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https://www.readbyqxmd.com/read/29040431/prevention-of-breast-cancer-induced-osteolytic-bone-resorption-by-benzyl-isothiocyanate
#1
Subrata K Pore, Eun-Ryeong Hahm, Joseph D Latoche, Carolyn J Anderson, Yongli Shuai, Shivendra V Singh
Osteolytic bone resorption is the primary cause of pain and suffering (e.g., pathological bone fracture) in women with metastatic breast cancer. The current standard of care for patients with bone metastasis for reducing the incidence of skeletal complications includes bisphosphonates and a humanized antibody (denosumab). However, a subset of patients on these therapies still develops new bone metastasis or experience adverse effects. Moreover, some bisphosphonates have poor oral bioavailability. Therefore, orally-bioavailable and non-toxic inhibitors of breast cancer-induced osteolytic bone resorption are still clinically desirable...
October 11, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29036807/obtaining-and-characterization-of-monoclonal-antibodies-against-recombinant-extracellular-domain-of-human-epidermal-growth-factor-receptor-2
#2
Sarina Nurgul, Abeldenov Sailau, Turgimbayeva Aigerim, Zhylkibayev Assylbek, Ramankulov Erlan, Khassenov Bekbolat, Eskendirova Saule
Human epidermal growth factor receptor 2 (HER2) is an important biomarker for detection and treatment of different types of cancers such as breast, ovarian, stomach cancer. In this study, we developed a monoclonal antibody against the extracellular domain (ECD) of HER2 biomarker of breast cancer. For this purpose, the ECD-HER2 gene was amplified and cloned into an expression vector. Gene was generated in Escherichia coli BL21 (DE3) strain for expression of recombinant protein. The expressed protein was separated by SDS-PAGE and detected by anti-his monoclonal antibody in immunoblotting...
September 8, 2017: Human Antibodies
https://www.readbyqxmd.com/read/29036567/extra-pituitary-expressed-fsh-is-it-physiologically-important
#3
Anushka Jayaraman, T Rajendra Kumar
Pituitary gonadotropes synthesize and secrete follicle-stimulating hormone (FSH). FSH is a heterodimer that consists of an α-and a β-subunit. The α - subunit is common to other pituitary and placental glycoprotein hormones and the β-subunit is the hormone/receptor specific subunit. Although the pituitary is the main tissue that accounts for circulating hormone, previous and recent reports indicate extra-pituitary sources of FSH production including mouse gonads, human stomach, prostate, umbilical cord vein endothelial cells, uterine myometrium, placenta and chicken abdominal adipose tissue...
September 20, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29035637/design-and-characterization-of-mp0250-a-tri-specific-anti-hgf-anti-vegf-darpin%C3%A2-drug-candidate
#4
H Kaspar Binz, Talitha R Bakker, Douglas J Phillips, Andreas Cornelius, Christof Zitt, Thomas Göttler, Gabriel Sigrist, Ulrike Fiedler, Savira Ekawardhani, Ignacio Dolado, Johan Abram Saliba, Gaby Tresch, Karl Proba, Michael T Stumpp
MP0250 is a multi-domain drug candidate currently being tested in clinical trials for the treatment of cancer. It comprises one anti-vascular endothelial growth factor-A (VEGF-A), one anti-hepatocyte growth factor (HGF), and two anti-human serum albumin (HSA) DARPin® domains within a single polypeptide chain. While there is first clinical validation of a single-domain DARPin® drug candidate, little is known about DARPin® drug candidates comprising multiple domains. Here, we show that MP0250 can be expressed at 15 g/L in soluble form in E...
