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1.
An. bras. dermatol ; 96(6): 712-716, Nov.-Dec. 2021. tab
Article in English | LILACS | ID: biblio-1355629

ABSTRACT

Abstract Background: The treatment of advanced periocular basal cell carcinomas becomes a challenge as surgery may involve highly mutilating procedures. Vismodegib is the first selective hedgehog inhibitor approved for the treatment of locally advanced tumors or metastatic disease. Objective: Analyze the results of treatment with vismodegib for advanced periocular basal cell carcinomas in a real-life setting of a reference center between 2014 and 2020. Methods: Retrospective longitudinal study. The patient's demographic profile, comorbidities, tumor characteristics, and treatment outcomes were analyzed. Results: A total of 13 patients were included. Median follow-up and treatment duration were 15.9 and 10.5 months, respectively. Objective clinical response rate was 76.9%: 30.8% had a complete response and 46.2% a partial response. The median duration of response was 13 months. Progressive disease was observed in 38.5% of cases, with a median of 19 months after the beginning of treatment. Eighty-four percent of the patients had at least one adverse event, and 61.54% needed to interrupt treatment temporarily or permanently to increase tolerability. Study limitations: Being a retrospective study in a real-life setting, the evaluation of objective clinical response was subjective to physician appreciation. Conclusion: Vismodegib is a safe and effective treatment for locally advanced basal cell carcinoma. To prevent recurrences, the drug should be used continually when tolerated. The role of neoadjuvant vismodegib before surgery is being investigated and might add an important step in searching for a definitive treatment for these cases.


Subject(s)
Humans , Carcinoma, Basal Cell/drug therapy , Neoplasms/drug therapy , Pyridines , Retrospective Studies , Longitudinal Studies , Hedgehog Proteins , Anilides , Neoplasm Recurrence, Local/drug therapy
2.
Brasília; CONITEC; set. 2021. 678 p. (Relatório para sociedade: informações sobre recomendações de incorporação de medicamentos e outras tecnologias no SUS, 282).
Monography in Portuguese | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1362845

ABSTRACT

Este documento é uma versão resumida do relatório técnico da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ Conitec e foi elaborado numa linguagem simples, de fácil compreensão, para estimular a participação da sociedade no processo de Avaliação de Tecnologias em Saúde (ATS) que antecede a incorporação, exclusão ou alteração de medicamentos, produtos e procedimentos utilizados no SUS. As recomendações da Comissão são submetidas à consulta pública pelo prazo de 20 dias. Após analisar as contribuições recebidas na consulta pública, a Conitec emite a recomendação final, que pode ser a favor ou contra a incorporação, exclusão ou alteração da tecnologia analisada. A recomendação final é, então, encaminhada ao Secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde -SCTIE/MS, que decide sobre quais tecnologias em saúde serão disponibilizadas no SUS


Subject(s)
Humans , Pyridines/therapeutic use , Carcinoma, Renal Cell/drug therapy , Antineoplastic Agents, Immunological/therapeutic use , Nivolumab/therapeutic use , Kidney Neoplasms/drug therapy , Anilides/therapeutic use , Technology Assessment, Biomedical , Cost-Benefit Analysis , Neoplasm Metastasis
3.
Brasília; MS; jun. 2021. 681 p. ilus, tab.(Relatório de recomendação: medicamento, 661).
Monography in Portuguese | ColecionaSUS, LILACS, ColecionaSUS, BRISA | ID: biblio-1362749

ABSTRACT

Relatório técnico com Leis que estabelece que a incorporação, a exclusão ou a alteração de novos medicamentos, produtos e procedimentos, bem como a constituição ou alteração de protocolo clínico ou de diretriz terapêutica são atribuições do Ministério da Saúde (MS). A estrutura de funcionamento da Conitec é composta por Plenário e Secretaria-Executiva. A gestão e a coordenação das atividades da Conitec, bem como a emissão do relatório de recomendação sobre as tecnologias analisadas são de responsabilidade da Secretaria-Executiva ­ exercida pelo Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde (DGITIS/SCTIE/MS).


