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1.
Talanta ; 273: 125856, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442565

RESUMO

Simultaneous detection of multiple tumor biomarkers with a simple and low-cost assay is crucial for early cancer detection and diagnosis. Herein, we presented a low-cost and simple assay for multiplexed detection of tumor biomarkers using a spatially separated electrodes strategy. The sensor is fabricated based on a metal-free thiol-yne click reaction, which is mediated by visible light, on commercially available indium tin oxide (ITO) electrodes. Four biomarkers, including p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA, were used as model analytes, and the corresponding oligonucleotide probes were modified on the desired electrode units sequentially with 530 nm irradiation light in the presence of photosensitizer Eosin Y. By this visible light-mediated coupling reaction, oligonucleotide probe densities of up to 9.2 ± 0.7 × 1010 molecules/cm2 were readily obtained on the ITO electrode surface. The proposed multiplexed E-NA sensor could detect four different nucleic acid targets concurrently without crosstalk among adjacent electrodes and was also successfully applied for detecting targets in a 20% fetal calf serum sample. The detection limits for p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA were 0.72 nM, 0.97 nM, 2.15 nM, and 1.73 nM, respectively. The developed approach not only has a great potential for developing cost-effective biosensors on affordable substrates for nucleic acid target detection, but also be easily extended to detect other targets by modifying the specific oligonucleotide probes anchored on the electrode.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Ácidos Nucleicos , Sondas de Oligonucleotídeos , Compostos de Sulfidrila , Proteína Supressora de Tumor p53/genética , DNA , Eletrodos , Ouro , Biomarcadores Tumorais , Luz , Técnicas Eletroquímicas
2.
J Nanobiotechnology ; 21(1): 6, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600299

RESUMO

While several artificial nanodrugs have been approved for clinical treatment of breast tumor, their long-term applications are restricted by unsatisfactory therapeutic outcomes, side reactions and high costs. Conversely, edible plant-derived natural nanotherapeutics (NTs) are source-widespread and cost-effective, which have been shown remarkably effective in disease treatment. Herein, we extracted and purified exosome-like NTs from tea leaves (TLNTs), which had an average diameter of 166.9 nm and a negative-charged surface of - 28.8 mV. These TLNTs contained an adequate slew of functional components such as lipids, proteins and pharmacologically active molecules. In vitro studies indicated that TLNTs were effectively internalized by breast tumor cells (4T1 cells) and caused a 2.5-fold increase in the amount of intracellular reactive oxygen species (ROS) after incubation for 8 h. The high levels of ROS triggered mitochondrial damages and arrested cell cycles, resulting in the apoptosis of tumor cells. The mouse experiments revealed that TLNTs achieved good therapeutic effects against breast tumors regardless of intravenous injection and oral administration through direct pro-apoptosis and microbiota modulation. Strikingly, the intravenous injection of TLNTs, not oral administration, yielded obvious hepatorenal toxicity and immune activation. These findings collectively demonstrate that TLNTs can be developed as a promising oral therapeutic platform for the treatment of breast cancer.


Assuntos
Exossomos , Neoplasias Mamárias Animais , Microbiota , Animais , Camundongos , Exossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Mamárias Animais/patologia , Apoptose , Folhas de Planta/metabolismo , Chá , Linhagem Celular Tumoral
3.
Pharmaceutics ; 14(8)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36015232

RESUMO

Clinically, cancer drug resistance to chemotherapy, targeted therapy or immunotherapy remains the main impediment towards curative cancer therapy, which leads directly to treatment failure along with extended hospital stays, increased medical costs and high mortality. Therefore, increasing attention has been paid to nanotechnology-based delivery systems for overcoming drug resistance in cancer. In this respect, novel tumor-targeting nanomedicines offer fairly effective therapeutic strategies for surmounting the various limitations of chemotherapy, targeted therapy and immunotherapy, enabling more precise cancer treatment, more convenient monitoring of treatment agents, as well as surmounting cancer drug resistance, including multidrug resistance (MDR). Nanotechnology-based delivery systems, including liposomes, polymer micelles, nanoparticles (NPs), and DNA nanostructures, enable a large number of properly designed therapeutic nanomedicines. In this paper, we review the different mechanisms of cancer drug resistance to chemotherapy, targeted therapy and immunotherapy, and discuss the latest developments in nanomedicines for overcoming cancer drug resistance.

