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1.
Cell Prolif ; : e12918, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025691

RESUMO

OBJECTIVES: Reprogramming of cellular metabolism is profoundly implicated in tumorigenesis and can be exploited to cancer treatment. Cancer cells are known for their propensity to use glucose-dependent glycolytic pathway instead of mitochondrial oxidative phosphorylation for energy generation even in the presence of oxygen, a phenomenon known as Warburg effect. The type II beta regulatory subunit of protein kinase A (PKA), PRKAR2B, is highly expressed in castration-resistant prostate cancer (CRPC) and contributes to tumour growth and metastasis. However, whether PRKAR2B regulates glucose metabolism in prostate cancer remains largely unknown. MATERIALS AND METHODS: Loss-of-function and gain-of-function studies were used to investigate the regulatory role of PRKAR2B in aerobic glycolysis. Real-time qPCR, Western blotting, luciferase reporter assay and chromatin immunoprecipitation were employed to determine the underlying mechanisms. RESULTS: PRKAR2B was sufficient to enhance the Warburg effect as demonstrated by glucose consumption, lactate production and extracellular acidification rate. Mechanistically, loss-of-function and gain-of-function studies showed that PRKAR2B was critically involved in the tumour growth of prostate cancer. PRKAR2B was able to increase the expression level of hypoxia-inducible factor 1α (HIF-1α), which is a key mediator of the Warburg effect. Moreover, we uncovered that HIF-1α is a key transcription factor responsible for inducing PRKAR2B expression in prostate cancer. Importantly, inhibition of glycolysis by the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) or replacement of glucose in the culture medium with galactose (which has a much lower rate than glucose entry into glycolysis) largely compromised PRKAR2B-mediated tumour-promoting effect. Similar phenomenon was noticed by genetic silencing of HIF-1α. CONCLUSIONS: Our study identified that PRKAR2B-HIF-1α loop enhances the Warburg effect to enable growth advantage in prostate cancer.

2.
BMC Cancer ; 20(1): 958, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008376

RESUMO

BACKGROUND: It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression. METHODS: We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC. RESULTS: A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC. CONCLUSION: Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33020156

RESUMO

Alternative therapeutic options are urgently needed against multidrug-resistant E. coli infections, especially in situations of pre-existing tigecycline and colistin resistances. Here, we investigated synergistic activity of the antiretroviral drug zidovudine in combination with tigecycline or colistin against E. coli harboring tet(X) and mcr-1 in vitro and in a murine thigh infection model. Zidovudine and tigecycline/colistin combinations achieved synergistic killing and significantly decreased bacterial burdens by >2.5 log10cfu/g in thigh tissues compared to each monotherapy.

5.
Plant Genome ; 13(2): e20020, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33016612

RESUMO

Long non-coding RNAs (lncRNAs) are essential regulators of a broad range of biological processes in plants. The spectacular progress made in next-generation sequencing technologies has enabled a genome-wide identification of lncRNAs in multiple plant species. In this study, a genome-wide lncRNA sequencing technology was used to identify cold-responsive lncRNAs at the booting stage in rice by comparing a tolerant variety, Kongyu131 (KY131) and a sensitive variety, Dongnong422 (DN422). A total of 1485 lncRNAs were identified, and 566 of these lncRNAs were defined as differential lncRNAs by comparing four samples. GO and KEGG enrichment analyses were performed, focusing on the cis- and trans- target genes of the differential lncRNAs. To identify cold-responsive genes, a meta-analysis was used to integrate 35 cold-tolerant QTLs at the booting stage. In summary, 12 candidate genes and their target lncRNAs were identified by qRT-PCR. LncTar was used to identify the interaction between lncRNAs and the candidate genes. In addition, 130 rice cultivars with rich genetic diversity were collected to verify the association of candidate genes with cold-resistance. The results revealed that five SNPs in LOC_Os07g42940, three SNP and one InDel in LOC_Os02g03410 were associated with cold-resistance at a significant level using association analysis. This study provides new gene resources and insights into cold-resistance research for rice.

