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30 result(s) for "Hong, Baoan"
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Basement membrane-related MMP14 predicts poor prognosis and response to immunotherapy in bladder cancer
Background Basement membrane (BM) is an important component of the extracellular matrix, which plays an important role in the growth and metastasis of tumor cells. However, few biomarkers based on BM have been developed for prognostic assessment and prediction of immunotherapy in bladder cancer (BLCA). Methods In this study, we used the BLCA public database to explore the relationship between BM-related genes (BMRGs) and prognosis. A novel molecular typing of BLCA was performed using consensus clustering. LASSO regression was used to construct a signature based on BMRGs, and its relationship with prognosis was explored using survival analysis. The pivotal BMRGs were further analyzed to assess its clinical characteristics and immune landscape. Finally, immunohistochemistry was used to detect the expression of the hub gene in BLCA patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy in our hospital. Results We comprehensively analyzed the relationship between BMRGs and BLCA, and established a prognostic-related signature which was an independent influence on the prognostic prediction of BLCA. We further screened and validated the pivotal gene-MMP14 in public database. In addition, we found that MMP14 expression in muscle invasive bladder cancer (MIBC) was significantly higher and high MMP14 expression had a poorer response to ICI treatment in our cohort. Conclusions Our findings highlighted the satisfactory value of BMRGs and suggested that MMP14 may be a potential biomarker in predicting prognosis and response to immunotherapy in BLCA.
Low-renin primary aldosteronism predicts superior surgical outcomes compared to high-renin disease
Objective To study the prognostic difference of unilateral adrenalectomy in patients with Primary Aldosteronism (PA) with different renin levels. Methods The clinical data of 159 patients with PA who underwent unilateral adrenalectomy at Beijing Anzhen Hospital of Capital Medical University from August 2022 to January 2025 were retrospectively analyzed. The mean age of the 159 patients was 51.98 ± 10.61 years old, the body mass index was 26.10 ± 3.94 kg/m2, and the preoperative glomerular filtration rate was 88.53 ± 20.30 ml/(min*1.73m2), preoperative serum creatinine 81.83 ± 27.66 µmol/L. The expression of aldosterone synthase in adrenal specimens was detected postoperatively and staged according to the 2022 World Health Organization Consensus on Histopathology of PA. The 159 patients with PA were divided into low and high renin groups according to the lower limit of the reference range of renin level of 4.4 µIU/ml in our institution, respectively. Both clinical success and biochemical success including complete, partial and no success were assessed with reference to the 2016 Consensus on Prognostic Evaluation of PA Surgery Comparison. The prognosis of different aldosterone level groups was compared using non-parametric tests. Results There were 121 cases in the low renin group, of which 87 cases (71.90%) were completely successful clinically, 32 cases (26.45%) were partially successful, and 2 cases (1.65%) were no success; 102 cases (84.20%) were completely successful biochemically, 8 cases (6.61%) were partially successful, and 11 cases (9.09%) were no success. In the high renin group, there were 38 cases, of which 19 cases (50.00%) were completely successful clinically, 15 cases (39.47%) were partially successful, and 4 cases (10.53%) were no success; 26 cases (68.42%) were completely successful biochemically, 7 cases (18.42%) were partially successful, and 5 cases (13.16%) were no success. The clinical prognosis ( P  = 0.011) and biochemical prognosis ( P  = 0.045) of PA patients in the low renin group were significantly different from those in the high renin group. A total of 101 out of 159 PA patients underwent adjunctive aldosterone synthase testing of postoperative adrenal specimens. There were 44 cases of Aldosterone-Producing Adenomas (APA), 1 case of Aldosterone-Producing Nodule (APN), Aldosterone-Producing Micronodules (APM) 5, Multiple Aldosterone-Producing Nodules (MAPN) 1, Multiple Aldosterone-Producing Micronodules (MAPM) 9, Aldosterone Producing Diffuse Hyperplasia (APDH) 4, all-negative 3 and mixed 19 in low renin group; and in high renin group, there are 7 cases of APA, 1 case of APM, 1 case of MAPN, 4 cases of MAPM, APDH 1 case, and mixed 1 case. Conclusion The prognosis of PA patients in the low renin group who underwent unilateral adrenalectomy was better than that of PA patients in the high renin group.
