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Objective: The aim of this study was to assess the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics signature model to predict disease-free survival (DFS) in patients with rectal cancer treated by surgery. Materials and methods: We evaluated data of 194 patients with rectal cancer who had undergone radical surgery between April 2016 and September 2021. The mean age of all patients was 62.6 ± 9.7 years (range: 37-86 years). The study endpoint was DFS and 1132 radiomic features were extracted from preoperative MRIs, including contrast-enhanced T1- and T2-weighted imaging and apparent diffusion coefficient values. The study patients were randomly allocated to training (n=97) and validation cohorts (n=97) in a ratio of 5:5. A multivariable Cox regression model was used to generate a radiomics signature (rad score). The associations of rad score with DFS were evaluated using Kaplan-Meier analysis. Three models, namely a radiomics nomogram, radiomics signature, and clinical model, were compared using the Akaike information criterion. Result: The rad score, which was composed of four MRI features, stratified rectal cancer patients into low- and high-risk groups and was associated with DFS in both the training (p = 0.0026) and validation sets (p = 0.036). Moreover, a radiomics nomogram model that combined rad score and independent clinical risk factors performed better (Harrell concordance index [C-index] =0.77) than a purely radiomics signature (C-index=0.73) or clinical model (C-index=0.70). Conclusion: An MRI radiomics model that incorporates a radiomics signature and clinicopathological factors more accurately predicts DFS than does a clinical model in patients with rectal cancer.
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INTRODUCTION: Small cell lung cancer (SCLC) is a highly aggressive lung cancer variant known for its elevated risk of brain metastases (BM). While earlier meta-analyses supported the use of prophylactic cranial irradiation (PCI) to reduce BM incidence and enhance overall survival, modern MRI capabilities raise questions about PCI's universal benefit for limited-stage SCLC (LS-SCLC) patients. As a response, we have created a predictive model for BM, aiming to identify low-risk individuals who may not require PCI. METHODS: A total of 194 LS-SCLC patients without PCI treated between 2009 and 2021 were included. We conducted both univariate and multivariate analyses to pinpoint the factors associated with the development of BM. A nomogram for predicting the 2- and 3-year probabilities of BM was then constructed. RESULTS: Univariate and multivariate analyses revealed several significant independent risk factors for the development of BM. These factors include TNM stage, the number of chemotherapy (ChT) cycles, Ki-67 expression level, pretreatment serum lactate dehydrogenase (LDH) levels, and haemoglobin (HGB) levels. These findings underscore their respective roles as independent predictors of BM. Based on the results of the final multivariable analysis, a nomogram model was created. In the training cohort, the nomogram yielded an area under the receiver operating characteristic curve (AUC) of 0.870 at 2 years and 0.828 at 3 years. In the validation cohort, the AUC values were 0.897 at 2 years and 0.789 at 3 years. The calibration curve demonstrated good agreement between the predicted and observed probabilities of BM. CONCLUSIONS: A novel nomogram has been developed to forecast the likelihood of BM in patients diagnosed with LS-SCLC. This tool holds the potential to assist healthcare professionals in formulating more informed and tailored treatment plans.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/prevención & control , Irradiación Craneana , Neoplasias Pulmonares/patología , Factores de RiesgoRESUMEN
For patients with locally unresectable recurrent nasopharyngeal carcinoma who relapsed after 2 years of radiotherapy, re-radiotherapy is also the preferred treatment. However, for patients relapsed within 2 years, the use of re-radiotherapy would be greatly limited by its adverse effects. Consequently, finding a new strategy to prolong the time of re-radiotherapy for locally recurrent nasopharyngeal carcinoma is very necessary to reduce the related side effects and improve the curative effect. Anlotinib is an orally available small molecule multi-target tyrosine kinase inhibitor that primarily inhibits VEGFR2/3, FGFR1-4, PDGFR α/ß, c-Kit, and Ret. However, whether recurrent nasopharyngeal carcinoma patients can be treated with anlotinib combined with ticeorgio (also called S-1) remains unknown. Herein, we report a nasopharyngeal carcinoma patient with local recurrence after radical radiotherapy who benefited from combination treatment of anlotinib with ticeorgio.
