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https://www.readbyqxmd.com/read/29036883/microrna-34a-a-versatile-regulator-of-myriads-of-targets-in-different-cancers
#1
REVIEW
Ammad Ahmad Farooqi, Sobia Tabassum, Aamir Ahmad
MicroRNA-34a (miR-34a) is a tumor suppressor that has attracted considerable attention in recent years. It modulates cancer cell invasion, metastasis, and drug resistance, and has also been evaluated as a diagnostic and/or prognostic biomarker. A number of targets of miR-34a have been identified, including some other non-coding RNAs, and it is believed that the modulation of these myriads of targets underlines the versatile role of miR-34a in cancer progression and pathogenesis. Seemingly appealing results from preclinical studies have advocated the testing of miR-34a in clinical trials...
October 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29036789/protein-kinase-c-%C3%AE-dependent-regulation-of-ubiquitin-proteasome-system-function-in-breast-cancer
#2
Si Sun, Qi Wu, Junlong Song, Shengrong Sun
Besides the crucial role of hyperinsulinemia in the development of breast cancer with Type 2 diabetes mellitus (T2DM), it has been shown that hyperglycemia could contribute to promote cancer progression. A remarkable association within hyperglycemia, PKCδ and Ubiquitin-proteasome system (UPS) has been reported, suggesting that PKCδ may mediate high glucose-induced UPS activation in breast cancer cells. Although the independent effects of PKCδ or UPS on breast cancer and T2DM are increasingly supported by experimental evidence, the complex interactional link between PKCδ and UPS is still unclear...
September 29, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29036688/a-cell-penetrating-antibody-inhibits-human-rad51-via-direct-binding
#3
Audrey Turchick, Denise C Hegan, Ryan B Jensen, Peter M Glazer
RAD51, a key factor in homology-directed repair (HDR), has long been considered an attractive target for cancer therapy, but few specific inhibitors have been found. A cell-penetrating, anti-DNA, lupus autoantibody, 3E10, was previously shown to inhibit HDR, sensitize tumors to radiation, and mediate synthetic lethal killing of BRCA2-deficient cancer cells, effects that were initially attributed to its affinity for DNA. However, as the molecular basis for its ability to inhibit DNA repair, we report that 3E10 directly binds to the N-terminus of RAD51, sequesters RAD51 in the cytoplasm, and impedes RAD51 binding to DNA...
September 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29035832/new-insights-into-vinca-alkaloids-resistance-mechanism-and-circumvention-in-lung-cancer
#4
REVIEW
Ying Zhang, Shao-Hui Yang, Xiu-Li Guo
Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29035643/role-of-bone-modifying-agents-in-metastatic-breast-cancer-an-american-society-of-clinical-oncology-cancer-care-ontario-focused-guideline-update
#5
Catherine Van Poznak, Mark R Somerfield, William E Barlow, J Sybil Biermann, Linda D Bosserman, Mark J Clemons, Sukhbinder K Dhesy-Thind, Melissa S Dillmon, Andrea Eisen, Elizabeth S Frank, Reshma Jagsi, Rachel Jimenez, Richard L Theriault, Theodore A Vandenberg, Gary C Yee, Beverly Moy
Purpose To update, in collaboration with Cancer Care Ontario (CCO), key recommendations of the American Society of Clinical Oncology (ASCO) guideline on the role of bone-modifying agents (BMAs) in metastatic breast cancer. This focused update addressed the new data on intervals between dosing and the role of BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted targeted systematic literature reviews to identify relevant studies. Results The Update Committee reviewed three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of BMAs, and two randomized trials of BMAs in control of pain secondary to bone metastases...
October 16, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29035540/targeted-clinical-nanoparticles-for-precision-cancer-therapy-based-on-disease-specific-molecular-inflection-points
#6
Charalambos Kaittanis, Alexander Bolaender, Barney Yoo, Nilesh Shah, Ouathek Ouerfelli, Jan Grimm
ional approaches based on clinical modular nanoplatforms are needed, in order to treat solid cancers according to their discrete molecular features. In the present study, we show that the clinical nanopharmaceutical Ferumoxytol, which consists of a glucose-based coat surrounding an iron oxide core, could identify molecular characteristics of prostate cancer, corresponding to unique phases of the disease continuum. By affixing a targeting probe for the prostate-specific membrane antigen on its surface, the nanopharmaceutical was able to assess the functional state of the androgen receptor pathway via MRI, guiding therapy and delivering it with the same clinical nanoparticle...
