cholecalciferol and Hodgkin-Disease

To provide further understanding of humoral hypercalcemia in Hodgkin's disease (HD) the authors describe the clinical features and laboratory investigation of three patients recently treated at Massachusetts General Hospital. All were middle-aged men who presented with symptomatic hypercalcemia which led to a diagnosis of bulky intraabdominal HD. None had evidence of bone involvement or hyperparathyroidism. In the two cases tested 1,25(OH)2D3 was elevated at the time of diagnosis. These characteristics are remarkably similar to those of ten patients with HD and probable humoral hypercalcemia described in the literature. The diagnosis of HD was supported in Cases 1 and 3 by genomic blot analysis which showed no evidence of T-cell or B-cell tumor origin. In an in vitro assay, primary tumor medium from Case 1 stimulated dose-dependent bone resorption which was not entirely ascribable to 1,25(OH)2D3. The authors conclude that humoral hypercalcemia in HD predominantly affects males of middle age, that intraabdominal bulky disease is common, and that hypercalcemia appears to be mediated by tumor related production of 1,25(OH)2D3 in concert with a second factor.

Topics: Adult; Aged; Antigens, Differentiation; Antigens, Surface; Cholecalciferol; DNA, Neoplasm; Hodgkin Disease; Humans; Hypercalcemia; Male; Middle Aged; Paraneoplastic Endocrine Syndromes

Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin's lymphoma (HL), a malignant pathology of B cell origin, in vitro.. Immunofluorescence staining showed the expression of VDR by primary Hodgkin's (H) and Reed-Sternberg (RS)-HRS-tumor cells in HL histological sections. Western blot analyses revealed expression of VDR in the HL cell lines Hs445, HDLM2, KMH2, and L428. One-way analysis of variance (ANOVA) on data obtained from water-soluble tetrazolium 1 (WST-1) cell proliferation assay showed decreased cell growth in HDLM2 and L428, 72 h after treatment with 10 µM of either VD3 of VDAs. Western blot analyses showed that treatment of L428 cells with the VDAs (calcipotriol and EB1089) resulted in modest increases in nuclear accumulation of VDR (nuVDR) compared to either dimethyl sulfoxide (DMSO) or VD3 treatments. nuVDR for DMSO control and VD3 was comparable. These results suggest that VD3 or VDAs may affect growth of HL.

Topics: Calcitriol; Cell Line, Tumor; Cell Proliferation; Cholecalciferol; Dimethyl Sulfoxide; Gene Expression Regulation, Neoplastic; Hodgkin Disease; Humans; Receptors, Calcitriol; Vitamin D

The histogenesis of the Reed-Sternberg (R-S) cell in Hodgkin's disease is uncertain. Some have suggested that it is a derivative of the monocyte/macrophage lineage. To explore this possibility, we have searched for the presence of mRNA corresponding to the c-fms proto-oncogene, a marker for cells of the monocyte/macrophage lineage which encodes the colony-stimulating factor-1 receptor. In situ hybridization was performed using a single-stranded c-fms complementary RNA (cRNA) to probe R-S cells, lymphocytes, and eosinophils from touch imprints of a lymph node from a 12-year-old boy with mixed cellularity Hodgkin's disease in relapse. The probe was synthesized from a bacterial plasmid, pSM3, into which a portion of v-fms (a viral-derived oncogene) had been inserted. The plasmid was linearized with a restriction endonuclease, and 35S-labeled cRNA was synthesized from the DNA template using T3 RNA polymerase and the nucleotide analog [35S]UTP. Positive control hybridizations were obtained with the human acute promyelocytic cell line HL-60 induced to monocyte differentiation. R-S cells were clearly negative, supporting a cell of origin other than the monocyte. In situ hybridization is a potentially powerful method for exploring differentiation and assigning cell lineage in R-S cells.

Topics: Child; Cholecalciferol; Eosinophils; Hodgkin Disease; Humans; Male; Nucleic Acid Hybridization; Proto-Oncogene Mas; Proto-Oncogenes; Receptors, Cell Surface; Receptors, Colony-Stimulating Factor; RNA, Messenger; Tumor Cells, Cultured