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1.
Biomed Pharmacother ; 174: 116522, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565055

RESUMO

In recent decades, there has been a surge in the approval of monoclonal antibodies for treating a wide range of hematological and solid malignancies. These antibodies exhibit exceptional precision in targeting the surface antigens of tumors, heralding a groundbreaking approach to cancer therapy. Nevertheless, monoclonal antibodies alone do not show sufficient lethality against cancerous cells compared to chemotherapy. Consequently, a new class of anti-tumor medications, known as antibody-drug conjugates (ADCs), has been developed to bridge the divide between monoclonal antibodies and cytotoxic drugs, enhancing their therapeutic potential. ADCs are chemically synthesized by binding tumor-targeting monoclonal antibodies with cytotoxic payloads through linkers that are susceptible to cleavage by intracellular proteases. They combined the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity and boasting superior lethality over standalone targeted drugs. The human epidermal growth factor receptor (HER) family, which encompasses HER1 (also known as EGFR), HER2, HER3, and HER4, plays a key role in regulating cellular proliferation, survival, differentiation, and migration. HER2 overexpression in various tumors is one of the most frequently targeted antigens for ADC therapy in HER2-positive cancers. HER2-directed ADCs have emerged as highly promising treatment modalities for patients with HER2-positive cancers. This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.


Assuntos
Imunoconjugados , Neoplasias , Receptor ErbB-2 , Humanos , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Neoplasias/tratamento farmacológico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/imunologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
2.
Langmuir ; 39(46): 16494-16502, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37940415

RESUMO

Low-salinity flooding has been well recognized as a promising strategy to increase shale oil recovery, but the underlying mechanism remains unclarified, especially for complex nanopore networks filled with oil-brine fluids. In this study, the pressure-driven flow of an oil-brine fluid with varying salinities in shale nanopore-throat channels was first investigated based on molecular dynamics simulations. The critical pressure driving oil to intrude into a nanothroat filled with brine of varying salinities was determined. Simulation results indicate that the salinity of brine exhibits great effects on the movability of oil, and low salinity favors the increase of oil movability. Further analysis of the interactions between fluid and pore walls as well as the displacement pressures reveals dual effects of brine salinity on oil transportation in a nanopore-throat. On the one hand, hydrated cations anchoring onto throat walls enlarge the effective flow width in the throat before the hydration complexes reach the maximum. On the other hand, the interfacial tension between oil and brine increases with the brine salinity, which increases the capillary resistance and leads to a higher displacement pressure. These findings highlight the effects of brine salinity on oil movability in a nanopore-throat, which will promote the understanding of oil accumulation and dissipation in petroleum systems, as well as help to develop enhanced oil recovery.

3.
World J Urol ; 40(3): 795-800, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34851436

RESUMO

BACKGROUND: The management of complete staghorn stones remains a challenge for urologists, owing to the high stone burden, low stone free rate, and high rate of complications. Hence, we aimed to evaluate the outcomes of a technique involving combination laparoscopy and nephrolithotomy in the same session in patient with complete staghorn stones and poor performance status. METHODS: We retrospectively evaluated seven patients with complete staghorn stones who underwent a combination of laparoscopy and nephrolithotomy in the same session in our center between December 2016 and October 2019. The surgical technique was as follows. Through a four-port transperitoneal laparoscopic approach, the kidney was mobilized after complete dissection of the renal pedicle. The renal pelvis was then incised with a cold scalpel. A nephroscope was inserted into the renal collecting system through both a laparoscopic port and the renal pelvis incision. This method enabled visualization of and access to almost all calyces for clearing the stones from the affected kidneys in a hand-assisted manner which a hand was inserted in the peritoneal cavity. The outcome data included the stone-free rate, short-term and long-term complication rates, and stone recurrence rate. RESULTS: The stone free rate was 85.70% (6/7). No patients had sepsis or required blood transfusion perioperatively, and no major short-term complications occurred. After 24.00 (15.00, 48.00) months' follow-up, no patients had long-term complications, and only one patient had stone recurrence. CONCLUSION: The technique of combining laparoscopy and nephrolithotomy in the same session was an effective and safe treatment for patients with complete staghorn stones and poor performance status. The method was scarcely affected by the stone burden and morphology, had a satisfactory stone free rate, and resulted in no major complications, particularly life-threatening sepsis. It might be an option for such patients.


