Serum Bcl-2 Research Articles

Statistical Interpretation of CA125 and Bcl-2 in Serum of Patients With Late Stage Ovarian Cancer

The present study was conducted to investigate the sensitivity, specificity, predictive values and accuracy of serum CA125 and Bcl-2 levels and their combination in advanced epithelial ovarian cancer patients. Healthy controls (n = 117) with no gynecologic problems and patients with ovarian carcinoma (n = 117), pathologically verified, consecutively admitted to the Istanbul University, Oncology Institute during a one-year period were investigated. Serum Bcl-2 and CA125 were determined by using enzyme linked immunosorbent assay method. The serum bcl-2 and CA125 levels were significantly higher in patients with ovarian cancer than in the control group (P < 0.001). The diagnostic sensitivity and specificity, predictive values and accuracies were calculated for each marker and their combination. The best result was achieved with the combination of CA125-bcl-2. This combination fulfills the need of diagnosis of ovarian carcinoma for the best sensitivity and specificity.

An Immunohistochemistry Study of Tissue Bcl‐2 Expression and Its Serum Levels in Breast Cancer Patients

Variations in Bcl-2 expression have been reported in malignant tissues with various origins. In the case of breast cancer, the involvement of Bcl-2 overexpression in tumorigenicity and metastatic potential has been stated. However, association of tumor progression and loss of Bcl-2 in tumor cells is also being investigated. Augmentation of plasma levels of Bcl-2 was speculated in patients with metastatic breast cancer. The present study was designed to evaluate Bcl-2 protein expression in breast tumor paraffin-embedded fixed tissue and sought to investigate association with the Bcl-2 protein release in patient serum, as well as its relationship with clinicopathological features. Immunohistochemistry methods were applied to breast tumor sections from 35 surgically removed patient samples and 35 normal or benign tissue samples. The sera taken from both the patient and control groups were tested for soluble Bcl-2 (BMs244/3 Kit) using ELISA technique. Tumor type, grade, and size and patient menopause status and age were considered to analyze the association between these parameters. The analysis shows that 67.6% of the tumor sections were positive for Bcl-2 expression and 32.4% negative. Bcl-2 protein expression was positive in 57.1% of normal/benign section tumors. The Bcl-2 serum levels were 3.6 +/- 1.1 ng/mL in the patient group and 3.23 +/- 0.06 ng/mL in the control group. A weak correlation was found between Bcl-2 serum levels and tissue expression of the molecules (r= 0.382, P= 0.049). A negative association (but not statically significant) was obtained between Bcl-2 and low-grade stages (r=-0.375, P= 0.08). A positive and significant correlation was shown between Bcl-2 and menopause (r= 0.523, P= 0.005) and between age and serum Bcl-2 (r= 0.488, P= 0.011). Although a majority of the breast tumor tissue expresses Bcl-2, the mean Bcl-2 serum levels were not different between patient and control groups. The present data would lead us to use the Bcl-2 expression in tissue at the level of protein expression or would suggest the use of mRNA levels, but the use of serum levels would be very limited for clinical purposes.

Circulating levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 (MMP-3), and BCL-2 in malignant melanoma

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis that stimulates proliferation, migration, and metastasis of melanoma. In literature, all studies concerning influences of matrix metalloproteinases (MMPs) and antiapoptotic proteins on VEGF-induced angiogenesis in melanoma patients have been performed in tissue scale in melanoma. The objective of this study was to determine the value of circulating serum VEGF and its possible mechanisms of angiogenesis by circulating VEGF, MMP-3, and Bcl-2 in patients with melanoma. Fifty-one patients with cutaneous melanoma pathologically verified at different stages, and eighteen healthy controls were investigated. Serum VEGF, MMP-3, and Bcl-2 levels were quantitatively analyzed by ELISA. The serum VEGF (P = 0.034) and Bcl-2 (P = 0.005) levels were significantly higher in patients with melanoma than in the control group. However, there was no significant difference in the serum MMP-3 level between melanoma patients and controls (P = 0.51). The serum levels of VEGF were significantly influenced only by Breslow thickness (P = 0.045) and mitosis (0.039) and were not positively correlated with the stage of the disease. Among serum parameters, a significant relationship was found only between serum levels of VEGF and MMP-3 (r = 0.32, P = 0.023). In conclusion, our study demonstrates increased concentrations of VEGF and Bcl-2, but not MMP-3, in serum of melanoma patients regardless of the stage of the disease. VEGF may be a potential endothelial cell growth and survival factor. The mechanism of VEGF regulation of angiogenesis may be in part due to enhanced proliferation and survival of endothelial cells by differential expression of antiapoptotic genes and in part by activation of MMPs.