6.
BMC Surg ; 20(1): 226, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028289

RESUMO

BACKGROUND: The incidence of fractures around the femoral prosthesis among patients undergoing hip arthroplasty is increasing and has become the third leading cause of hip revision. While numerous methods for the surgical treatment of periprosthetic femoral fractures (PFFs) have been proposed, only few reports have examined the long-term efficacy of surgical treatment. This study aims to examine the mid-and long-term efficacy of surgical treatment among patients with Vancouver B2 and B3 PFFs. METHODS: This retrospective study evaluated the surgical outcomes of patients with Vancouver B2 and B3 PFFs between 2007 and 2011. The minimum follow-up time was eight years. Fracture healing, prosthesis stability, complications, patient quality of life SF-36 score, and survival rate were evaluated during the follow-up assessments. RESULTS: A total of 83 patients were included and had an average follow-up period of 120.3 months. Among these patients, 69 were classified as Vancouver B2 and were treated with a distal fixation stem, whereas 14 cases were classified as Vancouver B3 and were treated with modular femoral prosthesis by using a proximal femoral allograft technique. A total of 15 patients underwent secondary revision surgery, and prosthesis dislocation was identified as the main cause of secondary revision. 80 (96.4%) cases of fractures were clinically healed. The mortality rate in the first year after surgery was 8.4% (7/83). The overall 5-year Kaplan-Meier survival rate for these patients was 75.9%. Meanwhile, the 5-year Kaplan-Meier survival rate for the implants was 86.9%. The final follow-up SF-36 score of the patients was 48.3 ± 9.8. CONCLUSIONS: Patients with Vancouver B2 and B3 PFFs show high mortality in the first year after their surgery, and the Kaplan-Meier analysis results showed that such mortality tends to plateau after 5 years. Prosthesis dislocation was identified as the primary cause of secondary revision.

7.
J Exp Clin Cancer Res ; 39(1): 209, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028359

RESUMO

BACKGROUND: Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC. METHODS: We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo. RESULTS: Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients. CONCLUSIONS: CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.

8.
Stem Cell Res Ther ; 11(1): 434, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032649

RESUMO

BACKGROUND: The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. OBJECTIVE: To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. METHODS: Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. RESULTS: Treatment BMSCs with 50 µM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3ß. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. CONCLUSIONS: The findings suggested that 50 µM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.

9.
Mol Med Rep ; 22(5): 4278-4288, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000275

RESUMO

The RNA quality of tissue biobank is crucial for translational research; however, the effects of the ex vivo ischemia time on RNA integrity and expression of genes related to hypoxia, stress, apoptosis and autophagy remains elusive. A total of 18 carcinoma tissues were stored at room temperature for 15 min, 30 min, 1, 2, 4, 8 and 24 h. The integrity and purity of isolated RNA were analyzed. Furthermore, the gene expression of mTOR, hypoxia­inducible factor 1α, phosphatidylinositol 4,5­bisphosphate 3­kinase catalytic subunit ß isoform (PI3KCB), threonine kinase 1 (AKT1), NF­κB, protein kinase AMP­activated catalytic subunit α1 (AMPKα1), caspase 8 (CASP8), unc­51 like autophagy activating kinase 1 and Fas cell surface death receptor were analyzed using reverse transcription­quantitative PCR. The results demonstrated that RNA integrity numbers (RINs) remained stable in carcinoma tissues following ex vivo ischemia for 2 h at room temperature and that degradation began at 4 h (P<0.001). Additionally, the expression of PI3KCB, AKT1, AMPKα1 and CASP8 decreased at time points 8­24 h following ex vivo ischemia and delayed processing (P<0.001). In conclusion, >2 h of ex vivo ischemia and delayed processing induced RNA degradation and RIN, and the gene expressions of PI3KCB, AKT, AMPKα1 and CASP8 may be considered as markers to evaluate tissue quality at the gene expression level, providing a method for the standard processing and assessment of tissue specimen.

