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https://www.readbyqxmd.com/read/29334665/i-7ab-inhibited-the-growth-of-tnbc-cells-via-targeting-hdac3-and-promoting-the-acetylation-of-p53
#1
Mei Yang, Xuefei Dang, Yue Tan, Meixing Wang, Xiaojing Li, Gang Li
Triple negative breast cancer (TNBC) is a heterogenous disease with high aggressive and poor outcome. The lack of biomarkers and targeted therapies makes it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis) are emerging as novel anti-tumor agents in many types of human cancers. In this study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC cells and induced the cell apoptosis. Mechanistically, I-7ab specifically decreased the expression of HDAC3 and promoted the acetylation of p53 at both Lys373 and Lys382 amino acids...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334604/breast-conservation-therapy-versus-mastectomy-in-patients-with-t1-2n1-triple-negative-breast-cancer-pooled-analysis-of-krog-14-18-and-14-23
#2
Kyubo Kim, Hae Jin Park, Kyung Hwan Shin, Jin Ho Kim, Doo Ho Choi, Won Park, Seung Do Ahn, Su Ssan Kim, Dae Yong Kim, Tae Hyun Kim, Jin Hee Kim, Jiyoung Kim
Purpose: The aim of this study is to compare the treatment outcomes of breast conserving surgery (BCS) plus radiotherapy (RT) vs. mastectomy for patients with pT1-2N1 triple negative breast cancer (TNBC). Methods: Using two multicenter retrospective studies on breast cancer, a pooled analysis was performed among 320 patients with pT1-2N1 TNBC. All patients who underwent BCS (n=212) received whole breast RT with or without regional nodal RT, while none who underwent mastectomy (n=108) received it...
January 8, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29334522/themes-in-literature-related-to-incidence-risk-and-prevention-of-cancer-in-solid-organ-transplantation-recipients-on-immunosuppressive-therapy
#3
Stefanie L Rashti
BACKGROUND: Solid-organ transplants provide a second chance to thousands of critically ill patients with end-organ failure each year. Immunosuppressants are administered to patients to prevent graft rejection of a transplanted organ, such as a heart, kidney, or liver, while placing the recipient at greater risk for infection and cancer. OBJECTIVE: The literature provides evidence of various cancers that have been found to develop in patients' posttransplantation...
January 12, 2018: Cancer Nursing
https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#4
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29334372/pharmacological-blockade-of-asct2-dependent-glutamine-transport-leads-to-antitumor-efficacy-in-preclinical-models
#5
Michael L Schulte, Allie Fu, Ping Zhao, Jun Li, Ling Geng, Shannon T Smith, Jumpei Kondo, Robert J Coffey, Marc O Johnson, Jeffrey C Rathmell, Joe T Sharick, Melissa C Skala, Jarrod A Smith, Jordan Berlin, M Kay Washington, Michael L Nickels, H Charles Manning
The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells, including biosynthesis, cell signaling, and oxidative protection. Herein we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux that selectively and potently targets the amino acid transporter ASCT2...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#6
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334363/macrophage-membrane-coated-iron-oxide-nanoparticles-for-enhanced-photothermal-tumor-therapy
#7
Qian-Fang Meng, Lang Rao, Minghui Zan, Ming Chen, Guang-Tao Yu, Xiaoyun Wei, Zhuhao Wu, Yue Sun, Shi Shang Guo, Xing-Zhong Zhao, Fu-Bing Wang, Wei Liu
Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should own long blood circulation and active cancer targeting. Additionally, they should be innoxious and invisible to the immune system. Here, we developed a biomimetic nanoplatform with the above properties for cancer therapy. Macrophage membranes were reconstructed into vesicles and then coated onto magnetic iron oxide nanoparticles (Fe3O4 NPs). Inherited from the Fe3O4 core and the macrophage membrane shell, the resulting Fe3O4@MM NPs exhibited good biocompatibility, immune evasion, cancer targeting, and light-to-heat conversion capabilities...
January 15, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29334356/p53-suppresses-mutagenic-rad52-and-pol%C3%AE-pathways-by-orchestrating-dna-replication-restart-homeostasis
#8
Sunetra Roy, Karl-Heinz Tomaszowski, Jessica W Luzwick, Soyoung Park, Jun Li, Maureen Murphy, Katharina Schlacher
Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks driving genomic instability genetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease...
