2011
A single-arm multicenter proof-of-concept study of denosumab to treat hypercalcemia of malignancy in patients who are refractory to IV bisphosphonates.
Hu M, Gucalp R, Insogna K, Glezerman I, Bone H, Jaccard A, Misiorowski W, Yu B, Yeh H. A single-arm multicenter proof-of-concept study of denosumab to treat hypercalcemia of malignancy in patients who are refractory to IV bisphosphonates. Journal Of Clinical Oncology 2011, 29: tps245-tps245. DOI: 10.1200/jco.2011.29.15_suppl.tps245.Peer-Reviewed Original Research
1990
Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase
Brown G, Morris C, Mitnick M, Insogna K. Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase. Journal Of Bone And Mineral Research 1990, 5: 1037-1041. PMID: 1964358, DOI: 10.1002/jbmr.5650051007.Peer-Reviewed Original ResearchConceptsSerum calciumBone resorptionHumoral hypercalcemiaCarbonic anhydrase inhibitorsNephrogenous cyclic AMP excretionCyclic AMP excretionMean serum calciumOsteoclastic bone resorptionDrug-treated animalsLeydig cell tumorMechanism of actionUrine phosphorusUrine calciumSerum phosphorusCell tumorsAcetazolamide treatmentHypercalcemiaSignificant fallFisher ratsObserved hypercalcemiaResorptionDirect inhibitionSignificant riseMalignancyRats
1989
Humoral Hypercalcemia of Malignancy: The Role of Parathyroid Hormone-related Protein
Insogna K. Humoral Hypercalcemia of Malignancy: The Role of Parathyroid Hormone-related Protein. Endocrinology And Metabolism Clinics Of North America 1989, 18: 779-794. PMID: 2673773, DOI: 10.1016/s0889-8529(18)30366-9.BooksConceptsMalignancy-associated hypercalcemiaHumoral hypercalcemiaRenal tubular calcium reabsorptionParathyroid hormone-related proteinIntense bone resorptionTubular calcium reabsorptionTumor-derived factorsCentral pathogenic roleHormone-related proteinTumor-derived tissueCalcium reabsorptionBone resorptionPathogenic roleCommon causeHypercalcemiaExperimental modelHHMDevelopment of antiseraMalignancyPTHrPAnalysis of mRNAAntiserumPreliminary studySyndromeAmino-terminal polypeptideNative and a synthetic analogue of the malignancy-associated parathyroid hormone-like protein have in vitro transforming growth factor-like properties.
Insogna KL, Stewart AF, Morris CA, Hough LM, Milstone LM, Centrella M. Native and a synthetic analogue of the malignancy-associated parathyroid hormone-like protein have in vitro transforming growth factor-like properties. Journal Of Clinical Investigation 1989, 83: 1057-1060. PMID: 2537846, PMCID: PMC303783, DOI: 10.1172/jci113947.Peer-Reviewed Original ResearchConceptsGrowth factor-like propertiesParathyroid hormone-like proteinHormone-like proteinNRK-49F cellsParaneoplastic syndromeHumoral hypercalcemiaLatter hormoneHuman tumorsPhysiological actionsPTHHuman dermal fibroblastsSignificant increaseSoft agarDisplay actionsDermal fibroblastsSynthetic peptidesSynthetic analoguesHypercalcemiaMalignancySyndromeTumorsUnique primary structure
1988
Isolation of 16,000-Dalton Parathyroid Hormone-Like Proteins from Two Animal Tumors Causing Humoral Hypercalcemia of Malignancy*
Weir EC, Burtis WJ, Morris CA, Brady TG, Insogna KL. Isolation of 16,000-Dalton Parathyroid Hormone-Like Proteins from Two Animal Tumors Causing Humoral Hypercalcemia of Malignancy*. Endocrinology 1988, 123: 2744-2751. PMID: 3197642, DOI: 10.1210/endo-123-6-2744.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAmino Acid SequenceAmino AcidsAnimalsDogsHumansHypercalcemiaLeydig Cell TumorMaleMolecular Sequence DataMolecular WeightNeoplasm ProteinsNeoplasmsParathyroid Hormone-Related ProteinRatsRats, Inbred F344Sequence Homology, Nucleic AcidSweat Gland NeoplasmsTesticular NeoplasmsConceptsPTH-like proteinAnimal tumorsPTH-like peptideHumoral hypercalcemiaParathyroid hormone-like proteinSynthetic human PTHLeydig cell tumorHuman PTH-like peptideHormone-like proteinTransplantable animal tumorsCell adenocarcinomaCanine proteinCell tumorsResponsible mediatorsHuman PTHImmunoradiometric assayTumorsHuman tumorsAdenylate cyclaseLike peptidesAnal sacHypercalcemiaBone cellsMalignancyPotent activatorRenal phosphate transport in humoral hypercalcemia of malignancy