Assuntos
Cálculos Renais , Laparoscopia , Nefrostomia Percutânea , Cálculos Coraliformes , Seguimentos , Humanos , Cálculos Renais/cirurgia , Nefrostomia Percutânea/métodos , Estudos Retrospectivos , Cálculos Coraliformes/cirurgia , Resultado do Tratamento
4.
Environ Sci Technol ; 55(23): 15921-15928, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34817156

RESUMO

Iron hydroxides are ubiquitous in soils and aquifers and have been adopted as adsorbents for As(V) removal. However, the complexation mechanisms of As(V) have not been well understood due to the lack of information on the reactive sites and acidities of iron hydroxides. In this work, we first calculated the acidity constants (pKas) of surface groups on lepidocrocite (010), (001), and (100) surfaces by using the first-principles molecular dynamics (FPMD)-based vertical energy gap method. Then, the desorption free energies of As(V) on goethite (110) and lepidocrocite (001) surfaces were calculated by using constrained FPMD simulations. The point of zero charges and reactive sites of individual surfaces were obtained based on the calculated pKas. The structures, thermodynamics, and pH dependence for As(V) complexation were derived by integrating the pKas and desorption free energies. The pKa data sets obtained are fundamental parameters that control the charging and adsorption behavior of iron oxyhydroxides and will be very useful in investigating the adsorption processes on these minerals. The pH-dependent complexation mechanisms of As(V) derived in this study would be helpful for the development of effective adsorbent materials and the prediction of the long-term behavior of As(V) in natural environments.


Assuntos
Compostos de Ferro , Simulação de Dinâmica Molecular , Adsorção , Compostos Férricos , Concentração de Íons de Hidrogênio , Hidróxidos , Ferro , Minerais
5.
Respir Res ; 22(1): 194, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217280

RESUMO

BACKGROUND: We recently reported histone methyltransferase enhancer of zeste homolog 2 (EZH2) as a key epigenetic regulator that contributes to the dysfunction of innate immune responses to sepsis and subsequent lung injury by mediating the imbalance of macrophage polarization. However, the role of EZH2 in acute respiratory distress syndrome (ARDS)-associated fibrosis remains poorly understood. METHODS: In this study, we investigated the role and mechanisms of EZH2 in pulmonary fibrosis in a murine model of LPS-induced ARDS and in ex-vivo cultured alveolar macrophages (MH-S) and mouse lung epithelial cell line (MLE-12) by using 3-deazaneplanocin A (3-DZNeP) and EZH2 the small interfering (si) RNA. RESULTS: We found that treatment with 3-DZNeP significantly ameliorated the LPS-induced direct lung injury and fibroproliferation by blocking EMT through TGF-ß1/Smad signaling pathway and regulating shift of macrophage phenotypes. In the ex-vivo polarized alveolar macrophages cells, treatment with EZH2 siRNA or 3-DZNeP suppressed the M1 while promoted the M2 macrophage differentiation through modulating the STAT/SOCS signaling pathway and activating PPAR-γ. Moreover, we identified that blockade of EZH2 with 3-DZNeP suppressed the epithelial to mesenchymal transition (EMT) in co-cultured bronchoalveolar lavage fluid (BALF) and mouse lung epithelial cell line through down-regulation of TGF-ß1, TGF-ßR1, Smad2 while up-regulation of Smad7 expression. CONCLUSIONS: These results indicate that EZH2 is involved in the pathological process of ARDS-associated pulmonary fibrosis. Targeting EZH2 may be a potential therapeutic strategy to prevent and treat pulmonary fibrosis post ARDS.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Macrófagos/metabolismo , Fenótipo , Fibrose Pulmonar/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Animais , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/fisiologia , Técnicas de Cocultura , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/prevenção & controle , RNA Interferente Pequeno/administração & dosagem , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/prevenção & controle
6.
Mediators Inflamm ; 2021: 7858746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35002536

