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  1. TI=Targeting macrophage anti tumor activity to suppress melanoma progression
  2. AU="Varadarajan, Nithya"

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  1. Artikel ; Online: Targeting macrophage anti-tumor activity to suppress melanoma progression.

    Wang, Huafeng / Zhang, Lijuan / Yang, Luhong / Liu, Chengfang / Zhang, Qi / Zhang, Linjing

    Oncotarget

    2017  Band 8, Heft 11, Seite(n) 18486–18496

    Abstract: ... that targeting the anti-tumor activity of macrophages remains a promising strategy for melanoma inhibition ... of an effective immunotherapy for treatment of metastatic melanoma. In this review, we focus on the anti-tumor ... activities of macrophages in melanoma and their potential as therapeutic targets in melanoma. Although macrophages can be re ...

    Abstract By phagocytosing cancer cells and their cellular debris, macrophages play a critical role in nonspecific defense (innate immunity) and, as antigen presenters, they help initiate specific defense mechanisms (adaptive immunity). Malignant melanoma is a lethal disease due to its aggressive capacity for metastasis and resistance to therapy. For decades, considerable effort has gone into development of an effective immunotherapy for treatment of metastatic melanoma. In this review, we focus on the anti-tumor activities of macrophages in melanoma and their potential as therapeutic targets in melanoma. Although macrophages can be re-educated through intercellular signaling to promote tumor survival owing to their plasticity, we expect that targeting the anti-tumor activity of macrophages remains a promising strategy for melanoma inhibition. The combination of tumoricidal macrophage activation and other treatments such as surgery, chemotherapy, and radiotherapy, may provide an effective and comprehensive anti-melanoma strategy.
    Mesh-Begriff(e) Animals ; Disease Progression ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; Humans ; Immunotherapy/methods ; Macrophages/immunology ; Melanoma/immunology ; Melanoma/therapy
    Chemische Substanzen Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Sprache Englisch
    Erscheinungsdatum 2017-01-04
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.14474
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Anti-cancer effect of targeting fibroblast activation protein alpha in glioblastoma through remodeling macrophage phenotype and suppressing tumor progression.

    Miao, Yazhou / Deng, Yuxuan / Liu, Jinqiu / Wang, Jing / Hu, Boyi / Hao, Shuyu / Wang, Herui / Zhang, Zhe / Jin, Zeping / Zhang, Yang / Li, Chunzhao / Zhang, Peng / Wan, Hong / Zhang, Shaodong / Feng, Jie / Ji, Nan

    CNS neuroscience & therapeutics

    2022  Band 29, Heft 3, Seite(n) 878–892

    Abstract: ... caused a decrease in the number of M2 macrophages. In vivo, PT100 was confirmed to suppress ... survival time. Fibroblast activation protein alpha (FAP) is a dual-specificity serine protease that is ... strongly associated with the development and progression of human carcinomas. However, relatively little is ...

    Abstract Introduction: Glioblastoma (GBM) is the most malignant form of glioma and has a poor median survival time. Fibroblast activation protein alpha (FAP) is a dual-specificity serine protease that is strongly associated with the development and progression of human carcinomas. However, relatively little is known about the function of FAP and its potential as a therapeutic target in GBMs.
    Aims: In this study, we aimed to explore the role of FAP in GBM through a series of experiments and to evaluate the therapeutic effect of PT100, a small molecule inhibitor of FAP, on GBM.
    Results: Increased FAP expression was associated with poor survival in glioma. In vitro, FAP knockdown inhibited the process of EMT and caused a decrease in the number of M2 macrophages. In vivo, PT100 was confirmed to suppress the progression of GBMs significantly.
    Conclusions: FAP could serve as a biomarker and novel therapeutic target for the treatment of GBM and that PT100 is a promising drug for the treatment of GBM.
    Mesh-Begriff(e) Humans ; Glioblastoma/genetics ; Serine Endopeptidases/genetics ; Glioma ; Phenotype ; Macrophages/pathology ; Cell Line, Tumor ; Brain Neoplasms/metabolism
    Chemische Substanzen fibroblast activation protein alpha (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-)
    Sprache Englisch
    Erscheinungsdatum 2022-11-15
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2423461-8
    ISSN 1755-5949 ; 1755-5930
    ISSN (online) 1755-5949
    ISSN 1755-5930
    DOI 10.1111/cns.14024
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  3. Artikel: Targeting Cellular Components of the Tumor Microenvironment in Solid Malignancies.

