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https://www.readbyqxmd.com/read/28102776/targeted-delivery-of-cisplatin-to-tumor-xenografts-via-the-nanoparticle-component-of-nano-diamino-tetrac
#1
Thangirala Sudha, Dhruba J Bharali, Murat Yalcin, Noureldien He Darwish, Melis Debreli Coskun, Kelly A Keating, Hung-Yun Lin, Paul J Davis, Shaker A Mousa
AIM: Nano-diamino-tetrac (NDAT) targets a receptor on integrin αvβ3; αvβ3 is generously expressed by cancer cells and dividing endothelial cells and to a small extent by nonmalignant cells. The tetrac (tetraiodothyroacetic acid) of NDAT is covalently bound to a poly(lactic-co-glycolic acid) nanoparticle that encapsulates anticancer drugs. We report NDAT delivery efficiency of cisplatin to agent-susceptible urinary bladder cancer xenografts. MATERIALS & METHODS: Cisplatin-loaded NDAT (NDAT-cisplatin) was administered to xenograft-bearing nude mice...
January 19, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28100188/high-expression-of-micro-rna-135a-in-hepatocellular-carcinoma-is-associated-with-recurrence-within-12%C3%A2-months-after-resection
#2
Johann von Felden, Denise Heim, Kornelius Schulze, Till Krech, Florian Ewald, Björn Nashan, Ansgar W Lohse, Henning Wege
BACKGROUND: Hepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. Early recurrence is driven by synchronous microscopic intrahepatic metastases. The predictive value of histological parameters is discussed controversially and adjuvant therapy is not established. The aim of this study was to identify patients at high risk for early intrahepatic recurrence by expression profiling of selected micro RNAs. METHODS: In 52 patients undergoing HCC resection between 2011 and 2014, liver and tumor tissue was collected during surgery...
January 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28099920/prognostic-implications-of-intratumoral-cd103-tumor-infiltrating-lymphocytes-in-pulmonary-squamous-cell-carcinoma
#3
Jaemoon Koh, Sehui Kim, Moon-Young Kim, Heounjeong Go, Yoon Kyung Jeon, Doo Hyun Chung
CD103 is the αE subunit of αEβ7 integrin that is expressed in tissue-resident memory T cells, where it promotes cytotoxic T cell responses against tumors. However, little is known about its expression or clinicopathological implications in non-small cell lung cancer (NSCLC). This study investigated the prognostic implications of CD103+ tumor-infiltrating lymphocytes (TILs) in NSCLC. We established two cohorts: patients with resected NSCLC (n = 132) and patients with pulmonary squamous cell carcinoma (pSCC), a subset of NSCLC (n = 378), to estimate the prognostic significance of CD103+ TILs...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098570/preferential-localization-of-met-expression-at-the-invasion-front-and-in-spreading-cells-through-air-spaces-in-non-small-cell-lung-carcinomas
#4
Camille Lapère, Alexis B Cortot, Valérie Grégoire, Vincent Cockenpot, David Tulasne, Marie-Christine Copin
The involvement of the HGF/MET pathway in acquisition of an invasive phenotype in non-small cell lung carcinomas (NSCLCs) suggests that MET inhibitors might prove effective against these cancers, but clinical trials have yielded conflicting results. The aim of our study was to evaluate how intratumoral heterogeneity (ITH) of MET staining affects the determination of MET status for therapeutic purposes. We analyzed 64 NSCLC samples, including 33 adenocarcinomas (ADCs) and 31 squamous cell carcinomas (SCCs). We used immunohistochemistry to detect MET and phospho-MET on whole slides and determined the MET SP44 immunoscore and the H-score...
January 16, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28096224/supra-and-infratentorial-ectopic-schwannoma-mimicking-a-meningioma
#5
Pedro Ribeiro da Cunha, José Luís Alves, Armando Rocha
We report the case of a supra and infratentorial ectopic schwannoma, mimicking a meningioma, that was surgically resected on a 75-year-old man, with a history of progressive visual loss and headaches. MRI was in favour of an occipital, cystic, tentorial-based meningioma extending to the posterior fossa, with signs of intratumoral haemorrhage. This is a unique case because of the rare type of lesion, in a very atypical location, completely unexpected by the preoperative imaging analysis, and to the best of our knowledge it is the oldest patient reported in the literature with this kind of tumour...
