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Hepatocellular carcinoma (HCC) is one the most common primary malignancies with high mortality and morbidity. The melanoma-associated antigen (MAGE) gene family includes several genes that are highly expressed in numerous human cancers, making many of them part of the cancer-testis antigen (CTA) family. MAGE-C1 is expressed in various malignancies but is absent in normal cells, except for the male germ line. Its presence is associated with a worse prognosis, increased tumor aggressiveness, and lymph node invasion. Similarly, MAGE-C2 is linked to the development of various malignant tumors. Despite these associations, the roles and mechanisms of MAGE-C1/MAGE-C2 in HCC remain unclear. This study aimed to evaluate the expression of MAGE-C1 and MAGE-C2 in HCC and correlate it with clinicohistological characteristics. Our findings indicated that MAGE-C1 expression is associated with a higher number of nodules, elevated AFP levels, HBV or HCV positivity, older age, male sex, and lymph node invasion. MAGE-C2 expression was correlated with these characteristics and the presence of cirrhosis. These results align with the limited literature, which suggests a correlation between MAGE expression and older age and HBV infection. Consequently, our study suggests that MAGE-C1 and MAGE-C2 are promising novel biomarkers for prognosis and potential therapeutic targets in HCC.
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To investigate the correlation of melanoma-associated antigen-C gene expression with clinicopathologic characteristics and prognosis in patients with breast cancer through a meta-analysis. PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang and VIP databases were searched from the establishment of the databases to December 2022. The New castle-Ottawa Scale (NOS) was used for literature quality evaluation, and meta-analysis of all studies was performed using Rev Man 5.3 and Stata14.0. A total of 11 studies and 1146 samples were included in the meta-analysis. High expression of MAGE-C gene was significantly correlated with tumor grade (OR = 8.06, 95%CI:4.14-15.67, P < .00001), lymph node metastasis (OR = 8.06, 95%CI:4.14-15.67, P < .00001), tumor type (OR = 0.36, 95%CI: 0.23-0.49, P < .00001), tumor stage (OR = 0.14, 95%CI: 0.05-0.38, P = .0001<.05), ER expression (OR = 0.14, 95%CI: 0.05-0.38, P = .0001<.05), HER-2 expression (OR = 0.24, 95%CI:0.11-0.57, P = .001<.05) and tumor embolus (OR = 0.24, 95%CI:0.11-0.57, P = .001<.05). In addition, the MAGE-C expression was correlated with the reduced overall survival (HR = 2.13, 95%CI: 1.52-2.99, P < .0001), recurrence-free survival (HR = 2.59, 95%CI:1.47-4.56, P = .0010) and metastasis-free survival (OR = 2.52, 95%CI: 1.38-4.59, P = .003). The high expression of MAGE-C gene is closely related to some clinicopathological parameters and poor prognosis of breast cancer, which may be used as a potential biomarker to determine the prognosis of breast cancer.
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Neoplasias da Mama , Melanoma , Humanos , Feminino , Neoplasias da Mama/genética , Melanoma/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Metástase LinfáticaRESUMO
Circulating endothelial cell progenitors originating from the bone marrow are considered to be a powerful tool in the repair of endothelium damage. Due to their unique properties, endothelial progenitors are now broadly investigated to assess their clinical significance in diseases e.g., associated with brain endothelial dysfunction. However, their distinction in terms of the expression of specific markers remains ambiguous. Additionally, endothelial progenitor cells may change their repertoire of markers depending on the microenvironment of the tissue in which they are currently located. Here, we applied the label-free Raman and FTIR imaging to discriminate mice brain endothelium and endothelial progenitors. Cells cultured separately showed distinctly different spectral signatures extracted from the whole cellular interior as well as the detected intracellular compartments (nucleus, cytoplasm, perinuclear area, and lipid droplets). Then, we used these spectroscopic signals to examine the cells co-cultured for 24Â h. Principal cluster analysis showed their grouping with the progenitor cells and segregation from brain endothelium at a level of the entire cell machinery (in FTIR images) which resulted from biochemical alternations in the cytoplasm and lipid droplets (in Raman images). The models included in partial least square regression indicated that lipid droplets are the key element for the classification of endothelial progenitor-brain endothelial cells interactions.
