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1.
Waste Manag ; 103: 370-377, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31927327

RESUMO

To understand the evolution and mechanism of the hydrothermal carbonization products of colored cotton fiber, hydrothermal carbonization experiments were carried out on colored cotton fiber dyed with reactive red X-3B and reactive blue KN-R. Fourier transform infrared spectroscopy, X-ray diffraction, and elemental analysis were used to characterize the hydrochar from colored cotton fiber and the hydrothermal behavior of reactive dyes under different reaction temperatures and time conditions. The study showed that when the reaction temperature was in the range of 210-250 °C, hydrolysis of reactive dyes was complete in 6 h, and organic acid that is produced by the degradation of cotton fiber accelerates the hydrolysis of dyes. Also, the hydrolysis products of dyes were involved in the hydrothermal carbonization of cotton fiber and covered the inside of the carbon microspheres; this led to changes in the elemental composition and functional group of the hydrochar. However, the dye content in colored fabric was limited because of limited dye-uptake. Consequently, the reactive activity of dyes was not strong enough to change the hydrothermal behavior of cotton fiber.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31713023

RESUMO

PBC is a chronic progressive autoimmune disorder involving the destruction of intrahepatic small bile ducts, cholestasis, fibrosis, and ultimately cirrhosis if left untreated. It is largely driven by the autoimmune response, but bile acids and the intestinal microbiota are implicated in disease progression as well. The only drugs licensed for PBC are UDCA and OCA. UDCA as a first-line and OCA as a second-line therapy are safe and effective, but the lack of response in a significant portion of patients and inadequate control of symptoms such as fatigue and pruritus remain as concerns. Liver transplantation is an end-stage therapy for many patients refractory to UDCA, which gives excellent survival rates but also moderate to high recurrence rates. The limited options for FDA-approved PBC therapies necessitate the development of alternative approaches. Currently, a wide variety of experimental drugs exist targeting immunological and physiological aspects of PBC to suppress inflammation. Immunological therapies include drugs targeting immune molecules in the B cell and T cell response, and specific cytokines and chemokines implicated in inflammation. Drugs targeting bile acids are also noteworthy as bile acids can perpetuate hepatic inflammation and lead to fibrosis over time. These include FXR agonists, ASBT inhibitors, and PPAR agonists such as bezafibrate and fenofibrate. Nonetheless, many of these drugs can only delay disease progression and fail to enhance patients' quality of life. Nanomedicine shows great potential for treatment of autoimmune diseases, as it provides a new approach that focuses on tolerance induction rather than immunosuppression. Tolerogenic nanoparticles carrying immune-modifying agents can be engineered to safely and effectively target the antigen-specific immune response in autoimmune diseases. These may work well with PBC especially, given the anatomical features and immunological specificity of the disease. Nanobiological therapy is thus an area of highly promising research for future treatment of PBC.

3.
J Orthop Surg Res ; 14(1): 239, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358044

RESUMO

BACKGROUND: This study aimed to confirm the diagnostic accuracy of ultrasound (US) on gout and explore the potential risk factors for double-contour sign and tophi formation in gout patients. METHODS: The US analyses were performed on all knee, ankle, and first metatarsophalangeal (MTP 1) joints to reveal the type and location of lesions. While a questionnaire and blood biochemical index were used to explore the potential risk factors for double-contour sign and tophi in gout, the SPSS17.0 software was used for statistical analysis in the present study. RESULTS: Totally, 117 gout patients with 702 joints (38 lesions in knee joint, 93 lesions in ankle joint, and 112 lesions in MTP 1 joint) were enrolled in current analyses. Double-contour sign and joint effusion were the two most outstanding lesion manifestations in knee joints and ankle joints. Tophi and double-contour sign were the two most outstanding lesion manifestations in TMP 1 joints. Moreover, factors including uric acid (UA) level and the highest blood UA were potential risk factors of the double-contour sign, while age and history of US were potential risk factors for tophi. CONCLUSION: US was effective on the joints of gout patients. There was US sensitivity for tophi and double-contour sign in MTP 1 joints. The double-contour sign was a potential specific manifestation in knee joints and ankle joints. Furthermore, UA and highest blood UA level were potential risk factors for double-contour sign, while age and US history were potential risk factors for tophi.


Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Gota/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Articulação Metatarsofalângica/diagnóstico por imagem , Adulto , Articulação do Tornozelo/metabolismo , Feminino , Gota/metabolismo , Humanos , Articulação do Joelho/metabolismo , Masculino , Articulação Metatarsofalângica/metabolismo , Pessoa de Meia-Idade , Fatores de Risco , Ácido Úrico/metabolismo
4.
J Exp Clin Cancer Res ; 38(1): 84, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30777099

RESUMO

BACKGROUND: A promising arsenal of histone deacetylase (HDAC)-targeted treatment has emerged in the past decade, as the abnormal targeting or retention of HDACs to DNA regulatory regions often occurs in many cancers. Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies worldwide associated with poor overall survival in late-stage patients. HDAC inhibitors have great potential to treat this devastating disease; however, few has been studied regarding the beneficial role of HDAC inhibition in anti-HNSCC therapy and the underlying molecular mechanisms remain elusive. METHODS: Cell migration and invasion were examined by wound closure and Transwell assays. Protein levels and interactions were assessed by Western blotting and immunoprecipitation. HDAC activity was measured with the fluorometric HDAC Activity Assay. Phospho-receptor tyrosine kinase (RTK) profiling was determined by the Proteome Profiler Human Phospho-RTK Array. RESULTS: ADP-ribosylation factor 1 (Arf1), a small GTPase coordinating vesicle-mediated intracellular trafficking, can be inactivated by HDAC inhibitors through histone acetylation-independent degradation of epidermal growth factor receptor (EGFR) in HNSCC cells. Mechanistically, high levels of Arf1 activity are maintained by binding to phosphorylated EGFR which is localized on HNSCC cell plasma membrane. Decreased EGFR phosphorylation is associated with reduced EGFR protein levels in the presence of TSA, which inactivates Arf1 and eventually inhibits invasion in HNSCC cells. CONCLUSIONS: Our insights explore the critical role of EGFR-Arf1 complex in driving HNSCC progression, and demonstrate the selective action of HDAC inhibitors on this specific axis for suppressing HNSCC invasion. This novel finding represents the first example of modulating the EGFR-Arf1 complex in HNSCC by small molecule agents.


Assuntos
Fator 1 de Ribosilação do ADP/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/patologia , Inibidores de Histona Desacetilases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fator 1 de Ribosilação do ADP/metabolismo , Animais , Linhagem Celular Tumoral , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Histonas/metabolismo , Humanos , Camundongos , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
5.
Oncogene ; 38(13): 2394-2404, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30518874

RESUMO

The fibroblast growth factor 19 gene FGF19 has previously been reported to be amplified in several cancer types and encodes for a key autocrine signaler known to promote tumorigenic growth. Thus, it is imperative to understand which cancers are oncogenically addicted to FGF19 amplification as well as the role it serves in these cancer types. We report for the first time high FGF19 amplification in head and neck squamous cell carcinomas (HNSCC), which is associated with increased autocrine secretion of FGF19 and poor patient outcome in HNSCC. FGF19 amplification corresponded with constitutive activation of FGF receptor 4 (FGFR4)-dependent ERK/AKT-p70S6K-S6 signaling activation in HNSCC cells, and addition of human recombinant FGF19 could promote cell proliferation and soft agar colony formation in HNSCC cells with low FGF19 expression through activation of FGFR4 and downstream signaling cascades. In contrast, FGF19 knockout counteracts the observed effects in HNSCC cells carrying high endogenous FGF19, with knockout of FGF19 significantly suppressing tumor growth in an orthotopic mouse model of HNSCC. Collectively, this study demonstrates that FGF19 gene amplification corresponds with an increased dependency upon FGF19/FGFR4 autocrine signaling in HNSCC, revealing a therapeutic target for this cancer type.