Subject(s)
Humans , Pyridines/therapeutic use , Carcinoma, Renal Cell/drug therapy , Antineoplastic Agents, Immunological/therapeutic use , Nivolumab/therapeutic use , Kidney Neoplasms/drug therapy , Anilides/therapeutic use , Technology Assessment, Biomedical , Cost-Benefit Analysis , Neoplasm Metastasis
4.
Article in English | WPRIM | ID: wpr-922183

ABSTRACT

BACKGROUND@#In recent years, heated tobacco products (HTPs), which are widely used in Japan, have been sold by various brands using additives such as flavors. It has been reported that the components of mainstream smoke are different from those of conventional cigarettes. In this study, we established an analytical method for furans and pyridines in the mainstream smoke, which are characteristic of HTPs and particularly harmful among the generated components, and investigated the amount of component to which the smokers are exposed.@*METHODS@#We established a simple analytical method for simultaneous analysis of gaseous and particulate compounds in the mainstream smoke of HTPs (IQOS, glo, ploom S) in Japan by combining a sorbent cartridge and glass fiber filter (Cambridge filter pad (CFP)). Both the sorbent cartridge and CFP were extracted using 2-propanol and analyzed via GC-MS/MS to determine the concentration of furans and pyridines generated from each HTP.@*RESULTS@#The results showed that the levels of target furans such as furfural, 2-furanmethanol, 2(5H)-furanone, and 5-methylfurfural tended to be higher in the mainstream smoke of glo than in standard cigarettes (3R4F). Pyridine, which is generated at a high level in 3R4F as a combustion component, and 4-ethenylpyridine (EP), which is a known marker of environmental tobacco smoke, were detected. Among these components, 2-furanmethanol and pyridine are classified as Group 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer (IARC). Therefore, it is possible that they will contribute to the health effects caused by use of HTPs.@*CONCLUSIONS@#Using the new collection and analytical method for furans and pyridines in the mainstream smoke of HTPs, the level of each compound to which smokers are exposed could be clarified. By comprehensively combining information on the amount of ingredients and toxicity, it will be possible to perform a more detailed calculation of the health risks of using HTPs. In addition, the components detected in this study may be the causative substances of indoor pollution through exhaled smoke and sidestream smoke; therefore, environmental research on the chemicals generated from HTPs would be warranted in future studies.


Subject(s)
Furans/analysis , Gas Chromatography-Mass Spectrometry , Humans , Japan , Pyridines/analysis , Smoke/analysis , Tandem Mass Spectrometry , Tobacco Products
5.
Arq. bras. med. vet. zootec. (Online) ; 72(3): 719-728, May-June, 2020. tab
Article in English | LILACS, VETINDEX | ID: biblio-1128887

ABSTRACT

Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)


This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)


Subject(s)
Animals , Rats , Pesticides/adverse effects , Pyridines , Teratogens/analysis , Fetal Development/drug effects , Rats, Wistar/embryology , Zika Virus , Microcephaly/veterinary
6.
Rev. Soc. Bras. Med. Trop ; 53: e20190489, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057274

ABSTRACT

Abstract INTRODUCTION: In Brasilia, pyriproxyfen (PPF; 0.01 mg/L) has been used for the larval control of Aedes aegypti mosquitoes since 2016. Information on the susceptibility of Ae. aegypti to PPF, and the development of resistance in populations from the Federal District of Brazil (FD) is limited. It is essential to monitor the susceptibility of Ae. aegypti to insecticides in order to improve vector control strategies. This study aimed to evaluate the susceptibility of Ae. aegypti populations from five areas of Brasilia to PPF. METHODS: We performed dose-response tests to estimate the emergence inhibition and resistance ratio of each field population, including the Rockefeller reference population. We also analyzed egg positivity, and the density and mortality of larvae and pupae. RESULTS: Populations from Vila Planalto (RR50=1.7), Regiment Guards Cavalry (RR50=2.5), and Sub-secretary of Justice Complex (RR50=3.7) presented high susceptibility to PPF, while the RR values of populations from Lago Norte (RR50=7.7) and Varjão (RR50=5.9) were moderately high, suggesting the emergence of insipient resistance to PPF in Brasilia. At 30 ng/mL, the highest larvae mortality rate was 2.7% for the population from Lago Norte, while that of pupae was 92.1% for Varjão and Vila Planalto. CONCLUSIONS: The five populations of Ae. aegypti from the FD are susceptible to PPF and there is a need to monitor the susceptibility of Ae. aegypti in new areas of the FD.


