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1.
J Orthop Surg Res ; 17(1): 27, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35033125

RESUMO

BACKGROUND: Anteromedial cortical support apposition (positive and/or neutral cortical relations) is crucial for surgical stability reconstruction in the treatment of trochanteric femur fractures. However, the loss of fracture reduction is frequent in follow-ups after cephalomedullary nail fixation. This paper aimed to investigate the possible predictive risk factors for postoperative loss of anteromedial cortex buttress after nail fixation. METHODS: A retrospective analysis of 122 patients with AO/OTA 31A1 and A2 trochanteric femur fractures treated with cephalomedullary nails between January 2017 and December 2019 was performed. The patients were classified into two groups according to the postoperative status of the anteromedial cortical apposition in 3D CT images: Group 1 with contact "yes" (positive or anatomic) and Group 2 with contact "No" (negative, loss of contact). The fracture reduction quality score, tip-apex distance (TAD), calcar-referenced TAD (Cal-TAD), Parker ratio, neck-shaft angle (NSA), and the filling ratio of the distal nail segment to medullary canal diameter in anteroposterior (AP) and lateral fluoroscopies (taken immediately after the operation) were examined in univariate and multivariate analyses. Mechanical complications were measured and compared in follow-up radiographs. RESULTS: According to the postoperative 3D CT, 84 individuals (69%) were categorized into Group 1, and 38 individuals (31%) were classified as Group 2. The multivariate logistic regression analysis showed that the poor fracture reduction quality score (P < 0.001) and decreasing filling ratio in the lateral view (P < 0.001) were significant risk factors for the loss of anteromedial cortical contact. The threshold value for the distal nail filling ratio in lateral fluoroscopy predicting fracture reduction re-displacement was found to be 53%, with 89.3% sensitivity and 78.9% specificity. The mechanical complication (varus and over lateral sliding) rate was higher in Group 2. CONCLUSIONS: The fracture reduction quality score and the decreasing filling ratio of the distal nail to the medullary canal in the lateral view (a novel parameter causing pendulum-like movement of the nail) were possible risk factors for postoperative loss of anteromedial cortical support.

2.
Front Oncol ; 11: 705929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722250

RESUMO

Background: Alternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC). Methods: AS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established. Results: We identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC. Conclusion: Through the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.

3.
Cancer Med ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723436

RESUMO

PURPOSE: Marital status has emerged as an important influence on several cancer outcomes, but its role in medullary thyroid cancer (MTC) remains unclear. This study was to explore the effects of marital status on the prognosis of MTC patients and to determine whether its effects vary by age. PATIENTS AND METHODS: We retrospectively extracted 1344 eligible patients diagnosed with MTC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the marital status, we divided those patients into married and unmarried groups. We compared the difference in overall survival (OS) and cancer-specific survival (CSS) between married and unmarried via the Kaplan-Meier analysis. Univariate and multivariate Cox proportional models were performed to identify the prognostic factors of OS and CSS. RESULTS: There were 1344 MTC eligible patients in a total of which 883 (65.7%) were married and 461 (34.3%) were unmarried. The comparison observed between married and unmarried patients was as follows: male (45.2% vs. 28.0%), age (≥52 years) (55.9% vs. 44.6%), White (86.7% vs. 78.7%), and undergo surgery (97.7% vs. 93.3%). Multivariate analysis revealed unmarried status as a risk factor independently associated with worse OS (HR: 2.15, 95% CI: 1.59-2.92) rate and CSS (HR: 1.70, 95% CI: 1.17-2.47) rate. In a further analysis stratified by age, there was no significant difference in OS and CSS between married and unmarried patients younger than 52 years. For the remaining group with 52 years old and higher, unmarried patients showed significantly higher risk of OS and CSS than married patients at all stages of the pathology except M1 stage. CONCLUSION: Married patients with MTC have a better prognosis than unmarried ones. Age can affect the association between marital status and the survival of MTC, and married elders may benefit more than youngers.

4.
Biomater Sci ; 9(23): 7799-7810, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34747953

RESUMO

Nerve injury is a common complication of surgery. Accidental nerve damage or transection can lead to severe clinical symptoms including pain, numbness, paralysis and even expiratory dyspnoea. In recent years, with the rise of the field of fluorescence-guided surgery, researchers have discovered that nerve-specific fluorescent agents can serve as nerve markers in animals and can be used to guide surgical procedures and reduce the incidence of intraoperative nerve damage. Currently, researchers have begun to focus on biochemistry, materials chemistry and other fields to produce more neuro-specific fluorescent agents with physiological relevance and they are expected to have clinical applications. This review discusses the agents with potential to be used in fluorescence-guided nerve imaging during surgery.


