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1.
MedComm (2020) ; 5(4): e543, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38585233

RESUMO

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR-1246 levels. Specially, miR-1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR-1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR-1246 in vivo. Collectively, our findings suggest that miR-1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA-targeted gene activation and the potential of miR-1246 for osteosarcoma metastasis therapy.

2.
J Biomol Struct Dyn ; : 1-17, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38555737

RESUMO

PURPOSE: The present investigation focuses on Skin Cutaneous Melanoma (SKCM), a melanocytic carcinoma characterized by marked aggression, significant heterogeneity, and a complex etiological background, factors which collectively contribute to the challenge in prognostic determinations. We defined a novel classifier system specifically tailored for SKCM based on multiomics. METHODS: We collected 423 SKCM samples with multi omics datasets to perform a consensus cluster analysis using 10 machine learning algorithms and verified in 2 independent cohorts. Clinical features, biological characteristics, immune infiltration pattern, therapeutic response and mutation landscape were compared between subtypes. RESULTS: Based on consensus clustering algorithms, we identified two Multi-Omics-Based-Cancer-Subtypes (MOCS) in SKCM in TCGA project and validated in GSE19234 and GSE65904 cohorts. MOCS2 emerged as a subtype with poor prognosis, characterized by a complex immune microenvironment, dysfunctional anti-tumor immune state, high cancer stemness index, and genomic instability. MOCS2 exhibited resistance to chemotherapy agents like erlotinib and sunitinib while sensitive to rapamycin, NSC87877, MG132, and FH355. Additionally, ELSPBP1 was identified as the target involving in glycolysis and M2 macrophage infiltration in SKCM. CONCLUSIONS: MOCS classification could stably predict prognosis of SKCM; patients with a high cancer stemness index combined with genomic instability may be predisposed to an immune exhaustion state.Communicated by Ramaswamy H. Sarma.

3.
Mediators Inflamm ; 2024: 3188216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38385005

RESUMO

Background: Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods: We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results: Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion: CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients.


Assuntos
Artrite Reumatoide , Neoplasias , Humanos , Silício , Metaloproteinase 13 da Matriz , Biomarcadores , Algoritmos
4.
Nat Commun ; 15(1): 1300, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346942

RESUMO

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.


Assuntos
Reabsorção Óssea , Osteoclastos , Animais , Camundongos , Osteoclastos/metabolismo , Kisspeptinas/genética , Kisspeptinas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Quinases da Família src/genética , Quinases da Família src/metabolismo , Camundongos Knockout , Reabsorção Óssea/genética , Receptores de Kisspeptina-1
5.
J Cancer Res Clin Oncol ; 150(2): 95, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369555

RESUMO

PURPOSE: There is no approved targeted therapy for chordoma at present. Although several preclinical studies have implied the potential applicability of CDK4/6 inhibitor for this rare tumor, no clinical evidence has been documented so far. The purpose of this study was to elucidate the therapeutic efficacy of CDK4/6 inhibitor for chordoma. METHODS: The next generation sequencing (as for whole-exome sequencing, WES assay) and immunohistochemical (IHC) staining of the chordoma tissue from a patient with an advanced lesion were performed before treatment. Then, the patient was treated with Palbociclib for 4 months until progression occurred in the 5th month. Surgical resection was implemented and the tumor tissue was obtained postoperatively for assessment of molecular alterations. RESULTS: Molecular features of the tumor before medical treatment suggested applicability of CDK4/6 inhibitor and the patient showed partial response (PR) according to Choi Criteria after 4 months treating with Palbociclib until progression occurred. Then, a drastic molecular alteration of the tumor as represented by emergence of dramatic E2F amplification, which is known to induce CDK4/6 independent cell-cycle entry and progression after treatment, was detected. The findings in this patient demonstrated tumor evolution under drug pressure. CONCLUSION: The findings of the present study suggest the feasibility of Palbociclib for the clinical treatment of chordoma, and imply the necessity of combination therapies rather single drug administration due to the quick resistance of the tumor to Palbociclib treatment.


