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https://www.readbyqxmd.com/read/28344893/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-in-malignant-pleural-mesothelioma
#1
Kazuma Kiyotani, Jae-Hyun Park, Hiroyuki Inoue, Aliya Husain, Sope Olugbile, Makda Zewde, Yusuke Nakamura, Wickii T Vigneswaran
To investigate the link between the genomic landscape of cancer cells and immune microenvironment in tumor tissues, we characterized somatic mutations and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM), including mutation/neoantigen load, spatial heterogeneity of somatic mutations of cancer cells and TILs (T-cell receptor β (TCRβ) repertoire), and expression profiles of immune-related genes using specimens of three different tumor sites (anterior, posterior, and diaphragm) obtained from six MPM patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#2
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28343015/systemic-delivery-of-the-tumor-necrosis-factor-gene-to-tumors-by-a-novel-dual-dna-nanocomplex-in-a-nanoparticle-system
#3
Vasundhara Shukla, Manu Dalela, Manika Vij, Munia Ganguli, Ralph Weichselbaum, Surender Kharbanda, Donald Kufe, Harpal Singh
Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving DNA expression vectors encoding inflammatory cytokines in tumor cells. The DNP system consists of a DNA expression vector-cationic nanocomplex (NC) surrounded by a diblock polymeric NP...
March 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28341760/intratumoral-heterogeneity-in-breast-cancer-a-comparison-of-primary-and-metastatic-breast-cancers
#4
Yu-Jie Shi, Julia Y S Tsang, Yun-Bi Ni, Gary M Tse
Intratumoral heterogeneity presents challenges in the management of cancer. To gain deeper insight in intratumoral heterogeneity at different levels and tumor sites for common biomarkers in breast cancers, this report examines seven cases of invasive breast cancer with multiple axillary nodal metastases and/or recurrences for immunohistochemical expression of estrogen receptors, progesterone receptors, human epidermal growth receptor 2, and Ki67 on all tissue blocks in both primary and metastatic tumors. The Oncologist 2017;22:1-4...
March 24, 2017: Oncologist
https://www.readbyqxmd.com/read/28340497/p450-inhibitor-ketoconazole-increased-the-intratumor-drug-levels-and-antitumor-activity-of-fenretinide-in-human-neuroblastoma-xenograft-models
#5
Lluis Lopez-Barcons, Barry J Maurer, Min H Kang, C Patrick Reynolds
We previously reported that concurrent ketoconazole, an oral anti-fungal agent and P450 enzyme inhibitor, increased plasma levels of the cytotoxic retinoid, fenretinide (4-HPR) in mice. We have now determined the effects of concurrent ketoconazole on 4-HPR cytotoxic dose-response in four neuroblastoma (NB) cell lines in vitro and on 4-HPR activity against two cell line-derived, subcutaneous NB xenografts (CDX) and three patient-derived NB xenografts (PDX). Cytotoxicity in vitro was assessed by DIMSCAN assay...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28339788/intravenous-dendritic-cell-administration-enhances-suppression-of-lung-metastasis-induced-by-carbon-ion-irradiation
#6
Ken Ando, Hidetoshi Fujita, Akihiro Hosoi, Liqiu Ma, Masaru Wakatsuki, Ken-Ichiro Seino, Kazuhiro Kakimi, Takashi Imai, Takashi Shimokawa, Takashi Nakano
Carbon-ion radiotherapy (CIRT) is an advanced radiotherapy and has achieved good local control, even in tumors that are resistant to conventional photon beam radiotherapy (PBRT). However, distant metastasis control is an important issue. Recently, the combination of radiotherapy and immunotherapy has attracted the attention. In immunotherapy, dendritic cells (DCs) play a pivotal role in the anti-tumor immune system. However, the mechanisms underlying the combination therapy of DCs and radiotherapy have been unclear...
February 27, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28339582/hypoxia-in-the-glioblastoma-microenvironment-shaping-the-phenotype-of-cancer-stem-like-cells
#7
Nicole Colwell, Mioara Larion, Amber J Giles, Ashlee N Seldomridge, Saman Sizdahkhani, Mark R Gilbert, Deric M Park
Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity...
