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https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#1
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346807/anti-angiogenic-activity-of-rotenoids-from-the-stems-of-derris-trifoliata
#2
Yanisa Mittraphab, Nattaya Ngamrojanavanich, Kuniyoshi Shimizu, Kiminori Matsubara, Khanitha Pudhom
The plants in the genus Derris have proven to be a rich source of rotenoids, of which cytotoxic effect against cancer cells seem to be pronounced. However, their effect on angiogenesis playing a crucial role in both cancer growth and metastasis has been seldom investigated. This study aimed at investigating the effect of the eight rotenoids (1: -8: ) isolated from Derris trifoliata stems on three cancer cells and angiogenesis. Among them, 12a-hydroxyrotenone (2: ) exhibited potent inhibition on both cell growth and migration of HCT116 colon cancer cells...
January 18, 2018: Planta Medica
https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#3
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/29346580/smoking-sex-and-non-small-cell-lung-cancer-steroid-hormone-receptors-in-tumor-tissue-s0424
#4
Ting-Yuan David Cheng, Amy K Darke, Mary W Redman, Gary R Zirpoli, Warren Davis, Rochelle Payne Ondracek, Wiam Bshara, Angela R Omilian, Robert Kratzke, Mary E Reid, Julian R Molina, Jill M Kolesar, Yuhchyau Chen, Robert M MacRae, James Moon, Philip Mack, David R Gandara, Karen Kelly, Regina M Santella, Kathy S Albain, Christine B Ambrosone
Background: To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Methods: Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)...
January 13, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29346447/pik3ca-is-required-for-mouse-uterine-gland-development-and-pregnancy
#5
Hye Jin Chang, Hee Sung Shin, Tae Hoon Kim, Jung-Yoon Yoo, Hanna E Teasley, Jean J Zhao, Un-Hwan Ha, Jae-Wook Jeong
The PI3K/AKT signaling pathway plays a critical role in the maintenance of equilibrium between cell survival and apoptosis. The Pik3ca gene is mutated in a range of human cancers. It has been found to be oncogenic, and mutations lead to constitutive activation of the PI3K/AKT pathway. The expression patterns of PIK3CA proteins in the uterus of mice during early pregnancy indicate that it may play a role in the regulation of glandular epithelial cells, which is required to support uterine receptivity. To further investigate the role of Pik3ca in uterine function, Pik3ca was conditionally ablated only in the PGR-positive cells (Pgrcre/+Pik3caf/f; Pik3cad/d)...
2018: PloS One
https://www.readbyqxmd.com/read/29346386/histological-subtypes-of-mouse-mammary-tumors-reveal-conserved-relationships-to-human-cancers
#6
Daniel P Hollern, Matthew R Swiatnicki, Eran R Andrechek
Human breast cancer has been characterized by extensive transcriptional heterogeneity, with dominant patterns reflected in the intrinsic subtypes. Mouse models of breast cancer also have heterogeneous transcriptomes and we noted that specific histological subtypes were associated with particular subsets. We hypothesized that unique sets of genes define each tumor histological type across mouse models of breast cancer. Using mouse models that contained both gene expression data and expert pathologist classification of tumor histology on a sample by sample basis, we predicted and validated gene expression signatures for Papillary, EMT, Microacinar and other histological subtypes...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29346310/ar-signaling-in-human-malignancies-prostate-cancer-and-beyond
#7
EDITORIAL
Emmanuel S Antonarakis
The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer...