4.
Adv Healthc Mater ; 11(14): e2200255, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35536883

RESUMO

Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Linhagem Celular Tumoral , Doxorrubicina/química , Humanos , Verde de Indocianina/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fototerapia/métodos , Microambiente Tumoral
5.
Front Immunol ; 13: 1087620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618371

RESUMO

Ovarian cancer (OC) is a common gynecologic malignancy with poor prognosis and high mortality. Changes in the OC microenvironment are closely related to the genesis, invasion, metastasis, recurrence, and drug-resistance. The OC microenvironment is regulated by Interferons (IFNs) known as a type of important cytokines. IFNs have a bidirectional regulation for OC cells growth and survival. Meanwhile, IFNs positively regulate the recruitment, differentiation and activation of immune cells. This review summarizes the secretion and the role of IFNs. In particular, we mainly elucidate the actions played by IFNs in various types of therapy. IFNs assist radiotherapy, targeted therapy, immunotherapy and biotherapy for OC, except for some IFN pathways that may cause chemo-resistance. In addition, we present some advances in OC treatment with the help of IFN pathways. IFNs have the ability to powerfully modulate the tumor microenvironment and can potentially provide new combination strategies for OC treatment.


Assuntos
Interferons , Neoplasias Ovarianas , Feminino , Humanos , Diferenciação Celular , Citocinas , Interferons/metabolismo , Neoplasias Ovarianas/patologia , Microambiente Tumoral
6.
Front Bioeng Biotechnol ; 9: 786621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900973

RESUMO

Mitochondria, a kind of subcellular organelle, play crucial roles in cancer cells as an energy source and as a generator of reactive substrates, which concern the generation, proliferation, drug resistance, and other functions of cancer. Therefore, precise delivery of anticancer agents to mitochondria can be a novel strategy for enhanced cancer treatment. Mitochondria have a four-layer structure with a high negative potential, which thereby prevents many molecules from reaching the mitochondria. Luckily, the advances in nanosystems have provided enormous hope to overcome this challenge. These nanosystems include liposomes, nanoparticles, and nanomicelles. Here, we summarize the very latest developments in mitochondria-targeting nanomedicines in cancer treatment as well as focus on designing multifunctional mitochondria-targeting nanosystems based on the latest nanotechnology.

7.
BMC Cancer ; 21(1): 968, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454455

RESUMO

BACKGROUND: The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types. METHODS: We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings. RESULTS: Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC. CONCLUSION: ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Padrão de Cuidado/estatística & dados numéricos , Idoso , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Revisões Sistemáticas como Assunto
8.
Pain Physician ; 24(3): 275-281, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33988947