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Células Endoteliais , Análise Espectral Raman , Animais , Camundongos , Células Endoteliais/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman/métodos , Células Cultivadas , Gotículas Lipídicas/metabolismoRESUMO
Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma progression, we have compared gene and small non-coding RNA expression profiles from cell lines derived from primary melanoma (MelJuSo), lymph node metastasis (MNT-1) and brain metastasis (VMM1), representing distinct stages of malignant progression. Our preliminary results highlighted the aberrant regulation of molecular markers involved in several processes that aid melanoma progression and metastasis development, including extracellular matrix remodeling, migratory potential and angiogenesis. Moreover, bioinformatic analysis revealed potential targets of the microRNAs of interest. Confocal microscopy and immunohistochemistry analysis were used for validation at the protein level. Exploring the molecular landscape of melanoma may contribute to the achievement of future efficient targeted therapy, as well as better prevention, diagnosis and clinical management.
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Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Biomarcadores , Metástase Neoplásica , Melanoma Maligno CutâneoRESUMO
PURPOSE: Early onset scoliosis (EOS) is defined as spinal curvature affecting children below 10 years of age. Non-operative treatment can consist of casting and bracing. When curvature progresses despite these treatments, operative intervention is indicated. Traditional growing rods (TGR) have been a mainstay of treatment. Unfortunately, TGR's require planned return to the operating room every 6-9 months. Magnetic controlled growing rods (MCGR) ideally provide curve correction and allow the spine to grow without frequent surgeries. However, the ability to correct and maintain correction after MCGR has not been well-characterized. The purpose of this study is to evaluate maintenance of curve correction in patients treated primarily with MCGR and analyze the rate of complications including unplanned return to the operating room (UPROR). METHODS: 24 patients with EOS were retrospectively reviewed. These patients were subdivided into 4 subcategories: congenital, idiopathic, neuromuscular (NMS), and syndromic. The major curve correction (%) and T1-S1 distance were assessed utilizing scoliosis plain film radiographs over time. Complications and return to the operating room for any reason were recorded. Patients were followed until conversion to posterior spinal fusion (PSF) or most recent lengthening of MCGR. RESULTS: There were 11 male and 13 female patients averaging 8 years at the time of index surgery. The average preoperative curve angle was 61.1°. Initial curve correction with MCGR obtained at the index procedure was 46.2%, reducing the mean curve angle to 32.7° (p < 0.05). Curve correction at a mean 6.2 years (2.4-7.4) follow-up was 36.1°, 40.9% curve correction. 75% of patients underwent conversion to PSF during the study period 4.8 years (2.4-7.0) after initial MCGR surgery. 15% of patients were still undergoing MCGR lengthening after 6.1 years. 54.2% of patients had at least one UPROR. CONCLUSIONS: For patients with EOS with curve progression, MCGRs can maintain curve correction well after 2 years. Furthermore, MCGR allowed patients to grow over time to safely delay timing to definitive fusion. On average, patients underwent conversion to PSF after 4.7 years at an average age of 13.5. Although the complication rate in the first 2 years is relatively low, 54.2% of patients underwent an UPROR. As the use of MCGR increases, surgeons should be aware of possible complications associated with this technology and counsel patients accordingly. Further research is needed to continue to evaluate the efficacy and safety of MCGR in this challenging patient population.
