Circulating heat shock protein 27 (HSPB1) levels in prediction of pre-eclampsia: A pilot study.

OBJECTIVE: To determine whether circulating heat shock proteins HSP27/HSPB1 and HSP90α/HSPC1 may be useful for early prediction of the occurrence of pre-eclampsia in asymptomatic women. METHODS: We have measured by ELISA the levels of HSPB1, HSPC1, and placental protein 13 (PP13) in serum samples from 44 women in the first trimester (10-12 weeks) and second trimester (17-20 weeks) of pregnancy. Western blot and immunohistochemistry for HSPB1 and HSPC1 were performed. RESULTS: HSPB1 serum levels were higher in women with pre-eclampsia than in normotensive pregnant women at the first and second trimester (P = 0.003), whereas PP13 levels decreased in women with pre-eclampsia only in the first trimester of gestation (P = 0.021). We also observed higher HSPB1 levels in patients with early-onset pre-eclampsia in the first and second trimester (P = 0.014). CONCLUSION: This pilot study points out that circulating HSPB1 levels in first and second trimester might be useful for predicting the occurrence of pre-eclampsia in asymptomatic women. Further validation studies are needed to finally establish this protein as a candidate predictive biomarker of pre-eclampsia.

PROGRESS STUDY: Progression of chronic kidney disease in children and heat shock proteins.

Various molecular and cellular processes are involved in renal fibrosis, such as oxidative stress, inflammation, endothelial cell injury, and apoptosis. Heat shock proteins (HSPs) are implicated in the progression of chronic kidney disease (CKD). Our aim was to evaluate changes in urine and serum HSP levels over time and their relationships with the clinical parameters of CKD in children. In total, 117 children with CKD and 56 healthy children were examined. The CKD group was followed up prospectively for 24 months. Serum and urine HSP27, HSP40, HSP47, HSP60, HSP70, HSP72, and HSP90 levels and serum anti-HSP60 and anti-HSP70 levels were measured by ELISA at baseline, 12 months, and 24 months. The urine levels of all HSPs and the serum levels of HSP40, HSP47, HSP60, HSP70, anti-HSP60, and anti-HSP70 were higher at baseline in the CKD group than in the control group. Over the months, serum HSP47 and HSP60 levels steadily decreased, whereas HSP90 and anti-HSP60 levels steadily increased. Urine HSP levels were elevated in children with CKD; however, with the exception of HSP90, they decreased over time. In conclusion, our study demonstrates that CKD progression is a complicated process that involves HSPs, but they do not predict CKD progression. The protective role of HSPs against CKD may weaken over time, and HSP90 may have a detrimental effect on the disease course.

Heat shock protein 27 (HSP27) in patients with ovarian cancer.

OBJECTIVES: Ovarian cancer remains a very common cause of death among women worldwide. The cause is to be found in too late of a diagnostic process and therapeutic difficulties The presence of heat shock proteins in the serum of ovarian cancer patients is still a new area of study. It is necessary to continue studies on the possibilities for using these markers to predict a patient's response to a specific therapy and to monitor treatment progress. MATERIAL AND METHODS: The study included 52 women with ovarian cancer, hospitalised at the Department of Obstetrics, Gynaecology and Oncological Gynaecology, Medical University of Silesia. The control group consisted of 25 healthy women. The levels of HSP27 in the studied sera were determined by an immunoenzymatic method (ELISA). RESULTS: The mean concentration of HSP27 in the group of patients with ovarian cancer was significantly higher than in the control group of healthy women. We have shown that mean HSP27 levels in ovarian cancer patients increase with tumour progression and further depend on the clinical stage of the disease (FIGO). Positivity values analysis revealed in all clinical stages of ovarian cancer, excluding stage 1, it was significantly higher than in the control group, and at the 4th stage, it is significantly higher than at the 1st, 2nd, and 3rd stages. However, both for the untreated patients and those patients after chemotherapy, the mean HSP27 levels were significantly higher than in the control group. CONCLUSIONS: Our studies indicate a significant contribution of HSP27 to the pathogenesis of ovarian cancer. It seems that serum HSP27 can be a marker for this cancer's development, and a marker for the clinical stage.

