RESUMO
OBJECTIVES: In this meta-analysis, we conducted a comparative analysis of the safety and efficacy of hypofractionated and conventional fractionated radiotherapy in individuals who had undergone surgery for breast cancer. METHODS: This study involved a systematic and independent review of relevant research articles published in reputable databases such as PubMed, Embase, Cochrane Library, and Web of Science. Two investigators conducted the review, which included studies published up to January 3, 2023. The quality of the eligible studies was evaluated and data were extracted using Review Manager software 5.4 (RevMan 5.4) to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The analysis comprised 35 studies and encompassed a collective sample of 18,246 individuals diagnosed with breast cancer. We did not find a statistically significant disparity in efficacy between conventional fractionated (CF) radiotherapy and hypofractionated (HF) radiotherapy regarding local recurrence (LR; OR = 0.91, 95% CI: 0.76-1.09, P = 0.30), disease-free survival (DFS; OR = 1.20, 95% CI: 1.01-1.42, P = 0.03), and overall survival (OS; OR = 1.08, 95% CI: 0.93-1.26, P = 0.28). Concerning safety, there was no significant difference between the HF and CF regimens in terms of breast pain, breast atrophy, lymphedema, pneumonia, pulmonary fibrosis, telangiectasia, and cardiotoxicity. However, the HF regimen resulted in lower skin toxicity (OR = 0.43, 95% CI: 0.33-0.55, P < 0.01) and improved patient fatigue outcomes (OR = 0.73, 95% CI: 0.60 - 0.88, P < 0.01). CONCLUSIONS: Although there is no substantial difference in LR, DFS, OS, or many other side effects between the HF and CF regimens, the HF regimen reduces skin toxicity and relieves patient fatigue. If these two issues need to be addressed in clinical situations, the HF regimen may be a superior alternative to conventional radiotherapy in postoperative breast cancer patients.
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Neoplasias da Mama , Feminino , Humanos , Mama/patologia , Neoplasias da Mama/radioterapia , Intervalo Livre de Doença , Intervalo Livre de Progressão , Hipofracionamento da Dose de RadiaçãoRESUMO
BACKGROUND: Circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) has previously been reported to play a key role in carcinogenesis. Nevertheless, the role of circ-ITCH in nasopharyngeal carcinoma (NPC) remains to be explored. METHODS: Gene expression analysis was performed using a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. The role of circ-ITCH in NPC was explored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, colony formation, transwell invasion, scratch healing and xenograft tumor assays. Furthermore, luciferase reporter assay was carried out to assess the interactions among circ-ITCH, microRNA-214 (miR-214) and phosphatase and tensin homolog (PTEN). RESULTS: The levels of circ-ITCH and PTEN were decreased, whereas the level of miR-214 was increased in NPC tissues collected from 28 subjects compared to normal nasopharynx tissues collected from 15 subjects. Moreover, a negative correlation between circ-ITCH and miR-214 expression and a positive correlation between circ-ITCH and PTEN expression were observed in NPC tissues. Downregulation of circ-ITCH expression was also observed in NPC cell lines. In addition, upregulation of circ-ITCH markedly inhibited NPC cell proliferation, migration and invasion. Furthermore, circ-ITCH was confirmed to exert its function by sponging miR-214. PTEN was found to be a direct target gene of miR-214 and its expression was negatively correlated with miR-214 expression in NPC tissues. Moreover, our results showed that the circ-ITCH/miR-214 axis regulated NPC proliferation, migration and invasion through regulating the expression of PTEN. Upregulation of circ-ITCH or PTEN blocked miR-214-mediated promotion of NPC tumorigenesis in vitro. Additionally, upregulation of circ-ITCH also suppressed NPC tumorigenesis in vivo. CONCLUSIONS: The present study demonstrated that circ-ITCH suppressed NPC tumorigenesis by upregulating PTEN expression through interacting with miR-214, thus proposing a novel mechanism for NPC inhibition.
