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1.
Nat Immunol ; 25(3): 483-495, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38177283

RESUMO

Tumor cells and surrounding immune cells undergo metabolic reprogramming, leading to an acidic tumor microenvironment. However, it is unclear how tumor cells adapt to this acidic stress during tumor progression. Here we show that carnosine, a mobile buffering metabolite that accumulates under hypoxia in tumor cells, regulates intracellular pH homeostasis and drives lysosome-dependent tumor immune evasion. A previously unrecognized isoform of carnosine synthase, CARNS2, promotes carnosine synthesis under hypoxia. Carnosine maintains intracellular pH (pHi) homeostasis by functioning as a mobile proton carrier to accelerate cytosolic H+ mobility and release, which in turn controls lysosomal subcellular distribution, acidification and activity. Furthermore, by maintaining lysosomal activity, carnosine facilitates nuclear transcription factor X-box binding 1 (NFX1) degradation, triggering galectin-9 and T-cell-mediated immune escape and tumorigenesis. These findings indicate an unconventional mechanism for pHi regulation in cancer cells and demonstrate how lysosome contributes to immune evasion, thus providing a basis for development of combined therapeutic strategies against hepatocellular carcinoma that exploit disrupted pHi homeostasis with immune checkpoint blockade.


Assuntos
Carcinoma Hepatocelular , Carnosina , Neoplasias Hepáticas , Humanos , Homeostase , Lisossomos , Hipóxia , Concentração de Íons de Hidrogênio , Microambiente Tumoral
2.
Neurospine ; 20(3): 1040-1046, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37798996

RESUMO

OBJECTIVE: Although endoscopic drill has the advantages in manipulation and hemostasis, whose low efficiency and blurred vision reduce the efficacy of lumbar endoscopic unilateral laminotomy with bilateral decompression (LE-ULBD). The present study was designed to evaluate the safety and efficacy of full-visualized trephine/osteotome in the LE-ULBD surgery for severe lumbar stenosis. METHODS: Fifty-seven severe lumbar stenosis patients who underwent LE-ULBD between January 2020 to January 2023 were enrolled, who were divided into drill and visualized trephine groups. The medical records including demographics, operative duration, intraoperative electrophysiological findings, postoperative hospital stay or hospital stay, postoperative outcomes and complications were retrospectively reviewed and analyzed. RESULTS: A total of 57 patients included 15 in drill and 42 in trephine group were enrolled in the study. There was significant difference in the pre- and postoperative visual analogue scale and Oswestry Disability Index scores in both groups (p < 0.05). The mean operative duration in the trephine group (101.05 ± 12.18 minutes) was shorter than that in the drill group (134.67 ± 9.68 minutes) (p < 0.05). There was no statistical difference between the 2 groups in electrophysiological monitoring, posthospital stays, postoperative outcomes and complications. Abnormal free-electromyography (EMG) were recorded in 2 (13.3%) and 5 patients (11.9%) in the drill and trephine group. Intraoperative somatosensory evoked potential changes occurred in 3 (20%) and 3 patients (7.1%) in the drill and trephine group and all patients recovered immediately when surgery ended. No serious complications and recurrence occurred in all the patients. CONCLUSION: Full-visualized trephine/osteotome has been approved to be convenient, safe and efficient in our study, which combined with translaminar inside-out technique and EMG monitoring especially free-EMG may offer a new choice in LE-ULBD surgery for lumbar stenosis patients.