Heat Shock Protein 27 Is an Emerging Predictor of Contrast-Induced Acute Kidney Injury on Patients Subjected to Percutaneous Coronary Interventions.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication associated with considerable morbidity and mortality. Heat-shock protein 27 (HSP27) plays a role in the defense of the kidney tissue against various forms of cellular stress, including hypoxia and oxydative stress, both features associated with CI-AKI. The aim of our study was to evaluate a potential predictive value of HSP27 for CI-AKI in patients subjected to percutaneous coronary interventions (PCI). Included were 343 selected patients subjected to PCI. Exclusion criteria were conditions that potentially might influence HSP27 levels. HSP27 serum levels were evaluated prior to PCI, together with serum creatinine, the concentration of which was also evaluated twice at 48 and 72 h post PCI. CI-AKI was diagnosed in 9.3% of patients. Patients in whom CI-AKI was diagnosed were older (p < 0.001), were more often females (p = 0.021), had higher prevalence of diabetes (p = 0.011), hypotension during PCI (p < 0.001), albuminuria (p = 0.004) as well as multivessel disease (p = 0.002), received higher contrast volume (p = 0.006), more often received contrast volume (CV) above the maximum allowed contrast dose (MACD) (p < 0.001), and had lower HSP27 level (p < 0.001). On multivariate analysis, CV > MACD (OR 1.23, p = 0.001), number of diseased vessels (OR 1.27, p = 0.006), and HSP27 (OR 0.81, p = 0.001) remained independent predictors of CI-AKI. Low concentration of HSP27 is an emerging, strong and independent predictor of CI-AKI in patients subjected to PCI.

Effects of high-intensity interval exercise under hyperoxia on HSP27 and oxidative stress responses.

Hypoxia in working muscles during exercise may be associated with increased oxidative stress. Inhalation of hyperoxic gas diminishes the hypoxia within working muscles during exercise. Exposure to hyperoxia increases the expression of the antioxidant HSP27. We investigated the effects of acute high-intensity interval exercise (HIE) under hyperoxia on HSP27 levels and oxidative stress responses. Eight male subjects participated in two experiments: 1) normoxic HIE (NHIE) and 2) hyperoxic (60 % oxygen) HIE (HHIE). HIE consisted of four 30-s all-out cycling bouts with 4-min rest between bouts. Levels of serum oxidative stress markers (d-ROMs and LPO), HSP27, BAP, IL-6, and TNF-α significantly increased after both trials. The HIE-induced changes in d-ROMs, LPO, and HSP27 levels were significantly lower in the HHIE trial than in the NHIE trial. These findings suggest that inhaling hyperoxic gas during exercise might diminish oxidative stress induced by all-out HIE.

Role of Heat Shock Protein 27 in Modulating Atherosclerotic Inflammation.

Atherosclerosis is the primary cause of heart attacks, and while efforts to prevent its development or progression have historically focused largely on reducing cholesterol levels, there is now important proof-of-principle data that supports the role that inflammation plays in atherogenesis. Heat shock protein 27 (HSP27) is a novel biomarker of atherosclerosis that is also atheroprotective. Through a series of murine and in vitro experiments, an iterative narrative is emerging that demonstrates how HSP27 can act as an extracellular mediator that reduces plaque inflammation-either directly via transcriptional pathways, or indirectly via important effects on macrophage biology. While there is much more to learn about the biology of HSP27, we now review the strong foundation of knowledge that highlights the potential anti-inflammatory role of HSP27 as a novel therapeutic for not only atherosclerosis but potentially other inflammatory disorders.

Soluble heat-shock protein 27 in blood serum is a non-invasive prognostic biomarker for ovarian cancer.

OBJECTIVES: Ovarian cancer (OC) is the leading cause of death in gynecological oncology, primarily caused by limited prognostic and therapeutic options. The heat shock protein 27 (HSP27) is recognized as a prominent factor in OC, playing a pivotal role in cancer progression machinery such as treatment resistance. Thus, HSP27 may represent an appropriate biomarker for OC diagnosis, prognosis, and therapy response. MATERIALS & METHODS: Extracellular HSP27 levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples of OC patients (n = 242) and compared to a non-malignant control group without any history of cancer (n = 200). Correlations between serum levels of HSP27 and clinical pathological parameters were analyzed by bivariate analysis. Survival analyses were carried out by Kaplan-Meier test. RESULTS: This study demonstrated that protein levels of HSP27 are comparable in the blood serum of healthy women and OC patients. However, HSP27 levels are significantly correlated with the volume of ascites, residual tumor mass, and age at first diagnosis in OC patients. Notably, elevated levels of HSP27 demonstrate significantly higher overall survival. CONCLUSION: Taken together, our findings demonstrate that high levels of circulating HSP27 in serum are associated with improved overall survival of OC patients. Even though functionality of secreted HSP27 is still unclear, serum levels of HSP27 represent a putative non-invasive prognostic biomarker candidate for OC progression.

