Journal of Nanomaterials
·
2018
·
IF 2.207
Mingkai Zhang,Yang Gao,Jialiang Wang,Zhanbo Liu,Zaishun Jin,Jianbo Yu,Yukuan Feng,Qiang Lü
In order to determine a particular tumor cell via nanomaterials, we introduce the preparation of CD20 and CD5 coupled nanoprobes (denoted as CD20 and CD5 nanoprobes for convenience) and an application in identification of mantle cell lymphoma (MCL) from B-cell lymphoma. In this work, CD20 and CD5 nanoprobes were prepared by selectively oxidizing the carbon-carbon double bonds of oleate ligands on the surfaces of NaYF4:Yb3+,Tm3+ and NaYF4:Yb3+,Er3+ nanoparticles and, respectively, coupling carboxyl groups on the particles’ surfaces with CD20 and CD5 monoclonal antibodies through EDC/NHS crosslinking agents. After in situ hybridized Jeko-1 cells and Raji cells as a reference with CD20 and CD5 nanoprobes, in vitro double-color upconversion fluorescence imaging of Jeko-1 cells was demonstrated through visualization of blue and green fluorescence under a 980 nm laser excitation. Moreover, in vivo upconversion fluorescence imaging of the transplanted cancer model was also measured. These experimental results indicate that Jeko-1 cells have been specifically labeled by CD20 and CD5 nanoprobes. It is therefore concluded that CD20 and CD5 nanoprobes could be used to specially differentiate mantle cell lymphoma (MCL) from B-cell lymphoma.
研究领域:
生物医学工程
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癌症研究
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纳米技术
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免疫学
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产品关联
DOI
高影响因子
Cell Host & Microbe
·
2022
·
IF 31.316
Haiyang Lu,Xiaoqiang Xu,Di Fu,Yubei Gu,Rong Fan,Hongmei Yi,Xiangyi He,Chaofu Wang,Binshen Ouyang,Ping Zhao,Li Wang,Pengpeng Xu,Shu Cheng,Zhifeng Wang,Duowu Zou,Lizhong Han,Weili Zhao
Summary Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role of gut microbiota in lymphoma progression, we performed metagenomic sequencing on human primary gastrointestinal B cell lymphomas. We identified a distinct microbiota profile of intestinal lymphoma, with significantly decreased symbiotic microbes, particularly the genus Eubacterium and notably butyrate-producing Eubacterium rectale . Transfer of E. rectale -deficit microbiota of intestinal lymphoma patients to mice caused inflammation and tumor necrosis factor (TNF) production. Conversely, E. rectale treatment reduced TNF levels and the incidence of lymphoma in sensitized Eμ-Myc mice. Moreover, lipopolysaccharide from the resident microbiota of lymphoma patients and mice synergizes with TNF signaling and reinforces the NF-κB pathway via the MyD88-dependent TLR4 signaling, amalgamating in enhanced intestinal B cell survival and proliferation. These findings reveal a mechanism of inflammation-associated lymphomagenesis and a potential clinical rationale for therapeutic targeting of gut microbiota.
研究领域:
肿瘤学
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免疫学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-12
·
IF 4.996
Zhang Shangkun,Gu Chaojiang,Huang Lifang,Wu Han,Shi Jiangzhou,Zhang Zijian,Zhou Yong,Zhou Jingjiao,Gao Yang,Liu Jiaxing,Leng Yingqi,Liu Xiyu,Zhang Qinxing,Huang Liang,Tong Xiqin,Young Ken H.,Li Jiapeng,Zhu Haichuan,Zhang Tongcun
CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.
