Clinical Association of CD44 Expression with Proliferative Activity and Apoptotic State in Egyptian Patients Suffering from Ulcerative Colitis and Colorectal Carcinoma.

BACKGROUND AND AIM: Cancer stem cell markers were thoroughly investigated as a promising strategy for the prediction of patient outcome and therapeutic response. The prospective role of CD44 cell adhesion molecule in tumorigenic potential and its association with the proliferative activity and apoptotic status of Egyptian patients with ulcerative colitis (UC) and colorectal cancer (CRC) were investigated in this study. MATERIAL AND METHOD: Flow cytometric analyses of CD44, DNA cell cycle, and apoptosis identified by Annexin V/PI were performed on colonic tissue specimens obtained from 44 CRC patients, 36 UC patients, and 30 controls. RESULTS: The CRC patients showed overexpression of CD44 marker (p < 0.0001) in comparison with UC and control groups. Regression analysis identified CD44 marker as an independent predictor for tumor staging and grading (p < 0.0001) of CRC patients. The CD44 expression was positively correlated with tumor stage (r = 0.656), tumor grade (r = 0.645), and the proliferative activity of DNA cell cycle (S phase, r = 0.396). However, CD44 expression was negatively correlated with early apoptosis (r = - 0.525). CONCLUSION: According to our findings, there was a significant and  positive association between CD44 dysregulated expression and S phase of DNA cell cycle but a negative association with early apoptosis in CRC patients, suggesting CD44 role in apoptosis suppression reducing the tumor growth reserve.

Redox State of Human Serum Albumin and Inflammatory Biomarkers in Hemodialysis Patients with Secondary Hyperparathyroidism During Oral Calcitriol Supplementation for Vitamin D.

BACKGROUND: Hemodialysis (HD) patients with secondary Hyperparathyroidism (s-HPT) are exposed to increased inflammation and oxidative stress. In HD patients, oxidized albumin is a reliable marker of oxidative stress and its clinical significance has been rarely studied. OBJECTIVE: The objective of this study was to evaluate Cys34 Human Serum Albumin (HSA) as oxidative stress biomarker in HD patients with s-HPT and its relationship with inflammation on bone turnover markers during oral calcitriol supplementation for vitamin D. PATIENTS AND METHODS: Fifteen stable hemodialysis patients with s-HPT (mean age 48.67±8.15, 11 males and 4 females) were used in the experiment to receive calcitriol treatment for 16 weeks (0.25mcg or 0.5 mcg once a day according to serum level of Ca and P for each). The changes in the serum biochemical parameters (Ca, P, ALP, and iPTH), inflammatory markers (CRP and IL-6 levels) and serum oxidative stress condition (SOD, IS and albumin ratio HNA/HMA) were evaluated before and at 8 and 16 weeks of calcitriol treatment. The correlations between those factors were studied. RESULTS: All patients responded to oral calcitriol therapy, with a significant decrease in the serum iPTH. The results showed that calcitriol could effectively suppress iPTH secretion with a significant elevation of serum Ca and P but ALP remained unchanged during the study. It can also effectively reduce the inflammatory markers (CRP and IL-6), while increasing the oxidative markers (SOD and IS). Oxidative albumin ratio HNA/HMA showed a significant (p=0.001) reduction after 16 weeks of calcitriol treatment and the redox state of HSA showed a positive prediction for hyperparathyroidism and for inflammation. CONCLUSION: The redox state of HSA could be used as a predictor for monitoring hyperparathyroidism and inflammation during calcitriol treatment by retarding albumin oxidation in HD patients with secondary hyperparathyroidism.

Serum Cytokine of IL-10 and IL-12 in Chronic Liver Disease: The Immune and Inflammatory Response.

The current study was designed to investigate the potential association of serum interleukin-10 and interleukin-12 with HCV infection in chronic liver disease and to evaluate their possible role as new biomarkers in HCC development. Material and Methods. Forty-one patients suffering from chronic liver disease (33 patients harbor HCV infection and 8 are HCV-negative patients) were enrolled in the present study and histopathologically diagnosed into 15 patients with HCC, 16 patients with LC, and 10 patients with liver histology compatible with precirrhotic hepatitis (PCH). Ten patients complaining of cholecystitis were included as nondisease control. Serum levels of IL-10 and IL-12 were measured by enzyme linked immunosorbent assay (ELISA). Results. HCV-infected patients showed elevated expression of IL-10 and IL-12 compared to nondisease controls (P < 0.0001) but there is no significant difference with respect to their expression in HCV-negative patients. Serum IL-10 and IL-12 were elevated significantly with disease progression (P < 0.0001) and a positive correlation coefficient was detected between IL-10, IL-12 (r = 0.785, P < 0.0001), and transaminase values suggesting their possible role in chronic inflammation progression leading to HCC. Conclusion. IL-10 and IL-12 might be involved in chronic inflammation progression leading to HCC and their evaluation could be used as new biomarkers to reflect the degree of inflammation in HCC development.

