Advanced Composites and Hybrid Materials
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2024
·Vol. 8
·期 1
·1-19
·
IF 23.2
Ye Fangdie,Ye Chen,Zhao Yufeng,Li Weijian,Zhang Jinhao,Ou Yuxi,Chen Ziang,Cheng Zhang,Zhang Jing,Ali Shujaat,Qureshi Omer Salman,Liu Yufei,Dai Xiangpeng,Huang Hang,Jiang Haowen
Bladder cancer (BLCA), particularly due to the high recurrence and progression rates of non-muscle-invasive bladder cancer (NMIBC), is a significant global health challenge. Current treatments, such as Bacillus Calmette-Guérin (BCG) immunotherapy and intravesical chemotherapy, often cause substantial side effects and exhibit limited efficacy, highlighting the urgent need for novel therapeutic strategies. Single-cell spatial transcriptomic advancements have identified cuproptosis as a critical pathway in BLCA, presenting a promising target for treatment. In this study, these insights were leveraged to design Cu-VT nanoparticles (NPs), an innovative composite material that combines the unique properties of copper ions and the natural flavonoid vitexin, to induce cuproptosis. Cu-VT NPs could effectively induce apoptosis and oxidative stress in BLCA cells concurrently modulating the immune response within the tumor microenvironment. Comprehensive in vitro and in vivo experiments demonstrated that Cu-VT NPs significantly inhibited tumor growth and reduced lung metastasis through cuproptosis induction. This dual-function composite material enhances therapeutic efficacy and minimizes side effects, showcasing its potential as a revolutionary treatment for BLCA. Our findings highlight the transformative potential of Cu-VT NPs in the context of BLCA treatment, establishing a new paradigm in the use of composite materials for the treatment of advanced cancer.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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免疫学
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产品关联
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Tianmin Tang,Shuying Kong,Junyi Xie,Qiurong Deng,Cong Lai,Shuanshuan Guo,Hao Yu,Jianhua Zhou
Intravesical Bacillus Calmette–Guérin (BCG) immunotherapy is a standard treatment for intermediate-risk and high-risk nonmuscle-invasive bladder cancer. The prolonged duration of BCG in the bladder can enhance the immunotherapeutic efficacy. However, intravesical BCG is rapidly excreted with urine by urination at 2 h postinstillation, compromising therapeutic outcomes. Here, this study develops a floating drug delivery system based on air microbubbles to achieve long-term retention of BCG in the bladder. By encapsulating BCG within floating air microbubbles, we successfully develop BCG-loaded microbubbles (BCG-MBs) that are capable of prolonged release of BCG in the bladder. Compared with conventional intravesical BCG immunotherapy, intravesical instillation of BCG-MBs induces more durable immune responses and demonstrates enhanced therapeutic efficacy in SD rats with orthotopic bladder cancer. Furthermore, the floating drug delivery system based on air-microbubbles not only represents a potential intravesical drug carrier for bladder cancer, but also a versatile platform that can encapsulate diverse therapeutic agents, thereby showing great potential applications in immunotherapy, targeted drug delivery, and combination therapy.
研究领域:
免疫治疗
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药物递送
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泌尿学
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Cancer Communications
·
2025
·
IF 24.9
Jie Zhang,Chen Zhang,Ruichen Zang,Weiwu Chen,Yining Guo,Haofei Jiang,Jing Le,Kunyu Wang,Haobo Fan,Xudong Wang,Sisi Mo,Peng Gao,Wenhao Guo,Xinrong Jiang,Fengbin Gao,Junming Jiang,Juyan Zheng,Yuxing Chen,Yicheng Chen,Yanlan Yu,Guoqing Ding
Background: Only a few bladder cancer patients benefit from anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy. The cluster of differentiation 47 (CD47) plays an important role in tumor immune evasion. CD47 is a highly glycosylated protein, however, the mechanisms governing CD47 glycosylation and its potential role in immunosuppression are unclear. Therefore, this study aimed to evaluate the function of CD47 glycosylation in bladder cancer. Methods: Western blotting, immunohistochemistry, and flow cytometry were used to measure protein expression, protein-protein interactions, and phagocytosis in bladder cancer. A murine model was employed to investigate the impact of mannosidase alpha class 1B member 1 (MAN1B1) modification of CD47 on anti-phagocytosis in vivo. An ex vivo model, patient-derived tumor-like cell clusters, was used to examine the effect of targeting MAN1B1 on phagocytosis. Results: Our research identified that aberrant CD47 glycosylation was responsible for its immunosuppression. The glycosyltransferase MAN1B1 responsible for CD47 glycosylation was highly expressed in bladder cancer. Abnormal activation of extracellular signal-regulated kinase (ERK) was significantly associated with MAN1B1 stability by regulating the interaction between MAN1B1 and the E3 ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1). Mechanistically, abnormally activated ERK stabilized MAN1B1, resulting in the glycosylation of CD47 and facilitating immune evasion by enhancing its interaction with signal-regulatory protein alpha (SIRP-α). In vitro and in vivo experiments demonstrated that MAN1B1 knockout weakened CD47-mediated anti-phagocytosis. MAN1B1 inhibitors promoted phagocytosis without causing anemia, offering a safe alternative to anti-CD47 therapy. Conclusions: This comprehensive analysis uncovered that ERK activation stabilizes MAN1B1 by regulating the interaction between MAN1B1 and HRD1, facilitates immune evasion via CD47 glycosylation, and presents new potential targets and strategies for cancer immunotherapy that do not cause anemia.
