Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2−negative (p < 0.001), estrogen receptor−positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.

Assessment of apheresis platelets during 5 days of storage: A National Cancer Institute, Cairo University experience.

BACKGROUND: Platelet transfusion therapy is widely used to prevent hemorrhage in patients with thrombocytopenia and platelet disorders. The platelet concentrate (PC) quality is affected by increased storage time, as reflected in the decreased number of platelets, morphological changes, and impaired functions. This study aimed to analyze the impact of 5 days storage on platelets count and the expression of CD63, and Annexin V as activation markers during PC storage. METHODS: Fifty PCs collected from single donors were tested for platelet count on days 0, 3, and 5 using a Sysmex blood counter. CD61, CD63, and Annexin V expression was analyzed by a multicolor Navios flow cytometer. RESULTS: There was a significant decrease in platelet count during 5 days of storage. There was a direct relationship between storage time and degree of platelet activation. CD63 had almost double increased expression on day 5 than day 3. Annexin V showed significantly increased expression on day 3 with minor differences between days 3 and 5. CONCLUSION: According to standard blood bank conditions, PC stored for 5 days showed a degree of in vitro activation as evidenced by CD63 and Annexin V expression, may lead to reduced therapeutic efficacy. Flow cytometry monitoring platelet activation in PC offers a better understanding of the changes during PC storage and may help improve platelet products.

Pomegranate extract ameliorates renal ischemia/reperfusion injury in rats via suppressing NF-κB pathway.

Inflammation and oxidative stress are the major pathways involved in ischemia-reperfusion (I/R)-induced renal injury. This study was designed to evaluate the potential effect of pomegranate against I/R-induced renal injury. I/R injury was induced in nephrectomized rats by unilateral occlusion of the left renal pedicle for 45 min followed by 24 h of perfusion. Pomegranate succeeded to decrease serum levels of creatinine, potassium, and urea nitrogen, along with increasing creatinine clearance. Pomegranate also decreased I/R-induced changes in histopathological examination. Pomegranate attenuated the renal inflammatory response reflected by the suppression of nuclear factor κB p65 DNA binding activity, the upregulation of inhibitory protein kappa B-alpha mRNA expression, the downregulation of mRNA and protein expression of tumor necrosis factor α, in addition to the reduced myeloperoxidase activity and mRNA expression. Additionally, pomegranate attenuated oxidative stress likely through the modulation of lipid peroxidation and antioxidant levels reflected by the decreased MDA content and the increased glutathione level and superoxide dismutase activity. Results confirm the potential protective effect of pomegranate against I/R-induced renal injury through its anti-inflammatory and anti-oxidant effects mediated through the upregulation of inhibitory protein kappa B-alpha, the inhibition of NF-κB activity, and the associated TNF-α release, neutrophil infiltration, and oxidative stress.

Mortality of dialysis patients in Qatar: A retrospective epidemiologic study.

BACKGROUND: End-stage kidney disease (ESKD) patients on maintenance renal replacement therapy (RRT) have far lower life spans than those of the general population. No previous studies have been performed to assess the mortality of dialysis patients in the State of Qatar. We designed this study to assess the mortality of dialysis patients in Qatar and the impact of dialysis modality. METHODS: All chronic ambulatory dialysis patients (both on hemodialysis (HD) and peritoneal dialysis (PD) between 2014 and 2016) were included in the study, whereas patients undergoing dialysis for less than 3 months were excluded. We reviewed patients' demographics, comorbidities, and general laboratory investigations through our electronic record system and collected and analyzed them. We identified patients who died during that period and compared them to those who survived. We performed a subanalysis for HD versus PD patients who died. RESULTS: The total number of deceased dialysis patients was 164, with an overall crude mortality rate of 6.4%. They were significantly older than those who survived (p = 0.0001). The mortality rate was significantly higher in female than in male patients (51.2% and 38.9%, respectively) (p = 0.004) but significantly lower in PD than HD patients (1.36%, PD; 5.0%, HD; p = 0.007). It was also significantly higher in natives than in the expats (60.3% and 39.6%, respectively) (p = 0.0008); however, no significant differences were noted between deceased natives and expats in most demographic and laboratory characteristics. The most common cause of patient death was CVD (62 patients, 37.8%), followed by sepsis (44 patients, 26.8%). Diabetes, cerebrovascular accident, and dyslipidemia were more common in HD deceased patients than in PD patients (80.6%, 47%, and 59%, respectively, in HD patients vs 68.5%, 42%, and 31%, respectively, in PD patients). Albumin and potassium levels in deceased PD patients were significantly lower than in HD patients (p = 0.001). CONCLUSION: Our study found that the high-risk population had a significant mortality, which was higher in HD than PD patients. This is the first study to look at these outcomes in Qatar. We identified multiple mortality associated factors, such as comorbid conditions and old age. We believe that improving treatment and close monitoring for comorbid conditions in the dialysis population might improve survival.

Isotretinoin Induced Hyperlipidemia and Impact of Leptin Gene rs 7799039 Polymorphism in Safety of Acne Patients.