Sartori L, Insogna KL, Barrett PQ. Renal phosphate transport in humoral hypercalcemia of malignancy. American Journal Of Physiology 1988, 255: f1078-f1084. PMID: 2974244, DOI: 10.1152/ajprenal.1988.255.6.f1078.Peer-Reviewed Original ResearchConceptsLeydig cell tumorHumoral hypercalcemiaOnset of hypercalcemiaTumor-bearing animalsPhosphate metabolismRenal phosphate transportCortical brush border membraneParathyroid hormoneDaily injectionsTumor transplantationCell tumorsDichloromethylene diphosphonateMicrovillus membrane vesiclesRenal cortexRenal cortical brush border membraneSodium-dependent phosphate uptakeFisher ratsAnimal modelsPersistent impairmentHypercalcemiaLow-affinity systemBrush border membraneSpecific decreaseMalignancyRatsIdentification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy.
Ikeda K, Mangin M, Dreyer BE, Webb AC, Posillico JT, Stewart AF, Bander NH, Weir EC, Insogna KL, Broadus AE. Identification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy. Journal Of Clinical Investigation 1988, 81: 2010-2014. PMID: 2454953, PMCID: PMC442656, DOI: 10.1172/jci113551.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCloning, MolecularHumansHypercalcemiaKidney NeoplasmsMolecular Sequence DataNeoplasm ProteinsNucleic Acid HybridizationParaneoplastic SyndromesParathyroid HormoneParathyroid Hormone-Related ProteinPoly ARNARNA, MessengerRNA, NeoplasmSequence Homology, Nucleic AcidTranscription, GeneticConceptsPTH-like peptideParathyroid hormone-like peptideAnimal tumorsHumoral hypercalcemiaHormone-like peptideSyndrome of HHMVariety of humanHuman PTH-like peptideSimilar histological typeHistological typeHuman PTHTumor typesTumorsHHMHypercalcemiaMalignancySyndromeMessenger RNAMRNAWide spectrumHumansPeptidesMammalian speciesRNAPTHIn vitro adenylate cyclase-stimulating activity predicts the occurrence of humoral hypercalcemia of malignancy in nude mice.
Weir EC, Insogna KL, Brownstein DG, Bander NH, Broadus AE. In vitro adenylate cyclase-stimulating activity predicts the occurrence of humoral hypercalcemia of malignancy in nude mice. Journal Of Clinical Investigation 1988, 81: 818-821. PMID: 3343341, PMCID: PMC442531, DOI: 10.1172/jci113389.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityNude miceHumoral hypercalcemiaSyndrome of HHMMean tumor sizeReliable predictive markersHuman renal carcinoma cell linesCyclase-stimulating activityCell linesRenal carcinoma cell linesCultured tumor cellsHypercalcemic animalsTumor sizeCarcinoma cell linesPredictive markerBone resorptionTumor extractsTumor cellsMiceNormocalcemic animalsPotential mediatorsHypercalcemiaHHMCell assayMalignancySYNTHETIC AND PARTIALLY-PURIFIED ADENYLATE CYCLASE-STIMULATING PROTEINS FROM TUMORS ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY INHIBIT PHOSPHATE TRANSPORT IN A PTH-RESPONSIVE RENAL CELL LINE
