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Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
Vivek Murthy, Janna Minehart, Daniel H Sterman
Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses...
December 1, 2017: Journal of the National Cancer Institute
Yong Cui, Xiaoting Li, Shunyu Gao, Zhongwu Li, Yanling Li, Ming Lu, Yingshi Sun
Objective: To determine the capability of dynamic enhanced computed tomography (CT) to differentiate liver metastases (LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Methods: Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Yimin Niu, Jianhua Zhu, Yang Li, Huihui Shi, Yaxiang Gong, Rui Li, Qiang Huo, Tao Ma, Yang Liu
The penetration of nanomedicine into solid tumor still constitutes a great challenge for cancer therapy, which lead to the failure of thorough clearance of tumor cells. Aiming at solving this issue, lots of encouraging progress has been made in the development of multistage nanoparticles triggered by various stimuli in the past few years. Besides, the therapeutical effects of nanoagents are also greatly impacted by the complex tumor microenvironment, and remodeling tumor microenvironment has become another important approach for promoting nanoparticles penetration...
March 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hiroaki Kobayashi, Takeo Kosaka, Shuji Mikami, Yasumasa Miyazaki, Kazuhiro Matsumoto, Eiji Kikuchi, Akira Miyajima, Kaori Kameyama, Yasufumi Sato, Mototsugu Oya
Background: We previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer. Results: Pathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group)...
February 13, 2018: Oncotarget
Peng Wu, Jia-Li Liu, Shi-Mei Pei, Chang-Peng Wu, Kai Yang, Shu-Peng Wang, Song Wu
BACKGROUND: Renal cell carcinoma (RCC) account for over 80% of renal malignancies. The most common type of RCC can be classified into three subtypes including clear cell, papillary and chromophobe. ccRCC (the Clear Cell Renal Cell Carcinoma) is the most frequent form and shows variations in genetics and behavior. To improve accuracy and personalized care and increase the cure rate of cancer, molecular typing for individuals is necessary. METHODS: We adopted the genome, transcriptome and methylation HMK450 data of ccRCC in The Cancer Genome Atlas Network in this research...
March 13, 2018: BMC Cancer
Jessica Wagner, C Leah Kline, Lanlan Zhou, Kerry S Campbell, Alexander W MacFarlane, Anthony J Olszanski, Kathy Q Cai, Harvey H Hensley, Eric A Ross, Marie D Ralff, Andrew Zloza, Charles B Chesson, Jenna H Newman, Howard Kaufman, Joseph R Bertino, Mark N Stein, Wafik El-Deiry
ONC201 is a first-in-class, orally active anti-tumor agent that upregulates cytotoxic TRAIL pathway signaling in cancer cells. ONC201 has demonstrated safety and preliminary efficacy in the first-in-human trial where patients were dosed every 3 weeks. We hypothesized that dose-intensification of ONC201 may impact anti-tumor efficacy. We discovered that ONC201 exerts dose- and schedule-dependent effects on tumor progression and cell-death signaling in vivo. With dose intensification, we note a potent anti-metastasis effect and inhibition of cancer cell migration and invasion...
March 13, 2018: Journal of Clinical Investigation
Bowen Yang, Han Lin, Chen Dai, Yu Chen, Jianlin Shi
"Smart" bioresponsive materials, which are sensitive to biological signals or pathological abnormalities, are appealing therapeutic platforms for the development of next-generation cancer theranostics. In this work, a novel "stepwise extraction" strategy has been proposed and demonstrated in constructing injectable bioresponsive composite implant, which features unique theranostic responsivenesses to exogenous and external triggers. The as-designed implant exhibits theranostic functions and biodegradability for cancer treatment based on the change of intratumoral microenvironment and the needs of therapeutic process...
March 7, 2018: Biomaterials
Devin C Flaherty, John R Jalas, Myung S Sim, Alexander Stojadinovic, Mladjan Protic, Delphine J Lee, Anton J Bilchik
BACKGROUND: The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment. METHODS: For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer...