January 17, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28096186/translation-reprogramming-is-an-evolutionarily-conserved-driver-of-phenotypic-plasticity-and-therapeutic-resistance-in-melanoma
#6
Paola Falletta, Luis Sanchez-Del-Campo, Jagat Chauhan, Maike Effern, Amy Kenyon, Christopher J Kershaw, Robert Siddaway, Richard Lisle, Rasmus Freter, Matthew J Daniels, Xin Lu, Thomas Tüting, Mark Middleton, Francesca M Buffa, Anne E Willis, Graham Pavitt, Ze'ev A Ronai, Tatjana Sauka-Spengler, Michael Hölzel, Colin R Goding
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood...
January 17, 2017: Genes & Development
https://www.readbyqxmd.com/read/28094402/mesoporous-carbon-nanoshells-for-high-hydrophobic-drug-loading-multimodal-optical-imaging-controlled-drug-release-and-synergistic-therapy
#7
Hui Wang, Kui Wang, Qingxin Mu, Zachary R Stephen, Yanyan Yu, Shuiqin Zhou, Miqin Zhang
Loading and controlled release of sufficient hydrophobic drugs to tumor cells has been the bottleneck in chemotherapy for decades. Herein we report the development of a fluorescent and mesoporous carbon nanoshell (FMP-CNS) that exhibits a loading capacity for the hydrophobic drug paclitaxel (PTX) as high as ∼80 wt% and releases the drug in a controllable fashion under NIR irradiation (825 nm) at an intensity of 1.5 W cm(-2). The high drug loading is primarily attributed to its mesoporous structure and to the supramolecular π-stacking between FMP-CNSs and PTX molecules...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#8
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28092682/limited-heterogeneity-of-known-driver-gene-mutations-among-the-metastases-of-individual-patients-with-pancreatic-cancer
#9
Alvin P Makohon-Moore, Ming Zhang, Johannes G Reiter, Ivana Bozic, Benjamin Allen, Deepanjan Kundu, Krishnendu Chatterjee, Fay Wong, Yuchen Jiao, Zachary A Kohutek, Jungeui Hong, Marc Attiyeh, Breanna Javier, Laura D Wood, Ralph H Hruban, Martin A Nowak, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Christine A Iacobuzio-Donahue
The extent of heterogeneity among driver gene mutations present in naturally occurring metastases-that is, treatment-naive metastatic disease-is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#10
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#11
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28075526/cetuximab-strongly-enhances-immune-cell-infiltration-into-liver-metastatic-sites-in-colorectal-cancer
#12
Yuka Inoue, Shoichi Hazama, Nobuaki Suzuki, Yukio Tokumitsu, Shinsuke Kanekiyo, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Hiroaki Nagano
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28073839/unsupervised-clustering-of-quantitative-image-phenotypes-reveals-breast-cancer-subtypes-with-distinct-prognoses-and-molecular-pathways
#13
Jia Wu, Yi Cui, Xiaoli Sun, Guohong Cao, Bailiang Li, Debra M Ikeda, Allison W Kurian, Ruijiang Li
PURPOSE: To identify novel breast cancer subtypes by extracting quantitative imaging phenotypes of the tumor and surrounding parenchyma, and to elucidate the underlying biological underpinnings and evaluate the prognostic capacity for predicting recurrence-free survival (RFS). METHODS: We retrospectively analyzed dynamic contrast-enhanced magnetic resonance imaging data of patients from a single-center discovery cohort (n=60) and an independent multi-center validation cohort (n=96)...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28073783/podoplanin-expression-in-primary-brain-tumors-induces-platelet-aggregation-and-increases-risk-of-venous-thromboembolism
#14
Julia Riedl, Matthias Preusser, Pegah Mir Seyed Nazari, Florian Posch, Simon Panzer, Christine Marosi, Peter Birner, Johannes Thaler, Christine Brostjan, Daniela Lötsch, Walter Berger, Johannes A Hainfellner, Ingrid Pabinger, Cihan Ay
Venous thromboembolism (VTE) is common in patients with brain tumors, and underlying mechanisms are unclear. We hypothesized that podoplanin, a sialomucin-like glycoprotein, increases the risk of VTE in primary brain tumors via its ability to induce platelet aggregation. Immunohistochemical staining against podoplanin and intratumoral platelet aggregates was performed in brain tumor specimens of 213 patients (mostly high-grade gliomas [89%]) included in the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study of patients with newly diagnosed cancer or progressive disease aimed at identifying patients at risk of VTE...