The release of phosphorylated-HSP27 from activated platelets of obstructive sleep apnea syndrome (OSAS) patients.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a well known risk of arterial thrombosis that results in cardiovascular morbidity. It has been reported that platelet aggregability is enhanced in patients with OSAS. In the present study, we investigated whether phosphorylated-HSP27 is released from the activated platelets of OSAS patients. METHODS: Patients diagnosed with OSAS (n = 21) were recruited, and platelet-rich plasma (PRP) was stimulated by ADP, ristosetin, collagen, and thrombin receptor-activating peptide. Platelet aggregation was measured using an aggregometer with a laser-scattering system. The levels of protein phosphorylation and the released levels of phosphorylated-HSP27 were determined by Western blot analysis and an ELISA, respectively. RESULTS: The phosphorylation of HSP27 in the platelets was induced by the stimulators. The released levels of phosphorylated-HSP27 was correlated with the levels of phosphorylated-HSP27 stimulated by ADP or collagen. The levels of ADP-induced phosphorylated-HSP27 were correlated with those of both phosphorylated-protein kinase B (Akt) and phosphorylatd-p38 mitogen-activated protein kinase; however, the levels of phosphorylated-HSP27 stimulated by collagen were correlated with phosphorylated-Akt levels only. The ED50 value of ADP on the platelet aggregation in OSAS (1.067 ± 0.128 µM) was lower than that in healthy subjects (1.778 ± 0.122 µM) and was inversely correlated with both the value of minimum SpO2 and the released level of phosphorylated-HSP27 stimulated by ADP. CONCLUSION: The results strongly suggest that phosphorylated-HSP27 is released from the activated platelets of OSAS patients.

Systemic release of heat-shock protein 27 and 70 following severe trauma.

Trauma represents a major cause of morbidity and mortality worldwide. The endogenous inflammatory response to trauma remains not fully elucidated. Pro-inflammation in the early phase is followed by immunosuppression leading to infections, multi-organ failure and mortality. Heat-shock proteins (HSPs) act as intracellular chaperons but exert also extracellular functions. However, their role in acute trauma remains unknown. The aim of this study was to evaluate serum concentrations of HSP 27 and HSP 70 in severely injured patients. We included severely injured patients with an injury severity score of at least 16 and measured serum concentration of both markers at admission and on day two. We found significantly increased serum concentrations of both HSP 27 and HSP 70 in severely injured patients. Concomitant thoracic trauma lead to a further increase of both HSPs. Also, elevated concentrations of HSP 27 and HSP 70 were associated with poor outcome in these patients. Standard laboratory parameters did not correlate with neither HSP 27, nor with HSP 70. Our findings demonstrate involvement of systemic release of HSP 27 and HSP 70 after severe trauma and their potential as biomarker in polytraumatized patients.

Protective effect of HSP27 in atherosclerosis and coronary heart disease by inhibiting reactive oxygen species.

OBJECTIVE: To clarify the mechanism of heat shock protein 27 (HSP27) as a diagnostic biomarker in coronary heart disease (CHD) and atherosclerosis (AS). METHOD: Expressions of HSP27 in patients with CHD and healthy controls were determined by enzyme-linked immunosorbent assay and the expressions of HSP27 in aortas of patients with CHD and healthy controls were measured by immunohistochemistry. Receiver operating characteristic curve was applied to assess the diagnostic performance of HSP27 in CHD. ApoE-/- mice were included and accordingly grouped. The expressions of HSP27 in AS plaque were measured by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. AS plaque was observed using hematoxylin and eosin staining. DHE was used to detect reactive oxygen species (ROS) levels in aortas. The expressions of mitochondrial apoptosis-related proteins were measured by Western blot analysis. Cell apoptosis was determined by TUNEL staining. RESULTS: HSP27 was highly expressed in patients with CHD than in healthy controls ( P < 0.01). In comparison to the normal group, the model group had increased the relative positive area of HSP27 and higher expressions of HSP27, Bax, caspase-3, and apoptosis index (AI) but decreased Bcl-2 expression in AS plaque, as well as larger plaque areas and elevated ROS levels in the aorta (all P < 0.05). The HSP27-small interfering RNA group had increased expressions of Bax, caspase-3, and AI but decreased Bcl-2 and HSP27 expressions in AS plaque, as well as larger plaque areas, the relative positive area of HSP27 and higher ROS levels in aorta when compared with those in the model group (all P < 0.05). CONCLUSION: HSP27 exerts its protective role by suppressing ROS and AS progression by inhibiting mitochondria apoptosis pathway in CHD.

