas

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“…Amongst these, IL-6 is important in the development of human cancer and activates oncogenic pathways, and it is known to be deregulated in cancer [77]. Overexpression of IL-6 in many types of tumours, such as colorectal cancer [3], prostate cancer [5], breast cancer [4], ovarian carcinoma [6], pancreatic cancer [7], lung cancer [8], renal cell carcinoma [9], cervical cancer [10], multiple myeloma [11] and lymphomas [78], suggests a strong link between this cytokine and cancer. The high susceptibility and incidence of liver cancer in males is also found to be associated with high levels of IL-6 [79].…”

Section: Role Of Il-6 and Associated Signalling In Cancermentioning

confidence: 99%

“…It is involved in the proliferation and differentiation of malignant cells and found to be high in serum and tumour tissues of a majority of cancers, viz. colorectal cancer [3], breast cancer [4], prostate cancer [5], ovarian carcinoma [6], pancreatic cancer [7], lung cancer [8], renal cell carcinoma [9], cervical cancer [10] and multiple myeloma [11]. Elevated levels of IL-6 are associated with aggressive tumour growth and response to therapies in many types of cancer [12,13].…”

Section: Introductionmentioning

confidence: 99%

Role of interleukin-6 in cancer progression and therapeutic resistance

et al. 2016

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In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities. The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease. Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth. Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer. Its overexpression has been reported in almost all types of tumours. The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism. Moreover, IL-6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways. Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling.

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“…Circulating levels of IL6 in Apc Min/+ mice were significantly correlated with Apc Min/+ mouse body weight, and with the level of STAT3 phosphorylation in slow oxidative and fast glycolytic skeletal muscles [70]. IL6 plasma levels have also been examined in cancer patients, and they were found to be variably but consistently elevated in cancer patients compared to healthy controls [71,72,73,74]. Moreover, plasma levels of IL6 were significantly correlated to the degree of tumor progression and symptoms of cachexia (loss of lean mass, severe fatigue, and anorexia) in humans.…”

Section: Stat3 Signaling Contributes To Muscle Wasting In Cancer Cmentioning

confidence: 99%

STAT3 in Skeletal Muscle Function and Disorders

Guadagnin

Mázala

Chen

2018

IJMS

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Signal transducer and activator of transcription 3 (STAT3) signaling plays critical roles in regulating skeletal muscle mass, repair, and diseases. In this review, we discuss the upstream activators of STAT3 in skeletal muscles, with a focus on interleukin 6 (IL6) and transforming growth factor beta 1 (TGF-β1). We will also discuss the double-edged effect of STAT3 activation in the muscles, including the role of STAT3 signaling in muscle hypertrophy induced by exercise training or muscle wasting in cachectic diseases and muscular dystrophies. STAT3 is a critical regulator of satellite cell self-renewal after muscle injury. STAT3 knock out affects satellite cell myogenic progression by impairing proliferation and inducing premature differentiation. Recent studies in STAT3 signaling demonstrated its direct role in controlling myogenic capacity of myoblasts and satellite cells, as well as the potential benefit in using STAT3 inhibitors to treat muscle diseases. However, prolonged STAT3 activation in muscles has been shown to be responsible for muscle wasting by activating protein degradation pathways. It is important to balance the extent of STAT3 activation and the duration and location (cell types) of the STAT3 signaling when developing therapeutic interventions. STAT3 signaling in other tissues and organs that can directly or indirectly affects skeletal muscle health are also discussed.

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Characterization of Patients With Advanced Pancreatic Cancer and High Serum Interleukin-6 Levels

Abstract: High serum IL-6 was related to advanced age, the presence of hepatic metastasis, large tumor burden in liver, severe fatigue, high carcinoembryonic antigen, high C-reactive protein, and anemia in patients with treatment-naive advanced PC.

Cited by 74 publications

References 35 publications

Weight Loss, Diabetes, Fatigue, and Depression Preceding Pancreatic Cancer

Weight Loss, Diabetes, Fatigue, and Depression Preceding Pancreatic Cancer

Role of interleukin-6 in cancer progression and therapeutic resistance

STAT3 in Skeletal Muscle Function and Disorders

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