Heat Shock Protein 70 Serum Levels Differ Significantly in Patients with Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

Gehrmann, Mathias; Cervello, Melchiorre; Montalto, Giuseppe; Cappello, Francesco; Gulino, Alessandro; Knape, Clemens; Specht, Hanno M.; Multhoff, Gabriele

doi:10.3389/fimmu.2014.00307

Cited by 70 publications

(62 citation statements)

References 23 publications

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“…Importantly, Multhoff and colleagues have demonstrated that serum Hsp70 levels in patients with liver cancer are significantly higher than those that are measured in a control group of individuals without liver disease, and (importantly) are also higher than individuals with chronic hepatitis (95). The same study showed that serum Hsp70 levels in a subgroup of patients with liver cirrhosis who subsequently developed liver cancer were higher than those in individuals with liver cirrhosis alone (95).…”

Section: Extracellular Cell Stress Proteins In Cancermentioning

confidence: 99%

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Extracellular cell stress (heat shock) proteins—immune responses and disease: an overview

Pockley

Henderson

2017

Phil. Trans. R. Soc. B

118

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Contribution to a theme issue 'Heat shock proteins in health and disease: integrating knowledge to better understand the role of heat shock proteins as therapeutic targets and disease modulators' Keywords:Heat shock (stress) proteins, extracellular, immunity Author for correspondence:A. Graham Pockley, PhD e-mail: graham.pockley@ntu.ac.ukHeat shock proteins in health and disease: integrating knowledge to better understand the role of heat shock proteins as therapeutic targets and disease modulators 2 | P a g e Abstract Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory "danger signals" for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells.The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals / non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining / regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins therefore form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease.Heat shock proteins in health and disease: integrating knowledge to better understand the role of heat shock proteins as therapeutic targets and disease modulators 3 | P a g e 1. Background 'Chance favours the prepared mind ' -Louis Pasteur (1822 -1895 The presence of additional new 'puffs' in the polytene chromosomes of cultured Drosophila larva which were induced following their incubation at an inadvertently high temperature and observed by Ferruccio Ritossa (25 th February 1936 -9 th January 2014) in the early 1960s was unexpected and puzzling. He realised the potential importance of this first evidence that stress can influence gene transcription and induce the synthesis of new proteins, yet found it surprisingly difficult to publish this discovery. It was eventually published in Experientia (1, 2).Ritossa's findings were extended and expanded upon during the next decade and by the mid-to-late 1960s it was clear that exposure of cells containing polytene chromosomes to a variety of environmental stressors resulted in the transcription of novel genes and, presumably, in the synthesi...

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Section: Extracellular Cell Stress Proteins In Cancermentioning

confidence: 99%

“…A subgroup of patients with cirrhosis who subsequently developed liver cancer (95) Heat shock proteins in health and disease: integrating knowledge to better understand the role of heat shock proteins as therapeutic targets and disease modulators 18 | P a g e …”

Section: )mentioning

confidence: 99%

Extracellular cell stress (heat shock) proteins—immune responses and disease: an overview

Pockley

Henderson

2017

Phil. Trans. R. Soc. B

118

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“…Cancer cells can actively (exosomal) and/or passively (by dying tumour cells) release HSP70 into the extracellular space (Vega et al 2008;Gehrmann et al 2014). Also in animal model studies a correlation between serum Hsp70 levels and tumor volume has been indicated (Bayer et al 2014).…”

Section: Al 2010)mentioning

confidence: 99%

Elevated Serum Levels of Heat Shock Protein 70 Are Associated with Breast Cancer

Günaldı

Afşar

Okuturlar

et al. 2015

Tohoku J. Exp. Med.

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Breast cancer (BC) is the most frequent cause of cancer death in women throughout the world. Thus, it is necessary to establish sensitive screening, diagnosis and treatment methods for BC. Heat shock protein 70 (HSP70) is an important cellular stress response protein that protects cells from apoptosis. Recent studies have shown that serum HSP70 levels may provide clinically important information in various types of cancer. HSP70 is also overexpressed in BC, which is known to be associated with cancer progression, apoptosis and cell proliferation. However, the serum level of HSP70 and its diagnostic and prognostic potential in BC have not been investigated yet. The aim of this study was to determine the usefulness of serum HSP70 level as a diagnostic test and its predictive value in patients with BC. This prospective study consisted of 45 female patients diagnosed with BC and 16 healthy women who were matched for age and body mass index (BMI). Enzyme-linked immunosorbent assay (ELISA) technique was used to measure the serum level of HSP70. The serum level of HSP70 was significantly higher in patients with BC than in the healthy control group (5.98 ± 2.05 vs. 1.49 ± 0.47 ng/ml, p = 0.001). HSP70 level > 2.41 ng/ml was the best cutoff value to predict BC (97.78% sensitivity and 93.75% specificity). This study shows that HSP70 can be used as an adjunct to other diagnostic tests for BC and may be helpful for identifying patients at increased risk of BC.

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“…ELISA was performed to detect levels of SH2B1 in the pre-diagnostic serum in patients with GC and in matched controls (14,15). Serum SH2B1 levels were measured using an SH2B1 (human) ELISA kit (cat.…”

Section: Sh2b1-expressing Plasmids/empty Vectors and Transfectionmentioning

confidence: 99%

Circulating SH2B1 is associated with an increased risk of gastric cancer

Lundbäck

Zhao

et al. 2018

Oncol Lett

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Abstract. Gastric cancer (GC) is one of the most common types of cancer in humans and the second leading cause of cancer-associated mortality worldwide. Identifying novel risk factors will facilitate the development of therapeutic strategies to prevent and treat GC. Increased expression of the Src homology 2 B adaptor protein 1 (SH2B1) may stimulate the malignant progression of lung cancer, esophageal cancer and neuroblastoma. However, its function in GC has not yet been investigated. To identify whether increased serum SH2B1 is a risk factor for GC, the present study performed a nested case-control study of patients within the Chinese cohort study. Levels of serum SH2B1 were measured in 563 patients diagnosed with GC during the follow-up period and in 1,126 matched healthy controls. The results demonstrated that high levels of serum SH2B1 were associated with an increased GC risk (odds ratio, 3.23; 95% confidence interval, 2.45-5.65). When analyses were stratified further by sex, age and smoking, an association between increased levels of SH2B1 and GC was identified in males but not in females. Furthermore, the association between SH2B1 levels and GC was more evident in younger than in older participants, and statistically significant in current smokers but not in nonsmokers. These results were not altered following the exclusion of outliers. Furthermore, it was demonstrated that overexpression of SH2B1 contributes to the malignant transformation of normal gastric epithelial cells. Thus, the present study demonstrated that elevated serum SH2B1 levels may increase the risk of GC.

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Heat Shock Protein 70 Serum Levels Differ Significantly in Patients with Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

Cited by 70 publications

References 23 publications

Extracellular cell stress (heat shock) proteins—immune responses and disease: an overview

Extracellular cell stress (heat shock) proteins—immune responses and disease: an overview

Elevated Serum Levels of Heat Shock Protein 70 Are Associated with Breast Cancer

Circulating SH2B1 is associated with an increased risk of gastric cancer

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