Assuntos
Tecido Nervoso , Nervos Periféricos , Animais , Diagnóstico por Imagem , Fluorescência , Corantes Fluorescentes
5.
Geriatr Orthop Surg Rehabil ; 12: 21514593211056739, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840855

RESUMO

Background: The new edited AO/OTA-2018 classification of pertrochanteric fractures was revised and no longer based on the status of lesser trochanter. This paper aimed to explore the clinical and technical outcomes among the subgroups (31A1 and 31A2) of the new classification treated with cephalomedullary nails. Methods: A retrospective research of 154 patients diagnosed with pertrochanteric fractures (AO/OTA-2018 31A1.2/3 and 31A2.1/2/3) treated with intramedullary nails was conducted. The baseline data and outcomes were compared among the subgroups. The outcomes included tip-apex distance (TAD), Cal-TAD, Parker ratio, neck shaft angle (NSA), blood loss, varus displacement, and over lateral sliding rate of the blade. Results: There were 154 cases involving 48 males and 106 females. The average age was higher in the sub-classifications of A2.2 and A2.3 than A1.2. Furthermore, the subgroups of A2.2 and A2.3 presented inferior outcomes with regard to blood loss and reduction quality score than A1.2 and A1.3. The subgroup of A2.3 was further poor with respect to calcar fracture gapping in the anteroposterior view and excessive lateral migration occurrence rate than A1.2. Conclusions: Complex pertrochanteric fractures indicated inferior outcomes compared to simple sub-classifications, which might lead by the incompetent of lateral wall and instability of the fracture. The newly proposed AO/OTA-2018 classification was conductive to forecast the prognosis.

6.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445087

RESUMO

The miR-31 host gene (MIR31HG) encodes a long non-coding RNA (LncRNA) that harbors miR-31 in its intron 2; miR-31 promotes malignant neoplastic progression. Overexpression of MIR31HG and of miR-31 occurs during oral squamous cell carcinoma (OSCC). However, the downstream effectors modulated by MIR31HG during OSCC pathogenesis remain unclear. The present study identifies up-regulation of MIR31HG expression during the potentially premalignant disorder stage of oral carcinogenesis. The potential of MIR31HG to enhance oncogenicity and to activate Wnt and FAK was identified when there was exogenous MIR31HG expression in OSCC cells. Furthermore, OSCC cell subclones with MIR31HG deleted were established using a Crispr/Cas9 strategy. RNA sequencing data obtained from cells expressing MIR31HG, cells with MIR31HG deleted and cells with miR-31 deleted identified 17 candidate genes that seem to be modulated by MIR31HG in OSCC cells. A TCGA database algorithm pinpointed MMP1, BMP2 and Limb-Bud and Heart development (LBH) as effector genes controlled by MIR31HG during OSCC. Exogenous LBH expression decreases tumor cell invasiveness, while knockdown of LBH reverses the oncogenic suppression present in MIR31HG deletion subclones. The study provides novel insights demonstrating the contribution of the MIR31HG-LBH cascade to oral carcinogenesis.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Humanos , Neoplasias Bucais/patologia , Regulação para Cima
7.
Int J Endocrinol ; 2021: 6621067, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306071

RESUMO

The health problems caused by the frequent relapse of papillary thyroid carcinoma (PTC) remain a worldwide concern since the morbidity rate of PTC ranks the highest among thyroid cancers. Residues from contralateral central lymph node metastases (con-CLNM) are the key reason for persistence or recurrence of unilateral papillary thyroid carcinoma (uni-PTC); however, the ability to assess the status of con-CLNM in uni-PTC patients is limited. To clarify the risk factors of con-CLNM, a total of 250 patients with uni-PTC who underwent total thyroidectomy and bilateral central lymph node dissection were recruited in this study. We compared the clinical, sonographic, and pathological characteristics of patients with con-CLNM to those without con-CLNM and established a nomogram for con-CLNM in uni-PTC. We found that male sex, without Hashimoto's thyroiditis, present capsular invasion, with ipsilateral lateral lymph node metastases, and the ratio of ipsilateral central lymph node metastases ≥0.16 were independent con-CLNM predictors of uni-PTC (ORs: 2.797, 0.430, 2.538, 2.202, and 26.588; 95% CIs: 1.182-6.617, 0.211-0.876, 1.223-5.267, 1.064-4.557, and 7.596-93.069, respectively). Additionally, a preoperative nomogram for the prediction of con-CLNM based on these risk factors showed good discrimination (C-index 0.881; 95% CI: 0.840-0.923; sensitivity 85.3%; specificity 76.0%) and good agreement via the calibration plot. Our study provided a way to quantitatively and accurately predict whether con-CLNM occurred in patients with uni-PTC, which may guide surgeons to evaluate the nodal status and perform tailored therapeutic central lymph node dissection.