January 15, 2018: ELife
https://www.readbyqxmd.com/read/29334302/mirnas-as-potential-regulators-of-mtor-pathway-in-renal-cell-carcinoma
#9
Inês Nogueira, Francisca Dias, Ana Luísa Teixeira, Rui Medeiros
Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the adult kidney with the majority of RCC cases being detected accidentally. The most aggressive subtype is clear cell RCC (ccRCC). miRNAs, a family of small noncoding RNAs regulating gene expression have been identified as key biological modulators. The von Hippel-Lindau pathway is one of the signaling pathways involved in the pathophysiology of ccRCC. Another oncogenic mechanism involves the activation of PI3K/AKT/mTOR signaling and serves as a central regulator of cell metabolism, proliferation and survival...
January 15, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29334216/lysosome-independent-intracellular-drug-gene-co-delivery-by-lipoprotein-derived-nanovector-for-synergistic-apoptosis-inducing-cancer-targeted-therapy
#10
Wei Wang, Kerong Chen, Yujie Su, Jielei Zhang, Min Li, Jianping Zhou
In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, were constructed for co-delivery of paclitaxel (PTX) and wild type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses...
January 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29334189/a-multifunctional-micellar-nanoplatform-with-ph-triggered-cell-penetration-and-nuclear-targeting-for-effective-cancer-therapy-and-inhibition-to-lung-metastasis
#11
Yuting Jing, Xiang Xiong, Yang Ming, Jingya Zhao, Xing Guo, Guang Yang, Shaobing Zhou
The enhancement of cellular internalization and subsequent achievement of a nuclear targeting of nanocarriers play an important role in maximizing the therapeutic potency and minimizing the side effects of encapsulated drugs. Herein, a multifunctional micellar nanoplatform simultaneously with high cell penetration and nuclear targeting through pH-triggered surface charge reversal is presented. The miscellar system is constructed from poly(ethylene glycol)-poly(ε-caprolactone) with 2,3-dimethylmaleic anhydride-Tat decoration (PECL/DA-Tat)...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29334184/ph-responsive-peg-doxorubicin-encapsulated-aza-bodipy-nanotheranostic-agent-for-imaging-guided-synergistic-cancer-therapy
#12
Dapeng Chen, Qianyun Tang, Jianhua Zou, Xiaoyan Yang, Wei Huang, Qi Zhang, Jinjun Shao, Xiaochen Dong
Synergistic cancer therapy is of great interest for multiple advantages, such as excellent targeting accuracy, low side effects, and enhanced therapeutic efficiency. Herein, a near-infrared photosensitizer aza-BODIPY (AB) with high singlet oxygen quantum yield (ΦΔ = 82%) is designed and synthesized. With Schiff's base obtained from condensation reaction between doxorubicin (DOX) and polyethylene glycol-benzaldehyde (PEG-CHO) as the polymer matrix, aza-BODIPY is encapsulated to afford hydrophilic nanoparticles (DAB NPs)...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29334169/impact-of-baseline-clinical-and-laboratory-features-on-the-risk-of-thrombosis-in-children-with-acute-lymphoblastic-leukemia-a-prospective-evaluation
#13
Uma H Athale, T Mizrahi, C Laverdière, T Nayiager, Y-L Delva, G Foster, L Thabane, M David, J-M Leclerc, A K C Chan
BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study...
January 15, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29334123/cancer-associated-fibroblasts-tailored-tumor-microenvironment-of-therapy-resistance-in-gastrointestinal-cancers
#14
REVIEW
Yeqi Sun, Ruifen Wang, Meng Qiao, Yanchun Xu, Wenbin Guan, Lifeng Wang
Gastrointestinal cancers (GI) are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis and also therapy resistance...
