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Xenograft AND pancreas

Daniel Delitto, Sarah M Judge, Andrea E Delitto, Rachel L Nosacka, Fernanda G Rocha, Bayli B DiVita, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Shannon M Wallet, Andrew R Judge, Jose G Trevino
Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia...
November 25, 2016: Oncotarget
Daisuke Komura, Takayuki Isagawa, Kazuki Kishi, Ryohei Suzuki, Reiko Sato, Mariko Tanaka, Hiroto Katoh, Shogo Yamamoto, Kenji Tatsuno, Masashi Fukayama, Hiroyuki Aburatani, Shumpei Ishikawa
BACKGROUND: Cancer microenvironment plays a vital role in cancer development and progression, and cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze whole cancer-stromal interactome. RESULTS: We present CASTIN (CAncer-STromal INteractome analysis), a novel framework for the evaluation of cancer-stromal interactome from RNA-Seq data using cancer xenograft models...
November 9, 2016: BMC Genomics
Qing Chang, Olga I Ornatsky, Iram Siddiqui, Rita Straus, Vladimir I Baranov, David W Hedley
Imaging mass cytometry was used for direct visualization of platinum localization in tissue sections from tumor and normal tissues of cisplatin-treated mice bearing pancreas cancer patient-derived xenografts. This recently-developed technology enabled simultaneous detection of multiple markers to define cell lineage, DNA damage response, cell proliferation and functional state, providing a highly detailed view of drug incorporation in tumor and normal tissues at the cellular level. A striking and unanticipated finding was the extensive binding of platinum to collagen fibers in both tumor and normal mouse tissues...
November 4, 2016: Scientific Reports
Sharon K Michelhaugh, Otto Muzik, Anthony R Guastella, Neil V Klinger, Lisa A Polin, Hancheng Cai, Yanchun Xin, Thomas J Mangner, Shaohui Zhang, Csaba Juhasz, Sandeep Mittal
: Abnormal tryptophan metabolism via the kynurenine pathway (KP) is involved in the pathophysiology of a variety of human diseases including cancers. α-[(11)C]-methyl-L-tryptophan ((11)C-AMT) positron emission tomography (PET) imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of (11)C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-[(18)F]fluoroethyl)-L-tryptophan ((18)F-FETrp) may be useful to assess tryptophan metabolism via the KP...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Meike Hohwieler, Anett Illing, Patrick C Hermann, Tobias Mayer, Marianne Stockmann, Lukas Perkhofer, Tim Eiseler, Justin S Antony, Martin Müller, Susanne Renz, Chao-Chung Kuo, Qiong Lin, Matthias Sendler, Markus Breunig, Susanne M Kleiderman, André Lechel, Martin Zenker, Michael Leichsenring, Jonas Rosendahl, Martin Zenke, Bruno Sainz, Julia Mayerle, Ivan G Costa, Thomas Seufferlein, Michael Kormann, Martin Wagner, Stefan Liebau, Alexander Kleger
OBJECTIVE: The generation of acinar and ductal cells from human pluripotent stem cells (PSCs) is a poorly studied process, although various diseases arise from this compartment. DESIGN: We designed a straightforward approach to direct human PSCs towards pancreatic organoids resembling acinar and ductal progeny. RESULTS: Extensive phenotyping of the organoids not only shows the appropriate marker profile but also ultrastructural, global gene expression and functional hallmarks of the human pancreas in the dish...
September 15, 2016: Gut
Simone U Dalm, Ingrid L Bakker, Erik de Blois, Gabriela N Doeswijk, Mark W Konijnenberg, Francesca Orlandi, Donato Barbato, Mattia Tedesco, Theodosia Maina, Berthold A Nock, Marion de Jong
INTRODUCTION: Since overexpression of the gastrin releasing peptide receptor (GRPR) has been reported on various cancer types, e.g. prostate cancer and breast cancer, targeting this receptor with radioligands might have significant impact on staging and treatment of GRPR-expressing tumors. NeoBOMB1 is a novel DOTA-coupled GRPR antagonist with high affinity for GRPR and excellent in vivo stability. The purpose of this preclinical study was to further explore the use of NeoBOMB1 for theranostic application by determining the biodistribution of (68)Ga-NeoBOMB1 and (177)Lu-NeoBOMB1...