10.
J Appl Microbiol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33034112

RESUMO

AIMS: The aim at this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0.03, 0.3, and 3 mmol L-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harboring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analyzed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria, CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33057710

RESUMO

OBJECTIVES: To determine the dissemination and molecular characteristics of NDM-producing Escherichia coli strains from duck farms in south-east coastal China and their threats to human health. METHODS: A total of 232 NDM-producing E. coli were recovered from 1505 samples collected from 25 duck farms and their surrounding environments in five provinces in China. Resistance genes were confirmed using PCR. Genomic characteristics of the carbapenemase-producing isolates were determined by WGS and bioinformatic analysis. RESULTS: The rate of NDM-positive E. coli detected in samples from the five provinces ranged from 3.7% to 28.5%. There was substantial variation in the prevalence of NDM-positive E. coli from different duck farms in each province studied. Three variants (blaNDM-1, blaNDM-4 and blaNDM-5) were found in 232 NDM-positive E. coli; blaNDM-5 (94.8%, 220/232) was the most prevalent. WGS analysis indicated that ST746, ST48, ST1011 and ST167 E. coli isolates were prevalent in the current study and poultry was likely the primary reservoir for NDM-positive ST746 and ST48 E. coli in China. Phylogenomic analysis showed that NDM-positive E. coli isolates from ducks were closely related to those of human origin. In addition, WGS analysis further revealed that blaNDM co-existed with other antibiotic resistance genes, conferring resistance to nine classes of antimicrobials. CONCLUSIONS: This study revealed that ducks farm in China are an important reservoir for NDM-positive E. coli and STs of the isolates showed obvious distinctive diversities in geographical distribution. The distribution and spread of NDM-positive E. coli in duck farms poses a threat to public health.

12.
Crit Care ; 24(1): 614, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076940

RESUMO

Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury.

13.
J Therm Biol ; 93: 102722, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33077135

RESUMO

Megaselia spiracularis Schmitz, 1938 (Diptera: Phoridae) is a pest that often appears in human living areas where it can spread pathogens. Besides, the species is of forensic value. Currently, studies focusing on the development of this species are limited. Understanding the developmental patterns of M. spiracularis, therefore, is important for controlling populations of this pest and for estimating the minimum postmortem interval (PMImin). Here, we studied the development of M. spiracularis exposed to seven constant temperatures ranging from 16 to 34 °C. The developmental durations, accumulated degree hours and larval body length changes were measured. Three kinds of development models that can be used to estimate the PMImin were established, including isomorphen diagram, isomegalen diagram and thermal summation model. The duration of M. spiracularis development at 16, 19, 22, 25, 28, 31 and 34 °C from egg to adult stage were 1131.1 ± 34.5, 807.3 ± 9.3, 529.6 ± 1.8, 367.0 ± 8.8, 302.4 ± 7.0, 250.0 ± 2.1 and 232.6 ± 1.9 h, respectively. The developmental threshold temperature and the thermal summation constant were estimated as 12.0 ± 0.5 °C and 4989.7 ± 308.9° hours, respectively. A general model represented by a logistic equation describing how larval body length will change with the time after hatching was fit to data. The present study provides basic developmental data of M. spiracularis, which can be used for achieving better control of this noxious insect as well as for estimation of its PMImin at different temperatures.

14.
Medicine (Baltimore) ; 99(41): e22386, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031274

RESUMO

BACKGROUND: This study will assess the efficacy and safety of ventilator for the management of severe pneumonia (SP). METHODS: This study will search the following electronic databases in MEDLINE, EMBASE, Web of Science, PsycINFO, Cochrane Library, CNKI, and Scopus from the beginning to present without language restrictions. Two authors will screen all records according to the eligibility criteria; assess study quality; and extract all essential data from eligible studies. If sufficient studies are included, we will pool the extracted data and carry out meta-analysis. RESULTS: This study will summarize published studies to assess the efficacy and safety of ventilator for patients with SP. CONCLUSION: The results of this study may supply a genuine understanding of perspective from a scientific basis on ventilator for the management of patients with SP.


