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Paula D Bos
A prerequisite for tumor evolution toward a malignant state is the establishment of cell intrinsic and extrinsic mechanisms of immune suppression (Hanahan and Weinberg, 2000, 2011; Schreiber, Old, and Smyth, 2011). Widespread recruitment of Foxp3(+) regulatory T cells (TREG) is a prevailing means to dampen antitumor immunity. Advances in the characterization of TREG cell heterogeneity and physiological function of tissue resident TREG cells unfold new possibilities for nontraditional tumor-promoting functions of intratumoral TREG cells...
October 19, 2016: Immunological Investigations
Vidhya Kumar, Yves Boucher, Hao Liu, Diego Ferreira, Jacob Hooker, Ciprian Catana, Andrew J Hoover, Tobias Ritter, Rakesh K Jain, Alexander R Guimaraes
PURPOSE: Losartan, an angiotensin II receptor blocker, can reduce desmoplasia and enhance drug delivery and efficacy through improving interstitial transport and vascular perfusion in pancreatic ductal adenocarcinoma (PDAC) models in mice. The purpose of this study was to determine whether magnetic resonance imaging (MRI) of magnetic iron oxide nanoparticles (MNPs) and micro-positron emission tomography (PET) measurements could respectively detect improvements in tumor vascular parameters and drug uptake in orthotopic PDAC in mice treated with losartan...
October 2016: Translational Oncology
Jia-Jie Hao, De-Chen Lin, Huy Q Dinh, Anand Mayakonda, Yan-Yi Jiang, Chen Chang, Ye Jiang, Chen-Chen Lu, Zhi-Zhou Shi, Xin Xu, Yu Zhang, Yan Cai, Jin-Wu Wang, Qi-Min Zhan, Wen-Qiang Wei, Benjamin P Berman, Ming-Rong Wang, H Phillip Koeffler
Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others...
October 17, 2016: Nature Genetics
Saranya C Balasubramaniam, Marco Pellegrini, Giovanni Staurenghi, Jose S Pulido
PURPOSE: To describe the features of choroidal tumors on infrared (IR) imaging and to determine the diagnostic sensitivity and specificity of intratumoral choroidal vascular loops on IR imaging for circumscribed choroidal hemangioma (CCH). METHODS: Infrared and indocyanine green images of CCH, choroidal metastases, and choroidal melanomas were reviewed. The main outcome measure was the presence of intratumoral choroidal vascular loops and tufts on IR images. The secondary outcome measure was the presence of peritumoral vascular expansion on indocyanine green images...
October 4, 2016: Retina
Kuan-Yin Ko, Chia-Ju Liu, Chi-Lun Ko, Ruoh-Fang Yen
PURPOSE: The aim of this study was to investigate whether the textural features of pretreatment F-FDG PET images can predict prognosis for nasal type extranodal natural killer/T-cell lymphoma (ENKTL). MATERIALS AND METHODS: A retrospective analysis of the pretreatment F-FDG PET images of the patients with newly diagnosed nasal type ENKTL from 2008 to 2013 was conducted. Progression-free survival (PFS) was the main outcome measure. The primary tumor was identified and then delineated using the 40% maximum standardized uptake value (SUVmax) thresholding method...
October 5, 2016: Clinical Nuclear Medicine
Caiyun Tang, Lingqi Gong, Wenli Zou, Jie Zhang, Yuqian Zhou, Xiaoping Wu, Fanggen Lu, Chunhui Ouyang, Xiaowei Liu
Gastroenteropancreatic neuroendocrine tumors (GEP‑NETs) are relatively uncommon. Unfortunately, epidemiological studies on the incidence of GEP‑NETs worldwide have reported a marked increase in the detection of these tumors. Although they often exhibit relatively indolent clinical courses, GEP‑NETs have the potential for lethal progression, especially in patients who present with advanced disease. Early detection and surgical removal is currently the only reliable curative treatment for GEP‑NET patients...
October 13, 2016: Oncology Reports
Sankar N Maity, Mark A Titus, Revekka Gyftaki, Guanglin Wu, Jing-Fang Lu, S Ramachandran, Elsa M Li-Ning-Tapia, Christopher J Logothetis, John C Araujo, Eleni Efstathiou
Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a validated treatment target for the treatment of metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) inhibits both 17α-hydroxylase (hydroxylase) and 17,20-lyase (lyase) reactions catalyzed by CYP17A1 and thus depletes androgen biosynthesis. However, coadministration of prednisone is required to suppress the mineralocorticoid excess and cortisol depletion that result from hydroxylase inhibition. VT-464, a nonsteroidal small molecule, selectively inhibits CYP17A1 lyase and therefore does not require prednisone supplementation...
October 17, 2016: Scientific Reports
Gustavo Dix Junqueira Pinto, Luciano de Souza Viana, Cristovam Scapulatempo Neto, Sérgio Vicente Serrano
Lung cancer is the leading world cause of cancer-related death, in both genders, and smoking is the main etiological factor. The discovery of immune checkpoints corroborates the hypothesis that ligands presented in tumors modulate the mechanisms of carcinogenesis and the immune activity of tumor microenvironment. Among the most studied coregulatory molecules, PD-1 (programmed cell death 1) and its ligand PD-L1 (programmed cell death 1 ligand 1) are noteworthy. The present study aims to enhance the understanding of the tumor microenvironment of lung cancer patients who underwent surgery, by means of analysis of PD-L1 expression in tumor cells and in intratumoral immune cells (IICs)...
2016: Journal of Immunology Research
Joo Hwa Lee, Nam Jin Yoo, Min Sung Kim, Sug Hyung Lee
Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H)...
October 15, 2016: Pathology Oncology Research: POR
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No abstract text is available yet for this article.