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Background: Sterol-regulatory element-binding protein 1 (SREBP1) is a transcription factor involved in lipid metabolism that is encoded by sterol regulatory element binding transcription factor 1(SREBF1). SREBP1 overexpression is associated with the progression of several human tumors; however, the role of SREBP1 in head and neck squamous cell carcinoma (HNSC) remains unclear. Methods: SREBF1 expression in pan-cancer was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data, and the association between SREBF1 expression and clinical characteristics of HNSC patients was examined using the UALCAN database. Enrichment analysis of SREBF1-related genes was performed using the Cluster Profiler R package. TCGA database was used to investigate the relationship between immune cell infiltration and SREBF1 expression. CCK-8, flow cytometry, and wound healing assays were performed to investigate the effect of SREBF1 knockdown on the proliferation and migration of HNSC cells. Results: SREBF1 was significantly upregulated in several tumor tissues, including HNSC, and SREBF1 overexpression was positively correlated with sample type, cancer stage, tumor grade, and lymph node stage in HNSC patients. Gene enrichment analysis revealed that SREBF1 is associated with DNA replication and homologous recombination. SREBF1 upregulation was positively correlated with the infiltration of cytotoxic cells, B cells, T cells, T helper cells, and NK CD56 bright cells in HNSC. Knockdown of SREBF1 inhibited the proliferation and migration of HNSC cells (Hep2 and TU212) and induced apoptosis by downregulating the expression of steroidogenic acute regulatory protein-related lipid transfer 4 (STARD4). Conclusions: SREBF1 may promote HNSC proliferation, migration and inhibit apoptosis by upregulating STARD4 and affecting the level of immune cell infiltration.
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Neoplasias de Cabeza y Cuello , Factores de Transcripción , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/genética , Proliferación Celular/genética , EsterolesRESUMEN
Breast cancer threatens the health of women worldwide, and its molecular subtypes largely determine the therapy and prognosis of patients. However, an uncomplicated and accurate method to identify subtypes is currently lacking. This study utilized photoacoustic spectral analysis (PASA) based on the partial least squares discriminant algorithm (PLS-DA) to identify molecular breast cancer subtypes at the biomacromolecular level in vivo. The area of power spectrum density (APSD) was extracted to semi-quantify the biomacromolecule content. The feature wavelengths were obtained via the variable importance in projection (VIP) score and the selectivity ratio (Sratio), to identify the biomarkers. The PASA achieved an accuracy of 84%. Most of the feature wavelengths fell into the collagen-dominated absorption waveband, which was consistent with the histopathological results. This paper proposes a successful method for identifying molecular breast cancer subtypes and proves that collagen can be treated as a biomarker for molecular breast cancer subtyping.
