Bo Hyung Yoon, Su Mae Ang, Andre Alabd, Kevin Furlong, Charles J Yeo, Harish Lavu, Jordan M Winter
BACKGROUND: Type 3c diabetes mellitus (T3cDM) is diabetes secondary to other pancreatic diseases such as chronic pancreatitis, pancreatic resection, cystic fibrosis, and pancreatic ductal adenocarcinoma (PDA). Clinically, it may easily be confused with conventional type 2 diabetes mellitus (T2DM). A delay in pancreatic cancer diagnosis and treatment leads to a worse outcome. Therefore, early recognition of PDA-associated T3cDM and distinction from conventional T2DM represents an opportunity improve survival in patients with PDA...
January 13, 2021: Journal of Surgical Research
Erin R Okawa, Manoj K Gupta, Sevim Kahraman, Praneeth Goli, Masaji Sakaguchi, Jiang Hu, Kaiti Duan, Brittany Slipp, Jochen K Lennerz, Rohit N Kulkarni
The insulin and insulin-like growth factor-1 (IGF-1) receptors are important for the growth and development of embryonic tissues. To directly define their roles in the maintenance of pluripotency and differentiation of stem cells, we knocked out both the receptors in induced pluripotent stem cells (iPSCs). iPSCs lacking both the insulin and IGF-1 receptors (double knock-out, DKO) exhibited preserved pluripotency potential despite decreased expression of the transcription factors, Lin28a and Tbx3, compared to control iPSCs...
January 13, 2021: Molecular Metabolism
Jiawei Chen, Songsong Zheng, Yongbin Hu, Xin Mou, Huiyang Wang
OBJECTIVE: Glucose-dependent insulinotropic polypeptide receptor (GIPR) has been identified as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). Therefore, we developed the anti-GIPR antagonistic monoclonal antibody (mAb) alone and in combination with DPP-4 inhibitor as potential therapeutic strategy for treating obesity and dyslipidemia based on this genetic evidence. METHODS: Fully neutralized GIPR activity of GIPR-monoclonal antibody (mAb) was assessed by regulating the in vitro production of cAMP in the mouse GIPR stably expressing cells...
January 13, 2021: Life Sciences
Abhilasha Purohit, Sugandha Saxena, Michelle Varney, Dipakkumar R Prajapati, Jessica A Kozel, Audrey Lazenby, Rakesh K Singh
Pancreatic ductal adenocarcinoma (PDAC) manifests aggressive tumor growth and early metastasis. Crucial steps in tumor growth and metastasis are survival, angiogenesis, invasion, and immunosuppression. Previously we have shown that CXCR2 is expressed on endothelial cells, innate immune cells, and fibroblasts and regulates angiogenesis and immune responses. In this report, we examined whether tumor angiogenesis, growth, and metastasis of CXCR2-ligands expressing PDAC cells are regulated in vivo by a host CXCR2-dependent mechanism...
January 13, 2021: American Journal of Pathology
Rumi Itoyama, Hirohisa Okabe, Yo-Ichi Yamashita, Fumimasa Kitamura, Norio Uemura, Yosuke Nakao, Toshihiko Yusa, Katsunori Imai, Hiromitsu Hayashi, Hideo Baba
BACKGROUND: Postoperative complications after pancreaticoduodenectomy (PD) is still a major concern. The aim of this study was to propose how to choose antibiotics, based on bacterial sensitivity profiling involved in postoperative complications after PD. METHODS: Two hundred and thirty patients underwent PD between 2008 and 2018 at Kumamoto University Hospital. We enrolled 121 patients who had both intraoperative bile culture and drain culture on postoperative day (POD) 3...
January 16, 2021: Journal of Hepato-biliary-pancreatic Sciences
Yoshihiro Furuichi, Masakazu Abe, Yoshitaka Kasai, Hirohito Takeuchi, Yuu Yoshimasu, Takao Itoi
BACKGROUND: Red dichromatic imaging (RDI) is next-generation image-enhanced endoscopy technique released in July 2020. We previously reported that RDI can predict esophageal varices (EV) depth and decrease their recurrence rate by accurate intravariceal injections during endoscopic injection sclerotherapy (EIS) using unreleased prototype RDI endoscope. In this study, we analyzed whether RDI improves the overall survival (OS) rate and whether it is more accurate independent predictor of EV recurrence than white light imaging (WLI), using propensity score matching...