TRIB3 Promotes the Proliferation and Invasion of Renal Cell Carcinoma Cells via Activating MAPK Signaling Pathway
Tribbles pseudokinase 3 (TRIB3) is a member of the mammalian pseudokinase tribbles family and is involved in multiple biological processes. However, the role of TRIB3 in renal cell carcinoma (RCC) remains unclear. In this study, we aimed to elucidate the biological functions of TRIB3 in RCC and explore its underlying mechanisms. TRIB3 expression and its correlation with clinicopathological features was evaluated in 123 patients with RCC. A series of cytological experiments were performed to clarify the biological functions of TRIB3, and potential molecular regulatory mechanisms were explored using transcriptome sequencing. TRIB3 expression was significantly elevated in RCC tissues compared to that in paracancerous tissues, and high expression of TRIB3 was correlated with both advanced tumor stage and unfavorable prognosis. TRIB3 knockdown markedly inhibited RCC cell proliferation, migration and invasion. Furthermore, overexpression of TRIB3 promoted RCC cell proliferation, migration, invasion and xenograft tumor growth. Notably, TRIB3 expression was modulated by hypoxia-inducible factor-1α (HIF-1α), which enhanced cell viability and invasiveness via targeting the MAPK signaling pathway. This study reveals the potential oncogenic role of TRIB3 in RCC pathogenesis and illustrates the mechanisms underlying TRIB3-mediated tumor progression, providing new insight into the development of TRIB3 as a tumor biomarker and therapeutic target.
Anticancer Drugs Associated With Tumor Lysis Syndrome: Insights From the US Food and Drug Administration Adverse Event Reporting System
•In total, 118 antineoplastic drugs were identified as being statistically associated with tumor lysis syndrome (TLS).•Chemotherapy anticancer drugs were the most common type of drugs associated with TLS.•Rasburicase, tagraxofusp, and pentostatin were identified as the anticancer drugs statistically most associated with TLS.•The clinical profile of TLS was reported in the US Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the third quarter of 2024. Tumor lysis syndrome (TLS) is a life-threatening metabolic emergency caused by rapid tumor cell breakdown, either spontaneously or after therapy, leading to electrolyte imbalances that can result in acute kidney injury, arrhythmias, seizures, and multiorgan failure. Despite its clinical importance, the relationship between anticancer drugs and TLS, particularly newer targeted therapies, remains poorly understood. We analyzed the US Food and Drug Administration (FDA) Adverse Events Reporting System database, a repository of adverse events associated with medical products, to identify TLS cases reported from the first quarter of 2004 to the third quarter of 2024. For signal detection, we used disproportionality analysis with 4 algorithms—reported odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean. These algorithms assessed statistical correlations between anticancer drugs and TLS, based on a 2 × 2 contingency table framework. From the first quarter of 2004 to the third quarter of 2024, a total of 7340 TLS cases were documented in the FDA Adverse Events Reporting System database. Clinical characteristics, including age, sex, and outcomes, were analyzed. Among all reported TLS cases, 53.0% were men, and the mean age across all individuals was 56.9 ± 21.5 years. The incidence of TLS peaked in 2022, with a 42% increase from 2016 to 2017. A total of 118 antineoplastic drugs were identified as highly associated with TLS, of which only 18 had FDA-labeled TLS-related adverse reactions. Chemotherapy drugs were the most frequently associated with TLS. Venetoclax emerged as the top drug associated with TLS, comprising 10.72% of all TLS reports. Our findings highlight critical drug-induced TLS associations, particularly with emerging targeted therapies such as venetoclax. The study underscores the need for clinicians to monitor TLS closely in patients receiving certain anticancer treatments and to refine therapeutic strategies to mitigate TLS risk, ensuring safer cancer care outcomes. Further longitudinal studies are warranted to validate these findings and enhance pharmacovigilance efforts.
