Browsing by Author "Stupakov, Pavel"

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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.
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.
Patterns and Relevance of Langerhans Islet Invasion in Pancreatic Cancer
(MDPI, 2021-01-01) Goess, Ruediger; Mutgan, Ayse Ceren; Calisan, Umut; Erdogan, Yusuf Ceyhun; Ren, Lei; Jager, Carsten; Safak, Okan; Stupakov, Pavel; Istvanffy, Rouzanna; Friess, Helmut; Ceyhan, Guralp O.; Demir, Ihsan Ekin
Simple Summary The pathogenesis of pancreatic cancer-associated diabetes mellitus is poorly understood. We analyzed tumor infiltration into Langerhans islets and characterized it systematically for the first time, identifying four different main patterns of islet invasion. In a cohort of 68 pancreatic ductal adenocarcinoma (PDAC) patients, these islet invasion patterns were not related to occurrence of diabetes mellitus. However, severe islet invasion was associated with worsened overall survival. Background: Pancreatic cancer-associated diabetes mellitus (PC-DM) is present in most patients with pancreatic cancer, but its pathogenesis remains poorly understood. Therefore, we aimed to characterize tumor infiltration in Langerhans islets in pancreatic cancer and determine its clinical relevance. Methods: Langerhans islet invasion was systematically analyzed in 68 patients with pancreatic ductal adenocarcinoma (PDAC) using histopathological examination and 3D in vitro migration assays were performed to assess chemoattraction of pancreatic cancer cells to islet cells. Results: Langerhans islet invasion was present in all patients. We found four different patterns of islet invasion: (Type I) peri-insular invasion with tumor cells directly touching the boundary, but not penetrating the islet