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https://www.readbyqxmd.com/read/29691399/a-serum-microrna-signature-predicts-trastuzumab-benefit-in-her2-positive-metastatic-breast-cancer-patients
#1
Huiping Li, Jiang Liu, Jianing Chen, Huiyun Wang, Linbin Yang, Fei Chen, Siting Fan, Jing Wang, Bin Shao, Dong Yin, Musheng Zeng, Mengfeng Li, Jun Li, Fengxi Su, Qiang Liu, Herui Yao, Shicheng Su, Erwei Song
Trastuzumab is a standard treatment for HER2-positive (HER2+ ) breast cancer, but some patients are refractory to the therapy. MicroRNAs (miRNAs) have been used to predict therapeutic effects for various cancers, but whether miRNAs can serve as biomarkers for HER2+ metastatic breast cancer (MBC) patients remains unclear. Using miRNA microarray, we identify 13 differentially expressed miRNAs in the serum of HER2+ MBC patients with distinct response to trastuzumab, and four miRNAs are selected to construct a signature to predict survival using LASSO model...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691296/tryptophan-metabolism-contributes-to-radiation-induced-immune-checkpoint-reactivation-in-glioblastoma
#2
Pravin Kesarwani, Antony Prabhu, Shiva Kant, Praveen Kumar, Stewart F Graham, Katie L Buelow, George D Wilson, Christopher Ryan Miller, Prakash Chinnaiyan
PURPOSE: Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. Tryptophan metabolism represents an immune checkpoint and targeting this pathway's rate limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).  Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691294/reciprocal-network-between-cancer-stem-like-cells-and-macrophages-facilitates-the-progression-and-androgen-deprivation-therapy-resistance-of-prostate-cancer
#3
Hai Huang, Chao Wang, Fei Liu, Hui-Zhen Li, Guang Peng, Xu Gao, Ke-Qin Dong, Hong-Ru Wang, De-Pei Kong, Min Qu, Li-He Dai, Kai-Jian Wang, Zhe Zhou, Jun Yang, Ze-Yu Yang, Yan-Qiong Cheng, Qin-Qin Tian, Dan Liu, Chuan-Liang Xu, Dan-Feng Xu, Xin-Gang Cui, Ying-Hao Sun
PURPOSE: Cancer stem-like cells (CSCs) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. Since CSCs depend on their specific niche, including tumor-associated macrophages (TAMs), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer. EXPERIMENTAL DESIGN: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA-seq, co-IP, ChIP and other assays...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691282/the-compound-millepachine-and-its-derivatives-inhibit-tubulin-polymerization-by-irreversibly-binding-to-the-colchicine-binding-site-in-%C3%AE-tubulin
#4
Yang Jianhong, Yan Wei, Yu Yamei, Wang Yuxi, Yang Tao, Xue Linlin, Yuan Xue, Long Caofeng, Liu Zuowei, Chen Xiaoxin, Hu Mengshi, Zheng Li, Qiu Qiang, Pei Heying, Li Dan, Wang Fang, Bai Peng, Wen Jiaolin, Ye Haoyu, Chen Lijuan
Inhibitors that bind to the paclitaxel- or vinblastine-binding sites of tubulin have been part of the pharmacopoeia of anticancer therapy for decades. However, tubulin inhibitors that bind to the colchicine-binding site are not used in clinical cancer therapy, because of their low therapeutic index. To address multidrug resistance to many conventional tubulin-binding agents, numerous efforts have attempted to clinically develop inhibitors that bind the colchicine-binding site. Previously, we have found that millepachine (MIL), a natural chalcone-type small molecule extracted from the plant Millettia pachycarpa, and its two derivatives (MDs) SKLB028 and SKLB050 have potential antitumor activities both in vitro and in vivo...