SARTORI L, WEIR EC, STEWART AF, BROADUS AE, MANGIN M, BARRETT PQ, INSOGNA KL. SYNTHETIC AND PARTIALLY-PURIFIED ADENYLATE CYCLASE-STIMULATING PROTEINS FROM TUMORS ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY INHIBIT PHOSPHATE TRANSPORT IN A PTH-RESPONSIVE RENAL CELL LINE. The Journal Of Clinical Endocrinology & Metabolism 1988, 66: 459-461. PMID: 3339117, DOI: 10.1210/jcem-66-2-459.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityHumoral hypercalcemiaPhosphate metabolismCyclase-stimulating activityCell linesSodium-dependent phosphate transportRenal cell linesEpithelial cell lineTumor productsTumor decreaseRenal epithelial cellsRenal epithelial cell lineAmino acid peptidePhosphate transportHypercalcemiaAnimal tumorsTumorsHuman tumorsEpithelial cellsHHMMalignancyNaPiTInhibitory activityMinutes exposureEpithelial monolayers
1987
CO-PURIFICATION OF TRANSFORMING GROWTH FACTOR LIKE ACTIVITY WITH PTH-LIKE AND BONE-RESORBING ACTIVITIES FROM A TUMOR ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY
INSOGNA K, WEIR E, WU T, STEWART A, BROADUS A, BURTIS W, CENTRELLA M. CO-PURIFICATION OF TRANSFORMING GROWTH FACTOR LIKE ACTIVITY WITH PTH-LIKE AND BONE-RESORBING ACTIVITIES FROM A TUMOR ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY. Endocrinology 1987, 120: 2183-2185. PMID: 3494596, DOI: 10.1210/endo-120-5-2183.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityBone-resorbing factorsBone-resorbing activityHumoral hypercalcemiaGrowth factor beta-like activityPTH-like proteinLeydig cell tumorReverse-phase HPLC stepsBeta-like activityCyclase-stimulating activityGrowth factor betaCell tumorsResponsible mediatorsGrowth factor activityTumor extractsFisher ratsAnimal modelsFactor betaTumor tissueSingle fractionGrowth factorHypercalcemiaMalignancyPTHSequential treatmentIdentification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy.
Burtis WJ, Wu T, Bunch C, Wysolmerski JJ, Insogna KL, Weir EC, Broadus AE, Stewart AF. Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. Journal Of Biological Chemistry 1987, 262: 7151-7156. PMID: 3584110, DOI: 10.1016/s0021-9258(18)48217-8.Peer-Reviewed Original ResearchThe relative potency of a human tumor‐derived PTH‐like adenylate cyclase‐stimulating preparation in three bioassays
Stewart A, Wu T, Burtis W, Weir E, Broadus A, Insogna K. The relative potency of a human tumor‐derived PTH‐like adenylate cyclase‐stimulating preparation in three bioassays. Journal Of Bone And Mineral Research 1987, 2: 37-43. PMID: 3455155, DOI: 10.1002/jbmr.5650020107.Peer-Reviewed Original ResearchConceptsFetal bone resorptionRat osteosarcomaPTH standardRelative potencyCyclase assaysPTH target tissuesAdenylate cyclase assayHumoral hypercalcemiaBone resorptionPTH receptorBPTH 1Target tissuesDistinct subpopulationsPotencyAssaysHypercalcemiaPrevious studiesMalignancyOsteosarcomaTumorsResorptionReceptorsHypercalcemia of Malignancy
Insogna KL, Broadus AE. Hypercalcemia of Malignancy. Annual Review Of Medicine 1987, 38: 241-256. PMID: 3555293, DOI: 10.1146/annurev.me.38.020187.001325.Books
1986
Two Species of Adenylate Cyclase-Stimulating Activity in a Murine Squamous Carcinoma Model of Humoral Hypercalcemia of Malignancy*
BURTIS W, BROADUS A, INSOGNA K, WEIR E, STEWART A. Two Species of Adenylate Cyclase-Stimulating Activity in a Murine Squamous Carcinoma Model of Humoral Hypercalcemia of Malignancy*. Endocrinology 1986, 118: 1982-1988. PMID: 3009144, DOI: 10.1210/endo-118-5-1982.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBiological AssayCarcinoma, Squamous CellChromatography, High Pressure LiquidDisease Models, AnimalDogsHypercalcemiaKidney CortexMiceNeoplasm ProteinsOsteosarcomaParathyroid HormonePeptide FragmentsRatsReceptors, Cell SurfaceReceptors, Parathyroid HormoneSkin NeoplasmsConceptsAdenylate cyclase-stimulating activityCyclase-stimulating activityTumor extractsPTH antagonistHumoral hypercalcemiaRat osteosarcomaCarcinoma modelDose-response curve parallelRat Leydig cellsAdenylate cyclase activityAdenylate cyclase systemDose-response curvePostreceptor stepPTH (3-34) amideLeydig cellsReversed-phase HPLCCyclase systemCyclase activityPeak IICommon mediatorPTHCyclase assaysHypercalcemiaMalignancyPhase HPLCFrequency and partial characterization of adenylate cyclase‐stimulating activity in tumors associated with humoral hypercalcemia of malignancy