研究领域:
免疫疗法
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Wenhao Zhong,Xinyu Zhang,Xiao Duan,Hengyu Liu,Yifen Fang,Moucheng Luo,Zhengwen Fang,Congxiu Miao,Dongjun Lin,Jun Wu
Gemcitabine , as a standard and classic strategy for B-cell lymphoma in the clinic, is limited by its poor pharmacodynamics . Although stimuli-responsive polymeric nanodelivery systems have been widely investigated in the past decade, issues such as complicated procedures, low loading capacity, and uncontrollable release kinetics still hinder their clinical translation. In view of the above considerations, we attempt to construct hyperbranched polyprodrug micelles with considerable drug loading via simple procedures and make use of the particularity of the tumor microenvironment to ensure that the micelles are “inactivated” in normal tissues and “activated” in the tumor microenvironment. Hence, in this work, a redox-responsive polymeric gemcitabine-prodrug (GEM-S-S-PEG) was one-pot synthesized via facile esterification and acylation . The self-assembled subsize (< 100 nm) GEM-S-S-PEG (GSP NPs) with considerable loading capacity (≈ 24.6%) exhibited on-demand and accurate control of gemcitabine release under a simulated tumor microenvironment and thus significantly induced the apoptosis of B-cell lymphoma in vitro . Moreover, in the A20 tumor xenograft murine model, GSP NPs efficiently decreased the expansion of tumor tissues with minimal systemic toxicity. In summary, these redox-responsive and self-assembling GSP NPs with a facile one-pot synthesis procedure may hold great potency in clinical translation for enhanced chemotherapy of B-cell lymphoma. Statement of significance A redox-responsive polymeric gemcitabine-prodrug (GEM-S-S-PEG) was one-pot synthesized via facile esterification and acylation. The self-assembled subsize (< 100 nm) GEM-S-S-PEG (GSP NPs) exhibited significant tumor therapeutic effects in vitro and in vivo . The polyprodrug GEM-S-S-PEG prepared in this study shows the great potential of redox-responsive nanodrugs for antitumor activity , which provides a reference value for the optimization of the design of functional polyprodrugs.
研究领域:
肿瘤学
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药剂学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
·
2020
·Vol. 20
·期 13
·1571-1581
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IF 2.049
Luo Yang,Fu Xiaoyi,Han Bin,Zhang Fafu,Yuan Lihong,Men Hongsheng,Zhang Shulin,Tian Sujuan,Dong Bin,Meng Minjie
Aims: The purpose of our study was to explore the combination effect of epirubicin and Bacillus Calmette Guerin (BCG) and its mechanism. Background: Bladder cancer is a threat to human health worldwide. Commonly used chemotherapy drugs and biotherapy have significant therapeutic
effects on bladder cancer, but the mechanism and combined effects are still unclear. Objective: To evaluate the anti-cancer effect of epirubicin combined with BCG on human bladder cancer cells, our studies were carried out. Methods: The viability of human bladder cancer cells with
epirubicin and/or BCG treatments was examined by Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma
2 (Bcl-2) were detected by western blot. Results: The viability of human bladder cancer with epirubicin or BCG treatment was decreased and the viability with epirubicin combined with BCG treatment was decreased more, which were determined by CCK-8 assay. Both epirubicin and BCG increased
the apoptosis rate of human bladder cancer and arrested more cells into G0/G1 phase, which were tested by flow cytometry. The expression of caspase-3, p53 and Bax was increased and the expression of Bcl-2 was decreased with epirubicin treatment on human bladder cells, which were analyzed by
western blot. The expression of caspase-3 and p53 was increased with BCG treatment, which was examined by western blot. Conclusion: Epirubicin induced apoptosis in human bladder cancer cells by up-regulating the expression of proapoptotic factors (caspase-3, p53 and Bax) and down-regulating
the expression of anti-apoptotic factor (Bcl-2). BCG promoted apoptosis of human bladder cancer cells by up-regulating the expression of caspase-3 and p53. BCG plays a potential role at the time of the combination of epirubicin and BCG on bladder cancer cells in early stage. Both epirubicin
and BCG affected cell cycle distribution via arresting more bladder cancer cells at G0/G1 phase, which ultimately led bladder cancer proliferation in vitro and promoted apoptosis.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MASS SPECTROMETRY
·
2017
·Vol. 53
·期 2
·172-182
·
IF 2.381
Yunchen Le,Xiaoyan Shen,Hongyan Kang,Qizheng Wang,Kejia Li,Jie Zheng,Yunqiu Yu
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms. Clinical management is stage based but diagnosis and prognosis could be extremely challenging. The presented study aims to explore the metabolic profiling of CTCL by an accelerated untargeted metabolomics data analysis tool “Mummichog” to facilitate the discoveries of potential biomarkers for clinical early stage diagnosis, prognosis, and treatments in CTCL. Ultra high-performance liquid chromatography–quadrupole time-of-flight–based untargeted metabolomics were conducted on the skin and plasma of CTCL mice. It showed that the metabolism of skin changed greatly versus control samples in the development of CTCL. Increased l -glutamate and decreased adenosine monophosphate were the most essential metabolic features of CTCL tumor and tumor adjacent skins. Unique metabolism changes in tumor adjacent non-involved skin tissues (ANIT) occurred in the progress of carcinogenesis, including upregulated cytidine-5′-triphosphate, aberrant biosynthesis of prostaglandins, pyrimidine, mevalonate pathway, and tryptophan degradation. Sharply elevated 5-phospho-α- d -ribose 1-diphosphate (PRPP) marked the final state of tumor in CTCL. In the plasma, systematic shifts in corticosterone, sphingolipid, and ceramide metabolism were found. These uncovered aberrant metabolites and metabolic pathways suggested that the metabolic reprogramming of PRPP in tumor tissues may cause the disturbance of cytidine and uridine metabolic homeostasis in ANIT. Accumulative cytidine-5′-triphosphate in ANIT may exert positive feedback on the PRPP level and leads to CTCL further development. In addition, the accelerated data analysis tool “Mummichog” showed good practicability and can be widely used in high-resolution liquid chromatography mass spectrometry–based untargeted metabolomics.
