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1.
Crit Rev Oncol Hematol ; 196: 104316, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432444

ABSTRACT

To evaluate the efficacy, feasibility and safety of neoadjuvant therapy (NAT) for renal cell carcinoma with tumor thrombus (RCC-TT) in terms of response, perioperative and oncological outcomes, and compare the results between neoadjuvant and non-neoadjuvant groups. Overall, 29 single-arm studies and 5 cohort studies were included. Of the 204 patients undergoing NAT, 16.2% were level I, 35.3% level II, 24.0% level III and 18.6% level IV thrombus. Most of patients underwent preoperative targeted therapy, immunotherapy-based combination therapy was applied in 5.4% patients. The total reduction rate of thrombus level was 29.4%. NAT is associated with a shorter operative time, less blood loss (p<0.05 for both). Rate of complications and oncological outcomes were similar between two groups. Overall, 32.1% (34/106) ≥ grade 3 adverse events occurred in patients undergoing NAT. Neoadjuvant therapy is safe and feasible with acceptable perioperative outcomes in RCC-TT.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Thrombosis , Humans , Carcinoma, Renal Cell/drug therapy , Neoadjuvant Therapy , Kidney Neoplasms/drug therapy , Treatment Outcome , Vena Cava, Inferior/pathology , Vena Cava, Inferior/surgery , Retrospective Studies , Thrombosis/etiology
2.
Oncogene ; 43(20): 1534-1548, 2024 May.
Article in English | MEDLINE | ID: mdl-38548966

ABSTRACT

While Stimulator-of-interferon genes (STING) is an innate immune adapter cruicial for sensing cytosolic DNA and modulating immune microenvironment, its tumor-promoting role in tumor survival and immune evasion remains largely unknown. Here we reported that renal cancer cells are exceptionally dependent on STING for survival and evading immunosurveillance via suppressing ER stress-mediated pyroptosis. We found that STING is significantly amplified and upregulated in clear cell renal cell carcinoma (ccRCC), and its elevated expression is associated with worse clinical outcomes. Mechanically, STING depletion in RCC cells specifically triggers activation of the PERK/eIF2α/ATF4/CHOP pathway and activates cleavage of Caspase-8, thereby inducing GSDMD-mediated pyroptosis, which is independent of the innate immune pathway of STING. Moreover, animal study revealed that STING depletion promoted infiltration of CD4+ and CD8+ T cells, consequently boosting robust antitumor immunity via pyroptosis-induced inflammation. From the perspective of targeted therapy, we found that Compound SP23, a PROTAC STING degrader, demonstrated comparable efficacy to STING depletion both in vitro and in vivo for treatment of ccRCC. These findings collectively unveiled an unforeseen function of STING in regulating GSDMD-dependent pyroptosis, thus regulating immune response in RCC. Consequently, pharmacological degradation of STING by SP23 may become an attractive strategy for treatment of advanced RCC.


Subject(s)
Carcinoma, Renal Cell , Intracellular Signaling Peptides and Proteins , Kidney Neoplasms , Membrane Proteins , Phosphate-Binding Proteins , Pyroptosis , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Phosphate-Binding Proteins/metabolism , Phosphate-Binding Proteins/genetics , Humans , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/genetics , Animals , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Cell Line, Tumor , Activating Transcription Factor 4/metabolism , Activating Transcription Factor 4/genetics , Transcription Factor CHOP/metabolism , Transcription Factor CHOP/genetics , Signal Transduction , Gasdermins
3.
Exp Cell Res ; 437(1): 113977, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38373588

ABSTRACT

Serine metabolic reprogramming is known to be associated with oncogenesis and tumor development. The key metabolic enzyme PSAT1 has been identified as a potential prognostic marker for various cancers, but its role in ccRCC remains unkown. In this study, we investigated expression of PSAT1 in ccRCC using the TCGA database and clinical specimens. Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells. Inhibition of PSAT1 increased the sensitivity of drug-resistant tumors to sunitinib in vivo. Collectively, our investigation identifies PSAT1 as an independent prognostic biomarker for advanced ccRCC patients and as a prospective therapeutic target.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Drug Resistance , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Sunitinib , Up-Regulation/genetics
4.
Int Wound J ; 21(2): e14667, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38339793

ABSTRACT

Chronic wounds have been a major factor of serious harm to global public health. At present, it is known that almost all chronic wounds contain biofilms, which seriously hinder the healing process. Removal of biofilms can effectively promote the healing of chronic wounds. As the study of wound biofilms deepens, many new treatment methods have emerged, thus bringing revolutionary means for the treatment of chronic wound biofilm. This review summarizes various methods for the treatment of chronic wound biofilm worldwide to provide a theoretical summary and practical basis for the selection of suitable wound biofilm treatment methods in clinical practice.