    Belli, Carmen / Antonarelli, Gabriele / Repetto, Matteo / Boscolo Bielo, Luca / Crimini, Edoardo / Curigliano, Giuseppe

    Cancers

    2022  Band 14, Heft 17

    Abstract: ... Molecular characterization of tumor-TME interactions led to the introduction of novel anti-cancer therapies ... with malignant cells actively imposing an immune-suppressive and tumor-promoting state on surrounding, non ... the so-called tumor microenvironment (TME), which plays a key role in tumorigenesis, cancer progression ...

    Abstract Cancers are composed of transformed cells, characterized by aberrant growth and invasiveness, in close relationship with non-transformed healthy cells and stromal tissue. The latter two comprise the so-called tumor microenvironment (TME), which plays a key role in tumorigenesis, cancer progression, metastatic seeding, and therapy resistance. In these regards, cancer-TME interactions are complex and dynamic, with malignant cells actively imposing an immune-suppressive and tumor-promoting state on surrounding, non-transformed, cells. Immune cells (both lymphoid and myeloid) can be recruited from the circulation and/or bone marrow by means of chemotactic signals, and their functionality is hijacked upon arrival at tumor sites. Molecular characterization of tumor-TME interactions led to the introduction of novel anti-cancer therapies targeting specific components of the TME, such as immune checkpoint blockers (ICB) (i.e., anti-programmed death 1, anti-PD1; anti-Cytotoxic T-Lymphocyte Antigen 4, anti-CTLA4). However, ICB resistance often develops and, despite the introduction of newer technologies able to study the TME at the single-cell level, a detailed understanding of all tumor-TME connections is still largely lacking. In this work, we highlight the main cellular and extracellular components of the TME, discuss their dynamics and functionality, and provide an outlook on the most relevant clinical data obtained with novel TME-targeting agents, with a focus on T lymphocytes, macrophages, and cancer-associated fibroblasts.
    Sprache Englisch
    Erscheinungsdatum 2022-09-01
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14174278
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  4. Artikel ; Online: Bufalin suppresses hepatocellular carcinogenesis by targeting M2 macrophage-governed Wnt1/β-catenin signaling.

    Zhang, Xuemei / Lu, Xiaona / Shi, Jia / Li, Yuyao / Li, Yue / Tao, Ru / Huang, Lingying / Tang, Yifei / Zhu, Xiaojun / Li, Man / Gao, Yueqiu / Feng, Hai / Yu, Zhuo

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2024  Band 126, Seite(n) 155395

    Abstract: ... from the traditional Chinese medicine (TCM) Chansu, has been evidenced to possess anti-HCC activity by directly suppressing tumor ... TAM-governed tumor cell proliferation and the inhibitory effect of bufalin on HCC growth by targeting ... Background: The interplay of tumor-associated macrophages (TAMs) and tumor cells plays a key role ...