September 8, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Martin Perreault, René Maltais, Raphaël Dutour, Donald Poirier
RM-133 is a key representative of a new family of aminosteroids reported as potent anticancer agents. Although RM-133 produced interesting results in 4 mouse xenograft cancer models when injected subcutaneously, it needs to be improved to increase its in vivo potency. Thus, to obtain an analog of RM-133 with a better drug potential, a structure-activity relationship study was conducted by synthesizing eleven RM-133-related compounds and addressing their antiproliferative activity on 3 human cancer cells (HL-60, OVCAR-3 and PANC-1) and 3 human normal cell lines (primary ovary, pancreas and renal proximal tubule) as well as their metabolic stability in human liver microsomes...
November 2016: Steroids
Christina M MacLaughlin, Lili Ding, Cheng Jin, Pingjiang Cao, Iram Siddiqui, David M Hwang, Juan Chen, Brian C Wilson, Gang Zheng, David W Hedley
No abstract text is available yet for this article.
August 1, 2016: Journal of Biomedical Optics
Ananda Kumar Kanduluru, Madduri Srinivasarao, Philip S Low
The neurokinin-1 receptor (NK1R) is implicated in the growth and metastasis of many tumors, including cancers of the brain (e.g., gliomas, glioblastomas, and astrocytomas), skin (e.g., melanomas), and neuroendocrine tissues (cancers of the breast, stomach, pancreas, larynx, and colon). Because overexpression of NK1R has been reported in most of these malignancies, we have undertaken designing an NK1R-targeted near-infrared (NIR) fluorescent dye for fluorescence-guided surgeries of these cancers. We demonstrate here that an NK1R-binding ligand linked to the NIR dye LS288 selectively accumulates in NK1R-expressing tumor xenografts with high affinity (Kd = 13 nM), allowing intraoperative imaging of these cancers in live mice...
September 21, 2016: Bioconjugate Chemistry
Wayne J Hawthorne, Andrew M Lew, Helen E Thomas
PURPOSE OF REVIEW: Despite the benefits of islet and pancreas allotransplantation, their widespread use in type 1 diabetes is limited because of the paucity of suitable donors. Porcine xenotransplantation offers an alternative, and advances in genetic modification of pigs have opened up new potential for its clinical use. This review outlines the barriers to successful islet xenotransplantation, and genetic modifications that have been tested to overcome these. RECENT FINDINGS: Islets from pigs lacking α1,3-galactosyltransferase, to prevent hyperacute rejection, are now used as a background strain for further genetic modifications...
October 2016: Current Opinion in Organ Transplantation
Juehua Yu, Shi-He Liu, Robbi Sanchez, John Nemunaitis, Enrique Rozengurt, F Charles Brunicardi
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis and a low median survival due to lack of the early and reliable detection and effective therapeutic options, despite improvements observed for many other cancers in last decade. Pancreatic and duodenal homeobox 1 (PDX1), which is a homeodomain-containing transcription factor and a key regulator for insulin gene expression, β cell maturation and proper β cell function maintenance in the pancreas. Our previous studies revealed that PDX1 promotes tumorigenesis and it is a promising therapeutic target for PDAC...
June 2016: Annals of Translational Medicine
Xing Gong, Ali Azhdarinia, Sukhen C Ghosh, Wei Xiong, Zhiqiang An, Qingyun Liu, Kendra S Carmon
Gastrointestinal cancer is one of the leading causes of cancer-related mortality in men and women worldwide. The adult stem cell marker LGR5 (leucine-rich repeat-containing, G protein-coupled receptor 5) is highly expressed in a significant fraction of gastrointestinal tumors of the colon, liver, pancreas, and stomach, relative to normal tissues. LGR5 is located on the cell surface and undergoes rapid, constitutive internalization independent of ligand. Furthermore, LGR5-high cancer cells have been shown to exhibit the properties of tumor-initiating cells or cancer stem cells (CSC)...
July 2016: Molecular Cancer Therapeutics
Christopher C DuFort, Kathleen E DelGiorno, Sunil R Hingorani
The microenvironment influences the pathogenesis of solid tumors and plays an outsized role in some. Our understanding of the stromal response to cancers, particularly pancreatic ductal adenocarcinoma, has evolved from that of host defense to tumor offense. We know that most, although not all, of the factors and processes in the microenvironment support tumor epithelial cells. This reappraisal of the roles of stromal elements has also revealed potential vulnerabilities and therapeutic opportunities to exploit...