Subject(s)
Wound Infection , Humans , Wound Infection/therapy , Wound Healing , Biofilms
5.
J Exp Clin Cancer Res ; 43(1): 2, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38163881

ABSTRACT

BACKGROUND: Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains a major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators in carcinogenesis and cancer progression. However, the role of circRNAs in mediating CDDP chemosensitivity has yet to be well elucidated in BCa. METHODS: CircSTX6 (hsa_circ_0007905) was identified by mining the public circRNA datasets and verified by Sanger sequencing, agarose gel electrophoresis, RNase R treatment and qRT-PCR assays. Then, function experiments were performed to evaluate the effects of circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), RNA stability assay, Fluorescence in situ hybridization (FISH) and Immunofluorescence (IF) were conducted to evaluate the interaction among circSTX6, miR-515-3p, PABPC1 and SUZ12. Animal experiments were performed to explore the function of circSTX6 in tumor metastasis and CDDP sensitivity. RESULTS: We identified that circSTX6 was significantly upregulated in clinical samples and cells of BCa. Functionally, circSTX6 promoted cell migration and invasion both in vitro and in vivo. Mechanistically, circSTX6 could act as a miR-515-3p sponge and abolish its effect on SUZ12. Moreover, circSTX6 was confirmed to increase the stability of SUZ12 mRNA by interacting with a mRNA stabilizer PABPC1 and subsequently promote the expression of SUZ12. Importantly, silencing of circSTX6 improved the chemosensitivity of CDDP-resistant bladder cancer cells to CDDP. Furthermore, in vivo analysis supported that knockdown of circSTX6 attenuated CDDP resistance in BCa tumors. CONCLUSION: These studies demonstrate that circSTX6 plays a pivotal role in BCa metastasis and chemoresistance, and has potential to serve as a therapeutic target for treatment of BCa.


Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Animals , Humans , Cisplatin/pharmacology , Cisplatin/therapeutic use , MicroRNAs/genetics , RNA, Circular/genetics , In Situ Hybridization, Fluorescence , Gene Expression Regulation, Neoplastic , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , RNA-Binding Proteins/genetics , RNA, Messenger , Cell Proliferation , Cell Line, Tumor , Eukaryotic Initiation Factor-4A/genetics , DEAD-box RNA Helicases/genetics
6.
Int J Surg ; 110(1): 4-10, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37830951

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a principal cause of mortality and adverse oncologic outcomes in patients with renal tumor and inferior vena cava tumor thrombus (RT-IVCTT). However, the preoperative thrombotic risk factors in these patients remain not fully characterized. OBJECTIVES: To identify preoperative thrombotic risk factors in patients with RT-IVCTT. PATIENTS/METHODS: Two hundred fifty-seven consecutive postsurgical patients with RT-IVCTT aged 18-86 years were enrolled between January 2008 and September 2022. Clinicopathological variables were retrospectively reviewed. A multivariate logistic regression model was performed. Preoperative hemoglobin, neutrophils, and serum albumin levels were analyzed as both continuous and categorical variables. RESULTS: VTE was identified in 63 patients (24.5%). On both continuously and categorically coded variables, advanced IVC thrombus (OR 3.2, 95% CI: 1.4-7.0; OR 2.7, 95% CI: 1.2-6.1), renal sinus fat invasion (OR 3.4, 95% CI: 1.6-7.0; OR 3.7, 95% CI: 1.8-7.7), IVC wall invasion (OR 3.6, 95% CI: 1.6-7.9; OR 4.3, 95% CI: 1.9-10.0), IVC blockage status of greater than 75% (OR 5.2, 95% CI: 1.7-15.8; OR 6.1, 95% CI: 1.9-19.7), and higher neutrophils (OR 1.3, 95% CI: 1.0-1.7; OR 2.4, 95% CI: 1.1-5.4) were significantly associated with increased VTE risk in patients with RT-IVCTT. Except hemoglobin, categorically coded serum albumin (OR 0.36, 95% CI: 0.17-0.75) was validated as an independent risk factor for VTE. CONCLUSIONS: This study provided an insight of risk factors contributing to preoperative VTE in patients with RT-IVCTT, which may be beneficial for optimizing strategies to manage VTE in clinical practice.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Venous Thromboembolism , Venous Thrombosis , Humans , Retrospective Studies , Venous Thromboembolism/etiology , Case-Control Studies , Vena Cava, Inferior/surgery , Kidney Neoplasms/complications , Kidney Neoplasms/surgery , Venous Thrombosis/etiology , Venous Thrombosis/surgery , Risk Factors , Serum Albumin , Hemoglobins
7.
Nat Commun ; 14(1): 704, 2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36759601