Assuntos
Pneumonia/terapia , Respiração Artificial , Ventiladores Mecânicos , Humanos , Gravidade do Paciente , Projetos de Pesquisa , Respiração Artificial/efeitos adversos , Respiração Artificial/instrumentação , Revisões Sistemáticas como Assunto , Ventiladores Mecânicos/efeitos adversos
15.
Org Lett ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074676

RESUMO

With glycosyl o-alkynylbenzotes as donors, a highly efficient protocol to construct the challenging glycosidic linkages at C3-OH of C23-oxo oleanane triterpenoids is disclosed, on the basis of which different strategies for the highly efficient synthesis of QS-21 analogues with the west-wing trisaccharide of QS-21 have been established.

16.
Cell Mol Biol (Noisy-le-grand) ; 66(5): 73-79, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33040817

RESUMO

This study aimed to investigate the effect of dexmedetomidine combined with ropivacaine on inflammatory factors in children with axillary brachial plexus block. Ninety patients who underwent upper limb surgery in our hospital from January 2017 to December 2018 were enrolled and divided into groups A and B. Group A (n=40) was treated with ropivacaine as a local anesthetic, and group B (n= 50) was treated with dexmedetomidine combined with ropivacaine as a local anesthetic during surgery. Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Pain Assessment Scale was employed to evaluate the pain behavior of the children. Intravenous blood (3 ml) was taken before surgery (T0), 30 min (T1) and 3 hours after surgery (T2) respectively to detect serum TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6) and IL-1ß (interleukin-1ß) levels using ELISA. The adverse reactions in the two groups were observed, and the MAP (mean arterial pressure) and HR (heart rate) were compared before anesthesia, 30 min and 1 hour after block. The FLACC score of both groups showed a marked upward trend (p< 0.001), with that of group B being significantly lower than group A (p< 0.001). Group B presented a remarkably shorter onset time than group A, and the analgesic time was significantly longer (p< 0.001). The incidence of adverse reactions in group B was significantly lower than that in group A (p< 0.05). MAP and HR dropped significantly 30 min and 1 h after block (p< 0.05). MAP and HR were significantly lower in group B than those in group A 30 min and 60 min after block (p< 0.05). As to serum levels of TNF-α, IL-6, and IL-1ß, both groups presented notably increased ones after block (p< 0.05). The application of dexmedetomidine combined with ropivacaine in upper limb surgery has a faster onset time and longer duration than ropivacaine alone, which is of certain clinical effect.

17.
Food Chem ; : 128243, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33069529

RESUMO

Tea saponins from Camellia oleifera Abel. seed pomace are new sources of commercial saponins. This study established an eco-friendly and efficient extraction method for tea saponins from C. oleifera seed pomace. A ternary deep eutectic solvent (DES) composed of l-proline, glycerol and sucrose (4:10:1 in molar ratio, abbreviated as PGS-5) achieved the highest extraction yield of tea saponins among all screened DESs. A maximum extraction yield of 23.22 ± 0.28% was obtained using PGS-5 under the optimized extraction time, DES concentration and liquid-solid ratio. Through ultraviolet, Fourier transform infrared spectroscopy and ultrahigh-performance liquid chromatography-Q Exactive HF mass spectroscopy, as well as analyses of antioxidant and antimicrobial activities, it was determined that extracted saponins did not altered during processing. Therefore, PGS-5 can serve as a solvent to obtain stable and beneficial tea saponins from C. oleifera seed pomace.

