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  1. AU="Madheswaran, Suresh"
  2. AU=Rogerio Alexandre de Paula
  3. AU=Warshaw A L
  4. AU="Waqar Ahmed"
  5. AU="Harper, William A."
  6. AU="Fargo, Keith"
  7. AU=Reed Matthew J
  8. AU="Harris, Hannah L"
  9. AU="Asahi, Hiroko"
  10. AU="Mohamed El Mohadab"
  11. AU="Jamjoom, Maan"
  12. AU="Benjamin K. Harley"
  13. AU="Redpath, Stephanie"
  14. AU="Costa Oliveira, Diogo"
  15. AU="Ibarra-Meneses, Ana Victoria"
  16. AU=Ozgenel Guzin Yesim
  17. AU="Shu-Ying Li"
  18. AU="Umemura, Yutaka"
  19. AU=Eiring A M
  20. AU="Eunhee Ha"
  21. AU="Espíndola, Otávio M"
  22. AU=Shahbazian Heshmatollah
  23. AU="Esmaeel Panahi kokhdan"
  24. AU=Peekhaus N
  25. AU="Ferrari-Toniolo, Simone"
  26. AU="Oleg M. Mikhailenok"

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  1. Artikel ; Online: Syk Inhibition Reprograms Tumor-Associated Macrophages and Overcomes Gemcitabine-Induced Immunosuppression in Pancreatic Ductal Adenocarcinoma.

    Rohila, Deepak / Park, In Hwan / Pham, Timothy V / Weitz, Jonathan / Hurtado de Mendoza, Tatiana / Madheswaran, Suresh / Ishfaq, Mehreen / Beaman, Cooper / Tapia, Elisabette / Sun, Siming / Patel, Jay / Tamayo, Pablo / Lowy, Andrew M / Joshi, Shweta

    Cancer research

    2023  Band 83, Heft 16, Seite(n) 2675–2689

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an insidious disease with a low 5-year survival rate. PDAC is characterized by infiltration of abundant tumor-associated macrophages (TAM), which promote immune tolerance and immunotherapeutic resistance. Here ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is an insidious disease with a low 5-year survival rate. PDAC is characterized by infiltration of abundant tumor-associated macrophages (TAM), which promote immune tolerance and immunotherapeutic resistance. Here we report that macrophage spleen tyrosine kinase (Syk) promotes PDAC growth and metastasis. In orthotopic PDAC mouse models, genetic deletion of myeloid Syk reprogrammed macrophages into immunostimulatory phenotype, increased the infiltration, proliferation, and cytotoxicity of CD8+ T cells, and repressed PDAC growth and metastasis. Furthermore, gemcitabine (Gem) treatment induced an immunosuppressive microenvironment in PDAC by promoting protumorigenic polarization of macrophages. In contrast, treatment with the FDA-approved Syk inhibitor R788 (fostamatinib) remodeled the tumor immune microenvironment, "re-educated" protumorigenic macrophages towards an immunostimulatory phenotype and boosted CD8+ T-cell responses in Gem-treated PDAC in orthotopic mouse models and an ex vivo human pancreatic slice culture model. These findings illustrate the potential of Syk inhibition for enhancing the antitumor immune responses in PDAC and support the clinical evaluation of R788 either alone or together with Gem as a potential treatment strategy for PDAC.
    Significance: Syk blockade induces macrophage polarization to an immunostimulatory phenotype, which enhances CD8+ T-cell responses and improves gemcitabine efficacy in pancreatic ductal adenocarcinoma, a clinically challenging malignancy.
    Mesh-Begriff(e) Mice ; Animals ; Humans ; Gemcitabine ; Tumor-Associated Macrophages ; Carcinoma, Pancreatic Ductal/pathology ; Pancreatic Neoplasms/pathology ; Immune Tolerance ; Immunosuppression Therapy ; Tumor Microenvironment ; Cell Line, Tumor ; Pancreatic Neoplasms
    Chemische Substanzen Gemcitabine
    Sprache Englisch
    Erscheinungsdatum 2023-06-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-22-3645
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Microarray and pattern miner analysis of AXL and VIM gene networks in MDA‑MB‑231 cells.