研究领域:
肿瘤学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ONCOGENE
·
2025
·
IF 7.3
Wei Xiaosong,Wang Beibei,Yang Yang,Fang Zhiwei,Yi Chengzhi,Zhang Liuhui,Fan Xin,Tang Dongdong,Zhang Lirong,Yang Xiaoming,Song Dongkui
Zinc finger protein 24 (ZNF24) is a conserved multifunctional transcription factor associated with tumorigenesis, but its function in bladder carcinogenesis remains unclear. Herein, the expression of ZNF24 was decreased in bladder cancer (BC) cells and tissues, and patients with higher expression of ZNF24 had a better prognosis. Doxycycline-induced overexpression and knockdown of ZNF24 identified its anti-proliferative and anti-metastasis role in BC in vitro and in vivo. The potential genes for the anti-cancer role of ZNF24, involving transcriptional regulation of several factors, such as dual-specificity phosphatase 1 and squalene epoxidase. E2 conjugating enzyme UBC9 and small ubiquitin-like modifier (SUMO) 1 were found to interact with ZNF24, suggesting that ZNF24 may be SUMOylated. Consistent with the expression, ZNF24 SUMOylation levels were decreased in BC cells and tissues. Pan-SUMOylation inhibition promoted protein degradation of ZNF24. UBC9 SUMOylated ZNF24 at Lys-27 (K27) site with SUMO1 modification and the K27 mutation of ZNF24 greatly damaged the protein stability of ZNF24. Cullin 3 (CUL3), a E3 ubiquitin ligase, was responsible for the degradation of ZNF24. ZNF24 SUMOylation prevented CUL3-mediated protein degradation of ZNF24. Overall, the crosstalk between the SUMOylation and ubiquitination of ZNF24 may be a novel regulatory mechanism to block tumorigenesis and development of BC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2024
·
IF 2.7
Zhiren Zhou,Yuting Tian,Lina Zou,Yanan Liu,Xueqing Zhang,Xiaojing Huang,Huanyu Ren,Zheng Li,Huiru Niu,Hao Liao,Xiaojing Zhang,Hongzhi Pan,Shengzhong Rong,Hongkun Ma
Nuclear matrix protein 22 (NMP22) is one of the most important tumor markers of bladder cancer and is significantly elevated in the urine of bladder cancer patients. Therefore, in this work, a highly sensitive ratiometric electrochemical immunosensor was constructed to detect NMP22 based on ZIF-8@MWCNTs@Chit@Fc@AuNPs composites. ZIF-8 had a large surface area and good adsorption ability. Multi-Walled Carbon Nanotubes (MWCNTs) can optimize the electrical conductivity of ZIF-8, so that the electrode surface of ferrocene (Fc) obtains a stable and strong electrochemical signal. In addition, AuPt-MB provided another strong detection signal methylene blue (MB) while immobilizing the secondary antibody (Ab2) through Au–N and Pt–N bonds. A ratiometric electrochemical sensor was formed based on ZIF-8@MWCNTs@Chit@Fc@AuNPs and AuPt-MB, which showed a great linear connection between IMB/IFc and the logarithmic concentration of NMP22 with a detection limit of 3.33 fg mL−1 (S/N = 3) under optimized specifications in the concentration interval of 0.01 pg mL−1 to 1000 ng mL−1. In addition, the ratiometric immunosensor showed good selectivity and stability.
