iScience
·
2024
·
IF 4.6
Wei Yao,Yihui Wang,Xin Zhang,Yuhe Lin
Pancreatic cancer (PC) is one of the most lethal malignancies and new therapeutic strategies are urgently needed. β1,3-N-acetylglucosaminyltransferase V (B3GNT5) may be a potential option for cancer treatment, but its role in PC remains unknown. In this study, we first demonstrated through bioinformatics analysis that B3GNT5 was high expression in PC and predicted poor prognosis. We further constructed B3GNT5 overexpression or knockdown cell lines by employing lentivirus packaging techniques and confirmed that B3GNT5 could promote tumor cell viability and autonomous growth using cultured cells and vivo xenograft models. In addition, we found that knockdown of B3GNT5 in PC cells inhibited cell migration, invasion, and angiogenesis, as well as stemness of cancer stem cells and enhanced chemotherapy sensitivity to gemcitabine. Mechanistically, overexpression of the transcription factor STAT5B in PC cells enhanced the transcriptional activity of the B3GNT5 promoter. Our work confirmed a tumor-promotive role of B3GNT5 in PC pathogenesis.
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Dandan Wu,Zongchao Zuo,Xinning Sun,Xin Li,Fangzhou Yin,Wu Yin
Long-chain fatty acyl-Coa ligase 4 (ACSL4) is an important enzyme that converts fatty acids to fatty acyl-Coa esters, there is increasing evidence for its role in carcinogenesis. However, the precise role of ACLS4 in hepatocellular carcinoma (HCC) is not clearly understood. In the present study, we provide evidence that ACSL4 expression was specifically elevated in HCC and is associated with poor clinical outcomes. ACSL4 significantly promotes the growth and metastasis of HCC both in vitro and in vivo . RNA sequencing and functional experiments showed that the effect of ACSL4 on HCC development was heavily dependent on PAK2. ACSL4 expression is well correlated with PAK2 in HCC, and ACSL4 even transcriptionally increased PAK2 gene expression mediated by Sp1. In addition, emodin, a naturally occurring anthraquinone derivative, inhibited HCC cell growth and tumor progression by targeting ACSL4. In summary, ACSL4 plays a novel oncogene in HCC development by regulating PAK2 transcription. Targeting ACSL4 could be useful in drug development and therapy for HCC.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2024
·
IF 3.8
Zhenghua Zhang,Yang Tian,Wenjun Gao,Yubin Hu,Liangping Luo,Lichang Lei,Shasha Shen,Dan Han
Objectives: Immune checkpoint inhibitors (ICIs) have demonstrated potential in inhibiting the growth of malignant pleural mesothelioma (MPM), and their efficacy is associated with the expression of programmed death-ligand 1(PD-L1). This study evaluated a PD-L1-targeted nanoprobe for detecting PD-L1 expression in a nude mouse model of malignant pleural mesothelioma (MPM).Methods: A PD-L1-binding peptide (WL-12) was conjugated with superparamagnetic iron oxide nanoparticles (SPIONs) to create the nanoprobe WL-12@Fe₃O₄. The nanoprobe’s stability, biotoxicity, targeting ability, and in vivo magnetic resonance (MR) imaging effects were assessed and compared to non-targeted Fe₃O₄ nanoparticles. ΔT2 values and PD-L1 expression were measured in H226 and MSTO-211H tumor tissues over 4 weeks to analyze correlations.Results: The WL-12@Fe₃O₄ nanoprobe demonstrated uniform distribution and a spherical shape, with a larger size (43.82 nm) and lower surface potential (−9.34 ± 0.54 mV) compared to Fe₃O₄ (32.67 nm, −20.20 ± 0.88 mV, P < 0.05). The XPS and FT-IR analysis results indicate the successful coupling of WL-12 with Fe3O4. It was well dispersed in serum and saline and showed no cytotoxicity or organ damage in vivo. The probe selectively accumulated in PD-L1-expressing MPM cells, especially MSTO-211H, and exhibited significantly higher uptake in high PD-L1-expressing H460 cells (930.22 ± 11.75 ng/mL) compared to low PD-L1-expressing A549 cells (254.89 ± 17.33 ng/mL, P < 0.05). Tumor iron levels in the WL-12@Fe₃O₄ group were significantly elevated (141.02 ± 17.33 μg/g) compared to controls (36.43 ± 3.56 μg/g, P < 0.05), with no significant differences in other organs (P > 0.05). The T2 values of H226 and MSTO-211H tumors decreased after probe injection, with ΔT2 values significantly higher in the targeted group than the nontargeted group (P < 0.05). ΔT2 values increased over 4 weeks, correlating strongly with PD-L1 expression (P < 0.05).Conclusion: The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.