3.
Curr Med Imaging ; 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37691213

RESUMO

BACKGROUND: Ganglioglioma is a rare, slowly proliferating mixed glioneuronal tumor, with the highest incidence observed in children and young adults, but it can also occur in adults. OBJECTIVE: This study aimed to compare the imaging characteristics of ganglioglioma in children/adolescents and adults to facilitate radiographic diagnosis. METHODS: In this retrospective study, a total of 32 patients were included and divided into two groups: the child/adolescent group (age < 18 years, n=19) and the adult group (age ≥ 18 years, n=13). Various variables were analyzed, including maximum diameter, location, periphery, border, calcification, unenhanced CT attenuation, T1WI, T2WI/FLAIR, and DWI signal intensity, enhancement pattern, degree of enhancement, homogeneity of enhancement, solid/cystic component, peri-tumoral edema, intra-tumoral septa, peri-tumoral capsule, and intra-tumoral hemorrhage. RESULTS: Most gangliogliomas were situated in the peripheral regions, particularly in the temporal lobe. The majority exhibited hypointense/isointense signals on T1WI and hyperintense signals on T2WI/FLAIR and DWI, with predominantly heterogeneous nodular enhancement. Peri-tumoral edema was significantly less frequent in the child/adolescent group, while marked enhancement was significantly more common in the adult group. There was no significant difference in maximum diameter between the child/adolescent group and the adult group. CONCLUSION: Peri-tumoral edema was significantly less prevalent in the child/adolescent group, whereas marked enhancement was significantly more frequent in the adult group. To ensure accurate results, a larger case series should be conducted to validate our findings.

4.
Acta Biochim Biophys Sin (Shanghai) ; 55(9): 1370-1379, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37580952

RESUMO

Tumor metabolic reprogramming and epigenetic modification work together to promote tumorigenesis and development. Protein lysine acetylation, which affects a variety of biological functions of proteins, plays an important role under physiological and pathological conditions. Here, through immunoprecipitation and mass spectrum data, we show that phosphoglycerate mutase 5 (PGAM5) deacetylation enhances malic enzyme 1 (ME1) metabolic enzyme activity to promote lipid synthesis and proliferation of liver cancer cells. Mechanistically, we demonstrate that the deacetylase SIRT2 mediates PGAM5 deacetylation to activate ME1 activity, leading to ME1 dephosphorylation, subsequent lipid accumulation and the proliferation of liver cancer cells. Taken together, our study establishes an important role for the SIRT2-PGAM5-ME1 axis in the proliferation of liver cancer cells, suggesting a potential innovative cancer therapy.


Assuntos
Neoplasias Hepáticas , Sirtuína 2 , Humanos , Sirtuína 2/genética , Sirtuína 2/metabolismo , Metabolismo dos Lipídeos , Fosfoglicerato Mutase/genética , Fosfoglicerato Mutase/metabolismo , Proliferação de Células , Lipídeos , Acetilação , Fosfoproteínas Fosfatases/metabolismo , Proteínas Mitocondriais/metabolismo
5.
Cell Rep ; 41(8): 111691, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417878

RESUMO

Branched-chain amino acid (BCAA) catabolism is related to tumorigenesis. However, the underlying mechanism and specific contexts in which BCAAs affect tumor progression remain unclear. Here, we demonstrate that BCAA catabolism is activated in liver cancer cells without glutamine. Enhanced BCAA catabolism leads to BCAA-derived carbon and nitrogen flow toward nucleotide synthesis, stimulating cell-cycle progression and promoting cell survival. Mechanistically, O-GlcNAcylation increases under glutamine-deprivation conditions and stabilizes the PPM1K protein, leading to dephosphorylation of BCKDHA and enhanced decomposition of BCAAs. Dephosphorylation of BCKDHA and high expression of PPM1K promote tumorigenesis in vitro and in vivo and are closely related to the poor prognosis of clinical patients with hepatocellular carcinoma (HCC). Inhibition of BCAA and glutamine metabolism can further retard HCC growth in vivo. These results not only elucidate a mechanism by which BCAA catabolism affects tumorigenesis but also identify pBCKDHA and PPM1K as potential therapeutic targets and predictive biomarkers.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Glutamina/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Carcinogênese
6.
EMBO J ; 41(23): e111550, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36314841