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BACKGROUND: The use of prophylactic cranial irradiation (PCI) in patients suffering from limited-stage small-cell lung cancer (LS-SCLC) remains controversial in modern brain magnetic resonance imaging (MRI) staging. To this end, a systematic review with meta-analysis was hereby performed to investigate the overall survival (OS) in these patients. METHODS: Relevant studies from the PubMed and EMBASE databases were reviewed, and pooled hazard risks were obtained using fixed-effects models. The PRISMA 2020 checklist was used. RESULTS: Fifteen retrospective studies were identified, with a total of 2,797 patients with LS-SCLC included in the analysis, 1,391 of which had received PCI. For all included patients, PCI was associated with improved OS [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.58-0.70]. The combination of subgroup analysis and sensitivity analysis suggested that the effect of PCI on OS was independent of primary tumor treatment, proportion of complete response (CR), median age, PCI dose, publication years, etc. Additionally, the OS curve of 1,588 patients having undergone thoracic radiotherapy (TRT) as the primary tumor treatment from 8 studies were reconstructed, and the pooled 2-, 3- and 5-year OS rates of limited stage patients were 59% vs. 42%, 42% vs. 29% and 26% vs. 19% (HR: 0.69, 95% CI: 0.61-0.77) in the PCI group and the no PCI group, respectively. Another reconstructed OS curve of 339 patients having undergone radical surgery as the primary tumor treatment from 2 studies presented better results, and the pooled 2-, 3- and 5-year OS rates of in the PCI group and the no PCI group were 85% vs. 71%, 70% vs. 56% and 52% vs. 39% (HR: 0.59, 95% CI: 0.40-0.87), respectively. CONCLUSIONS: This meta-analysis demonstrates a significant beneficial effect of PCI on the OS in patients with LS-SCLC in modern pretreatment MRI staging. However, considering the absence of a strict follow-up of brain MRI recommended by the guideline for the control group from most of the included studies, the superiority of PCI to the treatment strategy of no PCI plus brain MRI surveillance remains unclear.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Estudios Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/prevención & control , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Irradiación Craneana/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Olfactory neuroblastoma (ONB) is an ectodermal malignant tumor originating from the olfactory nerve epithelium of the nasal cavity and paranasal sinus. Olfactory neuroblastoma is a rare cancer, with an estimated incidence of 0.4 per million. Olfactory neuroblastoma often occurs in the top of the nasal cavity or near the lateral wall of the middle turbinate, which accounts for approximately 3% to 5% of the nasal cavity and paranasal sinus tumors. Olfactory neuroblastoma primarily in the nasopharynx is rare and tends to be misdiagnosed as nasopharyngeal carcinoma. Herein, we presented a case of ONB of the nasopharynx with recurrent nasopharyngeal tumor and by lymph node metastasis in both sides of the neck 14 months after surgical removal of the primary ONB. Long-term disease-free survival was achieved by definitive radiotherapy. Surgery combined with radiotherapy or definitive radiotherapy is recommended for primary ONB of the nasopharynx, radiotherapy target delineation including nasopharynx and pharyngeal lymph nodes, and neck lymph node drainage area of level Ib, â ¡, and â ¢.
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Estesioneuroblastoma Olfatorio , Neoplasias Nasofaríngeas , Neoplasias Nasales , Humanos , Recurrencia Local de Neoplasia , Cavidad NasalRESUMEN
Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.
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Background: Both the tumor environment and the genomic landscape of lung cancer may shape patient responses to treatments, including immunotherapy, but their joint impacts on lung adenocarcinoma (LUAD) prognosis are underexplored. Methods: RNA sequencing data and whole-exome sequencing results were downloaded from the TCGA database, and only LUAD-related data were included in this study. Based on gene expression data, the ESTIMATE algorithm was used to estimate stromal and immune scores, and CIBERSORT analysis was used for quantification of the relative abundances of immune cells. Somatic mutations were used for calculating tumor mutation burden (TMB). Specific mutations in genes involved in DNA damage repair (DDR) pathways were identified. The individual and joint associations of stromal and immune score, TMB, and DDR gene mutations with 5-year survival were analyzed by the Kaplan-Meier method and multivariate Cox model. Results: LUAD patients with a high (>highest 25%) stromal or immune score had prolonged survival as compared to those with a low (
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Tumor hyaluronan (HA) accumulation is closely associated with the formation of a hypoxic microenvironment that is highly immunosuppressive and severely hinders the efficacy of antitumor therapeutics. To address this problem, we develop an effective HA attenuation strategy that uses an integrated nanosystem based on mesoporous polydopamine (mPDA) with excellent photothermal conversion efficiency to boost hyaluronidase (HAase) activity remotely. Upon light irradiation, the thermal effect generated by mPDA not only directly kills tumor cells that produces an in situ vaccine effect, but also significantly boosts HAase activity (â¼5 folds), leading to marked HA break down. Photoheat and HA degradation synergistically reduce tumor HIF-1α expression and reverse immunosuppressive responses. Using the synergistic treatment in a breast cancer model, we find decreased infiltration of immunosuppressive cells, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells, increased immune-activated cells, such as mature dendritic cells and CD8+ T cells, and reduced immune checkpoint PD-L1 expression. The resulting relief from tumor microenvironment immunosuppression significantly contributes to an enhanced antitumor effect. This study provides an effective strategy to improve the hypoxic tumor microenvironment and simultaneously promote immune-mediated tumor regression.
