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.

Galanin-like peptide (GALP) neurons participate in the metabolic control of reproduction and are targets of insulin and leptin regulation. Phosphoinositide 3-kinase (PI3K) is common to the signaling pathways utilized by both insulin and leptin. Therefore, we investigated whether PI3K signaling in neurons expressing GALP plays a role in the transcriptional regulation of the GALP gene and in the metabolic control of luteinizing hormone (LH) release. To this end, we deleted PI3K catalytic subunits, p110α and p110β via conditional gene targeting (cKO) in mice (GALP-p110α/β cKO). To monitor PI3K signaling in GALP neurons these animals were also crossed with Cre-dependent FoxO1GFP reporter mice. Compared to insulin-infused control animals, the PI3K-Akt-dependent FoxO1GFP nuclear exclusion in GALP neurons was abolished in GALP-p110α/β cKO mice. We next used food deprivation to investigate if the GALP-neuron specific ablation of PI3K activity affected the susceptibility of the gonadotropic axis to negative energy balance. Treatment did not affect LH levels in either sex. However, a significant genotype effect on LH levels was observed in females. In contrast, no genotype effect on LH levels was observed in males. A sex-specific genotype effect on hypothalamic GALP mRNA was observed, with fed and fasted GALP-p110α/β cKO males having lower GALP mRNA expression compared to WT fed males. Finally, the effects of gonadectomy and steroid hormone replacement on GALP mRNA levels were investigated. Compared to vehicle-treated mice, steroid hormone replacement reduced MBH GALP expression in WT and GALP-p110α/β cKO animals. In addition, within the castrated and vehicle-treated group and compared to WT, LH levels were lower in GALP-p110α/β cKO males. Double immunofluorescence using GALP-Cre/R26-YFP mice showed androgen and estrogen receptor co-localization within GALP neurons. Our data demonstrate that GALP neurons are direct targets of steroid hormones and that PI3K signaling regulates hypothalamic GALP mRNA expression and LH levels in a sex-specific fashion.

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.

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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.