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intratumoral chemotherapy

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https://www.readbyqxmd.com/read/29161627/nanoscaled-red-blood-cells-facilitate-breast-cancer-treatment-by-combining-photothermal-photodynamic-therapy-and-chemotherapy
#1
Guoyun Wan, Bowei Chen, Ling Li, Dan Wang, Shurui Shi, Tao Zhang, Yue Wang, Lianyun Zhang, Yinsong Wang
Red blood cells (RBCs)-based vesicles have been widely used for drug delivery due to their unique advantages. Intact RBCs contain a large amount of oxyhemoglobin (oxyHb), which can assist with photodynamic therapy (PDT). Indocyanine green (ICG), a photosensitizer both for photothermal therapy (PTT) and PDT, shows potent anticancer efficacy when combined with chemotherapeutic drug doxorubicin (DOX). In this study, we prepared nanoscaled RBCs (RAs) containing oxyHb and gas-generating agent ammonium bicarbonate (ABC) for co-loading and controlled release of ICG and DOX, thus hoping to achieve synergistic effects of PTT/PDT and chemotherapy against breast cancer...
November 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/29155424/immune-checkpoint-inhibitors-in-sarcomas-in-quest-of-predictive-biomarkers
#2
Robin Veenstra, Marie Kostine, Anne-Marie Cleton-Jansen, Noel Fcc de Miranda, Judith Vmg Bovée
Sarcomas are a rare group of tumors of mesenchymal origin. Metastatic sarcomas are often difficult to treat and unresponsive to standard radio- and chemotherapy, resulting in a poor survival rate for patients. Novel treatments with immune checkpoint inhibitors have been proven to prolong survival of patients with a variety of cancers, including metastatic melanoma, lung, and renal cell carcinoma. Since immune checkpoint inhibitors could provide a novel treatment option for patients with sarcomas, clinical trials investigating their efficacy in these group of tumors are ongoing...
November 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29151166/t2-weighted-images-are-superior-to-other-mr-image-types-for-the-determination-of-diffuse-intrinsic-pontine-glioma-intratumoral-heterogeneity
#3
Stephen Harward, S Harrison Farber, Michael Malinzak, Oren Becher, Eric M Thompson
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) remains the main cause of death in children with brain tumors. Given the inefficacy of numerous peripherally delivered agents to treat DIPG, convection enhanced delivery (CED) of therapeutic agents is a promising treatment modality. The purpose of this study was to determine which MR imaging type provides the best discrimination of intratumoral heterogeneity to guide future stereotactic implantation of CED catheters into the most cellular tumor regions...
November 18, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29146246/nanoparticle-formulation-improves-doxorubicin-efficacy-by-enhancing-host-antitumor-immunity
#4
Eric M Mastria, Leon Y Cai, Matthew J Kan, Xinghai Li, Jeffrey L Schaal, Steven Fiering, Michael D Gunn, Mark W Dewhirst, Smita K Nair, Ashutosh Chilkoti
Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#5
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29132812/the-antitumor-effect-of-folic-acid-conjugated-auricularia-auricular-polysaccharide-cisplatin-complex-on-cervical-carcinoma-cells-in-nude-mice
#6
Junqiang Qiu, Hua Zhang, Zhenyu Wang, Didi Liu, Shumin Liu, Wei Han, Joe M Regenstein, Lin Geng
A tumor-targeted, folic acid (FA) conjugated-Auricularia auricular polysaccharide (AAP) -cis-diaminedichloroplatinum (CDDP) complex (FA-AAP-CDDP) was used for cervical carcinoma chemotherapy. The drug delivery system was able to enhance the antitumor potency of CDDP, and to reduce the toxic side effects of CDDP. The kidney of mice treated by FA-AAP-CDDP complex had higher superoxide dismutase, catalase, and glutathione peroxidase activities, and lower malondialdehyde. FA-AAP-CDDP complex could induce more interleukin-2, interleukin-4, and interferon-γ in mice...