RESUMO

We recently reported the differential circRNA expression patterns of the pulmonary macrophages in sepsis-induced acute respiratory distress syndrome (ARDS) mice model by microarray analysis. However, their function and hidden molecular mechanism in regulation of macrophage activation and inflammation remain poorly understood. In this study, we found that circN4bp1was overexpressed in PBMC and monocytes, and its expression levels were correlated with a poor prognosis in sepsis induced ARDS patients induced by sepsis. Knockdown of circN4bp1 inhibited the lung injury and improved the long-time survival through blunting the M1 macrophage activation in cecal ligation and puncture- (CLP-) induced ARDS mice. Moreover, bioinformatics analysis predicated a circN4bp1/miR-138-5p ceRNA network, which was confirmed by luciferase reporter assay and RNA binding protein immunoprecipitation (RIP). CircN4bp1 affected macrophage differentiation by binding to miR-138-5p, thus regulating the expression of EZH2 in vivo and ex vivo. Lastly, the m6A level of circN4bp1was found to be elevated in ARDS mice; inhibition of m6A methyltransferase METTL3 blocked this response in vitro. Therefore, circN4bp1 can function as a miR-138-5p sponge for the modulation of macrophage polarization through regulation the expression of EZH2 and may serve as a potential target and/or prognostic marker for ARDS patients following sepsis.


Assuntos
MicroRNAs , Proteínas Nucleares/genética , RNA Circular , Proteínas de Ligação a RNA/genética , Síndrome do Desconforto Respiratório , Sepse , Animais , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , Metiltransferases/metabolismo , Camundongos , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Síndrome do Desconforto Respiratório/genética , Sepse/genética , Sepse/metabolismo
7.
Langmuir ; 35(46): 14818-14832, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31660745

RESUMO

The value of crude oil accommodated in shale has been recognized and has attracted increasing attention from the academic and industrial society. The occurrence and mobility of crude oil in clay pores, therefore, become essential issues for evaluation and recovery of shale oil. The distribution, structure, and transport of the oil-brine mixture confined in a slit-shaped montmorillonite mesopore with different water amounts have been investigated using equilibrium molecular dynamics and nonequilibrium molecular dynamics (NEMD) simulations. A mimic model of crude oil, a mixture of 19 organic molecules, was employed, and thus the behavior of different organic molecules could be characterized in detail. A temperature of 410 K and a pressure of 300 atm corresponding to a buried depth of 3 km were employed. The simulations indicate that the water amount determines the distribution of crude oil. Water and metal ions prefer to cover on hydrophilic montmorillonite surfaces, while nonpolar hydrocarbons tend to be far away from clay surfaces. As the water amount is too low to completely cover the clay surfaces, some polar organic molecules will come into contact with the uncovered clay surface. Abundant organic acid molecules adsorb onto montmorillonite surfaces mainly through participating in the inner-sphere complexes of Na+ ions closely located at montmorillonite surfaces (i.e., Na+ cation bridge) and forming hydrogen bonds with water molecules in the vicinity. Carbazole molecules tend to aggregate together due to π-π stacking, while thioether molecules mix within alkane molecules and exhibit no characteristic distributions. The mobility of all oil components decreases with the decrease of the water amount, and the mobility of polar components (i.e., organic acid and carbazole) is relatively lower than that of nonpolar hydrocarbons. NEMD simulations clearly indicate that the transport velocity of crude oil markedly increases with the water amount under a specific pressure gradient. The brine covering on clay surfaces significantly weakens oil-clay interfacial interactions. Polar components, especially organic acid, exhibit relatively low transport velocity compared with nonpolar hydrocarbons. These findings highlight the understanding of physical-chemical behaviors of shale oil and provide atomistic information for technology development for enhancing oil recovery.