研究领域:
生物医学工程
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肿瘤学
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分析化学
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产品关联
DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2025
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IF 1.7
Qiu Yu,Ruan Huijie,Ji Decai,Cao Na
Bladder cancer is a common malignancy in the genitourinary system with its incidence rate among the world's highest. Neuralized E3 ubiquitin protein ligase 1 (NEURL1) belongs to the RING E3 ubiquitin ligase family, and its role in bladder cancer has not been reported yet. We aimed to explore the expression and roles of NEURL1 in bladder cancer. The NEURL1 expression was determined in clinical samples of bladder cancer. We stably overexpressed NEURL1 and NEURL1 with the RING domain deletion in human bladder cancer cell lines 5637 and RT-112 to investigate its functions. NEURL1 was confirmed to be significantly down-regulated in clinical bladder tumor specimens. NEURL1 overexpression significantly inhibited the growth, colony formation, and Ki-67 protein expression in both bladder cancer cells. The overexpression of NEURL1 also increased the apoptosis rate and cleaved caspase-3 protein expression in 5637 and RT-112 cells. As expected, the RING-deleted NEURL1 had no such effect. Moreover, NEURL1 overexpression facilitated the apoptosis of 5637/RT-112 cells under cisplatin conditions. NEURL1 promotes ubiquitination and proteasomal degradation of PDE9A. PDE9A protein expression was notably increased in bladder tumors from clinical specimens. Overexpressed NEURL1 inhibited PDE9A protein expression in both cell lines, whereas NEURL1 with the RING domain deletion did not. The addition of proteasome inhibitors MG-132 reversed the decrease in PDE9A expression by NEURL1 overexpression. Cell viability was inhibited and apoptosis was increased in the 5637 and RT-112 cells with stable knockdown of PDE9A. NEURL1 may be involved in the bladder cancer progression by increasing apoptosis, thereby leading to tumor cell growth inhibition.
研究领域:
肿瘤学
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分子生物学
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泌尿外科
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产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-21
·
IF 5.1
Liu Zhenghua,Xin Peng,Wu Weiwei,Jin Mingyue,Du Yang,Jiang Yuanjun,Liu Tao,Zhang Hao
Metastatic bladder cancer is characterized by its aggressive behavior and complex molecular mechanisms that remain largely undefined. This study explores the therapeutic potential of targeting peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) using liposomal nanoparticles to deliver PGC-1α siRNA to bladder cancer cells. We employed comprehensive transcriptomic, proteomic, and metabolomic analyses to investigate the impact of PGC-1α silencing. Our in vitro results demonstrate that targeting PGC-1α significantly impairs mitochondrial function and disrupts energy metabolism, affecting critical pathways such as glycolysis and the citric acid cycle, as well as altering mRNA nuclear export. In vivo experiments in animal models show that nanoparticles loaded with si-PGC-1α effectively reduce lung metastasis, indicating a significant impact on metastatic progression. These findings highlight PGC-1α as a key regulator of metabolic reprogramming in metastatic bladder cancer and suggest that its inhibition could serve as a promising therapeutic strategy. By elucidating the role of PGC-1α in cancer metabolism, this study provides new insights into the molecular underpinnings of bladder cancer metastasis and offers potential avenues for developing targeted therapies aimed at the metabolic vulnerabilities of this malignancy.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2018
·Vol. 22
·期 5
·2774-2790
·
IF 4.302
Qiongli Su,Ting Tao,Lei Tang,Jun Deng,Kwame Oteng Darko,Sichun Zhou,Mei Peng,Shanping He,Qing Zeng,Alex F. Chen,Xiaoping Yang
Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non-muscle-invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down-regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p-AMPK and p-STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan-Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder cancer cells and tissues, and down-regulation of PKM2 enhanced the sensitivity of THP in vitro. Activation of AMPK is essential for THP to exert anti-bladder cancer activities. On the other hand, down-regulating PKM2 activates AMPK and inhibits STAT3, correlated with THP sensitivity. Compared with THP alone (400 μmol L −1 , 50 μL), the combination with metformin (60 mmol L −1 , 50 μL) stopped growth of bladder cancer completely in vivo (combination group VS normal group P = .078). Down-regulating the expression of PKM2 enhances the anticancer efficiency of THP. This study provides a new insight for improving the chemotherapeutic effect of THP.
研究领域:
肿瘤学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2019
·
IF 6.944
Yingqian Wang,Zhihao Li,Qiaosong Lin,Yurong Wei,Jie Wang,Yingxue Li,Ronghua Yang,Quan Yuan
Detection of biomarkers in complex samples is a significant health plan strategy for medical diagnosis, therapy monitoring, and health management. However, high background noise resulting from impurities and other analytes in complex samples has hampered the improvement of detection sensitivity and accuracy. Herein, an ultralow background biochip based on time-gated luminescent probes supported by photonic crystals (PCs) was successfully developed for detection of bladder cancer (BC)-related miRNA biomarkers with high sensitivity and specificity in urine samples. Coupled with the time-gated luminescence of long-lifetime luminescence probes and the luminescence-enhanced capability of PCs, the short-lived autofluorescence can be efficiently removed; thus, the detection sensitivity will be significantly improved. Benefiting from these merits, a detection limit of 26.3 fM is achieved. Furthermore, the biochip exhibits excellent performance in urinary miRNA detection, and good recoveries are also obtained. The developed biochip possesses unique properties of ultralow background and luminescence enhancement, thus offering a suitable tool for the detection of BC-related miRNA in urine. With rational design of probe sequences, the biochip holds great potential for many other biomarkers in real patient samples, making it valuable in areas such as medical diagnosis and disease evaluation.
