ABSTRACT
There are two well-described syndromes caused by tumor production of parathyroid hormone-related peptide (PTHrP), namely osteolytic bone disease associated with breast cancer and humoral hypercalcemia of malignancy (HHM) that occurs with or without bone metastasis. Both syndromes have been shown experimentally to be inhibited by neutralizing antibodies to PTHrP. In a search for small-molecule inhibitors of PTHrP production or effects, we have identified guanine-nucleotide analogs as compounds that inhibit PTHrP expression by human tumor cells associated with these syndromes. We show in nude athymic murine models that these compounds reduce PTHrP-mediated osteolytic lesions associated with metastatic human breast-cancer cells as well as the degree of hypercalcemia caused by excessive PTHrP production by a squamous-cell carcinoma of the lung. These results suggest that the PTHrP gene promoter may be a suitable target for treating the skeletal effects of malignancy.
Subject(s)
Guanine Nucleotides/pharmacology , Guanosine/analogs & derivatives , Neoplasms/metabolism , Paraneoplastic Endocrine Syndromes/prevention & control , Peptide Hormones/metabolism , Animals , Bone Neoplasms/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cytokines/biosynthesis , Female , Gene Expression/drug effects , Guanosine/pharmacology , Humans , Hypercalcemia/metabolism , Hypercalcemia/prevention & control , Mice , Mice, Nude , Neoplasm Transplantation , Neoplasms/drug therapy , Neoplasms/genetics , Osteolysis/metabolism , Osteolysis/prevention & control , Paraneoplastic Endocrine Syndromes/genetics , Paraneoplastic Endocrine Syndromes/metabolism , Parathyroid Hormone-Related Protein , Peptide Hormones/genetics , Promoter Regions, Genetic , Thioguanine/pharmacology , Thionucleosides/pharmacology , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
Ectopic corticoadrenal tissue is not a very uncommon finding during orchiopexy in children. The causes can be found in the period of organ development and gonadal migration (spermatic cord). From 1986 to 1990, we have performed 88 orchiopexy procedures in the Urology Service of "San Antonio Abad de Gallarate" Hospital. Only one case (1.13%) of juxta-funicular corticoadrenal ectopia has been observed. The aim of the present study is to determine the correct surgical approach to this incidental finding during surgery of the inguinal canal in pediatric patients.