Inflammatory and Apoptotic Markers in Ischemic Heart Disease Patients

Inflammatory and Apoptotic Markers in Ischemic Heart Disease PatientsIschemic heart disease is the most frequent cause of cardiovascular morbidity and mortality. It is developed on the basis of atherosclerosis which is today considered a chronic inflammatory disease. It is documented by an increase in inflammatory and immune biomarkers, such as C-reactive protein, fibrinogen, neopterin, leukocytes, lymphocytes and others, that are significantly changed in patients with unstable angina or acute myocardial infarction. CRP is mostly studied. Increased concentrations of CRP are associated with a series of risk factors. CRP may predict recurrent events and mortality independently of cardiac troponin levels, and it is also an independent predictor of a cardiovascular event after adjustment for traditional risk factors. Although CRP currently appears to be the most promising biological marker, there is still controversy regarding its use in clinical practice. Both necrotic and apoptotic cell death are documented during atherogenesis, however, limited data are available about apoptotic markers in ischemic heart disease patients. Increasing evidence supports the existence of apoptotic death initiated by ligation of membrane-bound death receptors or by release of cytochrome c from mitochondria, as well as their regulators in the heart. The studies of serum markers show that the apoptotic process is disregulated in ischemic heart disease patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is present in stable atherosclerotic lesions, is increased in vulnerable plaques, but its serum levels are reduced significantly in patients with unstable angina. Serum Fas concentrations are increased and FasL are decreased in subjects at high cardiovascular risk. The results of our study show significant changes in serum Fas, FasL, and Bcl-2 concentrations, and lymphocyte caspase-3 activity in different stages of ischemic heart disease. For now, there is evidence that statins are effective in the regulation of some apoptotic markers. The better understanding of the pathways of apoptosis and their regulation is promissing in yielding novel therapeutic targets for cardiovascular disease.

Serum Bcl-2 level dynamics in acute EBV primary infection

Serum Bcl-2 level dynamics in acute EBV primary infection

SERUM LEVELS OF BCL-2 AND CELLULAR OXIDATIVE STRESS IN PATIENTS WITH VIRAL HEPATITIS

Purpose: This study was conducted to investigate the presence of bcl-2 protein in the serum of patients with viral hepatitis and to find out if there is any correlation between bcl-2 protein levels and cellular oxidative stress in the pathogenesis of viral hepatitis. Methods: This study was carried out on 130 patients with viral hepatitis, 70 with chronic hepatitis, 30 with liver cirrhosis and 30 with hepatocellular carcinoma (HCC) in addition to 20 healthy persons as the control. Serum bcl-2 protein was estimated by enzyme-linked immunosorbent assay, serum malondialdehyde (MDA), nitric oxide (NO) and antioxidant enzymes (GSH, GSH-px, GR and SOD) were measured using spectrophotometric analysis. Results: bcl-2 protein level was significantly elevated in the serum of HCC, cirrhosis and chronic hepatitis groups as compared to control group. There were significant positive correlations between higher bcl-2 protein level and viral hepatitis markers (HBsAg, anti-HCV antibodies) in HCC and cirrhotic patients as compared to chronic hepatitis group. An increase in oxidative stress markers (MDA, NO) and a decrease in antioxidant enzyme activities (SOD, GSH and GSH-px) were observed. However, there was a negative correlation between bcl-2 levels and GR in all studied patient groups. Conclusions: The release of oxidative free radicals, deficiency in antioxidant enzymes and the expression of bcl-2 protein might play a role in the pathogenesis of viral hepatitis. The ability to measure bcl-2 protein in the serum could be useful as a prognostic marker of cancer patients.

