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https://www.readbyqxmd.com/read/29683978/antimicrobial-peptide-human-neutrophil-peptide-1-as-a-potential-link-between-chronic-inflammation-and-ductal-adenocarcinoma-of-the-pancreas
#1
Thomas Pausch, Sarah Adolph, Klaus Felix, Andrea S Bauer, Frank Bergmann, Jens Werner, Werner Hartwig
OBJECTIVES: Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). METHODS: Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis...
April 19, 2018: Pancreas
https://www.readbyqxmd.com/read/29683142/diagnostic-intervals-and-pancreatic-ductal-adenocarcinoma-pdac-resectability-a-single-center-retrospective-analysis
#2
Amar B Deshwar, Elizabeth Sugar, Deirdre Torto, Ana De Jesus-Acosta, Matthew J Weiss, Christopher L Wolfgang, Dung Le, Jin He, Richard Burkhart, Lei Zheng, Daniel Laheru, Mark Yarchoan
Background: Pancreatic ductal adenocarcinoma (PDAC) often presents with nonspecific symptoms and the workup is not standardized. To study the impact of delays in diagnosis and in the initiation of treatment, we investigated the relationship between length of diagnostic intervals and surgical resectability. Methods: We performed a retrospective chart review of patients evaluated for PDAC at Johns Hopkins in 2014. Data were collected on the patient (date of first symptoms-first medical appointment), diagnostic (first medical appointment-diagnosis of PDAC), and treatment (diagnosis of PDAC-1st day of treatment) time intervals, and the upfront treatment received...
2018: Ann Pancreat Cancer
https://www.readbyqxmd.com/read/29682330/yes-associated-protein-yap-in-pancreatic-cancer-at-the-epicenter-of-a-targetable-signaling-network-associated-with-patient-survival
#3
Enrique Rozengurt, James Sinnett-Smith, Guido Eibl
Pancreatic ductal adenocarcinoma (PDAC) is generally a fatal disease with no efficacious treatment modalities. Elucidation of signaling mechanisms that will lead to the identification of novel targets for therapy and chemoprevention is urgently needed. Here, we review the role of Yes-associated protein (YAP) and WW-domain-containing Transcriptional co-Activator with a PDZ-binding motif (TAZ) in the development of PDAC. These oncogenic proteins are at the center of a signaling network that involves multiple upstream signals and downstream YAP-regulated genes...
2018: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29679211/surgery-after-folfirinox-treatment-for-locally-advanced-and-borderline-resectable-pancreatic-cancer-increase-in-tumour-attenuation-on-ct-correlates-with-r0-resection
#4
Giovanni Marchegiani, Valentina Todaro, Enrico Boninsegna, Riccardo Negrelli, Binit Sureka, Debora Bonamini, Roberto Salvia, Riccardo Manfredi, Roberto Pozzi Mucelli, Claudio Bassi
OBJECTIVES: To assess factors associated with radical resection (R0) of pancreatic ductal adenocarcinoma (PDAC) after induction treatment with FOLFIRINOX. METHODS: Patients with either locally advanced (LA) and borderline resectable (BR) PDAC undergoing surgical exploration after FOLFIRINOX were retrospectively enrolled. Two pancreatic radiologists reviewed the CT blinded to the final outcome and assessed chemotherapy response and resectability. Patients were then divided into R0 resected (group A) and not resected/R1 resected (group B), which were compared...
April 20, 2018: European Radiology
https://www.readbyqxmd.com/read/29675938/value-of-additional-endoscopic-ultrasonography-for-surveillance-after-surgical-removal-of-intraductal-papillary-mucinous-neoplasms
#5
Ken Kamata, Mamoru Takenaka, Kosuke Minaga, Shunsuke Omoto, Takeshi Miyata, Kentaro Yamao, Hajime Imai, Atsushi Nakai, Hidekazu Tanaka, Yasutaka Chiba, Tomohiro Watanabe, Toshiharu Sakurai, Naoshi Nishida, Takaaki Chikugo, Ippei Matsumoto, Yoshifumi Takeyama, Masayuki Kitano, Masatoshi Kudo
BACKGROUND AND AIMS: This study evaluated the utility of endoscopic ultrasonography (EUS), combined with contrast-enhanced harmonic EUS (CH-EUS), for surveillance of the remnant pancreas after surgery for intraductal papillary mucinous neoplasm (IPMN). METHODS: This was a single-center, retrospective, descriptive study. A total of 134 consecutive patients who underwent surgical resection for IPMN between April 2009 and March 2015 were evaluated. The rates of recurrence and development of IPMN-concomitant pancreatic ductal adenocarcinoma (PDAC) during follow-up were assessed...
