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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/29346776/loss-of-an-androgen-inactivating-and-isoform-specific-hsd17b4-splice-form-enables-emergence-of-castration-resistant-prostate-cancer
#2
Hyun-Kyung Ko, Michael Berk, Yoon-Mi Chung, Belinda Willard, Rohan Bareja, Mark Rubin, Andrea Sboner, Nima Sharifi
Castration-resistant prostate cancer (CRPC) requires tumors to engage metabolic mechanisms that allow sustained testosterone and/or dihydrotestosterone to stimulate progression. 17β-Hydroxysteroid dehydrogenase type 4 (17βHSD4), encoded by HSD17B4, is thought to inactivate testosterone and dihydrotestosterone by converting them to their respective inert 17-keto steroids. Counterintuitively, HSD17B4 expression increases in CRPC and predicts poor prognosis. Here, we show that, of five alternative splice forms, only isoform 2 encodes an enzyme capable of testosterone and dihydrotestosterone inactivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346580/smoking-sex-and-non-small-cell-lung-cancer-steroid-hormone-receptors-in-tumor-tissue-s0424
#3
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/29346484/association-of-dietary-inflammatory-potential-with-colorectal-cancer-risk-in-men-and-women
#4
Fred K Tabung, Li Liu, Weike Wang, Teresa T Fung, Kana Wu, Stephanie A Smith-Warner, Yin Cao, Frank B Hu, Shuji Ogino, Charles S Fuchs, Edward L Giovannucci
Importance: Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention. Objective: To examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346400/the-mechanisms-how-heparin-affects-the-tumor-cell-induced-vegf-and-chemokine-release-from-platelets-to-attenuate-the-early-metastatic-niche-formation
#5
Jan Moritz Ponert, Svenja Schwarz, Reza Haschemi, Jens Müller, Bernd Pötzsch, Gerd Bendas, Martin Schlesinger
Metastasis is responsible for the majority of cancer associated fatalities. Tumor cells leaving the primary tumor and entering the blood flow immediately interact with platelets. Activated platelets contribute in different ways to cancer cell survival and proliferation, e.g. in formation of the early metastatic niche by release of different growth factors and chemokines. Here we show that a direct interaction between platelets and MV3 melanoma or MCF7 breast cancer cells induces platelet activation and a VEGF release in citrated plasma that cannot be further elevated by the coagulation cascade and generated thrombin...
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/29346215/challenges-and-perspectives-for-immunotherapy-in-adenocarcinoma-of-the-pancreas-the-cancer-immunity-cycle
#8
Markus Kieler, Matthias Unseld, Daniela Bianconi, Gerald Prager
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a devastating 5-year overall survival of only approximately 7%. Although just 4% of all malignant diseases are accounted to PDAC, it will become the second leading cause of cancer-related deaths before 2030. Immunotherapy has proven to be a promising therapeutic option in various malignancies such as melanoma, non-small cell lung cancer (NSCLC), microsatellite instability-high gastrointestinal cancer, urinary tract cancer, kidney cancer, and others...
February 2018: Pancreas
https://www.readbyqxmd.com/read/29346117/the-deubiquitinase-usp9x-regulates-fbw7-stability-and-suppresses-colorectal-cancer
#9
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/29346108/modeling-of-electroporation-induced-by-pulsed-electric-fields-in-irregularly-shaped-cells
#10
Luciano Mescia, Michele A Chiapperino, Pietro Bia, Johan Gielis, Diego Caratelli
During the past decades, the poration of cell membrane induced by pulsed electric fields has been widely investigated. Since the basic mechanisms of this process have not yet been fully clarified, many research activities are focused on the development of suitable theoretical and numerical models. To this end, a nonlinear, nonlocal, dispersive, and space-time numerical algorithm has been developed and adopted to evaluate the transmembrane voltage and pore density along the perimeter of realistic irregularly shaped cells...
February 2018: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/29345974/cognitive-effects-of-cancer-and-cancer-treatments
#11
Tim A Ahles, James C Root
As the population of cancer survivors has grown into the millions, there has been increasing emphasis on understanding how the late effects of treatment affect survivors' ability to return to work/school, their capacity to function and live independently, and their overall quality of life. This review focuses on cognitive change associated with cancer and cancer treatments. Research in this area has progressed from a pharmacotoxicology perspective to a view of the cognitive change as a complex interaction of aspects of the treatment, vulnerability factors that increase risk for posttreatment cognitive decline, cancer biology, and the biology of aging...