June 2016: Gastroenterology
Sohel M Julovi, Aiqun Xue, Thao N Thanh LE, Anthony J Gill, Jerikho C Bulanadi, Mili Patel, Lynne J Waddington, Kerry-Anne Rye, Minoo J Moghaddam, Ross C Smith
BACKGROUND: Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo. METHODS: Cryo transmission electron microscopy (TEM) examined ApoA-II's influence on morphology of SMOFLipid emulsion...
2016: PloS One
Naoki Hijiya, Yoshiyuki Tsukamoto, Chisato Nakada, Lam Tung Nguyen, Tomoki Kai, Keiko Matsuura, Kohei Shibata, Masafumi Inomata, Tomohisa Uchida, Akinori Tokunaga, Kohei Amada, Kuniaki Shirao, Yasunari Yamada, Hiromu Mori, Ichiro Takeuchi, Masao Seto, Masahiro Aoki, Mutsuhiro Takekawa, Masatsugu Moriyama
The progression from precursor lesions of pancreatic cancer, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN), to invasive disease is characterized by stepwise accumulation of genetic alterations. However, it remains unclear whether additional alterations are required for the progression of high-grade neoplasms to invasive pancreatic carcinoma. We compared the genomic profiles of paired noninvasive and invasive carcinoma tissues collected from patients with IPMN...
May 1, 2016: Cancer Research
Bernhard J Hering, Philip J O'Connell
Patients in whom type 1 diabetes is complicated by impaired awareness of hypoglycemia and recurrent episodes of severe hypoglycemia are candidates for islet or pancreas transplantation if severe hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run-in period that provides access to hypoglycemia-specific education including behavioral therapies, insulin analogs, and diabetes technologies under the close supervision of a specialist hypoglycemia service...
January 2016: Xenotransplantation
Brittney S Harrington, Yaowu He, Claire M Davies, Sarah J Wallace, Mark N Adams, Elizabeth A Beaven, Deborah K Roche, Catherine Kennedy, Naven P Chetty, Alexander J Crandon, Christopher Flatley, Niara B Oliveira, Catherine M Shannon, Anna deFazio, Anna V Tinker, C Blake Gilks, Brian Gabrielli, Donal J Brennan, Jermaine I Coward, Jane E Armes, Lewis C Perrin, John D Hooper
BACKGROUND: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. METHODS: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined...
February 16, 2016: British Journal of Cancer
Elena Hernández-Agudo, Tamara Mondejar, Maria Luisa Soto-Montenegro, Diego Megías, Silvana Mouron, Jesus Sanchez, Manuel Hidalgo, Pedro Pablo Lopez-Casas, Francisca Mulero, Manuel Desco, Miguel Quintela-Fandino
BACKGROUND: Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with (18)F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib. METHODS: Two patient-derived pancreas xenografts (PDXs; Panc215 and Panc286) and the spontaneous breast cancer model MMTV-PyMT were used...
May 2016: Molecular Oncology
Theodosia Maina, Hendrik Bergsma, Harshad R Kulkarni, Dirk Mueller, David Charalambidis, Eric P Krenning, Berthold A Nock, Marion de Jong, Richard P Baum
PURPOSE: Gastrin-releasing peptide receptors (GRPR) represent attractive targets for tumor diagnosis and therapy because of their overexpression in major human cancers. Internalizing GRPR agonists were initially proposed for prolonged lesion retention, but a shift of paradigm to GRPR antagonists has recently been made. Surprisingly, radioantagonists, such as [(99m)Tc]DB1 ((99m)Tc-N4'-DPhe(6),Leu-NHEt(13)]BBN(6-13)), displayed better pharmacokinetics than radioagonists, in addition to their higher inherent biosafety...
May 2016: European Journal of Nuclear Medicine and Molecular Imaging
Xinzhe Yu, Hengchao Li, Deliang Fu, Chen Jin, J I Li
Currently, the use of photosensitizers as tracer agents to detect lymphatic metastases is a developing area of study in the field of pancreatic cancer treatment. In the present study, deuteporfin, a novel photosensitizer, was used as a tracer agent to detect lymphatic metastases in a pancreatic cancer xenograft model. The biodistribution and pharmacokinetics of deuteporfin, following intravenous administration and injection of deuteporfin into the left rear footpad, were investigated in Sprague-Dawley rats...
September 2015: Oncology Letters
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