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1.
Front Immunol ; 15: 1336311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585260

RESUMO

Envafolimab is a Chinese domestic innovative fusion of a humanized single-domain programmed death-ligand 1 (PD-L1) antibody (dAb) and human immunoglobulin IgG1 crystalline fragment (Fc) developed for subcutaneous injections. It was granted conditional market authorization by the China National Medical Product Administration (NMPA) in December 2021. Envafolimab is used to treat adult patients with previously treated microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) advanced solid tumors, including patients with advanced colorectal cancer disease progression who were previously administered fluorouracil, oxaliplatin, and irinotecan, as well as other patients with advanced solid tumors who experienced disease progression after receiving standard treatment and had no other alternative treatment options. However, the lack of post-marketing clinical trial data requires conducting more clinical studies on the safety and efficacy of envafolimab in order to provide scientific basis and a reference for future therapeutic applications. In this paper, we report a case of severe skin necrosis and bleeding in the area of injection after subcutaneous administration of envafolimab in a patient diagnosed with hepatocellular carcinoma. We discuss issues that must be considered before administration of a PD-L1 inhibitor subcutaneously, which could induce immune mechanisms leading to skin necrosis in the area of injection.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Imunoglobulina G , Progressão da Doença , Necrose
2.
Cell Commun Signal ; 22(1): 164, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448900

RESUMO

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.


Assuntos
Neoplasias Hepáticas , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Sequenciamento do Exoma , Tumores Neuroendócrinos/genética , Genômica , Neoplasias Hepáticas/genética , Neoplasias Pancreáticas/genética , Microambiente Tumoral
4.
Environ Sci Pollut Res Int ; 28(16): 20894-20902, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33405174

RESUMO

Both the environmental and the ecological protection are key issues in the sustainable development of tourism. As a well-known world natural and cultural heritage, intensive study about the environment of Jiuzhaigou scenic spot has been launched since China's natural landscape protection. The field of low-carbon tourism is starting to be explored in China, and this article uses the life cycle assessment theory to evaluate the footprint of Jiuzhaigou. We find that the air quality is closely related to the number of tourists. Therefore, to maintain the environment of Jiuzhaigou, the number of tourists is proposed to restrict. The contribution of this paper is to provide pricing theory for attracting potential tourists and to give a theoretical basis for controlling the number of tourists in Jiuzhaigou Scenic Area.


Assuntos
Poluição do Ar , Pegada de Carbono , Carbono , China , Turismo
5.
World J Gastrointest Oncol ; 12(10): 1195-1208, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33133386

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis. AIM: To explore blood exosomal micro ribonucleic acids (miRNAs) as potential biomarkers for HCC diagnosis. RESULTS: The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits. CONCLUSION: This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.

6.
Oncol Rep ; 41(1): 257-269, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30542726

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and current treatments exhibit limited efficacy against advanced HCC. The majority of cancer-related deaths are caused by metastasis from the primary tumor, which indicates the importance of identifying clinical biomarkers for predicting metastasis and indicating prognosis. Patient-derived cells (PDCs) may be effective models for biomarker identification. In the present study, a wound healing assay was used to obtain 10 fast-migrated and 10 slow-migrated PDC cultures from 36 HCC samples. MicroRNA (miRNA) signatures in PDCs and PDC-derived exosomes were profiled by microRNA-sequencing. Differentially expressed miRNAs between the low- and fast-migrated groups were identified and further validated in 372 HCC profiles from The Cancer Genome Atlas (TCGA). Six exosomal miRNAs were identified to be differentially expressed between the two groups. In the fast-migrated group, five miRNAs (miR-140-3p, miR-30d-5p, miR-29b-3p, miR-130b-3p and miR-330-5p) were downregulated, and one miRNA (miR-296-3p) was upregulated compared with the slow-migrated group. Pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were significantly enriched in the 'focal adhesion' pathway, which is consistent with the roles of these miRNAs in tumor metastasis. Three miRNAs, miR-30d, miR-140 and miR-29b, were significantly associated with patient survival. These findings indicated that these exosomal miRNAs may be candidate biomarkers for predicting HCC cell migration and prognosis and may guide the treatment of advanced HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Exossomos/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Movimento Celular/genética , Células Cultivadas , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/citologia , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Prognóstico , Análise de Sobrevida
7.
Am J Physiol Lung Cell Mol Physiol ; 312(4): L477-L487, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28130257

