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https://www.readbyqxmd.com/read/29453628/safety-tolerability-and-preliminary-activity-of-imgn529-a-cd37-targeted-antibody-drug-conjugate-in-patients-with-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma-a-dose-escalation-phase-i-study
#1
Anastasios Stathis, Ian W Flinn, Sumit Madan, Kami Maddocks, Arnold Freedman, Steven Weitman, Emanuele Zucca, Mihaela C Munteanu, M Lia Palomba
Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprising a CD37-binding antibody linked to the maytansinoid DM1, a potent anti-mitotic agent. Methods This first-in-human, phase 1 trial recruited adult patients with relapsed or refractory B-cell NHL. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose. Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity...
February 17, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29448305/development-and-validation-of-gc-ms-ms-method-for-simultaneous-quantitation-of-several-antipsychotics-in-human-plasma-and-oral-fluid
#2
Tiago Rosado, David Oppolzer, Belinda Cruz, Mário Barroso, Samira Varela, Victor Oliveira, Carlos Leitão, Eugenia Gallardo
RATIONALE: Antipsychotic drugs are prescription medications used to treat psychotic disorders, such as schizophrenia, schizoaffective disorder, or psychotic depression. With several antipsychotic drugs currently available all over the world, this class of drugs has quickly gotten importance in both clinical and forensic context. This work describes the development and validation of a methodology for the determination of seven antipsychotic drugs in plasma and oral fluid samples. METHODS: The antipsychotic drugs (chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, cyamemazine and, levomepromazine) were isolated from 0...
February 15, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29440181/a-first-in-human-study-of-the-new-oral-selective-estrogen-receptor-degrader-azd9496-for-hr-her2-advanced-breast-cancer
#3
Erika P Hamilton, Manish R Patel, Anne C Armstrong, Richard D Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin P O Lindemann, Shethah Morgan, Gaia Schiavon, Hazel M Weir, Seock-Ah Im
PURPOSE: AZD9496 is an oral non-steroidal, small-molecule inhibitor of estrogen receptor alpha (ERα), and a potent and selective antagonist and degrader of ERα. This first in human Phase 1 study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity. EXPERIMENTAL DESIGN: Forty-five patients received AZD9496 (20 mg once daily to 600 mg twice daily) in a dose-escalation, dose- expansion 'rolling 6' design...
February 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29435940/mechanism-and-method-for-generating-tumor-free-ips-cells-using-intronic-microrna-mir-302-induction
#4
Shi-Lung Lin, Shao-Yao Ying
Today's researchers generating induced pluripotent stem cells (iPS cells or iPSCs) usually consider their pluripotency rather than potential tumorigenicity. Oncogenic factors such as c-Myc and Klf4 are frequently used to boost the survival and proliferative rates of iPSCs, creating an inevitable problem of tumorigenicity that hinders the therapeutic usefulness of these iPSCs. To prevent stem cell tumorigenicity, we have examined mechanisms by which the cell cycle genes are regulated in embryonic stem cells (ESCs)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29429153/cancer-prevention-with-green-tea-and-its-principal-constituent-egcg-from-early-investigations-to-current-focus-on-human-cancer-stem-cells
#5
Hirota Fujiki, Tatsuro Watanabe, Eisaburo Sueoka, Anchalee Rawangkan, Masami Suganuma
Cancer preventive activities of green tea and its main constituent, (-)-epigallocatechin gallate (EGCG) have been extensively studied by scientists all over the world. Since 1983, we have studied the cancer chemopreventive effects of EGCG as well as green tea extract and underlying molecular mechanisms. The first part of this review summarizes groundbreaking topics with EGCG and green tea extract: 1) Delayed cancer onset as revealed by a 10-year prospective cohort study, 2) Prevention of colorectal adenoma recurrence by a double-blind randomized clinical phase II trial, 3) Inhibition of metastasis of B16 melanoma cells to the lungs of mice, 4) Increase in the average value of Young's moduli, i...
January 31, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29423221/a-phase-i-clinical-trial-of-dtcapfs-a-derivative-of-a-novel-human-hormone-peptide-for-the-treatment-of-advanced-metastatic-solid-tumors
#6
Salomon M Stemmer, Ofer Benjaminov, Michael H Silverman, Uziel Sandler, Ofer Purim, Naomi Sender, Chen Meir, Pnina Oren-Apoteker, Joel Ohana, Yoram Devary
The aim of the present phase I first-in-human study was to investigate the safety/efficacy of dTCApFs (a novel hormone peptide that enters cells through the T1/ST2 receptor), in advanced/metastatic solid tumors. The primary objective of this open-label dose-escalation study was to determine the safety profile of dTCApFs. The study enrolled patients (aged ≥18 years) with pathologically confirmed locally advanced/metastatic solid malignancies, who experienced treatment failure or were unable to tolerate previous standard therapy...