BACKGROUND: Acne vulgaris (AV) is a chronic inflammatory disease that affects the pilosebaceous unit. Leptin (LEP) gene polymorphisms is associated with higher risk of multiple disorders. Insulin-like growth factor-1 (IGF-1) exerts comedogenic effect by stimulating the sebaceous glands. Isotretinoin is an effective oral therapy for AV with many side effects including hyperlipidemia and increased serum levels of liver enzymes. PURPOSE: To evaluate the impact of LEP gene rs7799039 polymorphism in acne patients' clinical response lipid profile and liver enzymes following 6 months oral isotretinoin therapy in Egyptian AV patients. METHODS: One hundred eligible AV patients received 0.5 mg/kg oral isotretinoin for 6 months. Patients' demographics and clinical data were obtained. Body mass index (BMI), lipid profile, liver enzymes and IGF-1 were measured at baseline and after 6 months of therapy. Genotyping was done for LEP gene rs 7799039. RESULTS: Six month administration of oral isotretinoin in Egyptian AV patients is associated with significantly elevated aspartate transaminase (AST) in CC and AC genotypes (P<0.001). Significant alanine aminotransferase (ALT) elevation was observed in CC, AC and AA genotypes (P <0.001, 0.004, 0.002, respectively). Total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) were elevated significantly P<0.001) in the three genotypes. IGF-1 was decreased significantly in CC and AC genotypes (P<0.001). CC genotype is associated with highest response (P<0.001). CONCLUSION: LEP rs7799039 gene had an impact on the clinical response, lipid profile and liver enzymes in AV patients treated with oral isotretinoin. LEP rs7799039 CC genotype is predicted to be the treatment candidate for 6 month oral isotretinoin.

Association of CXCR4 Expression and Clinical Outcome in Different Subsets of De Novo Acute Myeloid Leukemia Patients.

BACKGROUND: Acute myeloid leukemia is a heterogeneous group of diseases characterized by the uncontrolled proliferation of hematopoietic stem cells (HSCs) and progenitor cells with a reduced capacity to differentiate into mature cells. CXC chemokine receptor (CXCR4) and its ligand stromal derived factor-1 (SDF-1/CXCL12) are important players involved in cross-talk between leukemia cells and the bone marrow (BM) microenvironment. The aim to study the association between the immunohistochemical CXCR4 expression and the clinical outcome of AML in adult Egyptian patients. METHODS: Fifty-eight patients suffering from AML were recruited for this study, with an age range from 18 to 60 years and presenting from January 2013 to March 2017. All patients were subjected to complete blood count, BM aspiration, immunophenotyping, BM trephine biopsy, immunohistochemical staining with CXCR4 McAb and cytogenetics when feasible. RESULTS: CXCR4 was widely expressed (55.2%) among the studied patients. There was a significant relationship between CXCR4 and patients' outcomes. Fifteen (71.4%) patients who died were CXCR4 positive. The estimated mean time until death among CXCR4 negative cases was 37.6 ± 4.04 months which was longer than that of CXCR4 positive cases who had mean of 20.04 ± 4.9 months p = 0.016. The risk for death among CXCR4 positive cases was higher than CXCR4 negative cases with hazard ratio (HR) = 2.147 (p = 0.048). CONCLUSIONS: These results suggest that CXCR4 was expressed in a subset of AML patients and was associated with poor prognosis. CXCR4 expression appears to be an independent prognostic factor for survival in a heterogeneous group of AML patients.

CD200 Expression in Diagnostic and Prognostic Assessment of Mature B Cell Lymphophoproliferative Neoplasms

Background: Multiparameter flow cytometry is a useful tool for diagnostic evaluation of mature B-cell neoplasms (MBN). Recently, it has been shown that assessment of CD200 expression may improve the distinction between chronic lymphocytic leukemia (CLL; CD200 positive) and mantle cell lymphoma (MCL; CD200 negative), but any potential as a prognostic marker for CLL remains to be established. Materials and methods: This cross sectional study was conducted on sixty-seven patients newly diagnosed as having mature B-cell lymphoproliferative disorders Levels of CD 200 in lymphoma cells were assessed. Results: CD200 was consistently expressed in CLL and hairy cell leukemia B cells, but not in MCL cells. Heterogeneous expression was noted in other CD5 positive Non-Hodgkin lymphomas. High CD200 expression (≥50%) was associated with a higher CD5, 19 and CD23 expression, older age, higher TLC and absolute lymphocyte count, hepatomegaly, splenomegaly and a higher Rai stage. There were no significant correlations between CD200 expression and response to treatment. Conclusion: CD200 could be of high value in distinguishing CLL, MCL, and atypical CLL. CD200 expression can also be of prognostic and therapeutic value in CLL cases.

Influence of inhaled beclomethasone and montelukast on airway remodeling in mice.

This study examined the effect of montelukast and beclomethasone on airway remodeling in murine model of asthma. Mice were sensitized by i.p. injection of ovalbumin (OVA) on days 0 and 14, and then challenged by nebulization of 1% OVA 3 days/week for 6 or 10 weeks. Results of 6-week OVA-challenged group showed moderate inflammation, but the 10-week OVA-challenged group exhibited mild inflammation. The OVA challenge (6 and 10 weeks) exhibited marked airway fibrosis, illustrated by significant increase in goblet cell hyperplasia and epithelial thickness, increased lung content of collagen and transforming growth factor-ß(1), together with a decrease in nitric oxide production; also, there was an increase in bronchoalveolar lavage fluid level of interleukin-13. Administration of montelukast or beclomethasone before each OVA challenge was capable of restoring most of the measured parameters to near normal levels. Inhalation of beclomethasone has a similar role in airway remodeling as montelukast, but its effects in regulating inflammatory changes is less pronounced than montelukast.