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Neoplasias , Microambiente Tumoral , Linfocitos T CD8-positivos , Línea Celular Tumoral , Humanos , Hialuronoglucosaminidasa , Inmunoterapia/métodosRESUMEN
BACKGROUND: Existing evidence demonstrates that radiotherapy and antiangiogenic drugs have synergistic antitumour effects and may be a promising treatment option for patients with solid tumour. Thus, we performed a phase II trial to evaluate the efficacy and safety of whole-brain radiotherapy (WBRT) combined with anlotinib for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC) without targetable driver mutations. METHODS: Patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations who failed to respond to at least first-line chemotherapy were enrolled. Eligible patients received WBRT (30 Gy/10 f, 5 f/week) and anlotinib (12 mg/day, day 1-14 of 21 days per cycle, 2 cycles) until disease progression or treatment intolerance. The primary endpoint was intracranial objective response rate (iORR) and secondary endpoints included intracranial progression-free survival (iPFS), disease control rate (DCR), overall survival (OS), and safety. RESULTS: Between April 2019 and March 2021, 21 patients were enrolled in the trial, of which 12 were aged ⩾60 years (57.1%), 13 were men (61.9%), 7 had an Eastern Cooperative Oncology Group Performance Status score of 0 to 1 (81.0%), 18 had adenocarcinoma (85.7%), and 11 had ⩾6 BMs (52.4%). Of the 21 evaluable patients, the iORR was 66.7% (1 complete response + 13 partial response [PR]), and 28.6% (7PR) had extracerebral lesions. The DCRs for intracerebral and extracerebral lesions were 90.5% and 81.0%, respectively. The iPFS and OS were 10.3 months (95% confidence interval [CI]: 0-24.8 months) and 13.4 months (95% CI: 0-27.9 months), respectively. The most frequently observed toxicities were loss of appetite (61.9%), hypertension (52.4%), fatigue (47.6%), diarrhoea (28.6%), vomiting (19.0%), dizziness (42.9%), and headache (33.3%). None of the patients developed grade 4 or higher grade adverse reactions. CONCLUSIONS: Anlotinib combined with WBRT is effective and well tolerated in patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations. Therefore, further validation studies are required.Clinical trial registration number: ChiCTR 1900027769.
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Pathology is currently the gold standard for grading prostate cancer (PCa). However, pathology takes considerable time to provide a final result and is significantly dependent on subjective judgment. In this study, wavelet transform-based photoacoustic power spectrum analysis (WT-PASA) was used for grading PCa with different Gleason scores (GSs). The tumor region was accurately identified via wavelet transform time-frequency analysis. Then, a linear fitting was conducted on the photoacoustic power spectrum curve of the tumor region to obtain the quantified spectral parameter slope. The results showed that high GSs have small glandular cavity structures and higher heterogeneity, and consequently, the slopes at both 1210 nm and 1310 nm were high (p < 0.01). The classification accuracy of the PA time frequency spectrum (PA-TFS) of tumor region using ResNet-18 was 89% at 1210 nm and 92.7% at 1310 nm. Further, the testing time was less than 7 mins. The results demonstrated that identification of PCa can be rapidly and objectively realized using WT-PASA.