研究领域:
肿瘤学
·
医学影像学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
PeerJ
·
2024
·
IF 2.3
Ying Zhang,Fengrui Cheng,Xingrui Cai,Jingping Wu
Background Epstein-Barr virus induced gene 3 ( EBI3 ), a member of the IL-12 family, is known to be involved in malignant progression in a variety of cancers, but its role in melanoma is unclear. The aim of this study was to explore the effects of EBI3 on the malignant phenotype melanoma to reveal its potential as a therapeutic target. Methods In this study, we used bioinformatics to analyze the expression of EBI3 in pan-cancer and verified its expression level in melanoma cells by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the effects of EBI3 knockdown on cell proliferation, migration and invasion were detected using the Cell Counting Kit-8 (CCK-8) and Transwell assays. Changes in immune-related cytokines were detected by ELISA, and macrophage polarization was observed using immunofluorescence. Finally, the phosphorylation levels of signaling pathways such as Smad3, STAT6 and cGAS-STING were analyzed by Western blot. Results EBI3 was evidently highly-expressed in melanoma, and silencing of EBI3 could visibly suppress the survival and migration/invasion of melanoma cells, concurrent with the increased levels of BAX and CDH1 and the decreased expressions of BCL2 and CDH2 . Meanwhile, EBI3 knockdown diminished the phosphorylation levels of both Smad3 and STAT6 and the levels of immune response-relevant cytokines in melanoma cells, while aggravating the macrophage M1 polarization and the expression of cGAS, p-STING and p-IRE1 α in THP-1 monocyte-derived macrophages co-cultured with EBI3 -silenced melanoma cells. Conclusion This study filled the blank on the involvement of EBI3 in melanoma, hinting the possibility of controlling EBI3 as a therapeutic strategy in the management of melanoma.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2025
·
IF 3.3
Keke Shang,Yang Chen,Jingjie Jin,Tong Wang,Gong Zhang
Genome instability, a hallmark of cancer, leads to endless mutations that eventually cause drug resistance against almost all chemotherapy drugs. This poses a significant obstacle to the success of cancer treatments. Here, we report that aurintricarboxylic acid (ATCA) effectively suppresses the malignant phenotypes, including proliferation, migration, invasion, and clone formation, of cancer cells of multiple cancers, including cisplatin-resistant lung cancer cells, paclitaxel-resistant lung cancer cells, and doxorubicin-resistant breast cancer cells. Interestingly, ATCA does not cause acute cytotoxicity. Proteome analysis of the whole proteome and nascent chains showed that ATCA reduced translation initiation and thus reduced the abundance of the highly abundant respiratory chain complex. This lowered the potential of the mitochondrial membrane and thus restricted the energy production. This principle could be hardly circumvented by cancer cells and thus may serve as a promising and universal candidate for a second-line therapeutic agent to control cancer progression after drug resistance.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Yongjun Tang,Zhengning Feng,Chenlu Ma,Nian Jang,Xiaolong Chen,Yingxu He,Francis L. Martin,Hui Liu,Weiyi Pang
Breast cancer has a high global incidence, and benzo[ a ]pyrene (B[ a ]P) is considered a contributing factor that increases carcinogenic risk. This study examined B[ a ]P's oncogenic mechanisms in mammary epithelial cells. Chronic B[ a ]P exposure induced morphological changes and enhanced proliferative/clonogenic capacity in MCF-10A cells. Chronic B[ a ]P exposure altered gene expression in MCF-10A cells, revealing differential levels of circRNAs, lncRNAs, miRNAs, and mRNAs. qRT-PCR validation demonstrated strong alignment with RNA-seq results, ensuring sequencing reliability. Additionally, chronic B[ a ]P exposure upregulated the protein expression of AhR and ARNT, as well as TGF- β , pSmad2/3, and KRT14 , while increasing Vimentin expression and decreasing E-cadherin expression. Notably, treatment with the TGF- β inhibitor SB431542 reversed these protein expression changes in transformed cells. These results show that exposure to Chronic B[ a ]P induces MCF-10A cell transformation. The underlying mechanisms involve significant transcriptional alterations, AhR/ARNT expression regulation, TGF- β signaling pathway activation, KRT14 protein modulation, and EMT. Furthermore, Chronic B[ a ]P exposure may drive transformation through TGF- β modulation. Chronic B[ a ]P exposure promotes breast carcinogenesis, revealing mechanistic insights and potential preventive biomarkers.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2025
