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1.
Drug Deliv ; 27(1): 128-136, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31894722

RESUMO

Receptor-mediated active targeting and tumor microenvironment responsive systems from polymeric micelles have been studied for rapid cellular internalization and triggered drug release. Previously we have constructed redox-responsive polymeric micelles composed of vitamin E succinate conjugated hyaluronic acid (HA-ss-TOS), which are able to actively target CD44 proteins and quickly release loaded drugs upon exposure to high levels of glutathione (GSH) in tumor cells. In the present study, we found that despite different cellular internalization mechanisms, micelles showed strong antineoplastic effects on 4T1 and B16F10 cells due to redox responsiveness. HA-ss-TOS-PTX micelles exhibited an excellent tumor targeting ability and prolonged retention time compared to Taxol in vivo. In addition, a superior antitumor effect was achieved compared to PTX-loaded insensitive micelles (HA-TOS-PTX) and Taxol. Our results revealed that PTX-loaded HA-ss-TOS micelles could enhance the antineoplastic efficacy of PTX for breast cancer and melanoma treatment and, thus, deserve further attention.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Liberação Controlada de Fármacos , Humanos , Receptores de Hialuronatos/efeitos dos fármacos , Ácido Hialurônico/química , Micelas , Oxirredução , Células Oxífilas/efeitos dos fármacos , Tamanho da Partícula , alfa-Tocoferol/química
2.
Kidney Int ; 92(5): 1217-1222, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28750928

RESUMO

The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.


Assuntos
Calcimiméticos/farmacologia , Cinacalcete/farmacologia , Ergocalciferóis/farmacologia , Hiperparatireoidismo Secundário/terapia , Células Oxífilas/efeitos dos fármacos , Glândulas Paratireoides/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Calcimiméticos/uso terapêutico , Calcitriol/análogos & derivados , Transdiferenciação Celular/efeitos dos fármacos , Cinacalcete/uso terapêutico , Quimioterapia Combinada/métodos , Ergocalciferóis/uso terapêutico , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/urina , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/citologia , Glândulas Paratireoides/metabolismo , Glândulas Paratireoides/cirurgia , Paratireoidectomia , Receptores de Detecção de Cálcio/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/urina , Uremia/complicações , Uremia/tratamento farmacológico , Uremia/urina , Vitamina D/análogos & derivados
3.
J Clin Pathol ; 64(9): 756-60, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21565858

RESUMO

BACKGROUND: Cinacalcet treatment for secondary hyperparathyroidism (SHPT) has demonstrated parathyroid size regression and morphological changes, such as cystic degeneration and hypovascularisation, on ultrasonography. However, there have been very few reports regarding the histopathological alterations of hyperplastic parathyroid glands in patients with SHPT after administration of cinacalcet. The aim of this study was to elucidate the effects of cinacalcet for histopathological alterations on the parathyroid glands. METHODS: A total of 92 hyperplastic parathyroid glands were obtained from 24 dialysis patients with severe SHPT who underwent total parathyroidectomy and were enrolled in this study. Patients were divided into those treated with and without cinacalcet (cinacalcet group and conventional group, respectively; both n=12). The areas of oxyphil cells, cystic degeneration, haemorrhagic changes and haemosiderin deposition were assessed semiquantitatively. RESULTS: Total maximal parathyroid gland weight and maximal-to-minimal parathyroid gland weight ratio were significantly higher in the cinacalcet group compared with the conventional group (1798.7±1658.3 mg vs 764.2±471.1 mg, p=0.018, 15.8±13.9 vs p=0.047, 6.6±4.2, respectively). Significant increases were observed in oxyphil cell area (61.7%±17.1% vs 36.7%±15.6%, p=0.001) and haemosiderosis score (1.50±1.24 vs 0.42±0.51, p=0.029) in the former rather than the latter group. CONCLUSIONS: These results suggest that cinacalcet may induce specific qualitative alterations of hyperplastic parathyroid glands in patients with severe SHPT.


