Researcher:
Kurtoğlu, Metin

Profile Picture
ORCID

Job Title

Researcher

First Name

Metin

Last Name

Kurtoğlu

Name

Name Variants

Kurtoğlu, Metin

Email Address

Birth Date

Filters

2016 - 20193

Advanced Search

Filter by

Settings

Researcher Of Publications: search.filters.isAuthorOfPublication.c691bf44-6d5c-47ed-828d-05f7e307dc04

Search Results

Now showing 1 - 3 of 3
  • Placeholder
    PublicationMetadata only
    The role of hypoxia in pancreatic cancer: a potential therapeutic target?
    (Taylor and Francis Ltd, 2016) Kleeff, Jorg; N/A; Erkan, Murat Mert; Kurtoğlu, Metin; Faculty Member; Researcher; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; Koç University Hospital; 214689; N/A
    One of the key factors that correlates with poor survival of patients with pancreatic cancer is the extent of hypoxic areas within the tumor tissue. The adaptation of pancreatic cancer cells to limited oxygen delivery promotes the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development, which resist in most cases adjuvant therapies following tumor resection. In this article, the authors summarize the evidence demonstrating the significance of hypoxia in pancreatic cancer pathogenesis and discuss the possible hypoxia-induced mechanisms underlying its aggressive nature. We then conclude with promising strategies that target hypoxia-adapted pancreatic cancer cells.
  • Thumbnail Image
    PublicationOpen Access
    Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells
    (Elsevier, 2019) N/A; Department of Chemical and Biological Engineering; Oran, Dilem Ceren; Lokumcu, Tolga; Bal, Tuğba; İnceoğlu, Yasemin; Albayrak, Özgür; Erkan, Murat Mert; Kurtoğlu, Metin; Can, Füsun; Önder, Tuğba Bağcı; Kızılel, Seda; Akolpoğlu, Mükrime Birgül; Faculty Member; Faculty Member; Master Student; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; Graduate School of Health Sciences; College of Engineering; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 103165; 184359; 28376; N/A
    Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients’ own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward ​the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.
  • Thumbnail Image
    PublicationOpen Access
    Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress
    (Impact Journals, 2016) Liu, Huaping; Lucia Leon; Annicchiarico, Clara; Munoz-Pinedo, Cristina; Barredo, Julio; Leclerc, Guy; Merchan, Jaime; Liu, Xiongfei; Lampidis, Theodore J.; Kurtoğlu, Metin; Graduate School of Health Sciences
    Unregulated growth and replication as well as an abnormal microenvironment, leads to elevated levels of stress which is a common trait of cancer. By inducing both energy and endoplasmic reticulum (ER) stress, 2-Deoxy-glucose (2-DG) is particularly well-suited to take advantage of the therapeutic window that heightened stress in tumors provides. Under hypoxia, blocking glycolysis with 2-DG leads to significant lowering of ATP resulting in energy stress and cell death in numerous carcinoma cell types. In contrast, under normoxia, 2-DG at a low-concentration is not toxic in most carcinomas tested, but induces growth inhibition, which is primarily due to ER stress. Here we find a synergistic toxic effect in several tumor cell lines in vitro combining 2-DG with fenofibrate (FF), a drug that has been safely used for over 40 years to lower cholesterol in patients. This combination induces much greater energy stress than either agent alone, as measured by ATP reduction, increased p-AMPK and downregulation of mtor. Inhibition of mtor results in blockage of GRP78 a critical component of the unfolded protein response which we speculate leads to greater ER stress as observed by increased p-eif2 alpha. Moreover, to avoid an insulin response and adsorption by the liver, 2-DG is delivered by slow-release pump yielding significant anti-tumor control when combined with FF. Our results provide promise for developing this combination clinically and others that combine 2-DG with agents that act synergistically to selectively increase energy and ER stress to a level that is toxic to numerous tumor cell types.