April 19, 2018: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
https://www.readbyqxmd.com/read/29675761/vitamin-d-supplementation-is-a-promising-therapy-for-pancreatic-ductal-adenocarcinoma-in-conjunction-with-current-chemoradiation-therapy
#6
Yosuke Mukai, Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Tadafumi Asaoka, Takehiro Noda, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
BACKGROUND: The cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) are well known to play a dominant role in distant metastasis. Nevertheless, the effect on CAFs with current chemoradiation therapies remains uncertain. OBJECTIVE: This study aimed to reveal the role of CAFs under current chemoradiation therapy (CRT) and investigate the factors regulating CAFs. METHODS: α-SMA-positive cells in 86 resected PDAC specimens with/without preoperative CRT were evaluated by immunohistochemistry...
April 19, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29675111/a-survival-model-in-locally-advanced-and-metastatic-pancreatic-ductal-adenocarcinoma
#7
Yi Wang, Xiuying Xiao, Tianyi Wang, Lin Li, Yue Zhu, Haiyan Xu, Yuening Chu, Feng Jiao, Jiujie Cui, Liwei Wang
The prognostic role of serum LDH, CA19-9, CRP and ALB in PDAC patients are controversial. In contrast to single factor, there is much less information about the prognostic value of the combination of the four factors in locally advanced and metastatic PDAC patients. It's essential to set up a survival model with the combination of tumor metabolism, tumor biomarker, systemic inflammation and nutritional status to eliminate the prognostic inaccuracy in single biomarker. 94 advanced PDAC patients who received palliative chemotherapy from 2009 to 2017 were recruited for this study...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29675033/identification-and-validation-of-a-diagnostic-and-prognostic-multi-gene-biomarker-panel-for-pancreatic-ductal-adenocarcinoma
#8
Hagen Klett, Hannah Fuellgraf, Ella Levit-Zerdoun, Saskia Hussung, Silke Kowar, Simon Küsters, Peter Bronsert, Martin Werner, Uwe Wittel, Ralph Fritsch, Hauke Busch, Melanie Boerries
Late diagnosis and systemic dissemination essentially contribute to the invariably poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Therefore, the development of diagnostic biomarkers for PDAC are urgently needed to improve patient stratification and outcome in the clinic. By studying the transcriptomes of independent PDAC patient cohorts of tumor and non-tumor tissues, we identified 81 robustly regulated genes, through a novel, generally applicable meta-analysis. Using consensus clustering on co-expression values revealed four distinct clusters with genes originating from exocrine/endocrine pancreas, stromal and tumor cells...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29672406/number-of-examined-lymph-nodes-and-nodal-status-assessment-in-distal-pancreatectomy-for-body-tail-ductal-adenocarcinoma
#9
Giuseppe Malleo, Laura Maggino, Cristina R Ferrone, Giovanni Marchegiani, Mari Mino-Kenudson, Paola Capelli, Borislav Rusev, Keith D Lillemoe, Claudio Bassi, Carlos Fernàndez-Del Castillo, Roberto Salvia
OBJECTIVE: First, to assess the impact of the number of examined lymph nodes (ELNs) on staging and survival after distal pancreatectomy (DP) for pancreatic adenocarcinoma (PDAC). Second, to identify the minimum number of ELNs (MNELNs) ensuring an accurate detection of nodal involvement. Third, to reappraise the role of lymph node (LN) parameters, including N-status and lymph node ratio (LNR). BACKGROUND: In contrast with pancreatoduodenectomy, information on LN staging and the MNELN required in DP is lacking...
