Biomedical subjects

Salah Aref

Publications and source records attributed to Salah Aref.

8 recordsLinked to original sources

PubMed2006

Cyclin D1 expression in acute leukemia.

BACKGROUND: Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the involvement of cyclin D1 in acute leukemia. PATIENTS AND METHODS: In this study, we analyzed the expression of cyclin D1 at protein level in, 40 newly diagnosed patients with acute myeloid leukemia (AML), 10 patients with acute lymphoblastic leukemia (ALL), and 11 normal controls using flow cytometry. RESULTS: The expression of cyclin D1 was not significantly different in AML group as compared to normal controls. On the other hand, over expression of cyclin D1 was evident in ALL group (4/10) as compared to that in healthy control. The ALL cases with cyclin D1 over expression were significantly correlated to blast cell counts in the peripheral blood and bone marrow (BM) but not with hemoglobin level, WBC, and platelets count. The ALL group with lymphadenopathy and organomegaly express significantly higher cyclin D1 over expression as compared to those without. CONCLUSION: The biological value of cyclin D1 over expression might be different in AML and ALL.

Adult↗

PubMed2005

Soluble VEGF/sFLt1 ratio is an independent predictor of AML patient out come.

Angiogenesis is the formation of new blood vessels and is controlled by a balance between positive and negative angiogenic regulatory factors. Soluble vascular endothelial growth factor receptors 1,2 (Flt-1, KDR) are the negative counterpoint to the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulator in human angiogenesis. In the present work, we tested the differential prognostic relevance of soluble vascular endothelial growth factor (VEGF), their receptors 1 (Flt-1), 2 (KDR), and the ratio between sVEGF/sFlt-1 in 43 patients with acute myeloid leukemia (AML). sVEGF and its soluble receptors were assessed using an ELISA. Soluble VEGF, sFLT-1 and sKDR concentration levels were significantly higher in AML patients at diagnosis when compared to the levels in normal controls. sVEGF, sFlt1 and the sVEGF/sFlt1 ratio were significantly higher in non responders when compared to responders (P < 0.001 for all). However, there was no significant difference regarding sKDR levels (P > 0.05). sVEGF, the sVEGF/sFlt1 ratio but not sFlt1 and sKDR levels were significantly elevated in those who did not survive, when compared to survivors. sVEGF, sFlt1 levels were significantly correlated to WBC counts (R = 0.93, P = 0.000, R = 0.56, P = 0.000, respectively); bone marrow blast cell counts (R = 0.92, P = 0.000; R = 56, P = 0.000, respectively); peripheral blood blast cell counts (R = 0.91, P = 0.000; R = 0.52, P = 0.000, respectively); sKDR was only correlated to peripheral blood blast cell counts(R=0.37,P=0.014). Cox regression analysis results with sVEGF, sFlt1, sKDR, sVEGF/sFlt1 ratio suggest that the most important predictor for AML outcome is the sVEGF/sFlt1 ratio. In conclusion, sVEGF/sVEGF ratio is independent predictor of AML patient out come, and its significance should be assessed when considering antiangiogenic therapy.

Biomarkers, Tumor↗

PubMed2005

Soluble P-selectin levels in diabetes mellitus patients with coronary artery disease.

