Heterogeneity of neuropeptide Y immunoreactivity in patients with pheochromocytoma: influence on the diagnostic power of measuring plasma NPY using antisera with different specificities

Tabarin, Antoine; Cassiède, Pierre; Minot, Anne Perrot; Cuber, Jean‐Claude; Roger, Patrick; Ducassou, D.

doi:10.1530/acta.0.1280243

Cited by 13 publications

(5 citation statements)

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“…Elevated systemic NPY levels correlate with adverse tumor phenotype in Ewing's sarcoma and neuroblastoma 27,40 . There are associations of elevated plasma NPY with metastasis in pheochromocytoma 41,42 . An increase in NPY expression in tissues is an early event in PCa development 43 .…”

Section: Resultsmentioning

confidence: 99%

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Neuropeptide Y nerve paracrine regulation of prostate cancer oncogenesis and therapy resistance

et al. 2020

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Background: Nerves are key factors in prostate cancer (PCa) progression. Here, we propose that neuropeptide Y (NPY) nerves are key regulators of cancer-nerve interaction. Methods: We used in vitro models for NPY inhibition studies and subsequent metabolomics, apoptotic and migration assays, and nuclear transcription factor-κB (NF-κB) translocation studies. Human naïve and radiated PCa tissues were used for NPY nerve density biomarker studies. Tissues derived from a Botox denervation clinical trial were used to corroborate metabolomic changes in humans. Results: Cancer cells increase NPY positive nerves in vitro and in preneoplastic human tissues. NPY-specific inhibition resulted in increased cancer apoptosis, decreased motility, and energetic metabolic pathway changes. A comparison of metabolomic response in NPY-inhibited cells with the transcriptome response in human PCa patients treated with Botox showed shared 13 pathways, including the tricarboxylic acid cycle. We identified that NF-κB is a potential NPY downstream mediator. Using in vitro models and tissues derived from a previous human chemical denervation study, we show that Botox specifically, but not exclusively, inhibits NPY in cancer. Quantification of NPY nerves is independently predictive of PCa-specific death. Finally, NPY nerves might be involved in radiation therapy (RT) resistance, as radiation-induced apoptosis is reduced when PCa cells are cocultured with dorsal root ganglia/nerves and NPY positive nerves are increased in prostates of patients that failed RT. Conclusion: These data suggest that targeting the NPY neural microenvironment may represent a therapeutic approach for the treatment of PCa and resistance through the regulation of multiple oncogenic mechanisms.

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Section: Resultsmentioning

confidence: 99%

“…27,40 There are associations of elevated plasma NPY with metastasis in pheochromocytoma. 41,42 An increase in NPY expression in tissues is an early event in PCa development. 43 Our studies confirm that NPY is associated with increased PCa aggressiveness.…”

Section: F I G U R Ementioning

confidence: 99%

Neuropeptide Y nerve paracrine regulation of prostate cancer oncogenesis and therapy resistance

et al. 2020

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“…M-8701, Milab, Malmö, Sweden: dilution 1:640) according to the method described above. To study the possible coexistence of PACAP and NPY the elut ion-restaining technique or consecutive staining of adjacent cryo stat sections for PACAP and NPY were performed using an NPY antiserum obtained by immunizing rabbits against synthetic porcine NPY (Peninsula, Belmont, Calif., USA) conjugated with bovine serum albumin (code K02B; dilution 1:640) [15]. For control, the NPY antiserum was incubated with 10-100 pg of NPY before applying to the sections.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The concentrations are expressed as molar equivalents of PACAP-27 per unit weight. NPY-LI was measured by RIA as previously described [15] with the use of the K.02B antiserum.…”

Section: Peptide Extraction and Radioimmunoassaysmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Peptide in the Adrenal Gland of Mammals: Distribution, Characterization and Responses to Drugs

et al. 1994

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The occurrence, cellular distribution and nature of the 27-amino acid form of pituitary adenylate cyclase-activating peptide (PACAP-27) in the adrenal glands of mammals was investigated by means of immunohistochemistry, radioimmunoassay and chromatography. The concentrations (pmol/g wet weight) of PACAP-27-like immunoreactivity (LI) varied considerably between the species examined: mouse (n = 8), 12.1 ± 2.0; hamster (n = 4), 9.1 ± 1.5; rat (n = 13), 2.0 ± 0.3; cow (n = 3), 0.8 ± 0.1, and pig (n = 5), 0.7 ± 0.1. Upon HPLC, the immunoreactivity in extracts of rat, mouse and hamster adrenals coeluted with synthetic PACAP-27 while the immunoreactivity in extracts of cow and pig adrenals eluted as less hydrophobic material. Immunohistochemistry revealed the presence of PACAP-27-LI in the noradrenaline-storing chromaffin cells of the adrenal medulla. No nerve fibers exhibiting PACAP-27-LI could be detected. The effects of drug administration in vivo on the stores of PACAP-27-LI in the rat adrenal were studied and compared with the effects on the adrenal stores of neuropeptide Y (NPY)-LI. Splanchnic activation following insulin-induced hypoglycemia elicited a 41% depletion of NPY-LI 2 h after insulin injection, while the concentrations of PACAP-27-LI remained unchanged. Two days after reserpine administration the stores of PACAP-27-LI and NPY-LI were depleted by 62 and 41%, respectively. Two days later, the concentrations of NPY-LI were increased to 216% of controls, while the concentrations of PACAP-27-LI were similar to that of controls. Taken together with data from the literature, our findings suggest that PACAP may be involved in the regulation of adrenomedullary activity in more than one mammalian species. The stimuli that regulate the synthesis and release of PACAP-27 in the adrenal gland remains to be identified but seems to differ from those involved in the regulation of NPY.