Assuntos
Comunicação Autócrina/genética , Fatores de Crescimento de Fibroblastos/genética , Amplificação de Genes/genética , Neoplasias de Cabeça e Pescoço/genética , Oncogenes/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Transdução de Sinais/genética , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Masculino , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço
6.
J Cell Mol Med ; 23(2): 1174-1182, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30450674

RESUMO

The incidence rate of head and neck squamous cell carcinoma (HNSCC) has steadily increased over the past decade. However, treatment options for metastatic HNSCC are often limited and the 5-year survival rate has remained static. Therefore, the development and assessment of more efficient but less toxic therapeutic strategies is an unmet need for treatment of more extensive HNSCC. Here, we report that CYT997, a novel microtubule-disrupting agent, exerts strong activity in inhibiting HNSCC cell invasion and metastasis. The loss of invasion capacity by CYT997 was accompanied by an associated increase in cell adhesion and the reversal of epithelial-mesenchymal transition (EMT). Increased expression of E-cadherin protein and decreased expression of Vimentin protein became evident in HNSCC cells following CYT997 exposure, which were consistently observed in HNSCC xenografts from the mice receiving CYT997. Moreover, the capacity of invasive HNSCC cells to form pulmonary metastases was significantly blocked with CYT997 treatment, indicating that the diminishment of EMT traits contributes to CYT997-suppressed metastasis. Intriguingly, CYT997 impaired intracellular ATP levels in HNSCC cells, at least in part, through its inhibitory effect on the mitochondrial protein IF1. The addition of ATP attenuated CYT997-induced suppression of cell invasion, coupled with down-regulation of E-Cadherin and up-regulation of Vimentin. These findings support a critical role of ATP levels in cell invasion and metastasis under the influence of CYT997. Collectively, our data unveil the mechanism involved in mediating CYT997 action, and provide preclinical rationale for possible clinical application of CYT997 as a novel therapeutic strategy against aggressive HNSCC.

7.
Cereb Cortex ; 29(3): 994-1005, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29377991

RESUMO

Extracellular recording studies have revealed diverse and selective neural responses in the primary auditory cortex (A1) of awake animals. However, we have limited knowledge on subthreshold events that give rise to these responses, especially in non-human primates, as intracellular recordings in awake animals pose substantial technical challenges. We developed a novel intracellular recording technique in awake marmosets to systematically study subthreshold activity of A1 neurons that underlies their diverse and selective spiking responses. Our findings showed that in contrast to predominantly transient depolarization observed in A1 of anesthetized animals, both transient and sustained depolarization (during or beyond the stimulus period) were observed. Comparing with spiking responses, subthreshold responses were often longer lasting in duration and more broadly tuned in frequency, and showed narrower intensity tuning in non-monotonic neurons and lower response threshold in monotonic neurons. These observations demonstrated the enhancement of stimulus selectivity from subthreshold to spiking responses in individual A1 neurons. Furthermore, A1 neurons classified as regular- or fast-spiking subpopulation based on their spike shapes exhibited distinct response properties in frequency and intensity domains. These findings provide valuable insights into cortical integration and transformation of auditory information at the cellular level in auditory cortex of awake non-human primates.

8.
J Mol Med (Berl) ; 96(9): 929-938, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30022281

RESUMO

The functional relationship between apoptosis and autophagy in anticancer drug treatment is extremely complex, and the molecular machinery is obscure. This study aims to investigate the efficacy of CYT997, a novel microtubule-disrupting agent, in head and neck squamous cell carcinomas (HNSCCs) and complete the autophagy-apoptosis puzzle involved in drug action. We report here that CYT997 exhibits anticancer activity by triggering oxidative stress-associated apoptosis in HNSCC cells. Interestingly, upregulation of autophagy by mTOR-dependent pathways appears to have a cytoprotective role in preventing apoptosis by inhibiting CYT997-induced excessively high levels of reactive oxygen species (ROS). Blockade of autophagy by ATG7 depletion or addition of autophagy inhibitor hydroxychloroquine (HCQ) sensitizes HNSCC cells to CYT997 as evidenced by enhanced ROS-associated apoptosis. Moreover, HCQ exhibits a good synergism with CYT997 on induction of apoptosis in HNSCC xenografts without cytotoxicity, suggesting combined treatment of CYT997 with autophagy inhibitors would increase the anticancer efficacy of CYT997. These findings unveil the importance of ROS in crosstalk between autophagy and apoptosis in CYT997 treatment, raising concerns that genetic or pharmacologic blockade of autophagy should be considered in the design of new therapeutics for HNSCC. KEY MESSAGES: • CYT997 exhibits anticancer activity by induction of ROS-associated apoptosis. • mTOR-dependent cytoprotective autophagy prevents CYT997-induced apoptosis. • Blockade of autophagy augments CYT997 efficacy by enhanced ROS-associated apoptosis. • Combination of autophagy inhibitors with CYT997 is more effective against HNSCC.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Piridinas/farmacologia , Pirimidinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/ultraestrutura , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
J Pediatr Ophthalmol Strabismus ; 55(4): 219-224, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29709045

