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https://www.readbyqxmd.com/read/28930684/tumor-derived-mesenchymal-stem-cells-use-distinct-mechanisms-to-block-the-activity-of-natural-killer-cell-subsets
#1
Sabine Galland, Joanna Vuille, Patricia Martin, Igor Letovanec, Anne Caignard, Giulia Fregni, Ivan Stamenkovic
Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28929220/-pathogenesis-and-genetics-of-osteosarcoma-current-concepts-and-developments
#2
REVIEW
D Baumhoer
Osteosarcomas are genetically complex tumours for which the cell of origin and the molecular pathogenesis are still poorly understood. Despite intensive multimodal treatment protocols only two thirds of patients currently survive the disease which is at least partly due to the early occurring chromosomal instability resulting in marked inter- and intratumoral heterogeneity. This review article outlines the current state of osteosarcoma research with a particular focus on exome- and genome-wide sequencing analyses and potential impacts on new therapeutic opportunities...
September 19, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28927692/prognostic-influence-of-tumor-stroma-on-breast-cancer-subtypes
#3
Sandra Cid, Noemi Eiro, Berta Fernández, Rosario Sánchez, Alejandro Andicoechea, Pablo Ignacio Fernández-Muñiz, Luis O González, Francisco J Vizoso
INTRODUCTION: The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) on prognosis in different breast cancer subtypes. MATERIALS AND METHODS: A total of 247 tumors of patients with primary ductal invasive breast cancer were categorized into 1 of 4 major subtypes, using the 3 standard immunohistochemical markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor/Neu 2 [HER2] receptor status)...
August 19, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28927083/expression-of-thymidylate-synthase-predicts-clinical-outcomes-of-s-1-based-chemotherapy-in-squamous-cell-lung-cancer
#4
Yuichiro Honma, Shinsaku Togo, Kazue Shimizu, Miniwan Tulafu, Takuo Hayashi, Toshimasa Uekusa, Shigeru Tominaga, Kenji Kido, Yuichi Fujimoto, Yukiko Nanba, Kazuya Takamochi, Shiaki Oh, Kenji Suzuki, Kazuhisa Takahashi
Non-small cell lung cancer (NSCLC) patients with squamous cell carcinoma (SCC) histology have limited chemotherapeutic options. Treatment with S-1 combined with carboplatin (CBDCA) has been shown to provide a significant survival benefit in SCC patients compared with treatment with combined CBDCA and paclitaxel. The aim of the present study was to investigate the association between the expression of molecular markers related to the pharmacological action of S-1, including thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD), and the clinical efficacy of S-1-based chemotherapy in SCC patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926893/-effect-of-intratumor-heterogeneity-of-esophageal-squamous-cell-carcinoma-on-chemotherapy-sensitivity
#5
L Sun, W Wu, M Yan, P L Han, X Zhan, X W Ma, X G Cao, S Zhao, F Gao, Y Qi, W Cao
Objective: To investigate the relationship of heterogeneity of esophageal squamous cell carcinoma (ESCC) and chemotherapy sensitivity. Methods: Five different region specimens isolated from primary tumor(R1~R5)and 1 specimen(R6)isolated from adjacent non-neoplastic tissue from 10 ESCC patients who underwent surgical treatment were cultured in vitro. The inhibitory effect of cisplatin on proliferation of ESCC cells from different regions was determined by methyl thiazolyl tetrazolium (MTT). The cell cycle and apoptosis induced by cisplatin was determined by flow cytometry (FCM) analysis...
September 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28925392/atypical-e2fs-inhibit-tumor-angiogenesis
#6
B G M W Weijts, B Westendorp, B T Hien, L M Martínez-López, M Zijp, I Thurlings, R E Thomas, S Schulte-Merker, W J Bakker, A de Bruin
Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28923858/anti-cd137-suppresses-tumor-growth-by-blocking-reverse-signaling-by-cd137-ligand
#7
Sang W Kang, Sang Chul Lee, So H Park, Juyang Kim, Hyeon H Kim, Hyeon-Woo Lee, Su-Kil Seo, Byoung S Kwon, Hong R Cho, Byungsuk Kwon
CD137 (4-1BB) is a T cell co-stimulatory molecule and agonstic CD137 antibodies are currently being evaluated in clinic as cancer immunotherapy. Recently, it was found that CD137-/- mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923683/a-hydrogel-matrix-prolongs-persistence-and-promotes-specific-localization-of-an-oncolytic-adenovirus-in-a-tumor-by-restricting-nonspecific-shedding-and-an-antiviral-immune-response
#8
Bo-Kyeong Jung, Eonju Oh, JinWoo Hong, Yunki Lee, Ki Dong Park, Chae-Ok Yun
Currently, intratumoral injection of an oncolytic adenovirus (Ad) is the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, thus necessitating multiple injections to achieve a sufficient therapeutic index. In the present study, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-expressing oncolytic Ad (oAd-TRAIL) was encapsulated in a gelatin hydrogel (oAd-TRAIL/gel) to enhance and prolong antitumor efficacy of the virus after a single intratumoral injection...