RESUMO

To investigate the association between store-operated Ca2+ entry (SOCE) and reactive oxygen species (ROS) during hypoxia, this study determined the changes of transient receptor potential canonical 1 (TRPC1) and Orai1, two candidate proteins for store-operated Ca2+ (SOC) channels and their gate regulator, stromal interaction molecule 1 (STIM1), in a hypoxic environment and their relationship with ROS in pulmonary arterial smooth muscle cells (PASMCs). Exposure to hypoxia caused a transient Ca2+ spike and subsequent Ca2+ plateau of SOCE to be intensified in PASMCs when TRPC1, STIM1, and Orai1 were upregulated. SOCE in cells transfected with specific short hairpin RNA (shRNA) constructs was almost completely eliminated by the knockdown of TRPC1, STIM1, or Orai1 alone and was no longer affected by hypoxia exposure. Hypoxia-induced SOCE enhancement was further strengthened by PEG-SOD but was attenuated by PEG-catalase, with correlated changes to intracellular hydrogen peroxide (H2O2) levels and protein levels of TRPC1, STIM1, and Orai1. Exogenous H2O2 could mimic alterations of the interactions of STIM1 with TRPC1 and Orai1 in hypoxic cells. These findings suggest that TRPC1, STIM1, and Orai1 are essential for the initiation of SOCE in PASMCs. Hypoxia-induced ROS promoted the expression and interaction of the SOC channel molecules and their gate regulator via their converted product, H2O2.


Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Peróxido de Hidrogênio/farmacologia , Hipóxia/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/patologia , Animais , Catalase/metabolismo , Células Cultivadas , Técnicas de Silenciamento de Genes , Hipóxia/genética , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Proteína ORAI1/genética , Proteína ORAI1/metabolismo , Polietilenoglicóis/metabolismo , Ligação Proteica/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Superóxido Dismutase/metabolismo , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Acta Pharmacol Sin ; 36(12): 1487-96, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26592520

RESUMO

AIM: Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE(-/-) mice. In this study we investigated the bone phenotype and metabolism in aged apoE(-/-) mice. METHODS: Femurs and tibias were collected from 18- and 72-week-old apoE(-/-) mice and their age-matched wild-type (WT) littermates, and examined using micro-CT and histological analysis. Serum levels of total cholesterol, oxidized low-density lipoprotein (ox-LDL) and bone turnover markers were measured. Cultured bone mesenchymal stem cells (BMSCs) from tibias and femurs of 18-week-old apoE(-/-) mice were used in experiments in vitro. The expression levels of Sirt1 and Runx2 in bone tissue and BMSCs were measured using RT-PCR and Western blot analysis. RESULTS: Compared with age-matched WT littermates, young apoE(-/-) mice exhibited high bone mass with increased bone formation, accompanied by higher serum levels of bone turnover markers OCN and TRAP5b, and higher expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. In contrast, aged apoE(-/-) mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. After BMSCs were exposed to ox-LDL (20 µg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h. Treatment with the Sirt1 inhibitor EX527 (10 µmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs. CONCLUSION: In contrast to young apoE(-/-) mice, aged apoE(-/-) mice showe lower bone mass than age-matched WT mice. Long-lasting exposure to ox-LDL decreases the expression of Sirt1 and Runx2 in BMSCs, which may explain the decreased bone formation in aged apoE(-/-) mice.


Assuntos
Envelhecimento , Apolipoproteínas E/genética , Regulação para Baixo , Osteogênese , Sirtuína 1/genética , Animais , Densidade Óssea , Células Cultivadas , Deleção de Genes , Lipoproteínas LDL/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Tumour Biol ; 36(9): 7121-31, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25877754

RESUMO

Newcastle disease virus (NDV), an avian paramyxovirus, possesses the ability to kill tumor cells. Here, we report the effects of NDV strain D90, which was isolated in China, against oral squamous cell carcinoma (OSCC) cells. In this study, we showed that the cell death induced by D90 was apoptotic. Furthermore, the apoptosis induced by D90 was dependent on the mitochondrial pathway, and the death receptor pathway may be not involved. Bax and Bcl-2 also played a role in the apoptosis induced by D90. Lymph node metastasis is a serious problem for oral cancer; we therefore evaluated the impact of D90 on the migration and invasion of OSCC cells. NDV D90 affected microtubules and microfilaments to inhibit the motility of OSCC prior to apoptosis. The effects of D90 on the migration and invasion rates of OSCC cells were evaluated by migration and invasion assays. Subsequently, the changes in sp1, RECK, MMP-2, and MMP-9 induced by a low concentration of D90 were detected by western blot and gelatin zymography. D90 significantly inhibited the invasion and metastasis of OSCC cells by decreasing the expression of sp1 and increasing the expression of RECK to suppress the expression and activity of MMP-2 and MMP-9.


