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https://www.readbyqxmd.com/read/28822081/expression-profiling-of-the-map-kinase-phosphatase-family-reveals-a-role-for-dusp1-in-the-glioblastoma-stem-cell-niche
#1
Bradley N Mills, George P Albert, Marc W Halterman
The dual specificity phosphatases (DUSPs) constitute a family of stress-induced enzymes that provide feedback inhibition on mitogen-activated protein kinases (MAPKs) critical in key aspects of oncogenic signaling. While described in other tumor types, the landscape of DUSP mRNA expression in glioblastoma (GB) remains largely unexplored. Interrogation of the REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) revealed induction (DUSP4, DUSP6), repression (DUSP2, DUSP7-9), or mixed (DUSP1, DUSP5, DUSP10, DUSP15) DUSP transcription of select DUSPs in bulk tumor specimens...
August 18, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#2
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28822004/in-vitro-validation-of-the-hippo-pathway-as-a-pharmacological-target-for-canine-mammary-gland-tumors
#3
Samantha Guillemette, Charlène Rico, Philippe Godin, Derek Boerboom, Marilène Paquet
Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation...
August 18, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28821904/developmentally-regulated-signaling-pathways-in-glioma-invasion
#4
REVIEW
Shwetal Mehta, Costanza Lo Cascio
Malignant gliomas are the most common, infiltrative, and lethal primary brain tumors affecting the adult population. The grim prognosis for this disease is due to a combination of the presence of highly invasive tumor cells that escape surgical resection and the presence of a population of therapy-resistant cancer stem cells found within these tumors. Several studies suggest that glioma cells have cleverly hijacked the normal developmental program of neural progenitor cells, including their transcriptional programs, to enhance gliomagenesis...
August 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28821810/extracting-intercellular-signaling-network-of-cancer-tissues-using-ligand-receptor-expression-patterns-from-whole-tumor-and-single-cell-transcriptomes
#5
Joseph X Zhou, Roberto Taramelli, Edoardo Pedrini, Theo Knijnenburg, Sui Huang
Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of the cell community which forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on intercellular communication between cancer cells themselves and between cancer-stromal cells by secreted signaling molecules (ligands) and their cognate receptors. We analyzed public cancer transcriptome database for changes in cell-cell interactions as the characteristic of malignancy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#6
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821560/optoacoustic-detection-of-early-therapy-induced-tumor-cell-death-using-a-targeted-imaging-agent
#7
Bangwen Xie, Michal R Tomaszewski, Andre Neves, Susana Ros, De-En Hu, Sarah McGuire, Stefanie Roshy Mullins, David A Tice, Richard C A Sainson, Sarah E Bohndiek, Robert W Wilkinson, Kevin M Brindle
The development of new treatments and their deployment in the clinic may be assisted by imaging methods that allow an early assessment of treatment response in individual patients. The C2A domain of Synaptotagmin-I (C2Am), which binds to the phosphatidylserine (PS) exposed by apoptotic and necrotic cells, has been developed as an imaging probe for detecting cell death. Multispectral optoacoustic tomography (MSOT) is a real-time and clinically applicable imaging modality that was used here with a near infrared (NIR) fluorophore-labeled C2Am to image tumor cell death in mice treated with a TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) agonist and with 5-fluorouracil (5-FU)...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821557/selected-alkylating-agents-can-overcome-drug-tolerance-of-g0-like-tumor-cells-and-eradicate-brca1-deficient-mammary-tumors-in-mice
#8
Marina Pajic, Sohvi Blatter, Charlotte Guyader, Maaike Gonggrijp, Ariena Kersbergen, Aslı Küçükosmanoğlu, Wendy Sol, Rinske Drost, Jos Jonkers, Piet Borst, Sven Rottenberg
We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.<br /><br />Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Due to the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore no BRCA1-dependent acquired resistance occurs. To characterize the cell cycle stage from which Brca1(-/-);p53(-/-) mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell cycle indicator (FUCCI) construct into the tumor cells...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28820950/combined-aerobic-and-resistance-exercise-training-for-improving-reproductive-function-in-infertile-men-a-randomized-controlled-trial
#9
Behzad Hajizadeh Maleki, Bakhtyar Tartibian
This randomized controlled trial was conducted to examine the effects of 24 weeks of combined aerobic and resistance exercise training on seminal markers of inflammation and oxidative stress as well as markers of male reproductive function and reproductive performance in infertile patients. Of a total of 1296 infertile patients (aged 25-40 years) who were screened, 556 were randomly assigned to exercise (EX, n = 278) and non-exercise (NON-EX, n = 278) groups. Semen samples were taken before, 12 and 24 weeks as well as 7 and 30 days post intervention...