April 18, 2018: Annals of Surgery
https://www.readbyqxmd.com/read/29671412/possible-molecular-markers-for-the-diagnosis-of-pancreatic-ductal-adenocarcinoma
#10
Quan Shen, Miao Yu, Jiang-Kun Jia, Wen-Xi Li, Yu-Wei Tian, Huan-Zhou Xue
BACKGROUND We aimed to identify pivotal genes and pathways involved in pancreatic ductal adenocarcinoma (PDAC), and explore possible molecular markers for the early diagnosis of the disease. MATERIAL AND METHODS The array data of GSE74629, including 34 PDAC samples and 16 healthy samples, was downloaded from GEO (Gene Expression Omnibus) database. Then, the DEGs (differentially expressed genes) in PDAC samples were compared with healthy samples using limma (linear models for microarray). Gene functional interaction networks were analyzed with Cytoscape and ReactomeFIViz...
April 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29670543/phosphoinositide-3-kinase-signaling-pathway-in-pancreatic-ductal-adenocarcinoma-progression-pathogenesis-and-therapeutics
#11
REVIEW
Divya Murthy, Kuldeep S Attri, Pankaj K Singh
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by its sudden manifestation, rapid progression, poor prognosis, and limited therapeutic options. Genetic alterations in key signaling pathways found in early pancreatic lesions are pivotal for the development and progression of pancreatic intraepithelial neoplastic lesions into invasive carcinomas. More than 90% of PDAC tumors harbor driver mutations in K-Ras that activate various downstream effector-signaling pathways, including the phosphoinositide-3-kinase (PI3K) pathway...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29670110/tumor-associated-macrophages-promote-progression-and-the-warburg-effect-via-ccl18-nf-kb-vcam-1-pathway-in-pancreatic-ductal-adenocarcinoma
#12
Huilin Ye, Quanbo Zhou, Shangyou Zheng, Guolin Li, Qing Lin, Lusheng Wei, Zhiqiang Fu, Bin Zhang, Yimin Liu, Zhihua Li, Rufu Chen
Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic cancer, partially owing to paracrine induction of VCAM-1 in pancreatic cancer cells. Reciprocally, VCAM-1-induced lactate production from pancreatic cancer cells with enhanced aerobic glycolysis activates macrophages to a TAM-like phenotype, forming a positive feedback loop...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29670075/the-novel-trail-receptor-agonist-apg350-exerts-superior-therapeutic-activity-in-pancreatic-cancer-cells
#13
Karen Legler, Charlotte Hauser, Jan-Hendrik Egberts, Anna Willms, Carola Heneweer, Susann Boretius, Christoph Röcken, Claus-Christian Glüer, Thomas Becker, Michael Kluge, Oliver Hill, Christian Gieffers, Harald Fricke, Holger Kalthoff, Johannes Lemke, Anna Trauzold
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has raised attention as a novel anticancer therapeutic as it induces apoptosis preferentially in tumor cells. However, first-generation TRAIL-receptor agonists (TRAs), comprising recombinant TRAIL and agonistic receptor-specific antibodies, have not demonstrated anticancer activity in clinical studies. In fact, cancer cells are often resistant to conventional TRAs. Therefore, in addition to TRAIL-sensitizing strategies, next-generation TRAs with superior apoptotic activity are warranted...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29668571/evaluating-for-pseudoprogression-in-colorectal-and-pancreatic-tumors-treated-with-immunotherapy
#14
Christine M Parseghian, Madhavi Patnana, Priya Bhosale, Kenneth R Hess, Ya-Chen Tina Shih, Bumyang Kim, Scott Kopetz, Michael J Overman, Gauri R Varadhachary, Milind Javle, Aung Naing, Sarina Piha-Paul, David Hong, Hung Le, Vivek Subbiah, Shubham Pant
Pseudoprogression has been observed in patients with various tumor types treated with immunotherapy. However, the frequency of pseudoprogression is unknown in gastrointestinal malignancies. Metastatic colorectal cancer (mCRC) and advanced pancreatic ductal adenocarcinoma (PDAC) patients who progressed on treatment with immunotherapy beyond RECIST version 1.1 criteria were analyzed. Degree of progression, tumor markers, time to progression, overall survival, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and costs were analyzed for patients treated beyond progression (TBP) and not treated beyond progression...