April 24, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29691253/the-inhibitory-nkr-p1b-clr-b-recognition-axis-facilitates-detection-of-oncogenic-transformation-and-cancer-immunosurveillance
#5
Miho Tanaka, Jason H Fine, Christina L Kirkham, Oscar A Aguilar, Antoaneta Belcheva, Alberto Martin, Troy Ketela, Jason Moffat, David Sj Allan, James R Carlyle
Natural killer (NK) cells express receptors specific for MHC class I (MHC-I) molecules involved in "missing-self" recognition of cancer and virus-infected cells. Here we elucidate the role of MHC-I-independent NKR-P1B:Clr-b interactions in the detection of oncogenic transformation by NK cells. Ras oncogene overexpression was found to promote a real-time loss of Clr-b on mouse fibroblasts and leukemia cells, mediated in part via the Raf/MEK/ERK and PI3K pathways. Ras-driven Clr-b downregulation occurred at the level of the Clrb (Clec2d) promoter, nascent Clr-b transcripts, and cell surface Clr-b protein, in turn promoting missing-self recognition via the NKR-P1B inhibitory receptor...
April 24, 2018: Cancer Research
https://www.readbyqxmd.com/read/29690749/landscape-of-actionable-genetic-alterations-profiled-from-1-071-tumor-samples-in-korean-cancer-patients
#6
Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park
Purpose: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. Materials and Methods: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory...
April 23, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29690747/tumor-associated-macrophages-derived-tgf-%C3%AE-%C3%A2-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells-through-smad2-3-4-snail-signaling-pathway
#7
Jianhui Cai, Limin Xia, Jinlei Li, Shichang Ni, Huayu Song, Xiangbin Wu
Purpose: We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process. Materials and Methods: In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level...
April 25, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29690504/selective-inhibition-of-histone-deacetylation-in-melanoma-increases-targeted-gene-delivery-by-a-bacteriophage-viral-vector
#8
Samuel Campbell, Keittisak Suwan, Sajee Waramit, Eric Ofori Aboagye, Amin Hajitou
The previously developed adeno-associated virus/phage (AAVP) vector, a hybrid between M13 bacteriophage (phage) viruses that infect bacteria only and human Adeno-Associated Virus (AAV), is a promising tool in targeted gene therapy against cancer. AAVP can be administered systemically and made tissue specific through the use of ligand-directed targeting. Cancer cells and tumor-associated blood vessels overexpress the αν integrin receptors, which are involved in tumor angiogenesis and tumor invasion...
April 21, 2018: Cancers
https://www.readbyqxmd.com/read/29689709/a-blood-biomarker-for-monitoring-response-to-anti-egfr-therapy
#9
Nicholas P Hughes, Lingyun Xu, Carsten H Nielsen, Edwin Chang, Sharon S Hori, Arutselvan Natarajan, Samantha Lee, Andreas Kjær, Kian Kani, Shan X Wang, Parag Mallick, Sanjiv Sam Gambhir
BACKGROUND AND OBJECTIVE: To monitor therapies targeted to epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC), we investigated Peroxiredoxin 6 (PRDX6) as a biomarker of response to anti-EGFR agents. METHODS: We studied cells that are sensitive (H3255, HCC827) or resistant (H1975, H460) to gefitinib. PRDX6 was examined with either gefitinib or vehicle treatment using enzyme-linked immunosorbent assays. We created xenograft models from one sensitive (HCC827) and one resistant cell line (H1975) and monitored serum PRDX6 levels during treatment...
April 13, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29689640/haploid-genetic-screens-identify-genetic-vulnerabilities-to-microtubule-targeting-agents
#10
Nora M Gerhards, Vincent A Blomen, Merve Mutlu, Joppe Nieuwenhuis, Denise Howald, Charlotte Guyader, Jos Jonkers, Thijn R Brummelkamp, Sven Rottenberg
The absence of biomarkers to accurately predict anti-cancer therapy response remains a major obstacle in clinical oncology. We applied a genome-wide loss-of-function screening approach in human haploid cells to characterize genetic vulnerabilities to classical microtubule-targeting agents. Using docetaxel and vinorelbine, two well-established chemotherapeutic agents, we sought to identify genetic alterations sensitizing human HAP1 cells to these drugs. Despite the fact that both drugs act on microtubules, a set of distinct genes were identified whose disruption affect drug sensitivity...
