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pancreatic cancer neural invasion

Dhananjaya Sharma, Shuji Isaji
Focused pathological attention to tumor invasion of the retroperitoneal resection margin after pancreaticoduodenectomy for cancer of head of the pancreas led to the knowledge of strong tendency of cancer cells to infiltrate into the retropancreatic tissue and to spread along the peripancreatic neural plexuses as the cause of local recurrence. The term 'mesopancreas' was coined to describe perineural lymphatic layer located dorsally to the pancreas and it was suggested that its complete resection will minimize loco-regional recurrence and improve outcome...
October 12, 2016: Journal of Hepato-biliary-pancreatic Sciences
Shorook Na'ara, Ziv Gil, Moran Amit
One way that solid tumors disseminate is through neural invasion. This route is well-known in cancers of the head and neck, prostate, and pancreas. These neurotropic cancer cells have a unique ability to migrate unidirectionally along nerves towards the central nervous system (CNS). The dorsal root ganglia (DRG)/cancer cell model is a three dimensional (3D) in vitro model frequently used for studying the interaction between neural stroma and cancer cells. In this model, mouse or human cancer cell lines are grown in ECM adjacent to preparations of freshly dissociated cultured DRG...
2016: Journal of Visualized Experiments: JoVE
Dingkong Liang, Si Shi, Jin Xu, Bo Zhang, Yi Qin, Shunrong Ji, Wenyan Xu, Jiang Liu, Liang Liu, Chen Liu, Jiang Long, Quanxing Ni, Xianjun Yu
Pancreatic cancer is one of the most malignant human tumors. Perineural invasion, whereby a cancer cell invades the perineural spaces surrounding nerves, is acknowledged as a gradual contributor to cancer aggressiveness. Furthermore, perineural invasion is considered one of the root causes of the recurrence and metastasis observed after pancreatic resection, and it is also an independent predictor of prognosis. Advanced research has demonstrated that the neural microenvironment is closely associated with perineural invasion in pancreatic cancer...
April 2016: Biochimica et Biophysica Acta
Jun Yao, Wen-Yao Li, She-Gan Gao
Pancreatic cancer is a deadly malignancy associated with rapid progression and poor prognosis. Perineural invasion (PNI) in pancreatic cancer is one of the most common characteristics of this disease, with incidence of nerve invasion between 53.3% and 90%. PNI is also associated with disease recurrence and pain. Despite research efforts, the detailed mechanisms underlying PNI in pancreatic cancer remains unknown. The main factors of PNI in pancreatic cancer will be introduced in the following: 1. The anatomy of the pancreas nerve: The cancer cells along the blood vessels, lymphatic vessels, peripheral nerve gap and perineurium to Invasion...
2015: American Journal of Cancer Research
Elke Tieftrunk, Ihsan Ekin Demir, Helmut Friess, Güralp O Ceyhan
Neural invasion (NI) and severe pain are common features in patients with pancreatic cancer (PCa). Here, we present the case of a 67-year-old patient with PCa whose pre- and postoperative physical situation was clearly dominated by severe pain sensation. The resected pancreas specimen revealed severe and frequent NI by cancer cells. Seven months after R1 resection and additive chemotherapy, the patient presented with severe lumbar back pain. The CT scan showed liver metastasis and local recurrence around the celiac trunk...
2015: Journal of Surgical Case Reports
Ihsan Ekin Demir, Helmut Friess, Güralp O Ceyhan
Pancreatic nerves undergo prominent alterations during the evolution and progression of human chronic pancreatitis and pancreatic cancer. Intrapancreatic nerves increase in size (neural hypertrophy) and number (increased neural density). The proportion of autonomic and sensory fibres (neural remodelling) is switched, and are infiltrated by perineural inflammatory cells (pancreatic neuritis) or invaded by pancreatic cancer cells (neural invasion). These neuropathic alterations also correlate with neuropathic pain...
November 2015: Nature Reviews. Gastroenterology & Hepatology
Xuan Wang, Hongwei Zhang, Taihong Wang, Wan Yee Lau, Xin Wang, Jingfeng Sun, Zhenhua Yuan, Yewei Zhang
Pancreatic head cancer is a common but the most lethal cancer of the human digestive system. It is invasive, resulting in early infiltration of adjacent structures and lymph node and distant metastases. Its biological characteristics of neurotropic growth lead to early neural invasion (NI) which is an independent prognostic factor of survival for pancreatic cancer. Radical surgical resection remains the only form of curative treatment. The extent of surgical resection and whether extended resection results in better long-term survival have been controversial...
