The 1,25-dihydroxy-16-ene-23-yne-vitamin D3 [1,25(OH)2-16-ene-23-yne-D3] is a vitamin D analog that is very potent in inhibiting proliferation and inducing differentiation of myeloid leukemic cells in vitro. Also, 1,25(0H)2-16-ene-23-yne-D3 is 300 times less active in mediating intestinal calcium absorption and bone calcium mobilization as compared to 1,25-dihydroxyvitamin D3 [1,25(OH)2D31, the physiologically active metabolite. Furthermore, 1,25(OH)2-16-ene-23-yne-D3 is 10-25 times less potent than 1,25(OH)2D3 in causing hypercalcemia in BALB/c mice injected intraperitoneally (i.p.) every other day (q.o.d.) for 6 weeks. We explored the therapeutic potential of 1,25(OH)2-16-ene-23-yne-D3 by developing and using the following three leukemia models. Chemotherapy has improved survival of some cancer patients, but alternative approaches are still needed for many malignancies. Phenotypically, most cancer cells have a block in their ability to undergo terminal differentiation; the cells remain in the proliferative pool providing them a growth advantage over their normal counterparts. Induction of terminal differentiation of these cancer cells may be a therapeutic approach. We have used acute myelogenous leukemia as a prototype to study induction of differentiation and inhibition of proliferation of cancer (1). These results prompted us to develop several in vivo models of acute myelogenous leukemia. We found that WEHI 3BD+, a murine myeloid leukemia line (8), can be induced by either 1,25(OH)2D3 or 1,25(OH)2-16-ene-23-yne-D3 to lose clonal proliferative capacity as the cell terminally differentiates. We injected these cells into syngeneic BALB/ c mice; these mice developed and died of leukemia. Treatment of these mice with 1,25(OH)2-16-ene-23-yne-D3 considerably prolonged their survival and possibly even cured some mice.
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This study compares the effects of the cancer experience on various aspects of marital and sexual functioning (e.g., communication, emotional support, body image, sexual satisfaction and frequency) for two groups of long‐term cancer survivors (testicular cancer and Hodgkin's disease) and their spouses. Comparisons between the two patient groups showed significantly more survivors of Hodgkin's disease than testicular cancer reporting the emergence of special issues and changes in the marital relationship. No differences emerged between the spouse groups on sexual functioning variables; however, spouses of survivors of Hodgkin's disease were more likely than spouses of survivors of testicular cancer to report the development of special issues and communication difficulties. A substantial proportion of both survivor groups disclosed negative changes in body image and sexual frequency. Majorities of both survivors and spouses acknowledged that the illness had drawn them closer together. When representative marital/sexual functioning variables were used to predict Family Environment Scale (FES) scores for survivors and for spouses, changes in the spouse's importance, influence of the illness on the relationship, and changes in sexual frequency emerged as significant predictors. The clinical significance of long‐term changes in marital and sexual functioning for the couple and the need for therapeutic interventions are discussed.
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