MicroRNA-21 and MicroRNA-125b expression in skin tissue and serum as predictive biomarkers for psoriasis.

BACKGROUND/OBJECTIVE: Psoriasis is a chronic, inflammatory, and hyperproliferative skin disease. We have investigated the role of miR-21 and miR-125b in the development of psoriasis and atopic eczema and their relation with the severity of the diseases. METHODS: Participants included 40 psoriasis patients, 40 healthy controls, and 40 atopic eczema patients as a positive control group. In addition, analysis of mRNA expression of miR-125b and miR-21 was carried out utilizing quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) in serum samples and skin tissue. RESULTS: Our results have demonstrated that miR-21 was significantly overexpressed in the psoriatic and atopic eczema skin tissue and serum samples compared to controls, whereas miR-125b was significantly down-expressed in psoriatic and atopic eczema skin tissues and serum samples. There was a statistically significant positive correlation between the psoriasis area and severity index (PASI) score and miR-21 among the studied groups in both serum and tissue samples. In contrast, there was a statistically significant negative association between the miR-125b and PASI score. On the other hand, there was no significant relation between the extent of body surface area (BSA), intensity, and subjective symptoms using visual analog scale (VAS) of atopic eczema disease and miRNA-21 and miRNA-125b in both tissue and serum. CONCLUSION: In conclusion, miR-21 gene expression was significantly increased in psoriatic and atopic eczema skin samples and serum samples, whereas miR-125b was statistically lowered in psoriatic and atopic eczema patient samples. The miR-21 and miR-125b expression level has a possible predictive value as a marker for psoriasis severity but not for atopic eczema severity.

Clinical significance of EVI-1 gene expression and aberrations in patient with de-novo acute myeloid and acute lymphoid leukemia.

BACKGROUND: Acute leukemia is a common health problem in adults and children, however its exact molecular etiology is still unclear. METHODS: The expression of EVI-1 was assessed in the bone marrow of 178 de-novo acute leukemia patients (101 AML, 71 ALL and 6 MPAL), compared to 40 control subjects. EVI-1 gene aberrations were also assessed in 69 AML patients using Fluorescence in situ hybridization (FISH) technique. RESULTS: The expression of EVI-1 was significantly lower in ALL patients compared to control [0.177 (0.002-15.189) vs 0.953 (0.179-1.68); respectively, P = 0.009]. There was no significant difference between AML patients and control group [0.150 (0.0-641) vs 0.953 (0.179-1.68); respectively, P = 0.082]. The sensitivity, specificity, AUC of EVI-1 in ALL were (80.3 %, 60 % and 0.778; respectively, P = 0.009), and (67.3 %, 60 %, 0.667; respectively P = 0.082) in AML patients. One patient showed EVI-1 gene rearrangement in a complex karyotype and four patients showed EVI-1 amplification in hyperdiploid karyotypes. All patients with BCR-ABL fusion were EVI-1 over-expressers (P = 0.010). AML patients with EVI-1 low expression were positively associated with t(8;21)(q22;q22)RUNX1:RUNX1T1 fusion, favorable recurrent translocation, and low genetic risk (P = 0.037, P = 0.023, and P = 0.013; respectively). There was a significant association between low EVI-1 expression and prolonged overall survival (OS) in AML patients, while there was no significant association with the disease-free survival (DFS) (P = 0.048 and P = 0.419). There was no significant impact of EVI-1 expression on OS and DFS rates in ALL patients. CONCLUSION: EVI-1 expression could be a helpful diagnostic, prognostic, and predictive biomarker for acute leukemia especially in AML.

Evaluation of the relation between size of stone and its attenuation measured by Hounsfield units and the total laser energy required to fragment it.