    Natarajan, Sudhakar / Sumantran, Venil N / Ranganathan, Mohan / Madheswaran, Suresh

    Molecular medicine reports

    2018  Band 18, Heft 4, Seite(n) 4147–4155

    Abstract: MDA‑MB‑231 cells represent malignant triple‑negative breast cancer, which overexpress epidermal growth factor receptor (EGFR) and two genes (AXL and VIM) associated with poor prognosis. The present study aimed to identify novel therapeutic targets and ... ...

    Abstract MDA‑MB‑231 cells represent malignant triple‑negative breast cancer, which overexpress epidermal growth factor receptor (EGFR) and two genes (AXL and VIM) associated with poor prognosis. The present study aimed to identify novel therapeutic targets and elucidate the functional networks for the AXL and VIM genes in MDA‑MB‑231 cells. We identified 71 genes upregulated in MDA‑MB‑231 vs. MCF7 cells using BRB‑Array tool to re‑analyse microarray data from six GEO datasets. Gene ontology and STRING analysis showed that 43/71 genes upregulated in MDA‑MB‑231 compared with MCF7 cells, regulate cell survival and migration. Another 19 novel genes regulate migration, metastases, senescence, autophagy and chemoresistance. The Pattern Miner systems biology tool uses specific genes as inputs or 'baits' to identify outputs from the NCI‑60 database. Using five genes regulating cancer cell migration (AXL, VIM, EGFR, CAPN2, and COL4A1) as input 'baits', we used pattern miner to identify statistically significant, co‑expressed genes from the list of 71 genes upregulated in MDA‑MB‑231 compared with MCF7 cells. Outputs were subsets of the 71 genes, which showed significant co‑expression with one or more of the five input genes. These outputs were used to develop functional networks for AXL and VIM. Analysis of these networks verified known properties of AXL and VIM, and suggested novel functions for these two genes. Thus, genes in the AXL network promote migration, metastasis and chemoresistance, whereas the VIM gene network regulates novel tumorigenic processes, such as lipogenesis, senescence and autophagy. Notably, these two networks contain 12 genes not reported for TNBC.
    Mesh-Begriff(e) Cell Line, Tumor ; Data Mining ; Female ; Gene Expression Regulation, Neoplastic ; Gene Ontology ; Gene Regulatory Networks ; Humans ; Models, Genetic ; Oligonucleotide Array Sequence Analysis ; Protein Interaction Maps/genetics ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Triple Negative Breast Neoplasms/genetics ; Up-Regulation/genetics ; Vimentin/genetics ; Vimentin/metabolism
    Chemische Substanzen Proto-Oncogene Proteins ; Vimentin ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; axl receptor tyrosine kinase (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2018-08-20
    Erscheinungsland Greece
    Dokumenttyp Journal Article
    ISSN 1791-3004
    ISSN (online) 1791-3004
    DOI 10.3892/mmr.2018.9404
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Human Granzyme B Based Targeted Cytolytic Fusion Proteins.

    Hlongwane, Precious / Mungra, Neelakshi / Madheswaran, Suresh / Akinrinmade, Olusiji A / Chetty, Shivan / Barth, Stefan

    Biomedicines

    2018  Band 6, Heft 2

    Abstract: Cancer immunotherapy aims to selectively target and kill tumor cells whilst limiting the damage to healthy tissues. Controlled delivery of plant, bacterial and human toxins or enzymes has been shown to promote the induction of apoptosis in cancerous ... ...