Subject(s)
Animals , Pyridines/pharmacology , Insecticide Resistance , Aedes/drug effects , Mosquito Vectors/drug effects , Insecticides/pharmacology , Brazil , Larva/drug effects
7.
Journal of Experimental Hematology ; (6): 1081-1085, 2020.
Article in Chinese | WPRIM | ID: wpr-827157

ABSTRACT

OBJECTIVE@#To investigate the effect of sphingosine-1-phosphate receptor 2 (S1PR2) specific antagonist JTE-013 on the proliferation of human chronic myeloid leukemia (CML) cell line K562.@*METHODS@#K562 cells were treated with JTE-013 (0, 0.5, 1, 5, 10, 20 μmol/L) for 24 and 48 hours respectively, CCK8 assay was used to detect the cell viability. K562 cells were treated with JTE-013 (0, 5, 10, 20 μmol/L) for 24 hours, propidium iodide (PI) DNA staining was used to analyze the cell cycle, Western blot was used to determine the levels of P21 and Cyclin D1 protein expression.@*RESULTS@#JTE-013 inhibited the proliferation of CML cell line K562 in a dose dependent manner (r=-0.971). The proliferation rate of CML cells showed that the activity of CML cells decreased gradually with the increase of JTE-013 concentration (r=-0.971). The detection demonstrated that JTE-013 suppressed tumor cell proliferation through cell cycle arrest in G/G phase. Further detection of the protein expressions of G phase regulators showed that level of P21 increased, and expression of Cyclin D1 decreased.@*CONCLUSION@#JTE-013, a S1PR2 antagonist, can inhibit the proliferation of human CML K562 cells, which may be achieved by arresting the cells in G/G phase.


Subject(s)
Apoptosis , Cell Proliferation , Humans , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Pyrazoles , Pyridines , Receptors, Lysosphingolipid , Sphingosine-1-Phosphate Receptors
8.
Mem. Inst. Oswaldo Cruz ; 115: e200271, 2020. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1135271

ABSTRACT

BACKGROUND Aedes aegypti is the primary transmitter of several arbovirus with great impact in human health. Controlling vector mosquitoes is an essential and complex task. One promising control method is to use mosquitoes as a vehicle to disseminate tiny particles of juvenile-killing insecticides, such as pyriproxyfen (PPF), to breeding sites. OBJECTIVES We aimed to investigate the capacity of Ae. aegypti to disseminate two new formulations of PPF in two sites of Rio de Janeiro city for assessment of the efficacy of these products. METHODS Dissemination stations impregnated with powder and liquid new formulations of PPF were installed in two test sites. Ovitraps were used in the test sites and in a control site for monitoring the presence of Ae. aegypti throughout eggs collection. FINDINGS Entomological indices indicated that the new formulations of PPF were efficient in reducing eggs abundance. Liquid formulation performed better than powder formulation. Ready-to-use formulations of PPF can be quickly applied in the field and can be replaced after a few months. MAIN CONCLUSIONS New formulations of PPF associated with mosquito dissemination approach make a valuable vector control strategy, managing to cover places of difficult access for whatever reason. New formulations application requires less labour, being economically attractive.