Frequent gene mutations and the correlations with clinicopathological features in clear cell renal cell carcinoma: preliminary study based on Chinese population and TCGA database
Background Large-scale sequencing plays important roles in revealing the genomic map of ccRCC and predicting prognosis and therapeutic response to targeted drugs. However, the relevant clinical data is still sparse in Chinese population. Methods Fresh tumor specimens were collected from 66 Chinese ccRCC patients, then the genomic RNAs were subjected to whole transcriptome sequencing (WTS). We comprehensively analyzed the frequently mutated genes from our hospital’s cohort as well as TCGA-KIRC cohort. Results VHL gene is the most frequently mutated gene in ccRCC. In our cohort, BAP1 and PTEN are significantly associated with a higher tumor grade and DNM2 is significantly associated with a lower tumor grade. The mutant type (MT) groups of BAP1 or PTEN, BAP1 or SETD2, BAP1 or TP53, BAP1 or MTOR, BAP1 or FAT1 and BAP1 or AR had a significantly correlation with higher tumor grade in our cohort. Moreover, we identified HMCN1 was a hub mutant gene which was closely related to worse prognosis and may enhance anti-tumor immune responses. Conclusions In this preliminary research, we comprehensively analyzed the frequently mutated genes in the Chinese population and TCGA database, which may bring new insights to the diagnosis and medical treatment of ccRCC.
Construction of a 12-Gene Prognostic Risk Model and Tumor Immune Microenvironment Analysis Based on the Clear Cell Renal Cell Carcinoma Model
Objectives Accurate survival predictions and early interventional therapy are crucial for people with clear cell renal cell carcinoma (ccRCC). Methods In this retrospective study, we identified differentially expressed immune-related (DE-IRGs) and oncogenic (DE-OGs) genes from The Cancer Genome Atlas (TCGA) dataset to construct a prognostic risk model using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. We compared the immunogenomic characterization between the high- and low-risk patients in the TCGA and the PUCH cohort, including the immune cell infiltration level, immune score, immune checkpoint, and T-effector cell- and interferon (IFN)-γ-related gene expression. Results A prognostic risk model was constructed based on 9 DE-IRGs and 3 DE-OGs and validated in the training and testing TCGA datasets. The high-risk group exhibited significantly poor overall survival compared with the low-risk group in the training (P < 0.0001), testing (P = 0.016), and total (P < 0.0001) datasets. The prognostic risk model provided accurate predictive value for ccRCC prognosis in all datasets. Decision curve analysis revealed that the nomogram showed the best net benefit for the 1-, 3-, and 5-year risk predictions. Immunogenomic analyses of the TCGA and PUCH cohorts showed higher immune cell infiltration levels, immune scores, immune checkpoint, and T-effector cell- and IFN-γ-related cytotoxic gene expression in the high-risk group than in the low-risk group. Conclusion The 12-gene prognostic risk model can reliably predict overall survival outcomes and is strongly associated with the tumor immune microenvironment of ccRCC.
Establishment and evaluation of a patient-derived organoids-based xenograft model of primary aldosteronism using 18FAlF-NOTA-pentixather PET/CT: bridging preclinical and clinical imaging
Background Primary aldosteronism (PA) is a leading cause of secondary hypertension, but the lack of representative preclinical models hampers translational research and imaging evaluation. We aimed to establish a patient-derived organoids-based xenograft (PDOX) model of PA and to assess its imaging characteristics using [ 18 F]AlF-NOTA-pentixather PET/CT, with validation in clinical patients. Methods Adrenal tissues from patients with PA were used to generate adrenal organoids in vitro. After serial passaging, these organoids were implanted subcutaneously into immunodeficient mice to establish PA PDOX models. The xenografted mice were subjected to [ 18 F]AlF-NOTA-pentixather PET/CT to evaluate tracer uptake and lesion detectability. In parallel, clinical PA patients underwent [ 18 F]AlF-NOTA-pentixather PET/CT to assess the imaging performance in a clinical setting. Results The PDOX models successfully engrafted and proliferated in vivo, maintaining key pathological features of PA. [ 18 F]AlF-NOTA-pentixather PET/CT imaging in the PDOX models demonstrated high and specific tracer uptake in xenografted lesions, with strong concordance to histopathological findings. In clinical PA patients, [ 18 F]AlF-NOTA-pentixather PET/CT also showed excellent performance in localizing PA lesions and provided valuable diagnostic information. Conclusion We established a novel PDOX model of PA and demonstrated the effectiveness of [ 18 F]AlF-NOTA-pentixather PET/CT in both preclinical and clinical applications. This approach provides a robust translational platform for mechanistic studies and for advancing precision imaging and therapy in PA.