    Abstract Cancer immunotherapy aims to selectively target and kill tumor cells whilst limiting the damage to healthy tissues. Controlled delivery of plant, bacterial and human toxins or enzymes has been shown to promote the induction of apoptosis in cancerous cells. The 4th generation of targeted effectors are being designed to be as humanized as possible—a solution to the problem of immunogenicity encountered with existing generations. Granzymes are serine proteases which naturally function in humans as integral cytolytic effectors during the programmed cell death of cancerous and pathogen-infected cells. Secreted predominantly by cytotoxic T lymphocytes and natural killer cells, granzymes function mechanistically by caspase-dependent or caspase-independent pathways. These natural characteristics make granzymes one of the most promising human enzymes for use in the development of fusion protein-based targeted therapeutic strategies for various cancers. In this review, we explore research involving the use of granzymes as cytolytic effectors fused to antibody fragments as selective binding domains.
    Sprache Englisch
    Erscheinungsdatum 2018-06-20
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines6020072
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Antibody-Based Targeted Interventions for the Diagnosis and Treatment of Skin Cancers.

    Madheswaran, Suresh / Mungra, Neelakshi / Biteghe, Fleury A N / De la Croix Ndong, Jean / Arowolo, Afolake T / Adeola, Henry A / Ramamurthy, Dharanidharan / Naran, Krupa / Khumalo, Nonhlanhla P / Barth, Stefan

    Anti-cancer agents in medicinal chemistry

    2020  Band 21, Heft 2, Seite(n) 162–186

    Abstract: Background: Cutaneous malignancies most commonly arise from skin epidermal cells. These cancers may rapidly progress from benign to a metastatic phase. Surgical resection represents the gold standard therapeutic treatment of non-metastatic skin cancer ... ...

    Abstract Background: Cutaneous malignancies most commonly arise from skin epidermal cells. These cancers may rapidly progress from benign to a metastatic phase. Surgical resection represents the gold standard therapeutic treatment of non-metastatic skin cancer while chemo- and/or radiotherapy are often used against metastatic tumors. However, these therapeutic treatments are limited by the development of resistance and toxic side effects, resulting from the passive accumulation of cytotoxic drugs within healthy cells.
    Objective: This review aims to elucidate how the use of monoclonal Antibodies (mAbs) targeting specific Tumor Associated Antigens (TAAs) is paving the way to improved treatment. These mAbs are used as therapeutic or diagnostic carriers that can specifically deliver cytotoxic molecules, fluorophores or radiolabels to cancer cells that overexpress specific target antigens.
    Results: mAbs raised against TAAs are widely in use for e.g. differential diagnosis, prognosis and therapy of skin cancers. Antibody-Drug Conjugates (ADCs) particularly show remarkable potential. The safest ADCs reported to date use non-toxic photo-activatable Photosensitizers (PSs), allowing targeted Photodynamic Therapy (PDT) resulting in targeted delivery of PS into cancer cells and selective killing after light activation without harming the normal cell population. The use of near-infrared-emitting PSs enables both diagnostic and therapeutic applications upon light activation at the specific wavelengths.
    Conclusion: Antibody-based approaches are presenting an array of opportunities to complement and improve current methods employed for skin cancer diagnosis and treatment.
    Mesh-Begriff(e) Animals ; Antigens, Neoplasm/analysis ; Antigens, Neoplasm/immunology ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Drug Delivery Systems ; Humans ; Immunoconjugates/administration & dosage ; Immunoconjugates/pharmacology ; Immunoconjugates/therapeutic use ; Molecular Targeted Therapy ; Photochemotherapy ; Photosensitizing Agents/administration & dosage ; Photosensitizing Agents/pharmacology ; Photosensitizing Agents/therapeutic use ; Prognosis ; Skin Neoplasms/diagnosis ; Skin Neoplasms/drug therapy ; Skin Neoplasms/immunology
    Chemische Substanzen Antigens, Neoplasm ; Antineoplastic Agents, Immunological ; Immunoconjugates ; Photosensitizing Agents
    Sprache Englisch
    Erscheinungsdatum 2020-08-11
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2217610-X
    ISSN 1875-5992 ; 1871-5206
    ISSN (online) 1875-5992
    ISSN 1871-5206
    DOI 10.2174/1871520620666200728123006
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 5583: Hefte anzeigen Standort:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
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