Higher cytotoxic activities of CD8+ T cells and natural killer cells from peripheral blood of early diagnosed lung cancer patients.

INTRODUCTION: Cytotoxic (CD8+) and natural killer (NK) cells play critical roles in anti-tumor immunity. Dysfunction in these cells is considered as one of the extrinsic mechanisms for tumor relapse. AIM: We aimed in this study to assess cytotoxic activities of CD8 + T and NK cells in the peripheral blood from lung cancer patients before and after induction of chemotherapy. SUBJECTS AND METHODS: Healthy (n = 5) volunteers and lung cancer patients (n = 15:5 before, 5 during, and 5 after induction of chemotherapy) were recruited. Flow cytometry was used to analyze the numbers of CD8 + T cells, NK and CD56+T cells and their intracellular expression of granzyme B (GzB) in fresh peripheral blood mononuclear cells (PBMCs) and after 72 h of their culture in vitro and stimulation with 5 µg/ml Concanavalin A (Con A) and 50ng/ml IL-2). In addition, the plasma levels of inflammatory cytokines were measured using luminex. RESULTS: After culture, significant increases in the number of GzB expressing cells gated on CD3+, CD4+, CD8 + and NKCD8 + T cells in the PBMCs from lung cancer patients before induction of chemotherapy as compared to control individuals as well as patients during and after induction of chemotherapy. Serum levels of IL-1 and CXCL8 in patients before induction of chemotherapy showed 37- and 40-fold increases, respectively, as compared to control individuals. Both GzB expression and cytokines levels in patients during and after chemotherapy were similar. CONCLUSION: Polyclonal stimulation of PBMCs can restore the cytolytic activities of cytotoxic CD8 and NK cells from lung cancer patients even after chemotherapy.

Prognostic Role of Oncogenic and Tumor-Suppressing miRNA Types in Egyptian Uterine Cancer Patients.

OBJECTIVE: Uterine or endometrial cancer affects many women postmenopausal and may reach an advanced stage before signs and symptoms can be noticed. Micro RNAs (miRNAs), non-coding RNAs, play key roles in gene expression regulation and are linked to cancer. This study aimed to elucidate whether some specific types of miRNAs (miRNA133-a, miRNA-21, miRNA-205) can act as prognostic or diagnostic biomarkers for endometrial carcinoma (ER) in Egyptian patients. METHODS: Blood samples from 36 patients suffering from endometrial carcinoma and 15 healthy volunteers were tested for expression levels of miRNA 133a-2, 21 and 205. RESULTS: The expression levels of miRNA133a-2, miRNA-21, and miRNA-205 were significantly elevated in ER patients when compared with the control group, the highest levels were noticed in miRNA133a-2. The CA125 levels were significantly higher in all patients as compared with healthy subjects. CONCLUSION: The findings could support the use of circulating miR133a-2, miR-21 and miR-205 as virtuous prognostic biomarkers for EC in Egyptian patients. The studied miRNA species warrant validation for prospective targeting inhibitory protocols in EC.

Serum FBLN1 and STK31 as biomarkers of colorectal cancer and their ability to noninvasively differentiate colorectal cancer from benign polyps.

PURPOSE: The aim of this work is to evaluate Fibulin-1 (FBLN1) and serine threonine kinase-31 (STK31) as colorectal cancer (CRC) tumour markers and their ability to differentiate it from colorectal benign lesions. MATERIAL AND METHODS: In this case-control study, FBLN1 and STK31 serum levels were measured in 120 participants; 49 CRC patients (group I), 26 patients with benign colorectal polyps (group II) and 45 healthy controls (group III). RESULTS: The means of serum FBLN1 were 1.02 ±â€¯0.95, 6.36 ±â€¯2.55 and 6.26 ±â€¯2.76 in group I, II and III respectively. Significant lower levels were found in group I compared to group II and III (both p < 0.001) with no significant difference between group II and III (p = .983). The means of serum STK31 were 13.51 ±â€¯7.67, 5.98 ±â€¯3.3 and 1.37 ±â€¯1.22 in group I, II and III respectively with significant differences in-between the 3 groups (p < 0.001). Both FBLN1 and STK31 were superior to CEA as CRC screening biomarkers; with sensitivity 90.1% and 93% respectively and specificity 93.9% and 95.9% respectively. FBLN1 differentiated CRC from benign polyps with 91.8% sensitivity and 100% specificity. STK31 differentiated CRC from benign polyps with 93.9% sensitivity and 84.6% specificity. CONCLUSION: FBLN1 and STK31 can be possible screening and differentiating biomarkers of CRC.