Assuntos
Carcinoma de Células Escamosas/terapia , Proteínas Ligadas por GPI/biossíntese , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Neoplasias Bucais/terapia , Vírus da Doença de Newcastle/genética , Animais , Apoptose/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas Ligadas por GPI/genética , Humanos , Metástase Linfática , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Terapia Viral Oncolítica , Fator de Transcrição Sp1/biossíntese
10.
World J Gastroenterol ; 18(40): 5695-701, 2012 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-23155309

RESUMO

AIM: To investigate the incidence of clinically detected port-site metastasis (PSM) in patients who underwent robotic surgery for biliary malignancies. METHODS: Using a prospective database, the patients undergoing fully robotic surgery for biliary malignancies between January 2009 and January 2011 were included. Records of patients with confirmed malignancy were reviewed for clinicopathological data and information about PSM. RESULTS: Sixty-four patients with biliary tract cancers underwent robotic surgery, and sixty patients met the inclusion criteria. The median age was 67 year (range: 40-85 year). During a median 15-mo follow-up period, two female patients were detected solitary PSM after robotic surgery. The incidence of PSM was 3.3%. Patient 1 underwent robotic anatomatic left hemihepatectomy and extraction of biliary tumor thrombi for an Klatskin tumor. She had a subcutaneous mass located at the right lateral abdominal wall near a trocar scar. Patient 2 underwent robotic pancreaticoduodenectomy for distal biliary cancer. She had two metachronous subcutaneous mass situated at the right lateral abdominal wall under a same trocar scar at 7 and 26 mo. The pathology of the excised PSM masses confirmed metastatic biliary adenocarcinoma. CONCLUSION: The incidence of PSMs after robotic surgery for biliary malignancies is relatively low, and biliary cancer can be an indication of robotic surgery.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias do Sistema Biliar/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Inoculação de Neoplasia , Robótica , Cirurgia Assistida por Computador/efeitos adversos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Ultrason Sonochem ; 19(5): 1033-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22440718

RESUMO

Amidinohydrazone compounds are very important synthetic intermediates and can serve as versatile precursors in synthesis of many natural products and drug molecules. The use of ultrasound, p-dodecylbenzenesulfonic acid (DBSA) and water as solvent improved the synthesis of different 2-(1,5-diaryl-1,4-pentadien-3-ylidene)-hydrazinecarboximidamide hydrochlorides. The best reaction conditions for the condensation of 1,5-diphenyl-1,4-pentadien-3-one with aminoguanidine hydrochloride were as follows: 1,5-diphenyl-1,4-pentadiene-3-one (1, 1 mmol), aminoguanidine hydrochloride (1.1 mmol), DBSA (0.5 mmol), water 10 mL, reaction temperature 25-27°C, irradiation frequency 25 kHz. 2a was achieved in 94% yield within 2h. The other seven amidinohydrazones were obtained in 84-94% yield within 2-3h under the same conditions. Compared to the method involving catalysis by hydrochloric acid in refluxing EtOH, the advantages of present procedure are milder conditions, shorter reaction times, higher yields, and environmental friendly conditions, which make it a useful strategy for the synthesis of analogues.