RESUMO

PURPOSE: To investigate the efficacy of a modified surgical procedure for esotropia fixus with high myopia. METHODS: Thirteen patients (15 eyes) with esotropia fixus and high myopia who underwent the Jensen procedure for superior and lateral rectus muscles at Southwest Hospital between February 2014 and December 2015 were retrospectively analyzed. Intraoperatively, the superior rectus and lateral rectus muscles were separated up to 12 to 14 mm posterior to their respective insertion. A medial rectus large recession or rectus tenotomy was performed based on the degree of fibrosis of the medial rectus muscle. Postoperative examinations were performed at 1 day, 2 weeks, 3 months, and 6 months. RESULTS: On the first postoperative day, 12 eyes (10 patients) were in the primary position (80.0%), 2 eyes (2 patients) exhibited 5° to 10° esotropia (13.3%), and 1 eye (1 patient) exhibited 15° esotropia (6.7%). At the 2-week follow up, 1 eye (1 patient) was lost to follow-up, 9 eyes (7 patients) were in the primary position (64.3%), 3 eyes (3 patients) exhibited 10° esotropia (21.4%), and 2 eyes (2 patients) exhibited 15° to 20° esotropia (14.3%). At the 3-month follow-up, the patient whose ocular alignment was 20° esotropia at 2 weeks was found to have developed 30° esotropia; no change was observed in the other patients. A remarkable improvement in ocular motility was observed in all patients. CONCLUSIONS: The Jensen procedure for the union of the superior rectus and lateral rectus muscles, using two pairs of sutures applied 12 to 14 mm posterior to their respective insertions, yielded favorable outcomes. [J Pediatr Ophthalmol Strabismus. 2018;55(4):219-224.].


Assuntos
Esotropia/cirurgia , Miopia Degenerativa/complicações , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Adulto , Idoso , Pesquisa Biomédica , Esotropia/diagnóstico por imagem , Esotropia/etiologia , Movimentos Oculares/fisiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/diagnóstico por imagem , Estudos Retrospectivos , Tenotomia , Resultado do Tratamento , Visão Binocular/fisiologia
10.
BMC Genomics ; 19(1): 38, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29320989

RESUMO

BACKGROUND: The growth of Inner Mongolian Cashmere goat skin hair follicle exhibits a periodic growth pattern. The hair growth cycle is distinguished as telogen, anagen, and catagen stages. The role of vimentin in the growth process of hair follicles is evident. To elucidate the mechanism underlying the vimentin activity in the growth cycle of hair follicles, transcriptome sequencing and liquid chromatography-tandem mass spectrometry were used to obtain the nucleic acid and amino acid sequences of VIIM gene and vimentin. The amino acid and nucleic acid sequences were analyzed by comparison. Real-time quantitative PCR, Western blot, and immunohistochemistry analyzed the expression level and sites of vimentin in the three growth stages of the Inner Mongolia Cashmere goat skin samples. RESULTS: VIM gene cDNA, obtained by transcriptome sequencing, was aligned against that of the Capra hircus VIM gene. The amino acid sequence of vimentin revealed a high similarity rate across other species. The expressions of both VIM gene and vimentin were highest during the growth period and lowest in the rest period. Furthermore, vimentin was primarily expressed in the outer root sheath of the hair follicle as assessed by staining. CONCLUSIONS: The sequences of the gene and protein are similar to that of other species and identical to Capra hircus. However, the expression of VIM and vimentin was proportional to that of the growth of hair follicles. And vimentin expressed only in the outer root sheath of hair follicles. Thus, vimentin was speculated to participate in the regulation of the hair follicle growth cycle by affecting the outer root sheath.