Augmented antitumor effects of combination therapy with VEGF antibody and cisplatin on murine B16F10 melanoma cells

Our previous studies with EAC tumor model demonstrated that a VEGF polyclonal antibody combined with cisplatin inhibited tumor growth. Here we report the antitumor effect of VEGF antibody plus cisplatin on a murine metastatic tumor model specially emphasizing its effect on different angiogenic parameters both in vitro and in vivo. Mouse B16F10 melanoma cells were cultured in vitro in DMEM media containing 10% FBS, nonessential amino acids and antibiotics in a 5% CO2 incubator at 37 °C and the effect of VEGF antibody singly and in combination with cisplatin on this cell was assessed by MTT assay, matrigel invasion study and MMP-9 expression study in vitro. In vivo studies were performed by two tumor models viz B16F10 solid tumor model and B16LuF10 lung tumor model. The mice treated with VEGF antibody (PAb) alone, cisplatin alone and combination of VEGF antibody and cisplatin on alternative days from the next day of tumor transplantation. Antitumor as well as antiangiogenic efficacy was monitored by measuring tumor burden, survivability, MVD measurement, serum NO value measurement and bcl-2 expression study. It was observed that administration of combined therapy with VEGF antibody and cisplatin augmented antitumor activity in B16F10 melanoma models than the either agents alone. Thus our experiments show a successful VEGF antibody based combination therapy with cisplatin and suggests that the enhancement of antitumor activity could be explained by a concomitant effect on both endothelial and tumor cell compartment.

Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type

To describe clinicopathologic features and to identify prognostic factors in a large series of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT), as defined in the recent World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. Retrospective multicenter study from the French Study Group on Cutaneous Lymphomas. Nineteen departments of dermatology in 10 regions of France. Sixty patients with a PCLBCL LT included in the registry of the French Study Group on Cutaneous Lymphomas. Age, sex, outcome, therapy, B symptoms, cutaneous extent, number of lesions, location (leg vs nonleg), serum lactate dehydrogenase level, and MUM-1 and Bcl-2 expression were recorded. Disease-specific survival was used as the main end point. Prognostic factors were identified using a Cox proportional hazards model. Primary cutaneous diffuse large B-cell lymphoma, leg type is characterized by a predilection for the leg (72%), a high proportion of Bcl-2 expression (85%), an advanced age at onset (mean age, 76 years), and frequent relapses and extracutaneous dissemination. The overall 5-year disease-specific survival rate was 41%. Location on the leg and multiple skin lesions were predictive of death in multivariate analysis. Although no variable related to therapy was significantly associated with survival, patients recently treated with combinations of anthracycline-containing chemotherapies and rituximab had a more favorable short-term outcome. Primary cutaneous diffuse large B-cell lymphoma, leg type is a distinct entity with a poor prognosis, particularly in patients with multiple tumors on the legs. Despite the advanced age of many patients, the prognosis could be improved with combinations of anthracycline-containing chemotherapies and rituximab.

2011 POSTER Serum BCL-2 and VEGF in women with breast cancer – can they detect the recurrence before CEA and CA15–3?

2011 POSTER Serum BCL-2 and VEGF in women with breast cancer – can they detect the recurrence before CEA and CA15–3?

Serum levels of bcl-2 and cellular oxidative stress in patients with viral hepatitis