March 12, 2018: Annals of Surgical Oncology
Hirokazu Sadahiro, Kyung-Don Kang, Justin T Gibson, Mutsuko Minata, Hai Yu, Junfeng Shi, Rishi Raj Chhipa, Zhihong Chen, Songjia Lu, Yannick Simoni, Takuya Furuta, Hemragul Sabit, Suojun Zhang, Soniya Bastola, Shinobu Yamaguchi, Heba Allah Alsheikh, Svetlana Komarova, Jun Wang, Sung-Hak Kim, Dolores Hambardzumyan, Xinghua Lu, Evan W Newell, Biplab Dasgupta, Mitsutoshi Nakada, Ly James Lee, Louis B Nabors, Lyse A Norian, Ichiro Nakano
Glioblastoma (GBM) is a lethal disease with no effective therapies available. We previously observed upregulation of the TAM (Tyro-3, Axl, and Mer) receptor tyrosine kinase family member AXL in mesenchymal GBM and showed that knockdown of AXL induced apoptosis of mesenchymal, but not proneural, glioma sphere cultures (GSC). In this study, we report that BGB324, a novel small molecule inhibitor of AXL, prolongs the survival of immunocompromised mice bearing GSC-derived mesenchymal GBM-like tumors. We show that protein S (PROS1), a known ligand of other TAM receptors, was secreted by tumor-associated macrophages/microglia and subsequently physically associated with and activated AXL in mesenchymal GSC...
March 12, 2018: Cancer Research
Ornella Franzese, Fiorenzo Battaini, Grazia Graziani, Lucio Tentori, Maria Luisa Barbaccia, Angelo Aquino, Mario Roselli, Maria Pia Fuggetta, Enzo Bonmassar, Francesco Torino
In recent years, immune checkpoint inhibitors (ICpI) have provided the ground to bring tumor immunity back to life thanks to their capacity to afford a real clinical benefit in terms of patient's survival. Essential to ICpI success is the presence of tumor-associated neoantigens generated by non-synonymous mutations, since a direct relationship between mutation load of malignant cells and susceptibility to ICpI has been confidently established. However, it has been also suggested that high intratumor heterogeneity (ITH) associated with subclonal neoantigens could not elicit adequate immune responses...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tigran Khachatryan, Marina Khachatryan, Ruben Fanarjyan, Mikayel Grigoryan, Arthur Grigorian
Background: Currently, transsphenoidal surgery (TSS) is the preferred method for surgical treatment of intrasellar pituitary adenomas. However, it carries some risk of intraoperative arterial injuries, which is mainly attributed to direct iatrogenic rupture of the internal carotid artery (ICA). There is anecdotal evidence suggesting that intracranial aneurysms are coincidentally found significantly more frequently in the setting of pituitary adenomas than when the incidence is compared to other intracranial neoplasms...
2018: Surgical Neurology International
Ralitza Staneva, Jorge Barbazan, Anthony Simon, Danijela Matic Vignjevic, Denis Krndija
Cell migration is a process that ensures correct cell localization and function in development and homeostasis. In disease such as cancer, cells acquire an upregulated migratory capacity that leads to their dissemination throughout the body. Live imaging of cell migration allows for better understanding of cell behaviors in development, adult tissue homeostasis and disease. We have optimized live imaging procedures to track cell migration in adult murine tissue explants derived from: (1) healthy gut; (2) primary intestinal carcinoma; and (3) the liver, a common metastatic site...
2018: Methods in Molecular Biology
C Burkart, A Mukhopadhyay, S A Shirley, R J Connolly, J H Wright, A Bahrami, J S Campbell, R H Pierce, D A Canton
The use of immunomodulatory cytokines has been shown effective in regressing a wide range of tumors. However, systemic delivery of recombinant cytokines results in serious, potentially life-threatening, adverse effects. By contrast, nucleic acid transfer via electroporation (EP) is a safe and effective method of delivering plasmid-encoded cytokines to tumors. Intratumoral delivery of IL-12 plasmid DNA by electroporation (IT-pIL12-EP) produced objective response rates in Phase 2 clinical trials in metastatic melanoma...