Assuntos
Cabras/crescimento & desenvolvimento , Folículo Piloso/crescimento & desenvolvimento , Vimentina/metabolismo , Sequência de Aminoácidos , Animais , China , Feminino , Expressão Gênica , Cabras/genética , Cabras/metabolismo , Folículo Piloso/metabolismo , RNA Mensageiro/química , Alinhamento de Sequência , Análise de Sequência de RNA , Vimentina/química , Vimentina/genética
11.
Cell Oncol (Dordr) ; 41(1): 85-91, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28983785

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC), a primary neoplasm derived from hepatocytes, is the second leading cause of cancer mortality worldwide. Previous work has shown that fibroblast growth factor 19 (FGF19), an oncogenic driver, acts as a negative regulator of the therapeutic efficacy of the tyrosine kinase inhibitor sorafenib in HCC cells. The FGF19-mediated mechanism affecting sorafenib treatment, however, still remains to be resolved. Here, we hypothesize that the FGF19-FGFR4 axis may affect the effectiveness of sorafenib in the treatment of HCC. METHODS: FGF19 and FGFR4 cDNAs were cloned into a pcDNA3.1 vector and subsequently used for exogenous over-expression analyses. FGF19 knockdown cells were generated using a lentiviral-mediated short hairpin RNA (shRNA) methodology and FGFR4 knockout cells were generated using a CRISPR-Cas9 methodology. FGFR4 activation in HCC cells was inhibited by BLU9931. The effects of exogenous gene over-expression, expression knockdown and knockout, as well as drug efficacies in HCC cells, were validated using Western blotting. HCC cell proliferation was assessed using a CellTiter 96® AQueous One Solution Cell Proliferation Assay, whereas NO levels were assessed using DAF-FM DA staining in conjunction with electrochemical biosensors. RESULTS: We found that FGF19, when exogenously overexpressed, results in a reduced sorafenib-induced NO generation and a decreased proliferation of HCC cells. In contrast, we found that either FGF19 silencing or knockout of its receptor FGFR4 sensitized HCC cells to sorafenib through the induction of NO generation. Concordantly, we found that inactivation of FGFR4 by BLU9931 enhanced the sensitivity of HCC cells to sorafenib. CONCLUSION: From our data we conclude that the FGF19-FGFR4 axis may play a critical role in the effects elicited by sorafenib in HCC cells. Blocking the FGF19-FGFR4 axis may provide novel opportunities to improve the efficacy of sorafenib in the treatment of patients with HCC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Neoplasias Hepáticas/metabolismo , Niacinamida/análogos & derivados , Óxido Nítrico/metabolismo , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Acrilamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Células Hep G2 , Humanos , Niacinamida/farmacologia , Óxido Nítrico/biossíntese , Quinazolinas/farmacologia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Sorafenibe
12.
Cancer Res ; 77(22): 6215-6225, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28951455

RESUMO

The tumor microenvironment induces endoplasmic reticulum (ER) stress in tumor cells, an event that can promote progression, but it is unknown how tumor cells adapt to this stress. In this study, we show that the fibroblast growth factor FGF19, a gene frequently amplified in hepatocellular carcinoma (HCC), facilitates a survival response to ER stress. Levels of FGF19 expression were increased in stressed HCC cells in culture and in a mouse xenograft model. Induction of ER stress required the transcription factor ATF4, which directly bound the FGF19 promoter. In cells where ER stress was induced, FGF19 overexpression promoted HCC cell survival and increased resistance to apoptosis, whereas FGF19 silencing counteracted these effects. Mechanistic investigations implicated glycogen synthase kinase-3ß (GSK3ß) in regulating nuclear accumulation of the stress-regulated transcription factor Nrf2 activated by FGF19. Our findings show how FGF19 provides a cytoprotective role against ER stress by activating a FGFR4-GSK3ß-Nrf2 signaling cascade, with implications for targeting this signaling node as a candidate therapeutic regimen for HCC management. Cancer Res; 77(22); 6215-25. ©2017 AACR.


