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1.
J Cancer Res Ther ; 17(5): 1179-1185, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34850765

RESUMO

Objective: Imaging examination, tumor marker detection, bladder biopsy, and other methods are the common methods for the diagnosis of bladder cancer (BC). This study was aimed to assess the value of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) in the diagnosis of BC. Materials and Methods: Fifty-nine patients with BC were recruited in our hospital from September 2012 to December 2015, who had CEUS and magnetic resonance diffusion-weighted imaging (MRI + DWI). All patients underwent surgical treatment and definite pathological stage. The series and parallel combined diagnosis methods were applied to calculate the diagnostic sensitivity, specificity, and accuracy through using quantitative apparent diffusion coefficient (ADC) and receiver operating characteristic curve. Results: The accuracies of CEUS and MRI + DWI examination for T staging of BC were 74.6% and 76.3%, respectively. Compared with the single diagnostic methods, the two combined diagnosis accuracy was 91.5%, which was significantly improved in diagnosis accuracy (P < 0.05). The diagnostic accuracies of CEUS, MRI + DWI, and ADC for muscle invasion of BC were 81.4%, 83.1%, and 84.7%, respectively. The diagnostic accuracy of CEUS parallel combined with MRI + DWI (91.5%) was obviously enhanced, compared with that with the single diagnostic method. Conclusion: The accuracy of CEUS and MRI + DWI combined diagnosis was higher than that with the single diagnostic method. CEUS and MRI + DWI combined diagnosis was a feasible and effective method for the clinical diagnosis of BC.

2.
Cancer Imaging ; 21(1): 65, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863282

RESUMO

PURPOSE: The Ki67 expression is associated with the advanced clinicopathological features and poor prognosis in bladder cancer (BCa). We aimed to develop and validate magnetic resonance imaging (MRI)-based radiomics signatures to preoperatively predict the Ki67 expression status in BCa. METHODS AND MATERIALS: We retrospectively collected 179 BCa patients with Ki67 expression and preoperative MRI. Radiomics features were extracted from T2-weighted (T2WI) and dynamic contrast-enhancement (DCE) images. The synthetic minority over-sampling technique (SMOTE) was used to balance the minority group (low Ki67 expression group) in the training set. Minimum redundancy maximum relevance was used to identify the best features associated with Ki67 expression. Support vector machine and Least Absolute Shrinkage and Selection Operator algorithms (LASSO) were used to construct radiomics signatures in training and SMOTE-training sets, and diagnostic performance was assessed by the area under the curve (AUC) and accuracy. The decision curve analyses (DCA) and calibration curve and were used to investigate the clinical usefulness and calibration of radiomics signatures, respectively. The Kaplan-Meier test was performed to investigate the prognostic value of radiomics-predicted Ki67 expression status. RESULTS: 1218 radiomics features were extracted from T2WI and DCE images, respectively. The SMOTE-LASSO model based on nine features achieved the best predictive performance in the SMOTE-training (AUC, 0.859; accuracy, 80.3%) and validation sets (AUC, 0.819; accuracy, 81.5%) with a good calibration performance and clinical usefulness. Immunohistochemistry-based high Ki67 expression and radiomics-predicted high Ki67 expression based on the SMOTE-LASSO model were significantly associated with poor disease-free survival in training and validation sets (all P < 0.05). CONCLUSIONS: The SMOTE-LASSO model could predict the Ki67 expression status and was associated with survival outcomes of the BCa patients, thereby may aid in clinical decision-making.