8.
Int Immunopharmacol ; 76: 105899, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518916

RESUMO

The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown. We reported here that the expression of EZH2 and H3K27me3 was significantly upregulated in the circulation of septic patients, whereas patients who survived presented downregulated the expression of EZH2 on CD14+ monocytes. We further identified increased expression of EZH2 in the circulation, peritoneal fluid, and septic lungs from CLP mice. 3-DZNeP treated CLP mice improved mortality and protected from organ injury. EZH2 inhibition not only suppressed the activation of inflammatory cells and release of cytokines in the circulation and infectious sites, but also promoted bacteria clearance and replenished the circulating monocyte and neutrophil pool from bone marrow. Blockage of EZH2 also suppressed the progression of lung injury and alleviated inflammation by decreasing the pulmonary cell apoptosis, reducing inflammatory cells infiltration and cytokines release through inhibition of the STAT3 signaling pathway and recovery of PPARγ activation. In addition, EZH2 inhibitor blunted macrophage M1 polarization by SOCS3/STAT1 pathway. Overall, these data suggest that EZH2 could be a potential biomarker predicting clinical outcome and a new target for therapeutic interference in sepsis.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Sepse/imunologia , Adenosina/análogos & derivados , Adenosina/farmacologia , Adenosina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carga Bacteriana , Citocinas/imunologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Histona Desmetilases com o Domínio Jumonji/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Fagocitose , Sepse/tratamento farmacológico , Sepse/microbiologia , Sepse/patologia
9.
Shock ; 50(4): 455-464, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29194342

RESUMO

We recently reported that CD4CD25 regulatory T cells (Tregs) contributed to the recovery of patients with acute lung injury (ALI) by upregulating T cell immunoglobulin and mucin-domain containing-3 (Tim-3). However, the molecular mechanism by which Tim-3 regulates Tregs' function in the resolution and fibroproliferation after ALI remains unknown. In this study, we adoptively transferred Tim-3Tregs or Tim-3Tregs into lipopolysaccharide -induced ALI mice model. Data demonstrated that Tim-3Tregs not only decreased indices of lung inflammation and injury but also mitigated lung fibrosis after ALI. Furthermore, we observed that the transfer of Tim-3Tregs led to M2-like macrophage differentiation as demonstrated by significantly upregulated levels of M2-associated phenotypic markers as well as downregulated expressions of M1-related markers in both the profibrotic lung tissue and sorted pulmonary monocytes after ALI. In addition, cytokines such as interleukin (IL)-10 and IL-4 were also upregulated in lung tissues after Tim-3Tregs transferring. In vitro experiments further demonstrated that cell-contact cocultures with Tregs lacking Tim-3 presented decreased polarization of M2-like macrophages partially mediated by a decreased expression and function of STAT-3. Therefore, these data demonstrate a previously unrecognized function of Tim-3 on Tregs in their ability to repress the fibroproliferation of ALI by inducing alternative macrophages polarization. Moreover, the data highlight that Tim-3Tregs-mediated induction of M2-like macrophages may be a novel treatment modality with transitional potential.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Pulmão/metabolismo , Macrófagos/metabolismo , Linfócitos T Reguladores/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Células Cultivadas , Imuno-Histoquímica , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
10.
Medicine (Baltimore) ; 96(42): e8310, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29049237

RESUMO

BACKGROUND: Breast cancer (BC) is considered a systemic disease with a primarily locoregional component. The accumulation of basic researches and clinical studies related to cytokine-induced killer (CIK) cells has confirmed their safety and feasibility in treating BC. By searching the PubMed, Embase, CNKI, and Wanfang databases, we conducted a meta-analysis to assess the efficacy and safety of DC/CIK plus chemotherapy regimen (Exp) compared with chemotherapy (Con) alone regimen for breast carcinoma. Studies were pooled, and the relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated. METHODS: Eleven relevant articles were included in this meta-analysis. We observed that complete response (CR) (RR = 1.54, 95% CI: 1.09-2.19, Pheterogeneity = .994, I = 0%), partial response (PR) (RR = 1.33, 95% CI: 1.11-1.59, Pheterogeneity = .802, I = 0%) and overall response rate (ORR) (RR = 1.37, 95% CI: 1.20-1.57, Pheterogeneity = .619, I = 0%) in BC patients treatment with DC/CIK plus chemotherapy regimen was improved than that with chemotherapy alone. There was no difference in the incidence of leukopenia, thrombocytopenia, hair loss, nausea/vomiting, hepatic complications, and neurologic complications in BC patient's treatment with DC/CIK plus chemotherapy regimen and with chemotherapy alone. RESULTS: Compared to chemotherapy alone, DC/CIK plus chemotherapy treatment significantly increased CR, PR, and ORR; however, there was no difference between the safeties. CONCLUSION: DC/CIK plus chemotherapy treatment may be a valuable new option for the treatment of breast carcinoma in women. The present study, therefore, provides valuable information to help physicians make treatment decisions for their patients with BC.


