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M El-Sherbiny

Publications and source records attributed to M El-Sherbiny.

7 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↗
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↗
PubMed2003

Urokinase plasminogen activator receptor and soluble matrix metalloproteinase-9 in acute myeloid leukemia patients: a possible relation to disease invasion.

Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) and metalloproteinase (MMP) family play a crucial role in the matrix degradation and tissue remodeling process characteristic of malignant disorders. The receptor for urokinase plasminogen activator (uPAR) serves to localize and intensify the action of UPA and is expressed on the surface of malignant cells. Although the biological significance of MMP-9 and soluble urokinase receptor in growth and progression of lymphoid neoplasm is understood, its clinical significance in acute myeloid leukemia (AML) has not been fully elucidated. In this study, we determined the levels of soluble urokinase-type plasminogen activator receptor (suPAR), cellular uPAR and sMMP-9 in 43 newly diagnosed AML patients at diagnosis, before chemotherapy, and also studied 10 normal subjects served as a control group. After chemotherapy suPAR and MMP-9 were determined at remission and relapse. The levels of suPAR, cellular PAR were significantly higher (P= 0.001, 0.001) and MMP-9 was significantly lower (P=0.001) in AML patients at diagnosis as compared to controls. suPAR and MMP-9 levels were significantly lower in AML patients who achieved complete remission (CR) as compared to those who did not (P= 0.001 for both). Levels of suPAR and MMP-9 were significantly correlated to peripheral blood blast cells (r= 0.88, P= 0.001; r= 0.65, P= 0.001, respectively) and blast cell distribution ratio (BCDR, r= 0.84, P= 0.001; r=65, P= 0.001, respectively). suPAR, cellular PAR and MMP-9 were significantly higher in patients with extramedullary infiltration as compared with those without (P= 0.001, 0.001, <0.05). The suPAR, cellular uPAR, and MMP-9 levels were uneven in AML FAB subtypes being highest in M5(P<0.05 for all). MMP-9 and suPAR levels were correlated with the disease status. In AML survivors, MMP-9, cellular uPAR and suPAR were significantly lower as compared to non-survivors (P= 0.001 for all). In conclusion, MMP-9 and su PAR levels might be used as a marker for disease activity and may contribute to blast cell dissemination. MMP-9 and suPAR may be target molecules in the strategy of treatment of AML.

Adult↗
PubMed2002

Soluble hepatocyte growth factor (sHGF) and vascular endothelial growth factor (sVEGF) in adult acute myeloid leukemia: relationship to disease characteristics.

UNLABELLED: There is little understanding of the factors controlling the mobilization of blast cells from bone marrow to peripheral blood and tissues. The aim of this study was to evaluate the soluble hepatocyte growth factor (sHGF) and vascular endothelial growth factor (sVEGF) levels in newly diagnosed patients with acute myeloid leukemia (AML) and to correlate these levels with the clinico-pathological features. Sixty-three patients with AML and 15 normal controls were included in this study. The levels of sHGF and sVEGF were determined by enzyme linked immunosorbent assay at diagnosis and after remission induction chemotherapy. Our results revealed significantly increased plasma levels of sHGF and sVEGF at diagnosis when compared to both control and remission levels (P=0.000 for both). The sHGF and sVEGF levels differed between AML FAB subtypes (P=0.000). The highest concentrations were found in M5 followed by M4. SHGF and sVEGF were directly correlated with peripheral white cell counts (WBC) (r=0.836, P=0.000, r=0.718; P=0.000, respectively), but inversely correlated with blast cell distribution ratio (BCDR) (r=-0.785, P=0.000, r=-0.664, P=0.000, respectively). Moreover, both sHGF and sVEGF levels were significantly elevated in AML patients with extra-medullary infiltration as compared to those without (P=0.000, 0.006, respectively). The sHGF but not sVEGF levels were significantly elevated in patients who died compared to those who relapsed and to patients in complete remission (P=0.02, 0.08, respectively). Logistic regression analysis revealed that the sHGF level at diagnoses is a powerful predictor of the patient outcome, compared to sVEGF. IN CONCLUSION: our data support the hypothesis that angiogenic factors play a functional role in blast cell movement from the bone marrow to peripheral tissues. Assessment of sHGF at AML diagnosis is likely to be helpful in predicting patient outcome and selecting optimal therapeutic regimen.

Acute Disease↗
PubMed2002

L and E selectins in acute myeloid leukemia: expression, clinical relevance and relation to patient outcome.

UNLABELLED: The aim of this study was to assess circulating soluble L (sL) and soluble E (sE) selectins adhesion molecules in acute myeloid leukemia (AML) blasts in order to evaluate their clinical significance. Fifty patients with AML (4 M0, 8 M1, 16 M2, 5 M3, 7 M4, 6 M5, 4 M6) were included in this study. sL and sE selectins were evaluated at diagnosis, remission and in relapsed patients; whole membrane expression of L and E selectins by AML blast was investigated only at diagnosis. In addition, 15 normal persons were studied as a control group. sL and sE selectins were significantly higher in AML patients at diagnosis when compared to controls (P<0.01), but less at remission (P<0.01). Furthermore, elevated sL and sE selectin levels were detected in patients with AML at relapse. sE and sL selectins were significantly higher in AML patients with extramedullary infiltration as compared to patients without extramedullary disease (P<0.001). Membrane expression of L selectin was positive in 20% of AML patients. However, none of the patients showed significant E selectin expression. Patients with higher sE and sL selectins at diagnosis have high probability of relapse compared to those with normal levels (P<0.01 and <0.001, respectively). The overall relapse predictability of sE and sL selectins was 84%. Moreover, patients with higher sE and sL selectins levels had shorter event free survival than patients with lower levels (P<0.001 for both). The overall mortality prediction using sE, sL, and cellular L selectin was 96%. IN CONCLUSION: (1) AML blast cell express and release sL selectins but not sE selectin, (2) sE and sL selectins and cellular L selectin may be useful prognostic markers in evaluating AML patients at diagnosis.

Acute Disease↗
PubMed1996

Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity.

Humans chronically infected with schistosomiasis usually have impaired parasite Ag-specific lymphocyte proliferation and IFN-gamma production that may facilitate persistence of the parasite while producing little clinical disease. The mechanisms that contribute to the immunologic hyporesponsiveness in these patients remain undefined. IL-10 has been shown to exert an inhibitory effect on cell-mediated immunity. To determine whether endogenous IL-10 has a role in regulating parasite-specific anergy in schistosomiasis, neutralizing anti-IL-10 added to PBMC from Schistosoma haematobium patients' enhanced adult worm (SWAP)- or egg Ag (SEA)-driven lymphocyte proliferation and/or IFN-gamma production by 2- to >100-fold in 32 of 38 subjects. In contrast, anti-IL-10 failed to significantly augment the mycobacterial Ag, purified protein derivative (PPD)-driven lymphocyte proliferation, or IFN-gamma production in 9 or 10 of 14 individuals, respectively. SWAP or SEA triggered IL-10 release from PBMC of both patients and healthy individuals; however, CD4+ cells were a significant source of IL-10 only in infected subjects. PPD relative to SWAP induced fivefold less IL-10 release by CD4+ cells (p < 0.01). A possible mechanism whereby IL-10 suppressed Ag-specific T cell responses was demonstrated by the ability of SWAP and not PPD to suppress B7 expression on PBMC. Anti-IL-10 completely inhibited the parasite Ag-induced down-regulation of B7 expression. These studies indicate that IL-10 contributes to parasite Ag-induced T cell hyporesponsiveness observed in patients with chronic schistosomiasis hematobia.

Adolescent↗