Assuntos
Cordoma , Piperazinas , Humanos , Estudos Retrospectivos , Cordoma/tratamento farmacológico , Cordoma/genética , Cordoma/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Piridinas , Quinase 4 Dependente de Ciclina/genética , Inibidores de Proteínas Quinases/farmacologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38239008

RESUMO

STUDY DESIGN: A retrospective case series. OBJECTIVE: This study developed a novel classification system based on imaging and anatomy to select optimal surgical approaches and reconstruction strategies to achieve total resection of cervical dumbbell tumors and restore spinal stability. SUMMARY OF BACKGROUND DATA: Total resection is necessary to decrease the recurrence rate of cervical dumbbell tumors. Previous cervical dumbbell tumor classifications are insufficient for determining surgical strategies, therefore, a practical classification is needed. METHODS: This study included 295 consecutive patients with cervical dumbbell tumors who underwent total surgical resection. A novel classification of cervical dumbbell tumors was developed based on magnetic resonance imaging and computed tomography. Continuous variables were expressed as mean±standard deviation (SD) and were compared using an unpaired two-tailed Student's t­test. The χ2 test or Fisher's exact test was used for categorical variables. Kendall's W test assessed three independent raters' inter- and intra-rater reliabilities on 140 cervical dumbbell tumors. RESULTS: The inter-rater and intra-rater consistency coefficient was 0.969 (χ2=404.3, P<0.001) and 0.984 (χ2=273.7, P<0.001). All patients with type I and II tumors underwent single-posterior surgeries to achieve total resection. Of the patients in this study, 86.1%, 25.9%, 75.9%, and 76.9% underwent posterior surgeries for types IIIa, IIIb, IVa, and V tumors, respectively. All patients with type IVb tumors underwent a combined anterior and posterior approach. Posterior internal fixation was used for all patients in posterior surgery. Anterior reconstruction was applied for patients with type IVb tumors (20/20, 100%) and some with Type V tumors (3/13, 23.1%). The mean follow-up duration was 93.6±2.6 months. Recurrence was observed in 19 (6.4%) patients. CONCLUSION: We describe a novel classification system that is of practical use for planning the complete resection of cervical dumbbell tumors.

7.
Spine J ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38272127

RESUMO

BACKGROUND CONTEXT: Cellular schwannoma (CS) is a rare tumor that accounts for 2.8%-5.2% of all benign schwannomas. There is a dearth of up-to-date information on spinal CS in the literature. PURPOSE: The aims of this study were to identify the proportion of CS cases amongst spinal benign schwannoma, describe the clinical features of spinal CS, and identify prognostic factors for local recurrence by analyzing data from 93 consecutive CS cases. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: We analyzed 93 PSGCT screened from 1,706 patients with spine CS who were treated at our institute between 2008 and 2021. OUTCOME MEASURES: Demographic, radiographic, operative and postoperative data were recorded and analyzed. METHODS: We compared the clinical features of spinal CS from the cervical, thoracic, lumbar and sacral segments. Prognostic factors for local recurrence-free survival (RFS) were identified by the Kaplan-Meier method. Factors with p≤.05 in univariate analysis were subjected to multivariate analysis by Cox regression analysis. RESULTS: The proportion of spinal CS in all benign schwannomas was 6.7%. The mean and median follow-up times for the 93 patients in this study were 92.2 and 91.0 months respectively (range 36-182 months). Local recurrence was detected in 11 cases, giving an overall recurrence rate of 11.7%, with one patient death. Statistical analysis revealed that tumor size ≥5 cm, intralesional resection, and Ki-67 ≥5% were independent negative prognostic factors for RFS in spinal CS. CONCLUSIONS: Whenever possible, en bloc resection is recommended for spinal CS. Long-term follow-up should be carried out for patients with tumor size ≥5 cm and postoperative pathological Ki-67 ≥5%.