3.
Aging (Albany NY) ; 13(24): 25886-25902, 2021 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-34923484

RESUMO

Pelvic organ prolapse is a worldwide health problem to elderly women. Understanding its pathogenesis and an ideal animal model are crucial to developing promising treatments. The present study aimed to investigate new clinical significance and detailed mechanism of pelvic organ prolapse by comparing the structural, functional and molecular dysfunctions of pelvic organ prolapse in patient and Loxl1 deficient mice. Our results showed that human vagina tissues from prolapsed site showed disarranged collagen and elastic fibers compared with the non-prolapse tissue. A gene ontology (GO) analysis of differentially expressed genes revealed molecular changes mainly related to inflammatory response and extracellular matrix (ECM) organization. While the mice lacking Loxl1 developed stable POP phenotype and disordered ECM structure in histology. Such Loxl1 knockout mice exhibited a significantly urinary dysfunction and decreased mechanical properties of the pelvic floor tissues, implying that POP in human condition might be induced by progressively decreased mechanics of pelvic tissues following ECM catabolism. Similarly, we not only identified significant up-regulated ECM catabolism processes and down-regulated ECM synthesis processes, but also characterized high level of inflammatory response in vagina tissue of the Loxl1 deficient mice. Thus, all these pathological changes in the POP mice model was consistent with those of the clinical elderly patients. These findings provide new insight into remodeling of POP by LOXL1 regulation and be of great importance to develop combination treatments of ECM metabolism and inflammation regulation strategy.

4.
Cell Mol Life Sci ; 78(24): 8127-8155, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34783870

RESUMO

Articular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and application, and, when used in combination, act as powerful tools for manipulating cellular fate. In this review, we present current achievements in the development of small molecular drugs for cartilage regeneration, particularly in the fields of chondrocyte generation and reversion of chondrocyte degenerative phenotypes. Several clinically or preclinically available small molecules, which have been shown to facilitate chondrogenesis, chondrocyte dedifferentiation, and cellular reprogramming, and subsequently ameliorate cartilage degeneration by targeting inflammation, matrix degradation, metabolism, and epigenetics, are summarized. Notably, this review introduces essential parameters for high-throughput screening strategies, including models of different chondrogenic cell sources, phenotype readout methodologies, and transferable advanced systems from other fields. Overall, this review provides new insights into future pharmaceutical therapies for cartilage regeneration.

5.
Ann Transl Med ; 9(18): 1438, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733990

RESUMO

Background: The tumor microenvironment (TME) is not only a key factor in the malignant progression of cancer but also plays an indispensable role in tumor immunotherapy. As an important regulatory factor in the TME, long non-coding RNAs (incRNA) are important for the development of bladder cancer. The purpose of this study was to explore the molecular mechanism of malignant progression of bladder cancer (BCa) from the perspective of immunology, establish a reliable signature, and evaluate its effect on prognosis, metastasis, and the effectiveness of immunotherapy. Methods: The TME was assessed by single-sample gene set enrichment analysis (ssGSEA) in 373 patients with muscle invasive bladder cancer (MIBC) in The Cancer Genome Atlas (TCGA). Combining RNA sequence data from 49 BCa patients in our center, we established TME-related prognostic signatures (TMERPS) based on TME-related immune prognosis genes using weighted gene correlation network analysis, selection operator Cox analysis, minimum absolute shrinkage, and survival analysis. Real-Time Quantitative PCR was used for expression level analysis of related genes. Functional enrichment analysis and nomograms were used to explore the potential impact of TMERPS on the immune system, prognosis, and metastasis. Results: The ssGSEA proved to be an accurate assessment of immune levels in BCa samples. TMERPS was established based on six TME-associated prognostic lncRNAs and was shown to be closely associated with prognosis, metastasis, and immune levels, and to have a significant stratifying effect on the therapeutic efficacy of immune checkpoint inhibitors. Finally, three TMERPS-based nomograms were shown to be effective in predicting prognosis, lymph node metastasis, and distant metastasis in BCa patients. Conclusions: TMERPS can stratify BCa patients into different risk groups with different prognoses, immunotherapy sensitivity, and risk of metastasis. TMERPS-based nomograms can effectively predict prognosis and metastasis in BCa patients.

