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D Dajee

Publications and source records attributed to D Dajee.

9 recordsLinked to original sources

Extracellular matrix interactions. 2: Extracellular matrix structure is important for growth factor localization and function.

The influence of extracellular matrix components and of extracellular matrix structure on in vitro cell growth was investigated in the UWOV2 (Pf), protein-free cell culture model. This cell line constitutively produces an ordered extracellular matrix in the absence of any exogenous protein or growth factor. Extracellular matrix from UWOV2 (Pf) cells was found to contain both transforming growth factor beta (TGF beta) and platelet-derived growth factor (PDGF), which were shown to have an autostimulatory role for UWOV2 (Pf) cell growth. Matrix structure was shown to be important for allowing expression of the functional activity of these two growth factors. In addition, a nonuniform distribution of PDGF, embedded within the matrix structure, was demonstrated by immunoelectronmicroscopy. Apart from these two well-defined growth factors, additional but as yet unidentified growth stimulatory factor(s) were extractable from UWOV2 (Pf) extracellular matrix. These investigations indicate the potential role of extracellular matrix both as a mechanism for concentrating as well as modulating the function of cellular growth factors.

3T3 Cells↗

Tissue platelet derived-growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancer.

In a study of plasma and tissue platelet derived growth factor (PDGF) concentration in patients with breast cancer, elevated levels of plasma PDGF were found in a significant proportion, 11/37 (30%), of patients. Sixteen patients (43%) had tumors which expressed PDGF-AA and 6 patients had tumors which in addition expressed the BB isoform of PDGF. All patients with elevated plasma levels of platelet derived growth factor had tumors which expressed the growth factor on immunohistochemical staining of tumor cells. Furthermore there was a significant correlation between plasma levels of platelet derived growth factor and the intensity of tissue staining. Patients with stage four breast cancer with tumors which were positive for platelet derived growth factor had a significantly lower response rate to chemotherapy as well as significantly shorter duration of survival. In addition, patients with stage four breast cancer who had elevated plasma PDGF levels had a significantly shorter survival. These results indicate that elevated plasma levels of platelet derived growth factor in patients with breast cancer are derived from the tumor cells and suggest that platelet derived growth factor may play a significant role in control tumor cell growth.

Adult↗

Lack of involvement of T-lymphocytes in the leukaemic population during prolonged chronic phase of Philadelphia chromosome positive chronic myeloid leukaemia.

Nine patients with prolonged (> 2 years) chronic phase chronic myeloid leukaemia (CML) were investigated for the presence of T-cell involvement in the leukemic clone. Pure populations of peripheral blood T-cell populations were obtained by culturing separated mononuclear cells in the presence of pokeweed mitogen and IL2, until cultures showed > 99% pure T-cells. Purified T-cells and bone marrow and peripheral blood hematopoietic precursors were analysed for the presence of bcr-abl mRNA transcripts following RNA extraction and message amplification using polymerase chain reaction. In none of the 9 patients was bcr-abl mRNA found in T-lymphocytes while in all cases such transcripts were found in bone marrow and peripheral blood hematopoietic cells. Failure to detect T-cell involvement in patients with prolonged chronic phase CML using techniques designed to enhance even low level involvement of these cell populations supports the view that acquisition of the Ph chromosome abnormality does not occur in the totipotent stem cells but in more committed precursor cell/s with multilineage capacity but which only rarely retain the capacity for T-cell differentiation.

Biomarkers, Tumor↗

Plasma lactoferrin content in neutropenic patients: effects of treatment with recombinant granulocyte-macrophage colony-stimulating factor.

Plasma lactoferrin content was measured before and after therapy with recombinant granulocyte-macrophage colony-stimulating factor in five patients with aplastic anaemia, six with myelodysplasia, and three with prolonged, severe, chemotherapy-induced neutropenia. Before therapy plasma lactoferrin content was uniformly low. However, patients with aplastic anemia and those with chemotherapy-induced neutropenia had a normal lactoferrin:neutrophil ratio. The low levels of plasma lactoferrin thus reflected the low granulocyte mass. On the other hand, patients with myelodysplasia also had reduced lactoferrin:neutrophil ratios, suggesting qualitative/quantitative abnormalities of neutrophil lactoferrin production. After treatment with granulocyte-macrophage colony-stimulating factor, plasma lactoferrin levels increased in patients with aplastic anemia and in those with chemotherapy-induced neutropenia who showed a neutrophil response to treatment. In these patients, the lactoferrin:neutrophil ratio became elevated, suggesting increased synthesis/release of lactoferrin from neutrophils. However, patients with myelodysplasia continued to show depressed lactoferrin:neutrophil ratios, even when there had been an increase in granulocyte count, suggesting persistent abnormalities of neutrophil lactoferrin production/release. The implications of these findings for treatment of neutropenic patients with granulocyte-macrophage colony-stimulating factors are discussed.

Adult↗

Effects of alpha-interferon on iron-related measurements in human subjects.

Subcutaneous administration of alpha-interferon to normal volunteers caused hypoferraemia and hyperferritinaemia. There was, however, no concomitant rise in other components of the acute-phase response, including the serum C-reactive protein value, the granulocyte count and the plasma lactoferrin concentration. In fact, the latter two dropped significantly. The hypoferraemic response could be prolonged when a second dose was given 48 hours after the initial one. This hypoferraemic response may play a role similar to that induced by interleukin-1, which limits the proliferation of invading micro-organisms or neoplastic cells. The present findings may therefore have relevance to the clinical mechanism of action of the interferons.

C-Reactive Protein↗

Plasma lactoferrin content in pregnancy.

Plasma lactoferrin concentration, leucocyte count, serum prolactin concentration and storage iron status were studied in 313 women at various stages of pregnancy. The mean serum iron value, percentage saturation of transferrin and geometric mean serum ferritin concentrations decreased as pregnancy progressed. In contrast, the total iron-binding capacity showed a highly significant increase with advancing gestation. Plasma lactoferrin concentration showed a mild progressive increase during pregnancy (peaking 29-32 weeks). The increase in lactoferrin concentration was, however, disproportionately small when compared with the concomitant pregnancy-related elevation in leucocyte count. The ratio of plasma lactoferrin concentration to leucocyte count therefore appeared to be abnormally low during pregnancy suggesting an acquired defect of lactoferrin release by leucocytes of pregnant women. It is unlikely that prolactin was the factor responsible for the reduced leucocyte release of lactoferrin. The lactoferrin:leucocyte ratio was already significantly reduced early in pregnancy at a time when prolactin concentration was relatively low. Furthermore, the correlation between prolactin concentration and both lactoferrin concentration and lactoferrin:leucocyte ratio was positive. Pregnancy appears to be associated with an acquired abnormality of leucocyte degranulation, the cause of which is not clear at present.

Adult↗