Circulating tumor and cancer stem cells in hepatitis C virus-associated liver disease

AIM: To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C virus (HCV)-associated liver disease.METHODS: Blood and/or tissue samples were obtained from HCV (genotype 4)-associated hepatocellular carcinoma patients (HCC; n = 120), chronic hepatitis C patients (CH; n = 30) and 33 normal control subjects (n = 33). Serum levels of alpha-fetoprotein (AFP), alkaline phosphatase, and alanine and aspartate aminotransferases were measured. Cytokeratin 19 (CK19) monoclonal antibody was used to enumerate CTCs, and CD133 and CD90 were used to enumerate CSCs by flow cytometry. The expression levels of the CSCs markers (CD133 and CD90) as well as telomerase, melanoma antigen encoding gene 1 (MAGE1) and MAGE3 were assessed by RT-PCR and quantitative real-time polymerase chain reactions. The number of CTCs and/or the expression levels of CK19, CD133, telomerase, MAGE1 and MAGE3 were correlated to the standard clinicopathologic prognostic factors and disease progression.RESULTS: Levels of AFP, alkaline phosphatase and aspartate aminotransferase were significantly different among the HCC, CH and control groups (P < 0.001), whereas alanine aminotransferase differed significantly between patient (HCC and CH) and control groups (P < 0.001). At the specified cutoff values determine by flow cytometry, CK19 (49.8), CD90 (400) and CD133 (73) were significantly higher in the blood of HCC patients compared to those in the CH and control groups (P < 0.001). On the other hand, CD133 at a 69.5 cutoff was significantly higher in the CH compared to the control group (P ≤ 0.001). Telomerase, MAGE1 and MAGE3 RNA were expressed in 55.71%, 60.00% and 62.86% of the HCC patients, respectively, but were not detected in patients in the CH or control groups, which were statistically significant (Ps < 0.001). The expression levels of telomerase, CD90, MAGE3, CD133 and CK19 were all significantly associated with high tumor grade and advanced stage in HCC patients (all Ps < 0.05).CONCLUSION: CTC counts and AFP, CK19, telomerase, and MAGE1/MAGE3 expression predict disease progression in patients with HCV, whereas telomerase, MAGE3, CD90, CD133 and CK19 are prognostic markers in HCC.     

Prevalence of antinuclear antibodies in healthy Lebanese subjects, 2008–2015: a cross-sectional study involving 10,814 subjects

Antinuclear antibodies (ANA) are found at varying frequencies in healthy populations, depending on geographical location and ethnic background of participants. The main objective of this study was to determine the prevalence of ANA in healthy Lebanese population in the period 2008–2015. Study subjects comprised 10,851 individuals (3311 males and 7503 females). ANA positivity was determined using immunofluorescence on HEp-2 cells. The prevalence of positive ANA test at a titer of ≥1:100 was 26.4 %, with 696 individuals (6.4 %) having titers exceeding 1:100. Most ANA-positive cases were recorded between 2013 and 2015, which reflected increased assay sensitivity. ANA positivity was associated with increased age and with female gender. Significant increases in ANA positivity were seen with advanced age, with steady increases from the 30- to 40-year age group through the >70-year age group, with significantly higher prevalence noted in female participants. There was a steady and significant reduction in the number of ANA-positive cases with higher ANA titers, which ranged from 20.0 % (1/100) to 3.7 % (1/320), 1.7 % (1/640), and 1.1 % (1/1000). While 45 % of low ANA titer was seen in 31–60-year age category, compared with 19.8 % for 61+ year category, the distribution of high ANA titer was more uniform between 31+ year age categories, which ranged from 11.4 % (31–40 years) to 12.4 % (>70 years). This was consistently and significantly higher in female participants. The prevalence and distribution of ANA among Lebanese individuals were comparable to the rates established for Western countries and confirm the contribution of female gender and advanced age to ANA positivity.     

Liver fatty acid binding protein: A potential urinary and tissue biomarker for lupus nephritis

Aim of the work

To assess urinary liver fatty acid binding protein (uL-FABP) levels and tissue expression (tL-FABP) in renal biopsies of active and inactive lupus nephritis (LN) patients and examine their relationship with disease characteristics.

Evaluation of IL-34 in psoriasis and psoriatic arthritis patients: Correlation with disease activity and severity

Introduction

Interleukin-34 (IL-34) is a newly discovered cytokine essential for skin homoeostasis. It is involved in macrophage differentiation, osteoclastogenesis and inflammation. This could suggest a potential role in the pathogenesis of psoriasis and psoriatic arthritis (PsA).