8.
Orthop Surg ; 16(1): 78-85, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38014475

RESUMO

OBJECTIVE: Recurrent giant cell tumor (RGCT) of the spine represents a clinical challenge for surgeons, and the treatment strategy remains controversial. This study aims to describe the long-term follow-up outcomes and compare the efficacy of en bloc spondylectomy versus piecemeal spondylectomy in treating RGCT of the thoracolumbar spine. METHODS: A total of 32 patients with RGCT of the thoracolumbar spine treated from June 2012 to June 2019 were retrospectively reviewed. A total of 15 patients received total en bloc spondylectomy (TES) with wide or marginal margin while 17 patients received total piecemeal spondylectomy (TPS) with intralesional margin. Postoperative Eastern Cooperative Oncology Group Performance Score (ECOG-PS), Frankel classification and recurrence-free survival (RFS) were evaluated after surgery. Survival curves were estimated by the Kaplan-Meier method and differences were analyzed with the log-rank test. Multivariate analysis was performed with Cox regression to identify the independent prognostic factors affecting RFS. RESULTS: During a median follow-up of 41.9 ± 17.5 months, all patients with compromised neurologic functions exhibit significant improvement, with the mean ECOG-PS decreasing from 1.5 ± 1.3 to 0.13 ± 0.3 (p < 0.05). Among the 17 patients treated with TPS, eight patients developed local recurrence after a median time of 15.9 ± 6.4 months and four patients died from progressive disease. On the other hand, local recurrence were well managed with TES, since only one out of 15 patients experienced local relapse and all patients are alive with satisfied function at the latest follow-up. The median RFS for patients receiving TES and TPS are 75.0 months (95% CI: 67.5-82.5 m) and 38.3 months (95% CI: 27.3-49.3 m) respectively (p = 0.008). Multivariate analysis shows that the Ki67 index (p = 0.016), resection mode (p = 0.022), and denosumab (p = 0.039) are independent risk factors affecting RFS. CONCLUSIONS: TES with wide/marginal margin should be offered to patients with RGCT whenever feasible, given its long-term benefits in local control and symptom alleviation. Additionally, patients with lower Ki67 index and application of denosumab tend to have a better prognosis.


Assuntos
Tumores de Células Gigantes , Neoplasias da Coluna Vertebral , Humanos , Denosumab/uso terapêutico , Estudos Retrospectivos , Antígeno Ki-67 , Recidiva Local de Neoplasia/tratamento farmacológico , Coluna Vertebral/patologia , Resultado do Tratamento
9.
Adv Sci (Weinh) ; 11(5): e2305023, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38084002

RESUMO

Destruction of cartilage due to the abnormal remodeling of subchondral bone (SB) leads to osteoarthritis (OA), and restoring chondro-bone metabolic homeostasis is the key to the treatment of OA. However, traditional intra-articular injections for the treatment of OA cannot directly break through the cartilage barrier to reach SB. In this study, the hydrothermal method is used to synthesize ultra-small size (≈5 nm) selenium-doped carbon quantum dots (Se-CQDs, SC), which conjugated with triphenylphosphine (TPP) to create TPP-Se-CQDs (SCT). Further, SCT is dynamically complexed with hyaluronic acid modified with aldehyde and methacrylic anhydride (AHAMA) to construct highly permeable micro/nano hydrogel microspheres (SCT@AHAMA) for restoring chondro-bone metabolic homeostasis. In vitro experiments confirmed that the selenium atoms scavenged reactive oxygen species (ROS) from the mitochondria of mononuclear macrophages, inhibited osteoclast differentiation and function, and suppressed early chondrocyte apoptosis to maintain a balance between cartilage matrix synthesis and catabolism. In vivo experiments further demonstrated that the delivery system inhibited osteoclastogenesis and H-vessel invasion, thereby regulating the initiation and process of abnormal bone remodeling and inhibiting cartilage degeneration in SB. In conclusion, the micro/nano hydrogel microspheres based on ultra-small quantum dots facilitate the efficient penetration of articular SB and regulate chondro-bone metabolism for OA treatment.


Assuntos
Cartilagem Articular , Osteoartrite , Selênio , Humanos , Microesferas , Hidrogéis/metabolismo , Selênio/metabolismo , Cartilagem Articular/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo
11.
Cell Metab ; 35(12): 2183-2199.e7, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38006878

RESUMO

Methionine is an essential branch of diverse nutrient inputs that dictate mTORC1 activation. In the absence of methionine, SAMTOR binds to GATOR1 and inhibits mTORC1 signaling. However, how mTORC1 is activated upon methionine stimulation remains largely elusive. Here, we report that PRMT1 senses methionine/SAM by utilizing SAM as a cofactor for an enzymatic activity-based regulation of mTORC1 signaling. Under methionine-sufficient conditions, elevated cytosolic SAM releases SAMTOR from GATOR1, which confers the association of PRMT1 with GATOR1. Subsequently, SAM-loaded PRMT1 methylates NPRL2, the catalytic subunit of GATOR1, thereby suppressing its GAP activity and leading to mTORC1 activation. Notably, genetic or pharmacological inhibition of PRMT1 impedes hepatic methionine sensing by mTORC1 and improves insulin sensitivity in aged mice, establishing the role of PRMT1-mediated methionine sensing at physiological levels. Thus, PRMT1 coordinates with SAMTOR to form the methionine-sensing apparatus of mTORC1 signaling.