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MicroRNAs , Neoplasias Nasofaríngeas , RNA Circular , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Circular/genética , Ubiquitina-Proteína Ligases/genética , Regulação para CimaRESUMO
PURPOSE: Endometrial carcinoma (EC), a common gynecological malignancy with high incidence, affects the mental and physical health of women. Mounting evidence shows that long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) have instrumental roles in various biological processes associated with the pathogenesis of EC. In this research, we intend to further study the mechanism of EC and the potential predictive markers of EC. METHODS: First, we obtained original data of EC RNA transcripts from The Cancer Genome Atlas database and performed differential analysis. Subsequently, according to the miRcode online software, relationship pairs of lncRNA-miRNA were constructed, and miRNA-mRNA pairs were established based on miRDB, TargetScan, and miRTarBase. Then, we constructed the competing endogenous RNA (ceRNA) network based on lncRNA-miRNA and miRNA-mRNA pairs. To further explain the function of the ceRNA network and explore the potential prognostic markers, functional enrichment analysis, and survival analysis were carried out. RESULTS: The research showed that there were 744 differential expression lncRNAs (DElncRNAs), 164 differential expression miRNAs (DEmiRNAs), and 2447 differential expression mRNAs (DEmRNAs) between EC tissues and normal tissues. Subsequently, we built 103 DEmiRNA-DEmRNA interaction pairs and 369 DElncRNA-DEmiRNA pairs. Then, we established the ceRNA network of EC, including 62 DElncRNAs, 26 DEmiRNAs, and 70 DEmRNAs. Moreover, 10 of 62 lncRNAs, 19 of 70 mRNAs, and 4 of 26 miRNAs that closely related to the survival of EC with P < .05 were obtained. Notably, based on this network, it was found that LINC00261-hsa-mir-31 pair and LINC00261-hsa-mir-211 target pairs could be used as the potential prognostic markers of EC. CONCLUSION: This research recommended an available basis for the molecular mechanism of EC and prognosis prediction, which could help guide the subsequent treatments and predict the prognosis for patients with EC.
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Biomarcadores Tumorais/genética , Neoplasias do Endométrio/patologia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Neoplasias do Endométrio/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Prognóstico , Taxa de SobrevidaRESUMO
Rab31 belongs to the Ras superfamily of small GTP-binding proteins, which has been found to regulate the vesicle transport from the Golgi apparatus to early and late endosomes. The investigation here detected the expression of Rab31 in 96 patients with hepatocellular carcinoma (HCC) and tried to identify its significance on outcome of HCCs after liver resection. By immunohistochemistry staining, it was found that Rab31 expression in HCC tissues was remarkably higher than that in adjacent liver tissues. Aberrant Rab31 overexpression in HCC tissues was identified to be associated with worse prognosis after liver resection. Univariate analysis showed that advanced tumor-nodes-metastasis (TNM) staging of HCC, intrahepatic metastases, portal vein invasion, and higher Rab31 were the predictive factors of poor prognosis. Multivariate analysis demonstrated that intrahepatic metastases and higher Rab31 were the independent prognostic factors. Furthermore, forced expression of Rab31 in Huh7 cells was found to promote cell growth via upregulation of Bcl-2/BAX ratio induced by PI3K/AKT. Correspondingly, silencing Rab31 induced cell apoptosis and in turn suppressed the growth capacity of MHCC97 cells in vitro. Taken together, this study provides the evidence of Rab31 overexpression in HCC, and Rab31 is potentially used as a novel biomarker of poor prognosis in patients with HCC. PI3K/AKT/Bcl-2/BAX axis was involved in Rab31-promoting HCC progression.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Proteínas rab de Ligação ao GTP/genética , Adulto , Apoptose , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Proteínas rab de Ligação ao GTP/biossínteseRESUMO
Castleman's disease (CD) is an uncommon, benign, non-neoplastic, lymphoproliferative disease of uncertain etiology. Here, we report 6 cases of kidney disease-associated CD in China. All patients exhibited multicentric CD (MCD) with involvement of the mediastinum, neck, bilateral axillary, and bilateral inguinal regions. Clinical manifestations included fever, fatigue, edema, and swollen lymph nodes. Laboratory examinations of all 6 patients found proteinuria or renal insufficiency. Two of the patients were diagnosed with hyaline vascular type MCD, and 4 patients were diagnosed with plasma cell type CD. The case 1 and case 4 patients had mesangial proliferative glomerulonephritis, case 3 had type I membranoproliferative glomerulonephritis, case 2 and case 5 had interstitial nephritis, and case 6 had AA type amyloidosis nephropathy. Three patients were treated with prednisone plus cyclophosphamide, 1 patient received COP therapy (cyclophosphamide, vincristine and prednisone), and 2 patients received COP therapy supplemented by small doses of radiation therapy delivered to local lymph nodes. In all cases, the clinical manifestations of MCD, including fever, fatigue, edema, swollen lymph nodes, and proteinuria, were alleviated or abolished by treatment. One patient responded to treatment with complete MCD remission, and another 4 patients survived. However, 1 patient died due to renal failure. In conclusion, common diagnosis and treatment techniques are suitable for kidney disease-associated CD. However, treatment efficacy might be difficult to predict, and some cases may have poor prognosis with this treatment strategy. Therefore, additional studies investigating kidney disease-associated CD and treatment outcomes in larger patient populations are needed.
Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Nefropatias/etiologia , Adolescente , Adulto , Amiloidose/complicações , Anti-Inflamatórios/uso terapêutico , Hiperplasia do Linfonodo Gigante/patologia , Causas de Morte , Ciclofosfamida/uso terapêutico , Feminino , Seguimentos , Glomerulonefrite Membranoproliferativa/etiologia , Humanos , Imunossupressores/uso terapêutico , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/etiologia , Plasmócitos/patologia , Prednisona/uso terapêutico , Insuficiência Renal/etiologia , Proteína Amiloide A Sérica/análise , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Dysregulated ubiquitination modification occupies a pivotal role in hepatocellular carcinoma (HCC) tumorigenesis and progression. The ubiquitin aldehyde binding 1 (OTUB1) was aberrantly upregulated and exhibited the pro-tumorigenic function in HCC. However, the underlying mechanisms and responsible targets of OTUB1 remain unclear. METHODS: First, bioinformatics analysis, western blot and immunohistochemistry staining were applied to analyze OTUB1 expression in HCC specimens. Then, immunoprecipitation assay-tandem mass spectrometry (MS) combined with the gene set enrichment analysis (GSEA) was used to explore the downstream target of OTUB1. Co-immunoprecipitation and ubiquitination assays were used to identify the mechanisms involved. Finally, we explored the regulatory effect of MAZ on OTUB1 through ChIP-qPCR and dual-luciferase reporter assay. RESULTS: OTUB1 was broadly elevated in HCC tissues and promoted the proliferation and metastasis of HCC in vitro and in vivo. The receptor for activated C kinase 1 (RACK1) performed as a functional partner of OTUB1 and its hyperactivation was associated with aggressive development and other malignant features in HCC by activating oncogenes transcription. Mechanistically, OTUB1 directly bound to RACK1 at its C-terminal domain and decreased the K48-linked ubiquitination of RACK1 through its non-canonical suppression of ubiquitination activity, which stabilized RACK1 protein levels in HCC cells. Therefore, OTUB1 significantly increased multiple oncogenes expression and activated PI3K/AKT and FAK/ERK signaling in a RACK1-dependent manner in HCC. Moreover, the transcription factor MAZ upregulated OTUB1 expression through identifying a putative response element of OTUB1 promoter area. CONCLUSIONS: Our findings might provide a new therapeutic strategy for HCC by modifying the MAZ-OTUB1-RACK1 axis.
Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Proteínas de Neoplasias , Receptores de Quinase C Ativada , Ubiquitinação , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Receptores de Quinase C Ativada/metabolismo , Receptores de Quinase C Ativada/genética , Linhagem Celular Tumoral , Animais , Proliferação de Células/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Masculino , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Feminino , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Pessoa de Meia-Idade , Camundongos , Transdução de Sinais , Camundongos Endogâmicos BALB C , Estabilidade Proteica , Enzimas DesubiquitinantesRESUMO
Metabolic heterogeneity and the tumor immunosuppressive microenvironment (TIME) of triple-negative breast cancer (TNBC) hinder therapeutic effectiveness. Although emerging metabolic therapy and immunotherapy show promise, they are limited by off-target effects and immune escape. Here, a redox-activatable, sequentially-releasing nanoparticle (AMANC@M) for tumor-targeted delivery of anticancer agents and CRISPR/Cas9 has been developed. AMANC@M can reverse the TIME through dual metabolic inhibition, thereby enhancing TNBC therapy. AMANC@M demonstrates excellent biosafety and targets tumors precisely through biomimetic hybrid membrane-mediated homologous homing and the enhanced permeability and retention (EPR) effect. Once internalized into tumor cells, the CRISPR/Cas9 system ("energy nanolock") is released through glutathione (GSH) cleavage and effectively knocks down the expression of lactate dehydrogenase A (LDHA) to suppress glycolysis. After peeling off of the gene editing shell, a newly synthesized targeted drug, CPI-Z2 ("nutrihijacker" and "energy nanolock"), is released in a controlled manner to block the mitochondrial tricarboxylic acid (TCA) cycle. Nitric oxide (NO) produced from loaded L-arginine enhances the efficiency of CPI-Z2 and reduces drug resistance. Combined with NO therapy, both blockades of nutrients and energy production transform the hypoxia and acidic TIME into an immunocompetent tumor microenvironment (TME) for tumor elimination. Furthermore, AMANC@M offers capabilities for photothermal (PT) therapy and provides clear imaging through PT, photoacoustic (PA), or computed tomography (CT) signals in tumor tissue. Thus, this study provides a new and promising sequentially stimuli-responsive targeting strategy for nanoparticle development, making it a potential treatment candidate for TNBC and other tumors.
Assuntos
Antineoplásicos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Preparações de Ação Retardada/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified lecithin cholesterol acyltransferase (LCAT) as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth-promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and to dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC. Significance: Estrogen mediates the sex differences in hepatocellular carcinoma development by reducing cholesterol biosynthesis through activation of an LCAT/HDL-C axis, providing strategies for improving liver cancer prevention, prognosis, and treatment.
Assuntos
Carcinoma Hepatocelular , Colesterol , Estrogênios , Homeostase , Neoplasias Hepáticas , Fosfatidilcolina-Esterol O-Aciltransferase , Animais , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Camundongos , Estrogênios/metabolismo , Colesterol/metabolismo , Feminino , Masculino , Proliferação de Células/efeitos dos fármacos , Prognóstico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , HDL-Colesterol/metabolismo , HDL-Colesterol/sangue , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genéticaRESUMO
Non-alcoholic steatohepatitis (NASH) is rapidly surpassing viral hepatitis as the primary cause of hepatocellular carcinoma (HCC). However, understanding of NASH-progressed HCC remains poor, which might impede HCC diagnosis and therapy. In this study, we aim to identify shared transcriptional changes between NASH and HCC, of which we focused on E3 ligase TRIM45. We found TRIM45 exacerbates HCC cells proliferation and metastasis in vitro and in vivo. Further transcriptome analysis revealed TRIM45 predominantly affects fatty acid metabolism and oleic acid restored impaired proliferation and metastasis of TRIM45-deficient HCC cells. IP-tandem mass spectrum and FABP5 depriving experiment indicated that TRIM45 enhance fatty acid synthesis depending on FABP5 presence. Interestingly, we found TRIM45 directly added K33-type and K63-type poly-ubiquitin chains to FABP5 NLS domain, which ultimately promoted FABP5 nuclear translocation. Nuclear FABP5 interacted with PPARγ to facilitate downstream lipid synthesis gene expression. We observed TRIM45 accelerated NASH-to-HCC transition and exacerbated both NASH and NASH-HCC with the enhanced fatty acid production in vivo. Moreover, high concentration of fatty acid increased TRIM45 expression. The established mechanism was substantiated by gene expression correlation in TCGA-LIHC. Collectively, our research revealed a common lipid reprograming process in NASH and HCC and identified the cyclical amplification of the TRIM45-FABP5-PPARγ-fatty acid axis. This signaling pathway offers potential therapeutic targets for therapeutic intervention in NASH and NASH-progressed HCC.