January 18, 2018: Annual Review of Clinical Psychology
https://www.readbyqxmd.com/read/29345906/prediction-of-hot-spots-at-myeloid-cell-leukemia-1-inhibitors-interface-using-energy-estimation-and-alanine-scanning-mutagenesis
#12
Parthiban Marimuthu, Kalaimathy Singaravelu
Myeloid cell leukemia 1 (Mcl1) is an anti-apoptotic protein that plays central role in apoptosis regulation. Also, Mcl1 has the potency to resist apoptotic cues resulting in up-regulation and cancer cell protection. A molecular probe that has the potential to specifically target Mcl1, and thereby provoke its down-regulatory activity is very essential. The aim of the current study is to probe the internal conformational dynamics of protein motions and potential binding mechanism in response to a series of picomolar range Mcl1 inhibitors using explicit-solvent molecular dynamics (MD) simulations...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345842/pd-l1-is-a-promising-blood-marker-for-predicting-tumor-progression-and-prognosis-in-patients-with-gastric-cancer
#13
Masahiko Amatatsu, Takaaki Arigami, Yoshikazu Uenosono, Shigehiro Yanagita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Sumiya Ishigami, Shoji Natsugoe
Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. On the other hand, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Non-invasive liquid biopsy has recently been spotlighted as a promising approach to predicting tumor progression and prognosis...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345737/present-status-and-future-perspective-of-peptide-based-vaccine-therapy-for-urological-cancer
#14
REVIEW
Wataru Obara, Mitsugu Kanehira, Toyomasa Katagiri, Renpei Kato, Yoichiro Kato, Ryo Takata
The use of peptide-based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide-based vaccines are easily synthesized and the lack of significant side effects when administered in-vivo. Peptide-based vaccine therapy against several cancers including urological cancers had made progress for several decades, but there is no approval peptide vaccine all over the world. Peptides vaccines were also shown to induce a high frequency of immune response in patients who were accompanied by clinical efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345637/structural-basis-of-rna-polymerase-iii-transcription-initiation
#15
Guillermo Abascal-Palacios, Ewan Phillip Ramsay, Fabienne Beuron, Edward Morris, Alessandro Vannini
RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene transcription by Pol III requires the activity of the transcription factor TFIIIB to form a transcriptionally active Pol III preinitiation complex (PIC). Here we present electron microscopy reconstructions of Pol III PICs at 3.4-4.0 Å and a reconstruction of unbound apo-Pol III at 3.1 Å...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29345617/loss-of-functional-bap1-augments-sensitivity-to-trail-in-cancer-cells
#16
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/29345569/a-complex-scenario-and-underestimated-challenge-the-tumor-microenvironment-er-stress-and-cancer-treatment
#17
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/29345430/wearable-wireless-tyrosinase-bandage-and-microneedle-sensors-toward-melanoma-screening
#18
Bianca Ciui, Aida Martin, Rupesh K Mishra, Barbara Brunetti, Tatsuo Nakagawa, Thomas J Dawkins, Mengjia Lyu, Cecilia Cristea, Robert Sandulescu, Joseph Wang
Wearable bendable bandage-based sensor and a minimally invasive microneedle biosensor are described toward rapid screening of skin melanoma. These wearable electrochemical sensors are capable of detecting the presence of the tyrosinase (TYR) enzyme cancer biomarker in the presence of its catechol substrate, immobilized on the transducer surface. In the presence of the surface TYR biomarker, the immobilized catechol is rapidly converted to benzoquinone that is detected amperometrically, with a current signal proportional to the TYR level...
January 18, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29345394/viruses-as-key-modulators-of-the-tgf-%C3%AE-pathway-a-double-edged-sword-involved-in-cancer
#19
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/29345375/understanding-the-regulation-of-apobec3-expression-current-evidence-and-much-to-learn
#20
REVIEW
Daniela Angela Covino, Maria Cristina Gauzzi, Laura Fantuzzi
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function...
December 15, 2017: Journal of Leukocyte Biology
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