ABSTRACT

The large scale control over thousands of quantum emitters desired by quantum network technology is limited by the power consumption and cross-talk inherent in current microwave techniques. Here we propose a quantum repeater architecture based on densely-packed diamond color centers (CCs) in a programmable electrode array, with quantum gates driven by electric or strain fields. This 'field programmable spin array' (FPSA) enables high-speed spin control of individual CCs with low cross-talk and power dissipation. Integrated in a slow-light waveguide for efficient optical coupling, the FPSA serves as a quantum interface for optically-mediated entanglement. We evaluate the performance of the FPSA architecture in comparison to a routing-tree design and show an increased entanglement generation rate scaling into the thousand-qubit regime. Our results enable high fidelity control of dense quantum emitter arrays for scalable networking.

8.
Front Immunol ; 13: 982045, 2022.
Article in English | MEDLINE | ID: mdl-36353618

ABSTRACT

Background: RARRES1 is a tumor suppressor protein, and its expression is suppressed in various tumor cells. However, whether it participates in the immune response in kidney renal clear cell carcinoma (KIRC) is unknown, and the defined mechanism is not clear. Therefore, the mechanism of RARRES1 in KIRC is worthy of investigation. Methods: We analysed the expression and function of RARRES1 with The Cancer Genome Atlas (TCGA) database. The Kaplan-Meier curve was adopted to estimate survival. RARRES1-correlated genes were obtained from the UALCAN database and subjected to Gene Ontology (GO) enrichment and protein-protein interaction (PPI) network analyses. The correlation analysis between tumor-infiltrating immune cells and selected genes were performed with TIMER database. We also investigated the possible function of RARRES1 in KIRC by coculturing Caki-1 cells with THP-1 cells. Immunofluorescence assay was performed to study the RARRES1 expression in difference grade KIRC tissues. Results: The expression of RARRES1 was negatively correlated with survival in KIRC patients. The GO biological process term most significantly enriched with the RARRES1-correlated genes was regulation of cell adhesion. ICAM1, which exhibited a relatively highest correlation with RARRES1, is positively correlated with the infiltration level of macrophages. RARRES1 could enhance the expression of ICAM1 in Caki-1 cells and then induce the activation of M1 THP-1 cells to decrease the viability and induce the apoptosis of Caki-1 cells. Conclusion: RARRES1 plays an antitumor role by promoting ICAM1 expression and inducing the activation of M1 macrophages. We offer insights into the molecular mechanism of KIRC and reveal a potential therapeutic target.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Kidney Neoplasms/pathology , Prognosis , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Databases, Genetic , Carcinoma, Renal Cell/pathology , Macrophages/metabolism , Kidney/pathology , Membrane Proteins/genetics , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism
9.
Healthcare (Basel) ; 10(10)2022 Oct 18.
Article in English | MEDLINE | ID: mdl-36292516

ABSTRACT

We developed a workflow for the search and screening of natural products by drawing from worldwide experiences shared by online platform users, illustrated how to cope with COVID-19 with a text-mining approach, and statistically tested the natural product identified. We built a knowledge base, which consists of three ontologies pertaining to 7653 narratives. Mustard emerged from texting mining and knowledge engineering as an important candidate relating to COVID-19 outcomes. The findings indicate that, after controlling for the containment index, the net import of mustard is related with reduced total and new deaths of COVID-19 for the non-vaccination time period, with considerable effect size (>0.2).