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BACKGROUND AND AIMS: Therapeutic blockade of the programmed cell death protein-1 (PD-1) immune checkpoint pathways has resulted in significant reactivation of T cell-mediated antitumor immunity and is a promising clinical anticancer treatment modality in several tumor types, but the durable response rate remains relatively low (15%-20%) in most patients with HCC for unknown reasons. Evidence reveals that the interferon signaling pathway plays a critical role in modulating the efficacy and sensitivity of anti-PD-1 therapy against multiple tumor types, but the mechanisms are unclear. APPROACH AND RESULTS: Using Kaplan-Meier survival analysis based on HCC databases, we found that deceased expression of interferon regulatory factor (IRF) 8 in HCC, among all the nine IRF members that regulate interferon signals, was associated with poor prognosis of patients with HCC. Moreover, gene set enrichment analysis identified the interferon-gamma and PD-1 signaling signatures as the top suppressed pathways in patients with IRF8-low HCC. Contrarily, overexpression of IRF8 in HCC cells significantly enhanced antitumor effects in immune-competent mice, modulating infiltration of tumor-associated macrophages (TAMs) and T cell exhaustion in tumor microenvironment. We further demonstrated that IRF8 regulated recruitment of TAMs by inhibiting the expression of chemokine (C-C motif) ligand 20 (CCL20). Mechanically, IRF8-mediated repression of c-fos transcription resulted in decreased expression of CCL20, rather than directly bound to CCL20 promoter region. Importantly, adeno-associated virus 8-mediated hepatic IRF8 rescue significantly suppressed HCC progression and enhanced the response to anti-PD-1 therapy. CONCLUSIONS: This work identified IRF8 as an important prognostic biomarker in patients with HCC that predicted the response and sensitivity to anti-PD-1 therapy and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Factores Reguladores del Interferón/metabolismo , Microambiente Tumoral , Interferón gamma/metabolismo , Muerte CelularRESUMEN
Presbycusis, or age-related hearing loss (ARHL), is primarily associated with sensory or transduction nerve cell degeneration in the peripheral and/or central auditory systems. During aging, the auditory system shows mitochondrial dysfunction and increased inflammatory responses. Mitochondrial dysfunction promotes leakage of mitochondrial DNA (mtDNA) into the cytosol, which activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to induce type I interferon and inflammatory responses. However, whether this pathway is involved in the occurrence and development of ARHL is unknown. This study aimed to determine whether there are age-related changes in the levels of cytosolic mtDNA and cGAS-STING pathway activation in the auditory pathway and to explore their relationship with ARHL. The results showed that cGAS-positive immunoreactive cells were observed in the cochlea, inferior colliculus, and auditory cortex. Levels of cytosolic mtDNA, cGAS, STING, phosphorylated interferon regulatory factor 3, and cytokines were significantly increased in the cochlea, inferior colliculus, and auditory cortex of 6-, 9-, and 12-month-old mice compared with 3-month-old mice. These findings suggested that cytosolic mtDNA may play an important role in the pathogenesis of ARHL by activating cGAS-STING-mediated type I interferon and inflammatory responses.
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Interferones , Presbiacusia , Animales , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Nucleótidos Cíclicos , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismoRESUMEN
Prostate cancer (PCa) is one of the most common malignancies affecting men worldwide. Androgen receptor (AR) has been a target of PCa treatment for nearly six decades. AR antagonists/degraders can effectively treat PCa caused by increased AR overexpression. However, all approved AR antagonists have similar chemical structures and exhibit the same mode of action on the protein. Although initially effective, resistance to these AR antagonists usually develops. Therefore, this calls for the identification of novel chemical structures of AR antagonists to overcome the resistance. Herein, we employed the synergetic combination of virtual and experimental screening to identify a flavonoid compound which not only effectively inhibits AR transcriptional activity, but also induces the degradation of the protein. Based on this compound, we designed and synthesized a series of derivatives. We discovered that the most potent compound 10e could effectively inhibit AR transcriptional activity, and possessed a profound ability to cause degradation of both full length- and ARv7 truncated forms of human AR. Notably, 10e efficiently inhibited the growth of ARv7 dependent prostate cancer cell-lines, which are completely resistant to all current anti-androgens. Compound 10e also showed strong antitumor activity in the LNCaP (androgen dependent prostate cancer cell line) in vivo xenograft model. These results provide a foundation for the development of a new class of AR antagonists.