January 10, 2017: Blood
https://www.readbyqxmd.com/read/28073775/dasatinib-changes-immune-cell-profiles-concomitant-with-reduced-tumor-growth-in-several-murine-solid-tumor-models
#15
Can Hekim, Mette Ilander, Jun Yan, Erin Michaud, Richard Smykla, Markus Vähä-Koskela, Paula Savola, Siri Tähtinen, Leena Saikko, Akseli Hemminki, Panu E Kovanen, Kimmo Porkka, Francis Yf Lee, Satu Mustjoki
Dasatinib, a broad range tyrosine kinase inhibitor (TKI), induces rapid mobilization of lymphocytes and clonal expansion of cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects in solid tumor models. The effects on tumor growth and on the immune system were studied in four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, and 4T1 breast carcinoma). Both peripheral blood (PB) and tumor samples were immunophenotyped during treatment...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28073006/bcl9l-dysfunction-impairs-caspase-2-expression-permitting-aneuploidy-tolerance-in-colorectal-cancer
#16
Carlos López-García, Laurent Sansregret, Enric Domingo, Nicholas McGranahan, Sebastijan Hobor, Nicolai Juul Birkbak, Stuart Horswell, Eva Grönroos, Francesco Favero, Andrew J Rowan, Nicholas Matthews, Sharmin Begum, Benjamin Phillimore, Rebecca Burrell, Dahmane Oukrif, Bradley Spencer-Dene, Michal Kovac, Gordon Stamp, Aengus Stewart, Havard Danielsen, Marco Novelli, Ian Tomlinson, Charles Swanton
Chromosomal instability (CIN) contributes to cancer evolution, intratumor heterogeneity, and drug resistance. CIN is driven by chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through genomic analysis of colorectal cancers and cell lines, we find frequent loss of heterozygosity and mutations in BCL9L in aneuploid tumors. BCL9L deficiency promoted tolerance of chromosome missegregation events, propagation of aneuploidy, and genetic heterogeneity in xenograft models likely through modulation of Wnt signaling...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28069963/pathogen-boosted-adoptive-cell-transfer-immunotherapy-to-treat-solid-tumors
#17
Gang Xin, David M Schauder, Weiqing Jing, Aimin Jiang, Nikhil S Joshi, Bryon Johnson, Weiguo Cui
Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069723/a-novel-murine-gitr-ligand-fusion-protein-induces-antitumor-activity-as-a-monotherapy-which-is-further-enhanced-in-combination-with-an-ox40-agonist
#18
Rebecca Leyland, Amanda Watkins, Kathy Mulgrew, Nicholas Holoweckyj, Lisa Bamber, Natalie J Tigue, Emily Offer, John Andrews, Li Yan, Stefanie Mullins, Michael D Oberst, Jane Coates Ulrichsen, David A Leinster, Kelly A McGlinchey, Lesley Young, Michelle Morrow, Scott A Hammond, Philip R Mallinder, Athula Herath, Ching Ching Leow, Robert W Wilkinson, Ross Stewart
PURPOSE: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy. EXPERIMENTAL DESIGN: The EC50 value of the mGITRL-FP was compared to an anti-GITR antibody in an in vitro agonistic cell based reporter assay. We assessed the impact of dose, schedule and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared to an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28068934/concordance-between-pik3ca-mutations-in-endoscopic-biopsy-and-surgically-resected-specimens-of-esophageal-squamous-cell-carcinoma
#19
Ken Hatogai, Satoshi Fujii, Takashi Kojima, Hiroyuki Daiko, Toshihiko Doi, Atsushi Ohtsu, Atsushi Ochiai, Yuichi Takiguchi, Takayuki Yoshino
BACKGROUND: PIK3CA mutations are expected to be potential therapeutic targets for esophageal squamous cell carcinoma (ESCC). We aimed to clarify the concordance between PIK3CA mutations detected in endoscopic biopsy specimens and corresponding surgically resected specimens. METHODS: We examined five hotspot mutations in the PIK3CA gene (E542K, E545K, E546K, H1047R, and H1047L) in formalin-fixed and paraffin-embedded tissue sections of paired endoscopic biopsy and surgically resected specimens from 181 patients undergoing curative resection for ESCC between 2000 and 2011 using a Luminex technology-based multiplex gene mutation detection kit...
January 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28068318/magnesium-silicide-nanoparticles-as-a-deoxygenation-agent-for-cancer-starvation-therapy
#20
Chen Zhang, Dalong Ni, Yanyan Liu, Heliang Yao, Wenbo Bu, Jianlin Shi
A material that rapidly absorbs molecular oxygen (known as an oxygen scavenger or deoxygenation agent (DOA)) has various industrial applications, such as in food preservation, anticorrosion of metal and coal deoxidation. Given that oxygen is vital to cancer growth, to starve tumours through the consumption of intratumoral oxygen is a potentially useful strategy in fighting cancer. Here we show that an injectable polymer-modified magnesium silicide (Mg2Si) nanoparticle can act as a DOA by scavenging oxygen in tumours and form by-products that block tumour capillaries from being reoxygenated...
January 9, 2017: Nature Nanotechnology
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