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Escoliose , Criança , Humanos , Masculino , Feminino , Adolescente , Escoliose/cirurgia , Seguimentos , Salas Cirúrgicas , Estudos Retrospectivos , Coluna Vertebral/cirurgiaRESUMO
Like BRCA2, MAGEC3 is an ovarian cancer predisposition gene that has been shown to have prognostic significance in ovarian cancer patients. Despite the clinical significance of each gene, no studies have been conducted to assess the clinical significance of their combined expression. We therefore sought to determine the relationship between MAGEC3 and BRCA2 expression in ovarian cancer and their association with patient characteristics and outcomes. Immunohistochemical staining was quantitated on tumor microarrays of human tumor samples obtained from 357 patients with epithelial ovarian cancer to ascertain BRCA2 expression levels. In conjunction with our previously published MAGEC3 expression data, we observed a weak inverse correlation of MAGEC3 with BRCA2 expression (r = −0.15; p < 0.05) in cases with full-length BRCA2. Patients with optimal cytoreduction, loss of MAGEC3, and detectable BRCA2 expression had better overall (median OS: 127.9 vs. 65.3 months, p = 0.035) and progression-free (median PFS: 85.3 vs. 18.8 months, p = 0.002) survival compared to patients that were BRCA2 expressors with MAGEC3 normal levels. Our results suggest that combined expression of MAGEC3 and BRCA2 serves as a better predictor of prognosis than each marker alone.
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OBJECTIVE: It is unknown why some athletes develop chondromalacia and others do not, even when accounting for similar workloads between individuals. Genetic differences between individuals may be a contributing factor. The purpose of this work was to screen the entire genome for genetic markers associated with chondromalacia. DESIGN: Genome-wide association (GWA) analyses were performed utilizing data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. Chondromalacia cases were identified based on electronic health records from KPRB and UK Biobank. GWA analyses from both cohorts were tested for chondromalacia using a logistic regression model adjusting for sex, height, weight, age of enrollment, and race/ethnicity using allele counts for single-nucleotide polymorphisms (SNPs). The data from the 2 GWA studies (KPRB and UK Biobank) were combined in a meta-analysis. RESULTS: There were a total of 3,872 combined cases of chondromalacia from the KPRB and the UK Biobank cohorts. Genome-wide significant associations with chondromalacia were found for rs144449054 in the ARHGAP15 gene (OR = 3.70 [2.32-5.90]; P = 1.4 × 10-8) and rs188900564 in the MAGEC2 (OR = 2.07 [1.61-2.65]; P = 3.7 × 10-9). CONCLUSIONS: Genetic markers in ARHGAP15 and MAGEC2 appear to be associated with chondromalacia and are potential risk factors that deserve further validation regarding molecular mechanisms.
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Doenças das Cartilagens , Estudo de Associação Genômica Ampla , Marcadores Genéticos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
The tumor suppressor p53 is critical for the maintenance of genome stability and protection against tumor malignant transformation, and its homeostasis is usually regulated by ubiquitination. MDM2 is a major E3 ligase of p53 ubiquitination, and its activity is enhanced by TRIM28. TRIM28 also independently ubiquitinates p53 as an E3 ligase activated by MAGE-C2. Moreover, MAGE-C2 is highly expressed in various cancers, but the detailed mechanisms of MAGE-C2 involved in MDM2/TRIM28-mediated p53 ubiquitination remain unknown. Here, we found that MAGE-C2 directly interacts with MDM2 through its conserved MHD domain to inhibit the activity of MDM2 on p53 ubiquitination. Furthermore, TRIM28 acts as an MAGE-C2 binding partner and directly competes with MAGE-C2 for MDM2 interaction, thus releasing the inhibitory role of MAGE-C2 and promoting p53 ubiquitination. MAGE-C2 suppresses cell proliferation in TRIM28-deficient cells, but the overexpression of TRIM28 antagonizes the inhibitory role of MAGE-C2 and accumulates p53 ubiquitination to promote cell proliferation. This study clarified the molecular link of MAGE-C2 in two major E3 systems MDM2 and TRIM28 on p53 ubiquitination. Our results revealed the molecular function of how MAGE-C2 and TRIM28 contribute to p53 ubiquitination and cell proliferation, in which MAGE-C2 acts as a potential inhibitor of MDM2 and TRIM28 is a vital regulator for MAGE-C2 function in p53 protein level and cell proliferation. This work would be helpful to understand the regulation mechanism of tumor suppressor p53.
