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Biomedical subjects

A W Hamburger

Publications and source records attributed to A W Hamburger.

7 recordsLinked to original sources

The nature of cells generating human myeloma colonies in vitro.

Freshly explanted human myeloma cells formed colonies of monoclonal plasma cells in soft agar in the presence of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. The medium showed peak activity at a dilution of 1:4. 2-mercaptoethanol or monothioglycerol was necessary for colony formation. Other thiols tested were ineffective in promoting colony growth. Colony-forming cells adhered to nylon wool, but not glass beads or plastic dishes. The presence of E-rosetting cells was not required for myeloma colony formation. Antibody prepared against a human myeloma cell line, RPMI 8226, reduced colony formation. These studies demonstrate the usefulness of this bioassay for determining functional properties of the myeloma colony-forming cell.

Antibodies

A new basis for treatment of multiple myeloma.

In order to get a better understanding of tumor biology, prognostic factors and approaches to treatment, total body tumor cell number, cell kinetics and drug sensitivity have been studied in a series of patients with multiple myeloma. We found that the presenting tumor mass stage was inversely proportional to survival, but did not predict drug sensitivity. Patients with both a high tumor cell mass and a large proliferative compartment of tumor cells had a particularly poor prognosis. Studies of myeloma stem cells in agar culture showed individual patterns of drug sensitivity with a correlation between in vitro sensitivity to melphalan, adriamycin, and BCNU, with in vivo sensitivity to these same classes of agents. Use of such measurements may permit selection of useful new drugs as well as an individualized basis for treatment of multiple myeloma.

Carmustine

Immunoproliferation and cancer: a common macrophage-derived promoter substance.

It is suggested that a common proliferative factor is required for the growth of clones of both antigen-triggered B lymphocytes and carcinogen-triggered epithelial cells, and that the common growth-promoting substance is secreted by macrophages which have originally differentiated in support of the immune response. This macrophage-derived factor seems to be antigenically distinct from granulocyte colony-stimulating factor. Identification of the macrophage-derived clonal proliferative factor could provide new understanding of the proliferation of clones of immunocytes and neoplastic cells.

Animals

Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs.

With a direct in vitro tumor-colony assay developed to measure sensitity of human-tumor stem cells to anticancer drugs, we performed 32 retrospective or prospective clinical studies in nine patients with myeloma and nine with ovarian cancer treated with standard agents that were tested in vitro. The results were clearly correlated (P is less than 0.00001). Unique patterns of sensitivity and resistance to the six drugs tested were observed for individual patients. In eight cases of myeloma and three of obarian carcinoma in vitro sensitivity corresponded with in vivo sensitivity whereas in one case of myeloma it did not. In vitro resistance correlated with clinical resistance in all five comparisons in myeloma and all 15 in ovarian cancer. We conclude that this assay shows sufficient promise to warrant larger-scale testing to determine its efficacy for selection of new agents and individualized cancer chemotherapy regimens.

Antineoplastic Agents

Primary bioassay of human tumor stem cells.

A simple method has been developed to support human tumor stem cell colony growth in soft agar. The technique appears suitable for culture of a variety of neoplasms of differing histopathology. Tumor stem cell colonies arising from different types of cancer have differing growth characteristics and colony morphology. This bioassay should be suitable for clinical studies of effects of anticancer drugs or irradiation on human tumor stem cells.

Adenocarcinoma