Quantitative assessment of serum heat shock protein 27 for the diagnosis of epithelial ovarian cancer using targeted proteomics coupled with immunoaffinity enrichment.

BACKGROUND: Heat shock protein 27 (HSP27) may take part in the epithelial ovarian cancer (EOC) malignant process because it is elevated in the serum of EOC patients, suggesting that HSP27 may serve as an EOC biomarker to complement the standard serum carbohydrate antigen 125 (CA125) test. Thus, accurate quantification of serum HSP27 would assist the diagnosis of EOC. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics coupled with an immunoaffinity enrichment assay was developed and validated to monitor HSP27 concentrations in serum. RESULTS: Tryptic peptide 80QLSSGVSEIR89 was selected as a surrogate analyte for quantification, and an immuno-depleted serum extract was used as a surrogate matrix. Immunoaffinity enrichment was effective for protein enrichment and sensitivity enhancement, and the resulting LOQ was 500 pg/ml (>10-fold increase). Then, serum HSP27 concentrations in EOC patients, benign ovarian tumors patients and healthy volunteers were accurately determined to be 4.95 ±â€¯0.37 ng/ml, 2.98 ±â€¯0.16 ng/ml and 2.82 ±â€¯0.15 ng/ml, respectively, suggesting that the EOC samples had significantly higher concentrations of HSP27 than a sample from benign ovarian tumor patients. The experimental values for the samples were compared with those obtained from enzyme-linked immune sorbent assays (ELISAs). The ROC curve analysis showed that the combined area under the curve (AUC) for CA125 and HSP27 was 0.88, which is significantly superior to that of CA125 alone. CONCLUSIONS: Targeted proteomics coupled with immunoaffinity enrichment may provide more accurate quantification of low-abundant proteins.

Serum heat shock protein 27 levels predict cardiac mortality in hemodialysis patients.

BACKGROUND: Decreased heat shock protein 27 (HSP27) participates in many processes that are involved in cardiovascular (CV) disease. The objective of the study was to evaluate if HSP27 level was predictive of mortality as well as to evaluate factors associated with HSP27 level in a group of patients treated with HD. METHODS: Enrolled to the study were 202 HD patients. Clinical data, biochemical, echocardiographic, and carotid atherosclerosis parameters were evaluated. Patients were splited into groups on the basis of the cut-off lower and higher 50th percentile of serum HSP27 levels, and were followed-up for 28.68 ± 6.12 months. RESULTS: No significant difference was observed between serum HSP27 levels in patients and controls. Low HSP27 patients were older, had higher left ventricular mass index, lower ejection fraction, higher prevalence of diabetes, myocardial infarction and carotid atherosclerosis, higher C-reactive protein level, and worse oxidant/antioxidant status. The multiple regression analysis identified that HSP27 levels were independently, negatively associated with serum oxidized LDL and the number of carotid plaques. Using the Kaplan-Meier analysis it was shown that the cumulative incidences of both CV and sudden cardiac death (SCD) mortality were higher in low HSP27 group in comparison with high serum HSP27 group. A multivariate Cox analysis showed that HSP27 level is an independent and strong predictor of CV as well as SCD mortality. CONCLUSIONS: Low serum HSP27 level is independently associated with both CV and SCD mortality but not with all-cause mortality. Low serum HSP27 level is associated with carotid atherosclerosis and oxidative stress.

Plasma Paraoxonase, Sphingosine-1-phosphate, Total Sialic Acid, and Heat Shock Protein-27 in the Liver of the Sheep Naturally Infected with Cysticercus Tenuicollis: Evidence on Pathological Changes.