6.
Ann Transl Med ; 9(18): 1439, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733991

RESUMO

Background: Sulfatase 2 (SULF2) is a member of the sulfatase family, and its expression and clinical significance in bladder cancer (BCa) are not currently known. In this study, we attempted to evaluate SULF2 expression in BCa patients who underwent radical cystectomy (RC) and the relationship between SULF2 expression and clinical-pathological characteristics. Methods: Data on SULF2 expression in BCa tissues was obtained from the Oncomine database and the Gene Expression Omnibus (GEO). The expression of SULF2 and vascular endothelial growth factor-D (VEGF-D) in BCa was evaluated by immunohistochemistry (IHC) in tissues from 203 patients who had undergone RC. We also explored the value of the measurement of SULF2 and VEGF-D expression for diagnosis and prognosis in BCa patients with lymphatic metastasis. Results: We found an increase in SULF2 messenger RNA (mRNA) levels and gene amplification in BCa tissues from the Oncomine database. High expression of SULF2 was detected in 91/203 (44.8%) of BCa patients. Among these patients, 27 of 42 (64.3%) with lymphatic metastasis showed high SULF2 expression. Univariate analysis showed that tumor size, pathological stage, lymphatic metastasis, vascular infiltration, perineural infiltration, hydronephrosis, and VEGF-D and SULF2 expression were related to prognosis in BCa patients, and multivariable Cox regression analysis showed that SULF2 expression was an independent prognostic indicator. Receiver operating characteristic (ROC) analysis revealed that SULF2 expression resulted in an increased area under the curve (AUC) of 0.707, with a sensitivity of 71.4% and a specificity of 61.5%. Conclusions: The upregulation of SULF2 is associated with poor prognosis in high-grade BCa patients. It might be a novel diagnostic marker for BCa patients with lymphatic metastasis.

7.
Ann Transl Med ; 9(18): 1440, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733992

RESUMO

Background: Bladder cancer is one of the most common carcinomas and it brings about huge social economic burden. There is not a reliable way to predict the prognosis of bladder patients. We develop the nomogram to predict the prognosis of bladder cancer patients. Methods: A total of 127 bladder cancer patients after radical cystectomy were studied retrospectively. Their clinicopathological data were collected for statistical analysis. Results: The level of albumin/globulin ratio (AGR), C-reactive protein/albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) associated with pathological and hematological parameters like T stage and hemoglobin. Furthermore, the AGR was associated with overall survival (OS) and CAR, NLR, and PLR were associated with both OS and progression-free survival (PFS) (P<0.05). The multivariate analysis revealed that tobacco smoking, tumor T stage, M stage, NLR, CAR, and AGR were all independent predictors for OS of patients and tobacco smoking, tumor T stage, NLR, CAR, and AGR were independent predictors for PFS of patients. In addition, AGR, CAR, and NLR, as well as, the clinicopathological parameters in the development of nomograms with a C index of 0.901 (95% CI: 0.505-1.269) for OS, and 0.807 (95% CI: 0.755-0.858) for PFS. The nomograms were able to provide a prognosis of the OS with the area under the curve (AUC) =0.86. Further, tests assessed the PFS with the AUC =0.84. Conclusions: This study demonstrates that the nomograms of the inflammatory biomarkers were able to predict prognosis of bladder cancer patients after radical cystectomy.

8.
Ann Transl Med ; 9(18): 1441, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733993

RESUMO

Background: Bladder cancer (BC) is a common malignant neoplasm with a high rate of recurrence and progression, despite optimal treatment. There is a pressing need to identify new effective biomarkers for the targeted treatment of BC. Methods: The key gene CALD1 was screened via weighed gene co-expression network analysis (WGCNA) from encoding protein genes of BC. Clinical and prognostic significance was explored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell chamber experiment and nude mouse xenograft assay were performed to test cell growth, apoptosis, migration, invasion and tumorigenesis capacities. Immune correlation was analyzed in The Tumor Immune Estimation Resource (TIMER) database. Relevant signaling pathways were explored using gene set enrichment analysis (GSEA). Results: Increased expression of CALD1 was significantly correlated with histological grade, clinical stage, T stage, and lymphatic metastasis. Kaplan-Meier survival curves showed that high CALD1 expression was associated with poor overall survival (OS) and disease-free survival (DFS) in TCGA database, and with poor OS in the four GEO databases. CALD1 promotes growth, migration, invasion, and cell cycle of tumor cell, and inhibits tumor cell apoptosis in vitro and in vivo. CADL1 expression was positively correlated with increased CD274 levels (r=0.357, P=9.71e-14). JAK/STAT signaling pathway was significantly enriched in the high CALD1 expression group. CALD1-mediated PD-L1 overexpression (OE) was via the activation of the JAK/STAT signaling pathway; this effect was blocked by the specific JAK inhibitor Ruxolitinib. Conclusions: CALD1 is a potential molecular marker associated with prognosis. It promotes the malignant progression of BC and upregulates the PD-L1 expression via the JAK/STAT signaling pathway.