January 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29334095/gd3-doped-mose2-nanosheets-used-as-a-theranostic-agent-for-bimodal-imaging-and-highly-efficient-photothermal-cancer-therapy
#15
Jiali Pan, Xufeng Zhu, Xu Chen, Yingyu Zhao, Jie Liu
Recently, two dimensional transition metal dichalcogenides (TMDCs) being used as nanomedicine have aroused great interest because of their unique photothermal properties. A simple liquid-phase method was used to prepare gadolinium (Gd3+)-doped molybdenum selenide (MoSe2) nanosheets, and then using poly(ethylene glycol) (PEG) modification on the surface, MoSe2(Gd3+)-PEG nanosheets were obtained which had high stability in physiological solutions and showed no obvious toxicity in vivo. It revealed that Gd3+ used as a paramagnetic material for MoSe2(Gd3+)-PEG provided a strong contrast effect in magnetic resonance imaging, furthermore, the MoSe2 showed strong absorption in the near infrared region, and therefore, MoSe2(Gd3+)-PEG could be used as contrast agent for photoacoustic imaging (PAI)...
January 15, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29334090/supramolecular-photosensitizers-rejuvenate-photodynamic-therapy
#16
Xingshu Li, Songyi Lee, Juyoung Yoon
Owing to its spatiotemporal selectivity and noninvasive nature, photodynamic therapy (PDT) has become a clinically promising approach for the treatment of a wide range of cancers and other diseases. However, the full potential of PDT has not been achieved thus far as a consequence of the lack of optimal photosensitizers (PSs) and/or smart transport/activation strategies. These problems, which unfortunately lie at the core of the PDT paradigm, include the oxygen reliance limits, the effect of PDT on hypoxic tumors, limitations of light penetration, and undesired skin photosensitization induced by "always on" PSs...
January 15, 2018: Chemical Society Reviews
https://www.readbyqxmd.com/read/29333945/remarkable-response-with-pembrolizumab-plus-albumin-bound-paclitaxel-in-2-cases-of-her2-positive-metastatic-breast-cancer-who-have-failed-to-multi-anti-her2-targeted-therapy
#17
Bian Li, Wang Tao, Zhang Shao-Hua, Q U Ze-Rui, Jin Fu-Quan, L I Fan, Jiang Ze-Fei
In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab,lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients.Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab(2mg/Kg, day1) plus albumin-bound paclitaxel(125mg/m2, day1,8) every 3 weeks.CT evaluation and HER2 ECD test were performed every 2 cycles...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333926/engrailed-1-overexpression-as-a-potential-prognostic-marker-in-quintuple-negative-breast-cancer
#18
Yu Jin Kim, Minjung Sung, Ensel Oh, Michael Van Vrancken, Ji-Young Song, Kyungsoo Jung, Yoon-La Choi
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by poor patient prognosis and for which no targeted therapies are currently available. TNBC can be further categorized as either basal-like (BLBC) or quintuple-negative breast cancer (QNBC). In the present study, we aimed to identify novel molecular therapeutic targets for TNBC by analyzing the mRNA expression of TNBC-related genes in publicly available microarray data sets. We found that Engrailed 1 (EN1) was significantly overexpressed in TNBC...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333925/androgen-receptor-independent-prostate-cancer-an-emerging-clinical-entity
#19
Ilyas Sahin, Anthony E Mega, Benedito A Carneiro
Androgen deprivation therapy remains the backbone of prostate cancer treatment given its pivotal role in the pathogenesis of prostate cancer. The growing knowledge of androgen receptor-independent (i.e. AR-null) prostate cancer cells, however, might advance the treatment paradigm of prostate cancer particularly in castration resistance stage by targeting these pathways. Here, we examined the results of two recent studies, published in Cancer Cell by Bluemn and Shukla et al., and possible clinical impact of these studies in the near future in castration resistance prostate cancer...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333924/dynamic-mr-imaging-for-functional-vascularization-depends-on-tissue-factor-signaling-in-glioblastoma
#20
Xiao Chen, Tian Xie, Jingqin Fang, Wei Xue, Houyi Kang, Haipeng Tong, Yu Guo, Bo Zhang, Sumei Wang, Yizeng Yang, Weiguo Zhang
Glomeruloid vascular proliferation (GVP) is a diagnostic hallmark and links to aggressive behavior, therapy resistance and poor prognosis in glioblastoma (GBM). It lacks clinical approaches to predict and monitor its formation and dynamic change. Yet the mechanism of GVPs also remains largely unknown. Using an in situ GBM xenograft mouse model, combined clinical MRI images of pre-surgery tumor and pathological investigation, we demonstrated that the inhibition of tissue factor (TF) decreased GVPs in Mouse GBM xenograft model...
January 15, 2018: Cancer Biology & Therapy
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