April 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29689622/prognostic-value-of-chromosomal-imbalances-gene-mutations-and-bap1-expression-in-uveal-melanoma
#11
Serena Patrone, Irena Maric, Mariangela Rutigliani, Francesco Lanza, Matteo Puntoni, Barbara Banelli, Silvia Rancati, Giovanna Angelini, Adriana Amaro, Paolo Ligorio, Carlotta Defferrari, Mauro Castagnetta, Roberto Bandelloni, Carlo Mosci, Andrea DeCensi, Massimo Romani, Urlich Pfeffer, Silvia Viaggi, Domenico A Coviello
Uveal melanoma (UM) exhibits recurring chromosomal abnormalities and gene driver mutations, which are related to tumor evolution/progression. Almost half of the patients with UM develop distant metastases, predominantly to the liver, and so far there are no effective adjuvant therapies. An accurate UM genetic profile could assess the individual patient's metastatic risk, and provide the basis to determine an individualized targeted therapeutic strategy for each UM patient. To investigate the presence of specific chromosomal and gene alterations, BAP1 protein expression, and their relationship with distant progression free survival (DPFS), we analyzed tumor samples from 63 UM patients (40 men and 23 women, with a median age of 64 years), who underwent eye enucleation by a single cancer ophthalmologist from December 2005 to June 2016...
April 24, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29689435/exploring-radiotherapy-targeting-strategy-and-dose-a-pooled-analysis-of-cooperative-group-trials-of-combined-modality-therapy-for-stage-iii-non-small-cell-lung-cancer
#12
Steven E Schild, Wen Fan, Thomas E Stinchcombe, Everett E Vokes, Suresh S Ramalingam, Jeffrey D Bradley, Karen Kelly, Herbert H Pang, Xiaofei Wang
INTRODUCTION: Concurrent chemoradiotherapy(CRT) is standard therapy for locally-advanced non-small-cell lung cancer(LA-NSCLC)patients. This study was performed to examine thoracic radiotherapy(TRT) parameters and their impact on patient survival. METHODS: We collected Individual patient data(IPD) from 3600LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy(elective nodal irradiation(ENI) compared to involved field TRT(IF-TRT)), total dose, and biologically effective dose(BED)...
April 21, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29689091/higher-expression-of-mir-133b-is-associated-with-better-efficacy-of-erlotinib-as-the-second-or-third-line-in-non-small-cell-lung-cancer-patients
#13
Alessandra Bisagni, Maria Pagano, Sally Maramotti, Francesca Zanelli, Martina Bonacini, Elena Tagliavini, Luca Braglia, Massimiliano Paci, Andrea Mozzarelli, Stefania Croci
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib, erlotinib and afatinib) are indicated as first-line therapy in patients with non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations in the EGFR gene. Erlotinib is also used in second and third-line therapy for patients whose tumors have wild type EGFR but to date there are no validated biomarkers useful to identify which patients may benefit from this treatment. The expression level of four miRNAs: miR-133b, -146a, -7 and -21 which target EGFR was investigated by real-time PCR in tumor specimens from NSCLC patients treated with erlotinib administered as the second or third line...
2018: PloS One
https://www.readbyqxmd.com/read/29689030/checkpoint-inhibitor-immune-therapy-systemic-indications-and-ophthalmic-side-effects
#14
Lauren A Dalvin, Carol L Shields, Marlana Orloff, Takami Sato, Jerry A Shields
PURPOSE: To review immune checkpoint inhibitor indications and ophthalmic side effects. METHODS: A literature review was performed using a PubMed search for publications between 1990 and 2017. RESULTS: Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab)...
April 23, 2018: Retina
https://www.readbyqxmd.com/read/29688882/disparity-in-public-funding-of-therapies-for-metastatic-castrate-resistant-prostate-cancer-across-canadian-provinces
#15
Dixon T S Woon, Thenappan Chandrasekar, Lorne Aaron, Naveen S Basappa, Kim N Chi, Henry J Conter, Brita Danielson, Sebastien J Hotte, Shawn Malone, Fred Saad, Bobby Shayegan, Laura Park-Wyllie, Robert J Hamilton
INTRODUCTION: Treatment using abiraterone acetate, enzalutamide, cabazitaxel, and radium-223 (Ra-223) improve overall survival (OS) and quality of life for patients with metastatic castrate-resistant prostate cancer (mCRPC). Despite their proven benefits, access to these therapies is not equal across Canada. METHODS: We describe provincial differences in access to approved mCRPC therapies. Data sources include the pan-Canadian Oncology Drug Review database, provincial cancer care resources, and correspondence with pharmaceutical companies...