December 2015: International Journal of Oncology
Jun-Chao Guo, Jian Li, Yu-Pei Zhao, Li Zhou, Quan-Cai Cui, Wei-Xun Zhou, Tai-Ping Zhang, Lei You
It has long been regarded that pancreatic cancer (PC) is a life-threatening malignant tumor. Thus, much attention has been paid for factors, especially relative molecules, predictive for prognosis of PC. However, c-fos expression in PC was less investigated. In addition, its association with clinicopathologic variables and prognosis remains unknown. In the present study, expression of c-fos was detected by tissue microarray-based immunohistochemical staining in cancer and adjacent tissues from 333 patients with PC...
2015: PloS One
Tong Han, Xiao-Ping Yi, Bo Liu, Mu-Jing Ke, Yi-Xiong Li
MicroRNAs (miRNAs) represent a class of small non‑coding RNAs regulating gene expression by inducing the degradation of RNA or interfering with translation. Aberrant miRNA expression has been described in several types of cancer in humans. In the present study, it was demonstrated that miR‑145 is downregulated in pancreatic cancer tissues and the Panc‑1 cell line. Restoration of miR‑145 inhibited cell proliferation, invasion and migration in Panc‑1 cells. Neural precursor cell expressed, developmentally down‑regulated 9 (NEDD9) has been identified as a novel potential miR‑145 target using bioinformatics...
June 2015: Molecular Medicine Reports
Takehito Yamamoto, Shintaro Yagi, Hiromitsu Kinoshita, Yusuke Sakamoto, Kazuyuki Okada, Kenji Uryuhara, Takeshi Morimoto, Satoshi Kaihara, Ryo Hosotani
AIM: To retrospectively analyze factors affecting the long-term survival of patients with pancreatic cancer who underwent pancreatic resection. METHODS: From January 2000 to December 2011, 195 patients underwent pancreatic resection in our hospital. The prognostic factors after pancreatic resection were analyzed in all 195 patients. After excluding the censored cases within an observational period, the clinicopathological characteristics of 20 patients who survived ≥ 5 (n = 20) and < 5 (n = 76) years were compared...
January 7, 2015: World Journal of Gastroenterology: WJG
Florian Liebl, Ihsan Ekin Demir, Katharina Mayer, Tibor Schuster, Jan G DʼHaese, Karen Becker, Rupert Langer, Frank Bergmann, Kun Wang, Robert Rosenberg, Alexander R Novotny, Marcus Feith, Daniel Reim, Helmut Friess, Güralp O Ceyhan
OBJECTIVES: Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. BACKGROUND: The union internationale contre le cancer (UICC) recently added NI as a novel parameter in the current TNM classification. However, there are only a few existing studies with specific focus on NI, so that the distinct role of NI in GIMs is still uncertain...
November 2014: Annals of Surgery
Keisuke Taniuchi, Mutsuo Furihata, Kazuhiro Hanazaki, Motoaki Saito, Toshiji Saibara
Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that IGF2BP3 promoted the invasiveness and metastasis of pancreatic cancers through locally translated IGF2BP3-bound transcripts. In neural cells, transcripts sorted into cytoplasmic RNA granules are transported to dendrites and translated in these dendrites, thereby mediating long-term synaptic plasticity; however, such cytoplasmic RNA granules are not known to contribute to the progression of pancreatic cancer...
August 30, 2014: Oncotarget
Ihsan Ekin Demir, Alexandra Boldis, Paulo L Pfitzinger, Steffen Teller, Eva Brunner, Natascha Klose, Timo Kehl, Matthias Maak, Marina Lesina, Melanie Laschinger, Klaus-Peter Janssen, Hana Algül, Helmut Friess, Güralp O Ceyhan
BACKGROUND: In neural invasion (NI), cancer cells are classically assumed to actively invade nerves and to cause local recurrence and pain. However, the opposite possibility, that nerves may reach cancer cells even in their preinvasive stage and thereby promote cancer spread, has not yet been genuinely considered. The present study analyzes the reaction of Schwann cells of peripheral nerves to carcinogenesis in pancreatic cancer and colon cancer. METHODS: Two novel 3D migration and Schwann cell outgrowth assays were developed to monitor the timing and the specificity of Schwann cell migration and cancer invasion toward peripheral neurons through digital-time-lapse microscopy and after blockade of nerve growth factor (NGF) signalling via siRNA or a small-molecule inhibitor of the p75(NTR) receptor...