The present study aimed to investigate whether sphingosine 1 phosphate (S1P), paraoxonase (PON), total sialic acid (TSA), and heat shock protein-27 (HSP27) are altered in the sheep during infection of the liver with Cysticercus tenuicollis. This study was conducted on40 healthy sheep and40 sheep with Cysticercus tenuicollis infection. The infected and non-infected animals were selected based on the observation of severe Cysticercus tenuicollis infection in the liver and absence of any hepatic cysts, respectively. All parameters were measured in serum and plasma. The results revealed a significant decrease (P&lt;0.01) in PON, TSA, and albumin (Alb) in the infected group, compared with those in the healthy one. Furthermore, the infected sheep had a significant increase (P&lt;0.01) in S1P, HSP-27, malondialdehyde (MDA), total bilirubin, and unconjugated bilirubin as compared with those in their non-infected counterparts. Moreover, no significant change was observed in total plasma protein level in the infected animals in comparison to that in the healthy ones. The low levels of TSA and Alb revealed liver damage in the infected sheep. Moreover, the PON reduction might have resulted from hepatic steatosis and MDA enhancement. Meanwhile, S1P elevation could be attributed to the activation of platelets. In addition, HSP-27 increase was ascribed to the disease-induced stress conditions.

Association between circulating levels of heat-shock protein 27 and aggressive periodontitis.

Heat-shock protein (Hsp) 27 is a major intracellular molecular chaperone and controller of intracellular responses to inflammatory signals. In the extracellular space, recombinant Hsp27 has been described to exert anti-inflammatory activities. The aim of this study was to assess the association between circulating levels of Hsp27 and different types of periodontitis. Pro- and anti-inflammatory cytokines and the stress proteins Hsp27 and Hsp60 with proposed anti- and pro-inflammatory properties, respectively, were measured by two-site ELISA in the serum of patients with aggressive periodontitis (AgP, n = 30), chronic periodontitis (CP, n = 29) and periodontally healthy controls (H, n = 28). Furthermore, Hsp27 and Hsp60 levels were also measured longitudinally in 12 AgP patients at 6 time points up to 3 months after treatment. AgP patients had lower levels of Hsp27 compared to CP patients and healthy subjects (adjusted one-way ANOVA, p < 0.001, followed by post hoc Tukey HSD comparisons), while no differences in levels of Hsp60 or cytokines between the three groups were detected. In CP patients and H subjects, the systemic Hsp27 levels correlated with Hsp60 (r = 0.43, p < 0.001; r = 0.59, p < 0.001, respectively) and with pro-inflammatory cytokines TNF-α (r = 0.48, p < 0.001; r = 0.55, p < 0.001, respectively) and IL-6 (r = 0.44, p < 0.01). However, no such correlations were detected in AgP cases. No consistent temporal patterns of changes of Hsp27 concentration were detected across AgP patients following periodontal treatment. This study provides the first evidence that Hsp27 may be differentially expressed and regulated in AgP patients as compared with CP patients and healthy individuals.

Effects of aquatic and land-based exercises on amyloid beta, heat shock protein 27, and pulse wave velocity in elderly women.

BACKGROUND: Alzheimer's disease is a neurodegenerative brain disease resulting from the deterioration of neuronal cells and vascular dementia, the latter of which results from cerebrovascular disorders. Exercise is effective in preventing and treating degenerative brain diseases as it activates blood flow to the brain, increases nerve production in the hippocampus, and promotes the expression of synaptic plasticity-related proteins. Therefore, this study investigated the effects of 16-week aquatic and land-based exercise programs on amyloid beta (Aß), heat shock protein (HSP) 27 levels, and pulse wave velocity (PWV). MATERIALS AND METHODS: Forty elderly women, aged 60-70 years, voluntarily participated in the study. They were divided into control (n = 12), aquatic exercise (n = 14), and land-based exercise groups (n = 14). The variables of amyloid beta, heat shock protein 27, and pulse wave velocity were measured in all the participants before and after the 16-week study. RESULTS: Significantly higher levels of serum HSP27 (p < 0.05) and significantly lower levels of vascular elasticity (p < 0.05) were found in the aquatic exercise group after 16 weeks of exercise compared with the control group. Aß did not significantly differ between groups. Thirty minutes after the first exercise, Aß in the aquatic exercise group (p < 0.01) and HSP27 in the land-based exercise group (p < 0.05) were significantly higher than the corresponding levels in the resting condition before exercise. 30 min after the last exercise, Aß (p < 0.01) and HSP27 (p < 0.05) were significantly higher. CONCLUSIONS: Aquatic and land-based exercises increased serum Aß and HSP27 and decreased pulse wave velocity. Thus, they may play a positive role in the prevention of degenerative brain diseases and improvement of brain function in elderly people.