October 16, 2017: Nano Letters
https://www.readbyqxmd.com/read/29035465/enhanced-specificity-of-braf-v600e-genotyping-using-wild-type-blocker-coupled-with-internal-competitive-reference-in-a-single-tube
#7
Jia Peng, Kun Wei, Shu Yu, Xiang Yang, Xiang Zhao, Yu Liu, Xiao-Yan Zhu, Na Zhao, Qing Huang, Wei-Ling Fu
BACKGROUND: Mutations in the BRAF gene have been strongly associated with failure in cancer treatment using epidermal growth factor receptor (EGFR) antibodies. To better diagnose and assess the prognosis of cancer patients, mutation screening of the BRAFV600E gene should be performed prior to clinical anti-tumor drug therapy to avoid ineffective treatment. METHODS: In our previous study, we developed a real-time wild-type blocking PCR (WTB-PCR), which can amplify the mutant allele at high efficiency while simultaneously inhibiting the amplification of wild-type alleles...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29035371/lncrna-mir100hg-derived-mir-100-and-mir-125b-mediate-cetuximab-resistance-via-wnt-%C3%AE-catenin-signaling
#8
Yuanyuan Lu, Xiaodi Zhao, Qi Liu, Cunxi Li, Ramona Graves-Deal, Zheng Cao, Bhuminder Singh, Jeffrey L Franklin, Jing Wang, Huaying Hu, Tianying Wei, Mingli Yang, Timothy J Yeatman, Ethan Lee, Kenyi Saito-Diaz, Scott Hinger, James G Patton, Christine H Chung, Stephan Emmrich, Jan-Henning Klusmann, Daiming Fan, Robert J Coffey
De novo and acquired resistance, which are largely attributed to genetic alterations, are barriers to effective anti-epidermal-growth-factor-receptor (EGFR) therapy. To generate cetuximab-resistant cells, we exposed cetuximab-sensitive colorectal cancer cells to cetuximab in three-dimensional culture. Using whole-exome sequencing and transcriptional profiling, we found that the long non-coding RNA MIR100HG and two embedded microRNAs, miR-100 and miR-125b, were overexpressed in the absence of known genetic events linked to cetuximab resistance...
October 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29035367/targeting-glioma-stem-cells-through-combined-bmi1-and-ezh2-inhibition
#9
Xun Jin, Leo J Y Kim, Qiulian Wu, Lisa C Wallace, Briana C Prager, Tanwarat Sanvoranart, Ryan C Gimple, Xiuxing Wang, Stephen C Mack, Tyler E Miller, Ping Huang, Claudia L Valentim, Qi-Gang Zhou, Jill S Barnholtz-Sloan, Shideng Bao, Andrew E Sloan, Jeremy N Rich
Glioblastomas are lethal cancers defined by angiogenesis and pseudopalisading necrosis. Here, we demonstrate that these histological features are associated with distinct transcriptional programs, with vascular regions showing a proneural profile, and hypoxic regions showing a mesenchymal pattern. As these regions harbor glioma stem cells (GSCs), we investigated the epigenetic regulation of these two niches. Proneural, perivascular GSCs activated EZH2, whereas mesenchymal GSCs in hypoxic regions expressed BMI1 protein, which promoted cellular survival under stress due to downregulation of the E3 ligase RNF144A...
October 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29035366/cytoplasmic-p53-couples-oncogene-driven-glucose-metabolism-to-apoptosis-and-is-a-therapeutic-target-in-glioblastoma
#10
Wilson X Mai, Laura Gosa, Veerle W Daniels, Lisa Ta, Jonathan E Tsang, Brian Higgins, W Blake Gilmore, Nicholas A Bayley, Mitra Dehghan Harati, Jason T Lee, William H Yong, Harley I Kornblum, Steven J Bensinger, Paul S Mischel, P Nagesh Rao, Peter M Clark, Timothy F Cloughesy, Anthony Letai, David A Nathanson
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models...
October 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29034935/hedgehog-mesenchyme-gene-signature-identifies-bi-modal-prognosis-in-luminal-and-basal-breast-cancer-sub-types
#11
Wandaliz Torres-García, Maribella Domenech
Hedgehog signaling (Hh) has been shown to be hyper-activated in several cancers. However, active Hh signaling can promote or inhibit tumor growth; thus identification of markers beyond main canonical Hh target genes is needed to improve patient selection and clinical outcome in response to Hh inhibitors. Cancer-associated fibroblasts (CAFs) have been linked with tumor progression and beneficial response to Hh inhibitors. Thus, we hypothesized that genes associated with Hh-activated CAFs can be used for stratification of tumors that will benefit from Hh inhibitors...
October 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29034844/microrna-cancer-and-diet-facts-and-new-exciting-perspectives
#12
Maria Letizia Motti, Stefania D'Angelo, Rosaria Meccariello
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs able to regulate gene expression at multiple levels. They are detected in tissues, blood, and other body fluids with high stability and have a recognized role in the maintaining of tissue homeostasis. Aberrant expression profile of miRNAs has been observed in several diseases, primarily cancer. As a consequence, the analysis of miRNA signature has recognized diagnostic and prognostic role in human diseases, and the development of miRNA-based therapies is currently under investigation...