Assuntos
Hiperparatireoidismo Secundário/patologia , Naftalenos/uso terapêutico , Glândulas Paratireoides/patologia , Diálise Renal , Contagem de Células , Cinacalcete , Resistência a Medicamentos , Feminino , Humanos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Hiperplasia , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Naftalenos/farmacologia , Tamanho do Órgão , Células Oxífilas/efeitos dos fármacos , Células Oxífilas/patologia , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo
4.
J Environ Biol ; 30(5 Suppl): 917-22, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20143729

RESUMO

In order to record the effects of heroin on plasma calcium (Ca) and inorganic phosphate (Pi) levels as well as parathyroid gland and C cells, two sub-lethal doses (0.50 LD50 and 0.75 LD50) of the drug were administered intramuscularly in Rattus norvegicus for 30 days. Plasma Ca level of control rats ranged between 9.53 +/- 0.32 - 9.88 +/- 0.22 mg 100 ml(-1) while plasma Pi concentration fluctuated between 4.55 +/- 0.18 - 4.71 +/- 0.24 mg 100 ml(-1). Sub-lethal heroin administration induced progressive increase in plasma Ca level during the first seven days (p < 0.001), thereafter the level declined on day 15 and 30. However plasma Pi level of the heroin-treated rats registered increase with the peak value (p < 0.001) on day 30. The treatment elicited degenerative changes in parathyroid gland as evident by cytoplamic vacuolization, presence of more pycnotic nuclei and occurrence of patchy areas among the chief cells. Degenerative changes were also noticed in cristae of mitochondria, Golgi complex and endoplasmic reticulum. There was decrease in chromatin material in the nucleus and loss of hormone granules in the cytoplasm. Oxyphil cells of the heroin-treated rat depicted dilation of endoplasmic reticulum and damaged cristae. Sub-lethal heroin administration in the rat for 30 days induced dilation in endoplasmic reticulum and loss of secretory granules in C cells.


Assuntos
Cálcio/sangue , Heroína/toxicidade , Glândulas Paratireoides/efeitos dos fármacos , Fosfatos/sangue , Animais , Masculino , Células Oxífilas/efeitos dos fármacos , Células Oxífilas/patologia , Células Oxífilas/ultraestrutura , Glândulas Paratireoides/patologia , Glândulas Paratireoides/ultraestrutura , Ratos
5.
Clin J Am Soc Nephrol ; 3(3): 794-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18322048

RESUMO

BACKGROUND AND OBJECTIVES: Vitamin D receptor activation by vitamin D sterols and calcium-sensing receptor stimulation by cinacalcet are the most powerful treatments of secondary hyperparathyroidism. This study was aimed to assess a possible association between histopathologic changes of parathyroid tissue and treatment modality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were performed on 82 parathyroids of 22 adult white hemodialysis patients undergoing first parathyroidectomy. The type of hyperplasia and the distribution of chief and oxyphil cells, expressed as oxyphil/chief cell ratio, were assessed. Three groups could be studied according to treatment modality: group A consisted of 6 patients who were treated with cinacalcet, intravenous calcitriol, and phosphate binders; group B consisted of 6 patients who were treated with intravenous calcitriol and phosphate binders, and group C consisted of 10 patients who were treated with phosphate binders alone. RESULTS: Sixty-eight (82.9%) out of 82 glands removed showed nodular hyperplasia. It was more frequent in groups A and B than in group C. A stepwise forward logistic regression model showed that the probability of nodular hyperplasia was higher in patients who were on calcitriol and/or cinacalcet therapy, in female gender and in patients with a higher body mass index. Oxyphil/chief cell ratio also was significantly different among the three groups. Cinacalcet treatment was the only predictor of this ratio. CONCLUSIONS: An association was found between calcitriol and/or cinacalcet therapy and a high prevalence of nodular hyperplasia, and between cinacalcet therapy and high oxyphil/chief cell ratio. The meaning of the observed associations remains uncertain.


Assuntos
Calcitriol/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Naftalenos/uso terapêutico , Glândulas Paratireoides/efeitos dos fármacos , Receptores de Calcitriol/agonistas , Receptores de Detecção de Cálcio/agonistas , Uremia/complicações , Vitaminas/uso terapêutico , Adulto , Idoso , Índice de Massa Corporal , Calcitriol/efeitos adversos , Cinacalcete , Quimioterapia Combinada , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/patologia , Hiperparatireoidismo Secundário/cirurgia , Hiperplasia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Naftalenos/efeitos adversos , Células Oxífilas/efeitos dos fármacos , Células Oxífilas/patologia , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Paratireoidectomia , Fosfatos/uso terapêutico , Diálise Renal , Medição de Risco , Fatores de Risco , Fatores Sexuais , Falha de Tratamento , Uremia/tratamento farmacológico , Uremia/patologia , Uremia/cirurgia , Vitaminas/efeitos adversos
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