    Abstract Background: The interplay of tumor-associated macrophages (TAMs) and tumor cells plays a key role in the development of hepatocellular carcinoma (HCC) and provides an important target for HCC therapy. The communication between them is still on the investigation. Bufalin, the active component derived from the traditional Chinese medicine (TCM) Chansu, has been evidenced to possess anti-HCC activity by directly suppressing tumor cells, while its immunomodulatory effect on the tumor microenvironment (TME) is unclear.
    Purpose: To explore the mechanism of M2 TAM-governed tumor cell proliferation and the inhibitory effect of bufalin on HCC growth by targeting M2 macrophages.
    Methods: Morphology and marker proteins were detected to evaluate macrophage polarization via microscopy and flow cytometry. Cellular proliferation and malignant transformation of HCC cells cultured with macrophage conditioned medium (CM) or bufalin-primed M2-CM, were assessed by cell viability, colony formation and soft agar assays. Regulations of gene transcription and protein expression and release were determined by RT-qPCR, immunoblotting, immunoprecipitation, ELISA and immunofluorescence. Tumorigenicity upon bufalin treatment was verified in orthotopic and diethylnitrosamine-induced HCC mouse model.
    Results: In this study, we first verified that M2 macrophages secreted Wnt1, which acted as a mediator to trigger β-catenin activation in HCC cells, leading to cellular proliferation. Bufalin suppressed HCC cell proliferation and malignant transformation by inhibiting Wnt1 release in M2 macrophages, and dose-dependently inhibited HCC progression in mice. Mechanistically, bufalin specially targeted to block Wnt1 transcription, thus inactivating β-catenin signaling cascade in HCC cells and leading to tumor regression in HCC mouse model.
    Conclusion: These results clearly reveal a novel potential of bufalin to suppress HCC through immunomodulation, and shed light on a new M2 macrophage-based modality of HCC immunotherapy, which additively enhances direct tumor-inhibitory efficacy of bufalin.
    Mesh-Begriff(e) Animals ; Mice ; Carcinoma, Hepatocellular/metabolism ; beta Catenin/metabolism ; Liver Neoplasms/metabolism ; Cell Line, Tumor ; Macrophages/metabolism ; Carcinogenesis ; Tumor Microenvironment ; Bufanolides
    Chemische Substanzen beta Catenin ; bufalin (U549S98QLW) ; Bufanolides
    Sprache Englisch
    Erscheinungsdatum 2024-01-30
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2024.155395
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Specific targeting of CD163

    Etzerodt, Anders / Tsalkitzi, Kyriaki / Maniecki, Maciej / Damsky, William / Delfini, Marcello / Baudoin, Elodie / Moulin, Morgane / Bosenberg, Marcus / Graversen, Jonas Heilskov / Auphan-Anezin, Nathalie / Moestrup, Søren Kragh / Lawrence, Toby

    The Journal of experimental medicine

    2019  Band 216, Heft 10, Seite(n) 2394–2411

    Abstract: ... maintain immune suppression in an experimental model of melanoma that is resistant to anti-PD-1 checkpoint ... Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable ... of different TAM subsets to tumor progression. Here, we demonstrate that CD163-expressing TAMs specifically ...

    Abstract Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable of contributing to antitumor immunity. Recent studies have revealed an unprecedented heterogeneity among TAMs in both human cancer and experimental models. Nevertheless, we still understand little about the contribution of different TAM subsets to tumor progression. Here, we demonstrate that CD163-expressing TAMs specifically maintain immune suppression in an experimental model of melanoma that is resistant to anti-PD-1 checkpoint therapy. Specific depletion of the CD163
    Mesh-Begriff(e) Animals ; Antigens, CD/immunology ; Antigens, Differentiation, Myelomonocytic/immunology ; Humans ; Lymphocyte Activation ; Macrophages/immunology ; Macrophages/pathology ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Melanoma, Experimental/therapy ; Mice ; Monocytes/immunology ; Monocytes/pathology ; Receptors, Cell Surface/immunology ; T-Lymphocytes/immunology ; Tumor Microenvironment/immunology
    Chemische Substanzen Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD163 antigen ; Receptors, Cell Surface
    Sprache Englisch
    Erscheinungsdatum 2019-08-02
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20182124
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy.

    Zhu, Jianshu / Fan, Jiawei / Xia, Yuanliang / Wang, Hengyi / Li, Yuehong / Feng, Zijia / Fu, Changfeng

    Frontiers in pharmacology

    2023  Band 14, Seite(n) 1271321

    Abstract: ... of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity ... in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover ... tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive ...

    Abstract Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates. The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment. However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets. Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation. We also explored the clinical implementations of immunotherapy grounded on nanomedicine.
    Sprache Englisch
    Erscheinungsdatum 2023-09-21
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2023.1271321
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  7. Artikel ; Online: Targeting macrophage Syk enhances responses to immune checkpoint blockade and radiotherapy in high-risk neuroblastoma.