RESUMO

Phosphoglycerate dehydrogenase (PHGDH) is a key serine biosynthesis enzyme whose aberrant expression promotes various types of tumors. Recently, PHGDH has been found to have some non-canonical functions beyond serine biosynthesis, but its specific mechanisms in tumorigenesis remain unclear. Here, we show that PHGDH localizes to the inner mitochondrial membrane and promotes the translation of mitochondrial DNA (mtDNA)-encoded proteins in liver cancer cells. Mechanistically, we demonstrate that mitochondrial PHGDH directly interacts with adenine nucleotide translocase 2 (ANT2) and then recruits mitochondrial elongation factor G2 (mtEFG2) to promote mitochondrial ribosome recycling efficiency, thereby promoting mtDNA-encoded protein expression and subsequent mitochondrial respiration. Moreover, we show that treatment with a mitochondrial translation inhibitor or depletion of mtEFG2 diminishes PHGDH-mediated tumor growth. Collectively, our findings uncover a previously unappreciated function of PHGDH in tumorigenesis acting via promotion of mitochondrial translation and bioenergetics.


Assuntos
Neoplasias Hepáticas , Fosfoglicerato Desidrogenase , Humanos , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Linhagem Celular Tumoral , Serina , Neoplasias Hepáticas/genética , Carcinogênese , DNA Mitocondrial
7.
Nat Cancer ; 3(1): 75-89, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35121990

RESUMO

α-Enolase 1 (ENO1) is a critical glycolytic enzyme whose aberrant expression drives the pathogenesis of various cancers. ENO1 has been indicated as having additional roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we show that ENO1 suppresses iron regulatory protein 1 (IRP1) expression to regulate iron homeostasis and survival of hepatocellular carcinoma (HCC) cells. Mechanistically, we demonstrate that ENO1, as an RNA-binding protein, recruits CNOT6 to accelerate the messenger RNA decay of IRP1 in cancer cells, leading to inhibition of mitoferrin-1 (Mfrn1) expression and subsequent repression of mitochondrial iron-induced ferroptosis. Moreover, through in vitro and in vivo experiments and clinical sample analysis, we identified IRP1 and Mfrn1 as tumor suppressors by inducing ferroptosis in HCC cells. Taken together, this study establishes an important role for the ENO1-IRP1-Mfrn1 pathway in the pathogenesis of HCC and reveals a previously unknown connection between this pathway and ferroptosis, suggesting a potential innovative cancer therapy.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Proteína 1 Reguladora do Ferro/metabolismo , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Ferroptose/genética , Humanos , Ferro/metabolismo , Proteína 1 Reguladora do Ferro/genética , Neoplasias Hepáticas/genética , Fosfopiruvato Hidratase/genética , RNA Mensageiro/genética , Proteínas Supressoras de Tumor/metabolismo
8.
Childs Nerv Syst ; 38(4): 767-772, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35034138

RESUMO

OBJECTIVES: Pediatric trigeminal neuralgia has been rarely reported in the literature, which were only 28 cases. Although microvascular decompression (MVD) has been widely accepted as effective therapy for trigeminal neuralgia, the etiology and surgical treatment of pediatric ones are seldom addressed. We report our experience with MVD for pediatric trigeminal neuralgia patients with emphasis on the vascular conflict patterns and surgical skills. METHODS: This retrospective report included 11 pediatric TN patients, who underwent MVD and were followed for 3-86 months. The data were retrospectively analyzed with emphasis on the clinical features. RESULTS: This series included 4 boys and 7 girls with average age of 13 ± 3.4 years old, their onset age were from 7 to 18 years old. The singular vein and combined artery/vein conflictions account for 7/11. 9 (81.8%) patients achieved immediate excellent outcomes. One recurrence was observed after 5 months and refused the second surgery. CONCLUSIONS: The etiology of pediatric onset trigeminal neuralgia is still vascular conflict, whose patterns are different from adults, of which combined artery/vein and singular venous compression patterns have a much more higher proportion. Because of the smaller operative space and fragile-thin venous wall with adhesion to other structures, it is much more difficult to decompress the trigeminal nerve among pediatric patients. Sufficient arachnoid release, full exploration, and decompression along the trigeminal nerve were necessary, which will increase the excellent rate among pediatric patients.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/cirurgia , Veias
9.
Interact Cardiovasc Thorac Surg ; 34(6): 1160-1161, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34849945