10.
Front Endocrinol (Lausanne) ; 13: 876775, 2022.
Article in English | MEDLINE | ID: mdl-35757391

ABSTRACT

Backgrounds: A large number of studies have investigated the effect of early menopause on cardiovascular disease (CVD) outcomes and the relationship between the levels of lipid profile and primary ovarian insufficiency (POI). However, the results are inconsistent. The aim of this meta-analysis was to assess whether the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) changed in women with POI relative to healthy controls. Methods: To identify eligible studies, references published prior to December 2021 were searched in the PubMed, Embase, Cochrane Library and Web of Science databases. DerSimonian-Laird random-effects model was used to estimate the overall standard mean difference (SMD) between POI and healthy control subjects. Subgroup analysis and sensitivity analysis were preformed, and publication bias was assessed. Results: A total of 12 studies featuring 846 women with primary ovarian insufficiency and 959 healthy women were selected for analysis. The meta-analysis showed that the levels of TC (SMD: 0.60; 95% CI: 0.32 to 0.89; P<0.0001), TG (SMD: 0.36; 95% CI: 0.12 to 0.60; P=0.003), LDL (SMD: 0.46; 95% CI: 0.16 to 0.76; P=0.003) were significantly increased in women with POI. There was no significant change in the level of HDL (SMD: 0.25; 95% CI: -0.12 to 0.61; P=0.19). Subgroup analysis showed that the heterogeneity in this meta-analysis of the correlation between lipid profile and POI might come from by region, sample size, number of cases, mean body mass index (BMI) value of cases and mean age of cases. Conclusions: Scientific evidence suggests that the lipid profile levels were altered in patients with primary ovarian insufficiency compared to healthy controls. Therefore, we recommend that early medical intervention (e.g., hormone replacement therapy) to minimize the risk of CVD morbidity and mortality associated with dyslipidemia in patients with POI. Systematic Review Registration: PROSPERO, identifier CRD42021297088.


Subject(s)
Cardiovascular Diseases , Cardiovascular System , Primary Ovarian Insufficiency , Female , Humans , Triglycerides
11.
Int J Oncol ; 61(1)2022 Jul.
Article in English | MEDLINE | ID: mdl-35642672

ABSTRACT

Cell division cycle­associated 5 (CDCA5) protein, which is involved in cohesion, contributes to cell cycle regulation and chromosome segregation by maintaining genomic stability. Accumulating evidence indicates that CDCA5 expression is upregulated in a number of types of cancer associated with a poor prognosis. However, the biological function of CDCA5 in clear cell renal cell carcinoma (ccRCC) remains largely unknown. In the present study, The Cancer Genome Atlas data mining revealed that CDCA5 was more highly expressed in ccRCC than in adjacent normal tissues. Importantly, such a high expression was associated with a higher risk of distant metastasis and poorer clinical outcomes. Moreover, the clinical and prognostic value of CDCA5 expression was further investigated using immunohistochemistry on tissue microarrays containing paired tumor tissues and adjacent normal tissues from 137 patients with ccRCC. Functional analyses revealed that CDCA5 knockdown significantly inhibited the proliferation and migration of ccRCC cells, and suppressed the growth of xenografts in nude mice. Mechanistically, CDCA5 knockdown induced severe DNA damage with the persistent accumulation of γ­H2A histone family member X foci, resulting in G2/M cell cycle arrest and finally, in chromosomal instability and apoptosis. CDCA5 knockdown significantly decreased the phosphorylation levels of Stat3 and NF­κB, suggesting that CDCA5 plays a role in regulating the inflammatory response. Collectively, the findings of the present study indicate that ccRCC cells require CDCA5 for malignant progression, and that CDCA5 inhibition may enhance the outcomes of patients with high­risk ccRCC.


Subject(s)
Adaptor Proteins, Signal Transducing , Carcinoma, Renal Cell , Cell Cycle Proteins , DNA Damage , Kidney Neoplasms , Adaptor Proteins, Signal Transducing/genetics , Animals , Apoptosis/genetics , Carcinoma, Renal Cell/pathology , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cell Proliferation/genetics , G2 Phase Cell Cycle Checkpoints , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/pathology , Mice , Mice, Nude
12.
Natl Sci Rev ; 9(5): nwab122, 2022 May.
Article in English | MEDLINE | ID: mdl-35668749