    Rohila, Deepak / Park, In Hwan / Pham, Timothy V / Jones, Riley / Tapia, Elisabette / Liu, Kevin X / Tamayo, Pablo / Yu, Alice / Sharabi, Andrew B / Joshi, Shweta

    Frontiers in immunology

    2023  Band 14, Seite(n) 1148317

    Abstract: ... the suppressive TME towards immunostimulation and activating anti-tumor immune responses. Moreover, combining FDA ... tumor microenvironment (TME). In addition, the effect of Syk inhibitor, R788, on anti-tumor immunity alone or ... to complete tumor regression and durable anti-tumor immunity in mice bearing small tumors (50 mm: Conclusion ...

    Abstract Background: Neuroblastoma (NB) is considered an immunologically cold tumor and is usually less responsive to immune checkpoint blockade (ICB). Tumor-associated macrophages (TAMs) are highly infiltrated in NB tumors and promote immune escape and resistance to ICB. Hence therapeutic strategies targeting immunosuppressive TAMs can improve responses to ICB in NB. We recently discovered that spleen tyrosine kinase (Syk) reprograms TAMs toward an immunostimulatory phenotype and enhances T-cell responses in the lung adenocarcinoma model. Here we investigated if Syk is an immune-oncology target in NB and tested whether a novel immunotherapeutic approach utilizing Syk inhibitor together with radiation and ICB could provide a durable anti-tumor immune response in an MYCN amplified murine model of NB.
    Methods: Myeloid Syk KO mice and syngeneic MYCN-amplified cell lines were used to elucidate the effect of myeloid Syk on the NB tumor microenvironment (TME). In addition, the effect of Syk inhibitor, R788, on anti-tumor immunity alone or in combination with anti-PDL1 mAb and radiation was also determined in murine NB models. The underlying mechanism of action of this novel therapeutic combination was also investigated.
    Results: Herein, we report that Syk is a marker of NB-associated macrophages and plays a crucial role in promoting immunosuppression in the NB TME. We found that the blockade of Syk in NB-bearing mice markedly impairs tumor growth. This effect is facilitated by macrophages that become immunogenic in the absence of Syk, skewing the suppressive TME towards immunostimulation and activating anti-tumor immune responses. Moreover, combining FDA-approved Syk inhibitor, R788 (fostamatinib) along with anti-PDL1 mAb provides a synergistic effect leading to complete tumor regression and durable anti-tumor immunity in mice bearing small tumors (50 mm
    Conclusion: Collectively, our findings demonstrate the central role of macrophage Syk in NB progression and demonstrate that Syk blockade can "reeducate" TAMs towards immunostimulatory phenotype, leading to enhanced T cell responses. These findings further support the clinical evaluation of fostamatinib alone or with radiation and ICB, as a novel therapeutic intervention in neuroblastoma.
    Mesh-Begriff(e) Animals ; Mice ; Immune Checkpoint Inhibitors/pharmacology ; N-Myc Proto-Oncogene Protein/metabolism ; Macrophages ; Neuroblastoma/metabolism ; Tumor Microenvironment
    Chemische Substanzen fostamatinib (SQ8A3S5101) ; Immune Checkpoint Inhibitors ; N-Myc Proto-Oncogene Protein
    Sprache Englisch
    Erscheinungsdatum 2023-06-07
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1148317
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  8. Artikel ; Online: Chimeric antigen receptor macrophages activated through TLR4 or IFN-γ receptors suppress breast cancer growth by targeting VEGFR2.

    Duan, Zhaojun / Li, Zhen / Wang, Ziyuan / Chen, Chong / Luo, Yunping

    Cancer immunology, immunotherapy : CII

    2023  Band 72, Heft 10, Seite(n) 3243–3257

    Abstract: Chimeric antigen receptor macrophage (CAR-M) is a promising immunotherapy strategy of anti-tumor ... macrophages activation by Tlr4 and/or Ifn-γ receptors, and these CAR-Ms could effectively inhibit tumor growth ... by targeting vascular endothelial growth factor receptor-2 (VEGFR2), which highly expressed in tumor cells and ...