January 18, 2018: Cancers
https://www.readbyqxmd.com/read/29346309/the-role-of-e6-spliced-isoforms-e6-in-human-papillomavirus-induced-carcinogenesis
#8
REVIEW
Leslie Olmedo-Nieva, J Omar Muñoz-Bello, Adriana Contreras-Paredes, Marcela Lizano
Persistent infections with High Risk Human Papillomaviruses (HR-HPVs) are the main cause of cervical cancer development. The E6 and E7 oncoproteins of HR-HPVs are derived from a polycistronic pre-mRNA transcribed from an HPV early promoter. Through alternative splicing, this pre-mRNA produces a variety of E6 spliced transcripts termed E6*. In pre-malignant lesions and HPV-related cancers, different E6/E6* transcriptional patterns have been found, although they have not been clearly associated to cancer development...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29346307/knowledge-and-attitudes-of-general-practitioners-and-sexual-health-care-professionals-regarding-human-papillomavirus-vaccination-for-young-men-who-have-sex-with-men
#9
Samuel W D Merriel, Carrie Flannagan, Joanna M Kesten, Gilla K Shapiro, Tom Nadarzynski, Gillian Prue
Men who have sex with men (MSM) may be at higher risk for human papillomavirus (HPV)-associated cancers. Healthcare professionals' recommendations can affect HPV vaccination uptake. Since 2016, MSM up to 45 years have been offered HPV vaccination at genitourinary medicine (GUM) clinics in a pilot programme, and primary care was recommended as a setting for opportunistic vaccination. Vaccination prior to potential exposure to the virus (i.e., sexual debut) is likely to be most efficacious, therefore a focus on young MSM (YMSM) is important...
January 18, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#10
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29346117/the-deubiquitinase-usp9x-regulates-fbw7-stability-and-suppresses-colorectal-cancer
#11
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/29346059/fermented-extraction-of-citrus-unshiu-peel-inhibits-viability-and-migration-of-human-pancreatic-cancers
#12
Jungwhoi Lee, Jungsul Lee, Myungseung Kim, Jae Hoon Kim
Pancreatic cancer is one of the most dangerous cancers with high mortality rates. Despite continuous efforts, there has been limited improvement in its prognosis. In this study, we prepared fermented extract of Citrus unshiu peel (fCUP) from the by-product after juice processing and then examined the anticancer effects of fCUP on human pancreatic cancer cells. Treatment with fCUP inhibited the growth of human pancreatic cancer cells through induction of caspase-3 cleavage both in vitro and in vivo. Treatment with fCUP also blocked the migration of human pancreatic cancer cells through activation of intracellular signaling pathways such as MKK3/6 and P38...
January 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29346026/a-scintigraphic-method-for-quantitation-of-lymphatic-function-in-arm-lymphedema
#13
Svend Hvidsten, Navid M Toyserkani, Jens A Sørensen, Poul F Høilund-Carlsen, Jane A Simonsen
BACKGROUND: Lymphoscintigraphy is commonly used to assess breast cancer-related lymphedema. However, a reliable quantitative method that clearly distinguishes normal lymphatic function from lymphedema is desired. We propose a quantitative method based upon the physiological mean transit time (MTT) measure of lymph fluid passing through the arm. METHODS AND RESULTS: Eleven patients, aged 34-68 years, with unilateral arm lymphedema following breast cancer treatment underwent simultaneous bilateral lymphoscintigraphy using intradermal injection of 99mTc-labeled human serum albumin (HSA)...
January 18, 2018: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/29345976/synthetic-biology-immunotherapy-by-design
#14
Matthew J Brenner, Jang Hwan Cho, Nicole M L Wong, Wilson W Wong
Cellular immunotherapy holds great promise for the treatment of human disease. Clinical evidence suggests that T cell immunotherapies have the potential to combat cancers that evade traditional immunotherapy. Despite promising results, adverse effects leading to fatalities have left scientists seeking tighter control over these therapies, which is reflected in the growing body of synthetic biology literature focused on developing tightly controlled, context-independent parts. In addition, researchers are adapting these tools for other uses, such as for the treatment of autoimmune disease, HIV infection, and fungal interactions...
January 18, 2018: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/29345930/%C3%AE-amino-%C3%AE-carboxymuconate-%C3%AE%C2%B5-semialdehyde-decarboxylase-acmsd-inhibitors-as-novel-modulators-of-de-novo-nicotinamide-adenine-dinucleotide-nad-biosynthesis
#15
Roberto Pellicciari, Paride Liscio, Nicola Giacchè, Francesca De Franco, Andrea Carotti, Janet Robertson, Lucia Cialabrini, Elena Katsyuba, Nadia Raffaelli, Johan Auwerx
NAD+ has a central function in linking cellular metabolism to major cell signaling and gene regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Whilst the beneficial effects of NAD+ boosting are well established in mitochondrial fitness, metabolism, and lifespan, to date, no therapeutic enhancers of de novo NAD+ biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22) the first potent and selective inhibitor of human ACMSD (IC50 = 0...