RESUMO

The goal of this paper was to report a new variant of oesophageal atresia: an H-type congenital tracheo-oesophageal fistula associated with oesophageal segmental stenosis distal to the fistula. Although symptoms were present from birth, we did not differentiate the new anatomical variant preoperatively. The patient was treated by fistula ligation, segmental resection of the distal oesophagus and end-to-end anastomosis of the oesophagus by thoracoscopic surgery. Here we describe the clinical history and management of the newborn infant, together with diagnostic recommendations to prevent misdiagnosis in the management of this condition.


Assuntos
Atresia Esofágica , Estenose Esofágica , Fístula Traqueoesofágica , Anastomose Cirúrgica , Atresia Esofágica/complicações , Atresia Esofágica/diagnóstico por imagem , Atresia Esofágica/cirurgia , Estenose Esofágica/diagnóstico por imagem , Estenose Esofágica/etiologia , Estenose Esofágica/cirurgia , Humanos , Lactente , Recém-Nascido , Toracoscopia , Fístula Traqueoesofágica/diagnóstico por imagem , Fístula Traqueoesofágica/etiologia , Fístula Traqueoesofágica/cirurgia
10.
J Neurol Surg A Cent Eur Neurosurg ; 83(2): 118-121, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34237777

RESUMO

OBJECTIVE: The aim of the present study was to evaluate the efficacy and safety of microvascular decompression (MVD) for primary hemifacial spasm (HFS) in patients aged ≥70 years and to compare the outcome with a control cohort of younger patients(<70 years). METHODS: In this retrospective study, subjects were divided into two groups: an elderly group (patients who were ≥70 years) and a younger group. We compared demographic and clinical data, surgical outcome, MVD-related complications, and duration of operation and hospitalization after MVD between the two groups. RESULTS: At a mean follow-up of 32 ± 4.2 months, 188 elderly patients (90.4%) reported an effective outcome without need for any medication versus 379 (91.1%) of the younger cohort. There was no mortality in both cohorts. The prevalence of delayed facial palsy was 4.8% in the elderly group and 4.1% in the younger group. One (0.5%) patient in the elderly group and 3 (0.7%) patients in the younger group suffered cerebrospinal fluid (CSF) leakage. There was no significant difference between the two groups in terms of MVD-related complications, such as delayed facial palsy, hearing impairment, CSF leakage, and hematoma. CONCLUSIONS: MVD is an effective treatment option in elderly patients with HFS as well as in younger patients. Age itself seems to be no relevant contraindication or, alternatively, risk factor regarding MVD.


Assuntos
Paralisia Facial , Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Idoso , Paralisia Facial/etiologia , Espasmo Hemifacial/etiologia , Espasmo Hemifacial/cirurgia , Humanos , Cirurgia de Descompressão Microvascular/métodos , Estudos Retrospectivos , Resultado do Tratamento
11.
J Neurol Surg A Cent Eur Neurosurg ; 83(4): 338-343, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34781405

