1994
Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing.
Yang KH, dePapp AE, Soifer NE, Dreyer BE, Wu TL, Porter SE, Bellantoni M, Burtis WJ, Insogna KL, Broadus AE. Parathyroid hormone-related protein: evidence for isoform- and tissue-specific posttranslational processing. Biochemistry 1994, 33: 7460-9. PMID: 8003511, DOI: 10.1021/bi00189a054.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCHO CellsChromatography, AffinityChromatography, High Pressure LiquidCricetinaeCricetulusCulture Media, ConditionedHumansImmunohistochemistryMolecular Sequence DataParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsProtein Processing, Post-TranslationalProteinsTumor Cells, CulturedConceptsHormone-related proteinCarboxy-terminal fragmentCell linesTissue-specific posttranslational processingRat insulinoma cellsDistinct paracrineHuman PTHrP geneHumoral hypercalcemiaMalignant tumorsAutocrine roleRIN cell linesMidregion fragmentPTHrP isoformsMost human cell linesNonmalignant tissuesPhysiological rationalePTHrP geneInsulinoma cellsChinese hamster ovary cellsHuman cell linesHamster ovary cellsSecretory formCellsOvary cellsPosttranslational processing
1992
Parathyroid hormone‐related protein stimulates prostaglandin E2 release from human osteoblast‐like cells: Modulating effect of peptide length
Mitnick M, Isales C, Paliwal I, Insogna K. Parathyroid hormone‐related protein stimulates prostaglandin E2 release from human osteoblast‐like cells: Modulating effect of peptide length. Journal Of Bone And Mineral Research 1992, 7: 887-896. PMID: 1332431, DOI: 10.1002/jbmr.5650070805.Peer-Reviewed Original ResearchConceptsCyclic AMP accumulationPGE2 releaseAMP accumulationCultured fetal rat long bonesFetal rat long bonesSaos-2 cellsBone resorptive actionProstaglandin E2 secretionBone-active cytokineHormone-related proteinPrimary human bone cell culturesRelease of PGE2Prostaglandin E2 releaseEffects of PTHrPRat long bonesForm of PTHrPHuman osteoblast-like cellsMalignancy syndromeE2 secretionHumoral hypercalcemiaBasal secretionPGE2 secretionE2 releaseOsteoblast-like cellsPTHrPSynthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo
Weir E, Terwilliger G, Sartori L, Insogna K. Synthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo. Calcified Tissue International 1992, 51: 30-34. PMID: 1393774, DOI: 10.1007/bf00296214.Peer-Reviewed Original ResearchConceptsBovine parathyroid hormoneSerum calciumParathyroid hormone-like proteinDaily subcutaneous injectionsPotent bone-resorbing agentHormone-related proteinDose-dependent increaseDry bone weightHighest dose levelHormone-like proteinBone-resorbing agentsBone dry weightLow dosage levelsHumoral hypercalcemiaParathyroid hormoneDihydroxyvitamin DMale SpragueDawley ratsSubcutaneous injectionHuman PTHrPBone calciumAnabolic agentsPTHrP actionDose levelsHigh doses
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 structureSynthesis of a Gene Encoding Parathyroid Hormone-Like Protein-(1–141): Purification and Biological Characterization of the Expressed Protein*
THORIKAY M, KRAMER S, REYNOLDS F, SORVILLO J, DOESCHER L, WU T, MORRIS C, BURTIS W, INSOGNA K, VALENZUELA D, STEWART A. Synthesis of a Gene Encoding Parathyroid Hormone-Like Protein-(1–141): Purification and Biological Characterization of the Expressed Protein*. Endocrinology 1989, 124: 111-118. PMID: 2535801, DOI: 10.1210/endo-124-1-111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBiological AssayBone and BonesCalciumCloning, MolecularCyclic AMPDNADogsEscherichia coliGenes, SyntheticKidneyMolecular Sequence DataMolecular WeightNeoplasm ProteinsOsteosarcomaParathyroid HormoneParathyroid Hormone-Related ProteinPeptide FragmentsPlasmidsRatsRecombinant ProteinsTumor Cells, Cultured
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 monolayersHumoral Hypercalcemia of Malignancy in Canine Lymphosarcoma*
Weir EC, Norrdin RW, Matus RE, Brooks MB, Broadus AE, Mitnick M, Johnston SD, Insogna KL. Humoral Hypercalcemia of Malignancy in Canine Lymphosarcoma*. Endocrinology 1988, 122: 602-608. PMID: 2828006, DOI: 10.1210/endo-122-2-602.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityHypercalcemic dogsCanine lymphosarcomaFractional phosphorus excretionEvidence of tumorQuantitative bone histomorphometryBone-resorbing factorsImmunoreactive PTH levelsPathogenesis of hypercalcemiaIliac crest biopsiesTumor tissue extractsCyclase-stimulating activityBone histomorphometric findingsCalcium excretionPTH levelsHumoral hypercalcemiaDihydroxyvitamin DBone resorptionHistomorphometric findingsBone histomorphometryPTH receptorBiopsy siteCrest biopsiesTumor extractsCompensatory increaseSynthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats.
Stewart AF, Mangin M, Wu T, Goumas D, Insogna KL, Burtis WJ, Broadus AE. Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats. Journal Of Clinical Investigation 1988, 81: 596-600. PMID: 3339131, PMCID: PMC329608, DOI: 10.1172/jci113358.Peer-Reviewed Original ResearchConceptsBone-resorbing agentsMicrograms/hParathyroid hormone-like proteinFetal rat long bonesAdenylate cyclasePotent bone-resorbing agentHormone-like proteinRat long bonesMembrane adenylate cyclaseSerum calciumHumoral hypercalcemiaOsmotic minipumpsBone resorptionPotent agonistLong bonesSuch synthetic peptidesHypercalcemiaRatsDlVivo bioactivityCyclaseSynthetic peptidesAgentsMinipumpsPatients
1987
Skin-Derived Fibroblasts Respond to Human Parathyroid Hormone-Like Adenylate Cyclase-Stimulating Proteins*
WU T, INSOGNA K, HOUGH L, MILSTONE L, STEWART A. Skin-Derived Fibroblasts Respond to Human Parathyroid Hormone-Like Adenylate Cyclase-Stimulating Proteins*. The Journal Of Clinical Endocrinology & Metabolism 1987, 65: 105-109. PMID: 3034948, DOI: 10.1210/jcem-65-1-105.Peer-Reviewed Original ResearchConceptsPTH-like factorHumoral hypercalcemiaPTH analogsPTH-responsive adenylate cyclaseDermal fibroblast linesAdenylate cyclaseTumor-derived factorsAdenylate cyclase responseDermal fibroblastsAdenylate cyclase stimulationHuman dermal fibroblastsM bovine PTHDermal physiologyFibroblast linesHuman dermal fibroblast linesBovine PTHHigh prevalenceTumor extractsCyclase responseSkin-derived fibroblastsCyclase stimulationPTHKeratinocyte-conditioned mediumHuman tumorsApparent potencyCO-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 HPLC