August 18, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28820578/integrated-microfluidic-platform-with-multiple-functions-to-probe-the-tumor-endothelial-cell-interaction
#10
Ling Lin, Xuexia Lin, Luyao Lin, Qiang Feng, Takehiko Kitamori, Jin-Ming Lin, Jiashu Sun
Interaction between tumor and endothelial cells could affect tumor growth and progression, and induce drug resistance during cancer therapy. Investigation on tumor-endothelial cell interaction involves cell co-culture, protein detection, and analysis of drug metabolites, which are complicated and time-consuming. In this work, we present an integrated microfluidic device with three individual components (the cell co-culture component, the protein detection component, and the pre-treatment component for drug metabolites) to probe the interaction between tumor and endothelial cells...
August 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28820390/small-molecule-inhibitors-of-dna-pk-for-tumor-sensitization-to-anticancer-therapy
#11
M Pospisilova, M Seifrtova, M Rezacova
The most sensitive cell structure - a DNA molecule, is the common target of cancer therapy. DNA damage response (controlled by enzymes from the phosphatidylinositol 3-kinase-related kinases family - PIKK) presents many encouraging targets for improving both conventional cytotoxic anticancer therapy and individualized monotherapy. DNA-dependent protein kinase (DNA-PK) is a member of the PIKK superfamily and plays an important role in the detection and repair of DNA double-strand breaks via the non-homologous end-joining pathway...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820388/blockade-of-the-lrp16-pkr-nf-%C3%AE%C2%BAb-signaling-axis-sensitizes-colorectal-carcinoma-cells-to-dna-damaging-cytotoxic-therapy
#12
Xiaolei Li, Zhiqiang Wu, Xiaojing An, Qian Mei, Miaomiao Bai, Leena Hanski, Xiang Li, Tero Ahola, Weidong Han
Acquired therapeutic resistance by tumors is a substantial impediment to reducing the morbidity and mortality that are attributable to human malignancies. The mechanisms responsible for the dramatic shift between chemosensitivity and chemoresistance in colorectal carcinoma have not been defined. Here, we report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKβ, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-κB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#13
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819802/significance-of-human-chorionic-gonadotropin-as-a-predictor-of-resistance-to-standard-chemo-radiotherapy-for-pure-germinoma
#14
Akihiro Inoue, Takanori Ohnishi, Shohei Kohno, Shiro Ohue, Shinji Iwata, Shirabe Matsumoto, Masahiro Nishikawa, Saya Ozaki, Yawara Nakamura, Yosuke Mizuno, Riko Kitazawa, Takeharu Kunieda
Intracranial pure germinomas in children generally respond well to standard chemo-radiotherapy. However, some patients are refractory to standard therapy and require additional treatment. To investigate the characteristics of this subgroup, we retrospectively analyzed the clinical features and treatment outcomes of a cohort of 21 patients with intracranial pure germinomas who were diagnosed between April 2002 and December 2016 at Ehime University Hospital in Japan. Pure germinoma diagnosis was verified by histological examination of the tumor after surgery, and all patients received standard chemo-radiotherapy...
August 18, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28819657/dendrimers-meet-zwitterions-development-of-a-unique-antifouling-nanoplatform-for-enhanced-blood-pool-lymph-node-and-tumor-ct-imaging
#15
Zhijuan Xiong, Yue Wang, Jingyi Zhu, Xin Li, Yao He, Jiao Qu, Mingwu Shen, Jindong Xia, Xiangyang Shi
We report the synthesis and characterization of antifouling zwitterion carboxybetaine acrylamide (CBAA)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for enhanced CT imaging applications. The CBAA-modified nanodevice displays a better protein resistance property, less macrophage cellular uptake and liver accumulation, and longer blood half-delay time than the PEGylated counterpart material, thereby enabling enhanced blood pool, lymph node, and tumor CT imaging.