RESUMO

BACKGROUND: Resection of the ossification of the thoracic ligamentum flavum (OTLF) with a high-speed burr may cause a high rate of perioperative complications, such as dural laceration and/or iatrogenic spinal cord injury. OBJECTIVES: The aim of this study was to investigate the safety and feasibility of the endoscopic-matched ultrasonic osteotome in full-endoscopic spinal surgery for direct removal of OTLF. STUDY DESIGN: Retrospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: This study conducted between December 2017 and December 2018, included 27 consecutive patients who met the study criteria, had single-level OTLF, and underwent full-endoscopic decompression under local anesthesia. The postoperative follow-up was scheduled at 1, 3, 6, and 12 months postoperatively. Outcomes evaluations included the Visual Analog Scale (VAS) score for lower extremity pain and the modified Japanese Orthopaedic Association (mJOA) score and improvement rate for the assessment of thoracic myelopathy. Removal of OTLF was measured by comparing the pre- and postoperative computed tomography (CT) and magnetic resonance imaging (MRI) scans. RESULTS: The operation was completed in all patients without conversion to open surgery. The operation time ranged from 65 to 125 minutes (average, 83.7 ± 12.3 minutes). All patients were followed up for 12 to 18 months, with an average follow-up of 14.3 ± 1.3 months. Satisfactory neurologic decompression was confirmed by postoperative CT and MRI, and no revision surgery was required. The VAS and mJOA scores showed statistically higher improvement at the 1-month follow-up and the last follow-up compared with the preoperative assessment (P < 0.05). According to the improvement rate at the final follow-up, 20 cases were classified as good, 6 cases were fair, and 1 case remained unchanged. LIMITATIONS: A single-center, noncontrol study. CONCLUSIONS: The endoscopic-matched ultrasonic osteotome can be considered quite safe and feasible for direct removal of OTLF during full-endoscopic spinal surgery in strictly selected patients, as this allows for effective direct decompression of OTLF while minimizing trauma and instability. In addition, because of the design characteristics of the ultrasonic osteotome, surgical complications, especially dural tears and spinal cord injury, can also be effectively controlled.


Assuntos
Ligamento Amarelo , Ossificação Heterotópica , Descompressão Cirúrgica , Humanos , Ligamento Amarelo/cirurgia , Vértebras Lombares , Ossificação Heterotópica/cirurgia , Osteogênese , Estudos Retrospectivos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Ultrassom
9.
J Pain Res ; 13: 2799-2804, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173329

RESUMO

OBJECTIVE: To present the case of a patient on long-term anticoagulants who developed acute spinal epidural hematoma (SEH) after percutaneous kyphoplasty (PKP) without signs of major cement extravasation to the spinal canal. METHODS: A 64-year-old woman with long-term oral antiplatelet drugs underwent the L1 PKP. Immediately after the operation, the back pain improved significantly without neurological deficit. However, 12 hours later, she developed progressive weakness of the bilateral lower limbs. No intraspinal cement leakage was obvious on the postoperative lumbar radiograph and computed tomography. RESULTS: An emergency MRI examination revealed a high signal aggregation in front of the spinal cord from T12 to L1, indicating spinal cord compression. The SEH was verified and removed during the laminectomy from T12-L1. Following the decompression surgery, the neurological deficit of the lower limbs improved. On follow-up after 6 months, the muscle strength of the bilateral lower limbs had returned to normal. CONCLUSION: For the patient with long-term oral antiplatelet drugs or coagulation malfunction, the transpedicle approach or that via the costovertebral joint with a smaller abduction angle is recommended to reduce the risk of injury to the inner wall of the pedicle. For progressive aggravation of neurological dysfunction after surgery, SEH formation should be suspected despite the absence of intraspinal bone cement leakage. Secondary emergency decompression should be considered to avoid permanent damage to spinal cord nerve function caused by continuous compression.

10.
J Orthop Surg Res ; 15(1): 413, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933553

RESUMO

BACKGROUND: During the process of shearing the ligamentum flavum, rotating the working channel, and manipulating the annulus fibrosis, the sinuvertebral nerve and the spinal nerve root can be irritated, inducing intolerable back and leg pain. Thus, general anesthesia is recommended and well accepted by most surgeons when performing percutaneous endoscopic lumbar discectomy (PELD) via the interlaminar approach. The aim of our study was to explore the efficacy and safety of percutaneous endoscopy interlaminar lumbar discectomy with gradient local anesthesia (LA) in patients with L5/S1 disc herniation. METHODS: This retrospective study was conducted between December 2017 and June 2018. The study included 50 consecutive patients who met the study criteria, had single-level L5/S1 disc herniation, and underwent PELD via the interlaminar approach under gradient LA. Different concentrations of local anesthetic compound (LAC) were injected into different tissues inside and outside the ligamentum flavum to complete gradient LA. The evaluation criteria included the intraoperative satisfaction score, visual analog scale (VAS) score, Oswestry Disability Index (ODI), complications, and adverse reactions. RESULTS: The intraoperative satisfaction score was consistently over 7, with an average score of 9.3 ± 0.7, indicating that LAC can achieve satisfactory pain control throughout the PELD operation without additional anesthesia. The postoperative VAS score and ODI were dramatically improved at each follow-up interval (P < 0.001, respectively). There was no serious complication such as dural rupture caused by puncture, dural laceration caused by manipulation under endoscopy, total spinal anesthesia, iatrogenic nerve root injury, epidural hematoma, infections, or local anesthetic-related adverse reactions. Three patients experienced transient postoperative dysesthesia of the lower limbs that gradually recovered within 24 h. CONCLUSIONS: Gradient local anesthesia can satisfactorily and safely control intraoperative pain during the PELD via the interlaminar approach. It can not only improve intraoperative satisfaction, but also reduce local anesthesia-related adverse reactions and surgery-related complications.