Subject(s)
Humans , Animals , Adolescent , Pyridines/pharmacology , Mosquito Control/methods , Aedes/drug effects , Insecticides/pharmacology , Larva/drug effects , Cities , Mosquito Vectors/growth & development , Mosquito Vectors/drug effects , Larva/growth & development
9.
Article in Chinese | WPRIM | ID: wpr-880803

ABSTRACT

OBJECTIVE@#To investigate the effect of palbociclib on cell cycle progression and proliferation of human renal tubular epithelial cells.@*METHODS@#Human renal tubular epithelial cell line HK-2 was treated with 1, 5, 10, and 20 μmol/L of palbociclib, and the changes in cell proliferation and viability were examined by cell counting and CCK8 assay. EDU staining was used to assess the proliferation of HK-2 cells following palbiciclib treatment at different concentrations for 5 days. The effect of palbociclib on cell cycle distribution of HK-2 cells was evaluated using flow cytometry. SA-β-Gal staining and C12FDG senescence staining were used to detect senescence phenotypes of HK-2 cells after palbociclib treatment at different concentrations for 5 days. The relative mRNA expression levels of P16, P21, and P53 and the genes associated with senescence-related secretion phenotypes were detected by RT-PCR, and the protein expressions of P16, P21 and P53 were detected by Western blotting.@*RESULTS@#Palbociclib inhibited HK-2 cell proliferation and induced cell cycle arrest in G1 phase. Compared with the control cells, HK-2 cells treated with high-dose (10 μmol/L) palbociclib exhibited significantly suppressed cell proliferation activity, and the inhibitory effect was the most obvious on day 5 (@*CONCLUSIONS@#Palbociclib induces HK-2 cell senescence by causing cell growth arrest and delaying cell cycle progression.


Subject(s)
Cell Cycle , Cell Cycle Checkpoints , Cellular Senescence , Epithelial Cells , Humans , Piperazines/pharmacology , Pyridines/pharmacology , Tumor Suppressor Protein p53/genetics
10.
Braz. dent. j ; 30(3): 213-219, May-June 2019. graf
Article in English | LILACS | ID: biblio-1011553

ABSTRACT

Abstract The aim of this study was to assess cytotoxicity and cell migration of calcium hypochlorite [Ca(OCl)2] and octenidine hydrochloride - OCT (Octenisept®, Schülke & Mayr, Norderstedt, Germany) in L929 and human periodontal ligament (hPDL) cells. The cells were exposed to different doses of different solutions: 2.5% and 5% Ca(OCl)2, 0.1% OCT, 2.5% NaOCl and 2% CHX for 10 min. Cell viability was assessed by methyl-thiazol-tetrazolium (MTT) and neutral red (NR) assays, and cell migration was determined by wound-healing assay. Statistical analysis was performed by two-way ANOVA and Bonferroni tests (α=0.05). The MTT and NR assays revealed that 0.1% OCT was less cytotoxic in hPDL cells (p<0.05), followed by 2% CHX and 2.5% Ca(OCl)2 (p<0.05). There was no significant difference between 2.5% NaOCl and 5% Ca(OCl)2 (p>0.05), but these solutions showed greater cytotoxicity than the others. The result was the same for L929 cells, except that there was no significant difference between 2% CHX and 2.5% Ca(OCl)2 (p>0.05). Wound-healing assay in L929 and hPDL cells showed that cell migration of 0.1% OCT, 2% CHX and 2.5% Ca(OCl)2 groups was higher than 5% Ca(OCl)2 and 2.5% NaOCl groups at 24 h (p<0.05). In conclusion, 0.1% OCT had lower cytotoxicity in tested cell lines than CHX, Ca(OCl)2 and NaOCl. Cell migration was higher for 0.1% OCT, 2% CHX and 2.5% Ca(OCl)2. Therefore, in terms of cytotoxicity, OCT and Ca(OCl)2 have the potential to be used as root canal irrigants.