Stewart A, Insogna K, Burtis W, Aminiafshar A, Wu T, Weir E, Broadus A. Frequency and partial characterization of adenylate cyclase‐stimulating activity in tumors associated with humoral hypercalcemia of malignancy. Journal Of Bone And Mineral Research 1986, 1: 267-276. PMID: 2845726, DOI: 10.1002/jbmr.5650010305.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityCyclase-stimulating activityHumoral hypercalcemiaTumor extractsSyndrome of HHMBone-resorbing activityNonmalignant tissue samplesControl tumorsHumoral factorsControl groupTumorsTissue samplesHypercalcemiaPatientsMalignancyTissue culture mediumHigh-performance liquid chromatographyHHMLarge groupCulture mediumLiquid chromatographyGroupSyndromeActivityA Parathyroid Hormone-Like Protein from Cultured Human Keratinocytes
Merendino JJ, Insogna KL, Milstone LM, Broadus AE, Stewart AF. A Parathyroid Hormone-Like Protein from Cultured Human Keratinocytes. Science 1986, 231: 388-390. PMID: 2417317, DOI: 10.1126/science.2417317.Peer-Reviewed Original ResearchConceptsHumoral hypercalcemiaParathyroid hormoneHuman keratinocytesParathyroid hormone receptor agonistsParathyroid hormone-like proteinSquamous epithelial originExtracts of tumorsHormone receptor agonistsHormone-like proteinHormone-like factorsAdenylate cyclase activityRat osteosarcoma cellsAdenylate cyclase productionNative parathyroid hormoneCultured human keratinocytesNormal human keratinocytesReceptor agonistMalignant tumorsCyclic adenosine monophosphateHypercalcemiaEpithelial originKeratinocyte-conditioned mediumMalignancyCyclase activityCyclase productionNephrogenous Cyclic AMP, Adenylate Cyclase-Stimulating Activity, and the Humoral Hypercalcemia of Malignancy
GODSALL JW, BURTIS WJ, INSOGNA KL, BROADUS AE, STEWART AF. Nephrogenous Cyclic AMP, Adenylate Cyclase-Stimulating Activity, and the Humoral Hypercalcemia of Malignancy. 1986, 42: 705-750. PMID: 3016837, DOI: 10.1016/b978-0-12-571142-5.50021-5.BooksConceptsNephrogenous cyclic AMPCyclase-stimulating activityUcAMP excretionHumoral hypercalcemiaLocal osteolytic hypercalcemiaAdenylate cyclase-stimulating activityBone-resorbing activityCyclic AMPHPT groupNcAMP excretionNormocalcemic patientsPathophysiologic syndromeTumor extractsAnimal modelsHypercalcemiaAnimal tumorsTumorsNcAMPHHMExcretionPatientsMalignancyObserved elevationBasic proteinAMP
1983
Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy.
Stewart AF, Insogna KL, Goltzman D, Broadus AE. Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy. Proceedings Of The National Academy Of Sciences Of The United States Of America 1983, 80: 1454-1458. PMID: 6298791, PMCID: PMC393616, DOI: 10.1073/pnas.80.5.1454.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityCyclase-stimulating activityExtracts of tumorsHumoral hypercalcemiaPTH receptorTumor extractsPTH-sensitive adenylate cyclaseAdenylate cyclaseSensitive cytochemical bioassayRenal PTH receptorsParathyroid hormoneClinical studiesPTH resultsCompetitive inhibition studiesCytochemical bioassayTumorsPatientsHypercalcemiaGlucose-6-phosphate dehydrogenaseHHMFurther studiesMalignancyPTHFragment analogSpecific binding