This study was conducted to investigate the presence of bcl-2 protein in the serum of patients with viral hepatitis and to find out if there is any correlation between bcl-2 protein levels and cellular oxidative stress in the pathogenesis of viral hepatitis. This study was carried out on 130 patients with viral hepatitis, 70 with chronic hepatitis, 30 with liver cirrhosis and 30 with hepatocellular carcinoma (HCC) in addition to 20 healthy persons as the control. Serum bcl-2 protein was estimated by enzyme-linked immunosorbent assay, serum malondialdehyde (MDA), nitric oxide (NO) and antioxidant enzymes (GSH, GSH-px, GR and SOD) were measured using spectrophotometric analysis. bcl-2 protein level was significantly elevated in the serum of HCC, cirrhosis and chronic hepatitis groups as compared to control group. There were significant positive correlations between higher bcl-2 protein level and viral hepatitis markers (HBsAg, anti-HCV antibodies) in HCC and cirrhotic patients as compared to chronic hepatitis group. An increase in oxidative stress markers (MDA, NO) and a decrease in antioxidant enzyme activities (SOD, GSH and GSH-px) were observed. However, there was a negative correlation between bcl-2 levels and GR in all studied patient groups. The release of oxidative free radicals, deficiency in antioxidant enzymes and the expression of bcl-2 protein might play a role in the pathogenesis of viral hepatitis. The ability to measure bcl-2 protein in the serum could be useful as a prognostic marker of cancer patients.

253 POSTER Serum VEGF, c-erb-B2, p53m, bcl-2 vs CEA and CA15-3 in breast cancer. Which of them can detect the recurrence earlier?

253 POSTER Serum VEGF, c-erb-B2, p53m, bcl-2 vs CEA and CA15-3 in breast cancer. Which of them can detect the recurrence earlier?

273 POSTER The prognostic value of serum VEGF, c-erb-B2, p53m and bcl-2 in women with breast cancer, can they detect the recurrence before the clinical appearance?

273 POSTER The prognostic value of serum VEGF, c-erb-B2, p53m and bcl-2 in women with breast cancer, can they detect the recurrence before the clinical appearance?

Glomerular expression and elevated serum Bcl-2 and Fas proteins in lupus nephritis: preliminary findings

Programmed cell death (apoptosis) is involved in glomerular injuries leading to glomerulonephritis. Bcl-2 and Fas are proteins that promote cell survival and death, respectively. This study tests the hypothesis that lupus nephritis is associated with alterations of Bcl-2 and Fas protein expression. Thirty-six patients with lupus nephritis and 10 controls (normal individuals) were included in this study. Bcl-2 and Fas positive cells were examined in kidney biopsies by immunohistochemistry. Bcl-2 and Fas serum levels were evaluated by enzyme-linked immunosorbent assay (ELISA). In the glomeruli of normal kidneys, Bcl-2 and Fas proteins were completely absent. In lupus nephritis patients, glomerular expression of Bcl-2 and Fas was seen in mesangial cells (1.3 +/- 0.1 and 2.0 +/- 0.1 for Bcl-2 and Fas, respectively). Similarly, a statistically significantly higher Bcl-2 (217.1 +/- 85.9) and Fas (767.9 +/- 271) serum levels were found in lupus patients compared to controls (148.6 +/- 87, 550.3 +/- 91 for Bcl-2 and Fas, P < 0.05). A direct correlation between serum Bcl-2 and Fas and chronicity index was also found. Compared to normal controls, lupus nephritis is associated with glomerular expression and elevated serum levels of Bcl-2 and Fas proteins. These findings suggest possible roles for Bcl-2 and Fas in glomerular injury during evolution of lupus nephritis. The diagnostic, prognostic and therapeutic ramifications of our findings are open to further investigation.