Resumo Para a seleção do irrigante endodôntico deve-se considerar os possíveis efeitos citotóxicos. O objetivo foi avaliar os efeitos do hipoclorito de cálcio [Ca(OCl)2] e do cloridrato de octenidina (OCT) em células L929 e do ligamento periodontal humano (hPDL). As células foram expostas a diferentes doses das soluções: Ca(OCl)2 2,5% e 5%, OCT 0,1%, hipoclorito de sódio (NaOCl) 2,5% e clorexidina (CHX) 2%. A viabilidade celular foi avaliada pelos ensaios de metil-tiazol-tetrazólio (MTT) e vermelho neutro (NR), e a proliferação/migração pelo teste de cicatrização. Os resultados foram analisados por ANOVA de duas vias e Bonferroni (α=0,05). Os ensaios MTT e NR mostraram que OCT 0,1% foi menos citotóxico nas células do hPDL (p<0,05), seguido da CHX 2% e Ca(OCl)2 2,5% (p<0,05). Não houve diferença entre NaOCl 2,5% e Ca(OCl)2 5% (p>0,05). No entanto, estas soluções foram mais citotóxicas que as demais. O resultado foi o mesmo nas células L929, exceto que não houve diferença significativa entre CHX 2% e Ca(OCl)2 2,5% (p>0,05). A proliferação/migração das células L929 e do hPDL às 24 h nos grupos OCT 0,1%, CHX 2%, e Ca(OCl)2 2,5% foi maior que nos grupos Ca(OCl)2 5% e NaOCl 2,5% (p<0,05). Concluiu-se que OCT foi menos citotóxico que CHX, Ca(OCl)2 e NaOCl. Ca(OCl)2 2,5 e 5% apresentaram citotoxicidade menor ou similar ao NaOCl 2,5%, respectivamente. Os grupos OCT, CHX e Ca(OCl)2 2,5% apresentaram maior proliferação/migração celular do que os grupos do Ca(OCl)2 5% e NaOCl 2,5%. Portanto, OCT e Ca(OCl)2 têm potencial para serem utilizados como irrigantes endodônticos.


Subject(s)
Humans , Periodontal Ligament , Sodium Hypochlorite , Pyridines , Root Canal Irrigants , Chlorhexidine , Calcium Compounds
11.
Braz. j. biol ; 79(1): 29-37, Jan.-Mar 2019. tab, graf
Article in English | LILACS | ID: biblio-984009

ABSTRACT

Abstract Three phosphate solubilizing bacteria were isolated and identified by 16S rRNA sequencing as Pseudomonas putida, Pseudomonas sp and Pseudomonas fulva . The strains were subjected to plant biochemical testing and all the PGPR attributes were checked in the presence of pesticides (chlorpyrifos and pyriproxyfen). The phosphate solubilizing index of strain Ros2 was highest in NBRIP medium i.e 2.23 mm. All the strains showed acidic pH (ranges from 2.5-5) on both medium i.e PVK and NBRIP. Strain Ros2 was highly positive for ammonia production as well as siderophore production while strain Rad2 was positive for HCN production. The results obtained by the strains Rad1, Rad2 and Ros2 for auxin production were 33.1, 30.67 and 15.38 µg ml-1, respectively. Strain Rad1 showed 16% increase in percentage germination in comparison to control in the presence of pesticide stress. Most promising results for chlorophyll content estimation were obtained in the presence of carotenoids upto 6 mgg-1 without stress by both strains Rad1 and Rad2. Study suggests that especially strain Ros2 can enhance plant growth parameters in the pesticide stress.


Resumo Três bactérias solubilizantes de fosfato foram isoladas e identificadas por seqüenciamento de rRNA 16S como Pseudomonas putida, Pseudomonas sp e Pseudomonas fulva. As estirpes foram submetidas a testes bioquímicos de plantas e todos os atributos PGPR foram verificados na presença de pesticidas (clorpirifos e piriproxifeno). O índice de solubilização de fosfato da estirpe Ros2 foi mais elevado no meio NBRIP, isto é, 2,23 mm. Todas as estirpes apresentaram um pH ácido (varia de 2,5-5) em ambos os meios, isto é PVK e NBRIP. A estirpe Ros2 foi altamente positiva para a produção de amoníaco, bem como a produção de sideróforos enquanto a estirpe Rad2 foi positiva para a produção de HCN. Os resultados obtidos pelas estirpes Rad1, Rad2 e Ros2 para a produção de auxina foram 33,1, 30,67 e 15,38 μg ml-1 , respectivamente. A deformação Rad1 mostrou aumento de 16% na germinação percentual em comparação com o controlo na presença de stress de pesticida. Os resultados mais promissores para a estimativa do teor de clorofila foram obtidos na presença de carotenóides até 6 mgg-1 sem estresse por ambas as cepas Rad1 e Rad2. Estudo sugere que especialmente a estirpe Ros2 pode melhorar parâmetros de crescimento de plantas no estresse de pesticidas.