Assuntos
Anestesia Local/métodos , Discotomia Percutânea/métodos , Deslocamento do Disco Intervertebral/cirurgia , Complicações Intraoperatórias/prevenção & controle , Vértebras Lombares/cirurgia , Dor/prevenção & controle , Adulto , Estudos de Viabilidade , Feminino , Humanos , Ligamento Amarelo , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Segurança , Resultado do Tratamento , Adulto Jovem
11.
World Neurosurg ; 144: e368-e375, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32861904

RESUMO

OBJECTIVE: To compare clinical efficacy, radiographic outcome, and radiation exposure between mini-open pedicle screw (MPS) fixation with the Wiltse approach and percutaneous pedicle screw (PPS) fixation in treatment of young and middle-aged patients with thoracolumbar burst fractures. METHODS: Of 60 patients with thoracolumbar vertebrae fractures treated in our hospital from January 2017 to January 2018, 30 were randomly assigned to the MPS group and 30 were randomly assigned to the PPS group. Clinical efficacy, radiographic outcome, and radiation exposure were compared between the 2 groups. RESULTS: The average age of patients was 42.2 ± 6.7 years in the MPS group and 43.0 ± 6.9 years in the PPS group (P = 0.668). There was no significant difference between the 2 groups in blood loss, hospital stay, postoperative visual analog scale score for back pain, and Oswestry Disability Index score. The vertebral body height and vertebral body angle of the MPS group were significantly better than those of the PPS group at the last follow-up. There was no significant difference in the accuracy rate of pedicle screw placement between the MPS group and the PPS group; the facet joint violation was significantly higher in the PPS group. The average radiation exposure dosage was lower in the MPS group. CONCLUSIONS: Both MPS fixation with the Wiltse approach and PPS fixation are safe and effective in the treatment of single-segment thoracolumbar vertebral fractures. Nevertheless, considering the surgical duration, radiation exposure, facet joint violation, vertebral body height, and vertebral body angle at the last follow-up, MPS fixation with the Wiltse approach is a better choice than PPS.


Assuntos
Procedimentos Ortopédicos , Exposição à Radiação , Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Cirurgia Assistida por Computador , Adulto , Parafusos Ósseos , Feminino , Fluoroscopia , Fixação Interna de Fraturas/métodos , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Radiometria/instrumentação , Radiometria/métodos , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/métodos , Vértebras Torácicas/cirurgia , Resultado do Tratamento
12.
J Anesth ; 34(6): 825-833, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32627064