Serum Fas and Bcl-2 in patients with epilepsy

The present study aimed to investigate the levels of the biochemical markers of apoptosis (soluble Fas and Bcl-2) in the sera of children and adolescents with idiopathic epilepsy. The study included 30 children and adolescents (mean age 8.03 +/- 4.49 years) with idiopathic epilepsy, 16 of them were newly diagnosed, and 15 clinically healthy control subjects. Of the included patients, 22 had focal seizures and eight had generalized seizures. In addition to laboratory and radiological investigations needed for diagnosis and follow-up, soluble Fas (s.Fas) and Bcl-2 were assayed in sera of patients and controls by enzyme-linked immunosorbent assay technique. Serum levels of s.Fas and Bcl-2 were significantly higher in the patients group than in the control group; however, their levels were comparable in patients with different seizure types. Levels of s.Fas correlated positively with seizure severity and negatively with the duration from the last attack. Bcl-2 levels were positively correlated to each of the duration of epilepsy, the severity of seizures and its frequency. There was a significant positive correlation between serum levels of s.Fas and that of Bcl-2 and both were significantly increased in patients with uncontrolled epilepsy. The present data demonstrate that markers of apoptosis, both the proapoptotic Fas and the anti-apoptotic Bcl-2, were proportionately elevated in sera of patients with idiopathic epilepsy, and their levels were related to the seizure severity and frequency.

The Value of Serum bcl-2 Levels in Advanced Epithelial Ovarian Cancer

The present study was conducted to investigate the value of serum bcl-2 levels in advanced epithelial ovarian cancer patients. Twenty-two patients with advanced ovarian carcinoma pathologically verified were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum bcl-2 protein was determined by using ELISA. The baseline serum bcl-2 levels were significantly higher in patients with ovarian cancer than in the control group (p < 0.001). The sensitivity and specificity of serum bcl-2 were determined as 100% and 78%, respectively. None of the prognostic parameters analyzed such as age of patient, stage of disease, serum CA-125, albumin, hemoglobin, LDH, and response to chemotherapy was significantly correlated with bcl-2 serum concentrations. No prognostic value of serum bcl- 2 was determined. In conclusion, the results of the present study suggest that decreased apoptosis occurred due to the effect of serum bcl-2 elevation in advanced ovarian cancer patients. Also, serum bcl-2 level was a diagnostic but not a prognostic value in ovarian cancer. However, much researches still continues in this field, and exciting new knowledge will ultimately emerge.

Serum Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Levels in Advanced Stage Non-Small Cell Lung Cancer

The characteristic changes in cancer process are assumed to be genetic alterations about the imbalance of cell proliferation and apoptotic cell death. This study was conducted to determine the value of the circulating vascular endothelial growth factor (VEGF) and Bcl-2 in patients with advanced stage non-small cell lung cancer (NSCLC). These serum factors were measured of 52 NSCLC patients pathologically verified on before and after chemotherapy in comparison with 16 healthy controls by using ELISA method. Both of the serum levels of VEGF (p = 0.015) and Bcl-2 (p < 0.001) were increased significantly in NSCLC patients compared with the healthy controls. No statistically significant relationships between investigated elevated serum parameters and various characteristics of patients and disease such as stage and tumor burden were determined. Likewise, we also found no correlation between serum VEGF and Bcl-2. Cytotoxic therapy of patients was accompanied by unchanged serum levels of serum factors. The median survival of all patients was 27 weeks and one-year survival rate was 22.4 percent. With the median serum levels as the cut-off value, patients were divided into high- and low-serum parameter groups. While we found that patients' performance status (p < 0.0001), serum LDH level (p = 0.0002), response to chemotherapy (p = 0.0023), and stage of the disease (p = 0.0085) were prognostic factors for survival, serum VEGF (p = 0.48) and Bcl-2 (p = 0.91) levels were determined as ineffective on survival in patients with advanced NSCLC. In conclusion, our data suggest that these serum factors, VEGF and Bcl-2, are useful diagnostic factors, not predictive and prognostic markers for overall survival in advanced NSCLC patients.

The Value of Serum Bcl-2 Levels in Advanced Lung Cancer Patients

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.