January 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29345736/palbociclib-in-combination-with-letrozole-as-first-line-treatment-for-advanced-breast-cancer-a-japanese-phase-ii-study
#16
Norikazu Masuda, Reiki Nishimura, Masato Takahashi, Kenichi Inoue, Shinji Ohno, Hiroji Iwata, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Takashi Nagasawa, Yoshiko Umeyama, Masakazu Toi
This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). The primary endpoint of investigator-assessed 1-year progression-free survival probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345708/triphenylstannyl-arylimino-methyl-benzoates-with-selective-potency-that-induce-g1-and-g2-m-cell-cycle-arrest-and-trigger-apoptosis-via-ros-in-human-cervical-cancer-cells
#17
Tushar S Basu Baul, Imliwati Longkumer, Andrew Duthie, Priya Singh, Biplob Koch, M Fátima C Guedes da Silva
Metal complexes with organelle specificity and potent but selective cytotoxicity are highly desirable. A novel series of triphenylstannyl 4-((arylimino)methyl)benzoates (2-8) were obtained by the reactions of triphenylstannyl 4-formylbenzoate [Ph3Sn(L1)] 1 with primary aromatic amines. Two representative compounds (10, 11) were also synthesized by reacting aqua-triphenylstannyl 2-formylbenzoate [Ph3Sn(L9)(H2O)] (9) with aniline and p-fluoroaniline, respectively. These compounds were characterized by elemental analysis, IR and 1H, 13C and 119Sn NMR spectroscopy, as well as single-crystal X-ray diffraction for compounds 5, 7-11 and three pro-ligands...
January 18, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29345617/loss-of-functional-bap1-augments-sensitivity-to-trail-in-cancer-cells
#18
Krishna Kalyan Kolluri, Constantine Alifrangis, Neelam Kumar, Yuki Ishii, Stacey Price, Magali Michaut, Steven Williams, Syd Barthorpe, Howard Lightfoot, Sara Busacca, Annabel Sharkey, Zhenqiang Yuan, Elizabeth K Sage, Sabarinath Vallath, John Le Quesne, David A Tice, Doraid Alrifai, Sylvia von Karstedt, Antonella Montinaro, Naomi Guppy, David A Waller, Apostolos Nakas, Robert Good, Alan Holmes, Henning Walczak, Dean A Fennel, Mathew Garnett, Francesco Iorio, Lodewyk Wessels, Ultan McDermott, Samuel M Janes
Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15 exome-sequenced MM lines and the discovery of a subset defined by loss of function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). This association is observed across human early passage MM cultures, mouse xenografts and human tumour explants...
January 18, 2018: ELife
https://www.readbyqxmd.com/read/29345474/total-synthesis-of-antiproliferative-parvifloron-f
#19
Yohei Saito, Masuo Goto, Kyoko Nakagawa-Goto
The first total synthesis of parvifloron F, a bioactive highly oxidized abietane diterpene, was achieved. The abietane skeleton was constructed by Lewis acid promoted cyclization. Preliminary structure-activity relationship correlations were established for the synthetic intermediates against human tumor cell lines. Certain compounds showed unique selective antiproliferative activity against triple-negative breast cancer. The oxidation level of the abietane ring affected the selectivity.
January 18, 2018: Organic Letters
https://www.readbyqxmd.com/read/29345429/engineering-3d-hydrogels-for-personalized-in-vitro-human-tissue-models
#20
REVIEW
Chya-Yan Liaw, Shen Ji, Murat Guvendiren
There is a growing interest in engineering hydrogels for 3D tissue and disease models. The major motivation is to better mimic the physiological microenvironment of the disease and human condition. 3D tissue models derived from patients' own cells can potentially revolutionize the way treatment and diagnostic alternatives are developed. This requires development of tissue mimetic hydrogels with user defined and tunable properties. In this review article, a recent summary of 3D hydrogel platforms for in vitro tissue and disease modeling is given...
January 18, 2018: Advanced Healthcare Materials
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