August 2014: Journal of the National Cancer Institute
L-N Xue, F H Bai, X-Y Wang, M Lin, Y Tan, X-Y Yao, K-Q Xu
We investigated the clinical significance of RUNX3 gene expression in human pancreatic carcinoma. Five samples of pancreatic tissues and 30 samples of pancreatic cancer tissues and paracancerous tissues were collected. RUNX3 expression was detected by real-time PCR and immunohistochemistry. The relationships between clinicopathological findings and the expression of RUNX3 were analyzed. The relative quantification level of RUNX3 mRNA expression in human pancreatic carcinoma tissues and paracancerous tissues was 2...
2014: Genetics and Molecular Research: GMR
Motokazu Sugimoto, Shuichi Mitsunaga, Kiyoshi Yoshikawa, Yuichiro Kato, Naoto Gotohda, Shinichiro Takahashi, Masaru Konishi, Masafumi Ikeda, Motohiro Kojima, Atsushi Ochiai, Hironori Kaneko
BACKGROUND: Neural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC. METHODS: Participants comprised 170 patients who underwent curative pancreaticoduodenectomy for pancreatic IDC...
July 2014: European Journal of Cancer
Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao
AIM: To investigate midkine (MK) and syndecan-3 protein expression in pancreatic cancer by immunohistochemistry, and to analyze their correlation with clinicopathological features, perineural invasion, and prognosis. METHODS: Pancreatic cancer tissues (including adequately sized tumor tissue samples and tissue samples taken from areas less than 2.0 cm around the tumor) were taken from 42 patients who were undergoing a partial duodenopancreatectomy. MK and syndecan-3 proteins were detected by immunohistochemistry using a standardized streptavidin-peroxidase method, and analyzed for their correlation with clinicopathological features, perineural invasion, and prognosis...
March 21, 2014: World Journal of Gastroenterology: WJG
Corina Kim-Fuchs, Caroline P Le, Matthew A Pimentel, David Shackleford, Davide Ferrari, Eliane Angst, Frédéric Hollande, Erica K Sloan
Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated...
August 2014: Brain, Behavior, and Immunity
Akiko Matsubara, Satoshi Nara, Shigeki Sekine, Hidenori Ojima, Tomoo Kosuge, Kazuaki Shimada, Ryoji Kushima, Yae Kanai, Nobuyoshi Hiraoka
It has been speculated that intraductal dissemination, via the pancreatic duct, bile duct, or mammary duct, is a unique form of cancer cell spread. However, clinical evidence to confirm this form of dissemination has been lacking. Here we report a case of papillary adenocarcinoma of the ampulla of Vater in which retrograde dissemination to the pancreatic duct was strongly suggested. A 79-year-old woman underwent pancreatoduodenectomy for a 22 mm microinvasive papillary adenocarcinoma of the ampulla. Multiple carcinomas in situ were found in the pancreatic duct distant from the ampulla...
January 2014: Pathology International
Andreas Göhrig, Katharina M Detjen, Georg Hilfenhaus, Jan L Körner, Martina Welzel, Ruza Arsenic, Rosa Schmuck, Marcus Bahra, Jane Y Wu, Bertram Wiedenmann, Christian Fischer
Pancreatic ductal adenocarcinoma (PDAC) metastasizes by neural, vascular, and local invasion routes, which limit patient survival. In nerves and vessels, SLIT2 and its ROBO receptors constitute repellent guidance cues that also direct epithelial branching. Thus, the SLIT2-ROBO system may represent a key pinch point to regulate PDAC spread. In this study, we examined the hypothesis that escaping from repellent SLIT2-ROBO signaling is essential to enable PDAC cells to appropriate their local stromal infrastructure for dissemination...
March 1, 2014: Cancer Research
Ihsan Ekin Demir, Güralp O Ceyhan, Florian Liebl, Jan G D'Haese, Matthias Maak, Helmut Friess
In the past 15 years, invasion of nerves by cancer cells has escaped from its role as a mere bystander in cancer biology and turned into an attractive niche to study the heterotypic interaction between cancer cells and neurons. Today, neural invasion (NI) in pancreatic cancer (PCa) stands out due to the recent demonstration of its association with tumor progression, local recurrence and neuropathic pain. Accordingly, recent research on NI in PCa revealed the critical involvement of numerous nerve- or cancer cell-derived molecules in several novel in vitro and in vivo models of NI, which, however, still need further major improvement...
2010: Cancers
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