Proteomic effects of wet cupping (Al-hijamah).

Wet cupping (Al-hijamah) is a therapeutic technique practiced worldwide as a part of the Unani system of medicine. It involves bloodletting from acupoints on a patient's skin to produce a therapeutic outcome. A thorough review of research articles on wet cupping with relevance to proteomics field that are indexed by Google Scholar, PubMed, and/or Science Direct databases was performed. Eight original research articles were summarized in this paper. Overall, wet cupping did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid exchanges, and cell replication index. In contrast, wet cupping was found to produce higher oxygen saturation, eliminate lactate from subcutaneous tissues, remove blood containing higher levels of malondialdehyde and nitric oxide, and produce higher activity of myeloperoxidase. The proteomic effects of wet cupping therapy have not been adequately investigated. Thus, future studies on wet cupping that use systemic and sound protocols to avoid bias should be conducted.

Circulating levels of Hsp27 in microvascular complications of diabetes: Prospects as a biomarker of diabetic nephropathy.

AIM: Heat shock protein 27 (Hsp27) is a small heat shock protein known to protect the cells from apoptosis under stress. In the present study, we determined the plasma Hsp27 levels in type 2 diabetes subjects without and with microvascular complications- diabetic retinopathy (DRe), diabetic nephropathy (DNe), and diabetic neuropathy (DNu) to understand if it could serve as a marker for these complications. METHODS: This is a hospital-based case-control study with 754 subjects including 247 controls, 195 subjects with diabetes, 123 with DRe, 80 with DNe and 109 with DNu. Plasma Hsp27 levels were measured by ELISA. RESULTS: The mean plasma Hsp27 was higher in the DNe group (631.5±355.2) compared to the control (496.55±308.54), diabetes (523.41±371.01), DRe (494.60±391.48) and DNu (455.21±319.74) groups with a p-value of 0.018. Receiver operating characteristic (ROC) curve analysis of Hsp27 in DNe group showed an area under the curve (AUC) of 0.617. Spearman correlation analysis shows a positive correlation of plasma Hsp27 with serum creatinine (p=0.053, r-value 0.083). Gender, age and BMI did not affect the plasma Hsp27 levels. CONCLUSION: The plasma Hsp27 levels in the DNe group are higher compared to the control and other complications, thereby it could be explored to be used as a potential biomarker of DNe.

A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial.

LESSONS LEARNED: The addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation. BACKGROUND: This randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer. METHODS: Patients were randomized 1:1 to Arm A (gemcitabine/nab-paclitaxel plus apatorsen) or Arm B (gemcitabine/nab-paclitaxel plus placebo). Treatment was administered in 28-day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS). RESULTS: One hundred thirty-two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment-related adverse events for both arms. Median progression-free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor-prognosis subgroup who may have derived modest benefit from addition of apatorsen. CONCLUSION: Addition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first-line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup.

Heat shock protein 27 acts as a predictor of prognosis in chronic heart failure patients.

BACKGROUND: Heat shock proteins (HSPs) represent intracellular mechanisms of stress response. Clinical implications of their (systemic) expression in patients with chronic heart failure (HF) remain inconclusive. METHODS: In outpatients with chronic stable HF plasma HSP27 levels were measured using ELISA. Patients were followed for a minimum of one year, and a multivariate Cox proportional hazard model was built for cardiovascular death or HF-associated hospitalisations. RESULTS: A total of 134 patients with chronic HF (mean age 71±10years, 34% female, mean LVEF 36±12%) were included. During a mean follow-up of 527±260days, 44 patients (33%) experienced an event. Mean time to event was 350±236days. In a Kaplan-Meier survival analysis HSP27 levels above the median (3820pg/ml) indicate a higher risk for an event (p=0.03). Increased HSP27 levels remained an independent predictor of events (HR, 2.33 CI 95% 1.12-4.87, p=0.024) even after adjustment for age, gender, NT-proBNP, LVEF, aetiology, smoking status, kidney function and NYHA class. CONCLUSIONS: HSP27 is an independent predictor of prognosis in chronic HF. Our findings suggest that HSP27 may improve risk-stratification in chronic HF beyond known prognostic predictors.