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https://www.readbyqxmd.com/read/29346757/p53-suppresses-metabolic-stress-induced-ferroptosis-in-cancer-cells
#1
Amy Tarangelo, Leslie Magtanong, Kathryn T Bieging-Rolett, Yang Li, Jiangbin Ye, Laura D Attardi, Scott J Dixon
How cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, and high-resolution, time-lapse imaging, we find that stabilization of wild-type p53 delays the onset of ferroptosis in response to cystine deprivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#2
Janina-Miriam Noy, Hongxu Lu, Philip Hogg, Jia-Lin Yang, Martina H Stenzel
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anti-cancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition fragmentation chin transfer) polymerization with poly(polyethylene glycol methyl ether methacrylate) (PEGMA) as comonomer and poly(methylmethacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt...
January 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29346433/vault-rnas-partially-induces-drug-resistance-of-human-tumor-cells-mcf-7-by-binding-to-the-rna-dna-binding-protein-psf-and-inducing-oncogene-gage6
#3
Jianjun Chen, Hui OuYang, Xuemei An, Shixi Liu
BACKGROUND: Vault is the largest nonicosahedral cytosolic nucleoprotein particle, which is widely involved in induction of chemoresistance and lead to failure in long-term chemotherapy. Vault contains three different major vault proteins (MVPs) and four vault RNAs paralogues (vtRNAs, vtRNA1-1, vtRNA1-2, vtRNA1-3 and vtRNA2-1). Disruption of the MVPs do not induce hypersensitivity while expression of vtRNAs contributes to cells' drug resistance, indicates that vtRNAs, but not MVPs play an important role in causing drug resistance...
2018: PloS One
https://www.readbyqxmd.com/read/29346131/toxicological-profile-and-safety-pharmacology-of-a-single-dose-of-fibroblast-activation-protein-%C3%AE-based-doxorubicin-prodrug-in-vitro-and-in-vivo-evaluation
#4
Sichao Huang, Yuchen Zhang, Jinsong Zhong, Ying Pan, Shaohui Cai, Jun Xu
Fibroblast activation protein-α (FAPα) is a promising tumor-associated target expressed by reactive stromal fibroblasts in tumor tissue. FAPα has a postprolyl peptidase activity and can specifically cleave N-terminal benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC. Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly limited by toxic adverse effects owing to poor tumor selectivity. Based on these facts, we previously designed a FAPα-targeting prodrug of doxorubicin (FTPD) which can be selectively hydrolyzed by FAPα...
January 17, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29346117/the-deubiquitinase-usp9x-regulates-fbw7-stability-and-suppresses-colorectal-cancer
#5
Omar M Khan, Joana Carvalho, Bradley Spencer-Dene, Richard Mitter, David Frith, Ambrosius P Snijders, Stephen A Wood, Axel Behrens
The tumor suppressor FBW7 targets oncoproteins such as c-MYC for ubiquitylation and is mutated in several human cancers. We noted that in a significant percentage of colon cancers, FBW7 protein is undetectable despite the presence of FBW7 mRNA. To understand the molecular mechanism of FBW7 regulation in these cancers, we employed proteomics and identified the deubiquitinase USP9X as an FBW7 interactor. USP9X antagonised FBW7 ubiquitylation, and Usp9x deletion caused Fbw7 destabilization. Mice lacking Usp9x in the gut showed reduced secretory cell differentiation and increased progenitor proliferation, phenocopying Fbw7 loss...
January 18, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29346116/4d-computed-tomography-scans-for-conformal-thoracic-treatment-planning-is-a-single-scan-sufficient-to-capture-thoracic-tumor-motion
#6
Yolanda D Tseng, Landon Wootton, Matthew Nyflot, Smith Apisarnthanarax, Ramesh Rengan, Charles Bloch, George Sandison, Sara St James
Four dimensional computed tomography (4DCT) scans are routinely used in radiation therapy to determine the internal treatment volume for targets that are moving (e.g. lung tumors). The use of these studies has allowed clinicians to create target volumes based upon the motion of the tumor during the imaging study. The purpose of this work is to determine if a target volume based on a single 4DCT scan at simulation is sufficient to capture thoracic motion. Phantom studies were performed to determine expected differences between volumes contoured on 4DCT scans and those on the evaluation CT scans (slow scans)...
January 18, 2018: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29345977/targeted-and-nontargeted-%C3%AE-particle-therapies
#7
Michael R McDevitt, George Sgouros, Stavroula Sofou
α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy...