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Carcinoma Hepatocelular , Proteínas de Ligação a Ácido Graxo , Ácidos Graxos , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Ubiquitinação , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Ácidos Graxos/metabolismo , Camundongos , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Progressão da DoençaRESUMO
BACKGROUND: What is highlighted in this study refers to the role and molecular mechanism of long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) in cells with insulin resistance (IR). METHODS: In this study, LX-2 cells were applied to establish IR model in vitro. The expressions of lncRNA XIST, phosphoenolpyruvate carboxykinase (PEPCK,) and glucose-6-phosphatase (G6Pase) were quantified by quantitative reverse transcription polymerase chain reaction. The 2-deoxy-d-glucose-6-phosphate (2-DG6P) level was detected utilizing 2-deoxy-d-glucose (2-DG) uptake measurement kit. Western blot was adopted to measure the protein expressions of insulin-like growth factor-1 receptor (IGF-1R), G6Pase, PEPCK, and phosphatidylinositol 3-kinase (PI3K)/Akt pathway-related genes. StarBase was used to predict the targeting relationship between lncRNA XIST or IGF-1R with miR-182-5p, the results of which were verified by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. Rescue experiments were conducted to investigate the effect of miR-182-5p on IR cells. Next, low-expressed lncRNA XIST and high-expressed miR-182-5p were observed in IR cells. RESULTS: Upregulation of lncRNA XIST increased IGF-1R and 2-DG6P levels, decreased G6Pase and PEPCK expressions, and promoted PI3K/Akt pathway activation in IR cells. LncRNA XIST sponged miR-182-5p which targeted IGF-1R. MiR-182-5p mimic reversed the above effects of lncRNA XIST overexpression on IR cells. CONCLUSIONS: In conclusion, lncRNA XIST/miR-182-5p axis alleviates hepatic IR in vitro via IGF-1R/PI3K/Akt signaling pathway, which could be the promising therapeutic target.
Assuntos
Hepatócitos , Resistência à Insulina , MicroRNAs , RNA Longo não Codificante , Humanos , Resistência à Insulina/genética , MicroRNAs/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Hepatócitos/metabolismoRESUMO
With the development of artificial intelligence (AI) technologies, biomedical imaging data play an important role in scientific research and clinical application, but the available resources are limited. Here we present Open Biomedical Imaging Archive (OBIA), a repository for archiving biomedical imaging and related clinical data. OBIA adopts five data objects (Collection, Individual, Study, Series, and Image) for data organization, and accepts the submission of biomedical images of multiple modalities, organs, and diseases. In order to protect personal privacy, OBIA has formulated a unified de-identification and quality control process. In addition, OBIA provides friendly and intuitive web interfaces for data submission, browsing, and retrieval, as well as image retrieval. As of September 2023, OBIA has housed data for a total of 937 individuals, 4136 studies, 24,701 series, and 1,938,309 images covering 9 modalities and 30 anatomical sites. Collectively, OBIA provides a reliable platform for biomedical imaging data management and offers free open access to all publicly available data to support research activities throughout the world. OBIA can be accessed at https://ngdc.cncb.ac.cn/obia.
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Inteligência Artificial , HumanosRESUMO
There is uncertainty regarding the benefits and drawbacks of various radiation protocols for the treatment of left-sided breast cancer. To address this issue, we conducted a Bayesian network analysis. First, we searched several electronic databases for eligible literature. Next, we pooled the data from twelve studies concerning three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), combined with either deep inspiratory breath-holding (DIBH) or free-breathing (FB) modalities. The integrated cardiac and pulmonary dosimetric indexes for all included treatments were compared using Bayesian networks. A direct meta-analysis indicated that for the two methods of 3D-CRT and IMRT, DIBH technology was more effective than FB in reducing the radiation dose to the heart and lungs. Additionally, according to the network results, DIBH was superior to FB in all six treatment options, regardless of whether the plan was 3D-CRT, IMRT, or VMAT. Besides, the combined data indicated that the FB-3D-CRT regimen had the weakest dosimetric advantage of all the treatments. Excluding FB-3D-CRT, each of the other five treatments had its own specific benefits. This is the first Bayesian study of several radiotherapy regimens for breast cancer patients on the left side, and the findings can be used to select appropriate radiotherapy programs for breast cancer patients.