Assuntos
Metionina , Transdução de Sinais , Animais , Camundongos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metionina/metabolismo , Racemetionina/metabolismo , Metilação
12.
Medicine (Baltimore) ; 102(43): e34231, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904412

RESUMO

To clarify the epidemiology, treatment, and prognosis of sarcomas occurring in the bones and joints. The surveillance, epidemiology, and end results (SEER) 18 registries, comprising sarcoma diagnoses made between 2008 and 2014, were queried for sarcomas arising in bones or joints. Kaplan-Meier analysis, multivariate logistic regression analysis, Cox proportional hazards model, and nomograms were used to identify prognostic factors. 2794 patients aged from 1 to 99 (55.8% male) with microscopically confirmed diagnosed as sarcomas (including osteosarcoma, chondrosarcoma, Ewing sarcoma, and soft tissue sarcomas) which primary site limited to bone and joint were identified. Eight independent factors, including age, race, sex, tumor site, histology, pathology grade, tumor size, and total number of malignant tumors (TNOMT), were associated with tumor metastasis. Nine independent prognostic factors, including age (>=60 year, hazard ratio [HR] = 4.145, 95% confidence interval [CI], P < .001), sex (female, HR = 0.814, 95%CI, P = .007), tumor site (spine, HR = 2.527, 95%CI, P < .001), histology, pathology grade (undifferentiated, HR = 5.816, 95%CI, P < .001), tumor size (>=20 cm, HR = 3.043, 95%CI, P < .001), tumor extent (distant, HR = 4.145, 95%CI, P < .001), surgery (no performed, HR = 2.436, 95%CI, P < .001), and TNOMT (1, HR = 0.679, 95%CI, P < .001, were identified and incorporated to construct a nomogram for 2- and 5-year overall survival (OS). The calibration curve for the probability of survival showed good agreement between prediction by the nomogram and actual observation. The C-index of the nomogram for survival prediction was 0.814. Patients who received chemotherapy had a significantly decreased risk of death only for Ewing sarcoma, poorly differentiated tumors, undifferentiated tumors, and distant tumor invasion (P < .05). However, radiotherapy did not show significant differences in OS. This study presents population-based estimates of prognosis for patients with bone sarcomas and demonstrates the impact of age, race, sex, tumor site, histology, pathology grade, tumor size, tumor extent, surgery, radiotherapy, chemotherapy, and the TNOMT on OS. Moreover, the nomogram resulted in a more accurate prognostic prediction. However, in our study, radiotherapy showed no survival benefit, perhaps because detailed data on treatment factors were unavailable and which may have influenced the results.


Assuntos
Neoplasias Ósseas , Tumores Neuroectodérmicos Primitivos Periféricos , Osteossarcoma , Sarcoma de Ewing , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Feminino , Sarcoma de Ewing/epidemiologia , Sarcoma de Ewing/terapia , Sarcoma de Ewing/patologia , Prognóstico , Programa de SEER , Sarcoma/epidemiologia , Sarcoma/terapia , Nomogramas , Osteossarcoma/patologia , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/terapia , Neoplasias Ósseas/diagnóstico
13.
Am J Cancer Res ; 13(8): 3721-3740, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693165

RESUMO

Understanding the specificity and complexity of the tumor microenvironment (TME) of Ewing sarcoma (ES) is essential for identifying the immune characteristics of ES, improving the prediction of immunotherapeutic response, and facilitating therapeutic target discovery. In this study, we not only evaluated the gene sets associated with TME in ES using ESTIMATE and WGCNA algorithms based on the transcriptome data of ES, but also constructed a prognostic model (ES Score) using univariate Cox regression and Lasso regression and assessed its predictive ability on immune cell infiltration. Subsequently, we identified ARAP3 as a key gene affecting the TME of ES. In addition, bioinformatic analyses and in vitro experiments proved that the high expression of ARAP3 regulated ES cell proliferation, migration, as well as apoptosis via the p53 signaling pathway and affected macrophage infiltration and osteoclast differentiation through regulating IL1B and IL11 secretion of tumor cells.