Perceived Risk of Cervical Cancer and Barriers to Screening among Secondary School Female Teachers in Al Hassa,Saudi Arabia

Background: No previous studies had addressed the perceived risk of cervical cancer (CC) and its influence on screening practices and perceived barriers in Saudi Arabia. Methods: This cross-sectional study was conducted on 506 randomly selected Saudi female secondary school teachers in Al Hassa, Saudi Arabia to assess their level of knowledge about risk factors and signs of CC in relation to perceived risk and to characterize CC screening compliance using a self-administered questionnaire. Results: Of the included female Saudi teachers, 65.4% and 63.4% were considered less-knowledgeable about CC risk factors and early signs and symptoms respectively. Only 17.2% reported being previously examined for CC. The majority of participants perceived themselves to be at an average or below average risk of CC. Residing in urban areas was the strongest predictor of CC screening (Odds ratio ‘OR’= 3.39; 95% confidence intervals ‘CI= 1.76-6.46; P=0.001). Awareness of risk factors was significantly associated with higher awareness of signs of CC (OR 2.5; 95% CI=, P=0.001). Exploratory factor analysis showed that personal fears (of screening being embarrassing) was the major factor that hindered CC screening with a high loading eigenvalue of 4.392, explaining 30.8% of the barriers toward utilization, followed by health care related factors. Conclusion: Secondary school teachers in Al Hassa, Saudi Arabia showed low perceived risk, poor awareness about risk factors, signs and symptoms of CC and limited uptake of screening practices. This underlines the need for education programs on CC targeting this group.     

The normal inferior turbinate: histomorphometric analysis and clinical implications

OBJECTIVE: To study the histological and morphometric features of the normal inferior turbinate. STUDY DESIGN: A prospective, nonrandomized study. METHODS: Sixteen specimens were removed at autopsy and during septoplasty operations, stained with H&E, and investigated microscopically. The soft tissue and bony elements were measured. Morphometric analysis included measurements of the relative proportions of the soft tissue constituents. RESULTS: The medial mucosal layer is thicker than the bone and the lateral mucosa; the difference between the mucosal layers is statistically significant. The inferior turbinate is almost exclusively covered with a pseudostratified ciliated columnar epithelium that houses more goblet cells on its lateral side. It has a well-defined basement membrane zone that is significantly thicker on the medial side. The main bulk of the inferior turbinate is the lamina propria that is built of loose connective tissue and superficially harbors an inflammatory cell infiltrate. The area fraction of glands in the lateral mucosa significantly exceeds that of the medial and inferior mucosal layers, whereas that of venous sinusoids varies significantly, with the greatest difference inferiorly. Decreased proportion of glands and an increase in venous sinusoids are associated with advanced age. The cancellous central bony layer is made of interwoven trabeculae and houses the major arterial supply of the turbinate. After the major arteries exit the bone, they lie in the deepest portions of the medial and lateral mucosal layers but are missing from the inferior layer. CONCLUSION: In-depth histomorphometric analysis can assist in developing new function-preserving approaches to turbinate surgery.     

CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin

CUB-domain-containing protein 1 (CDCP1) is a novel transmembrane molecule that is expressed in metastatic colon and breast tumors as well as on the surface of hematopoietic stem cells. In this study, we used multiparameter flow cytometry and antibodies against CDCP1 to analyze the expression of CDCP1 on defined hematopoietic cell subsets of different sources. In addition, CDCP1 expression on leukemic blasts and on cells with nonhematopoietic stem/progenitor cell phenotypes was determined. Here we demonstrate that a subset of bone marrow (BM), cord blood (CB), and mobilized peripheral blood (PB) CD34+ cells expressed this marker and that CDCP1 was detected on CD34(+)CD38- BM stem/progenitor cells but not on mature PB cells. Analysis of leukemic blasts from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia in blast crisis revealed that CDCP1 is predominantly expressed on CD34(+)CD133+ myeloid leukemic blasts. However, CDCP1 was not strictly correlated with CD34 and/or CD133 expression, suggesting that CDCP1 is a novel marker for leukemia diagnosis. Stimulation of CD34+ BM cells with CDCP1-reactive monoclonal antibody CUB1 resulted in an increased (approximately twofold) formation of erythroid colony-forming units, indicating that CDCP1 plays an important role in early hematopoiesis. Finally, we show that CDCP1 is also expressed on cells phenotypically identical to mesenchymal stem/progenitor cells (MSCs) and neural progenitor cells (NPCs). In conclusion, CDCP1 is not only a novel marker for immature hematopoietic progenitor cell subsets but also unique in its property to recognize cells with phenotypes reminiscent of MSC and NPC.