8.
Vet Med Sci ; 7(5): 1989-1998, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34236772

RESUMO

BACKGROUND: The cellular mechanisms involved in the development of proximal tubules are not only associated with morphogenesis in fetal life, but also with restoration of damaged tubules in adulthood. Knowledge about morphological features of cell differentiation and proliferation along the developing tubule is insufficient, which hinders identification of the cellular origin. OBJECTIVES: This study aimed to investigate ultrastructures of the proximal tubule at different stages of nephrogenesis. METHODS: Electron microscopy was used and guided by computer-assisted tubular tracing to identify the cellular structures. RESULTS: Renal vesicles and S-shaped bodies revealed more proliferative features, such as densely-packed fusiform-shaped cells with numerous protein-producing organelles than membrane specializations typical for mature tubules. At the capillary-loop stage the proximal tubules demonstrated all characteristics of the mature tubules, but not as developed, including shorter but densely packed microvilli, fewer lateral processes with cell-cell contacts, lower basal membrane infoldings, and lower mitochondrial volume density. However, they exhibited an elaborated endocytic system above the nucleus, indicating a membrane transport is being established. Abundant free- and endoplasmic reticulum-adhered ribosomes and Golgi complexes reflected active protein synthesis for cell growth and proliferation. Interestingly, electron dense cells were occasionally intermixed with electron lucent cells characterized by various organelles in less cytosol and a larger nucleus with abundant euchromatin, which is a feature of active proliferation. CONCLUSIONS: These ultrastructures indicate that the morphogenesis of the developing proximal tubule corresponds to the gradually established physiological activities. The two different cellular electron densities may suggest distinctive differentiation of the cells along the tubule.

10.
Respirol Case Rep ; 9(6): e00765, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33976894

RESUMO

Acute silicoproteinosis is a disease that develops in weeks, and lasting for years, after massive exposure to silica dust in relatively closed spaces. It was rare, but the cases have recently increased worldwide due to the development of artificial stone industry. Compared with traditional silicosis, artificial stone-associated silicosis is more rapidly progressive and lethal. Hence, a correct diagnosis and optimal treatment are crucial. Here, we present the clinical course of a 33-year-old artificial stonemason who suffered from acute silicoproteinosis with concurrent Cryptococcus infection resulting in profound respiratory failure. This patient was treated by bronchoscope-assisted therapeutic segmental lung lavage and antifungal agent, under mechanical ventilator and ECMO support and recovered well. A brief review of acute silicoproteinosis and artificial stone-associated silicosis is also presented and highlights the new form of industry exposure to silica.

11.
Chin J Nat Med ; 19(2): 90-99, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33641788

RESUMO

This study was to investigate the protective effect of paeoniflorin (PF) on hydrogen peroxide-induced injury. Firstly, "SMILES" of PF was searched in Pubchem and further was used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Injury-related molecules were obtained from GeenCards database, and the predicted targets of PF for injury treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, and the KEGG analysis was conducted in Webgestalt. Then, cell viability and cytotoxicity assay were established by CCK8 assay. Also, the experimental cells were allocated to control, model (200 µmol·L-1 H2O2), SB203580 10 µmol·L-1 (200 µmol·L-1 H2O2+ SB203580 10 µmol·L-1), PF 50 µmol·L-1 (200 µmol·L-1 H2O2+ PF 50 µmol·L-1), and PF 100 µmol·L-1 (200 µmol·L-1 H2O2+ PF 100 µmol·L-1) groups. We measured the intracellular ROS, Hoechst 33258 staining, cell apoptosis, the levels of Bcl-xl, Bcl-2, Caspase-3, Cleaved-caspase3, Cleaved-caspase7, TRPA1, TRPV1, and the phosphorylation expression of p38MAPK. There are 96 potential targets that may be associated with PF for injury treatment. Then, we chose the "Inflammatory mediator regulation of TRP channels" pathway for the experimental verification from the first 10 KEGG pathway. In experimental verification, H2O2 decreased the cell viability moderately (P < 0.05), and 100 µmol·L -1 PF increased the cell viability significantly (P < 0.05). Depending on the difference of intracellular ROS fluorescence intensity, PF inhibited H 2O2-induced reactive oxygen species production in Schwann cells. In Hoechst 33258 staining, PF reversed the condensed chromatin and apoptotic nuclei following H2O2 treatment. Moreover, Flow cytometry results showed that PF could substantially inhibit H2O2 induced apoptosis (P < 0.05). Pretreatment with PF obviously reduced the levels of Caspase3, Cleaved-caspase3, Cleaved-caspase7, TRPA1, TRPV1, and the phosphorylation expression of p38MAPK after H 2O2 treatment (P < 0.05), increased the levels of Bcl-2, and Bcl-xl ( P < 0.05). PF inhibited Schwann cell injury and apoptosis induced by hydrogen peroxide, which mechanism was linked to the inhibition of phosphorylation of p38MAPK.