Subject(s)
Phosphates/metabolism , Pseudomonas/physiology , Pyridines/administration & dosage , Triticum/growth & development , Chlorpyrifos/administration & dosage , Insecticides/administration & dosage , Pakistan , Pseudomonas/drug effects , Triticum/metabolism , Triticum/microbiology , RNA, Bacterial/analysis , RNA, Ribosomal, 16S/analysis , Pseudomonas putida/drug effects , Pseudomonas putida/physiology , Sequence Analysis, RNA
12.
Rev. méd. Chile ; 147(1): 73-82, 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-991375

ABSTRACT

Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.


Subject(s)
Humans , Blood Coagulation Factors/therapeutic use , Antithrombins/administration & dosage , Antithrombins/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/therapy , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects , Thiazoles/administration & dosage , Thiazoles/adverse effects , Administration, Oral , Risk Factors , Rivaroxaban/administration & dosage , Rivaroxaban/adverse effects , Dabigatran/administration & dosage , Dabigatran/adverse effects , Antidotes/therapeutic use
13.
Article in Chinese | WPRIM | ID: wpr-813277

ABSTRACT

To investigate the value of the total liver CT perfusion imaging in the evaluation of rabbit VX2 liver tumors treated with TACE and apatinib.
 Methods: Thirty-six rabbit VX2 liver cancer models were established and randomly divided into 4 groups. Group A: simple TACE group; Group B: simple oral administration of apatinib mesylate; Group C: TACE + oral apatinib mesylate; Group D: control group, administration of saline. CT perfusion imaging (CTPI) was performed before treatment and on the 7 and 14 days after the treatment to acquire perfusion parameters including blood flow (BF), blood volume (BV), MTT (mean transit time), surface permeability (PS), and hepatic artery fraction (HAF). One tumor rabbit was sacrificed in each group after the first perfusion scan, and the remaining tumor rabbits were sacrificed after the last perfusion scan on the 14th day of the treatment. The borders of the tumors were stained immunohistochemically, and microvascular density (MVD) was measured by anti-CD34. The differences of perfusion parameters were compared to evaluate the liver hemodynamic changes, and statistical repeated measurement variance analysist correlation analysis were performed.
 Results: There were no significant differences in CTPI parameters of BF, BV, MTT, HAF and PS between the 4 groups before treatment (P>0.05). After the treatment, HB, HAF and PS were decreased significantly in Group A, B, and C and slightly increased in the Group D. The value of MVD after 14 d treatment was 80.1±16.4 in Group A, 50.2±11.2 in Group B, 27.4±9.7 in Group C, 68.7±12.7 in Group D, respectively. The value of MVD in the Group C were significantly lower than that in Group A, B, and D. It showed positive correlation between BF, HAF, PS and MVD in Group B, C, and D, and there was no significant correlation between BV, MTT and MVD. It showed no significant correlation between MVD and each CTPI parameter in Group A.
 Conclusion: Total liver CT perfusion can quantitatively evaluate the blood perfusion information of rabbit liver VX2 tumor after TACE. TACE combined with oral apatinib can effectively inhibit tumor growth and improve the therapeutic effect of VX2 tumor.