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TRIM28 is a scaffold protein that interacts with DNA-binding proteins and recruits corepressor complexes to cause gene silencing. TRIM28 contributes to physiological functions such as cell growth and differentiation. In the chronic myeloid leukemia cell line K562, we edited TRIM28 using CRISPR/Cas9 technology, and the complete and partial knockout (KO) cell clones were obtained and confirmed using quantitative droplet digital PCR (ddPCR) technology. The amplicon sequencing demonstrated no off-target effects in our gene editing experiments. The TRIM28 KO cells grew slowly and appeared red, seeming to have a tendency towards erythroid differentiation. To understand how TRIM28 controls K562 cell proliferation and differentiation, transcriptome profiling analysis was performed in wild-type and KO cells to identify TRIM28-regulated genes. Some of the RNAs that encode the proteins regulating the cell cycle were increased (such as p21) or decreased (such as cyclin D2) in TRIM28 KO cell clones; a tumor marker, the MAGE (melanoma antigen) family, which is involved in cell proliferation was reduced. Moreover, we found that knockout of TRIM28 can induce miR-874 expression to downregulate MAGEC2 mRNA via post-transcriptional regulation. The embryonic epsilon-globin gene was significantly increased in TRIM28 KO cell clones through the downregulation of transcription repressor SOX6. Taken together, we provide evidence to demonstrate the regulatory network of TRIM28-mediated cell growth and erythroid differentiation in K562 leukemia cells.
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Edição de Genes , MicroRNAs , Sistemas CRISPR-Cas , Proliferação de Células/genética , Expressão Gênica , Subunidades de Hemoglobina/genética , Subunidades de Hemoglobina/metabolismo , Humanos , Células K562 , Fatores de Transcrição/metabolismo , Proteína 28 com Motivo Tripartido/metabolismoRESUMO
The expression of the melanoma/cancer-testis antigen MAGEC2/CT10 is restricted to germline cells, but like most cancer-testis antigens, it is frequently upregulated in advanced breast tumors and other malignant tumors. However, the physiological cues that trigger the expression of this gene during malignancy remain unknown. Given that malignant breast cancer is often associated with skeletal metastasis and co-morbidities such as cancer-induced hypercalcemia, we evaluated the effect of high Ca2+ on the calcium-sensing receptor (CaSR) and potential mechanisms underlying the survival of triple-negative breast cancer (TNBC) cells at high Ca2+. We show that chronic exposure of TNBC cells to high Ca2+ decreased the sensitivity of CaSR to Ca2+ but stimulated tumor cell growth and migration. Furthermore, high extracellular Ca2+ also stimulated the expression of early response genes such as FOS/FOSB and a unique set of genes associated with malignant tumors, including MAGEC2. We further show that the MAGEC2 proximal promoter is Ca2+ inducible and that FOS/FOSB binds to this promoter in a Ca2+- dependent manner. Finally, downregulation of MAGEC2 strongly inhibited the growth of TNBC cells in vitro. These data suggest for the first time that MAGEC2 is a high Ca2+ inducible gene and that aberrant expression of MAGEC2 in malignant TNBC tissues is at least in part mediated by an increase in circulating Ca2+via the AP-1 transcription factor.
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Hipercalcemia , Neoplasias de Mama Triplo Negativas , Antígenos de Neoplasias , Cálcio , Linhagem Celular Tumoral , Humanos , Masculino , Proteínas de Neoplasias , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Rare variants in MAGEC3 are associated with BRCA negative, early-onset ovarian cancers. Given this association, we evaluated the impact of MAGEC3 protein expression on prognosis and transcription. We quantified normal and tumor protein expression of MAGEC3 via immunohistochemistry in n = 394 advanced ovarian cancers, assessed the correlation of these values with clinicopathologic and immunological features and modeled survival using univariate and multivariate models. To extend these results, we quantified MAGEC3 protein expression in n = 180 cancers and used matching RNA sequencing data to determine MAGEC3-associated differentially expressed genes and to build an RNA-based model of MAGEC3 protein levels. This model was tested in a third independent cohort of patients from TCGA's OV dataset (n = 282). MAGEC3 protein was sporadically lost in ovarian cancers, with half of the cases falling below the 9.5th percentile of normal tissue expression. Cases with MAGEC3 loss demonstrated better progression-free survival [HR = 0.71, p = 0.004], and analyses performed on predicted protein scores were consistent [HR = 0.57 p = 0.002]. MAGEC3 protein was correlated with CD8 protein expression [Pearson's r = 0.176, p = 0.011], NY-ESO-1 seropositivity, and mRNA expression of tumor antigens at Xq28. Results of gene set enrichment analysis showed that genes associated with MAGEC3 protein expression cluster around G2/M checkpoint (NES = 3.20, FDR < 0.001) and DNA repair (NES = 2.28, FDR < 0.001) hallmark pathways. These results show that MAGEC3 is a prognostic biomarker in ovarian cancer.