January 18, 2018: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/29345574/role-of-cd73-in-disease-promising-prognostic-indicator-and-therapeutic-target
#8
Jiayin Yang, Xiaohong Liao, Jerry Yu, Ping Zhou
CD73, also known as ecto-5'-nucleotidase (eN, NT5E, EC3.13.5), is the rate-limiting enzyme for adenosine generation and is expressed on multiple cells. Its expression is significantly influenced by hypoxia and inflammatory factors. During inflammation, CD73 protects endothelial barrier function and inhibits leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory phenotype). In addition, CD73 is expressed on Treg cells and mediates immune suppression through adenosine. CD73 serves as an essential regulator for the immunity and inflammation...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345569/a-complex-scenario-and-underestimated-challenge-the-tumor-microenvironment-er-stress-and-cancer-treatment
#9
Oleg I Chen, Yaroslav P Bobak, Oleh V Stasyk, Leoni A Kunz-Schughart
The paradoxical role of ER stress in malignant diseases is only just being unraveled and remains incompletely understood. A particular challenge is the complex interplay between spaciotemporal and locoregional microenvironmental constraints in solid tumors and stress responses upon treatment; thus, the potential for new combinatorial therapeutic options to foster the coincidence of ER stress-related deadly events is likely to be underestimated. Without claiming this review to be complete, we present a comprehensive overview of the signaling mechanisms associated with the unfolded protein response (UPR) and the molecular link to cell survival and death mechanisms...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345523/hexim1-an-rna-controlled-protein-hub
#10
Annemieke A Michels, Olivier Bensaude
Hexim1 acts as a tumor suppressor and is involved in the regulation of innate immunity. It was initially described as a non-coding RNA-dependent regulator of transcription. Here, we detail how 7SK RNA binds to Hexim1 and turns it into an inhibitor of the positive transcription elongation factor (P-TEFb). In addition to its action on P-TEFb, it plays a role in a variety of different mechanisms: it controls the stability of transcription factor components and assists binding of transcription factors to their targets...
January 18, 2018: Transcription
https://www.readbyqxmd.com/read/29345412/wnt5a-promotes-migration-and-invasion-of-human-osteosarcoma-cells-via-src-erk-mmp-14-pathway
#11
Xingwen Wang, Xin Zhao, Zhigang Yi, Bing Ma, Hong Wang, Yanchuan Pu, Jing Wang, Shuanke Wang
WNT5A, a representative ligand of activating several non-canonical Wnt signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non-receptor tyrosine kinase SRC is required for WNT5A-induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings...
January 18, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29345394/viruses-as-key-modulators-of-the-tgf-%C3%AE-pathway-a-double-edged-sword-involved-in-cancer
#12
REVIEW
Habibollah Mirzaei, Ebrahim Faghihloo
Transforming growth factor-β (TGF-β) signaling pathway is a key network in cell signaling that controls vital processes such as proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and migration, thus acting as a double-edged sword in normal development and diseases, in particular organ fibrosis, vascular disorders, and cancer. Early in tumorigenesis, the pathway exerts anti-tumor effects through suppressing cell cycle and inducing apoptosis, while during late stages, it functions as a tumor promoter by enhancing tumor invasiveness and metastasis...
January 18, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29345391/nptx1-inhibits-colon-cancer-cell-proliferation-through-down-regulating-cyclin-a2-and-cdk2-expression
#13
Xiaofeng Peng, Kangming Pan, Wenli Zhao, Jianzhu Zhang, Shicheng Yuan, Xiang Wen, Wenquan Zhou, Zhijin Yu
Colon cancer is the third most common malignancy and one of the leading causes of cancer-associated mortality worldwide. Neuronal pentraxin 1 (NPTX1) is associated with tumor progression in some types of tumors. However, its expression and role in colon cancer has not been yet reported. Here we observed that NPTX1 was down-regulated in colon cancer. Additionally, we explored the functional significance of NPTX1 in colon cancer. We found that over-expression of NPTX1 inhibited colon cancer cell growth by performing MTT, colony formation, Edu corporation assays, and cell cycle analysis...
January 18, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29345363/effects-of-il-10-and-th-2-cytokines-on-human-m%C3%AF-phenotype-and-response-to-csf1r-inhibitor
#14
Leon P Pradel, Andreas Franke, Carola H Ries
Tumor-associated Mφs display a plastic phenotype that is regulated by the local tumor milieu. Gene expression analysis and functional characterization of Mφs exposed in vitro to individual cytokines aids to delineate the cross-talk between defined cytokines shaping the complex Mφ phenotype. Human monocyte-derived Mφs can be differentiated in vitro with the T helper cell type 2 response cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking antibody emactuzumab...