UNLABELLED: Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of coronary heart disease. Platelets play a significant role in coronary artery disease. Soluble P-selectin is an index of platelets activation. In this study, Soluble P-selectin levels were measured by ELISA in the peripheral blood of 55 diabetic patients with coronary artery disease [21 acute myocardial infarction (AMI), 20 with unstable angina (UA), 14 with stable angina (SA)], 20 patients with diabetes mellitus without coronary artery disease (DM without), and 10 healthy controls. Soluble P-selectin level was significantly higher in patients with AMI (M+/-SD; 239.3+/-13.0 ng/ml), than those with UA (141.5+/-15.2 ng/ml), SA (92.1+/-7.7 ng/ml), DM without (89.8+/-7.1 ng/ml), and healthy control (86.1+/-4.5 ng/ml) (P < 0.001). In patients with US, sP-selectin was found to be significantly elevated as compared to the SA, DM without and control group. sP-selectin was not significantly different in DM without as compared to healthy controls. The sP-selectin levels was correlated to the duration of diabetes mellitus(R=0.33, P=0.03 ). Moreover, sP-selectin level was significantly higher in AMI patients with recurrent anginal attack as compared to that in those with single attack Multivariate analysis revealed that sP-selectin level at presentation had high adverse influence on coronary artery insult compared to healthy LDL cholesterol level, and the degree of hypertension. IN CONCLUSION: Plasma levels of soluble P-selectin were increased in patients with AMI, and UA compared to patients with SA and normal controls. Measurement of soluble P-selectin may be helpful marker of impending coronary artery insult in diabetic patients.

Biomarkers↗

PubMed2004

Accelerated neutrophil apoptosis in neutropenic patients with hepatosplenic schistosomiasis is induced by serum Fas ligand.

Neutropenia in patients with hepatosplenic (HS) schistosomiasis may stem from enhanced neutrophil apoptosis. However, the molecular mechanism of neutrophil apoptosis has not been clearly defined. Neutrophils harvested from neutropenic patients with HS schistosomiasis (n = 25), non-neutropenic patients with hepatointestinal (HI) schistosomiasis (n = 10), and age- and sex-matched healthy control subjects (n = 10) were examined for the degree of apoptosis after incubation with autologous sera. Neutrophil apoptosis was quantified by flow cytometry through determination of propidium iodide nuclear staining and confirmed by DNA gel electrophoresis at 0 time (fresh neutrophil), 4 and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic serum, with and without anti-Fas ligand antibody. Serum Fas ligand levels were assessed in sera of patient groups and healthy controls by ELISA. Compared with normal controls and HI, HS group demonstrated greater neutrophil apoptosis in the presence of autologous serum (P < 0.01, < 0.05, respectively). Furthermore, compared with normal neutrophils exposed to heterologous normal serum, those exposed to heterologous neutropenic serum exhibited higher apoptosis rates (P < 0.01). The apoptotic effect of neutropenic sera is attenuated by anti-Fas ligand. Fas expression was significantly higher in HS group as compared to both HI and normal healthy controls (P < 0.05). Serum Fas ligand levels were significantly higher among HS group as compared to both HI and control groups (P < 0.01 for both). Neutrophil apoptosis was not correlated to the size of spleen in HS group. In conclusion, the rate of neutrophil apoptosis is accelerated in neutropenic HS schistosomiasis. These findings suggest that enhanced neutrophil apoptosis demonstrated in HS patients is triggered by soluble Fas ligand, which is mostly derived from spleen.

Adult↗

PubMed2004

Enhanced neutrophil apoptosis in neutropenic patients with hepatosplenic schistosomiasis: evidence of serum Fas ligand.

Enhanced neutrophil apoptosis has been reported in neutropenic hepatosplenic schistosomiasis. The shortening of neutrophil survival via apoptosis may explain the neutropenia that occur in these patients. However, the regulation of neutrophil apoptosis in hepatosplenic schistosomiasis has not been clearly defined. Neutrophils harvested from neutropenic patients with hepatosplenic (HS) schistosomiasis, (n=25), non-neutropenic patients with hepatointestinal (HI) schistosomiasis (n=10), and age-/gender-matched healthy control subjects (n=10) were incubated with autologous serum. Neutrophils apoptosis was quantified by flow cytometry through determination of propidium iodide nuclear staining and confirmed by DNA gel electrophoresis at 0 (i.e. fresh neutrophils), 4 and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic serum, with and without anti-Fas ligand antibody. Fas expression was assessed in fresh neutrophils using flow cytometry. Compared with normal healthy neutrophils, and HI neutrophils, neutropenic neutrophils demonstrated greater apoptosis in the presence of autologous serum (P<0.01, 0.05, respectively). Furthermore, compared with normal neutrophils exposed to heterologous normal serum, those exposed to heterologous neutropenic serum exhibited higher apoptosis rates ( P<0.01). Moreover, anti-Fas L antibody attenuated the neutropenic serum-induced neutrophil apoptosis in normal neutrophils. Fas expression was significantly higher in the neutropenic group when compared to both HI and normal healthy controls (P<0.05). In addition, Fas expression by neutrophils was paralleled by high neutrophil apoptosis. On the other hand, neutrophil apoptosis was not correlated to the size of spleen in neutropenic group. In conclusion, the rate of neutrophil apoptosis is accelerated in patients with neutropenic hepatosplenic schistosomiasisis. These findings suggest that the enhanced neutrophil apoptosis that occurs in neutropenic HS patients is triggered by a serum factor, which is mostly a Fas ligand.