Serum bcl-2 and survivin levels in melanoma

This study was conducted to investigate the serum levels of bcl-2 and survivin in patients with melanoma and the relationship with tumour progression and known prognostic parameters. Forty-four patients with cutaneous melanoma were investigated. Serum samples were obtained on first admission before adjuvant and metastatic treatment were given and at follow-up. Serum bcl-2 and survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA). The baseline serum bcl-2 levels were significantly higher in patients with melanoma than in the control group (P=0.01). For the serum survivin levels, no difference was found (P=0.6). No significant correlations were found between the prognostic parameters analysed and the serum survivin concentrations. The same was true of the serum bcl-2 values, except for the age of the patient (P=0.025) and nodal involvement (P=0.003). No significant relationship was found between the serum levels of bcl-2 and survivin (r=-0.13, P=0.4). In node-positive patients (n=8) both of these anti-apoptotic substances were unchanged after interferon-alpha-2b therapy. However, serum survivin concentrations were significantly increased in 10 patients with metastatic melanoma who underwent dacarbazine (DTIC)-based cytotoxic chemotherapy (P=0.047). A similar finding was not determined for the serum bcl-2 levels. In conclusion, the results of this study suggest that decreased apoptosis is associated partly with an increase in serum bcl-2. However, much research continues in this field, and exciting new knowledge will ultimately emerge.

Serum levels of bcl-2 in patients with colorectal cancer

Many recent studies focus on the immunohistochemical evaluation of Bcl-2 expression, and its prognostic significance in colorectal cancer (CRC). Our aim was to investigate the presence of bcl-2 protein in the serum and to examine the association between its levels, stage and tumour load, in patients with CRC. A commercially available ELISA was used for the estimation of bcl-2 levels, in 94 patients with different stages of CRC. Forty-eight healthy blood donors served as controls. Concentrations ranging 2SD above and below the controls median were accepted as "normal". bcl-2 was detected in the serum of patients with CRC. A significantly higher proportion of patients with non-metastatic disease (61%), had high serum bcl-2 values, compared to patients with metastatic disease (28%, p<0.0001). Serum bcl-2 in patients with CRC may reflect the degree of Bcl-2 expression in cancer tissue. Serum bcl-2 is easily determinable, and could be useful as a prognostic marker in CRC.

Ischemic preconditioning or heat shock pretreatment ameliorates neuronal apoptosis following hypothermic circulatory arrest

Objective Hypothermic circulatory arrest has been widely used in complex cardiac and aortic surgery. Stroke and/or neurologic injury can occur after prolonged hypothermic circulatory arrest, possibly due to apoptosis. Ischemic preconditioning has been widely used as a neuroprotective tool, but its application in neuronal injury under hypothermic circulatory arrest has never been studied. Methods Forty male New Zealand white rabbits were placed on closed-chest cardiopulmonary bypass, subjected to hypothermic circulatory arrest, and rewarmed to normothermia. Experimental groups were treated with heat shock or ischemic preconditioning before hypothermic circulatory arrest. Hippocampal CA1 neurons were analyzed histopathologically. Apoptosis was confirmed by TUNEL assay and Western blot analysis, and serum S-100β levels, c-Fos and Bcl-2 antibodies, and caspase-3 and heat shock protein 70 levels were measured. Results After 2-hour hypothermic circulatory arrest and 4-hour reperfusion, apoptosis was observed in hippocampal CA1 neurons with elevation of serum S-100β levels, which could be ameliorated by ischemic preconditioning or heat shock manipulations. TUNEL-positive nuclear expression of caspase-3 increased after hypothermic circulatory arrest (3.08% ± 0.71%, P < .001) and was diminished with ischemic preconditioning (1.61% ± 0.42%) and heat shock (1.72% ± 0.38%) manipulations. Ischemic preconditioning or heat shock manipulations produced diverse patterns of heat shock protein 70, c-Fos, and Bcl-2 protein expression, suggesting that these manipulations provide neuroprotection via different pathways. Conclusions Ischemic preconditioning and heat shock can attenuate hippocampal CA1 neuronal apoptosis after prolonged hypothermic circulatory arrest under cardiopulmonary bypass. The expression of heat shock protein 70 may not play a major role in the first window of ischemic preconditioning-induced neuroprotection.