October 15, 2016: Cancer Research
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
Chintan A Dalwadi, Gayatri C Patel
BACKGROUND: The objective of the study was to investigate the cytotoxicity and cellular uptake of prepared 5-Fluorouracil (5-FU) nanohydrogel formulation using KB oral cancer cell line and VERO fibroblast cell line. METHOD: The biodegradable thermoresponsive modified methylcellulose (MMC) polymer was used for the preparation of nanohydrogel whereas it shows sol-gel phase transition at 36˚C to 40˚C. The physical crosslinking method was used followed by probe sonication for the preparation of 5-FU loaded MMC nanohydrogel...
October 13, 2016: Current Drug Delivery
Michael Welter, Heiko Rieger
Tumor vasculature, the blood vessel network supplying a growing tumor with nutrients such as oxygen or glucose, is in many respects different from the hierarchically organized arterio-venous blood vessel network in normal tissues. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature. Integrative models, based on detailed experimental data and physical laws, implement, in silico, the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature...
2016: Advances in Experimental Medicine and Biology
Janine Stucke-Ring, Julian Ronnacker, Caroline Brand, Carsten Höltke, Christoph Schliemann, Torsten Kessler, Lars Henning Schmidt, Saliha Harrach, Verena Mantke, Heike Hintelmann, Wolfgang Hartmann, Eva Wardelmann, Georg Lenz, Bernhard Wünsch, Carsten Müller-Tidow, Rolf M Mesters, Christian Schwöppe, Wolfgang E Berdel
Truncated tissue factor (tTF), retargeted to tumor vasculature by GNGRAHA peptide (tTF-NGR), and doxorubicin have therapeutic activity against a variety of tumors. We report on combination experiments of both drugs using different schedules. We have tested fluorescence- and HPLC-based intratumoral pharmacokinetics of doxorubicin, flow cytometry for cellular phosphatidylserine (PS) expression, and tumor xenograft studies for showing in vivo apoptosis, proliferation decrease, and tumor shrinkage upon combination therapy with doxorubicin and induced tumor vascular infarction...
October 11, 2016: Oncotarget
Jason Miska, Aida Rashidi, Alan L Chang, Megan E Muroski, Yu Han, Lingjiao Zhang, Maciej S Lesniak
Regulatory T cells (Tregs) are potently immunosuppressive cells that accumulate within the glioma microenvironment. The reduction in their function and/or trafficking has been previously shown to enhance survival in preclinical models of glioma. Glucocorticoid-induced TNFR-related protein (GITR) is a tumor necrosis factor superfamily receptor enriched on Tregs that has shown promise as a target for immunotherapy. An agonistic antibody against GITR has been demonstrated to inhibit Tregs in a number of models and has only been recently addressed in glioma...
October 12, 2016: Cancer Immunology, Immunotherapy: CII
T Kunicka, P Prochazka, I Krus, P Bendova, M Protivova, S Susova, V Hlavac, V Liska, P Novak, M Schneiderova, P Pitule, J Bruha, O Vycital, P Vodicka, P Soucek
BACKGROUND: This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients. METHODS: Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients...
October 12, 2016: BMC Cancer
Yi-An Zhang, Hai-Ning Liu, Ji-Min Zhu, Dan-Ying Zhang, Xi-Zhong Shen, Tao-Tao Liu
BACKGROUND: The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABAA receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABAARγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1. METHODS: Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABAARγ2 protein expression in hepatocellular carcinoma...
October 12, 2016: Journal of Biomedical Science
Robert J Gillies, Thomas Beyer
Over the past decades, imaging in oncology has been undergoing a "quiet" revolution to treat images as data, not as pictures. This revolution has been sparked by technological advances that enable capture of images that reflect not only anatomy, but also of tissue metabolism and physiology in situ Important advances along this path have been the increasing power of MRI, which can be used to measure spatially dependent differences in cell density, tissue organization, perfusion, and metabolism. In parallel, PET imaging allows quantitative assessment of the spatial localization of positron-emitting compounds, and it has also been constantly improving in the number of imageable tracers to measure metabolism and expression of macromolecules...
October 11, 2016: Cancer Research
Ju Hwa Lee, Nam Jin Yoo, Min Sung Kim, Chang Hyeok An, Sug Hyung Lee
Loss of ZMPSTE24 is related to progeroid phenotypes in human. Cells in zmpste24-deficient mice show delayed DNA damage response, increased aneuploidy and increased genomic instability, which are considered features of cancer cells. The aim of this study was to address whether ZMPSTE24 gene was mutated in colorectal cancers (CRCs) and gastric (GCs), and its expression was altered. ZMPSTE24 possesses a T9 mononucleotide repeat in an exon, which could be mutated in cancers with defects in mismatch repair that can result in microsatellite instability (MSI)...
October 6, 2016: Pathology, Research and Practice
Shuji Nagata, Hiroshi Nishimura, Kimberly K Amrami, Jun Akiba, Tatsuyuki Tonan, Kiminori Fujimoto, Toshi Abe
OBJECTIVE: The purpose of this study is to evaluate the usefulness of MRI in differentiating between fibrous and cellular solitary fibrous tumors (SFTs). MATERIALS AND METHODS: This retrospective study included 17 patients with histopathologically confirmed SFTs, including 10 patients with fibrous SFTs and seven patients with cellular SFTs. We evaluated the differences between fibrous and cellular SFTs with regard to clinical data and MRI findings, such as tumor margin definition, signal intensity, heterogeneity on T1- and T2-weighted images, presence of capsules, intratumoral cystic changes, flow signal void, perilesional edema, enhancement pattern on dynamic contrast-enhanced MRI (DCE-MRI), and mean apparent diffusion coefficient (ADC) values...
October 11, 2016: AJR. American Journal of Roentgenology
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