Assuntos
Carcinoma Hepatocelular/metabolismo , Estresse do Retículo Endoplasmático , Fatores de Crescimento de Fibroblastos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Hepáticas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Animais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Fatores de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Transdução de Sinais , Transplante Heterólogo
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(4): 1101-1104, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28823276

RESUMO

OBJECTIVE: To observe the efficacy of chemotherapy consisted of bortezomib as main druy in maintenance therapy for recurrence of newly diagnosed MM patients. METHODS: The clinical data and outcome of 37 MM patients during 2008-2013 were analyzed retrospectively, the 37 MM patients were divided into 2 group: 19 cases including 13 cases of newly diagnosed MM with symptoms and 6 cases of relapsed refractory MM were enrolled in group A; 17 cases of newly diagnosed MM with symptoms were enrolled in group B. The patients of group A received maintenance therapy consisted of bortezomib plus dexamethasone (VD group), while the patient group B received maintenance therapy consisted of melphalan plus prednisone(MP group), then the therapeutic efficacy of 2 group was compared. RESULTS: The overall response rate(ORR) in VD groupe was 84.2%(16/19), out of which CR rate reached 42%(8/19), PR rate reached 31.6%(6/19), MR rate reached 10.5%(3/19). During median follow-up for 21.8(5-51) months, death occurred, while the ORR in MP group was 52(9/17), out of which CR rate was 23.5%(4/17), PR rate reached 23.5%(4/17), MR rate reached 5.9%(1/17). Druing median follow-up for 16.4(4-39) months, the worteity reaced 64.7%(11/17). The differencr between 2 groups was significant(P<0.05). The median OS time of patients in VD group was 21.6 months, that in MP group was 17.9 months(P<0.05). The median PFS in VD group and MP group were 13.4 and 9.4 months respectively(P<0.001). CONCLUSION: The ORR and CR rates of bortezomib maintenance therapy for newly diagnosed and relapsed / refractory MM patients are very high, and its toxicity can be controlled, therefore, the patients need maintenance therapy after remission.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica , Ácidos Borônicos , Bortezomib , Dexametasona , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento
14.
J Hematol Oncol ; 10(1): 118, 2017 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-28606127

RESUMO

BACKGROUND: Abnormalities of tubulin polymerization and microtubule assembly are often seen in cancer, which make them very suitable targets for the development of therapeutic approach against rapidly dividing and aggressive cancer cells. CYT997 is a novel microtubule-disrupting agent with anticancer activity in multiple cancer types including prostate cancer. However, the molecular mechanisms of action of CYT997 in prostate cancer have not been well characterized. METHODS: Src knockdown cells were achieved by lentiviral-mediated interference. The drug effects on cell proliferation were measured by MTS. The drug effects on cell viability and death were determined by Cell Titer-Glo® Luminescent cell viability kit and flow cytometry with Zombie Aqua™ staining. The drug effects on apoptosis were assessed by Cell Death Detection Elisa kit and Western blot with a cleaved PARP antibody. The drug effects on cell invasion were examined by Matrigel-coated Boyden chambers. Oxidative stress was detected by DCFH-DA staining and electrochemical biosensor. Mouse models generated by subcutaneous or intracardiac injection were used to investigate the in vivo drug efficacy in tumor growth and metastasis. RESULTS: CYT997 effectively inhibited proliferation, survival, and invasion of prostate cancer cells via blocking multiple oncogenic signaling cascades but not the Src pathway. Inhibition of Src expression by small hairpin RNA or inactivation of Src by dasatinib increased the CYT997-induced cytotoxicity of in vitro. Moreover, the combination of dasatinib and CYT997 exhibited a superior inhibitory effect on tumor growth and metastasis compared with either of the drugs alone. CONCLUSION: Our findings demonstrate that blockage of Src augments the anticancer effect of CYT997 on prostate cancer and suggest that co-treatment of dasatinib and CYT997 may represent an effective therapeutic regimen for limiting prostate cancer.