RESUMO

BACKGROUND: Microvascular decompression (MVD) has become accepted as an effective therapeutic option for hemifacial spasm (HFS); however, the curative rate of MVD for HFS varies widely (50-98%) in different medical centers. This study could contribute to the improvement of the MVD procedure. METHODS: We retrospectively analyzed 32 patients in whom initial MVD failed in other hospitals and who underwent a second MVD at our center. The clinical characteristics, operative findings, outcome of the second MVD, and complications were recorded. RESULTS: There were 18 women and 14 men (56.3 and 43.7%, respectively). The left-to-right ratio was 19:13. The mean age of the patients was 59.8 years. We found an undiscovered conflict site located in zone 4 in 10 patients and in the root entry zone in 8 patients. The initial MVD failed in nine patients because of ignorance of the arterioles that originate from the anterior inferior cerebellar artery. There were no special findings in four patients. No Teflon felts were found in the whole surgical field in one patient. CONCLUSION: Omission of the offending vessel is the most common cause of an unsuccessful MVD. Intraoperative abnormal muscle response associated with the Z-L response is a good measure to correctly identify the involved arterioles.


Assuntos
Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Artéria Basilar/cirurgia , Feminino , Espasmo Hemifacial/etiologia , Espasmo Hemifacial/cirurgia , Humanos , Masculino , Cirurgia de Descompressão Microvascular/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
12.
EMBO Rep ; 22(3): e51519, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33426808

RESUMO

The MYC oncoprotein activates and represses gene expression in a transcription-dependent or transcription-independent manner. Modification of mRNA emerges as a key gene expression regulatory nexus. We sought to determine whether MYC alters mRNA modifications and report here that MYC promotes cancer progression by down-regulating N6-methyladenosine (m6 A) preferentially in transcripts of a subset of MYC-repressed genes (MRGs). We find that MYC activates the expression of ALKBH5 and reduces m6 A levels in the mRNA of the selected MRGs SPI1 and PHF12. We also show that MYC-regulated m6 A controls the translation of MRG mRNA via the specific m6 A reader YTHDF3. Finally, we find that inhibition of ALKBH5, or overexpression of SPI1 or PHF12, effectively suppresses the growth of MYC-deregulated B-cell lymphomas, both in vitro and in vivo. Our findings uncover a novel mechanism by which MYC suppresses gene expression by altering m6 A modifications in selected MRG transcripts promotes cancer progression.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Neoplasias , Adenosina , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/genética , RNA Mensageiro/genética
13.
Cancer Res ; 81(5): 1265-1278, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33402389

RESUMO

Metastasis is responsible for the majority of breast cancer-related deaths, however, the mechanisms underlying metastasis in this disease remain largely elusive. Here we report that under hypoxic conditions, alternative splicing of MBD2 is suppressed, favoring the production of MBD2a, which facilitates breast cancer metastasis. Specifically, MBD2a promoted, whereas its lesser known short form MBD2c suppressed metastasis. Activation of HIF1 under hypoxia facilitated MBD2a production via repression of SRSF2-mediated alternative splicing. As a result, elevated MBD2a outcompeted MBD2c for binding to promoter CpG islands to activate expression of FZD1, thereby promoting epithelial-to-mesenchymal transition and metastasis. Strikingly, clinical data reveal significantly correlated expression of MBD2a and MBD2c with the invasiveness of malignancy, indicating opposing roles for MBD2 splicing variants in regulating human breast cancer metastasis. Collectively, our findings establish a novel link between MBD2 switching and tumor metastasis and provide a promising therapeutic strategy and predictive biomarkers for hypoxia-driven breast cancer metastasis. SIGNIFICANCE: This study defines the opposing roles and clinical relevance of MBD2a and MBD2c, two MBD2 alternative splicing products, in hypoxia-driven breast cancer metastasis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/5/1265/F1.large.jpg.