Evaluation of Anticancer Therapy‐Related Tumor Flare Reaction: Insights From Food and Drug Administration's Adverse Event Reporting System Dataset
Aim Tumor flare reaction (TFR) is characterized by an increase in tumor size during immunotherapy, often resembling disease progression. This study explores the relationship between anti‐tumor drugs and tumor flare reaction (TFR) through the FAERS database to assist clinicians in better patient management. Methods We analyzed the FAERS database to identify TFR cases reported from Q1 2004 to Q3 2024. For signal detection, we employed disproportionality analysis with four algorithms—reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). These algorithms assessed statistical correlations between anticancer drugs and TFR, based on a 2 × 2 contingency table framework. Results From Q1 2004 to Q3 2024, 566 TFR cases were recorded in the FAERS database. The incidence of TFR peaked in 2023, with the highest increase in cases from 2021 to 2022, at 4.9%. A total of 28 anticancer drugs were identified as strongly associated with TFR, of which only 4 are explicitly listed in the medication instructions as having TFR‐related adverse reactions. Lenalidomide was the most frequent drug causing TFR, accounting for 38% of all TFR reports. Conclusions Our findings highlight the key associations between treatment drugs and TFR, particularly targeted therapies such as Rituximab, which are not explicitly marked for this side effect in the FAERS database. The study emphasizes the need for clinicians to closely monitor TFR in patients receiving certain cancer treatments and improve therapeutic strategies to mitigate TFR risks, ensuring safer cancer treatment outcomes.
Cardiovascular Safety Landscape of ADT in Prostate Cancer Treatment Based on Real‐World Analysis
Background Prostate cancer is among the most prevalent malignancies worldwide, and cardiovascular disease (CVD) is a major non‐cancer cause of death in affected patients. Androgen deprivation therapy (ADT), a mainstay treatment, has raised concerns about cardiotoxicity, yet the CVD risks of individual ADT agents remain unclear. Objectives To assess cardiovascular adverse events (AEs) associated with specific ADT drugs using data from the U.S. FDA Adverse Event Reporting System (FAERS). Methods AE reports related to ADT drugs were extracted from FAERS (Q1 2004–Q3 2024). Disproportionality analyses—including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR)—were conducted to identify significant cardiovascular safety signals. Results Different ADT agents exhibited distinct cardiovascular AE profiles. Some drugs were linked to a broader range of CVD‐related AEs, while others had more limited associations. Conclusions ADT agents demonstrate heterogeneous cardiotoxicity profiles. These findings emphasize the need for individualized treatment strategies, particularly in patients with pre‐existing CVD risks, and may aid clinicians in balancing cancer control with cardiovascular safety.
Exploring the Potential Driver Gene Mutations That Promote Renal Cancer Cell Metastasis and Implantation Based on Circulating Tumor Cells Culture
Studies have shown that the circulating tumor cell (CTC) is a necessary condition for the invasion and distant metastasis of renal cell carcimona (RCC). However, few CTCs-related gene mutations have been developed which could promote the metastasis and implantation of RCC. The objective of this study is to explore the potential driver gene mutations that promote RCC metastasis and implantation based on CTCs culture. Fifteen patients with primary mRCC and three healthy subjects were included, and peripheral blood was obtained. After the preparation of synthetic biological scaffolds, peripheral blood CTCs were cultured. Successful cultured CTCs were applied to construct CTCs-derived xenograft (CDX) models, followed by DNA extraction, whole exome sequencing (WES) and bioinformatics analysis. Synthetic biological scaffolds were constructed based on previously applied techniques, and peripheral blood CTCs culture was successfully performed. We then constructed CDX models and performed WES, and explored the potential driver gene mutations that may promote RCC metastasis and implantation. Bioinformatics analysis showed that KAZN and POU6F2 may be closely related to the prognosis of RCC. We successfully performed the culture of peripheral blood CTCs and, on this basis we initially explored the potential driver mutations for the metastasis and implantation of RCC.