November 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29122657/diagnostic-significance-of-intratumoral-cd8-tumor-infiltrating-lymphocytes-in-medullary-carcinoma
#7
Fumie Igari, Eiichi Sato, Yoshiya Horimoto, Yuka Takahashi, Tatsuya Isomura, Atsushi Arakawa, Shigehisa Kitano, Mitsue Saito
Invasive ductal carcinomas of breast with marked stromal lymphocytic infiltration have come to be classified as lymphocyte predominant breast cancer (LPBC) because it obtains high pathological complete response rates with neoadjuvant chemotherapy. Medullary carcinoma (MC), which is independent from LPBC, is a rare histological subtype of invasive breast carcinoma accompanied by abundant lymphoplasmacytic infiltration as LPBC. Although MC shows marked cellular and structural atypia, it usually has a favorable outcome...
November 6, 2017: Human Pathology
https://www.readbyqxmd.com/read/29118984/clinical-trial-protocol-for-tardox-a-phase-i-study-to-investigate-the-feasibility-of-targeted-release-of-lyso-thermosensitive-liposomal-doxorubicin-thermodox%C3%A2-using-focused-ultrasound-in-patients-with-liver-tumours
#8
Paul C Lyon, Lucy F Griffiths, Jenni Lee, Daniel Chung, Robert Carlisle, Feng Wu, Mark R Middleton, Fergus V Gleeson, Constantin C Coussios
Background: TARDOX is a Phase I single center study of ultrasound triggered targeted drug delivery in adult oncology patients with incurable liver tumours. This proof of concept study is designed to demonstrate the safety and feasibility of targeted drug release and enhanced delivery of doxorubicin from thermally sensitive liposomes (ThermoDox®) triggered by mild hyperthermia induced by focused ultrasound in liver tumours. A key feature of the study is the direct quantification of the doxorubicin concentration before and after ultrasound exposure from tumour biopsies, using high performance liquid chromatography (HPLC)...
2017: Journal of Therapeutic Ultrasound
https://www.readbyqxmd.com/read/29118572/enhanced-antitumor-efficacy-of-poly-d-l-lactide-co-glycolide-based-methotrexate-loaded-implants-on-sarcoma-180-tumor-bearing-mice
#9
Li Gao, Lunyang Xia, Ruhui Zhang, Dandan Duan, Xiuxiu Liu, Jianjian Xu, Lan Luo
Purpose: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. Materials and methods: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide), and polyethylene glycol 4000 with the melt-molding technique...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29113399/dck-expression-a-potential-predictive-biomarker-in-the-adjuvant-gemcitabine-chemotherapy-for-biliary-tract-cancer-after-surgical-resection-results-from-a-phase-ii-study
#10
Sang Myung Woo, Kyong-Ah Yoon, Eun Kyung Hong, Weon Seo Park, Sung-Sik Han, Sang-Jae Park, Jungnam Joo, Eun Young Park, Ju Hee Lee, Yun-Hee Kim, Tae Hyun Kim, Woo Jin Lee
The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m(2) over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110683/array-comparative-genomic-hybridization-of-18-pancreatic-ductal-adenocarcinomas-and-their-autologous-metastases
#11
Valentin Rausch, Andreas Krieg, Jordi Camps, Bianca Behrens, Manfred Beier, Darawalee Wangsa, Kerstin Heselmeyer-Haddad, Stephan E Baldus, Wolfram T Knoefel, Thomas Ried, Nikolas H Stoecklein
BACKGROUND: Mortality rates of pancreatic cancer remain high, which is mainly due to advanced disease and metastasis. We hypothesized that genomic copy number alterations are enriched in metastatic cells compared to autologous primary tumors, which may inform on cancer-related pathways possibly serving as potential targets for specific therapies. We investigated 18 pancreatic ductal adenocarcinomas, including 39 lymph node and 5 distant metastases after surgical resection. Analysis was performed with array-based comparative genomic hybridization (aCGH)...