    Abstract Chimeric antigen receptor macrophage (CAR-M) is a promising immunotherapy strategy of anti-tumor due to its high infiltration, direct phagocytosis of tumor cells, immunomodulation of tumor microenvironment (TME) and linkage of innate and adaptive immunity. Here a series of novelly designed CAR-Ms by targeting vascular endothelial growth factor receptor-2 (VEGFR2), which highly expressed in tumor cells and TME, were evaluated. Their activation signals were transduced by Tlr4 or Ifn-γ receptors either alone or in combination, which were designed to mediate M1 polarization of macrophages as the downstream of lipopolysaccharide or Ifn-γ that had been widely reported. Our results showed that VEGFR2-targeting CAR-Ms could be activated under the stimulation of VEGFR2-expressing cells. They exhibited higher expression of CD86, MHCII and TNF-α in vitro and enhanced tumor suppressive abilities in vivo. Implantation of these CAR-Ms into 4T1 breast cancer-bearing mice could obviously inhibit the progression of tumor without significant toxic side effects, especially the group of mmC in which constructed with Tlr4 as the intracellular domain of CAR. In conclusion, this research provides a promising design of CAR that induce macrophages activation by Tlr4 and/or Ifn-γ receptors, and these CAR-Ms could effectively inhibit tumor growth through targeting VEGFR2.
    Mesh-Begriff(e) Mice ; Animals ; Receptors, Chimeric Antigen ; Toll-Like Receptor 4 ; Vascular Endothelial Growth Factor Receptor-2 ; Vascular Endothelial Growth Factor A ; Neoplasms ; Macrophages/metabolism ; Immunotherapy, Adoptive/methods ; Tumor Microenvironment
    Chemische Substanzen Receptors, Chimeric Antigen ; Toll-Like Receptor 4 ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; Vascular Endothelial Growth Factor A
    Sprache Englisch
    Erscheinungsdatum 2023-07-12
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-023-03490-8
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  9. Artikel ; Online: Targeting lactate metabolism and immune interaction in breast tumor via protease-triggered delivery.

    Zhao, Pengfei / Wang, Shuang / Jiang, Jizong / Gao, Yanrong / Wang, Yuewei / Zhao, Yuge / Zhang, Jiaxin / Zhang, Meng / Huang, Yongzhuo

    Journal of controlled release : official journal of the Controlled Release Society

    2023  Band 358, Seite(n) 706–717

    Abstract: ... lactate metabolism and stimulate anti-tumor immunity. To enhance tumor-targeting efficiency, we developed ... through chemotherapy and anti-tumor immunity. Besides, inhibition of lactate metabolism suppressed the HIF-1α/VEGF ... crosstalk between tumor cells and the immune microenvironment (TIME) to promote the progression of breast ...

    Abstract Lactate is abundant in cancer tissues due to active glycolysis (aka Warburg effect) and mediates crosstalk between tumor cells and the immune microenvironment (TIME) to promote the progression of breast cancer. Quercetin (QU) is a potent monocarboxylate transporters (MCT) inhibitor, which can reduce lactate production and secretion of tumor cells. Doxorubicin (DOX) can induce immunogenic cell death (ICD), which promotes tumor-specific immune activation. Thus, we propose a combination therapy of QU&DOX to inhibit lactate metabolism and stimulate anti-tumor immunity. To enhance tumor-targeting efficiency, we developed a legumain-activatable liposome system (KC26-Lipo) with modification of KC26 peptide for co-delivery of QU&DOX for modulation of tumor metabolism and TIME in breast cancer. The KC26 peptide is a legumain-responsive, hairpin-structured cell-penetrating peptide (polyarginine) derivative. Legumain is a protease overexpressed in breast tumors, allowing selective activation of the KC26-Lipo to subsequently facilitate intra-tumoral and intracellular penetration. The KC26-Lipo effectively inhibited 4T1 breast cancer tumor growth through chemotherapy and anti-tumor immunity. Besides, inhibition of lactate metabolism suppressed the HIF-1α/VEGF pathway and angiogenesis and repolarized the tumor-associated macrophages (TAM). This work provides a promising breast cancer therapy strategy by regulating lactate metabolism and TIME.
    Mesh-Begriff(e) Animals ; Humans ; Female ; Peptide Hydrolases ; Doxorubicin ; Breast Neoplasms/drug therapy ; Liposomes/therapeutic use ; Mammary Neoplasms, Animal ; Lactates ; Cell Line, Tumor ; Tumor Microenvironment
    Chemische Substanzen Peptide Hydrolases (EC 3.4.-) ; Doxorubicin (80168379AG) ; Liposomes ; Lactates
    Sprache Englisch
    Erscheinungsdatum 2023-05-25
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2023.05.024
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  10. Artikel ; Online: [Albumin-based Drug Delivery System Targeting Mannose Receptors and Its Application to Medical Treatments].