Diagnostic Value of Glypican-3 for Hepatocellular Carcinomas

Background: Hepatocellular carcinoma (HCC) is a common and dangerous malignancy in many parts of the world, and especially in Egypt. Early diagnosis is the most important step in successful HCC management. However most cases are detected at late stage making effective intervention impossible. Aim: The aim of this study was to evaluate the potential of Glypican-3 (GPC-3) to aid in diagnosis of HCC, especially in patients with low serum alpha-fetoprotein (AFP). Subjects and methods: Serum GPC-3 was assessed by flow-cytometry and serum AFP by enzyme-linked immunosorbent assay (ELISA) in 40 HCC patients with AFP< 400ug\l. (GI), 40 HCC patients with AFP> 400ug\l. (GII) and 20 healthy controls (GIII). Results: GPC-3 was found to be significantly elevated in HCC as compared to healthy subjects (GI 38.2±22. 5, GII 50.2±22.6, and GIII 2.24±1.19), with sensitivities of 85% for GI and 84% for GII and specificities of 95% for GI and 92% for GII. AFP showed respective sensitivities of 50% and 79%, and specificities of 80% and 90%, for HCC diagnosis. The combination of GPC-3 with AFP achieved the highest sensitivity (98.5%) and specificity (97.8%). Conclusion: Serum GPC-3 has a better sensitivity than AFP for the diagnosis of HCC. Combination of two markers appears warranted for greatest accuracy.

Epidemiology of liver cancer in Nile delta over a decade: A single-center study.

BACKGROUND: In Egypt, there has been a remarkable increase in the proportion of hepatocellular carcinoma (HCC) among chronic liver diseases patients. This rising proportion may be explained by the increasing risk factors as hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, improvement of the diagnostic tools of HCC as well as the extended survival among patients with cirrhosis to allow time for some of them to develop HCC. The aim of this study was to study the epidemiology of HCC in Nile delta over the last decade. METHODS: The study was carried out on patients diagnosed as HCC in liver cancer clinic in Tanta University Hospital, Egypt, from January 2005 to January 2015. This retrospective study reviewed the files of HCC patients with special stress on age, sex, residence, occupation, smoking, and viral markers. RESULTS: Over the last decade, 1440 HCC patients were diagnosed or referred to liver cancer clinic in Tropical Medicine Department in Tanta University Hospital from January 2005 to January 2015. The mean age of HCC patients was 56.13 ± 9.53 years. Nearly, half of the patients with HCC were smokers and quarter of HCC patients were diabetics. HBV surface antigen-positive patients were only 3.26%, and the majority of patients were HCV-Ab positive (94.86% of patients). CONCLUSIONS: In Nile delta, hepatitis C rather than hepatitis B was linked to the development of HCC in our region which may be related to the high prevalence of HCV in this area.

Cytokeratin-18 in Diagnosis of HCC in Patients with Liver Cirrhosis

Background: Hepatocellular carcinoma (HCC) is a common malignancy that occurs secondary to viral hepatitis B and C cirrhosis under the influence of environmental factors. In early stages, clinical diagnosis is often difficult and distinguishing HCC from cirrhosis and other hepatic masses by conventional tests is frequently not feasible. Physicians usually depend on measuring serum alpha-fetoprotein (AFP), but this marker has low sensitivity and specificity. The aim of this research was to determine any role of serum cytokeratin-18(Ck-18) as a marker for diagnosis of HCC in patients with liver cirrhosis. Patients and methods: We used ELISA to measure the serum levels of AFP and CK 18 in 60 Egyptian patients (30 cirrhotic and 30 with HCC) and 30 controls. Results: The Ck-18 level was significantly elevated in the HCC group (1247.8± 105.3U/L) when compared to the liver cirrhosis (834.1± 38.8 U/L) and control groups (265.2±83.1U/L). Ck-18 as a marker showed 95.6% sensitivity, 93.3% specificity and 98.8% accuracy. The mean serum AFP was 4901.4±2185.8ng/ml in the HCC group, 100.7±71.7 ng/ml in the cirrhotic group, and 4.0±1.2ng/ ml in controls. AFP showed 55. 7% sensitivity, 97. 7% specificity and 84.4% accuracy. Combined use of both Ck-18 and AFP improved the sensitivity to 98%. Conclusion: Serum cytokeratin-18 level can be used as a diagnostic biomarker for HCC with a higher sensitivity than AFP.

Immunohistochemical expression of proinflammatory enzyme COX-2 and p53 in ulcerative colitis and its associated dysplasia and colorectal carcinoma.

BACKGROUND/AIM: Ulcerative colitis (UC) patients are at increased risk for colorectal carcinoma (CRC). It is suggested that cyclooxygenase-2 (COX-2) plays a role in sporadic CRC. The p53 gene is a tumor-suppressor gene and the most frequent site of genetic alteration found in human cancer. The aim of this study was to analyze the immunoexpression of proinflammatory enzyme COX-2 and p53 in UC, UC-associated dysplasia, and CRC, in comparison with each other and with different clinical and histopathological parameters, to clarify if they have a possible role in the pathogenesis of CRC in UC patients. MATERIALS AND METHODS: In this cross-sectional study, 98 patients were divided into three groups: 39 patients with UC without dysplasia, 32 patients with UC with dysplasia, and 27 patients with colorectal cancer on top of UC, in addition to 10 healthy controls. All patients underwent colonoscopy, and multiple biopsies were taken for histopathological and COX-2 and p53 immunohistochemical studies. RESULTS: There was significant difference in the expression of COX-2 and p53 in UC-related dysplasia either without or with CRC, compared with their expression in the UC group without dysplasia. CONCLUSION: Adding immunohistochemical analysis of COX-2 enzyme and p53 gene to routine histological assessment may improve the accuracy of early detection of dysplasia and colorectal cancer. COX-2 and p53 can be promising chemotherapeutic/chemopreventive targets in UC patients.