9.
Ann Transl Med ; 9(20): 1544, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790750

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is the most common malignancy affecting the kidneys, accounting for approximately 75% of all kidney tumors. Recently, the impact of immune response, immunotherapy, and immune-related genes (IRGs) on tumor development has received much attention. This study sought to establish a reliable immunological signature and further explore whether this signature has prognostic significance in ccRCC patients. Methods: Differentially expressed IRGs in 611 patients with diagnosis of ccRCC from The Cancer Genome Atlas (TCGA) were analyzed along with the corresponding survival time and disease clinical data. Survival analysis, selection operator Cox analysis, and minimum absolute shrinkage were applied to establish an IRG prognostic signature (IRGPS). The expression levels of relevant genes were detected by real-time quantitative PCR. A Nomogram was used to explore the possible impact of the IRGPS on the immune system, prognosis, and metastasis, and the associated mechanisms were explored through functional enrichment analysis. Results: An IRGPS was established based on eight prognostic IRGs and was found to be closely associated with immune levels, metastasis, and prognosis. The IRGPS was determined to be a valid predictor of the efficacy of immune checkpoint inhibitors (ICIs). Three Nomograms based on the IRGPS and other clinical features were developed and could effectively predict prognosis, distant metastasis, and lymph node metastasis in patients with ccRCC. Conclusions: The IRGPS constructed in this study serves as a tool for assessing immune status, developing individualized treatment regimens, and predicting prognosis in patients with ccRCC.

10.
Clin Cancer Res ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740921

RESUMO

PURPOSE: Immunotherapy offers a second-line option for patients with metastatic urothelial carcinoma (mUC) who failed standard therapy, but the biomarkers for predicting response remain to be explored. This study aims to evaluate the safety, efficacy, and correlative biomarker of toripalimab in patients with previously treated mUC. EXPERIMENTAL DESIGN: Patients with mUC received toripalimab 3 mg/kg Q2W. Clinical response was assessed every 8 weeks by an independent review committee per RECIST v1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated. RESULTS: Among the intention-to-treat population (n = 151), 85% of the patients experienced treatment-related adverse event (TRAE) and 20% experienced grade 3 and above TRAE. The objective response rate (ORR) was 26% with a disease control rate (DCR) of 45%. The median duration of response, progression-free survival (PFS) and overall survival (OS) were 19.7 months (95% CI: 13.9 to NE), 2.3 months (95% CI: 1.8 to 3.6) and 14.4 months (95% CI: 9.3 to 23.1), respectively. Both PD-L1+ and TMB-high (10 mutations/Mb as the cut off) patients had better ORR than PD-L1- patients (42% versus 17%, p = 0.002) and TMB low patients (48% versus 22%, p = 0.014), respectively. The TMB-high group also showed better PFS (12.9 versus 1.8 months, p < 0.001) and OS (not reached versus 10.0 months, p = 0.018) than the TMB-low group. CONCLUSIONS: Toripalimab has demonstrated encouraging clinical activity in the second-line treatment of mUC with a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.