Assuntos
Neoplasias da Mama/terapia , Células Matadoras Induzidas por Citocinas/imunologia , Células Dendríticas/imunologia , Imunoterapia Adotiva/métodos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos
11.
Intern Emerg Med ; 11(3): 415-23, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26758063

RESUMO

Acute lung injury (ALI) is a common complication in elderly pneumonia patients who have a rapid progression, and is accompanied by a high mortality rate. Because the treatment options of ALI are limited to supportive care, identifying pneumonia patients who are at higher risk of ALI development is the emphasis of many studies. Here, we approach this problem from an immunological perspective by examining CD19(+)CD24(hi)CD38(hi) B cells, an important participant in acute and chronic inflammation. We find that elderly pneumonia patients have elevated CD19(+)CD24(hi)CD38(hi) B cell frequency compared to healthy individuals. This B cell population may express a higher level of IL-10, which has been was shown to suppress CD4(+) T cell-mediated proinflammatory cytokine interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) production, through an IL-10-dependent mechanism. We also observe that the frequency of CD19(+)CD24(hi)CD38(hi) B cell is positively correlated with the frequency of CD4(+)CD25(+)Foxp3(+)Tregs in peripheral blood. Moreover, consistent with CD19(+)CD24(hi)CD38(hi) B cell's anti-inflammatory role, we find that pneumonia patients who later developed ALI have reduced level of CD19(+)CD24(hi)CD38(hi) B cells. Together, our results demonstrated that CD19(+)CD24(hi)CD38(hi) B cells in pneumonia patients possess regulatory function in vivo, and are associated with a reduced ALI risk.


Assuntos
Lesão Pulmonar Aguda/imunologia , Antígenos CD19/metabolismo , Linfócitos B Reguladores/metabolismo , Pneumonia/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B Reguladores/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , China , Ensaio de Imunoadsorção Enzimática , Feminino , Avaliação Geriátrica , Hospitais Gerais , Humanos , Masculino , Pneumonia/microbiologia , Pneumonia/fisiopatologia , Prognóstico , Valores de Referência , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Regulação para Cima
12.
PLoS One ; 10(3): e0122047, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25822612

RESUMO

BACKGROUND: Docetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy. METHODS: We conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed. RESULTS: Obese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel. CONCLUSION: Obese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.


Assuntos
Antineoplásicos/administração & dosagem , Composição Corporal , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Índice de Massa Corporal , Docetaxel , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Resultado do Tratamento
13.
Asian Pac J Cancer Prev ; 15(7): 3045-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24815445

RESUMO

Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.


Assuntos
Carcinoma de Células Renais/genética , Fatores de Crescimento Endotelial/genética , Neoplasias Renais/genética , Neovascularização Patológica/genética , RNA Interferente Pequeno/administração & dosagem , Inibidores da Angiogênese/genética , Animais , Apoptose/genética , Proteínas de Ligação ao Cálcio , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Família de Proteínas EGF , Fatores de Crescimento Endotelial/biossíntese , Receptores ErbB/antagonistas & inibidores , Feminino , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Gefitinibe , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Zhongguo Gu Shang ; 27(1): 67-9, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24754151

RESUMO

OBJECTIVE: To explore the technique and clinical results of close reduction by manipulation and minimally invasive percutaneous osteosynthesis with intramedullary nail for the treatment of femur shaft fractures. methods: A retrospective study was conducted to analyze 96 patients with the femur shaft fractures who had been treated with close reduction by manipulation and minimally invasive percutaneous osteosynthesis with intramedullary nail. There were 67 males and 29 females. The average age of patients was 39 years old (ranging from 16 to 88). According to AO fracture classification for the femur shaft fractures,there were 29 cases of type A,46 type B,21 type C. RESULTS: All the patients were followed up and the duration ranged from 12 to 24 months (averaged, 15 months). All the fractures showed union. The time required for the bony union ranged from 3 to 10 months (averaged,4 months). The clinical results were evaluated by Thorsen classification system. At the latest follow-up, 87 patients obtained excellent results, 7 good, 2 fair. CONCLUSION: This treatment method combines advantages of intramedullary nail with close manipulative reduction, so can get satisfactory clinical results for the treatment of femoral shaft fracture with minimal trauma.