January 16, 2021: Journal of Hepato-biliary-pancreatic Sciences
Xueyou Zhang, Shi Feng, Qian Wang, Haitao Huang, Ruihan Chen, Qinfen Xie, Wu Zhang, Aodi Wang, Shuirong Zhang, Lingjian Wang, Ming Yao, Qi Ling
Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non-resectable (biopsy) PDACs using a next-generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts...
January 16, 2021: Journal of Cellular and Molecular Medicine
Xue Wang, Ying Liu, Wanjia Xu, Lirui Jia, Dongxu Chi, Jiang Yu, Jiamei Wang, Zhonggui He, Xiaohong Liu, Yongjun Wang
Onivyde is the first irinotecan (IRI) nanoliposome that could improve pharmacokinetics and tumor biodistribution of irinotecan. Although FDA approves Onivyde for the treatment of pancreatic cancer patients who are not effective for GEM, the gastrointestinal toxicity caused by Onivyde is still a problem to be solved in clinical application. Berberine (BER), an isoquinolone alkaloid extracted from several different plants, has been reported to exhibit beneficial effect in alleviating intestinal mucositis and generating synergistic anticancer effect in combination with cytotoxic drugs...
January 15, 2021: Drug Delivery and Translational Research
Hiroaki Fujita, Keinosuke Ishido, Norihisa Kimura, Taiichi Wakiya, Hayato Nagase, Tadashi Yoshizawa, Toshihiro Haga, Shintaro Goto, Hiroshi Kijima, Kenichi Hakamada
BACKGROUND: Intra-ampullary papillary-tubular neoplasm (IAPN) has been classified as a Vater papillary tumor. The prognosis of IAPN is generally relatively good. Here, we describe a patient with a mucinous adenocarcinoma cluster in the Vater papilla of IAPN origin. CLINICAL PRESENTATION: The patient was a 66-year-old man who was admitted to our hospital after a diagnosis of pancreatic head carcinoma based on a pancreatic duct dilatation found on abdominal ultrasound...
January 15, 2021: Surgical Case Reports
Xiao Zhang, Wenyu Song, Chunxia Qin, Fang Liu, Xiaoli Lan
PURPOSE: 68 Ga-Labelled Fibroblast Activation Protein Inhibitor (68 Ga-FAPI) has shown promise in tumour positron emission tomography (PET) imaging, including malignant pancreatic lesions. Here, we showed several non-malignant findings of focal 68 Ga-FAPI-04 uptake in the pancreas which were occasionally found by PET/MR. The study aimed to investigate the reasons for the focal uptake and remind caution for the diagnosis. METHODS: We retrospectively analysed imaging data of 103 patients who underwent 68 Ga-FAPI-04 PET/MR at our institute from May 22 to July 8, 2020...
January 15, 2021: European Journal of Nuclear Medicine and Molecular Imaging
Mary Dillhoff, Timothy M Pawlik
No abstract text is available yet for this article.
January 15, 2021: Annals of Surgical Oncology
Mihoko Yamada, Teiichi Sugiura, Yukiyasu Okamura, Takaaki Ito, Yusuke Yamamoto, Ryo Ashida, Katsuhisa Ohgi, Takeshi Aramaki, Masahiro Endo, Katsuhiko Uesaka
BACKGROUND: Lymph node metastasis is one of the strongest prognostic factors of pancreatic cancer. However, the clinical implication of pathologically node-negative pancreatic cancer (pN0-PC) has not been fully investigated. METHODS: Patients who underwent surgical resection for radiologically resectable pancreatic cancer between 2002 and 2018 were included in this study. A clinicopathological examination focusing on pN0-PC was performed. RESULTS: Of all 533 patients, 155 (29...
January 15, 2021: Annals of Surgical Oncology
Jaime Feliu, Mónica Jorge Fernández, Teresa Macarulla, Bartomeu Massuti, Ana Albero, José Federico González González, Guillermo Quintero-Aldana, Juan Ignacio Delgado-Mingorance, Ana Fernández Montes, Carmen García Piernavieja, Manuel Valladares-Ayerbes, Ana María López Muñoz, Rebeca Mondéjar Solís, Pilar Vicente, Esther Casado Gonzalez, Irene González Cebrián, Guillermo López-Vivanco
PURPOSE: To evaluate the health-related quality of life (HRQoL), global health status (GHS), and deterioration-free survival of an elderly population (> 70 years) with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (mPC) treated with nab-paclitaxel in combination with gemcitabine. METHODS: In this open-label, single-arm, multicenter, phase II trial, patients received 4-week cycles of intravenous (i.v.) nab-paclitaxel at a dose of 125 mg/m2 , followed by i...
