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pancreatic cancer microenvironment

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https://www.readbyqxmd.com/read/28638792/immunotherapy-in-pancreatic-cancer-unleash-its-potential-through-novel-combinations
#1
REVIEW
Songchuan Guo, Merly Contratto, George Miller, Lawrence Leichman, Jennifer Wu
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28631007/how-schwann-cells-facilitate-cancer-progression-in-nerves
#2
REVIEW
Sylvie Deborde, Richard J Wong
Recent studies have demonstrated a critical role for nerves in enabling tumor progression. The association of nerves with cancer cells is well established for a variety of malignant tumors, including pancreatic, prostate and the head and neck cancers. This association is often correlated with poor prognosis. A strong partnership between cancer cells and nerve cells leads to both cancer progression and expansion of the nerve network. This relationship is supported by molecular pathways related to nerve growth and repair...
June 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28628715/overcoming-the-resistance-of-pancreatic-cancer-to-immune-checkpoint-inhibitors
#3
REVIEW
Richard A Skelton, Ammar Javed, Lei Zheng, Jin He
Immunotherapy has become a new modality of cancer treatment, but has had a limited success in treating PDAC. A combination approach to immunotherapy, using both immune checkpoint inhibitors and immune activating agonists, is needed, as PDAC does not respond to single-agent checkpoint inhibitors. Studies have also supported using vaccine-based therapies to prime the tumor microenvironment of PDAC with effector T-cells. Other therapeutic strategies including epigenetic agents, stroma modulators, radiotherapy, and T-cell transfer therapies may also prime the tumor microenvironment to overcome resistance to immune checkpoint inhibitors...
June 19, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28626793/acidic-ph-targeted-chitosan-capped-mesoporous-silica-coated-gold-nanorods-facilitate-detection-of-pancreatic-tumors-via-multispectral-optoacoustic-tomography
#4
Matthew R Zeiderman, Desiree E Morgan, John D Christein, William E Grizzle, Kelly M McMasters, Lacey R McNally
We present a cancer nanomedicine based on acidic pH targeted gold nanorods designed for multispectral optoacoustic tomography (MSOT). We have designed gold nanorods coated with mesoporous silica and subsequently capped with chitosan (CMGs). We have conjugated pH-sensitive variant 7 pHLIP peptide to the CMGs (V7-CMG) to provide targeting specificity to the acidic tumor microenvironment. In vitro, treatment of S2VP10 and MiaPaca2 cells with V7-CMG containing gemcitabine resulted in significantly greater cytotoxicity with 97% and 96...
July 11, 2016: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28620142/magnetic-resonance-imaging-of-rrx-001-pharmacodynamics-in-preclinical-tumors
#5
Natarajan Raghunand, Jan Scicinski, Gerald P Guntle, Bhumasamudram Jagadish, Eugene A Mash, Elizabeth Bruckheimer, Bryan Oronsky, Ronald L Korn
RRx-001 is an anticancer agent that subjects cancer cells to reactive oxygen/nitrogen species (ROS/RNS) and acts as an epigenetic modifier. We have used a thiol-bearing MRI contrast agent, Gd-LC7-SH, to investigate the pharmacodynamics of RRx-001 in CHP-100 Ewing's Sarcoma, HT-29 colorectal carcinoma, and PANC-1 pancreatic carcinoma xenografts in SCID mice. Binding of Gd-LC7-SH to the Cys34 residue on plasma albumin prolongs retention in the tumor microenvironment and increases tumor enhancement on MRI. Mice were imaged by MRI and in vivo T1 maps acquired 50 min (T150 min) after injection of 0...