Assuntos
Pinos Ortopédicos , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Manipulações Musculoesqueléticas/métodos , Técnicas de Fechamento de Ferimentos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/terapia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
Zhongguo Gu Shang ; 24(8): 693-4, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21928683

RESUMO

OBJECTIVE: To explore the technique and clinical results of close reduction by manipulation and minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of supracondylar femur fractures. METHODS: A retrospective study was conducted to analyze 39 patients with the supracondylar femur fractures who had been treated with close reduction by manipulation and MIPPO. There were 24 males and 15 females. The average age of the patients was 47 years old (ranged, 19 to 81 years). According to AO fracture classification for the distal femur fractures, there were 14 patients with type A1, 16 patients with type A2 and 9 patients with type A3. RESULTS: All the patients were followed up, and the period ranged from 12 to 24 months (averaged 16 months). All the fractures showed union. The time required for the bony union ranged from 3 to 10 months (averaged 4 months). The patients were evaluated according to Kolmert distal femoral fracture functional evaluation system. Twenty-eight patients obtained an excellent result, 10 good and 1 fair. CONCLUSION: This method for the treatment of supracondylar femur fracture can get satisfactory function, high rate of bone union and less complications. Familiar with the close reduction technique and the geometry shape of anatomic plate as well as femoral supracondyar area are important to treat the supracondylar femur fractures.


Assuntos
Placas Ósseas , Fraturas do Fêmur/terapia , Fixação Interna de Fraturas/métodos , Manipulação Ortopédica/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos
16.
Zhongguo Gu Shang ; 24(5): 429-30, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21688548

RESUMO

OBJECTIVE: To investigate the technique and clinical results of minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of the distal fractures of tibia by an appropriate plate. METHODS: From Jan. 2005 to Dec. 2007, 56 patients with the distal tibia fractures were treated with MIPPO through two approaches and three types of plate involving clover plate in 35 cases, anterior L-shape anatomic plate in 12 cases, medial LCP in 9 cases. There were 38 males and 18 females with an average age of 41 years old ranging from 17 to 72 years. According to AO fracture classification for the distal tibial fractures, there were 28 cases of type A, 11 of type B, 17 type C. RESULTS: All the patients were followed up from 12 to 24 months (averaged 16 months). All of the fractures showed bone union. The time required for the bony union ranged from 3 to 11 months (averaged 4 months). The patients were evaluated on functional recovery according to Mazur Grating System for the Ankle. The results were excellent in 51 cases, good in 5. CONCLUSION: Choosing effective reasonable approach and plate for the treatment of the distal tibial fractures can obtain satisfactory function, high rate of bone union and less complications.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pele , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Tíbia/fisiopatologia , Resultado do Tratamento , Adulto Jovem
17.
Langmuir ; 24(19): 10929-35, 2008 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-18729339

RESUMO

The sorption and desorption of phenanthrene by three engineered nanoparticles including nanosize zerovalent iron (NZVI), copper (NZVC), and silicon dioxide (NSiO2) were investigated. The sorption of phenanthrene onto NSiO2 was linear and reversible due to the hydrophilic properties of NSiO2. In comparison, sorption of phenanthrene onto NZVI and NZVC was nonlinear and irreversible, which was potentially due to the existence of significantly heterogeneous surface energy distribution patterns detected by a standard molecular probe technique. Naphthalene exerted significant competitive sorption with phenanthrene for NZVI and NZVC, and the isotherm of phenanthrene changed from being significantly nonlinear to nearly linear when naphthalene was simultaneously absorbed. A surface adsorption mechanism was proposed to explain the observed sorption and competition of phenanthrene on both NZVI and NZVC. In contrast, no competition was observed for sorption onto NSiO2. The sorption of phenanthrene on all three nanoparticles significantly decreased with increasing pH. The sorption irreversibility of phenanthrene on NZVI and NZVC were significantly enhanced with decreasing pH. A pH-dependent hydrophobic effect and dipole interactions between the charged surface (electron acceptors) and phenanthrene with electron-rich pi systems (electron donors) were proposed to explain the observed pH-dependent sorption.


Assuntos
Cobre/química , Ferro/química , Nanopartículas/química , Fenantrenos/química , Dióxido de Silício/química , Adsorção , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Naftalenos/química , Difração de Raios X
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