Assuntos
Antineoplásicos/uso terapêutico , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Quinases da Família src/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Humanos , Masculino , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Quinases da Família src/metabolismo
15.
Oncotarget ; 8(28): 45356-45366, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28514761

RESUMO

Spinal cord injury (SCI) is currently incurable since treatments applied to clinic are limited to minimizing secondary complications and the mechanisms of injury-induced spinal cord damage are poorly understood. Zbtb38, also called CIBZ, is highly expressed in spinal cord and it functions as a negative regulator in SCI-induced apoptosis. We show here that Zbtb38 is downregulated under endoplasmic reticulum (ER) stress, which promotes ER stress-associated apoptosis in human bone marrow neuroblastoma cells. In the traumatic SCI mice, ER stress presented in injured spinal cord induced repression of Zbtb38 expression and triggered Zbtb38-mediated apoptosis. ChIP-QPCR analysis revealed that ATF4, an ER-stress inducible transcription factor, directly activated Zbtb38 transcription by binding to the Zbtb38 promoter. However, this binding was significantly reduced following SCI, leading to a sharp decrease in Zbtb38 expression. Restoring Zbtb38 function in injured spinal cord by injection of lentivirus containing Zbtb38 into SCI mice, significantly alleviated secondary damage of spinal cord with decreased ER stress-associated apoptosis and partially recovered spinal cord functions. These findings demonstrate that restoration of Zbtb38 expression can reduce secondary tissue damage after SCI, and suggest that a therapeutic strategy for targeting Zbtb38 may promote functional recovery of spinal cord for patients with SCI.


Assuntos
Proteínas Repressoras/metabolismo , Traumatismos da Medula Espinal/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose/genética , Células da Medula Óssea , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Modelos Biológicos , Regiões Promotoras Genéticas , Ligação Proteica , Recuperação de Função Fisiológica , Proteínas Repressoras/genética , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/patologia
16.
Immunol Lett ; 188: 9-12, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28528128

RESUMO

PURPOSE: We attempted to evaluate the diagnostic value of different salivary gland ultrasonography (SGUS) scoring systems for primary sjögren's syndrome (pSS). METHODS: Total 134 patients with pSS and 109 non-SS sicca controls were included in our study. All the cases were evaluated by four scoring systems (such as 0-16 SGUS, 0-3 SGUS, Parotid glands and Submandibular salivary glands scoring system). The receiver operating characteristic (ROC) analysis was performed for the four scoring systems. RESULTS: The mean scores of pSS patients were significantly higher than that of controls by four scoring systems (P<0.01). The AUC (area under the curve) of (0-16) SGUS scoring system (0.916) was higher than Submandibular salivary glands scoring system (0.885) (P=0.016). No significant difference of AUC was observed in (0-3) SGUS scoring system, compared with 0-16, parotid gland and submandibular salivary glands scoring system. The optimal cutoff value of (0-16) SGUS, (0-3) SGUS, Parotid gland, Submandibular salivary glands scoring system was 5, 2, 3, 2, respectively. There was no significant difference in the sensitivity and specificity of the four scoring systems. CONCLUSION: The simplified parotid gland scoring system may be the simplified and feasible method for pSS diagnosis.


Assuntos
Glândulas Salivares/patologia , Síndrome de Sjogren/diagnóstico , Adulto , Idoso , Área Sob a Curva , Autoanticorpos/imunologia , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença , Síndrome de Sjogren/imunologia , Ultrassonografia
17.
Future Med Chem ; 9(3): 335-345, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28176543

RESUMO

Autophagy is a self-protective mechanism of living cells or organisms under various stress conditions. Studies of human genetics and pathophysiology have implicated that alterations in autophagy affect the context of cellular homeostasis and disease-associated phenotypes. The molecular components of autophagy are currently being explored as new pharmacologic targets for drug development and therapeutic intervention of various diseases. Drugs that restore the normal autophagic pathways have the potential for effectively treating human disorders that depend on aberrations of autophagy. Here, we review the role of autophagy and its alterations in the pathogenesis of diverse diseases, and drug discovery strategies for modulating autophagy for therapeutic benefits as well as possible safety concerns and caveats associated with such approaches.