September 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28923105/genetic-engineering-of-human-nk-cells-to-express-cxcr2-improves-migration-to-renal-cell-carcinoma
#9
Veronika Kremer, Maarten Ligtenberg, Rosa Zendehdel, Christina Seitz, Annet Duivenvoorden, Erik Wennerberg, Eugenia Colón, Ann-Helén Scherman-Plogell, Andreas Lundqvist
BACKGROUND: Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923104/phase-1-study-of-intravenous-administration-of-the-chimeric-adenovirus-enadenotucirev-in-patients-undergoing-primary-tumor-resection
#10
Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo, Kerry Fisher
BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#11
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920000/oncolytic-peptide-ltx-315-induces-an-immune-mediated-abscopal-effect-in-a-rat-sarcoma-model
#12
Janne Nestvold, Meng-Yu Wang, Ketil A Camilio, Severin Zinöcker, Torunn Elisabeth Tjelle, Alf Lindberg, Bengt Erik Haug, Gunnar Kvalheim, Baldur Sveinbjørnsson, Øystein Rekdal
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration of CD8(+) T cells was observed in both treated and non-treated lesions, as shown by immunohistochemical and flow cytometric analysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#13
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28918263/dna-nanotechnology-based-composite-type-gold-nanoparticle-immunostimulatory-dna-hydrogel-for-tumor-photothermal-immunotherapy
#14
Tomoya Yata, Yuki Takahashi, Mengmeng Tan, Hirotaka Nakatsuji, Shozo Ohtsuki, Tatsuya Murakami, Hiroshi Imahori, Yuka Umeki, Tomoki Shiomi, Yoshinobu Takakura, Makiya Nishikawa
Success of tumor photothermal immunotherapy requires a system that induces heat stress in cancer cells and enhances strong anti-tumor immune responses. Here, we designed a composite-type immunostimulatory DNA hydrogel consisting of a hexapod-like structured DNA (hexapodna) with CpG sequences and gold nanoparticles. Mixing of the properly designed hexapodna and oligodeoxynucleotide-modified gold nanoparticles resulted in the formation of composite-type gold nanoparticle-DNA hydrogels. Laser irradiation of the hydrogel resulted in the release of hexapodna, which efficiently stimulated immune cells to release proinflammatory cytokines...
September 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/28918115/the-interplay-of-endocrine-therapy-steroid-pathways-and-therapeutic-resistance-importance-of-androgen-in-breast-carcinoma
#15
REVIEW
Kiyoshi Takagi, Yasuhiro Miki, Takanori Ishida, Hironobu Sasano, Takashi Suzuki
A great majority of breast carcinomas expresses estrogen receptor (ER) and estrogens have crucial roles in the progress of breast carcinomas. Endocrine therapy targeting ER and/or intratumoral estrogen production significantly improved clinical outcomes of the patients with ER-positive breast carcinomas. However, resistance to endocrine therapy is often observed and significant number of patients will recur after the treatment. In addition, treatment for the patients with triple-negative breast carcinomas (negative for all ER, progesterone receptor (PR) and HER2) are limited to cytotoxic chemotherapy and novel therapeutic targets need to be identified...
September 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28918059/regulatory-role-of-the-microrna-29b-il-6-signaling-in-the-formation-of-vascular-mimicry
#16
Jian-Hong Fang, Zhi-Yuan Zheng, Jin-Yu Liu, Chen Xie, Zi-Jun Zhang, Shi-Mei Zhuang
Vascular mimicry (VM) is a critical complement for microcirculation and is implicated in tumor progression. We showed that IL-6 derived from tumor cells and stroma cells promoted tumor cells to form a VM structure, whereas blocking the IL-6 signaling by RNA interference, IL-6-neutralizing antibody, or STAT3 inhibitor suppressed the VM formation of tumor cells. Mechanism investigations revealed that IL-6 stimulated VM formation by activating STAT3, in turn upregulating VE-cadherin expression and MMP2 activity...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918040/codon-optimized-p1a-encoding-dna-vaccine-toward-a-therapeutic-vaccination-against-p815-mastocytoma
#17
Alessandra Lopes, Kevin Vanvarenberg, Véronique Préat, Gaëlle Vandermeulen
DNA vaccine can be modified to increase protein production and modulate immune response. To enhance the efficiency of a P815 mastocytoma DNA vaccine, the P1A gene sequence was optimized by substituting specific codons with synonymous ones while modulating the number of CpG motifs. The P815A murine antigen production was increased with codon-optimized plasmids. The number of CpG motifs within the P1A gene sequence modulated the immunogenicity by inducing a local increase in the cytokines involved in innate immunity...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917532/effects-of-tumor-microenvironments-on-targeted-delivery-of-glycol-chitosan-nanoparticles
#18
Ji Young Yhee, Sangmin Jeon, Hong Yeol Yoon, Man Kyu Shim, Hyewon Ko, Jiwoong Min, Jin Hee Na, Hyeyoun Chang, Hyounkoo Han, Jong-Ho Kim, Minah Suh, Hyukjin Lee, Jae Hyung Park, Kwangmeyung Kim, Ick Chan Kwon
In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated...
September 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28916588/glioblastoma-stem-cell-clonal-dynamics-drive-intratumor-heterogeneity
#19
(no author information available yet)
GBM heterogeneity is primarily driven by the stochastic outcome of GBM stem cell hierarchical growth.
September 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28916497/two-step-polymer-and-liposome-enzyme-prodrug-therapies-for-cancer-pdept-and-pelt-concepts-and-future-perspectives
#20
Anna Scomparin, Helena F Florindo, Galia Tiram, Elaine L Ferguson, Ronit Satchi-Fainaro
Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results...
September 12, 2017: Advanced Drug Delivery Reviews
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