January 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28338197/predictive-value-and-modeling-analysis-of-msct-signs-in-gastrointestinal-stromal-tumors-gists-to-pathological-risk-degree
#8
J-K Wang
OBJECTIVE: By analyzing MSCT (multi-slice computed tomography) signs with different risks in gastrointestinal stromal tumors, this paper aimed to discuss the predictive value and modeling analysis of MSCT signs in GISTs (gastrointestinal stromal tumor) to pathological risk degree. PATIENTS AND METHODS: 100 cases of primary GISTs with abdominal and pelvic MSCT scan were involved in this study. All MSCT scan findings and enhanced findings were analyzed and compared among cases with different risk degree of pathology...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28336377/block-copolymer-boron-cluster-conjugate-for-effective-boron-neutron-capture-therapy-of-solid-tumors
#9
Peng Mi, Hironobu Yanagie, Novriana Dewi, Hung-Chi Yen, Xueying Liu, Minoru Suzuki, Yoshinori Sakurai, Koji Ono, Hiroyuki Takahashi, Horacio Cabral, Kazunori Kataoka, Nobuhiro Nishiyama
Boron neutron capture therapy is a promising tumor treatment method, though its wide application has been limited due to the poor tumor selectivity and intracellular delivery of (10)B-compounds. Here, block copolymer-boron cluster conjugate based on the clinically used sodium borocaptate (BSH) and poly(ethylene glycol)-b-poly(glutamic acid) copolymer have been developed for effectively penetrating tumor tissues and homogeneously delivering the boron clusters into cancer cells towards safe and efficient boron neutron capture therapy...
March 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28335080/comparisons-among-mri-signs-apparent-diffusion-coefficient-and-fractional-anisotropy-in-dogs-with-a-solitary-intracranial-meningioma-or-histiocytic-sarcoma
#10
Masae Wada, Daisuke Hasegawa, Yuji Hamamoto, Yoshihiko Yu, Aki Fujiwara-Igarashi, Michio Fujita
Although MRI has become widely used in small animal practice, little is known about the validity of advanced MRI techniques such as diffusion-weighted imaging and diffusion tensor imaging. The aim of this retrospective analytical observational study was to investigate the characteristics of diffusion parameters, that is the apparent diffusion coefficient and fractional anisotropy, in dogs with a solitary intracranial meningioma or histiocytic sarcoma. Dogs were included based on the performance of diffusion MRI and histological confirmation...
March 23, 2017: Veterinary Radiology & Ultrasound
https://www.readbyqxmd.com/read/28332605/janus-faced-acrolein-prevents-allergy-but-accelerates-tumor-growth-by-promoting-immunoregulatory-foxp3-cells-mouse-model-for-passive-respiratory-exposure
#11
Franziska Roth-Walter, Cornelia Bergmayr, Sarah Meitz, Stefan Buchleitner, Caroline Stremnitzer, Judit Fazekas, Anna Moskovskich, Mario A Müller, Georg A Roth, Krisztina Manzano-Szalai, Zdenek Dvorak, Alina Neunkirchner, Erika Jensen-Jarolim
Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332339/sonographic-and-cytologic-differences-of-niftp-from-infiltrative-or-invasive-encapsulated-follicular-variant-of-papillary-thyroid-carcinoma-a-review-of-179-cases
#12
REVIEW
Grace C H Yang, Karen O Fried, Theresa Scognamiglio
We reclassified 179 cases of the follicular variant (FV) of papillary thyroid carcinoma (PTC) into 72 (40.2%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), 37 (20.7%) encapsulated FVPTC with invasion (EFVPTC), and 70 (39.1%) infiltrative FVPTC (IFVPTC) without a capsule. In the NIFTP group, 5.6% cytology were hypercellular and the remainder low to moderate cellularity. PTC nuclei were absent in 18%, focally present in 37.5%, and diffusely present in 44.4%. In the EFVPTC group, 8...
March 22, 2017: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/28328191/enhancing-tumor-penetration-of-nanomedicines
#13
Qingxue Sun, Tarun Ojha, Fabian Kiessling, Twan Lammers, Yang Shi
Tumor-targeted nanomedicines have been extensively applied to alter the drawbacks and enhance the efficacy of chemotherapeutics. Despite the large number of preclinical nanomedicine studies showing initial success, their therapeutic benefit in the clinic has been rather modest, which is partially due to the inefficient tumor penetration caused by tumor microenvironment (high density of cells and extracellular matrix, increased interstitial fluid pressure). Furthermore, tumor penetration of nanomedicines is significantly influenced by physicochemical characteristics such as size, surface chemistry and shape...