14.
Oncogene ; 42(30): 2297-2314, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37349645

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest forms of human malignancy that currently lacks approved targeted therapeutics. Accumulating evidence suggests that SOX2 overexpression is a key driving factor for ESCC and various squamous cell carcinoma. Here, through screening a small-molecule kinase inhibitor library, we identified GSK3ß as a kinase that is critically required for robust SOX2 expression in ESCC cells. GSK3ß did not promote SOX2 transcriptionally but was required for SOX2 protein stability. We demonstrated that GSK3ß interacts with and phosphorylates SOX2 at residue S251, which blocks SOX2 from ubiquitination and proteasome-dependent degradation instigated by ubiquitin E3 ligase CUL4ADET1-COP1. Pharmacological inhibition or knockdown of GSK3ß by RNA interference selectively impaired SOX2-positive ESCC cell proliferation, cancer stemness, and tumor growth in mouse xenograft model, suggesting that GSK3ß promotes ESCC tumorigenesis primarily by driving SOX2 overexpression. GSK3ß was found to be frequently overexpressed in clinical esophageal tumors, and there was a positive correlation between GSK3ß and SOX2 protein levels. Notably, we found that SOX2 enhanced GSK3ß expression transcriptionally, suggesting the existence of a vicious cycle that drives a coordinated GSK3ß and SOX2 overexpression in ESCC cells. Finally, we demonstrated in tumor xenograft model that GSK3ß inhibitor AR-A014418 was effective in suppressing SOX2-positive ESCC tumor progression and inhibited tumor progression cooperatively with chemotherapeutic agent carboplatin. In conclusion, we uncovered a novel role for GSK3ß in driving SOX2 overexpression and tumorigenesis and provided evidence that targeting GSK3ß may hold promise for the treatment of recalcitrant ESCCs.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Neoplasias Esofágicas/patologia , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Culina/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo
15.
Clin Spine Surg ; 36(7): 256-264, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37296493

RESUMO

MAIN POINTS: Operational excision of tumor lesions in the upper cervical spine remains a tremendous challenge to surgeons due to the local complex anatomic relationships. Meanwhile, no commercially available device has been specially designed to address bone deficiency after surgical resection. Here, we described the reconstruction of unilateral bone deficiency after surgical resection of a giant cell tumor of the tendon sheath originating from the lateral atlantoaxial joint with the employment of a 3D printing technique and reviewed the relevant literature. In our study, 3 patients with giant cell tumor of the tendon sheath in the upper cervical spine achieved complete tumor removal, and received unilateral bone reconstruction with one-armed 3D-printed titanium prosthesis. During the follow-up, these patients remained neurologically intact and got back to a normal life without wearing the braces. Images demonstrated the satisfactory placement of 3D-printed prosthesis with no failure of fixation and no subsidence. In addition, 6 articles describing the employment of 3D-printed prostheses or models for tumor surgery in the upper cervical spine were reviewed, and satisfactory clinical outcomes were reported in these studies. Hence, 3D-printed titanium prosthetic reconstruction of bone deficiency in the upper cervical spine was a safe and effective technique. LEVEL OF EVIDENCE: Level IV.


Assuntos
Tumores de Células Gigantes , Titânio , Humanos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Implantação de Prótese , Tumores de Células Gigantes/cirurgia , Impressão Tridimensional
16.
World Neurosurg ; 176: e521-e534, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37263495

RESUMO

BACKGROUND: The spine is one of the common sites of esophageal cancer metastasis, with a worse prognosis than that of metastasis occurring in other sites. However, the exact mechanism underlying metastatic spinal esophageal cancer (MSEC) is poorly understood possibly due to the short survival time of patients. The aim of this study was to evaluate surgical outcomes and factors affecting the prognosis of patients with MSEC. METHODS: Enrolled in this retrospective study were 20 consecutive patients who received surgical treatment for MSEC in our hospital from 2013 to 2020. The impact of surgery on patient's quality of life was assessed by visual analog scale score and American Spinal Injury Association grade. Prognostic variables relative to traditional clinical parameters and inflammation and nutrition indicators were identified by univariate and multivariate analyses. RESULTS: The median survival time of patients with MSEC was 6 months, with a one-year survival rate of 20%. Pain relief was achieved in most patients, and nerve function was recovered in part of the patients after surgery. Analysis of clinical factors showed that total tumor resection was beneficial to overall survival of patients with MSEC. Laboratory indicators of erythrocyte sedimentation rate, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio were identified as independent prognostic factors for patients with MSEC. CONCLUSIONS: Timely surgical intervention can improve the quality of life of patients with MSEC. The preoperative erythrocyte sedimentation rate, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio could help predict the overall survival of patients with MSEC. These findings may help in decision-making for the treatment of patients with MSEC.