11.
Transl Androl Urol ; 10(10): 3826-3836, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804825

RESUMO

Background: At present, the low risk of bladder cancer (BCa)-specific death has allowed for investigation into treatment-related cardiotoxicity. To aid clinicians in selecting appropriate cardiovascular disease screening strategies and interventions, this study explored the heart-specific mortality and prognostic factors of patients with BCa after radical cystectomy (RC), radiotherapy (RT), or chemotherapy (CT), and compared their long-term heart-specific mortality with that of the general male population. Methods: We identified three different treatments for BCa patients from the Surveillance, Epidemiology, and End Results (SEER) database: RC, RT, and CT. Patients were included from 2000 to 2012 and followed through 2015. A cumulative mortality curve and competitive risk regression model were applied to evaluate the prognostic factors of heart-specific mortality, and standardized mortality ratios (SMRs) were calculated. Results: Of 39,500 men, 30.3%, 18.8%, and 50.9% received RC, RT, and CT, respectively. For patients with a survival period of less than 50 months, tumor-specific death exhibited a rapidly increasing trend, which subsequently flatlined. However, the rates heart-specific mortality and other causes exhibited a tendency to increase stably. The heart-specific and all-cause mortality rates of patients in any age group treated with the three abovementioned strategies were higher than those of the general population. The heart-specific mortality of patients with carcinoma in situ treated with RC and CT exceeded their all-cause mortality, while that of other tumor stages did not. The risks of heart-specific [sub-distribution hazard ratio (SHR) =1.38; 95% confidence interval (CI): 1.22-1.57] and tumor-specific (SHR =1.68; 95% CI: 1.60-1.77) deaths in patients who received RT were higher than those of patients who underwent CT. Conclusions: The risks of heart-specific and tumor-specific deaths in patients who received RT were higher than those of the RC and CT groups, especially in patients over 65 years of age who received RT.

12.
Cell Death Dis ; 12(11): 1081, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775467

RESUMO

Circular RNA (circRNA), a closed continuous loop formed by back-splicing, has been confirmed to be implicated in a variety of human diseases including cancers. However, the underlying molecular mechanism of circRNA regulating the progression of renal cell carcinoma (RCC) remains largely unclear. In the present study, we identified a novel circular RNA, circESRP1, that derived from the ESRP1 gene locus at 8q22.1 exons. Lower expression of circESRP1 was found in clear cell RCC (ccRCC) tissues and cell lines. Besides, circESRP1 expression level showed inversely correlated with the advanced tumor size, TNM stage and distant metastasis of ccRCC. The expression level of circESRP1 exhibited a positive correlation with CTCF protein but negatively correlated with miR-3942 in 79 ccRCC tissues. In vivo experiments, we found that overexpression of circESRP1 effectively repressed xenograft tumor growth and inhibited c-Myc-mediated EMT progression. CircESRP1 acted as a sponge to competitively bind with miR-3942 as confirmed through RNA pull-down, RIP and dual-luciferase reporter assays. Moreover, CTCF, a downstream target of miR-3942, was validated to specifically promote the circESRP1 transcript expression and regulated by circESRP1/miR-3942 pathway to form a positive feedback loop. We also revealed that the circESRP1/miR-3942/CTCF feedback loop regulated the ccRCC cell functions via c-Myc mediated EMT process. This study provides a novel regulatory model of circRNA via forming a positive-feedback loop that perpetuates the circESRP1/miR-3942/CTCF axis, suggesting that this signaling may serve as a novel target for the treatment of ccRCC.

13.
Biomaterials ; 278: 121177, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34653933

RESUMO

Although biomaterials are widely utilized in clinics, it still follows the "one-fits-all" strategy. Biological variables such as age and sexuality have an impact on the host immune response and are not fully considered in the practice guidelines of the biomaterial implantation. In this study, we investigated the immuno-material interactions of six commonly used biomaterials (agarose, alginate, chitosan, CMC, GelMA and collagen type I) and constructed a population (with different ages and sexes) based transcriptome atlas. Protein and polysaccharide-based biomaterials elicited distinctive immune responses that protein-based materials preferred the NKT pathway to activate innate and adaptive immune response, whereas polysaccharide-based materials activated the cDCs to present antigen. The atlas further revealed the sex/age-related variabilities on the immune response followed by the polysaccharide treatment. As for sex bias, alginate and agarose stimulation significantly increased the proportion of naive CD4+ T cells in the female group, accompanied by the Th1 differentiation tendency, compared to the male group. Age-biased transcript showed alginate and chitosan would impair the extracellular matrix remodeling and up-regulate the apoptosis process in the elderly groups, compared to the young group. More attentions on the ingredient, age and sexuality effect of biomaterial implants should be paid during the clinical practice, especially for the polysaccharide-based materials. This experimental result is of great significance for the selection of biomaterials, particularly the blood contact materials, such as vessel or cardiac device, drug vehicles and hemostatic materials.