November 6, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29106517/tpd52l2-impacts-proliferation-invasiveness-and-apoptosis-of-glioblastoma-cells-via-modulation-of-wnt-%C3%AE-catenin-snail-signaling
#12
Qiang Zhou, Jun-Jie Li, Hai Wang, Hong Li, Bing-Xi Lei, Lei Chen, Wei Xiang, Ya-Wei Liu, Annie Huang, Song-Tao Qi, Yun-Tao Lu
Intratumoral heterogeneity greatly hinders efficiency of target therapy in glioblastoma. To decipher the underlying mechanisms of heterogeneity, patient-derived adult glioblastoma (GBM) cells were separately isolated from margins of T1 gadolinium enhancing tumor lesions (PNCs) and T1 gadolinium enhancing core lesions (ECs). Single clone culture was conducted in ECs and U87MG cell line to screen clones with distinct biological phenotypes. Single cell clones with diverse phenotypes were simultaneously separated from ECs and U87 cell line...
November 2, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29100290/cd133-targeted-oncolytic-adenovirus-demonstrates-anti-tumor-effect-in-colorectal-cancer
#13
Mizuho Sato-Dahlman, Yoshiaki Miura, Jing Li Huang, Praveensingh Hajeri, Kari Jacobsen, Julia Davydova, Masato Yamamoto
Oncolytic Adenoviruses (OAds) are one of the most promising anti-cancer agents that can induce cancer specific cell death. Recently, we generated infectivity-selective OAd, and the resultant OAd tumor-specific binding shows strong efficacy and mitigates toxicity. In this study, we applied this strategy based on adenovirus library screening system for generation of CD133-targeted OAd, and examined their oncolytic activity against colorectal cancer (CRC) in vitro and in vivo. CD133 (Prominin-1) is an important cell surface marker of cancer stem (like) cells (CSCs) in various cancers, including CRC...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29094389/antiferromagnetic-pyrite-as-the-tumor-microenvironment-mediated-nanoplatform-for-self-enhanced-tumor-imaging-and-therapy
#14
Zhongmin Tang, Huilin Zhang, Yanyan Liu, Dalong Ni, Hua Zhang, Jiawen Zhang, Zhenwei Yao, Mingyuan He, Jianlin Shi, Wenbo Bu
Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH-sensitive imaging, acidity-sensitive starving therapy, and hydrogen peroxide-activated chemotherapy, etc. Herein, a novel TME-mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self-enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i...
November 2, 2017: Advanced Materials
https://www.readbyqxmd.com/read/29034313/newly-characterized-murine-undifferentiated-sarcoma-models-sensitive-to-virotherapy-with-oncolytic-hsv-1-m002
#15
Eric K Ring, Rong Li, Blake P Moore, Li Nan, Virginia M Kelly, Xiaosi Han, Elizabeth A Beierle, James M Markert, Jianmei W Leavenworth, G Yancey Gillespie, Gregory K Friedman
Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45) and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1)...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29030300/gold-nanocage-decorated-ph-sensitive-micelle-for-highly-effective-photothermo-chemotherapy-and-photoacoustic-imaging
#16
Guoyong Zhou, Hong Xiao, Xiaoxia Li, Yi Huang, Wei Song, Liang Song, Meiwan Chen, Du Cheng, Xintao Shuai
A pH-sensitive copolymer PAsp(DIP)-b-PAsp(MEA) (PDPM) was synthesized and self-assembled to micelle loading chemotherapeutic drug doxorubicin (DOX) and introducing a gold nanocage structure for photothermo-chemotherapy and photoacoustic imaging. After further surface modification with polyethylene glycol (PEG), the DOX-loaded pH-sensitive gold nanocage (D-PGNC) around 100 nm possessed a uniform spherical structure with a pH-sensitive core of PAsp(DIP) incorporating DOX, an interlayer crosslinked via disulfide bonds and decorated with discontinuous gold shell, and a PEG corona...