January 4, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345362/innate-lymphoid-cells-in-antitumor-immunity
#15
REVIEW
Bérengère Salomé, Camilla Jandus
Innate lymphoid cells (ILCs) are the most recently characterized subset of innate lymphocytes. Based on their specific transcriptional regulation, cytokine secretion pattern and effector functions ILCs mirror the different CD4 T helper cell subsets, with the unique attributes of acting locally in early phases of immune responses, in an antigen-independent manner. In this review, we discuss how ILCs have been implicated in tumorigenesis. Their presence might favor or inhibit tumor growth, depending on the cytokines released and the specific tumor microenvironment...
December 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345297/mir-135b-5p-promotes-gastric-cancer-progression-by-targeting-cmtm3
#16
Mingdong Lu, Yingpeng Huang, Weijian Sun, Pihong Li, Liyi Li, Leping Li
CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) is considered to be a tumor suppressor gene in multiple types of malignancies. Previous studies have indicated that CMTM3 suppresses metastasis and epithelial-mesenchymal transition (EMT) in gastric cancer. However, its role in gastric cancer cell proliferation has rarely been discussed. Moreover, the regulatory mechanisms of CMTM3 in gastric cancer remain unclear. In this study, RT‑qPCR and IHC were used to assess the expression of CMTM3 and miR‑135b‑5p in gastric cancer tissues and cell lines...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345295/upregulation-of-the-bdnf-trkb-pathway-promotes-epithelial-mesenchymal-transition-as-well-as-the-migration-and-invasion-of-cervical-cancer
#17
Yuan Yuan, Hai-Qiong Ye, Qian-Chuan Ren
Brain-derived neurotrophic factor (BDNF) has previously been demonstrated to be associated with several types of cancer. In addition, its receptor, tropomyosin related kinase B (TrkB) is involved in tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) is associated with metastasis in cancers. Thus, The aim of the present study was to examine whether BDNF/TrKB expression is linked to a poor survival and the acquisition of the EMT phenotype in cervical cancer. We found that a high positive expression of BDNF/TrKB was associated with poor survival in cervical cancer...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345294/hypoxia-stimulates-the-cytoplasmic-localization-of-oncogenic-long-noncoding-rna-linc00152-in-colorectal-cancer
#18
Yujiro Nishizawa, Masamitsu Konno, Ayumu Asai, Jun Koseki, Koichi Kawamoto, Norikatsu Miyoshi, Hidekazu Takahashi, Naohiro Nishida, Naotsugu Haraguchi, Daisuke Sakai, Toshihiro Kudo, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Recent studies have indicated that long noncoding RNAs (lncRNAs) play a pivotal role in almost all physiological cellular processes, including every stage of cancer development. Given that hypoxia in the tumor microenvironment is involved in the malignant behavior of tumors, such as invasion and metastasis, we investigated the cytoplasmic and nuclear localization of lncRNAs in colorectal cancer cells. A cell culture under hypoxic conditions revealed several lncRNAs, such as LINC00152, whose levels were increased in the cytoplasm of colorectal cancer cells...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345288/downregulation-of-mir%C3%A2-205-is-associated-with-glioblastoma-cell-migration-invasion-and-the-epithelial-mesenchymal-transition-by-targeting-zeb1-via-the-akt-mtor-signaling-pathway
#19
Wei Chen, Kuan-Kei Kong, Xin-Ke Xu, Cheng Chen, Hui Li, Fang-Yu Wang, Xiao-Fang Peng, Zhan Zhang, Ping Li, Jun-Liang Li, Fang-Cheng Li
Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of recent advancements in surgical techniques, chemotherapy, and radiation therapy, patients with GBM often face a dire prognosis. MicroRNAs have been shown to modulate the aggressiveness of various cancers, and have emerged as possible therapeutic agents for the management of GBM. miR‑205 is dysregulated in glioma and act as a prognostic indicator. However, the role of miR‑205 in the development of GBM has not been elucidated...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345201/clinical-validation-of-nuclear-factor-kappa-b-expression-in-invasive-breast-cancer
#20
Anil Kumar Agrawal, Ewa Pielka, Artur Lipinski, Michal Jelen, Wojciech Kielan, Siddarth Agrawal
Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status...
January 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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