January 15, 2021: Cancer Chemotherapy and Pharmacology
Arif A Arif, Peter T W Kim, Adrienne Melck, Andrew Churg, Zachary Schwartz, Heather C Stuart
BACKGROUND Neurofibromatosis type 1 (NF1) is a multi-tumor syndrome in which affected patients develop malignancies that are rare in the overall population, such as tumors of neural or endocrine origin. CASE REPORT A 67-year-old woman with a clinical diagnosis of NF1 presented with abdominal pain and pneumoperitoneum. She underwent small-bowel resections for a perforated jejunal lesion and a second lesion in the ileum; pathology showed a neurofibroma at the site of the perforation and a 1-cm low-grade GIST, respectively...
January 16, 2021: American Journal of Case Reports
(no author information available yet)
Sotigalimab had manageable toxicity and an early efficacy signal in a phase Ib pancreatic cancer trial.
January 15, 2021: Cancer Discovery
Alex Cazes, Oscar Betancourt, Edgar Esparza, Evangeline S Mose, Dawn Jaquish, Eric Wong, Alexis A Wascher, Hervé Tiriac, Marco Gymnopoulos, Andrew M Lowy
PURPOSE: Pancreatic cancer is an aggressive disease associated with a poor 5-year overall survival. Most patients are ineligible for surgery due to late diagnosis and are treated primarily with chemotherapy with very limited success. Pancreatic cancer is relatively insensitive to chemotherapy due to multiple factors including reduced bioavailability of drugs to tumor cells. One strategy to improve drug efficacy with reduced toxicity is the development of antibody-drug conjugates which have now been used successfully to treat both solid and liquid tumors...
January 15, 2021: Clinical Cancer Research
Stephen L Abrams, Shaw M Akula, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Massimo Libra, Saverio Candido, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Linda S Steelman, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic malignancy. Approximately 85% of pancreatic cancers are classified as PDACs. The survival of PDAC patients is very poor and only 5-10% of patients survive 5 years after diagnosis. Mutations at the KRAS and TP53 gene are frequently observed in PDAC patients. The PANC-28 cell line lacks wild-type (WT) TP53. In the following study, we have investigated the effects of restoration of WT TP53 activity on the sensitivity of PANC-28 pancreatic cancer cells to various drugs which are used to treat PDAC patients as well as other cancer patients...
January 7, 2021: Advances in Biological Regulation
L Sivapalan, H M Kocher, H Ross-Adams, C Chelala
Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes...
December 30, 2020: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Xing-Huang Gao, Ling Li, Marc Parisien, Jing Wu, Ilya Bederman, Zhaofeng Gao, Dawid Krokowski, Steven M Chirieleison, Derek Abbott, Benlian Wang, Peter Arvan, Mark Cameron, Mark Chance, Belinda Willard, Maria Hatzoglou
The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H2 S has been shown to persulfidate redox sensitive cysteine residues resulting in an H2 S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes...
May 2020: Molecular & Cellular Proteomics: MCP
Taewook Kang, Brandon B Boland, Pia Jensen, Cristina Alarcon, Arkadiusz Nawrocki, Joseph S Grimsby, Christopher J Rhodes, Martin R Larsen
The onset of obesity-linked type 2 diabetes (T2D) is marked by an eventual failure in pancreatic β-cell function and mass that is no longer able to compensate for the inherent insulin resistance and increased metabolic load intrinsic to obesity. However, in a commonly used model of T2D, the db/db mouse, β-cells have an inbuilt adaptive flexibility enabling them to effectively adjust insulin production rates relative to the metabolic demand. Pancreatic β-cells from these animals have markedly reduced intracellular insulin stores, yet high rates of (pro)insulin secretion, together with a substantial increase in proinsulin biosynthesis highlighted by expanded rough endoplasmic reticulum and Golgi apparatus...
June 2020: Molecular & Cellular Proteomics: MCP
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