BACKGROUND: Anticipating the total laser energy (TLE) of Holmium YAG laser required for ureteroscopic (URS) lithotripsy is essential to guide urologists in selecting the optimal fiber size. This study aimed at evaluating the relationship between stone size and stone attenuation measured by HU as predictors for the TLE during the procedure. METHODS: We conducted an observational prospective cohort study of patients undergoing URS lithotripsy at the Urology department of Ain Shams University Hospitals from September 2018 to September 2019 with the use of a holmium YAG laser as the lithotripsy method. Patients' demographic and clinical characteristics, stone location, stone size, stone attenuation measured by HU from the non-contrast CT, TLE, and procedure time were recorded. Data were analyzed using Jamovi software (version 2.0 for macOS). RESULTS: Forty patients were included in the study (22 males and 18 females) with a mean age of 57.8 years. The mean stone size was 9.8 mm3, the mean HU was 858.8 units, and the mean TLE was 3.5 KJ. Both stone size and stone attenuation measured by HU were positively correlated with TLE (r = 0.81 and 0.84, respectively; p < 0.001 for both). Further, regression analysis showed that both variables could significantly predict the TLE (ß = 0.001 and 0.71, respectively). CONCLUSIONS: Both stone attenuation, as measured by HU, and stone size positively correlate with TLE required for URS lithotripsy. Therefore, both HU and stone size can predict the TLE, which will be helpful to guide the urologist in selecting the optimal fiber size for the procedure.

Estrogen Receptor Gene Polymorphism as a Possible Genetic Risk Factor for Treatment Response in ER-Positive Breast Cancer Patients.

Estrogen receptor-α (ESR1) single nucleotide polymorphisms (SNPs) have been related to breast cancer (BC) susceptibility. In this retrospective study we investigated ESR1 SNPs in association with survival and treatment response in BC patients. Seven ESR1 SNPs were genotyped using TaqMan probe assay in 100 formalin-fixed paraffin embedded blocks of Egyptian ER+BC patients. Log-binomial regression was used to assess the association of 5 ESR1 SNPs with relative risk of non-response to adjuvant-hormonal treatment. We compared the performance of five machine learning classification models for prediction of treatment response. Predictive models were developed using rs1801132, rs2228480, and rs9322354 that were significantly associated with increased risk for non-response along with the relevant clinical features. Survival analysis was performed to detect prognostic significance of ESR1 SNPs in ESR+BC patients. rs1801132 (C), rs2228480 (A), and rs9322354 (G) minor alleles significantly increased the risk of non-response to tamoxifen by more than 81, 84, and 117%, respectively, in ER+BC patients on anthracycline/anthracycline-taxanes-based chemotherapy. Multivariate Cox regression survival analysis revealed that rs1801132 (C) and large tumor size were independent predictors for poor survival outcome in ER+BC. The best response predictive model was a combination random forest, K-nearest neighbor, and decision tree having an area under the curve of 0.94 and an accuracy of 90.8%. Our proposed predictive model based on ESR1 rs1801132, rs2228480, and rs9322354 SNPs represents a promising genetic risk stratification for selection patients who could benefit from tamoxifen therapy in such a way that might facilitate personalized medicine required to improve ER+BC patients' outcome.

Single-nucleotide polymorphism of ADRß2 and CDKN1B genes in Egyptian patients with coronary artery in-stent restenosis.

BACKGROUND: In-stent restenosis is a common complication after percutaneous coronary intervention. The purpose of the current study is to look for associations of genetic variation in adrenergic beta-2 receptor (ADRß2), and cyclin-dependent kinase inhibitor 1B (CDKN1B) genes in patients diagnosed with in-stent restenosis (ISR) after percutaneous coronary intervention in the Egyptians. METHODS: Polymorphisms in ADRß2 and CDKN1B were determined using PCR-restriction fragment length polymorphism in 200 Egyptian patients who underwent coronary angioplasty and stent placement of whom 100 patients developed ISR. RESULTS: We found that the GG genotype of ADRß2 and CC genotype of CDKN1B were more likely to develop restenosis after stenting (odds ratio = 3.7 and 3.2; P = 0.001, respectively). Our study considered that male sex, diabetes, obesity, bare-metal stents type of implanted stents, longer stents, GG genotype of ADRß2, and CC genotype of CDK1B were significant independent predictors for ISR. CONCLUSION: our results indicate that ADRß2 (rs1042713) and CDKN1B (rs36228499) could be associated with the development of ISR in Egyptians.