August 18, 2017: Nanoscale
https://www.readbyqxmd.com/read/28819582/relationship-of-metabolic-alterations-and-pd-l1-expression-in-cisplatin-resistant-lung-cancer
#16
M Wangpaichitr, H Kandemir, Y Y Li, C Wu, Djm Nguyen, L G Feun, M T Kuo, N Savaraj
Despite numerous reports on immune checkpoint inhibitor for the treatment of non-small cell lung cancer (NSCLC), the response rate remains low but durable. Thus cisplatin still plays a major role in the treatment of NSCLC. While there are many mechanisms involved in cisplatin resistance, alteration in metabolic phenotypes with elevated levels of reactive oxygen species (ROS) are found in several cisplatin resistant tumors. These resistant cells become more reliant on mitochondria oxidative metabolism instead of glucose...
April 28, 2017: Cell & Developmental Biology
https://www.readbyqxmd.com/read/28819559/growth-inhibitory-efficacy-of-natural-products-in-a-model-for-triple-negative-molecular-subtype-of-clinical-breast-cancer
#17
Nitin Telang
Global gene expression profiling identifies predictive and prognostic biomarkers and rationalizes breast cancer subtype-targeted treatment. The Anthracyclin/Taxol and survival pathway specific small molecular inhibitors, constitute current treatment options. These options are associated with acquired tumor resistance and emergence of drug-resistant cancer stem cells. Dietary supplements and constitutive bioactive phytochemicals with relatively low systemic toxicity may provide testable alternatives for current therapy...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28819441/vsv-based-virotherapy-in-ovarian-cancer-the-past-the-present-and-%C3%A2-future
#18
REVIEW
Beata Urszula Orzechowska, Marcin Jędryka, Katarzyna Zwolińska, Rafał Matkowski
The standard approach to treating patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery remains taxane and platinum-based chemotherapy. Despite treatment with this strategy, the vast majority of patients relapse and develop drug-resistant metastatic disease that may be driven by cancer stem cells (CSCs) or cancer initiating cells (CICs). Oncolytic viruses circumvent typical drug-resistance mechanisms, therefore they may provide a safe and effective alternative treatment for chemotherapy-resistant CSCs/CICs...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819436/epithelial-mesenchymal-transition-potential-regulator-of-abc-transporters-in-tumor-progression
#19
REVIEW
Zong-Sheng Jiang, Yan-Zi Sun, Shao-Ming Wang, Jun-Shan Ruan
Epithelial-mesenchymal transition (EMT) can directly contribute to some malignant phenotypes of tumor cells including invasion, metastasis and resistance to chemotherapy. Although EMT is widely demonstrated to play a critical role in chemoresistance and metastasis, the potential signaling network between EMT and drug resistance is still unclear. The distribution of drugs in the internal and external environment of the tumor cells is tightly linked with ATP-binding cassette (ABC) transporters. Recent studies have shown that ABC transporters expression changed continuously during EMT...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819429/map2k1-mutation-in-colorectal-cancer-patients-therapeutic-challenge-using-patient-derived-tumor-cell-lines
#20
J E Kim, K K Kim, S Y Kim, J Lee, S H Park, J O Park, Y S Park, H Y Lim, W K Kang, S T Kim
BACKGROUND: The MAP2K1 K57T mutation is known to be a potential mechanism of primary and secondary resistance to EGFR inhibitors in metastatic colorectal cancer (CRC) and has also been reported to promote resistance to BRAF and MEK inhibitors. It is important to overcome therapeutic resistance to EGFR inhibitors to improve the treatment outcomes of metastatic CRC. METHODS: We established patient-derived tumor cells (PDCs) from metastatic lesions that newly appeared during treatment with a BRAF inhibitor (LGX-818) plus an EGFR inhibitor (cetuximab) in a patient with BRAF-mutant CRC...
2017: Journal of Cancer
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