April 17, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29667116/intraoperative-pancreatic-cancer-detection-using-tumor-specific-multimodality-molecular-imaging
#15
Willemieke S Tummers, Sarah E Miller, Nutte T Teraphongphom, Adam Gomez, Idan Steinberg, David M Huland, Steve Hong, Sri-Rajasekhar Kothapalli, Alifia Hasan, Robert Ertsey, Bert A Bonsing, Alexander L Vahrmeijer, Rutger-Jan Swijnenburg, Teri A Longacre, George A Fisher, Sanjiv S Gambhir, George A Poultsides, Eben L Rosenthal
BACKGROUND: Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor...
April 17, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29665121/homoharringtonine-could-induce-quick-protein-synthesis-of-psmd11-through-activating-mek1-erk1-2-signaling-pathway-in-pancreatic-cancer-cells
#16
Lele Wang, Linlin Zhao, Guo Wei, Dieter Saur, Barbara Seidler, Junyan Wang, Chuanxin Wang, Tonggang Qi
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating disease with the 5-year survival rate less than 6%. In this study, we investigated if inhibiting protein synthesis directly with homoharringtonine (HHT) could induce acute apoptosis in pancreatic cancer cells through quick depletion of multiple short-lived critical members of the central proteome, example, PSMD11(26S proteasome non-ATPase regulatory subunit 11). It was shown that although HHT could inhibit proliferation and growth of MiaPaCa-2 and PANC-1 cells in a time- and dose-dependent manner, only part of pancreatic cancer cells could be induced to die through acute apoptosis...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29664340/pancreatic-ductal-adenocarcinoma-rim-enhancement-at-mr-imaging-predicts-prognosis-after-curative-resection
#17
Sunyoung Lee, Seong Hyun Kim, Hyung Kyu Park, Kee Taek Jang, Jeong Ah Hwang, Seonwoo Kim
Purpose To identify features at preoperative magnetic resonance (MR) imaging that could predict favorable prognosis after curative resection of pancreatic ductal adenocarcinoma (PDAC). Materials and Methods From January 2009 to December 2014, this retrospective study included 143 patients with surgically resected (ie, R0) PDAC who underwent preoperative MR imaging within 1 month before surgery. Clinical-pathologic and MR imaging findings for predicting disease-free survival (DFS) and overall survival (OS) were identified by using a Cox proportional hazards model...
April 17, 2018: Radiology
https://www.readbyqxmd.com/read/29662656/stereotactic-body-radiation-therapy-for-palliative-management-of-pancreatic-adenocarcinoma-in-elderly-and-medically-inoperable-patients
#18
John F Ryan, Lauren M Rosati, Vincent P Groot, Dung T Le, Lei Zheng, Daniel A Laheru, Eun J Shin, Juan Jackson, Joseph Moore, Amol K Narang, Joseph M Herman
Stereotactic body radiation therapy (SBRT) represents a promising treatment option for patients with localized pancreatic ductal adenocarcinoma (PDAC) who cannot tolerate surgical therapy. We retrospectively reviewed the records of patients with localized PDAC treated with SBRT at our institution between 2010 and 2016 to identify patients deemed medically inoperable due to poor performance status, advanced age, and/or comorbid conditions. Overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were estimated using Kaplan-Meier curves...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#19
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29660901/no-evidence-of-pancreatic-ductal-adenocarcinoma-specific-autoantibodies-to-ezrin-in-a-liquid-phase-lips-immunoassay
#20
Daniela Liberati, Ilaria Marzinotto, Cristina Brigatti, Erica Dugnani, Valentina Pasquale, Michele Reni, Gianpaolo Balzano, Massimo Falconi, Lorenzo Piemonti, Vito Lampasona
BACKGROUND: Sensitive and specific biomarkers of Pancreatic Ductal Adenocarcinoma (PDAC) are desperately needed to allow early diagnosis and improve patient's survival. Ezrin autoantibodies were recently described as present in 93% of PDAC patients and 40% of healthy subjects who later developed PDAC. However, another prospective study failed to replicate these findings. Both studies were based on the use of a solid phase ELISA immunoassay. OBJECTIVE: We aimed at re-evaluating the usefulness of Ezrin autoantibodies as PDAC biomarkers using the Luciferase Immuno Precipitation System (LIPS), an alternative immunoassay format that found successful application for the measurement of autoantibodies against pancreatic autoantigens...
April 3, 2018: Cancer Biomarkers: Section A of Disease Markers
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