研究领域:
肿瘤学
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代谢组学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Zhihua Wang,Mingda Han,Yiqiao Wang,Ning Wang,Yilin Yang,Bingru Shao,Qiannan Miao,Zhan Shi,Fei Yan,Shouhua Feng
B-cell lymphoma (BCL) is a hematological malignancy with high heterogeneity and represents an aggressive proliferation of mature B-cells. Despite the initial success of traditional treatments for BCL in clinical trials, a majority of patients eventually develop resistance to therapy and have poor clinical outcomes. Epigenetic dysregulation is a major contributor to the pathogenesis of BCL, and therapies targeting epigenetic pathways is a promising alternative strategy for treating BCL. Herein, we developed a metal–organic framework (MOF)-based nano-sonosensitizer for ultrasound-driven cascade immunotherapy against BCL. The nano-sonosensitizer was synthesized by encapsulating copper complex of the m6A-mRNA demethylase inhibitor into UiO-66-NH2, which possesses a Z-scheme heterostructure and allows efficient electron–hole pair separation for generating reactive oxygen species (ROS) under ultrasound activation. These CuR@UiO66 sonosensitizers were functionalized with mPEG-PO3 and anti-CD19 antibody, and the resulting CRUPPA19 particles could specifically accumulate in the BCL tissue and also target lymphoma cells that infiltrated into the bone marrow. Once internalized, CRUPPA19 could induce intracellular ROS production and apoptosis under ultrasound irradiation. Subsequently, ultrasonic stimulation triggered autophagy-mediated release of Cu and Rhein from CRUPPA19, thereby increasing protein lipoylation and global mRNA methylation, which led to cuproptosis and the transcriptional repression PDL1, respectively. These cascades synergistically induced immunogenic cell death in the tumors and promoted activation of CD8+ T cells, eventually leading to an antilymphoma immune response. CRUPPA19-mediated sono-immunotherapy not only eliminated the primary and metastatic lymphomas but also cleared lymphoma cells from the bone marrow. This study provided an insight into a MOF-based nanoepigenetic therapy platform with ultrasound-triggered cascade amplification for enhanced antihematological tumor immunity.