Subject(s)
Animals , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Neovascularization, Pathologic , Perfusion Imaging , Pyridines , Rabbits , Tomography, X-Ray Computed
14.
Article in Chinese | WPRIM | ID: wpr-813060

ABSTRACT

To investigate the effect of SB203580, a p38MAPK specific inhibitor, on ropivacaine-induced cytotoxicity in PC12 cells.
 Methods: PC12 cells were divided into three groups: the normal group (Group N), cells were cultured for 48 h; the ropivacaine group (Group R), cells were cultured with 15 mmol/L ropivacaine hydrochloride for 48 h; the ropivacaine+SB203580 group (Group R+S), cells were cultured with 15 mmol/L ropivacaine hydrochloride plus 10 μmol/L SB203580 for 48 h. The cell survival rates were detected by MTT assay. The protein levels of cleaved caspase-3, phosphor-p38 (p-p38) and cystolic cytochrome C (Cyt C) were detected by Western blotting.
 Results: Compared with the Group N, the number and survival rate of PC12 cells in the Group R and the Group R+S were significantly reduced (all P<0.05); the number and survival rate of PC12 cells in the Group R+S were significantly higher than those in the Group R (both P<0.05). Compared with the Group N, the levels of p-p38 and cleaved caspase-3, and the content of cytoplasmic Cyt C in the PC12 cells from the Group R and the Group R+S were significantly enhanced (all P<0.05); compared with the Group R, the levels of p-p38 and cleaved caspase-3, and the content of cytoplasmic Cyt C in the PC12 cells from the Group R+S were decreased (all P<0.05).
 Conclusion: The ropivacaine-induced cytotoxicity can be attenuated via inhibition of p38MAPK; which is related to decrease in Cyt C content and cleaved caspase-3 expression.


Subject(s)
Anesthetics, Local , Toxicity , Animals , Apoptosis , Imidazoles , PC12 Cells , Pyridines , Rats , Ropivacaine , Toxicity , p38 Mitogen-Activated Protein Kinases , Metabolism
15.
Article in English | WPRIM | ID: wpr-772278

ABSTRACT

Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.


Subject(s)
Anilides , Pharmacology , Basal Cell Nevus Syndrome , Hedgehog Proteins , Genetics , Pharmacology , Humans , Molecular Targeted Therapy , Odontogenic Cysts , Genetics , Therapeutics , Odontogenic Tumors , Genetics , Therapeutics , Pyridines , Pharmacology
16.
Article in English | WPRIM | ID: wpr-772274

ABSTRACT

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.


Subject(s)
Administration, Oral , Anilides , Pharmacology , Animals , Bone Diseases, Developmental , Cell Proliferation , Physiology , Female , Frontal Bone , Congenital Abnormalities , Hedgehog Proteins , Limb Deformities, Congenital , Mice , Micrognathism , Osteogenesis , Pregnancy , Pyridines , Pharmacology , Signal Transduction
17.
Acta Physiologica Sinica ; (6): 248-260, 2019.
Article in English | WPRIM | ID: wpr-777191

ABSTRACT

Prostaglandin (PG) E plays critical roles during pregnancy and parturition. Emerging evidence indicates that human labour is an inflammatory event. We sought to investigate the effect of PGE on the output of proinflammatory cytokines in cultured human uterine smooth muscle cells (HUSMCs) from term pregnant women and elucidate the role of subtypes of PGE receptors (EP, EP, EP and EP). After drug treatment and/or transfection of each receptor siRNA, the concentrations of inflammatory secreting factors in HUSMCs culture medium were detected by the corresponding ELISA kits. The results showed that, PGE increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) output, decreased chemokine (c-x-c motif) ligand 8 (CXCL8) output in a dose-dependent manner, but had no effect on IL-1β and chemokine (c-c motif) ligand 2 (CCL-2) secretion of HUSMCs. EP/EP agonist 17-phenyl-trinor-PGE stimulated IL-6 and TNFα whilst suppressing IL-1β and CXCL8 output. The effects of 17-phenyl-trinor-PGE on IL-1β and CXCL8 secretion were remained whereas its effect on IL-6 and TNFα output did not occur in the cells with EP knockdown. The stimulatory effects of 17-phenyl-trinor-PGE on IL-6 and TNFα were remained whereas the inhibitory effects of 17-phenyl-trinor-PGE on IL-1β secretion was blocked in the cells with EP knockdown. Either of EP and EP agonists stimulated IL-1β and TNFα output, which was reversed by EP and EP siRNA, respectively. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked EP/EP modulation of TNFα and CXCL8 output. PI3K inhibitor LY294002 and P38 inhibitor SB202190 blocked 17-phenyl-trinor-PGE-induced IL-1β and IL-6 output, respectively. The inhibitors of adenylyl cyclase and PKA prevented EP and EP stimulation of IL-1β and TNFα output, whereas PLC and PKC inhibitors blocked EP- and EP-induced TNFα output but not IL-1β output. Our data suggest that PGE receptors exhibit different effects on the output of various cytokines in myometrium, which can subtly modulate the inflammatory microenvironment in myometrium during pregnancy.