December 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29029389/a-ketogenic-diet-supplemented-with-medium-chain-triglycerides-enhances-the-anti-tumor-and-anti-angiogenic-efficacy-of-chemotherapy-on-neuroblastoma-xenografts-in-a-cd1-nu-mouse-model
#17
Sepideh Aminzadeh-Gohari, René Günther Feichtinger, Silvia Vidali, Felix Locker, Tricia Rutherford, Maura O'Donnel, Andrea Stöger-Kleiber, Johannes Adalbert Mayr, Wolfgang Sperl, Barbara Kofler
Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction in aerobic energy metabolism. Recent preclinical data indicate that targeting this metabolic phenotype by a ketogenic diet (KD), especially in combination with calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide (CP) therapy of NB xenografts. Because calorie restriction would be contraindicated in most cancer patients, the aim of the present study was to optimize the KD such that the tumors are sensitized to CP without the need of calorie restriction...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29019266/liposome-loaded-thermo-sensitive-hydrogel-for-stabilization-of-sn-38-via-intratumoral-injection-optimization-characterization-and-antitumor-activity
#18
Ruixue Bai, Xueqing Deng, Qiong Wu, Xiaomian Cao, Tiantian Ye, Shujun Wang
Main challenges of the clinical use of 7-ethyl-10-hydroxycamptothecin (SN-38) are its facile transition between the active lactone form (SN-38A) and the inactive carboxylate form (SN-38I) under physiological conditions and its low solubility. The purpose of this study was to develop a thermo-sensitive hydrogel system with acidic SN-38 liposomes (SN-38-Lip-Gel) for local chemotherapy to solve these problems and to evaluate its antitumor activity and tissue distribution in tumor-bearing mice. A study of structural conversion between SN-38I and SN-38A under various pH conditions indicated that acidic solution could inhibit the conversion...
October 11, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29016938/preclinical-investigation-of-gene-mediated-cytotoxic-immunotherapy-and-checkpoint-blockade-in-glioblastoma
#19
Maria-Carmela Speranza, Carmela Passaro, Franz Ricklefs, Kazue Kasai, Sarah R Klein, Hiroshi Nakashima, Johanna K Kaufmann, Abdul-Kareem Ahmed, Michal O Nowicki, Prisca Obi, Agnieszka Bronisz, Estuardo Aguilar-Cordova, Laura K Aguilar, Brian W Guzik, Xandra Breakefield, Ralph Weissleder, Gordon J Freeman, David A Reardon, Patrick Wen, E Antonio Chiocca, Sean E Lawler
Background: Combined immunotherapy approaches are promising cancer treatments. We evaluated anti-PD-1 treatment combined with Gene-mediated cytotoxic immunotherapy (GMCI) performed by intratumoral injection of a prodrug metabolizing non-replicating adenovirus (AdV-tk), providing insitu chemotherapy and immune stimulation. Methods: The effects of GMCI on PD-L1 expression in glioblastoma were investigated in vitro and in vivo. The efficacy of the combination was investigated in two syngeneic mouse glioblastoma models (GL261 and CT-2A)...
July 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28962658/human-mesenchymal-stromal-cells-as-cellular-drug-delivery-vectors-for-glioblastoma-therapy-a-good-deal
#20
Anne Clavreul, Milad Pourbaghi-Masouleh, Emilie Roger, Nolwenn Lautram, Claudia N Montero-Menei, Philippe Menei
BACKGROUND: Glioblastoma (GB) is the most malignant brain tumor in adults. It is characterized by angiogenesis and a high proliferative and invasive capacity. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) is of limited efficacy. Innovative anticancer drugs targeting both tumor cells and angiogenesis are urgently required, together with effective systems for their delivery to the brain. We assessed the ability of human mesenchymal stromal cells (MSCs) to uptake the multikinase inhibitor, sorafenib (SFN), and to carry this drug to a brain tumor following intranasal administration...
September 29, 2017: Journal of Experimental & Clinical Cancer Research: CR
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