Assuntos
Benzenossulfonatos/química , Guanidinas/síntese química , Ultrassom , Catálise , Guanidinas/química , Estrutura Molecular , Água/química
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(7): 1942-5, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-21942057

RESUMO

In the present paper, the method for determining the trace elements Be, Cd, As and Pb in air of residential areas by inductively coupled plasma-mass spectrometry was established. Ultrasonic leaching procedures were applied to extract the trace elements from the filter membrane of the atmospheric particulates. The operating condition of the instrument was optimized. 72Ge, 115s In and 204Tl were chosen as the internal elements and the effect of matrix, interface and fluctuation of instrument was overcome effectively. Satisfactory linearity of working curves of four elements was obtained, giving all the correlation coefficients over 0.9995, and the detection limit of the method was between 0.006 and 0.045 ng x m(-3). The mean values of National Standard Reference Material GBW(E)080212 were in agreement with the certified values. The sampling filters membranes, divided into four equal parts and with added standard solution with different concentions were analyzed, and the recovery rate of samples were in the range of 91.6%-109.7% with the related standard deviation between 0.7% and 4.8%. The obtained results showed that the method of determining the trace elements Be, Cd, As and Pb in air of residential areas by inductively coupled plasma-mass spectrometry proved to be simple, accurate, sophisticated and stable.

13.
Ultrason Sonochem ; 18(1): 412-4, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20727812

RESUMO

Ultrasound-promoted synthesis of bis(indolyl)methanes catalyzed by ABS via the reaction of indole or N-methylindole with aromatic aldehyde was carried out in excellent yields in aqueous media at 23-25°C, providing a simple and efficient synthesis of these compounds.


Assuntos
Benzenossulfonatos/química , Indóis/síntese química , Ultrassom , Catálise , Indóis/química , Água/química
14.
Calcif Tissue Int ; 86(5): 404-10, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20354682

RESUMO

To explore the local mechanisms of fibroblast growth factor (FGF) 23 regulations, we examined the FGF23 expression patterns in an osteoblast culture model. The characteristics of cultured rat calvaria osteoblasts in half-confluence, confluence, osteoid deposition, and osteoid mineralization stages might reflect the proliferation, differentiation, maturation, and matrix mineralization stages, respectively. Compared with proliferating cells in half-confluence, FGF23 expression was upregulated by 7.5-fold at the mRNA level and 126% at the protein level in confluent differentiated cells as determined by real-time RT-PCR and Western blot analysis. Interestingly, mRNA levels of CYP27B1 (the gene coding for 1alpha-hydroxylase enzyme which catalyses the conversion of 1alpha,25-dihydroxyvitamin D, 1alpha,25[OH]2D, from its inactive form, 25-hydroxycholecalciferol, 25[OH]D) and CYP24A (the gene coding for 24-hydroxylase, a target gene of 1alpha,25[OH]2D) were significantly increased by twofold and 34-fold, respectively, in differentiated osteoblasts compared with proliferating cells. We next examined if the local production of 1alpha,25(OH)2D might contribute to the FGF23 upregulation. We cultured osteoblasts in serum-free medium with or without 25-(OH)D (the substrate of 1alpha-hydroxylase). FGF23 mRNA levels were increased in proliferating cells (16-fold) and in differentiated cells (28-fold) by the physiological dose of 25-(OH)D3 treatment. CYP27B1 was slightly but significantly upregulated and CYP24A was increased by 1,700-fold and 800-fold, respectively, in transcriptional levels. Because FGF23 was upregulated in confluent osteoblasts regardless of the presence or absence of 25-(OH)D in serum-free medium, we further examined the possible impact of cell communication on FGF23 expression. We treated osteoblasts with carbenoxolone, a gap junction Cx43 blocker in serum-free medium. The FGF23 mRNA level was reduced by 50% in confluent differentiated cells and slightly but not significantly reduced in half-confluent cells by carbenoxolone treatments. The results suggested that upregulation of FGF23 in differentiated osteoblast appeared to be due to increased autocrine/paracrine action of osteoblast-derived 1alpha,25(OH)2D and increased cell communication, which were identified in cultured rat calvaria osteoblasts. These results indicate that FGF23 expression was stimulated not only by circulating calcitriol but also by locally produced 1alpha,25(OH)2D. The local mechanisms of FGF23 expression remain to be characterized.


Assuntos
Comunicação Autócrina/efeitos dos fármacos , Calcitriol/farmacologia , Fatores de Crescimento de Fibroblastos/metabolismo , Osteoblastos/efeitos dos fármacos , Comunicação Parácrina/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Comunicação Autócrina/fisiologia , Western Blotting , Carbenoxolona/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fatores de Crescimento de Fibroblastos/genética , Expressão Gênica/efeitos dos fármacos , Osteoblastos/metabolismo , Comunicação Parácrina/fisiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Crânio/citologia , Regulação para Cima/efeitos dos fármacos
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