Assuntos
Glucosídeos/farmacologia , Peróxido de Hidrogênio , Monoterpenos/farmacologia , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Células de Schwann/efeitos dos fármacos , Apoptose , Sobrevivência Celular , Peróxido de Hidrogênio/toxicidade , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio
12.
Genetics ; 217(1): 1-17, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33683370

RESUMO

Infection with antibiotic-resistant bacteria is an emerging life-threatening issue worldwide. Enterohemorrhagic Escherichia coli O157: H7 (EHEC) causes hemorrhagic colitis and hemolytic uremic syndrome via contaminated food. Treatment of EHEC infection with antibiotics is contraindicated because of the risk of worsening the syndrome through the secreted toxins. Identifying the host factors involved in bacterial infection provides information about how to combat this pathogen. In our previous study, we showed that EHEC colonizes in the intestine of Caenorhabditis elegans. However, the host factors involved in EHEC colonization remain elusive. Thus, in this study, we aimed to identify the host factors involved in EHEC colonization. We conducted forward genetic screens to isolate mutants that enhanced EHEC colonization and named this phenotype enhanced intestinal colonization (Inc). Intriguingly, four mutants with the Inc phenotype showed significantly increased EHEC-resistant survival, which contrasts with our current knowledge. Genetic mapping and whole-genome sequencing (WGS) revealed that these mutants have loss-of-function mutations in unc-89. Furthermore, we showed that the tolerance of unc-89(wf132) to EHEC relied on HLH-30/TFEB activation. These findings suggest that hlh-30 plays a key role in pathogen tolerance in C. elegans.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Caenorhabditis elegans/genética , Infecções por Escherichia coli/genética , Imunidade Inata , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Escherichia coli Êntero-Hemorrágica/patogenicidade , Infecções por Escherichia coli/imunologia , Intestinos/microbiologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo
13.
Injury ; 52(11): 3535-3536, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33743983
14.
Mol Microbiol ; 116(1): 168-183, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33567149

RESUMO

Enterohemorrhagic Escherichia coli (EHEC), an enteropathogen that colonizes in the intestine, causes severe diarrhea and hemorrhagic colitis in humans by the expression of the type III secretion system (T3SS) and Shiga-like toxins (Stxs). However, how EHEC can sense and respond to the changes in the alimentary tract and coordinate the expression of these virulence genes remains elusive. The T3SS-related genes are known to be regulated by the locus of enterocyte effacement (LEE)-encoded regulators, such as Ler, as well as non-LEE-encoded regulators in response to different environmental cues. Herein, we report that OmpR, which participates in the adaptation of E. coli to osmolarity and pH alterations, is required for EHEC infection in Caenorhabditis elegans. OmpR protein was able to directly bind to the promoters of ler and stx1 (Shiga-like toxin 1) and regulate the expression of T3SS and Stx1, respectively, at the transcriptional level. Moreover, we demonstrated that the expression of ler in EHEC is in response to the intestinal environment and is regulated by OmpR in C. elegans. Taken together, we reveal that OmpR is an important regulator of EHEC which coordinates the expression of virulence factors during gastrointestinal infection in vivo.