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MAGnetic Expansion Control (MAGEC) rods are used in the surgical treatment of children with early onset scoliosis. The magnetically controlled lengthening mechanism enables rod distractions without the need for repeated invasive surgery. The CE certification of these devices was suspended in March 2021 due, primarily, to performance evidence gaps in the documents provided by the manufacturer to regulators and notified bodies. MAGEC rods are therefore not permitted for use in countries requiring CE marking. This was a survey of 18 MAGEC rod surgeons in the UK about their perception of the impact of the CE suspension on the clinical management of their patients. Unsurprisingly, virtually all perceived a negative impact, reflecting the complexity of this patient group. Reassuringly, these surgeons are highly experienced in alternative treatment methods. Cite this article: Bone Jt Open 2022;3(2):155-157.
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Coffin-Siris Syndrome (CSS) is a rare, genetic syndrome characterized by multiple anomalies, including scoliosis. However, there are only a few reports about the management of scoliosis in these patients. We present the case of an 8-year-old female with CSS presenting with a progressive, rigid thoracolumbar kyphoscoliosis. She was successfully treated with a magnetically controlled growing rod, demonstrating improved ambulatory capacity and performance of activities of daily living. In pediatric patients with Coffin-Siris syndrome, magnetic expandable rods can be considered as an option for the management of progressive early-onset scoliosis. Level of Evidence: V.
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Anormalidades Múltiplas , Micrognatismo , Escoliose , Atividades Cotidianas , Criança , Face/anormalidades , Feminino , Deformidades Congênitas da Mão , Humanos , Deficiência Intelectual , Pescoço/anormalidades , Escoliose/cirurgiaRESUMO
BACKGROUND: It is thought that cancer/testis antigens (CTAs) are expressed in a cascade-like manner in multiple myeloma as the disease progresses. In this pilot study, we investigated the co-expression of several CTAs in the peripheral blood (PB) during patient therapy to establish whether monitoring multiple CTAs allows for the prediction of relapse and clonal evolution. METHODS: We examined the co-expression of MAGEC1, MAGEA3, PRAME, and BAGE2 via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) duplex assays in the PB mononuclear cells of 10 patients on chemotherapy at 3-month intervals, and correlated the levels to those of two basic clinical monitoring markers, serum ï¢-2-microglobulin and serum M protein. Clonal evolution was investigated using flow cytometry to label the circulating malignant stem cell components with MAGEC1, PRAME, and MAGEA3 antibodies. RESULTS: Simultaneous monitoring of MAGEC1/PRAME provided sensitive detection of circulating malignant cells in easily accessible PB samples; transcript levels increased prior to changes in indicators of clinical relapse. While MAGEA3/BAGE2 expression levels did not offer earlier prediction of relapse, they provided insight into significant changes occurring within the malignant cell population; the addition of either CTA to a MAGEC1-monitoring panel allowed for better classification of the relapse event (clonal evolution), which in turn could potentially guide treatment strategies in the future. CONCLUSION: This pilot study supports the novel idea of determining the levels and CTA expression patterns of the total circulating malignant cell population (pro-B/pre-B stem cell progenitors and proliferating plasma cells) as an alternate disease monitoring methodology.