June 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#6
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611425/pancreatic-adenocarcinoma-response-to-chemotherapy-enhanced-with-non-invasive-radio-frequency-evaluated-via-an-integrated-experimental-computational-approach
#7
Matthew J Ware, Louis T Curtis, Min Wu, Jason C Ho, Stuart J Corr, Steven A Curley, Biana Godin, Hermann B Frieboes
Although chemotherapy combined with radiofrequency exposure has shown promise in cancer treatment by coupling drug cytotoxicity with thermal ablation or thermally-induced cytotoxicity, limited access of the drug to tumor loci in hypo-vascularized lesions has hampered clinical application. We recently showed that high-intensity short-wave capacitively coupled radiofrequency (RF) electric-fields may reach inaccessible targets in vivo. This non-invasive RF combined with gemcitabine (Gem) chemotherapy enhanced drug uptake and effect in pancreatic adenocarcinoma (PDAC), notorious for having poor response and limited therapeutic options, but without inducing thermal injury...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611041/an-immunosuppressive-dendritic-cell-subset-accumulates-at-secondary-sites-and-promotes-metastasis-in-pancreatic-cancer
#8
Justin A Kenkel, William W Tseng, Matthew G Davidson, Lorna Tolentino, Okmi Choi, Nupur Bhattacharya, E Scott Seeley, Daniel Winer, Nathan E Reticker-Flynn, Edgar G Engleman
Pancreatic ductal adenocarcinoma (PDAC) after complete surgical resection is often followed by distant metastatic relapse for reasons that remain unclear. In this study, we investigated how the immune response at secondary sites affects tumor spread in murine models of metastatic PDAC. Early metastases were associated with dense networks of CD11b(+)CD11c(+)MHC-II(+)CD24(+)CD64(low)F4/80(low) dendritic cells (DC), which developed from monocytes in response to tumor-released GM-CSF. These cells uniquely expressed MGL2 and PD-L2 in the metastatic microenvironment and preferentially induced the expansion of T regulatory cells (Treg) in vitro and in vivo...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28608409/neoadjuvant-chemoradiotherapy-of-pancreatic-cancer-induces-a-favorable-immunogenic-tumor-microenvironment-associated-with-increased-major-histocompatibility-complex-class-i-related-chain-a-b-expression
#9
Takashi Murakami, Yuki Homma, Ryusei Matsuyama, Ryutaro Mori, Kentaro Miyake, Yusaku Tanaka, Kanechika Den, Yoji Nagashima, Masatoshi Nakazawa, Yukihiko Hiroshima, Michio Ueda, Kuniya Tanaka, Robert M Hoffman, Michael Bouvet, Itaru Endo
BACKGROUND: Damage-associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor-infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. METHODS: NACRT was administered to 51 patients with borderline-resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28605029/the-pancreatic-cancer-microenvironment-a-true-double-agent
#10
REVIEW
Laleh G Melstrom, Marcela D Salazar, Don J Diamond
The tumor microenvironment in pancreatic cancer is a complex balance of pro- and anti-tumor components. The dense desmoplasia consists of immune cells, extracellular matrix, growth factors, cytokines, and cancer associated fibroblasts (CAF) or pancreatic stellate cells (PSC). There are a multitude of targets including hyaluronan, angiogenesis, focal adhesion kinase (FAK), connective tissue growth factor (CTGF), CD40, chemokine (C-X-C motif) receptor 4 (CXCR-4), immunotherapy, and Vitamin D. The developing clinical therapeutics will be reviewed...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28602029/the-prognostic-impact-of-programmed-cell-death-ligand-1-and-human-leukocyte-antigen-class-i-in-pancreatic-cancer
#11
Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Yuji Soejima, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara
Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis...
June 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28600474/use-of-angiotensin-system-inhibitors-is-associated-with-immune-activation-and-longer-survival-in-non-metastatic-pancreatic-ductal-adenocarcinoma
#12
Hao Liu, Kamila Naxerova, Matthias Pinter, Joao Incio, Hang Lee, Kohei Shigeta, William W Ho, Jonathan A Crain, Alex Jacobson, Theodoros Michelakos, Daniella Dias-Santos, Andrea Zanconato, Theodore S Hong, Jeffrey W Clark, Janet E Murphy, David P Ryan, Vikram Deshpande, Keith D Lillemoe, Carlos Fernandez-Del Castillo, Michael Downes, Ronald M Evans, James Michaelson, Cristina R Ferrone, Yves Boucher, Rakesh K Jain
Angiotensin system inhibitors (ASIs) can improve prognosis in multiple cancer types, including pancreatic ductal adenocarcinoma (PDAC). However, no study has examined the effect of ASIs alone or combined with adjuvant chemotherapy in resected PDAC patients.<br /><br />Experimental Design: We performed an analysis of the records of ASI users and non-user patients with PDAC seen at Massachusetts General Hospital between January 2006 and December 2010. To identify mechanisms of ASIs in PDAC, we performed RNA-Seq of resected primary lesions...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28595517/immunotherapy-for-pancreatic-cancer-present-and-future
#13
Francesca Aroldi, Alberto Zaniboni
Despite the identification of some efficient drugs for the treatment of metastatic pancreatic cancer, this tumor remains one of the most lethal cancers and is characterized by a strong resistance to therapies. Pancreatic cancer has some unique features including the presence of a microenvironment filled with immunosuppressive mediators and a dense stroma, which is both a physical barrier to drug penetration and a dynamic entity involved in immune system control. Therefore, the immune system has been hypothesized to play an important role in pancreatic cancer...