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Antagonistas de Receptores Androgénicos/farmacología , Antineoplásicos/farmacología , Flavonoides/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Antagonistas de Receptores Androgénicos/síntesis química , Antagonistas de Receptores Androgénicos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Flavonoides/síntesis química , Flavonoides/química , Humanos , Masculino , Estructura Molecular , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/genética , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
In incurable castration-resistant prostate cancer (CRPC), resistance to the novel androgen receptor (AR) antagonist enzalutamide is driven mainly by AR overexpression. Here we report that the expression of interferon regulatory factor 8 (IRF8) is increased in primary prostate cancer but decreased in CRPC compared with normal prostate tissue. Decreased expression of IRF8 positively associated with CRPC progression and enzalutamide resistance. IRF8 interacted with AR and promoted its degradation via activation of the ubiquitin/proteasome systems. Epigenetic knockdown of IRF8 promoted AR-mediated prostate cancer progression and enzalutamide resistance in vitro and in vivo. Furthermore, IFNα increased expression of IRF8 and improved the efficacy of enzalutamide in CRPC by targeting the IRF8-AR axis. We also provide preliminary evidence for the efficacy of IFNα with hormonotherapy in a clinical study. Collectively, this study identifies IRF8 both as a tumor suppressor in prostate cancer pathogenesis and a potential alternative therapeutic option to overcome enzalutamide resistance. SIGNIFICANCE: These findings identify IRF8-mediated AR degradation as a mechanism of resistance to AR-targeted therapy, highlighting the therapeutic potential of IFNα in targeting IRF8-AR axis in CRPC. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/13/2927/F1.large.jpg.
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Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos , Retroalimentación Fisiológica , Factores Reguladores del Interferón/metabolismo , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Anciano de 80 o más Años , Animales , Apoptosis , Benzamidas , Biomarcadores de Tumor/genética , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Factores Reguladores del Interferón/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nitrilos , Feniltiohidantoína/farmacología , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores Androgénicos/genética , Transducción de Señal , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This study presents a deep-learning method for characterizing carbon fiber (CF) distribution and predicting electrical conductivity of CF-reinforced cement-based composites (CFRCs) using scanning electron microscopy (SEM) images. First, SEM images were collected from CFRC specimens with different CF contents. Second, a fully convolutional network (FCN) was utilized to extract carbon fiber components from the SEM images. Then, DSEM and Dsample were used to evaluate the distribution of CFs. DSEM and Dsample reflected the real CF distribution in an SEM observation area and a specimen, respectively. Finally, a radial basis neural network was used to predict the electrical conductivity of the CFRC specimens, and its weights (di) were used to evaluate the effects of CF distribution on electrical conductivity. The results showed that the FCN could accurately segment CFs in SEM images with different magnifications. Dsample could accurately reflect the morphological distribution of CFs in CFRC. The electrical conductivity prediction errors were less than 6.58%. In addition, di could quantitatively evaluate the effect of CF distribution on CFRC conductivity.