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PURPOSE: Early-Onset Scoliosis (EOS) (defined as a curvature of the spine ≥ 10° with onset before 10 years of age) if not properly treated, can lead to increased morbidity and mortality. Traditionally Growing Rods (TGRs), implants fixated to the spine and extended every 6-8 months by surgery, are considered the gold standard, but Magnetically Controlled Growing Rods (MCGRs) avoid multiple surgeries. While the potential benefit of outpatient distraction procedure with MCGR is huge, concerns still remain about its risks, up to the release of a Medical Device Alert (MDA) by the Medicines and Healthcare Regulatory Agency (MHRA) advising not to implant MCGRs until further notice. The aim of this literature review is to (1) give an overview on the use of MCGRs and (2) identify what is currently understood about the surgical, implant and patient factors associated with the use of MCGRs. METHODS: Systematic literature review. RESULTS: Surgical factors such as use of single rod configuration or incorrect rod contouring might affect early failure of MCGRs. Patient's older age and higher BMI are correlated with rod slippage. Wear debris and distraction mechanism failure may result from implant design and iteration. CONCLUSION: Despite the complications reported, this technology still offers one of the best solutions to spine surgeons dealing with severe EOS. Lowering the complication rate by identifying risk factors for failure is possible and further studies in this direction are required. Once the risk factors are well described, some of these can be addressed enabling a safer use of MCGRs.
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Procedimentos Ortopédicos , Escoliose , Idoso , Humanos , Próteses e Implantes , Reoperação , Escoliose/cirurgia , Coluna Vertebral/cirurgiaRESUMO
PURPOSE: Determine the incidence of metallosis around MAGEC rods. METHODS: A multicentre explant database was searched to identify cases with complete intraoperative findings at rod removal. Surgeons removing rods detailed the presence or absence of tissue metallosis associated with rods. More recently surgeons measured the 'length' of tissue metallosis. Prior to rod disassembly, the majority underwent testing with an external remote controller (ERC). The impact of clinical and explant variables on metallosis was assessed. RESULTS: Sixty-six cases were identified. Mean age at insertion was 8.1 ± 2.3 years with mean duration of implantation 37.6 ± 15.1 months. Tissue metallosis was noted at revision surgery in 52/66 cases (79%). Metallosis was noted more commonly when rods were removed during fusion surgery than rod removal/exchange (97% vs. 58% (p = < 0.01)). The mass at insertion was greater in cases with metallosis (25.9 ± 7.8 kg vs. 21.1 ± 6.2 kg, p = 0.04). Length of tissue metallosis was reported for 45 rods, median 9 cm (range 1-25). Metallosis was noted in 43/59 (73%) rods that produced no force and 22/30 (73%) rods that produced some force on ERC activation (p = 0.96). Wear debris was found within the actuator in all rods, and all but 3 rods had damaged O-rings. CONCLUSION: MAGEC rods are associated with tissue metallosis in the majority of cases. It is seen with functional rods as well as failed rods and appears related to wear debris within the actuator and high rates of O-ring failure. Until the implications of metal debris in children are known, we urge caution with the use of this implant.
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Escoliose , Criança , Bases de Dados Factuais , Humanos , Próteses e Implantes , Reoperação , Escoliose/cirurgiaRESUMO
BACKGROUND: The aim of this study was to explore the relationship between melanoma antigen gene C1 (MAGE-C1) expression and the prognosis for colorectal cancer (CRC), and to establish a mathematical model to comprehensively evaluate the prognosis of patients with CRC. METHODS: MAGE-C1 was selected by bioinformatics for its greater expression differences in CRC patients. Immunohistochemistry (IHC) was used to detect the expression level of MAGE-C1 in tissue samples of 156 patients with CRC. Kaplan-Meier analysis was employed to assess the relationship between MAGE-C1 and the prognosis of patients with CRC. Univariate and multivariate Cox regression models analyzed the factors affecting the prognosis of CRC patients. Also, the clinicopathological characteristics of patients and genes with clinical concern were integrated to establish a model to comprehensively predict the prognosis of patients with CRC. RESULTS: MAGE-C1 was found to be highly expressed in 28.8% of CRC patients. MAGE-C1 expression was associated with tumor size, number, and metastasis. Survival analysis showed that CRC patients with high expression of MAGE-C1 had a poor prognosis. Regression analysis demonstrated that MAGE-C1 protein status, T stage, differentiation, Kirsten rat sarcoma (KRAS) status, and v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) status were the independent factors influencing the overall survival of patients with CRC. Meanwhile, MAGE-C1 combined with clinicopathological characteristics and hotspot gene mutations could be used to evaluate the prognosis of CRC. CONCLUSIONS: Our study shows that MAGE-C1 is differentially expressed in patients with CRC and affects the prognosis of patients. The combination of MAGE-C1, clinicopathological characteristics, and genes with clinical concern can be used to assess the prognosis of CRC.