Assuntos
Neoplasias da Mama , Radioterapia (Especialidade) , Neoplasias Unilaterais da Mama , Humanos , Feminino , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias da Mama/radioterapia , Teorema de Bayes , Protocolos ClínicosRESUMO
INTRODUCTION: Reports on the coexistence of epithelioid angiosarcoma (EA) and papillary thyroid carcinoma (PTC) are rare. Over the past 50 years, only 2 cases of coexistence of EA and PTC have been reported in English literature. Therefore, we report a rare case of coexistence of EA and PTC treated with surgery and adjuvant radiation therapy. PATIENT CONCERNS: A 64-year-old man visited our hospital with a painless mass in the left submandibular gland, with poor mobility. DIAGNOSIS: Neck ultrasonography revealed nodules in the left submandibular gland and multiple cystic-solid mixed nodules in the left thyroid gland. Pathological findings revealed coexistence of EA in the left submandibular gland area and PTC in the left thyroid gland. INTERVENTIONS: The patient underwent resection of the left submandibular gland, deep maxillofacial tumor, total thyroidectomy, left neck I, II, III, and VI regional lymph node dissection, and recurrent laryngeal nerve exploration under general anesthesia. Two months postoperatively, the patient also received adjuvant radiation therapy in the local and adjacent areas, with 4MV-X IMRT DT50GY at 2Gy/day 25 fractions. OUTCOMES: The follow-up period was 37 months. The patient recovered well without focal neurological deficits, local recurrence, or distant metastasis after surgery, except for grade I skin reaction after adjuvant radiation therapy. CONCLUSIONS: This is a rare case report of the coexistence of EA in the left submandibular gland and PTC in the left thyroid gland. Although multiple examinations were used, precise preoperative diagnosis was challenging owing to the coexistence of EA and PTC. Surgery and radiotherapy were effective treatments for the coexistence of EA and PTC in this case.
Assuntos
Hemangioendotelioma Epitelioide , Hemangiossarcoma , Neoplasias da Glândula Tireoide , Hemangiossarcoma/complicações , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço , Glândula Submandibular , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Endometrial carcinoma (EC), a common female reproductive system malignant tumor, affects thousands of people with high morbidity and mortality worldwide. This study was aimed at developing a prediction model for the diagnosis of EC in the general population. First, we obtained datasets GSE63678, GSE106191, and GSE115810 from the Gene Expression Omnibus (GEO) database, dataset GSE17025 from the GEO database, and the RNA sequence of EC from The Cancer Genome Atlas (TCGA) database to constitute the training, test, and validation groups, respectively. Subsequently, the 96 most significantly differentially expressed genes (DEGs) were identified and analyzed for function and pathway enrichment in the training group. Next, we acquired the disease-specific genes by random forest and established an artificial neural network for the diagnosis. Receiver operating characteristic (ROC) curves were utilized to identify the signature across the three groups. Finally, immune infiltration was analyzed to reveal tumor-immune microenvironment (TIME) alterations in EC. The top 96 DEGs (77 down-regulated and 19 up-regulated genes) were primarily enriched in the interleukin-17 signaling pathway, protein digestion and absorption, and transcriptional misregulation in cancer. Subsequently, 14 characterizing genes of EC were identified by random forest. In the training, test, and validation groups, the artificial neural network was constructed with high diagnostic accuracies of 0.882, 0.864, and 0.839, respectively, and areas under the ROC curve (AUCs) of 0.928, 0.921, and 0.782, respectively. Finally, resting and activated mast cells were found to have increased in TIME. We constructed an artificial diagnostic model with excellent reliability for EC and uncovered variations in the immunological ecosystem of EC through integrated bioinformatics approaches, which might be potential diagnostic targets for EC.