October 16, 2017: MAbs
https://www.readbyqxmd.com/read/29035379/lobular-carcinoma-in-situ-and-invasive-lobular-breast-cancer-are-characterized-by-enhanced-expression-of-transcription-factor-ap-2%C3%AE
#5
Mieke Raap, Malte Gronewold, Henriette Christgen, Silke Glage, Mohammad Bentires-Alj, Shany Koren, Patrick W Derksen, Mirjam Boelens, Jos Jonkers, Ulrich Lehmann, Friedrich Feuerhake, Elna Kuehnle, Oleg Gluz, Ronald Kates, Ulrike Nitz, Nadia Harbeck, Hans H Kreipe, Matthias Christgen
Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29034459/amelioration-of-autoimmunity-with-an-inhibitor-selectively-targeting-all-active-centers-of-the-immunoproteasome
#6
Michael Basler, Elmer Maurits, Gerjan de Bruin, Julia Koerner, Herman S Overkleeft, Marcus Groettrup
BACKGROUND AND PURPOSE: MECL-1 (β2i), LMP2 (β1i), and LMP7 (β5i) are the proteolytically active subunits of the immunoproteasome, a special type of proteasome mainly expressed in hematopoietic cells. Targeting LMP7 has been shown to be therapeutically effective in pre-clinical models of autoimmune diseases. In this study, a recently described inhibitor of the immunoproteasome LU-005i was investigated with respect to selectivity and biological activity. EXPERIMENTAL APPROACH: The specificity of LU-005i and other immunoproteasome selective inhibitors was characterized using fluorogenic peptide substrates...
October 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29034001/correction-to-mouse-mammary-tumour-virus-mmtv-and-human-breast-cancer-with-neuroendocrine-differentiation
#7
J S Lawson, C C Ngan, W K Glenn, D D Tran
[This corrects the article DOI: 10.1186/s13027-017-0135-8.].
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29033940/pi3k%C3%AE-inhibition-enhances-the-antitumor-fitness-of-adoptively-transferred-cd8-t-cells
#8
Jacob S Bowers, Kinga Majchrzak, Michelle H Nelson, Bulent Arman Aksoy, Megan M Wyatt, Aubrey S Smith, Stefanie R Bailey, Lillian R Neal, Jeffrey E Hammerbacher, Chrystal M Paulos
Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8(+) T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033351/mouse-cutaneous-melanoma-induced-by-mutant-braf-arises-from-expansion-and-dedifferentiation-of-mature-pigmented-melanocytes
#9
Corinna Köhler, David Nittner, Florian Rambow, Enrico Radaelli, Fabio Stanchi, Niels Vandamme, Arianna Baggiolini, Lukas Sommer, Geert Berx, Joost J van den Oord, Holger Gerhardt, Cedric Blanpain, Jean-Christophe Marine
To identify the cells at the origin of melanoma, we combined single-cell lineage-tracing and transcriptomics approaches with time-lapse imaging. A mouse model that recapitulates key histopathological features of human melanomagenesis was created by inducing a BRafV600E-driven melanomagenic program in tail interfollicular melanocytes. Most targeted mature, melanin-producing melanocytes expanded clonally within the epidermis before losing their differentiated features through transcriptional reprogramming and eventually invading the dermis...
October 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29032724/reintroducing-the-sodium-iodide-symporter-nis-to-anaplastic-thyroid-carcinoma
#10
Kathrin Alexandra Schmohl, Patrick Dolp, Christina Schug, Kerstin Knoop, Kathrin Klutz, Nathalie Schwenk, Peter Bartenstein, Peter Jon Nelson, Manfred Ogris, Ernst Wagner, Christine Spitzweg
Anaplastic thyroid carcinoma (ATC), the most aggressive form of thyroid cancer, is unresponsive to radioiodide therapy. In the current study, we aimed to extend the diagnostic and therapeutic application of radioiodide beyond the treatment of differentiated thyroid cancer by targeting the functional sodium iodide symporter (NIS) to ATC. We employed nanoparticle vectors (polyplexes) based on linear polyethylenimine (LPEI), shielded by polyethylene glycol (PEG) and coupled to the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand in order to target a <i>NIS</i>-expressing plasmid (LPEI-PEG-GE11/NIS) to EGFR overexpressing human thyroid carcinoma cell lines...
October 15, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29031938/design-synthesis-and-antiproliferative-effect-of-17%C3%AE-amide-derivatives-of-2-methoxyestradiol-and-their-studies-on-pharmacokinetics
#11
Xiufang Shi, Zhihao Wang, Feng Xu, Xiang Lu, Haifeng Yao, Dandan Wu, Shuaijun Sun, Ruifang Nie, Shuo Gao, Panpan Li, Liwen Xia, Zhenzhong Zhang, Cong Wang
A series of 17β-amide-2-methoxyestradiol compounds were synthesized with an aim to enhance the antiproliferative effect of 2-methoxyestradiol. The antiproliferative activity of 2-methoxyestradiol analogs against human cancer cells was investigated. 2-methoxy-3-benzyloxy-17β-chloroacetamide-1,3,5(10)-triene (5e) and 2-methoxy-3-hydroxy-17β-butyramide-1,3,5(10)-triene (6c) had comparable or better antitumor activity than 2-methoxyestradiol. The elimination half-life of 6c (t1/2β = 240.93 min) is ten times longer than 2-ME and the area under the curve was seven times (AUC0-tmin =2068...
