Browsing by Author "Ceyhan, Gueralp O."

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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.
Localisation analysis of nerves in the mouse pancreas reveals the sites of highest nerve density and nociceptive innervation
(WILEY, 2020-01-01) Saricaoglu, Oemer Cemil; Teller, Steffen; Wang, Xiaobo; Wang, Shenghan; Stupakov, Pavel; Heinrich, Tobias; Istvanffy, Rouzanna; Friess, Helmut; Ceyhan, Gueralp O.; Demir, Ihsan Ekin
Background Neuropathy and neuro-inflammation drive the severe pain and disease progression in human chronic pancreatitis and pancreatic cancer. Mice, especially genetically induced-mouse models, have been increasingly utilized in mechanistic research on pancreatic neuropathy, but the normal ``peripheral neurobiology{''} of the mouse pancreas has not yet been critically compared to human pancreas. Methods We introduced a standardized tissue-harvesting technique that preserves the anatomic orientation of the mouse pancreas and allows complete sectioning in an anterior to posterior fashion. We applied immunohistochemistry and quantitative colorimetry of all nerves from the whole organ for studying pancreatic neuro-anatomy. Key Results Nerves in the mouse pancreas appeared as ``clusters{''} of nerve trunks in contrast to singly distributed nerve trunks in the human pancreas. Nerve trunks in the mouse pancreas were exclusively found around intrapancreatic blood vessels, and around lymphoid structures. The majority of nerve trunks were located in the pancreatic head (0.15 +/- 0.08\% of tissue area) and the anterior/front surface of the corpus/body (0.17 +/- 0.27\%), thus significantly more than in the tail (0.02 +/- 0.02\%, P = .006). Nerves in the tail included a higher proportion of nociceptive fibers, but the absolute majority, ie, ca. 70\%, of all nociceptive fibers, were localized in the head. Mice heterozygous for Bdnf knockout allele (Bdnf(+/-)) exhibited enrichment of nitrergic nerve fibers specifically in the head and corpus. Conclusions \& Inferences Neuro-anatomy of the ``mesenteric type{''} mouse pancreas is highly different from the ``compact{''} human pancreas. Studies that aim at reproducing human pancreatic neuro-phenomena in mouse models should pay diligent attention to these anatomic differences.
Molecular Profiling in Pancreatic Cancer: Current Role and Its Impact on Primary Surgery
(KARGER, 2019-01-01) Mota Reyes, Carmen; Dogruoez, Alper; Istvanffy, Rouzanna; Friess, Helmut; Ceyhan, Gueralp O.; Demir, Ihsan Ekin
Background: The advent of next-generation sequencing technologies has enabled the identification of molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) with different biological traits and clinically targetable features. Summary: Although current chemotherapy trials are currently exploiting this knowledge, these molecular subtypes have not yet sufficiently caught the attention of surgeons. In fact, integration of these molecular subtypes into the timing of surgery can in theory improve patient outcome. Here, we present the molecular subtypes of PDAC from the surgeon's perspective and a clinically applicable algorithm that integrates the molecular subtyping of PDAC preoperatively into the decision of primary surgery versus neoadjuvant therapy. Furthermore, we point out the potential of ``tailored{''} (in addition to conventional) neoadjuvant treatment for exploiting the molecular subtypes of PDAC. Key Messages: We believe that for surgeons, the preoperative knowledge on the subtype of PDAC can properly guide in deciding between upfront surgery versus neoadjuvant treatment for improving patient outcome.