June 2017: Immunotherapy
https://www.readbyqxmd.com/read/28591747/identification-and-causes-of-metabonomic-difference-between-orthotopic-and-subcutaneous-xenograft-of-pancreatic-cancer
#14
Bohan Zhan, Shi Wen, Jie Lu, Guiping Shen, Xianchao Lin, Jianghua Feng, Heguang Huang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected for1H NMR spectroscopy followed by univariate and multivariate statistical analyses...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28577085/endoplasmic-reticulum-stress-regulates-tumor-growth-and-anti-tumor-immunity-a-promising-opportunity-for-cancer-immunotherapy
#15
REVIEW
Eslam Mohamed, Yu Cao, Paulo C Rodriguez
The endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes...
June 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28549596/emerging-roles-of-the-cxcl12-cxcr4-axis-in-pancreatic-cancer-progression-and-therapy
#16
REVIEW
Richard L Sleightholm, Beth K Neilsen, Jing Li, Maria M Steele, Rakesh K Singh, Michael A Hollingsworth, David Oupicky
Chemokine networks regulate a variety of cellular, physiological, and immune processes. These normal functions can become appropriated by cancer cells to facilitate a more hospitable niche for aberrant cells by enhancing growth, proliferation, and metastasis. This is especially true in pancreatic cancer, where chemokine signaling is a vital component in the development of the supportive tumor microenvironment and the signaling between the cancer cells and surrounding stromal cells. Although expression patterns vary among cancer types, the chemokine receptor CXCR4 has been implicated in nearly every major malignancy and plays a prominent role in pancreatic cancer development and progression...
May 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28548126/microrna-dysregulation-in-the-tumor-microenvironment-influences-the-phenotype-of-pancreatic-cancer
#17
Eva Karamitopoulou, Stefan Haemmig, Ulrich Baumgartner, Cornelia Schlup, Martin Wartenberg, Erik Vassella
Cellular interactions in the tumor microenvironment influence neoplastic progression in pancreatic ductal adenocarcinoma. One underlying mechanism is the induction of the prognostically unfavorable epithelial-mesenchymal-transition-like tumor budding. Our aim is to explore the expression of microRNAs implicated in the regulation of tumor budding focusing on the microenvironment of the invasive front. To this end, RNA from laser-capture-microdissected material of the main tumor, tumor buds, juxta-tumoral stroma, tumor-remote stroma, and non-neoplastic pancreatic parenchyma from pancreatic cancer cases with (n=7) and without (n=6) tumor budding was analyzed by qRT-PCR for the expression of a panel of miRNAs that are known to be implicated in the regulation of epithelial-mesenchymal transition, including miR-21, miR-183, miR-200b, miR-200c, miR-203, miR-205, miR-210, and miR-217...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#18
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28507714/targeting-the-tumour-microenvironment-with-an-enzyme-responsive-drug-delivery-system-for-the-efficient-therapy-of-breast-and-pancreatic-cancers
#19
Brigitte Renoux, Florian Raes, Thibaut Legigan, Elodie Péraudeau, Balkis Eddhif, Pauline Poinot, Isabelle Tranoy-Opalinski, Jérôme Alsarraf, Oleksandr Koniev, Sergii Kolodych, Stéphanie Lerondel, Alain Le Pape, Jonathan Clarhaut, Sébastien Papot
The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28499439/the-role-of-tgf-%C3%AE-and-its-crosstalk-with-rac1-rac1b-signaling-in-breast-and-pancreas-carcinoma
#20
REVIEW
Catharina Melzer, Ralf Hass, Juliane von der Ohe, Hendrik Lehnert, Hendrik Ungefroren
This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers...
May 12, 2017: Cell Communication and Signaling: CCS
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