Assuntos
Processamento Alternativo , Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/genética , Receptores Frizzled/genética , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Ilhas de CpG , Transição Epitelial-Mesenquimal/genética , Feminino , Receptores Frizzled/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , MicroRNAs/genética , Regiões Promotoras Genéticas , Fatores de Processamento de Serina-Arginina/genética , Hipóxia Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Nat Metab ; 2(3): 256-269, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32694775

RESUMO

The transcriptional role of cMyc (or Myc) in tumorigenesis is well appreciated; however, it remains to be fully established how extensively Myc is involved in the epigenetic regulation of gene expression. Here, we show that by deactivating succinate dehydrogenase complex subunit A (SDHA) via acetylation, Myc triggers a regulatory cascade in cancer cells that leads to H3K4me3 activation and gene expression. We find that Myc facilitates the acetylation-dependent deactivation of SDHA by activating the SKP2-mediated degradation of SIRT3 deacetylase. We further demonstrate that Myc inhibition of SDH-complex activity leads to cellular succinate accumulation, which triggers H3K4me3 activation and tumour-specific gene expression. We demonstrate that acetylated SDHA at Lys 335 contributes to tumour growth in vitro and in vivo, and we confirm increased tumorigenesis in clinical samples. This study illustrates a link between acetylation-dependent SDHA deactivation and Myc-driven epigenetic regulation of gene expression, which is critical for cancer progression.


Assuntos
Transformação Celular Neoplásica , Complexo II de Transporte de Elétrons/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Acetilação , Ciclo do Ácido Cítrico , Complexo II de Transporte de Elétrons/genética , Epigênese Genética , Células HEK293 , Humanos , Ácido Succínico/metabolismo
15.
Neurol Res ; 42(6): 504-514, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279611

RESUMO

Background: To verify the hypothesis that the nature of trigeminal neuralgia (TN) is an ectopic impulse induced by sodium channel modulated by cytokines, we conducted an animal study using the infraorbital nerve chronic constriction injury (CCI) model in rats.Method: The expression of Nav1.3 or IL-6 in the infraorbital nerve (ION) and trigeminal ganglion (TG) were detected by western blot and immunocytochemistry after administration of antisense oligodeoxynucleotide sequence (AS), IL-6 or Anti-IL-6.Results: With intrathecal administration of AS or mismatch oligodeoxynucleotide sequence (MM) in the CCI rats, the Nav1.3-IR in ION and TG accounted for 2.2 ± 0.51% and 8.5 ± 3.1% in AS+CCI group vs. 6.9 ± 1.3% and 38.7 ± 4.8% in MM+CCI group (p < 0.05), respectively. While with local administration of IL-6 in those with sham operation, it accounted for 7.4 ± 2.1% and 45.5 ± 3.4% in IL-6+ sham group vs. 1.9 ± 0.67% and 8.1 ± 1.3% in vehicle+sham group (p < 0.05); with local administration of anti-IL-6 in CCI rats, 4.5 ± 0.78% and 32.1 ± 9.6% in Anti-IL-6+ CCI group vs 8.9 ± 2.1% and 61.4 ± 11.2% in vehicle+CCI group (p < 0.05).Discussion: We believe that the emergence of Nav1.3 from the compressed trigeminal nerve might be an important structural basis for the development of the ectopic excitability on the axon and IL-6 may play a role of necessary precondition.


Assuntos
Interleucina-6/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo , Síndromes de Compressão Nervosa/metabolismo , Neuralgia do Trigêmeo/metabolismo , Animais , Constrição Patológica , Masculino , Ratos , Ratos Sprague-Dawley , Nervo Trigêmeo/metabolismo , Regulação para Cima
16.
Acta Neurochir (Wien) ; 162(5): 1081-1087, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32133573