Assuntos
Autofagia/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Homeostase/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Neoplasias/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
18.
Angle Orthod ; 87(4): 534-541, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28165289

RESUMO

OBJECTIVE: To evaluate the effect of material thickness and width of the gingival edge on the forces and moments delivered by aligners prepared from Duran foil (PET-G) to a maxillary incisor during tipping and intrusion. MATERIALS AND METHODS: Aligners prepared from PET-G of three material thicknesses (0.5, 0.625, and 0.75 mm) and three widths of gingival edges (0-1, 3-4, and 6-7 mm) were investigated during incisor palatal tipping and intrusion of 0.5 mm each. Forces and moments were measured with a six-component measuring device. The influence of aligner thickness and aligner extend on the force and moment development were tested for statistical significance (P < .05). RESULTS: The Fx and Fz forces produced during palatal tipping and intrusion by the 0.75-mm aligner material was significantly higher than those produced by the 0.5-mm-thick material (P = .005 and P = .047, respectively). There was no statistical difference between aligner thickness of 0.5 and 0.625 mm and between 0.625 and 0.75 mm. The same behavior was observed for the palatal moment (My). The Fx and Fz forces produced during palatal tipping and intrusion by the aligner with an extension of 0-1 mm edge was significantly lower than that of the aligner with a larger extension (3-4 mm edge: P = .003; 6-7 mm: P = .001). However, there was no statistical difference between aligners with a 3-4-mm and a 6-mm edge. The same behavior was observed for the palatal moment (My). CONCLUSIONS: The forces and moments exerted by the PET-G aligner on teeth vary, depending on the material thickness, width of the aligner edge, and direction of tooth movement.


Assuntos
Análise do Estresse Dentário , Desenho de Aparelho Ortodôntico , Aparelhos Ortodônticos Removíveis , Técnicas de Movimentação Dentária/instrumentação , Humanos , Incisivo , Maxila , Polietilenoglicóis , Polietilenotereftalatos
19.
Neuroscience ; 347: 36-47, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28188851

RESUMO

Neurons in the primary auditory cortex (A1) of adult animals exhibit short-term plasticity of frequency selectivity and tonotopic organization in behavioral contexts ranging from classical conditioning to attention tasks. However, it is still largely unknown whether short-term plasticity of spatial tuning takes place in A1 of adult animals and whether this spatial turning plasticity in A1 of adults is mediated by medial prefrontal cortex (mPFC) as there are reciprocal connection between mPFC and auditory cortex (AC). In the present study, we used extracellular recordings to test whether azimuth tuning in A1 of anesthetized rats can be reshaped by repeated sound stimuli at neurons' non-preferred azimuth. We also identified whether and how such A1 azimuth tuning plasticity was modulated by the neural activities of mPFC. Our results showed that A1 neurons in adult rats have azimuth tuning plasticity when repeated acoustic stimuli were delivered at the azimuth with a deviation by less than 15° from the best azimuth (BA). The BA shifted toward the exposure azimuth when repeated acoustic stimuli were played for 20-60min and plasticity decayed within one hour. The less the angle deviated from the BA, the shorter exposure time and longer decay time were required to induce azimuth tuning plasticity. Neural activity in mPFC modulated azimuth tuning plasticity of A1 neurons as reflected by the shorter induction time when mPFC was activated by focal electrical stimulation and the longer induction time when mPFC was inactivated by drug application. Our results suggest that spatial location selectivity in A1 neurons remains plastic in mature animals and that short-term plasticity of spatial tuning can be modulated by the neural activities of mPFC.


Assuntos
Córtex Auditivo/fisiologia , Plasticidade Neuronal , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Localização de Som/fisiologia , Estimulação Acústica , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
20.
Nanoscale Res Lett ; 12(1): 17, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28058651

RESUMO

A novel deoxyribose nucleic acid (DNA)-based photoelectrode consisting of DNA@Mn3(PO4)2 nanoparticles on graphene oxide (GO) sheets was successfully fabricated for photoelectrocatalysis. DNA served as a soft template to guide the nucleation and growth of Mn3(PO4)2 nanoparticles in the synthesis of Mn3(PO4)2 nanoparticles. More importantly, the DNA also serves as semiconductor materials to adjust charge transport. Under UV light irradiation (180-420 nm, 15 mW/cm2), the photocurrent density of DNA@ Mn3(PO4)2/GO electrodes reached 9 µA/cm2 at 0.7 V bias (vs. SCE). An applied bias photon-to-current efficiency (ABPE) of ~0.18% can be achieved, which was much higher than that of other control electrodes (<0.04%). In this DNA-based photoelectrode, well-matched energy levels can efficiently improve charge transfer and reduce the recombination of photogenerated electron-hole pairs.

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