Assuntos
Neoplasias Esofágicas , Neoplasias da Coluna Vertebral , Humanos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário , Qualidade de Vida , Prognóstico , Neoplasias Esofágicas/cirurgia , Resultado do Tratamento
18.
Eur Spine J ; 32(7): 2503-2512, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37193901

RESUMO

PURPOSE: Although total en bloc spondylectomy (TES) is strongly recommended for spinal giant cell tumor (GCT), it is extremely difficult to excise a L5 neoplasm intactly through the single-stage posterior approach. Given the risk of neurological and vascular injury, intralesional curettage (IC) is usually recommended for the treatment of L5 GCT. In this study, we presented our experience with the use of an improved TES to treat L5 GCT through the single-stage posterior approach. METHODS: This study included 20 patients with L5 GCT who received surgical treatment in our department between September 2010 and April 2021. Of them, seven patients received improved TES without iliac osteotomy, and the other 13 patients received IC (n = 8), sagittal en bloc resection (n = 1), TES with iliac osteotomy (n = 3), and TES with radicotomy (n = 1) as control. RESULTS: The mean operative time was 331.43 ± 92.95 min for improved TES group and 365.77 ± 85.17 min for the control group (p = 0.415), with the mean blood loss of 1142.86 ± 340.87 ml vs. 1969.23 ± 563.30 ml (p = 0.002). Postoperative treatment included bisphosphonates in nine patients and denosumab in 12 patients including one patient who changed from bisphosphonates to denosumab. Three patients who received IC experienced local recurrence, and no relapse was observed in improved TES group. CONCLUSION: Single-stage posterior TES for L5 GCT was previously considered impossible. In this study, we presented our experience with the use of an improved surgical technique for L5 TES through the single-stage posterior approach, which has proved to be superior to the conventional procedures in terms of blood loss control and complication and recurrence rates. LEVEL OF EVIDENCE: IV.


Assuntos
Tumor de Células Gigantes do Osso , Neoplasias da Coluna Vertebral , Humanos , Denosumab , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/patologia , Recidiva Local de Neoplasia/cirurgia , Vértebras Lombares/cirurgia , Vértebras Lombares/patologia , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Tumor de Células Gigantes do Osso/cirurgia , Tumor de Células Gigantes do Osso/patologia , Difosfonatos , Resultado do Tratamento
19.
Bone Joint J ; 105-B(6): 679-687, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37257861

RESUMO

Aims: The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). Methods: We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Results: Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Conclusion: Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH.


Assuntos
Histiocitose de Células de Langerhans , Vértebras Lombares , Humanos , Estudos Retrospectivos , Prognóstico , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Histiocitose de Células de Langerhans/complicações , Dor
20.
J Cancer Res Ther ; 19(1): 25-33, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37006039

RESUMO

Objectives: This meta-analysis aimed at determining the association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumors of the bone. Methods and Materials: Web of Science, EMBASE, Cochrane Library, and PubMed were comprehensively searched on April 20th, 2022. Data from the included articles were analyzed using meta-analysis. The bias of all included studies was evaluated according to ROBINS-I. Also, subgroup and sensitivity analyses were performed. Results: Eight studies with 1270 cases (195 in the denosumab group and 1075 in the control group) were eventually included. Patients receiving denosumab before curettage had a higher risk of local recurrence than those who underwent curettage alone (odds ratio: 2.29, 95% confidence intervals: 1.44-3.64, P = 0.0005). The denosumab group showed a significantly higher risk of local recurrence in most subgroup analyses, except for those with preoperative denosumab duration ≤six months/doses (P = 0.66) and sample size ranging from 100 to 180 (P = 0.69). Conclusion: Denosumab before curettage may increase the risk of local recurrence in patients with giant cell tumor of the bone. Preoperative denosumab should be used with caution after weighing an increased risk of local recurrence against the clinical benefits and a duration time of less than six months before surgery is recommended.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Humanos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Denosumab/efeitos adversos , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/cirurgia , Tumor de Células Gigantes do Osso/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
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