Browsing by Author "Reyes, Carmen Mota"

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    Clinically Actionable Strategies for Studying Neural Influences in Cancer
    (CELL PRESS, 2020-01-01) Demir, Ihsan Ekin; Reyes, Carmen Mota; Alrawashdeh, Wasfi; Ceyhan, Guralp O.; Deborde, Sylvie; Friess, Helmut; Gorgulu, Kivanc; Istvanffy, Rouzanna; Jungwirth, David; Kuner, Rohini; Maryanovich, Maria; Na'ara, Shorook; Renders, Simon; Saloman, Jami L.; Scheff, Nicole N.; Steenfadt, Hendrik; Stupakov, Pavel; Thiel, Vera; Verma, Divij; Yilmaz, Bengi Su; White, Ruth A.; Wang, Timothy C.; Wong, Richard J.; Frenette, Paul S.; Gil, Ziv; Davis, Brian M.
    Neuro-glial activation is a recently identified hallmark of growing cancers. Targeting tumor hyperinnervation in preclinical and small clinical trials has yielded promising antitumor effects, highlighting the need of systematic analysis of neural influences in cancer (NIC). Here, we outline the strategies translating these findings from bench to the clinic.
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    Future directions in preclinical and translational cancer neuroscience research
    (NATURE PORTFOLIO, 2020-01-01) Demir, Ihsan Ekin; Reyes, Carmen Mota; Alrawashdeh, Wasfi; Ceyhan, Gueralp O.; Deborde, Sylvie; Friess, Helmut; Goerguelue, Kivanc; Istvanffy, Rouzanna; Jungwirth, David; Kuner, Rohini; Maryanovich, Maria; Na'ara, Shorook; Renders, Simon; Saloman, Jami L.; Scheff, Nicole N.; Steenfadt, Hendrik; Stupakov, Pavel; Thiel, Vera; Verma, Divij; Yilmaz, Bengi Su; White, Ruth A.; Wang, Timothy C.; Wong, Richard J.; Frenette, Paul S.; Gil, Ziv; Davis, Brian M.; Res, Neural Influences Can N.I.C. Int
    Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here we outline recommendations for future preclinical and translational research in this field.
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    Regulatory T Cells in Pancreatic Cancer: Of Mice and Men
    (MDPI, 2022-01-01) Reyes, Carmen Mota; Demir, Elke; Cifcibasi, Kaan; Istvanffy, Rouzanna; Friess, Helmut; Demir, Ihsan Ekin
    Simple Summary Regulatory T cells (Treg) are a major immunosuppressive cell subset in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies, whereupon Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these compensatory mechanisms may be patients with locally advanced PCa undergoing neoadjuvant therapy (neoTx). In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform. Regulatory T cells (Treg) are one of the major immunosuppressive cell subsets in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells mechanisms form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies where after Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these complex compensatory mechanisms may be the tumors of patients who underwent neoTx. Here, we observed a parallel decrease in the numbers of both intratumoral Tregs and MDSC after neoTx even in locally advanced PCa. NeoTx also led to decreased amounts of alpha SMA(+) myofibroblastic cancer-associated fibroblasts (myCAF) and increased proportions of CD8(+) cytotoxic T lymphocytes in the tumor. In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform.
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    Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis
    (ELSEVIER, 2019-01-01) Demir, Ihsan Ekin; Heinrich, Tobias; Carty, Dominique G.; Saricaoglu, Omer Cemil; Klauss, Sarah; Teller, Steffen; Kehl, Timo; Reyes, Carmen Mota; Tieftrunk, Elke; Lazarou, Maria; Bahceci, Dorukhan H.; Gokcek, Betul; Ucurum, Bahar E.; Maak, Matthias; Diakopoulos, Kalliope N.; Lesina, Marina; Schemann, Michael; Erkane, Mert; Krueger, Achim; Algul, Hana; Friess, Helmut; Ceyhan, Guralp O.
    Background: Pain due to pancreatic cancer/PCa or chronic pancreatitis/CP, is notoriously resistant to the strongest pain medications. Here, we aimed at deciphering the specific molecular mediators of pain at surgical-stage pancreatic disease and to discover novel translational targets. Methods: We performed a systematic, quantitative analysis of the neurotransmitter/neuroenzmye profile within intrapancreatic nerves of CP and PCa patients. Ex vivo neuronal cultures treated with human pancreatic extracts, conditional genetically engineered knockout mouse models of PCa and CP, and the cerulein-induced CP model were employed to explore the therapeutic potential of the identified targets. Findings: We identified a unique enrichment of neuronal nitric-oxide-synthase (nNOS) in the pancreatic nerves of CP patients with increasing pain severity. Employment of ex vivo neuronal cultures treated with pancreatic tissue extracts of CP patients, and brain-derived-neurotrophic-factor-deficient (BDNF+/-) mice revealed neuronal enrichment of nNOS to be a consequence of BDNI loss in the progressively destroyed pancreatic tissue. Mechanistically, nNOS upregulation in sensory neurons was induced by tryptase secreted from perineural mast cells. In a head-to-head comparison of several genetically induced, painless mouse models of PCa (KPC, KC mice) or CP (Ptf1a-Cre