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“…O NPY like-immunoreactivity (NPY-LI) sofre um incremento nos níveis circulantes durante a manipulação tumoral cirúrgica, reduzindo em mais de 70% dos casos sua concentração em cerca de uma hora após a retirada do tumor. Aproximadamente 86% dos feocromocitomas apresentam elevação dos níveis de NPY-LI tecidual em relação as adrenais normais, e, apesar desta, sua utilização no diagnóstico ainda parece limitada 17 .…”

Section: E) Peptídeos Plasmáticosunclassified

Feocromocitoma: atualização diagnóstica e terapêutica

Faiçal¹,

Shiota²

1997

Rev. Assoc. Med. Bras.

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Feocromocitomas são tumores originários das células cromafins do eixo simpático adrenomedular, caracterizados pela autonomia na produção de catecolaminas, mais freqüentemente adrenalina e/ou noradrenalina 1 . A localização medular é a mais freqüente (90% dos casos), podendo, entretanto, ter origem em paragânglios da base do crânio até a bifurcação das artérias ilíacas, ou no órgão de Zuckerkandl, localizando-se mais raramente em tórax, bexiga ou cérebro, sendo assim denominados feocromocitomas extra-adrenais ou paragangliomas 2-5 . A incidência destes tumores situa-se em torno de 0,1% nos hipertensos diastólicos, sendo mais freqüentes entre a 3 a e 5 a décadas de vida, e com incidência ligeiramente maior em mulheres que em homens. Dentre eles, mais de 90% são benignos e únicos, e na maioria dos casos a ressecção tumoral leva à cura. Por outro lado, quando malignos, estes tumores apresentam metástases freqüentemente em ossos, linfonodos regionais, fíga-do, pulmões, cérebro e cordão espinhal 2-7 . Em estudo de Deal et al., 32% dos feocromocitomas são tumores múltiplos ou bilaterais, apresentando maior incidência em crianças e nos casos de caráter familiar (cerca de 10% a 15%). Essas características ocorrem mais freqüentemente na neoplasia endócrina múltipla -NEM -tipo 2a e 2b. A NEM tipo 2a é caracterizada pela presença de feocromocitoma, carcinoma medular de tiróide e hiperparatiroidismo. O feocromocitoma e o carcinoma medular de tiróide são diagnosticados simultaneamente em 73% dos casos, mas o intervalo de diagnóstico dos dois pode ser prolongado. Já a NEM tipo 2b consiste em feocromocitoma, carcinoma medular de tiróide, neuromas de mucosas, ganglioneuromatose e hábito marfanóide [2][3][4]8 . FISIOPATOLOGIAA hipertensão arterial é a manifestação clínica mais comum do feocromocitoma, acometendo mais de 90% dos pacientes, geralmente resistente ao tratamento anti-hipertensivo convencional, mas podendo responder a bloqueadores alfa-adrenér-gicos, bloqueadores dos canais de cálcio e nitroprussiato de sódio. A hipertensão arterial é sustentada em 50% das vezes, e o restante dos quadros hipertensivos, associando-se a paroxismos, com duração de minutos até horas, com intervalos variáveis, enquanto, por outro lado, cerca de 25% a 40% dos feocromocitomas manifestam-se isoladamente na forma de paroxismos hipertensivos. Ocasionalmente, a hipertensão arterial evolui com caráter maligno, acompanhado de proteinúria e/ ou retinopatia hipertensiva e, às vezes, complicando com encefalopatia hipertensiva 2,3,5,7 . A tríade clássica do feocromocitoma, associado à hipertensão arterial, é composta por cefaléia, sudorese profusa e palpitações. Entretanto, muitos pacientes não apresentam taquicardia, e durante os paroxismos raramente pode ser observada bradicardia. Outros sintomas são ansiedade, rubor facial, palidez cutânea, náuseas, vômitos, dispnéia e dor precordial, provavelmente provenientes das alterações vasomotoras 2-5,9 . Comprometimento cardiovascular no feocromocitoma pode caracterizar-se por angina do peito e infarto agudo...

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Heterogeneity of neuropeptide Y immunoreactivity in patients with pheochromocytoma: influence on the diagnostic power of measuring plasma NPY using antisera with different specificities

Cited by 13 publications

References 30 publications

Neuropeptide Y nerve paracrine regulation of prostate cancer oncogenesis and therapy resistance

Neuropeptide Y nerve paracrine regulation of prostate cancer oncogenesis and therapy resistance

Pituitary Adenylate Cyclase-Activating Peptide in the Adrenal Gland of Mammals: Distribution, Characterization and Responses to Drugs

Feocromocitoma: atualização diagnóstica e terapêutica

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