Assuntos
Materiais Biocompatíveis , Quitosana , Imunidade Adaptativa , Idoso , Matriz Extracelular , Feminino , Humanos , Masculino , Sexualidade
14.
ACS Appl Mater Interfaces ; 13(46): 54801-54816, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34706537

RESUMO

Irregular partial-thickness cartilage defect is a common pathogenesis of osteoarthritis (OA) with no available treatment in clinical practice. Currently, cartilage tissue engineering is only suitable for a limited area of full-thickness cartilage defect. Here, we design a biomimetic joint paint for the intractable partial-thickness cartilage defect repair. The joint paint, composed of a bridging layer of chondroitin sulfate and a surface layer of gelatin methacrylate with hyaluronic acid, can quickly and tightly adhere to the cartilage defect by light activation. Being treated by the joint paint, the group of rabbit and pig models with partial-thickness cartilage defects showed a restoration of a smooth cartilage surface and the preservation of normal glycosaminoglycan content, whereas the untreated control group exhibited serious progressive OA development. This paint treatment functions by prohibiting chondrocyte apoptosis, maintaining chondrocyte phenotype, and preserving the content of glycosaminoglycan in the partial-thickness cartilage defects. These findings illustrated that the biomimetic joint paint is an effective and revolutionary therapeutics for the patients with noncurable partial-thickness cartilage defects.

15.
J Exp Clin Cancer Res ; 40(1): 336, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696782

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have been shown to play vital biological functions in various tumors, including prostate cancer (PCa). However, the roles of circRNAs in the metastasis of PCa remain unclear. In the present study, differentially expressed circRNAs associated with PCa metastasis were screened using high-throughput RNA sequencing, from which hsa_circ_0004296 was identified. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ_0004296 in PCa tissues and adjacent normal tissues as well as in blood and urine. Gain and loss of function experiments were performed to investigate the function of circ_0004296 in PCa. Bioinformatics analyses, RNA pull-down assay, and mass spectrometry were conducted to identify RNA-binding proteins. RNA immunoprecipitation and RNA and protein nuclear-cytoplasmic fractionation were performed to investigate the underlying mechanism. A xenograft mouse model was used to analyze the effect of circ_0004296 on PCa growth and metastasis in vivo. RESULTS: The expression of circ_0004296 was decreased in PCa tissues, blood, and urine, which was negatively associated with metastasis. Furthermore, gain and loss of function experiments in vitro and in vivo showed that circ_0004296 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of PCa cells. Mechanistically, circ_0004296 regulated host gene ETS1 expression at the post-transcriptional level. EIF4A3 was identified and confirmed as the downstream binding protein of circ_0004296. EIF4A3 expression was significantly upregulated in PCa tissues and associated with PCa metastasis. Silencing EIF4A3 suppressed PCa cell proliferation, migration, invasion, and EMT. CONCLUSIONS: Circ_0004296 overexpression efficiently inhibited ETS1 mRNA nuclear export by promoting EIF4A3 retention in the nucleus, leading to the downregulation of ETS1 expression and suppression of PCa metastasis; thus, circ_0004296 might be a potential biomarker and therapeutic target for patients with PCa.