RESUMO

PURPOSE: Microvascular decompression (MVD) surgery has been accepted as a potentially curative method for hemifacial spasm (HFS). The primary cause of failure of MVD is incomplete decompression of the offending vessel due to inadequate visualization. This study is aimed at evaluating the benefit of endoscopic visualization and the value of fully endoscopic MVD. METHODS: From March 2016 to March 2018, 45 HFS patients underwent fully endoscopic MVD in our department. From opening the dura to preparing to close, the assistant held the endoscope and the surgeon operated. Abnormal muscle response (AMR) and brainstem auditory evoked potentials (BAEP) were monitored. For every patient, the offending vessel was transposed or interposed and achieved complete decompression. AMR was used to evaluate the adequacy of decompression at the end of the surgery. The intra-operative findings and postoperative outcomes and complications were analyzed. RESULTS: Immediately after surgeries, 39 patients (86.7%) achieved excellent result; 2 cases (4.4%) had good result. So the postoperative effective rate was 91.1% (41/45). During 12-36 month follow-up, the outcomes were excellent in 42 cases (93.3%) and good in 2 cases (4.4%), and the effective rate reached to 97.8% (44/45). No recurrence was noted. The postoperative complications were found in 2 patients (4.4%). One patient (2.2%) showed delayed facial palsy on the tenth day but was fully recovered 1 month later. Intracranial infection was noticed in 1 patient (2.2%) and was cured by using intravenous antibiotics for 2 weeks. There was no hearing impairment, hoarseness, or other complications. CONCLUSIONS: Fully endoscopic MVD is both safe and effective in the treatment of HFS. Electrophysiological monitoring is helpful to gain a good result and reduce hearing impairment.


Assuntos
Endoscopia/métodos , Perda Auditiva/epidemiologia , Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Endoscopia/efeitos adversos , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/etiologia , Humanos , Masculino , Cirurgia de Descompressão Microvascular/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia
17.
Stereotact Funct Neurosurg ; 98(2): 129-135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101860

RESUMO

BACKGROUND: Microvascular decompression (MVD) has been the right choice for glossopharyngeal neuralgia (GPN) patients. However, whether glossopharyngeal/vagal nerve root rhizotomy should be combined with MVD is still controversial. OBJECTIVE: To evaluate whether glossopharyngeal/vagal nerve root rhizotomy during MVD is necessary for the treatment of GPN. METHODS: We performed a retrospective study of 46 GPN patients who underwent MVD surgery alone in our hospital, and their patient demographics, clinical presentations, and intraoperative findings are shown. The immediate and long-term follow-up outcomes were investigated to show the treatment's efficiency and safety; the outcome was also compared with our previous study. The relevant literature was reviewed to show complications for GPN patients undergoing glossopharyngeal/vagal nerve root rhizotomy with MVD. RESULTS: The most common offending vessel was the posterior inferior cerebellar artery (60.9%). 100% of the patients were pain-free (score of I on the Barrow Neurological Institute pain intensity [BNI-P] scale) immediately after MVD surgery, while 1 patient relapsed with occasional pain 12 months after the operation (score of III on the BNI-P scale). Poor wound healing and hearing loss were found in 1 case each. No complications related to the glossopharyngeal nerve/vagal nerve were reported. Some surgical techniques, such as thorough exploration of the CN IX-X rootlets, full freeing from arachnoid adhesions, and usage of a moist gelatin sponge, can improve the success rate of the operation. CONCLUSIONS: MVD alone without rhizotomy is an effective and safe method for patients with GPN.


Assuntos
Doenças do Nervo Glossofaríngeo/cirurgia , Nervo Glossofaríngeo/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Rizotomia/métodos , Nervo Vago/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Nervo Glossofaríngeo/diagnóstico por imagem , Doenças do Nervo Glossofaríngeo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico por imagem , Dor/cirurgia , Medição da Dor/métodos , Estudos Retrospectivos , Resultado do Tratamento , Nervo Vago/diagnóstico por imagem
18.
World Neurosurg ; 133: e1-e5, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31252078

RESUMO

OBJECTIVE: We explored the remission rate of different branches of the trigeminal nerve after microvascular decompression. METHODS: A retrospective analysis of trigeminal neuralgia patients treated with microvascular decompression in our department from January 2014 to January 2015 was conducted to investigate the prognosis and factors affecting prognosis. RESULTS: One-hundred and fifty-five patients with trigeminal neuralgia including 2 patients with V1 division had a remission rate of 100% at 1 day, 3 months, 1 year, and 3 years after surgery; 93.5%, 93.5%, 90.3%, and 67.7% of patients with V1-2 division. The patients with V1-3 division had rates of 91.7%, 87.5%, 75.0%, and 66.7%; V2 division rates were 88.4%, 81.4%, 76.7%, and 69.8%; V2-3 division rates were 90.2%, 90.2%, 87.8%, and 75.6%; and V3 division were 100%, 100%, 92.9%, and 92.9%. CONCLUSIONS: Postoperative remission rate of non-V2-related branches (V1, V3) are higher than V2-related branches (V2, V1-2, V1-3, V2-3).