Investigating the Retrofitting Effect of Fiber-Reinforced Plastic and Steel Mesh Casting on Unreinforced Masonry Walls.

Unreinforced masonry (URM) is one of the most popular construction materials around the world, but vulnerable during earthquakes. Due to its brittle nature, the URM structures may lead to a possible collapse of the wall of a building during earthquake events causing casualties. In the current research, an attempt is made to enhance the seismic capacity of URM structures by proposing a new innovative composite material that can improve the shear strength and deformation capacity of the URM wall systems. The results revealed that the fiber-reinforced plastic having high tensile and shear stiffness can significantly increase in-plane as well as out-of-plane bending strength of the URM wall. It was recorded that the bending moment of the prism increased up to 549.5% by increasing the bending moment from 490 N*mm to 3183 N*mm per mm deflection of prism upon using glass fibers. Moreover, the ductility ratio amplified up to 5.73 times while the stiffness ratio increased up to 4.16 times with the aid of glass fibers. Since the material used in this research work is low cost, easily available, and no need for any skilled labor, which is economically good. Therefore, the URM walls retrofitted with fiber-reinforced plastic is an economical solution.

Hyperthermic Intraperitoneal Chemotherapy as a Treatment for Epithelial Ovarian Cancer.

Treatment by cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has been an option for selected patients with peritoneal carcinomatosis. This study aims to evaluate the impact of HIPEC in epithelial ovarian cancer (EOC). A retrospective observational cohort study including 48 EOC patients treated and followed up between 2012 and 2016. Thirty-seven cases were treated by CRS only, while 11 cases were treated by CRS and HIPEC. The study was performed at National Cancer Institute (NCI)-Cairo University. There was no statistically significant difference regarding overall survival or disease-free survival between the group of EOC patients treated by CRS only and the one treated by CRS and HIPEC. Presence of ascites and histological types (serous/non-serous) were the significant independent variables related to overall survival. Presence of ascites was the only independent variable associated with a significant relation to disease-free survival. No statistically significant impact of HIPEC in treatment of EOC was found in this study.

Serum TSLP is a potential biomarker of psoriasis vulgaris activity.

BACKGROUND: The proallergic cytokine, thymic stromal lymphopoietin (TSLP) may synergize with T cell-derived CD40 ligand (CD40L) to allow IL-23 production in patients with psoriasis. IL-23 is a central cytokine that mediates the inappropriate immune reaction in patients with psoriasis. OBJECTIVE: The aim of the study was to correlate serum level of TSLP with psoriasis severity. METHODS: The study was carried out on 53 patients with psoriasis. They were divided into mild, moderate, and severe according to PASI score. The patients' ages ranged from 10 to 62 years. The patients included 29 males and 24 females. A total of 53 healthy subjects with matched age and sex served as control group. Blood samples were collected from the venous blood of the patients and control subjects then the serum was separated. The serum samples were immediately frozen at -20°C. Serum TSLP was measured by Sandwich Enzyme-linked Immunosorbant Assay (ELISA). RESULTS: There was a statistically very highly significant increase (p<0.001) in serum TSLP levels among the case group (1042.7±812.93) compared to the control group (314.21±220.78). There was also a statistically very highly significant increase (p<0.001) in serum TSLP levels with increased psoriasis severity estimated by PASI score. CONCLUSION: In this study, we found that serum TSLP is elevated in psoriasis patients and is correlated with disease severity.

Myeloid Sarcoma.