March 22, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28323387/induction-of-tumor-regression-by-intratumoral-sting-agonists-combined-with-anti-programmed-death-l1-blocking-antibody-in-a-preclinical-squamous-cell-carcinoma-model
#14
Shekhar K Gadkaree, Juan Fu, Rupashree Sen, Michael J Korrer, Clint Allen, Young J Kim
BACKGROUND: Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have demonstrated antitumor activity in melanoma and breast tumors, although their role in immunotherapy of head and neck squamous cell cancers (HNSCCs) has not been well investigated. METHODS: We measured primary tumor growth rates, mechanism of antitumor activity, and efficacy of programmed death-L1 blockade combinatorial therapy in SCCFVII tumor-bearing C3H/HeOUJ mice undergoing intratumoral injections with RR-cyclic-di-guanine (synthetic CDG), CDG (natural cyclic-di-guanine), R848 (TLR 7/8 agonist), or phosphate buffered saline (PBS, control)...
March 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28323123/circumventing-intratumoral-heterogeneity-to-identify-potential-therapeutic-targets-in-hepatocellular-carcinoma
#15
Ao Huang, Xin Zhao, Xin-Rong Yang, Fu-Qiang Li, Xin-Lan Zhou, Kui Wu, Xin Zhang, Qi-Man Sun, Ya Cao, Hong-Mei Zhu, Xiang-Dong Wang, Huan-Ming Yang, Jian Wang, Zhao-You Tang, Yong Hou, Jia Fan, Jian Zhou
BACKGROUND AND AIMS: Intratumoral heterogeneity (ITH) challenges identifying mutations with target therapy potential whereas circulating cell-free DNAs (cfDNAs) in blood could possibly reflect the entire mutation spectrum in certain tumors. We investigated how to minimize the limit of ITH for profiling hepatocellular carcinoma (HCC). METHODS: Thirty-two multi-regional tumor samples from five patients were subjected to whole exome sequencing (WES) and targeted deep sequencing (TDS); matched preoperative cfDNAs were sequenced accordingly...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28321395/detection-of-intratumor-heterogeneity-in-modern-pathology-a-multisite-tumor-sampling-perspective
#16
Jesús M Cortés, Giovanni de Petris, José I López
Current sampling protocols of neoplasms along the digestive tract and in the urinary bladder have to be updated, as they do not respond to the necessities of modern personalized medicine. We show here that an adapted version of multisite tumor sampling (MSTS) is a sustainable model to overcome current deficiencies in digestive and bladder tumors when they are large enough so as to make unaffordable a total sampling. The new method is based on the divide-and-conquer algorithm and includes a slight modification of the MSTS, which proved to be useful very recently in clear cell renal cell carcinoma...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#17
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319088/reference-component-analysis-of-single-cell-transcriptomes-elucidates-cellular-heterogeneity-in-human-colorectal-tumors
#18
Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs)...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28319069/the-branched-chain-amino-acid-transaminase-1-sustains-growth-of-antiestrogen-resistant-and-er%C3%AE-negative-breast-cancer
#19
V Thewes, R Simon, M Hlevnjak, M Schlotter, P Schroeter, K Schmidt, Y Wu, T Anzeneder, W Wang, P Windisch, M Kirchgäßner, N Melling, N Kneisel, R Büttner, U Deuschle, H P Sinn, A Schneeweiss, S Heck, S Kaulfuss, H Hess-Stumpp, J G Okun, G Sauter, A E Lykkesfeldt, M Zapatka, B Radlwimmer, P Lichter, M Tönjes
Antiestrogen-resistant and triple-negative breast tumors pose a serious clinical challenge because of limited treatment options. We assessed global gene expression changes in antiestrogen-sensitive compared with antiestrogen-resistant (two tamoxifen resistant and two fulvestrant resistant) MCF-7 breast cancer cell lines. The branched-chain amino acid transaminase 1 (BCAT1), which catalyzes the first step in the breakdown of branched-chain amino acids, was among the most upregulated transcripts in antiestrogen-resistant cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28316008/cytogenetic-analysis-of-metaplastic-squamous-cell-carcinoma-of-the-breast-inter-and-intratumoral-heterogeneity
#20
Masahiro Oikawa, Akiko Igawa, Kenichi Taguchi, Kimiko Baba, Mayumi Ishida, Sayuri Akiyoshi, Hiroshi Yano, Takeshi Nagayasu, Shinji Ohno, Eriko Tokunaga
BACKGROUND: Squamous cell carcinoma (SCC) of the breast is a rare and generally aggressive disease that accounts for less than 0.1% of all breast carcinomas. Although SCCs have distinct morphological features, their origin and cytogenetic profile are not well understood. METHODS: Five patients with SCC were studied. The tumor area that was predominantly composed of SCC components was macrodissected and DNA was extracted. In three cases, an invasive or noninvasive ductal carcinoma of no special type (NST) component was also present...
March 18, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
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