研究领域:
医学诊断
·
分子生物学
✓ 已验证
DOI
高影响因子
DYES AND PIGMENTS
·
2025
·
IF 4.2
Xinlu Bao,Kebin Ye,Zhikang Song,Mingzhu Zhang,Shaohua Wei,Lin Zhou
Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) generated by photosensitizers under light to kill cancer cells. The phototoxic index (PI) indicates the safe therapeutic window of photosensitizers, and an ideal photosensitizer should have a high PI. Monosubstituted zinc phthalocyanine (ZnPc-COOH) exhibits excellent phototoxicity in bladder cancer cell (T24, IC 50 = 10.7 nM). However, its localization in mitochondria leads to high dark toxicity (IC 50 = 2.12 μM), resulting in a PI of less than 200. In this study, the binding ability of phthalocyanine to the cell membrane was significantly enhanced by side-chain modification with arginine. By taking advantage of the fluidity of the membrane structure, the drug was transported to the lysosome. After modification with Arg, the dark toxicity of ZnPc-COOH decreased by nearly 100 times, and the PI increased to 8979, which is 12 times that of the clinical photosensitizer Photosens®. In a mouse model of non-muscle-invasive bladder cancer (NMIBC), ZnPc-Arg demonstrated therapeutic effects comparable to those of the clinical drug mitomycin C (MMC). This study provides valuable references for the design of photosensitizers with high PI.
研究领域:
光动力疗法
·
生物化学
·
药物化学
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癌症生物学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Translational Andrology and Urology
·
2022
·
IF 2.479
Shujun Sun,Kehua Jiang,Jin Zeng
Background To investigate the potential mechanisms of chemoradiotherapy resistance in patients with bladder cancer. Methods We assessed three bladder cancer cell lines (5637, J82, and TCCSUP) for their sensitivity to chemoradiotherapy. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the expression of specific genes after chemoradiotherapy or combined with olaparib. The Genome Cancer Atlas (TGCA) database was used to analyze possible radioresistance-related genes and the relationship between their expression and bladder cancer survival and prognostic indicators. Results The 5637 cell line showed the most significant sensitivity to chemoradiotherapy. The expression levels of DNA damage repair genes in 5637 cells did not significantly change after chemoradiotherapy. In contrast, the expression levels of BRCA1 and RBBP8 genes significantly increased in J82 and TCCSUP cells after chemoradiotherapy. After combination with olaparib, which is a poly (ADP-ribose) polymerase inhibitor that initiates DNA repair, 5637 cells were significantly inhibited by chemoradiotherapy. However, chemoradiotherapy inhibition on J82 cells was weakened when combined with olaparib. A high reactive expression of BRCA1 and RBBP8 after combination with olaparib suggested that olaparib was ineffective because it did not induce synthetic lethality in which inhibiting PARP by olaparib coincided with suppression of BRCA1/2 expression result in cancer cell death. Conclusions The expression levels of RBBP8 and BRCA1 genes were associated with sensitivity to radiotherapy and chemotherapy in bladder cancer, and an increase in reactive expression after treatment led to worse sensitivity. Therefore, the reactive expression levels of BRCA1 and RBBP8 after chemoradiotherapy may be useful in evaluating the efficacy of olaparib combination therapy.
研究领域:
肿瘤学
·
分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2019
·Vol. 44
·期 5
·1952-1962
·
IF 2.928
Chao Yang,Xian Sun,Hengbing Wang,Ting Lu,Keqing Wu,Yusheng Guan,Jing Tang,Jian Liang,Rongli Sun,Zhongying Guo,Sinian Zheng,Xiaoli Wu,Hesong Jiang,Xi Jiang,Bing Zhong,Xiaobing Niu,Suan Sun,Xinru Wang,Minjian Chen,Guangbo Fu
Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultra‑performance liquid chromatography Q‑Exactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre‑ and post‑gemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pre‑gemcitabine BCa tissues differed significantly from those of pre‑gemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while glutathione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pre‑gemcitabine normal and post‑gemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesis‑free tissue‑based metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa.
研究领域:
肿瘤学
·
代谢组学
·
泌尿外科
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）