Assuntos
Ecossistema , Neoplasias do Endométrio , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , Reprodutibilidade dos Testes , Microambiente TumoralRESUMO
OBJECTIVE: This study aims to investigate the use of single residue substitution to promote the formation of pi-stacking interactions between peptides and Human leukocyte antigen (HLA)-A*2402 molecules to improve the affinity of peptides and HLA molecules, as well as the level of cytotoxic T lymphocyte (CTL) cells activated by peptides-HLA (p-HLA) complex. METHODS: Molecular docking and molecular dynamics simulation were used to simulate and analyze the interactions and binding free energies between HLA-A*2402-restricted antigen peptides and HLA molecules, before and after the single residue substitution. HLA-A*2402 restricted antigen peptides before and after the single residue replacement were loaded into dendritic cells (DCs) in vitro, and further Enzyme-Linked ImmunoSpot (ELispot) test was carried out to evaluate the effect of modified antigen peptides on the immune activation of CTL cells. RESULT: After replacing the antigen peptides with a single residue, some of them could promote the formation of pi-stacking interaction. The binding free energy between the modified antigen peptides and HLA-A*2402, as well as the level of immune activation of CTL cells were mostly higher than before, especially after the replacement of the 9th residue of the polypeptide, such as C9F and C9W. There was a significant negative correlation between the level of activated CTL cells by modified antigen peptides and the total interaction amount of hydrogen bonds and salt bridges. CONCLUSION: Promoting the formation of pi-stacking interaction between antigen peptides and HLA-A*2402 molecules could increase the total binding free energy of p-HLA complex and the level of CTL cells activation. In addition, the amount of hydrogen bonds and salt bridges between peptides and HLA could reduce the level of immune activation. All the characteristics above can improve the immunogenicities of the weak antigens.
RESUMO
BACKGROUND: Long intergenic noncoding RNA1184 (linc01184) has been recently discovered; however, its role in human diseases is limited to date. The present study is aimed at investigating the expression pattern and mechanism of linc01184 in colorectal cancer (CRC) tumorigenesis. METHODS: The expression of linc01184 in CRC tissues and cell lines was compared with that in normal controls. The functions of linc01184 in CRC cells were identified by overexpression and small interfering RNA (siRNA) approaches in vitro. Meanwhile, the target gene prediction software, luciferase reporter, RNA pull-down, and western blotting assays were used to analyze the oncogenic mechanism. RESULTS: We found that linc01184 was obviously upregulated in CRC tissues and cells when compared to normal controls, and its upregulation had a positive association with the CRC progression. linc01184 knockdown significantly suppressed CRC cell proliferation and invasion and promoted apoptosis. Besides, linc01184 acted as a competitive endogenous RNA (ceRNA) by directly binding to microRNA-331 (miR-331), and its overexpression resulted in notable increases of human epidermal growth factor receptor 2 (HER2), phosphorylated Ser/Thr kinases (p-Akt), and extracellular regulated protein kinase 1/2 (p-ERK1/2) at posttranscriptional levels in CRC cells, which were antagonized by miR-331. CONCLUSIONS: The findings reveal for the first time that linc01184 is an enhancer for the proliferation and invasion of CRC by functioning as a ceRNA through the linc01184-miR-331-HER2-p-Akt/ERK1/2 pathway regulatory network.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , Idoso , Biomarcadores Tumorais/metabolismo , Células CACO-2 , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Regulação para CimaRESUMO
Background: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment. Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. A metastatic breast cancer model was established using the intrahepatic growth of MCF-7 cells in immunodeficient rats. Results: Tam-Gel can transform from liquid to hydrogel at room temperature. An intratumoral injection of Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. Once Tam-Gel, but not Tam-Sol, was administered by intratumoral injection, it significantly decreased the uptake of radionuclide probes (18F-fluoroestradiol or 18F-fluorodeoxyglucose) by cells in rats' livers and the intrahepatic growth of MCF-7 cells in rats' livers. Conclusion: A novel slow-release system was successfully prepared to facilitate the long-term release of tamoxifen in breast cancer tissues, and achieved an antitumor effect in the long term.
RESUMO
AOC (allene oxide cyclase; EC 5.3.99.6), an essential enzyme in jasmonic acid and its methyl ester biosynthesis, was cloned from Camptotheca acuminata (named as CaAOC), a native medicinal plant species in China. CaAOC had significant similarity at the amino-acid level with AOCs from other plant species. Comparison between the sequences of the full-length cDNA and genomic DNA of CaAOC revealed that the genomic DNA of CaAOC contained an 89-bp intron and a 240-bp intron. Southern-blot analysis indicated that CaAOC was a multiple-copy gene, and real-time quantitative PCR analysis showed that CaAOC was expressed constitutively in all organs tested, with the highest expression level in leaves. The results from treatment experiments using different signalling components, including methyl jasmonate, abscisic acid, salicylic acid and H(2)O(2), revealed that expression of CaAOC had a prominent diversity. Heavy metal (copper) significantly enhanced CaAOC expression, whereas wounding (induced by UV-B) was not so effective.