RESUMO

PURPOSE: This study aimed to explore the effect of patient-controlled intravenous analgesia (PCIA) using tramadol combined with butorphanol on uterine cramping pain in women undergoing repeat caesarean section. METHODS: A total of 126 patients, who were scheduled to undergo repeat caesarean section under spinal anesthesia, were included. PCIA using tramadol combined with butorphanol or sufentanil was randomly performed for postoperative pain control. Postoperative uterine cramping pain and wound pain within 48 h after surgery were evaluated. Postoperative analgesic consumption, early activity time, and length of hospital stay were also recorded and analyzed. RESULTS: Uterine cramping pain intensity in women undergoing repeat caesarean section was significantly higher compared with their wound pain (P < 0.05). The mean visual analog scale (VAS) score for uterine cramping pain in the tramadol-butorphanol group was significantly lower than that in the sufentanil group at rest, and at 6 h and 12 h after surgery. VAS scores for uterine cramping pain during movement at 6 h, 12 h, and 24 h after surgery in the tramadol-butorphanol group were also significantly lower than that in sufentanil group (P < 0.05). There was no significant difference in VAS score for wound pain at the different time points between the tramadol-butorphanol and sufentanil groups (P > 0.05). Patient-controlled intravenous analgesia with tramadol accelerated early rehabilitation and decreased the length of hospital stay (P < 0.05). CONCLUSION: PCIA using tramadol combined with butorphanol provided a better analgesic effect and accelerated postoperative rehabilitation compared with sufentanil, and may be an optimal analgesic strategy for women undergoing repeat caesarean section. CLINICAL TRIAL REGISTRATION: The trial was registered at Chinese Clinical Trial Registry ( www.chictr.org.cn ) with ID: ChiCTR-1800014986.


Assuntos
Tramadol , Analgesia Controlada pelo Paciente , Analgésicos Opioides , Butorfanol , Cesárea , Recesariana , Método Duplo-Cego , Feminino , Humanos , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Tramadol/uso terapêutico
13.
Medicine (Baltimore) ; 99(5): e18738, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000377

RESUMO

BACKGROUND: To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer. METHODS: Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed. RESULTS: In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P < .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P < .001; heterogeneity: P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021). CONCLUSION: Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.


Assuntos
Carcinoma/terapia , Quimiorradioterapia , Histerectomia , Neoplasias do Colo do Útero/terapia , Feminino , Humanos
14.
J Pathol ; 248(4): 464-475, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30945288

RESUMO

Inflammation is well known as an important driver of the initiation of colitis-associated cancer (CAC). Some cytokines, such as IL-6 and TNF-α can activate expression of the oncogene c-Myc (MYC) and regulate its downstream effects. Cullin-RING E3 Ligases (CRLs) are emerging as master regulators controlling tumorigenesis. Here, we demonstrate that two cullin genes, CUL4A and CUL4B, but not other members, are specifically overexpressed in CAC tumour samples and positively correlate with levels of the proinflammatory cytokines IL-1ß and IL-6. In vitro experiments revealed that the transcription factor c-Myc can specifically activate the expression of CUL4A and CUL4B by binding to a conserved site (CACGTG) located in their promoters. Additionally, we found that both CUL4A and CUL4B can form an E3 complex with DNA damage-binding protein 1 (DDB1) and DDB1-CUL4-associated factor 4 (DCAF4). In vitro and in vivo ubiquitination analyses indicate that CRL4DCAF4 E3 ligase specifically directs degradation of ST7 (suppression of tumorigenicity 7). Overexpression of c-Myc in human colon epithelial cells resulted in the accumulation of CUL4A, CUL4B and DCAF4, but degradation of ST7. In contrast, knockdown of c-Myc, CUL4A or CUL4B in the colon adenocarcinoma cell line HT29 caused accumulation of ST7 and inhibition of cell proliferation, colony formation ability and in vivo tumour growth. Collectively, our results provide in vitro and in vivo evidence that c-Myc regulates CRL4DCAF4 E3 ligase activity to mediate ubiquitination of ST7, whose presence is physiologically essential for CAC tumorigenesis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Adenocarcinoma/metabolismo , Colite/metabolismo , Neoplasias do Colo/metabolismo , Lesões Pré-Cancerosas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adenocarcinoma/patologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Colite/patologia , Neoplasias do Colo/patologia , Proteínas Culina/metabolismo , Feminino , Células HT29 , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Lesões Pré-Cancerosas/patologia , Ubiquitinação , Regulação para Cima
15.
Macromol Rapid Commun ; 40(17): e1800731, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30672634

RESUMO

A new type of dynamic covalent macrocycle with self-promoted supramolecular gelation behavior is developed. Under oxidative conditions, the dithiol compound containing a diamide alkyl linker with an odd number (7) of carbon chain and an appended crown ether shows a remarkable gelation ability in acetonitrile, without any template molecules. Due to the existence of crown ethers and disulfide bonds, the obtained gel shows a multiple stimuli-responsiveness behavior. The mechanical properties and reversibility of the gel are investigated. Computational modeling suggests that the peripheral chain for diamide hydrogen bonding is responsible for the gelation process.