    Maeda, Hitoshi

    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

    2023  Band 143, Heft 11, Seite(n) 923–930

    Abstract: ... active macrophages and fibroblasts. Therefore, developing methods to suppress the activation of these cells has ... of the survival rate in mice with acute and chronic liver injuries. Tumor-associated macrophages (TAM) and cancer ... tumor growth by decreasing the number of TAM/CAF and the stroma area. For the present study, we focused ...

    Abstract The onset and progression of liver diseases and cancer have shown to be affected by over-active macrophages and fibroblasts. Therefore, developing methods to suppress the activation of these cells has become an urgent task. Prior to this study, a mannosylated-albumin (Man-HSA) that targets mannose receptors expressed in hepatic macrophages (Kupffer cells) or fibroblasts was created. Here, we report on the development of medical treatments based on Man-HSA. To target the reactive oxygen species or inflammation derived from Kupffer cells, we developed a nano-antioxidant, i.e., polythiolated (SH)-Man-HSA, by introducing thiol groups into Man-HSA, or a nano-anti-inflammatory drug, i.e., Man-HSA-IFNα2b, by fusing Man-HSA and IFNα2b. SH-Man-HSA or Man-HSA-IFNα2b attenuated Kupffer cell-derived oxidative stress or inflammation, respectively, resulting in the suppression of liver damage and overall improvement of the survival rate in mice with acute and chronic liver injuries. Tumor-associated macrophages (TAM) and cancer-associated fibroblasts (CAF), both of which are present in the stroma of intractable cancers, also express mannose receptors. Thus, mono-polyethylene glycol modified Man-HSA (monoPEG-Man-HSA) was synthesized as a novel drug delivery carrier targeting TAM/CAF. A complex of monoPEG-Man-HSA with paclitaxel suppressed tumor growth by decreasing the number of TAM/CAF and the stroma area. For the present study, we focused on the mannose receptors expressed in macrophages and fibroblasts, and developed drug delivery carriers that target these cells. Considering the excellent drug-carrying capacity and high biocompatibility of HSA, it is expected that this research will pave the way for innovative pharmacotherapy to treat unmet medical needs, i.e., intractable liver diseases and cancer.
    Mesh-Begriff(e) Humans ; Mice ; Animals ; Mannose Receptor ; Receptors, Albumin ; Mannose ; Albumins ; Drug Delivery Systems ; Drug Carriers ; Interferon-alpha ; Liver Diseases ; Inflammation ; Neoplasms/drug therapy
    Chemische Substanzen Mannose Receptor ; Receptors, Albumin ; Mannose (PHA4727WTP) ; Albumins ; Drug Carriers ; Interferon-alpha
    Sprache Japanisch
    Erscheinungsdatum 2023-11-01
    Erscheinungsland Japan
    Dokumenttyp English Abstract ; Journal Article
    ZDB-ID 200514-1
    ISSN 1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
    ISSN (online) 1347-5231
    ISSN 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
    DOI 10.1248/yakushi.23-00118
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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