17.
Front Surg ; 8: 716455, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557516

RESUMO

Introduction: The benefit of cytoreductive nephrectomy (CN) for metastatic kidney cancer has been challenged recently. The study aimed to evaluate the prognostic roles of surgical resection of primary tumor site for metastatic kidney cancer under a real-world setting. Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2015) and the overall survival (OS) and cancer-specific survival (CSS) were evaluated using the Cox proportional hazards regression model. One-to-one matching using the propensity score was used to estimate and compare the survival rates. Results: The SEER data contain records of 8,932 patients from 2010 to 2015. The data showed that 61.7% of the patients underwent CN while 38.2% did not receive any surgery. The median survival month for a patient without surgery was 4 months and for a patient with surgery was 19 months. The multivariate analysis showed that surgical resection of the primary tumor site was an independent favorable predictor for both OS and CSS (all p < 0.001) in the original and the matching cohort. Conclusions: In the era of target therapy, CN might still be a vital method to treat metastatic kidney cancer.

18.
Front Oncol ; 11: 632459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268106

RESUMO

The progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) increases the risk of death. It is therefore important to find new relevant molecular models that will allow for effective prediction of the progression and prognosis of bladder cancer (BC). Using RNA-Sequence data of 49 BC patients in Shanghai tenth people's hospital (STPH) and weighted gene co-expression network analysis methods, a co-expression network of genes was developed and three key modules associated with malignant progression were selected. Based on the genes in three key modules, an eight-gene risk signature was established using univariate Cox regression and the Least absolute shrinkage and selection operator Cox model in The Cancer Genome Atlas Program (TCGA) and validated in validation sets. Subsequently, a nomogram based on the risk signature was constructed for prognostic prediction. The mRNA and protein expression levels of eight genes in cell lines and tissues were further investigated. The novel eight-gene risk signature was closely related to the malignant clinical features of BC and could predict the prognosis of patients in the training dataset (TCGA) and four validation sets (GSE32894, GSE13507, IMvigor210 trial, and STPH). The nomogram showed good prognostic prediction and calibration. The mRNA and protein expression levels of the eight genes were differentially expressed in cell lines and tissues. In our study, we established a novel eight-gene risk signature that could predict the progression and prognoses of BC patients.

19.
J Oncol ; 2021: 5554708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122545

RESUMO

Background: Lymph node status is important for treatment decision making in prostate cancer (PCa). We aimed to develop a genomic-clinicopathologic nomogram for the prediction of lymph node invasion (LNI) in PCa. Methods: Differentially expressed genes between LNI and non-LNI PCa samples were identified in the Cancer Genome Atlas database. Univariate Cox regression analysis and minimum redundancy maximum relevance were performed for gene selection. The synthetic minority oversampling technique (SMOTE) was conducted to balance the minority group (LNI group). Machine learning models were constructed in the training set and assessed in the validation set. Univariable logistic regression and multivariable logistic regression were applied to build a nomogram. Furthermore, the RNA-sequence data from our center were used to validate the expression levels of hub genes between five matched primary PCa and the corresponding LNI samples. Results: The 37-gene-based support vector machine (SVM) model had the optimal synthesized performance in the SMOTE-balanced training (area under the curve (AUC): 0.947) and validation (AUC: 0.901) sets. Incorporating the SVM-based risk score and the Gleason grade, the genomic-clinicopathologic nomogram demonstrated good prediction and calibration both in the SMOTE-balanced training (AUC: 0.946) and validation (AUC: 0.910) sets. The dysregulated expression of hub genes between PCa and LNI samples was also validated. Conclusion: The proposed nomogram combining the 37-gene-based SVM model with the Gleason grade had the potential to preoperatively predict LNI in PCa. Some of the hub genes should be prioritized for functional studies and mechanistic analyses.

20.
Front Cell Dev Biol ; 9: 657621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150755

RESUMO

Tendon injury commonly occurs during sports activity, which may cause interruption or rapid decline in athletic career. Tensile strength, as one aspect of tendon biomechanical properties, is the main parameter of tendon function. Tendon injury will induce an immune response and cause the loss of tensile strength. Regulation of mechanical forces during tendon healing also changes immune response to improve regeneration. Here, the effects of internal/external forces and immune response on tendon regeneration are reviewed. The interaction between immune response and internal/external forces during tendon regeneration is critically examined and compared, in relation to other tissues. In conclusion, it is essential to maintain a fine balance between internal/external forces and immune response, to optimize tendon functional regeneration.

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