October 12, 2017: Steroids
https://www.readbyqxmd.com/read/29030986/the-small-molecule-au14022-promotes-colorectal-cancer-cell-death-via-p53-mediated-g2-m-phase-arrest-and-mitochondria-mediated-apoptosis
#12
Hwani Ryu, Ky-Youb Nam, Jae Sung Kim, Sang-Gu Hwang, Jie-Young Song, Jiyeon Ahn
The p53 tumor suppressor plays critical roles in cell cycle regulation and apoptotic cell death, with its activation capable of sensitizing cancer cells to radiotherapy or chemotherapy. To identify small molecules that induce apoptosis via increased p53 transcriptional activity, we used a novel in-house library containing 96 small-molecule compounds. Using a cell-based screening method with a p53-responsive luciferase-reporter assay system involving benzoxazole derivatives, we found that AU14022 administration significantly increased p53 transcriptional activity in a concentration-dependent manner...
October 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29030307/egfr-targeted-multifunctional-polymersomal-doxorubicin-induces-selective-and-potent-suppression-of-orthotopic-human-liver-cancer-in-vivo
#13
Yuan Fang, Weijing Yang, Liang Cheng, Fenghua Meng, Jian Zhang, Zhiyuan Zhong
Liver cancer is a globally leading malignancy that has a poor five-year survival rate of less than 20%. The systemic chemotherapeutics are generally ineffective for liver cancers partly due to fast clearance and low tumor uptake. Here, we report that GE11 peptide functionalized polymersomal doxorubicin (GE11-PS-DOX) effectively targets and inhibits epidermal growth factor receptor (EGFR)-positive SMMC7721 orthotopic human liver tumor xenografts in mice. GE11-PS-DOX with a GE11 surface density of 10% displayed a high drug loading of 15...
October 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29029446/a-potential-prognostic-biomarker-spc24-promotes-tumorigenesis-and-metastasis-in-lung-cancer
#14
Juan Zhou, Yang Yu, Yunfeng Pei, Chunping Cao, Chen Ding, Duping Wang, Li Sun, Guoping Niu
RESULTS: SPC24 is over-expressed in clinical lung adenocarcinoma samples, and high level of SPC24 is associated with advanced stages of lung tumors. Knocking down SPC24 repressed cell growth and promoted apoptosis. SPC24 deficiency reduced cancer cell migration as well. E-cadherin, one of the epithelial-mesenchymal transition markers, was up-regulated in the knockdown cells, along with down-regulation of N-cadherin and Vimentin. Oncomine expression analyses further confirmed that high level of SPC24 is associated with tumors from smokers, recurrent patients, or patients with shorter survivals...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029386/exome-sequencing-analysis-of-murine-medulloblastoma-models-identifies-wdr11-as-a-potential-tumor-suppressor-in-group-3-tumors
#15
Lei Wei, Brian L Murphy, Gang Wu, Matthew Parker, John Easton, Richard J Gilbertson, Jinghui Zhang, Martine F Roussel
Mouse models of human cancers are widely used in cancer research, yet questions frequently arise regarding their faithfulness in recapitulating their human counterparts. To compare the somatic mutations of murine models with human medulloblastoma (MB), we performed whole-exome sequencing on 12 tumors representing three distinct medulloblastoma subgroups: Wnt, Sonic Hedgehog (Shh) and Group 3 (G3). In total, 64 somatic mutations were identified and validated, including 40 predicted to cause amino acid changes...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027534/long-non-coding-rna-meg3-promotes-the-proliferation-of-glioma-cells-through-targeting-wnt-%C3%AE-catenin-signal-pathway
#16
X Gong, M Huang
Glioma has been identified as one of the most aggressive primary tumors. Long non-coding RNAs (lncRNAs), with length larger than 200 bp, have drawn increasing attention to their abnormal expression and regulation function in carcinogenesis. However, the role of lncRNAs in glioma remains largely unknown. Maternally expressed gene 3 (MEG3), also known as gene-trap locus 2 (GTL2), is an imprinted gene, and is encoded by the MEG3 transcript of the DLK1/MEG3 locus on human chromosome, or Meg3 on mouse chromosome...
