Noninvasive identification of molecular biomarkers of hepatocellular carcinoma in HCV-Egyptian patients.

BACKGROUND: This study was performed to investigate the expression of different biomarkers in patients with hepatocellular carcinoma and its connection with detective biomarkers. To achieve this objective, seventy subjects were examined in this study, sub-grouped to forty HCC patients and thirty HCV-affected patients with matched thirty healthy individuals. The study involved several groups of participants who were matched based on their age and gender. METHODS: The expression pattern of biomarkers was monitored by quantitative polymerase chain reaction (qRT-PCR). Finally, we utilized a ROC curve to investigate the predictive accurateness of those distinct biomarkers as well as a traditional tumor marker, AFP, in detecting HCC cases. RESULTS: The baseline biomarker expression levels were markedly greater in HCC patients than in those affected by HCV or healthy subjects. We stated that the sensitivity and the specificity of the different biomarkers alone did not improve than that of AFP alone. When comparing AFP with different biomarkers, the diagnostic validity improves only when combining with CK-1. CONCLUSIONS: Overall, our results indicate that CK-1 mRNA expression could help as a noninvasive tumor biomarker for HCC prognosis and diagnosis when combining with AFP.

Heparanase (HPSE) gene polymorphism (rs12503843) contributes as a risk factor for hepatocellular carcinoma (HCC): a pilot study among Egyptian patients.

BACKGROUND: Heparanase activity was found to be included in human cancer development and growth. Heparanase (HPSE) gene single nucleotide polymorphisms (SNPs) have been found to be correlated with different human cancers. In the current study, we investigated whether HPSE SNPs were a hepatocellular carcinoma (HCC) risk factor by carrying out a comprehensive case-control pilot study. HPSE rs12331678 and rs12503843 were genotyped in 70 HCC-diagnosed patients and 30 healthy controls by modified amplification refractory mutation system (ARMS PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: HPSE rs12331678 distributions showed that there were no statistically significant differences between both cohorts either in genotypic or allelic distribution but there was a significant correlation between the rs12503843 (T allele) and the HCC risk in the whole samples (P = 0.042). No significant association was observed between the HPSE rs12331678 and rs12503843 gene polymorphisms and all clinicopathologic markers or with SNP stratification based on HCV carrier in HCC groups. CONCLUSION: Our findings suggest for the first time the HPSE gene SNP characterization in HCC Egyptian patients, and our findings reveal there were associations between the HPSE rs12503843 (T allele) and the susceptibility to HCC.

Interruption of Autophagosome Formation in Cardiovascular Disease, an Evidence for Protective Response of Autophagy.

BACKGROUND: A heart attack occurs when coronary artery blockage interrupts the blood supply to the heart such as is seen in cardiovascular disease (CVD). Importantly, autophagy is commonly regarded as a host defense mechanism against microbial invaders. METHODS: A total of 50 blood samples were obtained from cardiovascular (CV) patients in addition to 30 samples that were obtained from healthy individuals and served as controls. Macrophages were isolated in vitro and propagated from the blood samples. Autophagosome formation, cytokine secretion, and apolipoprotein B (ApoB) gene expression were monitored in patient samples and their derived macrophages. RESULTS: The results showed that autophagy-related (Atg) LC3 and Atg5 genes were significantly down-regulated in all samples obtained from CV patients. Furthermore, the relative gene expression of ApoB, which plays the major role in lipoprotein metabolism, was significantly increased in CV patients. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were increased in these blood samples. Interestingly, targeting of ApoB by small interference RNA (siRNA) reduced the production levels of low-density lipoprotein (LDL), IL-6 and TNF-α in patient-derived macrophages. Further, treatment of patient-derived macrophages with rapamycin, an autophagy inducer agent, successfully regulated the production of LDL, IL-6, TNF-α, and ApoB expression via activation of autophagosome formation. CONCLUSION: The current data reveal the potential disturbance of autophagy in CV patients that accompanied ApoB over-expression. Furthermore, our findings provide evidence for the protective role of autophagy in accumulation of pro-inflammatory cytokines and intracellular LDL degradation in CV patient-derived macrophages.

Cerebral effect of acute normovolemic hemodilution during brain tumor resection.

BACKGROUND: Acute normovolemic hemodilution (ANH) is used in major surgery expected to be accompanied by excessive blood loss. Reducing the hemoglobin content may disturb cerebral oxygen balance. The aim of this study was to assess the effect of ANH on cerebral oxygen balance in patients subjected to brain tumor resection. METHODS: Forty patients were randomly allocated into 2 groups (hemodilution and control). In the hemodilution group (HG), 1000 mL of blood was drawn and replaced with the same volume of HES 130/0.4 (6%, Voluven) colloid. In the control group (CG), no blood was drawn, and hemodynamics were stabilized using normal saline until allogenic blood was needed. Arterial and jugular bulb blood samples obtained after induction (basal, sample 1), 40 minutes after induction (or on completion of hemodilution, sample 2), after surgical hemostasis (sample 3), and just before extubation (sample 4) were used for the calculation of arterial-jugular oxygen content difference "Ca-jO(2)," cerebral oxygen extraction "CEO(2)," estimated cerebral metabolic rate for oxygen "eCMRO(2)," cerebral blood flow equivalent "CBFe," and jugular-arterial lactate difference "J-ALD" in both groups. RESULTS: Jugular oxygen saturation "SjvO(2)", CEO(2), and J-ALD showed no significant difference when the 2 groups were compared at the corresponding time points and when the values obtained at different time points were compared with the basal value in the same group. In CG, "Ca-jO(2)" significantly decreased at the end of surgery and before tracheal extubation (P<0.003 and 0.002, respectively). In HG, it decreased after hemodilution, with P value of less than 0.032. eCMRO(2) was significantly reduced in CG 40 minutes after induction of anesthesia, at the end of surgery, and before tracheal extubation (P<0.021, 0.001, and 0.001, respectively). In HG, eCMRO(2) was significantly reduced at the end of hemodilution and at the end of surgery with P value of less than 0.005 and 0.034, respectively. CBFe was significantly increased in CG at the end of surgery and before tracheal extubation (P<0.005 and 0.022, respectively). It was also increased after hemodilution in HG (P<0.042). There were no significant differences in Ca-jvO(2), eCMRO(2), and CBFe between the 2 groups. CONCLUSION: ANH and allogenic blood transfusion used in this study design were accompanied by comparable cerebral oxygenation parameters in patients subjected to brain tumor resection.