Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: correlation with cytokines.

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N=100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean=30.7, SEM=2) decreased and IL-6 levels (mean=4.4, SEM=1) increased with age as did marrow fat (mean=1.2mmfat/g, SEM=0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.

Surgery following initial treatment of ovarian carcinoma: restaging (second-look) and palliative operations.

Of 73 patients treated for ovarian carcinoma at the University of Nebraska Medical Center between 1976 and 1982, 37 underwent a second operative procedure following initial surgery. A total of 14 had a second look following complete clinical response, 11 had intestinal diversion, and 12 underwent other procedures. Second-look surgery proved useful in evaluating patients in clinical remission and directing subsequent management. The majority of patients whose operations were for persistent or recurrent disease had short survival. However, such surgery helps occasional patients and should be considered when circumstances warrant.

Treatment of breast cancer with oral four-drug chemotherapy.

Seventy patients with advanced metastatic breast cancer were treated with an oral drug regime of prednisone, cytomel, cytoxan, and methotrexate. One half of the cases (50%) had a response. There were complete remissions in 7%, partial remissions in 27%, and arrests in 16%. The median duration of remissions was 8+ months. There was no significant difference in response between patients with predominant visceral or bone disease nor between pre- and post-menopausal women. One third of non-hormonally responsive patients responded to this treatment. Side effects consisted predominantly of glucocorticoid changes, including cushinoid facies and weight gain. The program was relatively bone marrow sparing. This drug regime is very convenient and safe to give on an outpatient basis.

Adriamycin, mitomycin C, and 5-fluorouracil in combination for advanced colorectal adenocarcinoma previously treated with 5-fluorouracil.

Twenty-one patients with progressing colorectal carcinoma previously treated with 5-FU were given a combination of 5-FU, adriamycin, and mitomycin C in an attempt to produce an objective response. No response was observed; 24% of patients had an arrest of their disease for a median of 18 weeks. 5-FU, adriamycin, and mitomycin C in combination failed to produce a response in patients with colorectal carcinoma previously treated with 5-FU.