October 13, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29025766/car-t-therapy-targeting-icam-1-eliminates-advanced-human-thyroid-tumors
#17
Irene M Min, Enda Shevlin, Yogindra Vedvyas, Marjan Zaman, Brian Wyrwas, Theresa Scognamiglio, Maureen D Moore, Weibin Wang, Susan Park, Spencer Park, Suraj Panjwani, Katherine D Gray, Andrew B Tassler, Rasa Zarnegar, Thomas J Fahey, Moonsoo M Jin
PURPOSE: Poorly-differentiated thyroid cancer and anaplastic thyroid cancer (ATC) are rare yet lethal malignancies with limited treatment options. Many malignant tumors including papillary thyroid cancer (PTC) and ATC are associated with increased expression of ICAM-1, providing a rationale for utilizing ICAM-1-targeting agents for the treatment of aggressive cancer. We developed a third-generation CAR targeting ICAM-1 to leverage adoptive T cell therapy as a new treatment modality. EXPERIMENTAL DESIGN: ICAM-1 CAR T cells were applied on multiple malignant and non-malignant target cells to investigate specific target cell death and 'off-tumor' toxicity in vitro...
October 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29025661/low-systemic-toxicity-nanocarriers-fabricated-from-heparin-mpeg-and-pamam-dendrimers-for-controlled-drug-release
#18
Vu Minh Thanh, Thi Hiep Nguyen, Tuong Vi Tran, Uyen-Thi Phan Ngoc, Minh Nhat Ho, Thi Thinh Nguyen, Yen Nguyen Tram Chau, Van Thu Le, Ngoc Quyen Tran, Cuu Khoa Nguyen, Dai Hai Nguyen
In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release...
January 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29025423/downregulation-of-nmi-promotes-tumor-growth-and-predicts-poor-prognosis-in-human-lung-adenocarcinomas
#19
Jingshu Wang, Kun Zou, Xu Feng, Miao Chen, Cong Li, Ranran Tang, Yang Xuan, Meihua Luo, Wangbing Chen, Huijuan Qiu, Ge Qin, Yixin Li, Changlin Zhang, Binyi Xiao, Lan Kang, Tiebang Kang, Wenlin Huang, Xinfa Yu, Xiaojun Wu, Wuguo Deng
BACKGROUND: N-myc (and STAT) interactor (NMI) plays vital roles in tumor growth, progression, and metastasis. In this study, we identified NMI as a potential tumor suppressor in lung cancer and explored its molecular mechanism involved in lung cancer progression. METHODS: Human lung cancer cell lines and a mouse xenograft model was used to study the effect of NMI on tumor growth. The expression of NMI, COX-2 and relevant signaling proteins were examined by Western blot...
October 12, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29024929/inhibition-of-microrna-21-5p-promotes-the-radiation-sensitivity-of-non-small-cell-lung-cancer-through-hmsh2
#20
Yu Song, Yun Zuo, Xiao-Lan Qian, Zhi-Peng Chen, Shao-Kai Wang, Lei Song, Li-Ping Peng
BACKGROUND: This study aimed to explore the effects of microRNA-21-5p (miR-21-5p) on the radiation sensitivity of non-small cell lung cancer (NSCLC) and the involvement of human MutS homolog 2 (hMSH2) One hundred fourteen NSCLC patients at stage II or III who received surgery and postoperative radiotherapy were enrolled in this study. METHODS: The patients were assigned into radiation-sensitive and -insensitive groups. NSCLC A549 cells were transfected to generate control, Negative control (NC), miR-21-5p inhibitor, miR-21-5p mimic, small interfering hMSH2 (sihMSH2), miR-21-5p inhibitor + sihMSH2 and hMSH2 overexpression groups...
October 9, 2017: Cellular Physiology and Biochemistry
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