ABSTRACT

Spin defects in silicon carbide (SiC) with mature wafer-scale fabrication and micro/nano-processing technologies have recently drawn considerable attention. Although room-temperature single-spin manipulation of colour centres in SiC has been demonstrated, the typically detected contrast is less than 2[Formula: see text], and the photon count rate is also low. Here, we present the coherent manipulation of single divacancy spins in 4H-SiC with a high readout contrast ([Formula: see text]) and a high photon count rate (150 kilo counts per second) under ambient conditions, which are competitive with the nitrogen-vacancy centres in diamond. Coupling between a single defect spin and a nearby nuclear spin is also observed. We further provide a theoretical explanation for the high readout contrast by analysing the defect levels and decay paths. Since the high readout contrast is of utmost importance in many applications of quantum technologies, this work might open a new territory for SiC-based quantum devices with many advanced properties of the host material.

13.
Lab Invest ; 102(9): 1011-1022, 2022 09.
Article in English | MEDLINE | ID: mdl-35585131

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors and is characterized by a poor prognosis. Although G2- and S -phase expressed-1 (GTSE1) is known to be involved in the progression and metastasis of various cancers, its significance and mechanism in ccRCC remain unknown. In the present study, we found that GTSE1 was overexpressed in ccRCC tissues, especially in metastatic samples. Moreover, high GTSE1 expression was positively correlated with higher pT stage, tumor size, clinical stage, and WHO/ISUP grade and worse prognosis. And GTSE1 expression served as an independent prognostic factor for overall survival (OS). In addition, GTSE1 knockdown inhibited ccRCC cell proliferation, migration, and invasion, and enhanced cell apoptosis in vitro and in vivo. GTSE1 was crucial for epithelial-mesenchymal transition (EMT) in ccRCC. Mechanistically, GTSE1 depletion could upregulate the expression of Krüppel-like factor 4 (KLF4), which acts as a tumor suppressor in ccRCC. Downregulation of KLF4 effectively rescued the inhibitory effect induced by GTSE1 knockdown and reversed the EMT process. Overall, our results revealed that GTSE1 served as an oncogene regulating EMT through KLF4 in ccRCC, and that GTSE1 could also serve as a novel prognostic biomarker and may represent a promising therapeutic target for ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Kruppel-Like Factor 4 , Microtubule-Associated Proteins , Neoplastic Processes , Prognosis
14.
Oncoimmunology ; 11(1): 2011673, 2022.
Article in English | MEDLINE | ID: mdl-35024247

ABSTRACT

Recent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly understood. Here, we show that CMTM6 is upregulated in ccRCC tissues and is strongly associated with advanced tumor grades, early metastases, and a worse prognosis. CMTM6 depletion significantly impaired the proliferation, migration, and invasion of ccRCC cells in vitro and in xenograft mouse models in vivo. In addition, targeting CMTM6 promotes anti-tumor immunity, represented by increased infiltration of CD4+ and CD8+ T cells in syngeneic graft mouse models. Further research revealed that loss of CMTM6 triggered aberrant activation of DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, finally leading to cellular senescence with robust upregulation of numerous chemokines and cytokines. Our findings show for the first time the novel role of CMTM6 in maintaining cancer genome stability and facilitating tumor-mediated immunosuppression, linking DNA damage signaling to the secretion of inflammatory factors. Targeting CMTM6 may improve the treatment of patients with advanced ccRCC.


Subject(s)
CD8-Positive T-Lymphocytes , MARVEL Domain-Containing Proteins , Animals , Cellular Senescence/genetics , DNA Damage/genetics , Humans , MARVEL Domain-Containing Proteins/genetics , Mice , Myelin Proteins/genetics
15.
Front Oncol ; 11: 756843, 2021.
Article in English | MEDLINE | ID: mdl-34956878