March 9, 2018: Gene Therapy
V G Deepagan, Hyewon Ko, Seunglee Kwon, N Vijayakameswara Rao, Sang Kyoon Kim, Wooram Um, Sohee Lee, Jiwoong Min, Jeongjin Lee, Ki Young Choi, Sol Shin, Minah Suh, Jae Hyung Park
Conventional cancer targeting with nanoparticles has been based on the assumed enhanced permeability and retention (EPR) effect. The data obtained in clinical trials to date, however, have rarely supported the presence of such an effect. To address this challenge, we formulated intracellular nitric oxide-generating nanoparticles (NO-NPs) for the tumor site-specific delivery of NO, a well-known vasodilator, with the intention of boosting EPR. These nanoparticles are self-assembled under aqueous conditions from amphiphilic copolymers of poly(ethylene glycol) and nitrated dextran, which possesses inherent NO release properties in the reductive environment of cancer cells...
March 9, 2018: Nano Letters
J Zhang, Y F Wang, B Wu, Z X Zhong, K X Wang, L Q Yang, Y Q Wang, Y Q Li, J Gao, Z S Li
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are one of the major participants in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of interaction between TILs and tumors is complex and remains unclear. OBJECTIVE: To evaluate the state of immunoreactions in PDAC tissues, and explore the prognostic value of these markers in a large sample, to provide a new theoretical basis for PDAC immunotherapy. METHOD: Immunohistochemical staining of CD4+ and CD8+T cells was performed in a tissue microarray (TMA) of 143 cases of PDAC...
March 7, 2018: Current Molecular Medicine
Weihua Li, Tian Qiu, Yun Ling, Shugeng Gao, Jianming Ying
Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting appropriate tissue samples to NGS testing were explored. The results showed that lower frequencies of HER2/BRAF/PIK3CA and acquired EGFR T790M mutations were observed in biopsy samples with <20% tumor cellularity than those with ≥20%, but there were no significant differences in the frequencies of EGFR or KRAS mutations...
March 8, 2018: Molecular Oncology
Aoi Hayasaki, Yasuhiro Murata, Masanobu Usui, Taemi Hibi, Takahiro Ito, Yusuke Iizawa, Hiroyuki Kato, Akihiro Tanemura, Yoshinori Azumi, Naohisa Kuriyama, Masashi Kishiwada, Shugo Mizuno, Hiroyuki Sakurai, Toshimichi Yoshida, Shuji Isaji
OBJECTIVES: Tenascin-C (TN-C) is an extracellular matrix protein that is up-regulated in pancreatic ductal adenocarcinoma (PDAC) stroma and associated with tumor invasion. We examined intratumor stromal expression of TN-C in resected specimens and the histologic effect of chemoradiotherapy (CRT) as prognostic indicators in initially locally advanced unresectable (UR-LA) PDAC. METHODS: Among 110 UR-LA PDAC patients enrolled in the CRT protocol from February 2005 to December 2015, 46 who underwent curative-intent resection were classified as high (tumor destruction >50%) and low (≤50%) responders according to the Evans grading system...
March 6, 2018: Pancreas
Yun Sol Jo, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee
MYH11 functions as a contractile protein, converting chemical energy into mechanical energy through adenosine triphosphate hydrolysis. In cancers, an oncogenic fusion CBFB/MYH11 and frameshift mutations have been reported. Truncating mutants of MYH11 exhibited increased ATPase and motor activity, suggesting their roles in energy balance and movement of cancer cells. MYH11 gene has a mononucleotide repeat (C8) in the coding sequences that could be a mutational target in the cancers exhibiting microsatellite instability (MSI)...
March 6, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
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