18.
Tree Physiol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079182

RESUMO

Conspicuous color is a common trait of foliar galls, but their relationship with gall-inducing insects is unknown. Red and green galls were taken from sunny or shady parts of peach species Prunus persica f. rubro-plena with peach aphid Tuberocephalus momonis infestation. We found that the loss of photosynthetic pigments was associated with the conspicuous coloration of green gall tissues. The concentrations of anthocyanins significantly increased following UV irradiation of green gall tissues, suggesting that accumulation of anthocyanins in red galls is related to UVB and UVC radiation. The expression of structural genes related to the biosynthesis of chlorogenic acid and malic acid benzoate were increased in all gall tissues and negatively correlated with the expression profiles of certain genes associated with photosynthetic biosynthesis, indicating that the increased transcript levels of the phenylpropanoid pathway might cause loss of photosynthetic efficiency in the gall tissues. Transcriptome and qRT-PCR analyses revealed that MYB transcription factors that up-regulate the biosynthesis of anthocyanins in red gall tissues might be activated by both UVB and UVC exposure. Comet assays suggest that green and red gall tissues have similar DNA damage following UV irradiation. No obvious effect of the up-regulated compounds on the growth of the peach aphid was observed. Interestingly, peach aphids under leaves painted with anthocyanins had lower mortality following UV irradiation than those in controls. These results suggest that the anthocyanins in red gall tissues have a defensive function for the peach aphid, protecting it against UV radiation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32981877

RESUMO

OBJECTIVES: The aim of this study was to retrospectively analyze the clinical characteristics, surgical treatment, and prognosis of patients with diffuse-type tenosynovial giant cell tumor (D-TGCT) involving the temporomandibular joint (TMJ) and the skull base. STUDY DESIGN: A retrospective study was performed in patients with D-TGCT involving the TMJ and the skull base at our institute from April 2009 to August 2018. Data on clinical characteristics, surgical treatment, and prognosis were collected and analyzed. A literature search on D-TGCT involving the TMJ was conducted and the data analyzed. RESULTS: The study included 22 patients (14 males and 8 females), with an average age of 44 years. The main symptoms were headache and hearing limitation, accompanied by a swelling in the TMJ area. Magnetic resonance imaging (MRI) showed low signals on T1- and T2-weighted images. All lesions were completely removed. Temporal bone flap, titanium mesh, and temporal muscle flap were used for reconstruction. The recurrence rate was 4.5%. In the literature, 115 cases were reported. Surgery alone was performed in 88 cases; postoperative radiotherapy was performed in 19 cases; the tumor recurrence rates were 9.1% and 15.8% for the 2 procedures, respectively. All patients were alive at the end of the follow-up period. CONCLUSIONS: D-TGCT involving the TMJ and the skull base is a locally aggressive but benign lesion necessitating complete resection and has a good prognosis.

20.
Liver Transpl ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32897657

RESUMO

Emerging evidence supports a role for immune checkpoint inhibitor therapy in addition to standard chemotherapy and/or targeted therapy for advanced malignancy. However, transplant patients usually are excluded from immune checkpoint inhibitor therapy due to the fear of possible graft rejection. We aimed to confirm that the lack of graft PD-L1 expression is a biomarker for the safety of using anti-PD1 therapy for liver transplant patients who suffered disease recurrence. We conducted a prospective, single-arm study of patients with recurrent hepatic tumors following liver transplantation whose allograft demonstrated absence of PD-L1 expression by immunohistochemistry (IHC) at Zhongshan Hospital. Participants who received a liver transplantation for hepatocellular carcinoma (HCC) or biliary tract cancers and experienced tumor recurrence or secondary primary hepatic malignancy were screened for PD-L1 expression in graft. Eligible patients (negative PD-L1 expression in graft) received toripalimab, 240mg every 3 weeks until graft rejection, grade 4 or unacceptable toxicity, or voluntary withdrawal. The primary study objective was to compare the graft rejection rate for liver (PD-L1 negative graft) transplant recipients receiving PD1 inhibitor to historical controls (liver transplant recipients with unknown PD-L1 status). The study was registered with ClinicalTrials.gov (NCT03966209). All the 5 patients without PD-L1 expression in their grafts received anti-PD1 therapy without developing graft-related immune-related adverse events (irAEs). One off study patient with positive graft PD-L1 expression suffered graft rejection. CONCLUSIONS: Graft PD-L1 expression may be a promising marker for transplant recipients' organ rejection following anti-PD1 immunotherapy. These findings need to be further investigated in patients with solid organ transplantation.

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