October 13, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29034837/dual-purpose-injectable-doxorubicin-conjugated-alginate-gel-containing-polycaprolactone-microparticles-for-anti-cancer-and-anti-inflammatory-therapy
#13
Vaishali Pawar, Vivek Borse, Riya Thakkar, Rohit Srivastava
In situ gel formulations have been widely reported as a carrier for sustained release delivery systems due to certain advantages such as targeted drug delivery, minimal invasiveness and potent therapeutic activity. Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for anti-cancer and anti-inflammatory activity is reported. Doxorubicin-conjugated alginate (dox-alg) gel was prepared using EDC-NHS chemistry and loaded with ibuprofen encapsulated polycaprolactone (PCL) microparticles (dox-alg composite)...
October 13, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29034543/pd-l1-expression-is-mainly-regulated-by-ifn-%C3%AE-associated-with-jak-stat-pathway-in-gastric-cancer
#14
Kousaku Mimura, Jun Liang Teh, Hirokazu Okayama, Kensuke Shiraishi, Ley-Fang Kua, Vivien Koh, Duane T Smoot, Hassan Ashktorab, Takahiro Oike, Yoshiyuki Suzuki, Zul Fazreen, Bernadette R Asuncion, Asim Shabbir, Wei-Peng Yong, Jimmy So, Richie Soong, Koji Kono
Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis still remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and immunotherapy utilizing anti-programmed death 1/-programmed death ligand-1 mAb is an attractive approach. However, as there is limited information on how programmed death ligand-1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand-1 regulation with a particular focus on interferon gamma in in-vitro setting and in clinical samples...
October 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/29034207/targeting-novel-but-less-common-driver-mutations-and-chromosomal-translocations-in-advanced-non-small-cell-lung-cancer
#15
REVIEW
Alia Daoud, Quincy S Chu
Discovery of the epidermal growth factor receptor gene mutation and the anaplastic lymphoma kinase chromosomal translocation in non-small cell lung cancer has prompted efforts around the world to identify many less common targetable oncogenic drivers. Such concerted efforts have been variably successful in both non-squamous and squamous cell carcinomas of the lung. Some of the targeted therapies for these oncogenic drivers have received regulatory approval for clinical use, while others have modest clinical benefit...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29034126/development-and-characterization-of-methylene-blue-oleate-salt-loaded-polymeric-nanoparticles-and-their-potential-application-as-a-treatment-for-glioblastoma
#16
J M Castañeda-Gill, A P Ranjan, J K Vishwanatha
Glioblastoma (GBM) is an aggressive, grade IV brain tumor that develops from astrocytes located within the cerebrum, resulting in poor prognosis and survival rates following an accepted treatment regimen of surgery, radiation, and temozolomide. Thus, development of new therapeutics is necessary. During the last two decades, methylene blue (MB) has received increased attention as a potential neurotherapeutic due to its duality in brain cancers and neurodegenerative diseases. While MB is capable of easily permeating the blood-brain barrier, its therapeutic concentrations in GBM are known to induce off-target cytotoxicity and thus, another mode of drug delivery must be considered...
August 2017: Journal of Nanomedicine & Nanotechnology
https://www.readbyqxmd.com/read/29033980/cellular-physiological-and-pathological-aspects-of-the-long-non-coding-rna-neat1
#17
Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou
BACKGROUND: The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs (lncRNAs) based on their transcript sizes larger than 200 nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and play regulatory roles in multiple aspects of biological processes. Dysregulation of lncRNA expression has also been linked to diseases, in particular cancer. Therefore, studies of lncRNAs have attracted significant interest in the field of medical research...
December 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/29033691/identification-of-genes-and-pathways-potentially-related-to-phf20-by-gene-expression-profile-analysis-of-glioblastoma-u87-cell-line
#18
Tianlong Liu, Tiejun Zhang, Feng Zhou, Jitao Wang, Xiaohu Zhai, Nan Mu, Jongsun Park, Minna Liu, Wenxing Liu, Peijin Shang, Yi Ding, Aidong Wen, Yuwen Li
BACKGROUND: Glioblastoma is the most common and aggressive brain tumor associated with a poor prognosis. Plant homeodomain finger protein 20 (PHF20) is highly expressed in primary human gliomas and its expression is associated with tumor grade. However, the molecular mechanism by which PHF20 regulates glioblastoma remains poorly understood. METHODS: Genome wide gene expression analysis was performed to identify differentially expressed genes (DEGs) in U87 cells with PHF20 gene knockdown...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29033586/targeting-the-androgen-receptor-in-triple-negative-breast-cancer-current-perspectives
#19
REVIEW
Alain Mina, Rachel Yoder, Priyanka Sharma
Triple-negative breast cancer (TNBC) is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR) signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29033568/in-vivo-evaluation-of-cetuximab-conjugated-poly-%C3%AE-glutamic-acid-docetaxel-nanomedicines-in-egfr-overexpressing-gastric-cancer-xenografts
#20
Maya Sreeranganathan, Saji Uthaman, Bruno Sarmento, Chethampadi Gopi Mohan, In-Kyu Park, Rangasamy Jayakumar
Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry...
2017: International Journal of Nanomedicine
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