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OBJECTIVE: The primary purpose of this study is to investigate the effect of hedgehog-interacting protein (HHIP) overexpression on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC). METHODS: Firstly, HHIP gene expression data of NSCLC tissues and normal tissues were obtained from GSE18842/GSE19804/GSE43458 databases of the Gene Expression Omnibus (GEO) database and then validated by TCGA NSCLC database in a cohort of 1027 cases of NSCLC patients and 108 cases of normal people. A chi-square test was used to analyze the relationship between HHIP expression and clinicopathological characteristics of NSCLC. The expression levels of HHIP in NSCLC cells were detected by quantitative-real time PCR. The function of HHIP was investigated by a series of in vitro assays. CCK-8, wounding healing, Transwell invasion assay were utilized to explore the mechanisms of HHIP. RESULTS: HHIP mRNA were significantly down-regulated in NSCLC in three GEO databases and TCGA database (P<0.05). This result was confirmed in NSCLC cell lines by qRT-PCR analysis, its expression in normal NSCLC cell line BEAS-2B was significantly higher than that in NSCLC cells. Chi-square test results showed that the low expression of HHIP was correlated with gender, cancer type, TNM stage and tumor size. Functional experimental results showed that over-expressing HHIP significantly decreased the ability of cell proliferation, migration and invasion in NSCLC cells (P<0.05). CONCLUSION: Overall, the above results indicated that HHIP could regulate proliferation, migration and invasion, and could be used as a judging criterion for identifying NSCLC classification and stage.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas Portadoras/metabolismo , Proliferación Celular , Neoplasias Pulmonares/patología , Glicoproteínas de Membrana/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteínas Portadoras/genética , Línea Celular Tumoral , Movimiento Celular , Bases de Datos Factuales , Regulación hacia Abajo , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
Cisplatinbased chemotherapy may greatly enhance patient prognosis; however, chemotherapy resistance remains an obstacle to curing patients with nonsmall cell lung cancer (NSCLC). The aim of the present study was to explore the microRNAs (miRs) that could regulate cisplatin sensitivity and provide a potential treatment method for cisplatin resistance in clinical. Results from the present study revealed that miR29a overexpression enhanced and miR29a inhibition reduced the sensitivity of two NSCLC cell lines, A549 and H1650, to cisplatin treatment. In addition, reduced miR29a expression levels were observed in cisplatinresistant A549 cells (A549rCDDP), and increased expression of miR29a augmented cisplatininduced inhibition of proliferation and apoptosis in A549rCDDP cells. These data indicated that miR29a expression may be involved in the development of cisplatin resistance. miR29a was revealed to negatively regulate REV3like DNAdirected polymerase ζ catalytic subunit (REV3L) expression in both A549 and H1650 cells; elevated expression of REV3L in A549rCDDP cells was also detected. REV3L encodes the catalytic subunit of DNA polymerase ζ and was hypothesized, based on results from the online tool TargetScan 7.1, to be a target gene of miR29a; this was confirmed with a dual luciferase assay. Cells treated with a very low concentration of cisplatin exhibited a significant reduction in proliferation and cell cycle arrest at the G2/M phase in REV3Lknockdown as well as in miR29aupregulated A549 cells. Notably, reduced miR29a expression and an increase in REV3L mRNA expression were observed in tumor tissues from patients with NSCLC. Additionally, a negative correlation between miR29a and REV3L mRNA expression levels in tumor tissues from patients with NSCLC was observed; low expression of miR29a and high expression of REV3L were closely associated with an advanced tumornodemetastasis classification. The results of the present study suggested a pivotal role of miR29a in mediating NSCLC cell sensitivity towards cisplatin through the regulation of REV3L.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Cisplatino/farmacología , Proteínas de Unión al ADN/genética , ADN Polimerasa Dirigida por ADN/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , MicroARNs/genética , Células A549 , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular , Línea Celular Tumoral , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Células HEK293 , Humanos , Neoplasias Pulmonares/patología , Pronóstico , Regulación hacia Arriba/genéticaRESUMEN
In the version of this article initially published, in Volume 21, issue 3, the first affiliation (affiliation number 1) was incorrectly stated as "Department of Pathology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey". The correct affiliation is "Department of Oncology, Shaoxing People's Hospital ,Shaoxing Hospital of Zhejiang University, Shaoxing 312000,China'. This error appeared only in the PubMed database and not in the print form of the Journal.