Subject(s)
Cells, Cultured , Chromones , Pharmacology , Cytokines , Metabolism , Female , Humans , Imidazoles , Pharmacology , Inflammation , Morpholines , Pharmacology , Myocytes, Smooth Muscle , Cell Biology , Myometrium , Cell Biology , Phosphatidylinositol 3-Kinases , Pregnancy , Pyridines , Pharmacology , Receptors, Prostaglandin E , Physiology
18.
Article in Chinese | WPRIM | ID: wpr-776054

ABSTRACT

Objective To assess the efficacy and safety of apatinib in the treatment of advanced colorectal cancer(CRC). Methods The clinical data of 16 CRC patients treated with apatinib after failure of prior lines of treatment were retrospectively analyzed in terms of objective response rate,disease control rate,progression-free survival,overall survival,adverse events,and prognostic factors. Results The efficacy was evaluable in 14 patients,among whom the objective response rate was 7.1% and the disease control rate was 50%.The median progression-free survival was 3 months(95%CI=1.57-4.42),and the median overall survival was 6.5 months(95%CI=4.10-8.89).The safety was evaluable in 16 patients,among whom the most common grade 3 adverse events were hypertensinon(37.5%)and proteinuria(25%).No grade 4 adverse event was observed.Multivariate analysis did not show any factor directly related to survival.Conclusion Apatinib may be effective in treating advanced CRC,with tolerable side effects.


Subject(s)
Antineoplastic Agents , Therapeutic Uses , Colorectal Neoplasms , Drug Therapy , Humans , Pyridines , Therapeutic Uses , Retrospective Studies , Survival Analysis
19.
Article in Chinese | WPRIM | ID: wpr-776037

ABSTRACT

Multi-target anticancer drugs have a more comprehensive and extensive range of action,and there is an uncertain risk in the combination of two drugs.A case of acute toxicity induced by erlotinib combined with cabozantinib is reported in this article.


Subject(s)
Anilides , Drug Eruptions , Drug Therapy, Combination , Erlotinib Hydrochloride , Humans , Myocardial Infarction , Pyridines
20.
Chinese Journal of Lung Cancer ; (12): 264-270, 2019.
Article in Chinese | WPRIM | ID: wpr-775633

ABSTRACT

BACKGROUND@#Lung cancer is one of the most deadly cancers in the world for human. In recent years, the effect of targeted therapy has become increasingly significant. Apatinib is a multi-target anti-tumor drug that is currently under study. The purpose of this study is to investigate the effects of Apatinib on the biological characteristics of lung cancer cells and its possible mechanism.@*METHODS@#Lung cancer cell lines H1299 and H3255 were cultured in vitro. The effects of Apatinib on proliferation, migration and invasion of H1299 and H3255 cells were detected by cell proliferation assays wound healing assays and Transwell assays. The protein expression related to cancer angiogenesis and invasion was detected by Western blot.@*RESULTS@#Apatinib significantly inhibited the proliferation, migration and invasion of H1299 and H3255 in a concentration-dependent manner. Western blot showed that with the increasing of drug concentration, VEGF, VEGFR2, N-cadherin, MMP9, MMP2 and Vimentin were down-regulated, and E-cadherin were up-regulated.@*CONCLUSIONS@#Apatinib can inhibit the invasion and migration of lung adenocarcinoma cells H1299 and H3255. By regulation of epithelial-mesenchymal transition and the expression of matrix metalloproteinase-related proteins.


Subject(s)
Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cell Movement , Humans , Lung Neoplasms , Pathology , Neoplasm Invasiveness , Pyridines , Pharmacology
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