研究领域:
肿瘤学
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生物医学工程
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免疫学
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产品关联
DOI
PubMed
高影响因子
LEUKEMIA RESEARCH
·
2021
·
IF 3.156
Mi Mi,Zijian Liu,Xin Zheng,Qiuyue Wen,Fang Zhu,Juan Li,Ishanee Devi Mungur,Liling Zhang
Background The varied clinical outcomes of patients with Diffuse Large B Cell Lymphoma (DLBCL) are attributed to the different genetic and phenotypic subtypes. The purpose of this study was to determine whether metabolic alterations were related to cell-of-origin subtypes of DLBCL and find some metabolites which are associated with the clinical outcomes. Methods Pre-treatment serum samples from eighty (80) newly diagnosed DLBCL patients, including twenty-eight (28) patients with Germinal Center B cell-like (GCB) subtypes and fifty-two (52) patients with non-GCB subtypes, were tested by the Gas Chromatography-Mass Spectrometry (GC–MS) technique. Univariate and multivariate analysis methods, principal component analysis (PCA), and partial least square discriminant analysis (PLS-DA) were conducted to examine the potential differential metabolites. Overall survival (OS) was calculated. Results Overall, 65 out of 1472 entities were identified for subsequent analysis. Unfortunately, the initial PLS-DA analysis failed to discriminate GCB from non-GCB samples. Intriguingly, further PLS-DA analysis identified two subgroups of DLBCL (named as group A and group B) and the metabolic subgroups were significantly associated with overall survival. Valine, hexadecenoic acid, and pyroglutamic acid were identified and verified as the most important altered metabolites and could be candidate biomarkers for the prognosis of DLBCL. Conclusions Our results demonstrated that metabolic alterations in serum could be helpful to predict different clinical outcomes of DLBCL patients. Further studies are warranted to understand whether the altered metabolites might serve as prognostic factors for DLBCL.
研究领域:
肿瘤学
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代谢组学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Targeted Oncology
·
2020
·Vol. 15
·期 3
·365-375
·
IF 4.036
Ding Shengnan,Mao Xia,Cao Yang,Wang Na,Xu Hao,Zhou Jianfeng
Background Although chimeric antigen receptor (CAR) T-cell therapy targeting antigens expressed in refractory and relapsed non-Hodgkin B-cell lymphoma, such as CD19 and CD22, has achieved encouraging clinical effects, some patients fail to attain remission, or relapse after CAR T-cell therapy, which has been ascribed to the loss of the target antigens. Objective To evaluate CD79b as an alternative target for CAR T-cell B-cell lymphoma therapy. Patient and methods The expression of CD79b in different B-cell lymphomas was determined. Anti-CD79b CAR T-cells expressing one of two different CARs were generated, and a series of in vitro and in vivo experiments were conducted to assess the CAR T-cell function. Results We found that CD79b was extensively expressed on the tumor cells of patients with various types of lymphoma regardless of stage, subtype, and cytogenetic and molecular features. Anti-CD79b CAR T-cells were highly specific and effective for the treatment of B-cell lymphomas. Conclusions Our data indicate that CD79b could be used as a target for CAR T-cell therapy of B-cell lymphomas, and further clinical development is warranted.
研究领域:
肿瘤学
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免疫学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
LASERS IN MEDICAL SCIENCE
·
2025
·Vol. 40
·期 1
·1-25
·
IF 2.4
Abd El-Kaream Samir Ali,Hamoda Safia Ali Hussein,El Kholey Sohier Mahmoud,El-sharkawy Awatef Mohamed
Sono-photodynamic therapy (SPDT) has attracted a lot of interest as a cutting-edge therapeutic strategy in the field of cancer treatment. The essential part of SPDT is the sensitizer, which under laser photon and pulsed cavitation ultrasound sono-irradiation may transform sono and photo- energy into cytotoxic molecules. Photon absorption, targeting, penetration, and oxygen dependence remain challenges in sono- -photosensitizer (SPs) design. Rapid advancements in material science have prompted the creation of several SPs that create cytotoxic species with great selectivity, safety, and noninvasiveness for the treatment of tumors. The current study aims to provide an advanced method of activated cancer treatment by using pulsed cavitation to assist the delivery of cardamom, pistacia and laurel conjugated micelles nanoparticles (CPL-Micelle NP) for the sono-photodynamic lymphoma in vivo and in vitro treatment. Human lymphoma cells (U-937) were used in the in vitro study, and the in vivo application groups of the study protocol were Swiss albino mice treated with 9,10-Dimethyl-1,2-Benzanthracene (DMBA) only; they were not given any treatment to induce lymphoma. The study treatment protocol started only after lymphoma induction, and involved