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Nervo Trigêmeo/patologia , Nervo Trigêmeo/cirurgia
19.
Cancer Res ; 79(19): 4923-4936, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31331910

RESUMO

DIS3-like 3'-5' exoribonuclease 2 (DIS3L2) degrades aberrant RNAs, however, its function in tumorigenesis remains largely unexplored. Here, aberrant DIS3L2 expression promoted human hepatocellular carcinoma (HCC) progression via heterogeneous nuclear ribonucleoproteins (hnRNP) U-mediated alternative splicing. DIS3L2 directly interacted with hnRNP U through its cold-shock domains and promoted inclusion of exon 3b during splicing of pre-Rac1 independent of its exonuclease activity, yielding an oncogenic splicing variant, Rac1b, which is known to stimulate cellular transformation and tumorigenesis. DIS3L2 regulated alternative splicing by recruiting hnRNP U to pre-Rac1. Rac1b was critical for DIS3L2 promotion of liver cancer development both in vitro and in vivo. Importantly, DIS3L2 and Rac1b expression highly correlated with HCC progression and patient survival. Taken together, our findings uncover an oncogenic role of DIS3L2, in which it promotes liver cancer progression through a previously unappreciated mechanism of regulating hnRNP U-mediated alterative splicing. SIGNIFICANCE: These findings establish the role and mechanism of the 3'-5' exoribonuclease DIS3L2 in hepatocellular carcinoma carcinogenesis.


Assuntos
Carcinoma Hepatocelular/patologia , Exorribonucleases/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/genética , Neoplasias Hepáticas/patologia , Processamento Alternativo/genética , Animais , Carcinoma Hepatocelular/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Camundongos , Camundongos Nus
20.
Childs Nerv Syst ; 35(7): 1173-1180, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31062140

RESUMO

PURPOSE: To compare the different levels of inflammatory markers, hormone markers, and radiological appearances between PCACP with and without calcification so as to explore the relationships between these markers and calcification. METHODS: The inflammatory markers, hormone markers, and radiological appearances were compared not only between PCACP with and without calcification, but also among its different forms of calcification. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic significance of all markers between these groups. RESULTS: It was showed that the white blood cell (WBC) count, neutrophil count, monocyte count, prognostic nutritional index (PNI), prolactin (PRL), and T1WI signal of cysts were higher in PCACP with calcification than in PCACP without calcification. The neutrophil count was significantly higher in PCACP with eggshell calcification than in other groups. The PCACP with mixed calcification had the highest PRL level in all kinds of PCACP with calcification. Only the area under curve (AUC) values of neutrophil count and PRL level were greater than 0.8. CONCLUSION: It is found that inflammation and hormone are related to PCACP's calcification. High neutrophil count and PRL level may indicate possible calcification tendency in PCACP. Improved intracystic therapies based on these results may help to inhibit the formation of calcification in PCACP in future.


Assuntos
Calcinose/etiologia , Craniofaringioma/complicações , Neoplasias Hipofisárias/complicações , Adolescente , Biomarcadores/sangue , Calcinose/sangue , Calcinose/diagnóstico por imagem , Criança , Pré-Escolar , Craniofaringioma/sangue , Craniofaringioma/diagnóstico por imagem , Feminino , Humanos , Lactente , Inflamação/sangue , Contagem de Leucócitos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico por imagem , Prognóstico , Prolactina/sangue
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