Goserelin acetate before transurethral resection of moderately enlarged benign prostatic hyperplasia: Prospective randomised-controlled clinical trial.

OBJECTIVE: To evaluate the impact of a luteinising hormone-releasing hormone (LHRH) agonist, goserelin acetate (GA), on surgical blood loss during transurethral resection of the prostate (TURP), as well as its histopathological effect on prostatic microvessel density (MVD). PATIENTS AND METHODS: Patients who underwent TURP due to benign prostatic enlargement (60-100 mL) were randomly subdivided into two equal groups according to whether they received preoperative GA administration (3.6 mg; group A) or not (group B). Evaluation parameters were operative time, weight of resected prostatic tissue, perioperative haematocrit (HCT) changes, estimation of intraoperative blood loss, and suburethral and stromal prostatic MVD. Effects of GA on prostate weight and any possible side-effects were also monitored. RESULTS: In all, 35 and 33 patients were included in groups A and B, respectively. Operative time and HCT values' changes were significantly less in group A (P < 0.05). Also, operative blood loss (both total and adjusted per weight of resected tissue) was lower in group A, at a mean (SD) of 178.13 (77.71) mL and 3.74 (1.52) mL/g vs 371.75 (91.09) mL and 8.59 (2.42) mL/g (P < 0.001). The median MVD in both suburethral [8 vs 11 vessels/high-power field (HPF)] and stromal tissues (9 vs 17 vessels/HPF) were significantly lower in group A (P < 0.001). Side-effects were minimal. CONCLUSION: A single dose of GA, a LHRH agonist, before TURP is safe and effective in reducing surgical blood loss. It significantly reduced MVD in both suburethral and stromal nodular prostatic tissues without regional discrepancy.

Predictive value of serum insulin-like growth factor-1 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Insulin-like growth factor-1 (IGF-1) levels reflect hepatic function and are inversely correlated with the severity of background chronic liver disease. OBJECTIVE: This study evaluated whether basal serum IGF-1 levels can predict prognosis of HCC patients according to different risks of disease progression. MATERIALS AND METHODS: A total of 89 patients with hepatocellular carcinoma (HCC) were recruited in 3 groups: Group I, 30 HCC patients receiving sorafinib; Group II, 30 HCC patients with best supportive care; and Group III include 29 patients undergoing transcatheter arterial chemoembolization (TACE). All patients were investigated for serum levels of AST, ALP, Bb, Cr, BUN, AFP and IGF-I. RESULTS: Patients with disease control had significantly higher baseline IGF-1 levels 210 (185-232.5) ng/mL (p value<0.01) than did patients without disease control. Low basal IGF-1 levels were associated with advanced HCC, such as multiple tumors and advanced stage, and low IGF-1 levels predicted shorter TTP and overall survival in patients treated with TACE. CONCLUSIONS: The levels of serum IGF-1, expressed as continuous values, may be helpful for accurately assessing hepatic function and the prognostic stratification of patients with HCC.

Plasma nuclear factor kappa B and serum peroxiredoxin 3 in early diagnosis of hepatocellular carcinoma.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-?B) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. MATERIALS AND METHODS: Plasma nuclear factor kappa B level (NF-?B) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. RESULTS: NF-?B and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-?B) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. CONCLUSIONS: NF-?B and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-?B) as a target for treatment of liver fibrosis and HCC must be widely evaluated.

Breast cancer laterality among Egyptian patients and its association with treatments and survival.

BACKGROUND AND AIM: Breast cancers (BCs) involve the left side (LS) more than the right side (RS). Among the Egyptians, neither BC laterality nor its association with demographic factors, tumor locations, treatments and outcomes were previously reported. PATIENTS AND METHODS: Laterality was analyzed among 5459 BCs from the Gharbiah population-based cancer registry covering >5% of the Egyptian population. Cox proportional model was used to assess the independent effect of stage, ER, and laterality on overall survival (OS). RESULTS: In Egypt, BCs involve LS more than RS with LS-to-RS ratio (LRR) of 1.16. LS predominance was evident among men and women and both younger (< 45 years) and older patients. HER2 over-expression and ductal cancers were significantly more in RSBCs while lobular cancers were significantly more in LSBCs. There were no significant differences in localization within the breast between LSBCs and RSBCs (p = 0.51). LS predominance was noticed across all subgroups except in patients with HER2 positive tumors (LRR = 0.63; p = 0.02). OS was significantly better in stage II and ER positive tumors than stage III and ER negative tumors. Despite OS of LSBCs being generally lower than RSBCs, this was not statistically significant. The significant impact of stage on OS was lost in LSBCs. CONCLUSIONS: Among Egyptian patients, the left breast is at greater risk of cancer than the right one. Despite right-sided tumors seemed more aggressive, Left-sided ones tend to confer worse survival than right-sided tumors.