daily administration of CPL-Micelle NP as SPDT sensitizer whether or not to be exposed to photo- (IRL) or sono- (US) or a combination of them for three minutes for a period of two weeks. Indicated that Micelle NP is a useful CPL delivery mechanism that targets lymphoma cells directly. Furthermore, CPL-Micelle NP is a promising SPS that, when used in conjunction with SPDT, can be very effective in in vitro treating lymphoma-U-937 (in a dose-dependent manner cell viability declined, an increase in the cells population during the S and G2/M phases indicates that the cell cycle was arrested, and an increase in cell population in the Pre-G, autophagic cell death, as well as necrosis and early and late apoptosis, indicate that cell death was induced) and DMBA-Lymphoma-induced mice in vivo (induced antiproliferative genes, repressed antiangiogenic and antiapoptotic genes), successfully slowing the growth of tumors and even killing cancer cells, as well as lowering oxidative stress malondialdehyde (MDA), improving the functions of the kidneys, liver, and enzymatic and non enzymatic antioxidants. SPDT, the photo- or sono- chemical CPL activation mechanism, and the antioxidant capacity of non-activated CPL can all be linked to this process. On the bases of the findings, CPL-Micelle NP shows a great promise as a novel, efficient selective delivery system for localized SPDT-activated lymphoma treatment.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Fang Nan,Zhongxin Zhou,Qian Bai,Kai Chen,Yu Liu,Shuqi Wu
Lymphoma is a malignant cancer characterized by a rapidly increasing incidence, complex etiology, and lack of obvious early symptoms. Efficient theranostics of lymphoma is of great significance in improving patient outcomes, empowering informed decision-making, and driving medical innovation. Herein, we developed a multifunctional nanoplatform for precise optical imaging and therapy of lymphoma based on a new photosensitizer (1-oxo-1H-benzoo[de]anthracene-2,3-dicarbonitrile-triphenylamine (OBADC-TPA)). OBADC-TPA is a donor–acceptor (D–A) molecule characterized by a novel small coplanar and strong electron-withdrawing acceptor skeleton, while the OBADC moiety facilitates strong intramolecular charge transfer. OBADC-TPA-based nanoparticles (NPs) were prepared through encapsulation with an amphiphilic polymer and subsequent modification with sialic acid (SA). Both in vitro and in vivo studies demonstrated that NPs-SA possessed good biocompatibility, effective tumor accumulation, high photoacoustic (PA) contrast, bright second near-infrared (NIR-II) fluorescence emission, and efficient photothermal/photodynamic conversion capabilities, which can serve as a multifunctional nanocomposite for targeted PA/NIR-II fluorescence imaging-guided synergistic type I/II photodynamic and photothermal therapy (PDT/PTT) of lymphoma. This work not only provides a new NIR-II fluorophore with a novel acceptor moiety but also offers a new, accurate, and effective approach for the targeted diagnosis and treatment of lymphoma, holding promising prospects for clinical application.
研究领域:
肿瘤学
·
生物医学工程
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Management and Research
·
2020
·
IF 2.886
Mei Zeng,Yuhua Chen,Xintao Jia,Yan Liu
Background Epstein-Barr virus (EBV) has been indicated in the development of some tumors, including lymphoma. However, the potential role of latent membrane protein 1 (LMP1) encoded by EBV in the tumorigenesis of lymphoma remains debated. Herein, we examined the function of LMP1 in lymphoma. Methods The expression of LMP1 was downregulated or upregulated in EBV negative cell line SNT-8 and positive cell line KHYG-1, respectively. Subsequently, the cell viability, apoptosis, as well as the expression patterns of p53, mouse double minute 2 (MDM2), B-cell CLL/lymphoma 2 (Bcl-2) and NF-κB were evaluated. Next, the binding relationship between MDM2 and p53 along with p53 ubiquitination in cells was tested by Western blot and co-immunoprecipitation. Finally, the effects of LMP1 on lymphoma cell growth through p53, Bcl-2 and NF-κB pathways were verified by functional rescue experiments. Results Overexpression of LMP1 promoted KHYG-1 cell growth and inhibited cell apoptosis. Moreover, LMP1 upregulation significantly enhanced the activation of NF-κB pathway, thus increasing MDM2 binding to p53, leading to p53 ubiquitination and degradation as well as Bcl-2 expression enhancement. Further inhibition of the NF-κB pathway or Bcl-2 expression significantly weakened the promotive role of LMP1 in the growth of KHYG-1 cells. Conclusion EBV-LMP1 promoted the p53 ubiquitination and degradation by activating NF-κB signaling pathway and the following binding of MDM2 and p53 in cells to enhance Bcl-2 expression, thus promoting the growth of lymphoma cells and inhibiting cell apoptosis.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
病毒学
✓ 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）