ABSTRACT

Clear cell renal cell carcinoma (ccRCC), which is the most prevalent renal cell carcinoma subtype, has a poor prognosis. Emerging strategies for enhancing the immune response in ccRCC therapy are currently being investigated. Fibrinogen-like Protein 1(FGL1) is a novel mechanism that tumors may use to evade the immune system by binding LAG-3 and negatively regulating T cells. In this study, we aimed at investigating the underlying mechanism of FGL1 in ccRCC, and its expression and prognostic value. We found that FGL1 was upregulated in tumor tissues and plasma specimens of ccRCC patients. High FGL1 expression predicted a poor prognosis for ccRCC patients. We also discovered that overexpression of FGL1 enhances RCC cell migration, invasion, and metastasis by activating the epithelial-to-mesenchymal transition (EMT). Consistent with these results, we identified a significant positive correlation between expression of FGL1 and EMT-related genes through tissue microarray analysis. Gene-expression analysis revealed that FGL1-deficient ccRCC cell lines had altered transcriptional output in inflammatory response, cell-cell signaling, negative regulation of T cell activation, and intracellular signal transduction. Depletion of FGL1 significantly inhibited tumor growth and lung metastasis in orthotopic xenograft mouse model. Infiltration of myeloid-derived CD11b+ and Ly6G+ immune cells in tumor microenvironment (TME) was strikingly decreased when FGL1 expression reduced. Therefore, increased FGL1 expression in ccRCC is positively correlated with poor prognosis. Mechanistically, FGL1 facilitates the EMT process and modulates TME, which promotes ccRCC progression and metastasis. Consequently, targeting FGL1 can potentially improve clinical outcome of ccRCC patients.

16.
Cancer Lett ; 514: 48-62, 2021 08 28.
Article in English | MEDLINE | ID: mdl-34019961

ABSTRACT

Enhanced synthesis or uptake of lipids contributes to rapid cancer cell proliferation and tumor progression. In recent years, cell cycle regulators have been shown to be involved in the control of lipid synthesis, in addition to their classical function of controlling the cell cycle. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is characterized by lipid-rich cytoplasmic deposition. However, the relationship between altered lipid metabolism and tumor progression in ccRCC is poorly understood. Here, we demonstrated that E2F transcription factor 1 (E2F1), in addition to its key role in regulating the cell cycle, induces extensive lipid accumulation and elevated levels of lipogenic enzymes in ccRCC cells by upregulating sterol regulatory element-binding protein 1 (SREBP1). E2F1 knockdown or SREBP1 suppression attenuated fatty acid (FA) de novo synthesis, cell proliferation and epithelial-mesenchymal transition (EMT) in ccRCC cells. Furthermore, overexpression of E2F1 promoted lipid storage, tumor growth and metastasis in a mouse xenograft model, whereas E2F1 downregulation or SREBP1 inhibition reversed these effects. In ccRCC patients, high levels of E2F1 and SREBP1 were associated with increased lipid accumulation and correlated with poor prognosis. Our results demonstrate that E2F1 can increase proliferation and metastasis through SREBP1-induced aberrant lipid metabolism, which is a novel critical signaling mechanism driving human ccRCC progression.


Subject(s)
Carcinoma, Renal Cell/genetics , Cell Proliferation/genetics , E2F1 Transcription Factor/genetics , Fatty Acids/biosynthesis , Kidney Neoplasms/genetics , Sterol Regulatory Element Binding Protein 1/genetics , Animals , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Down-Regulation/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Kidney Neoplasms/pathology , Lipid Metabolism/genetics , Lipogenesis/genetics , Mice , Mice, Nude , Signal Transduction/genetics
17.
Urol Oncol ; 39(5): 302.e1-302.e7, 2021 05.
Article in English | MEDLINE | ID: mdl-33678501

ABSTRACT

OBJECTIVES: To assess the impact of the presence of bland thrombus (BT) on prognosis of patients treated with resection of renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVCTT). MATERIALS AND METHODS: The medical records of a total of 145 consecutive postsurgical RCC patients with level I-IV IVCTT were reviewed from January 2008 to August 2018. Associations of BT with clinicopathological variables were estimated by chi-square test or Student's t-test. Kaplan-Meier method and multivariate Cox proportional hazard model were used. The eighth TNM staging system, "Spiess PE" model, University of California at Los Angeles Integrated Staging System and Stage, Size, Grade, and Necrosis (SSIGN) score were selected to assess whether BT could improve their predictive abilities. RESULTS: BT was observed in 34 (23.4%) patients and was significantly associated with increased levels of IVCTT (P = 0.004) and invasion of IVC wall (P = 0.030). Multivariable Cox analyses revealed that tumor grade, T stage, M stage, tumor thrombus consistency and BT were independent risk factors for both progression-free survival and overall survival. The concordance indexes ranged from a low of 0.652 in TNM to a high of 0.731 in SSIGN, and integrating BT into each base model led to an increased predictive accuracies of 6.2% for TNM (P = 0.025), 4.0% for "Spiess PE" model (P = 0.069), 2.1% for University of California at Los Angeles Integrated Staging System (P = 0.149) and 1.2% for SSIGN (P = 0.290), respectively. CONCLUSIONS: Presence of BT was independently associated with survival in postsurgical patients with RCC-IVCTT. Routine consideration of BT as an adjunct to TNM staging system may be suggested.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Neoplastic Cells, Circulating , Vena Cava, Inferior , Adult , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Female , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Neoplastic Cells, Circulating/pathology , Prognosis , Retrospective Studies , Survival Rate
18.
Surg Oncol ; 33: 32-37, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32561096