Adult↗

PubMed2004

Chlorambucil plus theophylline vs chlorambucil alone as a front line therapy for B-cell chronic lymphatic leukemia.

B-cell chronic lymphatic leukemia (B-CLL) has emerged as a prototype of malignancies characterized by a defective apoptosis that leads to a progressive accumulation of monoclonal B cells in the bone marrow, lymphoid tissues and peripheral blood. Chlorambucil, an aromatic derivative of nitrogen mustards, is the most common treatment for chronic lymphatic leukemia (CLL). The response rate with its use is 40 to 60%, with 3 to 10% only of patients achieving a complete response (CR). To improve response rates, chlorambucil has been combined with steroids or other agents. Theophylline, a methylxanthine commonly used as a treatment for asthma, has been shown to induce apoptosis in CLL cells both in vitro and in vivo. Chlorambucil induces apoptosis in CLL cells as well and synergy has been shown between the two drugs without affecting the normal B lymphocytes. The aim of this work was to evaluate the potential utility of this combination as a therapeutic modality for B-CLL. A total of 210 B-CLL patients were recruited and randomized to receive either chlorambucil in an oral dose of 0.1 mg/kg/day indefinitely (109 patients) or chlorambucil 0.1 mg/kg/day plus theophylline 200 mg bid, orally (101 patients). The main endpoints were overall survival from the time of randomization, disease status after 9 months and time to disease progression. After 9 months of treatment, clinical and hematological remission was achieved in 14 patients (12.8%) in the chlorambucil group, compared to 26 (25.7%) in the chlorambucil plus theophylline group (P value 0.01). Partial remission was observed for 38 patients (34.9%) in the chlorambucil group and 36 patients (35.7%) in the chlorambucil plus theophylline group. In patients treated with chlorambucil alone, the median progression-free survival (PFS) was 30 months and in patients treated with chlorambucil plus theophylline it was 44 months. Probabilities of PFS at 24 months for the chlorambucil-treated patients were 59% and 85% for the chlorambucil plus theophylline-treated patients. The difference was statistically significant (P = 0.006). The 3-year and 5-year overall survival rates were, respectively 75% and 38% in the chlorambucil group as opposed to 76% and 46% in the chlorambucil plus theophylline group. The median survival time was 55 months in the chlorambucil group and 56 months in the chlorambucil plus theophylline group. Forty-nine patients died in the chlorambucil group compared to 44 patients in the chlorambucil plus theophylline group (P = 0.371). The trial has demonstrated that adding theophylline to the standard treatment of B-CLL significantly increases effectiveness of treatment in terms of tumor response and time to disease progression. It could not improve the overall survival. Treatment with theophylline does not compromise quality of life or add significant toxicity. As newer drugs have recently become available for treating patients with CLL like fludarabine, further trials are needed to evaluate the effect of combining theophylline with these drugs.

Adult↗

PubMed2003

Syndecan-1 in multiple myeloma: relationship to conventional prognostic factors.

Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from the cell surface may contribute to myeloma cell proliferation and dissemination and influence the prognosis in patients with multiple myeloma (MM). In order to test this hypothesis, we have evaluated syndecan-1 expression on the surface of malignant plasma cells and soluble forms of syndecan-1 in the serum of 25 newly diagnosed MM patients by flow cytometry and immunosorbent assay. Soluble syndecan-1 levels were significantly higher in MM as compared to controls (P<0.001). Cellular and soluble syndecan-1 was significantly inversely correlated (r=-0.89, P<0.001). The soluble syndecan-1 was significantly higher in non- responders to chemotherapy when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.001). In contrast, cellular syndecan-1 expression was significantly lower in non- responders when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.05). The levels of soluble syndecan-1 increased from stage I through stage II to stage III, whereas cellular syndecan-1 expression were decreased from high levels in stage III down to a low in stage I, with a statistically significant difference (P<0.01, P<0.05, respectively). There was a significant positive correlation between soluble syndecan-1 and plasma cell count (r=0.079, P<0.001), beta2 microglobulin (r=0.85, P<0.001), serum creatinine (r=0.84, P<0.001), C-reactive protein (r=0.082, P<0.001), alkaline phosphatase (r=0.58, P<0.05) and serum calcium (r=0.77, P<0.01) and a negative correlation with hemoglobin level (r=-0.78, P<0.01), platelets count (r=-0.82, P<0.01) and Albumin level (r=-0.64, P<0.01). Cox regression analysis using soluble syndecan-1 at mean-2SD of the controls could correctly classify patient outcome in 84.0%. The addition of beta2 microglobulin to soluble syndecan-1 increased the predictability of the patients' outcome to 96.7%. We conclude that soluble syndecan-1 levels are negatively correlated to the cellular form and that high levels of soluble syndecan-1 and lower expression of cellular syndecan-1 at diagnosis are negative prognostic factors. Assessment of soluble syndecan-1 and beta2 microglobulin at diagnosis is an independent prognostic system for MM.

Biomarkers, Tumor↗

PubMedDate not supplied

Thrombopoietin (TPO) levels in hepatic patients with thrombocytopenia.

Thrombocytopenia is a common problem complicating the course of liver disease. One of the postulated mechanisms in chronic liver disease is impaired production of the hormone, thrombopoietin (TPO). The aim of present study was to evaluate the role of TPO on the occurrence of thrombocytopenia. Serum TPO levels was determined by ELISA in 40 patients with liver disease (11 seropositive with hepatitis C; 10 with mixed liver cirrhosis; 19 with bilharzial hepatic fibrosis), plus 14 normal healthy subjects as a control group. The sTPO levels were unevenly distributed among the liver disease subgroups being the highest in the group with HCV (median 1232.0, range 154.7-2042.0 pg/ml) followed by the mixed cirrhosis group (556.5; 342.0-1497.0 pg/ml) and lowest among the bilharzial hepatic fibrosis group (130.0; 22.0-204.0 pg/ml) (P<0.01). While sTPO levels in HCV and cirrhotic group were significantly higher when compared to the control group (97.0; 19.0-377.0 pg/ml), those in the Bilharzial hepatic fibrosis group were not significantly elevated (P>0.05). There is significant negative correlation between sTPO levels and spleen size (R=-0.3, P=0.043); but there was no correlation with platelet count (R=0.09, P>0.05). In addition, sTPO levels were significantly higher in patients with platelet counts >or=60x10(9)/l as compared to those with platelet counts <60x10(9)/l (P=0.04). Using the receiver operating curve (ROC) at sTPO cut off value >or= vs. <368 ng/ml, most of HCV and cirrhotic patients had higher sTPO levels (81.8 and 80.0%, respectively), while all Bilharzial hepatic fibrosis group (100%) had lower sTPO levels. In conclusion, sTPO levels had no role in the occurrence of thrombocytopenia in liver disease patients and other factors appear to be more important. It also appears that the mechanism controlling sTPO levels might be different in cirrhotic patients compared to Bilharzial hepatic fibrosis patients.

Adult↗