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BACKGROUND: Magnetically controlled growing rod (MCGR) systems have gained attention for their use in the treatment of early-onset scoliosis. Although traditional growing rods require frequent operations to lengthen the construct, MCGR allows for fewer open procedures and more frequent distractions by externally controlling rod elongation. Despite its appealing advantages, MCGR is not without limitations. OBSERVATIONS: The authors describe a case of premature spinal autofusion before growing rod removal and termination of rod distraction. LESSONS: This case highlights the limitations of MCGR systems, including length of use, body habitus restrictions, and risk of autofusion.
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Prostate cancer (PC) is the most common reproductive cancer in men and the third leading cause of cancer death among men worldwide. Recently targeted therapy showed a significant therapeutic effect on PC, whereas finding more PC therapeutic target is still urgently needed. Melanoma-associated antigen-encoding C2 (MAGE-C2/CT10), which have significant homology with the MAGE-C1/CT-7 gene, was known to be involved in the development of a variety of tumors. However, the role and mechanism of MAGE-C2/CT10 in prostate cancer remains unclear. Herein, we found the high levels of MAGE-C2/CT10 in highly metastatic prostate cancer. Our findings confirmed that the depletion of MAGE-C2/CT10 suppressed the growth of PC cells, and restrained PC cell migration and invasion in vitro. We noticed MAGE-C2/CT10 could stimulate c-Myc expression via FBP1, and further contributed to PC cell proliferation and motility. Performing in vivo assays, we demonstrated MAGE-C2/CT10 promoted tumor growth and metastasis of PC cells in mice. Collectively, we found the abnormal expression of MAGE-C2/CT10 in PC, and revealed the regulatory mechanism underlying MAGE-C2/CT10 promoting PC progression and metastasis.
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Antígenos de Neoplasias/fisiologia , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Proteínas de Neoplasias/fisiologia , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Frutose-Bifosfatase/metabolismo , Humanos , Masculino , Melanoma/patologia , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Ativação Transcricional , Regulação para CimaRESUMO
AIMS: Magnetically controlled growing rods (MCGR) have been gaining popularity in the management of early-onset scoliosis (EOS) over the past decade. We present our experience with the first 44 MCGR consecutive cases treated at our institution. METHODS: This is a retrospective review of consecutive cases of MCGR performed in our institution between 2012 and 2018. This cohort consisted of 44 children (25 females and 19 males), with a mean age of 7.9 years (3.7 to 13.6). There were 41 primary cases and three revisions from other rod systems. The majority (38 children) had dual rods. The group represents a mixed aetiology including idiopathic (20), neuromuscular (13), syndromic (9), and congenital (2). The mean follow-up was 4.1 years, with a minimum of two years. Nine children graduated to definitive fusion. We evaluated radiological parameters of deformity correction (Cobb angle), and spinal growth (T1-T12 and T1-S1 heights), as well as complications during the course of treatment. RESULTS: The mean Cobb angles pre-operatively, postoperatively, and at last follow-up were 70° (53 to 103), 35° (15 to 71) and 39° (15 to 65) respectively (p < 0.001). Further, there was a mean of 14° (-6 to 27) of additional Cobb angle correction upon graduation from MCGR to definitive fusion. Both T1-T12 and T1-S1 showed significant increase in heights of 27 mm and 45 mm respectively at last follow-up (p < 0.001). Ten children (23%) developed 18 complications requiring 21 unplanned operations. Independent risk factors for developing a complication were single rod constructs and previous revision surgery. CONCLUSION: MCGR has the benefit of avoiding multiple surgeries, and is an effective tool in treatment of early-onset scoliosis. It also maintains the flexibility of the spine, allowing further correction at the time of definitive fusion.Cite this article: Bone Joint Open 2020;1-7:405-414.