·
IF 3.9
Jing Wang,Chengxue He,Rui Guo,Li Wen,Jinping Tao,Huimao Zhang,HaiFeng Huang,Hua Zhu,Zhi Yang,Xianteng Yang
Malignant glioma highly expresses carbonic anhydrase IX (CAIX). This study aimed to develop [177Lu]Lu-XYIMSR-01, a small-molecule therapeutic agent CAIX, to assess its potential for treating malignant glioma. [177Lu]Lu-XYIMSR-01 was synthesized by radiolabeling DOTA-XYIMSR-01 with 177Lu. In vitro assays were conducted to evaluate the affinity for U87MG tumor cells. The probe was injected via the tail vein into subcutaneous and orthotopic U87MG models for micro-SPECT/CT imaging. The survival rates of tumor-bearing mice were assessed after [177Lu]Lu-XYIMSR-01 injection by intratumoral in orthotopic models, including untreated controls and those treated with Temozolomide or combination therapy. After purification, the radiochemical yield of [177Lu]Lu-XYIMSR-01 was 86.47 ± 2.42%, with a radiochemical purity (RCP) of 99%. Its cell uptake in U87MG cells was 3.70 ± 0.57 ‰ AD/105 cells, significantly higher than that in HCT116 cells (0.68 ± 0.16 ‰ AD/105 cells, P = 0.001). In the biodistribution study, [177Lu]Lu-XYIMSR-01 uptake in U87MG tumors was 6.19 ± 1.37%ID/g, with a tumor/muscle ratio of 20.14 ± 3.24. In the orthotopic glioma model, local injection combined with Temozolomide significantly improved survival and inhibited tumor growth. The results indicate that [177Lu]Lu-XYIMSR-01 is a promising therapeutic molecular probe for targeting CAIX, and its combination with Temozolomide significantly enhances treatment outcomes for malignant glioma.
研究领域:
肿瘤学
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分子影像学
·
核医学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Weiwei Zeng,Zhuoyao Wu,Yan Xu,Weitao Yang,Bingbo Zhang
Molecular magnetic resonance imaging (mMRI) of biomarkers is essential for accurate cancer detection in precision medicine. However, the current clinically used contrast agents provide structural magnetic resonance imaging (sMRI) information only and rarely provide mMRI information. Here, a tumor-specific furin-catalyzed nanoprobe (NP) was reported for differential diagnosis of malignant breast cancers (BCs) in vivo. This NP with a compact structure of Fe3O4@Gd-DOTA NPs (FFG NPs) contains an “always-on” T2-weighted MR signal provided by the magnetic Fe3O4 core and a furin-catalyzed enhanced T1-weighted MR signal provided by the Gd-DOTA moiety. The FFG NPs were found to produce an activated T1 signal in the presence of furin catalysis and an “always-on” T2 signal, providing mMRI and sMRI information simultaneously. Ratiometric mMRI:sMRI intensity can be used for differential diagnosis of malignant BCs MDA-MB-231 and MCF-7, where the furin levels relatively differ. The proposed probe not only provides structural imaging but also enables real-time molecular differential visualization of BC through enzymatic activities of cancer tissues.
研究领域:
医学影像学
·
肿瘤学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2018
·
IF 13.709
Wenfei Chen,Ying Wang,Ming Qin,Xudong Zhang,Zhirong Zhang,Xun Sun,Zhen Gu
The facultative anaerobe Salmonella strain VNP20009 selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. However, the phase 1 clinical trial of VNP20009 has been terminated mainly due to its weak antitumor effects and exhibition of dose-dependent toxicity. Here, we leveraged the advantages of VNP20009 biotherapy together with polydopamine-mediated photothermal therapy in order to enhance the antitumor efficacy toward malignant melanoma. VNP20009 was coated with polydopamine via oxidation and self-polymerization, which was then injected into tumor-bearing mice via the tail vein. Polydopamine-coated VNP20009 targeted hypoxic areas of the solid tumors, and near-infrared laser irradiation of the tumors induced heating due to polydopamine. This combined approach eliminated the tumors without relapse or metastasis with only one injection and laser irradiation. More importantly, we found both VNP and pDA potentiate the therapeutic ability of each other, resulting in a superior anticancer effect.