Hematological malignancies can manifest as extramedullary soft tissue masses in relatively rare cases. The rarity of it causes a diagnostic and therapeutic challenge. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. The tumor displays high myeloperoxidase expression, hence the color green, and is called chloroma. It most commonly appears in lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. Immunohistochemistry shows CD68-KP1 as the most commonly expressed marker, then myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozyme, CD34, terminal deoxynucleotidyl transferase, CD56, CD61, CD30, glycophorin A, and CD4. Different chromosomal abnormalities including MLL rearrangement, t(8; 21), monosomy 7, trisomy 8, trisomy 11, trisomy 4, inversion (16), monosomy 16,16q deletion, 5q deletion, and 20q deletion were reported. Most of the literature about MS are case reports and small retrospective studies, thus there is limited clinical knowledge of the cases and their presentation and management plans. Here, we provide a review of what has been reported in the literature about MS in the light of our experiences.

Crosstalk between liver-related microRNAs and Wnt/ß-catenin pathway in hepatocellular carcinoma patients.

BACKGROUND AND STUDY AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with highest incidence in Asia and Africa. MicroRNAs (miRNAs), a class of non-coding single stranded RNA, which not only post transcriptionally regulate gene expression but also respond to signaling molecules to affect cell functions such as Wnt/ß-catenin signaling specifically in HCC. The goal of this study is to investigate the crosstalk between Wnt/ß-catenin signaling proteins and microRNAs expression in HCC patients. PATIENTS AND METHODS: Fresh tissue samples of 30 primary HCC patients and 10 control subjects were included. Expression level of 13 different miRNAs (miR-10a- miR-106b- miR-99a- miR-148a- miR-125b- miR-30e- miR-183- miR-155- miR-199a- miR-199a3p- miR-24- miR-122 and miR-215) were examined using real-time PCR assay. Five proteins involved in the Wnt/ß-catenin pathway (ß-catenin, APC, c-myc, survivin and cyclin D1) were analysed by immunohistochemistry technique. The correlation between miRNAs expression levels with protein expressions was assessed. RESULTS: Up-regulation of miR-155 and miR-183 was reported in HCC patients compared to normal controls and this up-regulation was significantly correlated with liver cirrhosis in the case of miR-155 (p<0.05) referring to their oncogenic activity. Down-regulation was observed for 11 miRNAs in HCC indicating their tumour suppression activity. MiRNA-10a, miR-30e, miR-215, miR-125b and miR-148a were significantly correlated with the expression of important players in Wnt/ß-catenin pathway including ß-catenin, APC and c-myc (p<0.05). Detailed analysis revealed that miR-215 is associated with the grade of the disease and miR-125b is associated with HCV infection. CONCLUSION: Collectively, our data showed potential role of miR-10a, miR-30e, miR-215, miR-125b and miR-148a as important mediators in HCC progression. Furthermore, their association with Wnt/ß-catenin cascade proteins could be exploited to develop new therapeutic target strategies in HCC.

Human myeloid inhibitory C-lectin: a highly specific and stable acute myeloid leukemia marker.