Assuntos
Materiais Biocompatíveis/química , Coloides/química , Éteres de Coroa/química , Géis/química , Compostos Macrocíclicos/química , Simulação por Computador , Ligação de Hidrogênio , Estrutura Molecular
16.
Acta Radiol ; 55(3): 309-17, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24081215

RESUMO

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world, and is the leading cause of cancer-related mortality. Although there are no conclusive data to support the survival benefits of early detection or early treatment for recurrence, an early and accurate diagnosis of recurrence is critical to optimize therapy. PURPOSE: To compare the diagnostic value of positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) using fluorine-18 deoxyglucose (18FDG) with conventional imaging techniques (CITs) for the detection of lung cancer recurrence. MATERIAL AND METHODS: A meta-analysis was performed, with systematic searches conducted using PubMed and EMBASE databases (up to 31 December 2011). Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) values were calculated for 1035 patients reported in 13 articles. Summary receiver-operating characteristic curves (SROC) were also generated. RESULTS: The pooled sensitivity (95% CI) for PET, PET/CT, and CITs were 0.94 (0.91-0.97), 0.90 (0.84-0.95), and 0.78 (0.71-0.84), respectively. The pooled specificity (95% CI) for PET, PET/CT, and CITs were 0.84 (0.77-0.89), 0.90 (0.87-0.93), and 0.80 (0.75-0.84), respectively. Regarding sensitivity, lower values were associated with CITs than PET (P = 0.000) and PET/CT (P = 0.005), and there was no significant difference between PET/CT and PET (P = 0.102). Regarding specificity, values for PET/CT and PET were significantly higher than for CITs (both P = 0.000), and there was no significant difference between PET/CT and PET (P = 0.273). In the SROC curves, a better diagnostic accuracy was associated with PET/CT than PET and CITs. CONCLUSION: PET/CT and PET were found to be superior modalities for the detection of recurrent lung cancer, and PET/CT was superior to PET.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Imagem Multimodal , Recidiva Local de Neoplasia/diagnóstico por imagem , Meios de Contraste , Humanos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
17.
Chin J Integr Med ; 17(5): 381-5, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21611903

RESUMO

OBJECTIVE: To investigate the changing trends of clinical management for severe acute pancreatitis (SAP) with integrative medicine. METHODS: Clinical data of 1 561 patients with SAP from 1980 to 2005 was retrospectively analyzed. The mortality and morbidity of complications were compared. RESULTS: Of the 1 561 patients, 400 patients accepted surgical operation, while the rest were treated conservatively with integrative medicine. There was a change toward conservative management together with Chinese purgative herbal medication use after 1990 (22.4% from 1980-1990 compared with 45.5% from 1991-1993) because of high postoperative mortality. From 1994-2005, the treatment integrating Western medicine with Chinese herbal medications came to be preferred over the classic Western operation-based method. This change was associated with decreased morbidity (35.4% in 1980-1990 compared with 24.7% in 1991-1993 and 11.0% in 1994-2005, P<0.05) and lower mortality (40.52% of 1980-1990 compared with 17.17% of 1991-1993 and <10.25% of 1994-2005, P<0.05). CONCLUSION: The combination of conservative management with Chinese herbal medicines is preferable to classic Western medicine treatment to reduce morbidity and mortality of SAP, while surgery becomes a supplemental option.


Assuntos
Medicina Integrativa , Pancreatite/terapia , Doença Aguda , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/mortalidade
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