15.
Geriatr Orthop Surg Rehabil ; 12: 2151459321990640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628611

RESUMO

Background: InterTAN is a specific type of cephalomedullary nail with a twin interlocking de-rotation and compression screw, which has inherent ability of anti-rotation. Whether to tighten or not to tighten the preloaded setscrew to allow or not allow secondary sliding in InterTan nail is controversial in clinical practice. Methods: We retrospectively collected 4 nonunion cases of unstable pertrochanteric femur fractures (AO/OTA-31A2), all were treated with InterTan nail and the preloaded setscrew was tightened in order to prevent further secondary sliding and femoral neck shortening. Results: After 6 months to 2 years follow-up, the fractures showed nonunion in radiography and the patients complained slight to middle degrees of pain, and had to use walking stick assistant in activities of daily life. Tightening the pre-loaded setscrew to prevent postoperative secondary sliding as static constructs might keep the femoral neck length, but lose the opportunity of telescoping for fracture impaction, and take the risk of healing complications, such as fracture nonunion, femoral head cutout or nail breakage. Conclusions: As the harm outweighs benefit, we advocate the preloaded setscrew in InterTan nail should not be tightened in standard-obliquity pertrochanteric hip fractures (AO/OTA-31A1 and A2).

16.
Ann Plast Surg ; 87(4): 451-456, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587459

RESUMO

BACKGROUND: Dynamic infrared thermography provides a new imaging method of perforator detection. This study introduces an augmented technique to improve its accuracy by tourniquet-reperfusion and reports its preliminary use in the distal lower leg reconstruction. METHODS: A tourniquet (450 mm Hg) was applied for 3 minutes on proximal thighs. After the tourniquet release, the rewarming rate and pattern of hotspots were observed by thermography to delineate the location and quality of perforators. The results were compared with those detected by computed tomographic angiography. Clinically, the local transferred posterior tibial artery or peroneal artery propeller perforator flap was performed in 9 patients for the distal lower leg reconstruction. RESULTS: There was a 20- to 140-second "perforator observing window" after the tourniquet release. Tourniquet-reperfusion augmented thermal imaging method (TRATIM) had a sensitivity of 90.3% and a positive predictive value of 93.3%. The TRATIM and computed tomographic angiography had an excellent concordance with a kappa index value of 0.839 (P < 0.001). Based on the TRATIM, 9 propeller perforator flaps were successfully designed and raised for the distal lower leg resurfacing. All flaps survived entirely, except one with size of 1.0 cm × 2.0 cm that had terminal necrosis. CONCLUSIONS: The TRATIM is a quick, easy, cheap, and reliable approach for perforator detection in the lower leg. With the aid of TRATIM, a customized propeller perforator flap could be raised efficiently for the distal lower leg reconstruction.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Humanos , Perna (Membro)/cirurgia , Reperfusão , Termografia , Torniquetes
17.
Microorganisms ; 9(2)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540892

RESUMO

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

18.
J Cancer Res Clin Oncol ; 147(2): 323-337, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387037

RESUMO

The incidence of papillary thyroid cancer (PTC), the major type of thyroid cancer, is increasing rapidly around the world, and its pathogenesis is still unclear. There is poor prognosis for PTC involved in rapidly progressive tumors and resistance to radioiodine therapy. Kinase gene fusions have been discovered to be present in a wide variety of malignant tumors, and an increasing number of novel types have been detected in PTC, especially progressive tumors. As a tumor-driving event, kinase fusions are constitutively activated or overexpress their kinase function, conferring oncogenic potential, and their frequency is second only to BRAFV600E mutation in PTC. Diverse forms of kinase fusions have been observed and are associated with specific pathological features of PTC (usually at an advanced stage), and clinical trials of therapeutic strategies targeting kinase gene fusions are feasible for radioiodine-resistant PTC. This review summarizes the roles of kinase gene fusions in PTC and the value of clinical therapy of targeting fusions in progressive or refractory PTC, and discusses the future perspectives and challenges related to kinase gene fusions in PTC patients.


Assuntos
Fusão Gênica , Proteínas Quinases/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Quinase do Linfoma Anaplásico/genética , Fusão Gênica/efeitos dos fármacos , Fusão Gênica/fisiologia , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptor trkA/genética , Câncer Papilífero da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico
19.
Nat Commun ; 12(1): 90, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397943

RESUMO

Enterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Escherichia coli Êntero-Hemorrágica/fisiologia , Interações Hospedeiro-Patógeno , Microvilosidades/microbiologia , Microvilosidades/patologia , Actinas/metabolismo , Animais , Células CACO-2 , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/ultraestrutura , Carboidratos Epimerases/metabolismo , Escherichia coli Êntero-Hemorrágica/patogenicidade , Forminas , Humanos , Intestinos/microbiologia , Microvilosidades/metabolismo , Fosforilação , Fosfotreonina/metabolismo , Virulência
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