The prognosis of acute myeloid leukemia (AML) is poor because of relapses occurring on conventional chemotherapy. The distinction between leukemic and normal stem cells relies on the expression of antigen combinations defining leukemia-associated immunophenotypes (LAIPs), which are absent or extremely infrequent in normal bone marrow. However, LAIPs are very different from patient to patient and are not necessarily stable over the course of the disease. Accordingly, we addressed the applicability of human myeloid inhibitory C-lectin (hMICL) by flow cytometry as a specific leukemic myeloid stem cell marker for the diagnosis of AML in CD34+ and CD34- cases and evaluated the stability of hMICL during the course of the disease. hMICL expression was assessed in 78 bone marrow aspirate specimens obtained from AML patients at diagnosis (n = 40), complete remission (CR) (n = 28), and relapse (n = 10). AML patients at diagnosis were compared to 20 newly diagnosed acute lymphoblastic leukemia (ALL) patients and 20 healthy controls. hMICL was reevaluated in CR and relapse specimens. hMICL was expressed in 100% AML patients at diagnosis (mean ± standard deviation [SD], 60.3 ± 19.9%), both CD34+ and CD34- , but not in ALL (mean ± SD, 3.3 ± 1.9%) or healthy controls (mean ± SD, 3.4 ± 2.6%) (P < .001). hMICL median fluorescence intensity ratio was higher in AML (mean ± SD, 15.9 ± 11.7) compared to ALL (mean ± SD, 4.5 ± 1.4) and healthy controls (mean ± SD, 4.4 ± 1.6) (P < .001). hMICL was expressed in all studied AML morphologic subtypes. Preserved stable expression of hMICL was found in CR and relapse specimens with no antigen loss. hMICL is a robust pan-AML-associated antigen with excellent diagnostic impact, extreme specificity to AML blasts, and stability throughout the course of the disease. hMICL could be incorporated into the routine flow cytometry setting within the initial diagnostic work-up and follow-up of AML.

Circulating DNA in Egyptian Women with Breast Cancer.

The commonest cancer in Egyptian females occurs in the breast cfDNA is a non-invasive marker for tumor detetion and prognostic assessment in many types of cancer including breast cancer. This study aimed to assess the role of cfDNA and its fragmentation pattern in breast cancer prognosis and treatment response. Forty female patients with malignant breast tumors and a comparable group of healthy blood donors were enrolled prospectively. cfDNA levels and fragmentation patterns were investigated after cfDNA extraction, gel electrophoresis and gel analysis. The percentage of breast cancer patients positive for cfDNA (92.5%) was significantly higher than that of controls (55%). Also, mean concentration of cfDNA was significantly higher than in the control group (<0.05). Most Her-2 positive patients had long cfDNA fragments, this being significant as compared to Her-2 negative patients (<0.05). Metastasis was also positively linked to significantly higher cfDNA (<0.05) and the mean cfDNA integrity index was significantly higher in non-responders compared to treatment responders (<0.05). In conclusion, both qualitative and quantitative aspects of cfDNA and its different fragments in breast cancer patients could be related to prognosis, metastasis and treatment response. Long cfDNA fragments could be particularly useful for prediction purposes.

Prevalence of the frequency of JAK2 (V617F) mutation in different myeloproliferative disorders in Egyptian patients.

BACKGROUND AND OBJECTIVES: Detection of chromosomal abnormalities in myeloproliferative disorders is important for proper diagnosis of these disorders. This study has investigated the presence of JAK2 mutation (V617F) in Egyptian patients with myeloproliferative disorders referred to National Cancer institute, Cairo University. METHODS: The study involved 110 cases of Philadelphia negative Myeloproliferative diseases (MPDs), 70 cases with Polycythemia Vera (PV), 24 cases with Essential Thrombocytosis (ET) and 16 cases with Idiopathic Myelofibrosis (IMF) and 20 cases as a control group which represented as; (10 cases with secondary erythrocytosis, 1 case with reactive thrombocytosis, 4 cases as normal control and 5 as Philadelphia positive Chronic Myeloid Leukemia cases), they were collected from National Cancer Institute (NCI) over 3 years. We used ARMS technique for mutation detection. RESULTS: The frequency of the V617F JAK2 mutation was highest in patients with PV where 56 out of 70 cases (80%) carried the mutation, followed by ET with 6 of 24 (25) and IMF with 2 of 16 (12.5%) . None of the cases with secondary Erythrocytosis, reactive thrombocytosis, the normal controls or Philadelphia positive CML cases carried the mutation. CONCLUSIONS: Our results are concordant with international published results for detection of this mutation. It is unequivocal now that V617F is met in many MPDs especially PRV. Finding this mutation in those patients is thought to have a big impact on the diagnosis and treatment of these disorders.