研究领域:
肿瘤学
·
生物医学工程
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2024
·
IF 5.9
Zhijin Zhang,Wentao Zhang,Huan Wang,Haotian Chen,Hong Wang,Yang Yu,Danjing Shen,Man Pi,Yang Wu,Ming Luo,Yanyan He,Shiyu Mao,Jiang Geng,Wei Li,Guangchun Wang,Changcheng Guo,Daqiang Yin,Xudong Yao
Epidemiological studies indicate that prostate cancer (PCa) is the second prevalent malignant tumor affecting men globally. Environmental pollution such as cigarette smoke is one of the important risk factors for the development of prostate cancer. However, as one of the main carcinogens in cigarette smoke, the role of benzo[a]pyrene (BaP) in prostate cancer is still unclear. The current study aimed to investgate the impacts of BaP exposure on the progression of PCa toward malignancy and the regulation of the immune microenvironment. We verified that BaP exposure can promote the proliferation, migration, and apoptosis of prostate cancer cells through in vitro experiments. We constructed a subcutaneous xenograft tumor model of BaP exposure mouse and found that can promote the proliferation of tumors in vivo . Organoids-driven by PCa patients showed higher growth rate under BaP exposure. Flow cytometric analysis demonstrated a remarkable decrease in CD4 + T and CD8 + T cell infiltration levels. Moreover, we identified four genes ( Mdm2, Ar, Foxo1, Crebbp ) were strongly associated with BaP exposure by combining mouse tumor RNA-seq and CTD database. Additionally, a nomogram integrating clinicopathological features was constructed to assess the prognosis of prostate cancer patients under BaP exposure. This study systematically proved that BaP exposure promotes malignant progression of PCa and suppresses the immune microenvironment, in which Mdm2, Ar, Foxo1, Crebbp may play a crucial role in inhibiting apoptosis. These findings offer novel insights into the mechanisms via which BaP exposure contributes to PCa development.
研究领域:
肿瘤学
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免疫学
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环境医学
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产品关联
DOI
高影响因子
LABORATORY INVESTIGATION
·
2005
·Vol. 85
·期 12
·1555-1564
·
IF 3.702
Angeletti Cesar,Harvey Neal R,Khomitch Vitali,Fischer Andrew H,Levenson Richard M,Rimm David L
Despite low sensitivity (around 60%), cytomorphologic examination of urine specimens represents the standard procedure in the diagnosis and follow-up of bladder cancer. Although color is information-rich, morphologic diagnoses are rendered almost exclusively on the basis of spatial information. We hypothesized that quantitative assessment of color (more precisely, of spectral properties) using liquid crystal-based spectral fractionation, combined with genetic algorithm-based spatial analysis, can improve the accuracy of traditional cytologic examination. Images of various cytological specimens were collected every 10?nm from 400 to 700?nm to create an image stack. The resulting data sets were analyzed using the Los Alamos-developed GENetic Imagery Exploitation (GENIE) package, a hybrid genetic algorithm that segments (classifies) images using automatically ‘learned’ spatio-spectral features. In an evolutionary fashion, GENIE generates a series of algorithms or ‘chromosomes’, keeping the one with best fitness with respect to a user-defined training set. First, we tested the system to determine if it could recognize malignant cells using artificial cytology specimens constructed to completely avoid the requirement for human interpretation. GENIE was able to differentiate malignant from benign cells and to estimate their relative proportions in controlled mixtures. We then tested the system on routine cytology specimens. When targeted to detect malignant urothelial cells in cytology specimens, GENIE showed a combined sensitivity and specificity of 85 and 95%, in samples drawn from two separate institutions over a span of 4 years. When trained on cases initially diagnosed as ‘atypical’ but with unequivocal follow-up by biopsy, surgical specimen or cytology, GENIE showed efficiency superior to the cytopathologist with respect to predicting the follow-up result in a cohort of 85 cases. We believe that, in future, this type of methodology could be used as an ancillary test in cytopathology, in a manner analogous to immunostaining, in those situations when a definitive diagnosis cannot be rendered based solely on the morphology.
研究领域:
肿瘤学
·
细胞病理学
·
生物医学工程
·
分子诊断
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转化医学
·
光谱成像
✓ 已验证
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 21
·5070
·
IF 4.2
Yupeng Bi,Longlong Li,Jin Liu,Yao Wang,Boying Wang,Yanxin Wang,Christopher D. Snow,Jun Li,Matt J. Kipper,Laurence A. Belfiore,Jianguo Tang
To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu3+/Tb3+complexes for effective drug loading and release, respectively. These special Eu3+/Tb3+-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu3+/Tb3+-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells.
研究领域:
生物医学工程
·
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）