Search PubMed⌕ Search

Biomedical subjects

E Marshall

Publications and source records attributed to E Marshall.

At least 163 records · Page 9Linked to original sources
PubMed1998

Mode of adsorption and orientation of an extracellular matrix protein affect its cell-adhesion-promoting activity.

Cell adhesion to extracellular matrix contributes to the organization of tissues and modulates cell behavior. In conventional cell adhesion assays, plastic wells are coated with matrix proteins and assayed for their adhesion-promoting activity. We show here that factors such as sample composition, coating buffers, and manufacturers' plastic treatment markedly affect cell adhesion to the extracellular matrix protein laminin-5 (Ln-5). These factors were shown to affect adsorption efficiency as determined by measuring total adsorbed protein with a polyclonal anti-Ln-5 antiserum. They also influence the availability of the epitope for an adhesion-blocking anti-Ln-5 monoclonal antibody, suggesting that coating conditions affect the orientation of Ln-5. Generally, cell adhesion correlates more strongly with the availability of the epitope for the adhesion-blocking antibody than with total adsorbed Ln-5. Our data further indicate that cell adhesion to other matrix proteins may be influenced by similar factors. Adding Ln-5 samples to plastic wells that had been precoated with non-adhesion-blocking anti-Ln-5 antibodies made cell adhesion independent of factors such as sample composition, coating buffers, and source of plastic. Thus, the control of adsorption efficiency and orientation of extracellular matrix proteins is essential for creation of reliable and reproducible conditions in cell adhesion assays.

Adsorption↗
PubMed1998

A randomized phase-II study of BB-10010 (macrophage inflammatory protein- 1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy.

BB-10010 is a variant of the human form of macrophage inflammatory protein-1alpha (MIP-1alpha), which has been shown in mice to block the entry of hematopoietic stem cells into S-phase and to increase their self-renewal capacity during recovery from cytotoxic damage. Its use may constitute a novel approach for protecting the quality of the stem cell population and its capacity to regenerate after periods of cytotoxic treatment. Thirty patients with locally advanced or metastatic breast cancer were entered into the first randomized, parallel group controlled phase II study. This was designed to evaluate the potential myeloprotective effects of a 7-day regimen of BB-10010 administered to patients receiving six cycles of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) chemotherapy. Patients were randomized, 10 receiving 100 microgram/kg BB-10010, 11 receiving 30 microgram/kg BB-10010, and nine control patients receiving no BB-10010. BB-10010 was well-tolerated in all patients with no severe adverse events related to the drug. Episodes of febrile neutropenia complicated only 4% of the treatment cycles and there was no difference in incidence between the treated and nontreated groups. Studies to assess the generation of progenitor cells in long-term bone marrow cultures were performed immediately preceding chemotherapy and at the end of six dosing cycles in 18 patients. Circulating neutrophils, platelets, CD 34(+) cells, and granulocyte/macrophage colony-forming cell (GM-CFC) levels were determined at serial time points in cycles 1, 3, and 6. The results showed similar hemoglobin and platelet kinetics in all three groups. On completion of the six treatment cycles, the average pretreatment neutrophil levels were reduced from 5.3 to 1.7 x 10(9)/L in the control patients and from 4.3 to 1.9 and 4.5 to 2.5 x 10(9)/L in the 30/100 microgram/kg BB-10010 groups, respectively. Relative to their pretreatment values, 50% of the patients receiving BB-10010 completed the treatment with neutrophil values significantly higher than any of the controls (P = .02). Mobilization of GM-CFC was enhanced by BB-10010 with an additional fivefold increase over that generated by chemotherapy alone, giving a maximal 25-fold increase over pretreatment values. Bone marrow progenitor assays before and after this standard regimen of chemotherapy indicated little long-term cumulative impairment to recovery from chemotherapy. Despite the limited cumulative damage to the bone marrow, which may have minimized the protective value of BB-10010 during this regimen of chemotherapy, better recovery of neutrophils in the later treatment cycles with BB-10010 was indicated in a number of patients.

Adult↗