Prognostic significance of three hepatitis markers (p53 antibodies, vascular endothelial growth factors and alpha fetoprotein) in patients with hepatocellular carcinoma.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death in the world. Of patients with HCC, the diagnostic capacity of Alpha Fetoprotein (AFP) depends on its elevation in the serum. Concentration of AFP greater than the upper reference limit indicate the presence of HCC, but values below this level are less useful because they may also occur in chronic liver disease. To improve the sensitivity of HCC detection by AFP, this work was conducted to study serum expression of p53 Antibodies (p53 Abs) and Vascular Endothelial Growth Factors (VEGF) as a biomarkers in combination with AFP in patients with HCC. METHODOLOGY: The study included 67 patients with HCC (58 males and 9 females with a mean age of 53.7 years) and 27 patients with liver cirrhosis (23 males and 4 females with a mean age of 42 years). Ten healthy volunteers served as control group. Sera of all cases were examined for p53 Abs and VEGF by Enzyme linked immunosorbent assay (ELISA) and correlate its levels with serum AFP expression. RESULTS: Serum level of p53 Abs was detected in HCC patients (0.54 +/- 23) with a significant elevation (p < 0.0001) than liver cirrhosis (0.26 +/- 0.1) and healthy individuals (0.21 = 0.068). The higher percentage of p53 Abs (73.07%) was detected in HCC patients than in liver cirrhosis (7.4%) (p < 0.0001). Serum expression of VEGF was significantly elevated (p < 0.0001) in HCC patients and in cirrhotic patients than healthy individuals (0.52 +/- 0.25, 0.55 +/- 0.25 vs 0.17 +/- 0.034) while there was no significant difference in VEGF between HCC and cirrhotic patients (p > 0.05). There was no association between either p53 Abs or VEGF and AFP concentrations. However, a greater incidence of VEGF and accumulation of p53 Abs expression was detected in positive cases for AFP where VEGF was detected in 85.3% and p53 Abs was detected in 83.3% of positive cases for AFP. Also, p53 Abs positive patients showed a significant high serum level of VEGF; so both can be used in association for screening of patients with HCC. CONCLUSION: It could be concluded that p53 Abs can be considered as an additional tumor marker to increase the diagnostic potential of AFP in HCC patients and VEGF may offer a novel diagnostic value for HCC.

Apoptosis dysregulation in human gastric carcinomas: relationship to anti- and pro-apoptotic protein expression.

Apoptosis and the genes regulating this process have recently become a focus of interest in the study of cancer development and progression. Both Bcl-2 and Bax are transcriptional targets for the tumor supressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. The coordinate performance of these molecules is crucial for controlling life or death of a cell. Correlations between apoptosis and protein expression of genes controlling this process including Bcl-2, Bax and p53 in gastric cancer were here investigated with gastric tumor samples of forty patients . DNA ploidy pattern was analyzed using flow cytometry and Bcl-2, Bax, and p53 were immunohistochemically localized using specific monoclonal antibodies. In addition, serum Bcl-2 protein was estimated by enzyme linked immunosorbant assay (ELISA). The obtained data showed that the mean serum Bcl-2 protein concentration demonstrated a significant increase (P<0.0001) in positive cases (61.5+/-11.0 unit/ml) compared to the negative ones (47.5+/-3.5 unit/ml). Serum Bcl-2 protein positivity was detected in 13/40 of gastric cancer patients. Immunohistochemical positivity for Bcl-2, Bax, and p53 was shown in 45%, 68%, and 63% of samples, respectively. Positive Bcl-2 and p53 immunostaining was significantly linked with the histological grade (P<0.02 and P<0.009 respectively) and lymph duct invasion (P<0.02 and P<0.001 ). On the other hand, Bax was significantly differed with lymph duct invasion and the ploidy pattern (P<0.03 and P<0.002). In conclusion, the apoptosis-related genes p53, Bcl-2, and Bax are all linked to the occurrence of gastric cancer. Therefore, analysis of their expressions may add useful information concerning tumor behavior.

Susceptibility of neonate mice born to Schistosoma mansoni-infected and noninfected mothers to subsequent S. mansoni infection.

The present study tested the hypothesis that prenatal exposure of neonate Outbred albino mice to Schistosoma mansoni antigens (Ags) or antibodies (Abs) modulates their immunity against postnatal responses to infection. Persistence of maternal S. mansoni Abs and/or Ags in mice born to S. mansoni-infected mothers (IF-IMs) and noninfected mothers (IF-NMs) for up to 8 weeks after delivery was investigated. A higher level of anti-S. mansoni IgG Ab was detected in sera of 1-week-old mice born to IF-IM compared to controls. Then, immunoglobulin (Ig)G gradually decreased to the eight week. No anti-S. mansoni IgM Ab was detected in sera of these offspring at any week after delivery. Schistosoma Ags were detected in liver and kidney tissues of mice born to infected mothers. However, Ags decreased markedly till the sixth week in the liver but increased significantly at the sixth week in the kidney. Eight-week-old mice born to infected and noninfected mothers were infected with 200 S. mansoni ceracriae. Their sera and livers were collected for testing IgG and granuloma formation 6 weeks postinfection. Worms were collected via portal perfusion and counted. Anti-S. mansoni IgG level, size and number of liver granuloma, and worm burden were significantly reduced in the offspring of infected mothers. These data suggest that in utero exposure of Outbred albino mice to S. mansoni may attenuate the pathogenesis of S. mansoni in subsequent challenge.