April 12, 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29688614/paclitaxel-loaded-polylactide-polyethylene-glycol-fibers-with-long-term-antitumor-activity-as-a-potential-drug-carrier-for-local-chemotherapy
#16
Johana Plch, Kristyna Venclikova, Olga Janouskova, Jan Hrabeta, Tomas Eckschlager, Katerina Kopeckova, Zuzana Hampejsova, Zuzana Bosakova, Jakub Sirc, Radka Hobzova
Local application of anticancer agents prolongs the presence time and increases the concentration of drug in the target place and therefore may reduce serious side effects compared to drug systemic administration. The preparation of fibrous materials of polylactide (PLA) and polyethylene glycol (PEG) loaded with paclitaxel (PTX, 1 or 10 wt%) is presented. Scanning electron microscopy proves that PTX is homogeneously incorporated into the fibers. The addition of PEG of various molecular weights (6, 20, or 35 kDa) ensures the release of significantly higher amounts of hydrophobic PTX in a prolonged release time compared to the fibers containing PTX only...
April 24, 2018: Macromolecular Bioscience
https://www.readbyqxmd.com/read/29688306/emudra-ensemble-of-multiple-drug-repositioning-approaches-to-improve-prediction-accuracy
#17
Xianxiao Zhou, Minghui Wang, Igor Katsyv, Hanna Irie, Bin Zhang
Motivation: Availability of large-scale genomic, epigenetic and proteomic data in complex diseases makes it possible to objectively and comprehensively identify therapeutic targets that can lead to new therapies. The Connectivity Map has been widely used to explore novel indications of existing drugs. However, the prediction accuracy of the existing methods, such as Kolmogorov-Smirnov statistic remains low. Here we present a novel high-performance drug repositioning approach that improves over the state-of-the-art methods...
April 24, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29688101/the-efficiency-of-lipid-nanoparticles-with-an-original-cationic-lipid-as-a-sirna-delivery-system-for-macrophages-and-dendritic-cells
#18
Yasunori Uemura, Tomoyuki Naoi, Yasumasa Kanai, Katsuya Kobayashi
Small interfering of RNA (siRNA) technology has the potential to be a next-generation therapy. However, naked siRNA does not have high transfection efficiency and is rapidly degraded after systemic injection, so an appropriate drug delivery system (DDS) is required for clinical use. Several potential systems have been assessed, clinically focusing on hepatocyte or cancer tissue using siRNA. However, targeting immune cells using siRNA is still challenging, and a new DDS is required. In this study, we prepared lipid nanoparticles (LNP) composed of original cationic lipid, neutral lipid of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and PEG2000-DMPE (N- (Carbonyl-methoxypolyethyleneglycol 2000) -1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, sodium salt)...
April 24, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29687994/hairpin-hairpin-molecular-beacon-interactions-for-detection-of-survivin-mrna-in-malignant-sw480-cells
#19
Katarzyna Ratajczak, Bartlomiej E Krazinski, Anna E Kowalczyk, Beata Dworakowska, Slawomir Jakiela, Magdalena Stobiecka
Cancer biomarkers offer unique prospects for the development of cancer diagnostics and therapy. One of such biomarkers, protein survivin (Sur), exhibits strong anti-apoptotic and proliferation-enhancing properties and is heavily expressed in multiple cancers. Thus, it can be utilized to provide new modalities for modulating the cell-growth rate, essential for an effective cancer treatment. Herein, we have focused on the development of a new survivin-based cancer detection platform for colorectal cancer cells SW480 using a turn-on fluorescence oligonucleotide molecular beacon (MB) probe, encoded to recognize Sur mRNA...
April 24, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29687878/anthracycline-and-trastuzumab-induced-cardiotoxicity-in-breast-cancer
#20
M A Nicolazzi, A Carnicelli, M Fuorlo, A Scaldaferri, R Masetti, R Landolfi, A M R Favuzzi
OBJECTIVE: Breast cancer is the most common cancer among women. In the last twenty years early diagnosis, neoadjuvant and adjuvant systemic treatment that targeted to specific molecular targets have significantly reduced the mortality from breast cancer. However, the increase in survival has allowed to observe the cardiotoxic effects of anticancer therapy and increased mortality from cardiovascular causes, resulting in a large literature where experts try to identify the correct management of this critical problem...
April 2018: European Review for Medical and Pharmacological Sciences
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