ABSTRACT

BACKGROUND: In clinical practice, objective basis for the choice between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) is scarce. To evaluate surgical outcomes, assess the individual benefit from LPN to RAPN, which can guide clinical decision-making. METHODS: Patients underwent LPN or RAPN for a localized renal mass in our center between Jan 2013 and Dec 2016 were included. The surgical outcome of LPN and RAPN was the pentafecta achievement. A multivariable model was fitted to predict the probability of pentafecta achievement after LPN. Model-derived coefficients were applied to calculate the probability of pentafecta achievement in case of LPN among patients treated with RAPN. Locally weighted scatterplot smoothing method was applied to plot the observed probability of pentafecta achievement against the predicted pentafecta probability in case of LPN. RESULTS: RAPN group had a significantly higher pentafecta achievement (54.6% vs. 41.1%, P < 0.001) than LPN. Multivariable analyses identified that tumor size, distance of the tumor to collecting system or sinus, and preoperative eGFR were independent predictors of pentafecta after LPN. When RAPN was chosen over LPN, the increase in the probability of pentafecta achievement was greatest in intermediate-probability patients. With the increase or decrease of the probability of pentafecta, the benefit of RAPN decreased. CONCLUSION: When pentafecta achievement are assessed, the benefit of RAPN over LPN varies from patient to patient. Patients at intermediate-probability of pentafecta achievement after LPN benefit the most from robotic surgery, which may be the potential ideal candidates for RAPN.


Subject(s)
Clinical Decision Rules , Kidney Neoplasms/surgery , Laparoscopy/methods , Nephrectomy/methods , Robotic Surgical Procedures/methods , Adult , Clinical Decision-Making , Cold Ischemia/statistics & numerical data , Female , Glomerular Filtration Rate , Humans , Logistic Models , Male , Margins of Excision , Middle Aged , Multivariate Analysis , Postoperative Complications/epidemiology , Renal Insufficiency, Chronic/metabolism , Treatment Outcome , Warm Ischemia/statistics & numerical data
19.
Sensors (Basel) ; 20(11)2020 Jun 08.
Article in English | MEDLINE | ID: mdl-32521762

ABSTRACT

With the development of technology, the network structure has changed a lot. Many people regard the Internet of Things as the next-generation network structure, which means all the embedded devices can communicate with each other directly. However, some problems remain in IoT before it can be applied in a large scale. Blockchain, which has become a hot research topic in recent years, may be one of the solutions. However, currently, the transaction speed of blockchain is still a disadvantage compared to traditional transaction methods. This paper focuses on to implement a high-performance blockchain platform. After investigation of the current blockchain consensus algorithm and blockchain architecture, we propose: (1) an improved blockchain consensus algorithm, which is implemented based on the mortgage model instead of probability model; (2) a cross-chain protocol with transverse expansion capacity, which would support the message transmission among chains; (3) a high-performance cross-chain blockchain network structure, which could handle more than 1000 transactions per second per chain by verification. Experiments have been carried out, and shown that the cross-chain blockchain network structure we provided is feasible to meet the requirement of large-scale distributed IoT applications.

20.
Sensors (Basel) ; 20(8)2020 Apr 23.
Article in English | MEDLINE | ID: mdl-32340292

ABSTRACT

Digital image projection (DIP) with traditional vertical calibration cannot be used for measuring the water droplets/film on a curved surface, because significant systematic error will be introduced. An improved DIP technique with normal calibration is proposed in the present paper, including the principles, operation procedures and analysis of systematic errors, which was successfully applied to measuring the water droplets/film on a curved surface. By comparing the results of laser profiler, traditional DIP, improved DIP and theoretical analysis, advantages of the present improved DIP technique are highlighted.

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