January 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29422862/geraniol-pharmacokinetics-bioavailability-and-its-multiple-effects-on-the-liver-antioxidant-and-xenobiotic-metabolizing-enzymes
#7
Barbara Pavan, Alessandro Dalpiaz, Luca Marani, Sarah Beggiato, Luca Ferraro, Donatella Canistro, Moreno Paolini, Fabio Vivarelli, Maria C Valerii, Antonietta Comparone, Luigia De Fazio, Enzo Spisni
Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29407800/novel-aspects-of-uptake-patterns-metabolite-formation-and-toxicological-responses-in-salmon-exposed-to-the-organophosphate-esters-tris-2-butoxyethyl-and-tris-2-chloroethyl-phosphate
#8
Augustine Arukwe, Camilla Catarci Carteny, Trine Eggen, Monika Möder
Given the compound differences between tris(2-butoxyethyl)- and tris(2-cloroethyl) phosphate (TBOEP and TCEP, respectively), we hypothesized that exposure of juvenile salmon to TBOEP and TCEP will produce compound-specific differences in uptake and bioaccumulation patterns, resulting in potential formation of OH-metabolites. Juvenile salmon were exposed to waterborne TCEP or TBOEP (0.04, 0.2 and 1 mg/L) for 7 days. The muscle accumulation was measured and bioconcentration factor (BCF) was calculated, showing that TCEP was less accumulative and resistant to metabolism in salmon than TBOEP...
January 30, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29407711/photodegradation-of-sulfasalazine-and-its-human-metabolites-in-water-by-uv-and-uv-peroxydisulfate-processes
#9
Yuefei Ji, Yan Yang, Lei Zhou, Lu Wang, Junhe Lu, Corinne Ferronato, Jean-Marc Chovelon
The widespread occurrence of pharmaceuticals and their metabolites in natural waters has raised great concerns about their potential risks on human health and ecological systems. This study systematically investigates the degradation of sulfasalazine (SSZ) and its two human metabolites, sulfapyridine (SPD) and 5-aminosalicylic acid (5-ASA), by UV and UV/peroxydisulfate (UV/PDS) processes. Experimental results show that SPD and 5-ASA were readily degraded upon UV 254 nm direct photolysis, with quantum yields measured to be (8...
January 31, 2018: Water Research
https://www.readbyqxmd.com/read/29401246/anti-napi2b-antibody-drug-conjugate-lifastuzumab-vedotin-dnib0600a-compared-to-pegylated-liposomal-doxorubicin-in-patients-with-platinum-resistant-ovarian-cancer-in-a-randomized-open-label-phase-ii-study
#10
S Banerjee, A M Oza, M J Birrer, E P Hamilton, J Hasan, A Leary, K N Moore, B Mackowiak-Matejczyk, J Pikiel, I Ray-Coquard, P Trask, K Lin, E Schuth, A Vaze, Y Choi, J C Marsters, D J Maslyar, V Lemahieu, Y Wang, E W Humke, J F Liu
Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent anti-mitotic agent, monomethyl auristatin E (MMAE), which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug-conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and Methods: Platinum-resistant OC patients were randomized to receive LIFA (2.4 mg/kg, intravenously, every 3 weeks [Q3W]), or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W)...
February 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29401002/phosphatidylinositol-3-kinase-%C3%AE-selective-inhibition-with-alpelisib-byl719-in-pik3ca-altered-solid-tumors-results-from-the-first-in-human-study
#11
Dejan Juric, Jordi Rodon, Josep Tabernero, Filip Janku, Howard A Burris, Jan H M Schellens, Mark R Middleton, Jordan Berlin, Martin Schuler, Marta Gil-Martin, Hope S Rugo, Ruth Seggewiss-Bernhardt, Alan Huang, Douglas Bootle, David Demanse, Lars Blumenstein, Christina Coughlin, Cornelia Quadt, José Baselga
Purpose We report the first-in-human phase Ia study to our knowledge ( ClinicalTrials.gov identifier: NCT01219699) identifying the maximum tolerated dose and assessing safety and preliminary efficacy of single-agent alpelisib (BYL719), an oral phosphatidylinositol 3-kinase α (PI3Kα)-selective inhibitor. Patients and Methods In the dose-escalation phase, patients with PIK3CA-altered advanced solid tumors received once-daily or twice-daily oral alpelisib on a continuous schedule. In the dose-expansion phase, patients with PIK3CA-altered solid tumors and PIK3CA-wild-type, estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer received alpelisib 400 mg once daily...
February 5, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29399158/microrna-1-inhibits-tumorigenicity-of-esophageal-squamous-cell-carcinoma-and-enhances-sensitivity-to-gefitinib
#12
Qianqian Yu, Yiqian Liu, Chengcai Wen, Yongzhao Zhao, Shidai Jin, Youfang Hu, Feng Wang, Liang Chen, Bin Zhang, Wei Wang, Quan Zhu, Renhua Guo
Dysregulation of microRNAs in various types of human cancer promote or suppress oncogenesis. MicroRNA (miR)-1 was previously revealed to function as a tumor suppressor in prostate cancer cells, and its expression was associated with reduced metastatic potential in lung cancer. The present study investigated the role of miR-1 and its association with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) in the pathophysiology of esophageal squamous cell carcinoma (ESCC), and analyzed the effects of miR-1 inhibitor or mimics on sensitivity to epidermal growth factor receptor-tyrosine kinase inhibitors, the alterations of cell cycle distribution and apoptosis in ESCC cells...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29389882/validation-of-a-method-for-cylindrospermopsin-determination-in-vegetables-application-to-real-samples-such-as-lettuce-lactuca-sativa-l
#13
Ana I Prieto, Remedios Guzmán-Guillén, Leticia Díez-Quijada, Alexandre Campos, Vitor Vasconcelos, Ángeles Jos, Ana M Cameán
Reports on the occurrence of the cyanobacterial toxin cylindrospermopsin (CYN) have increased worldwide because of CYN toxic effects in humans and animals. If contaminated waters are used for plant irrigation, these could represent a possible CYN exposure route for humans. For the first time, a method employing solid phase extraction and quantification by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) of CYN was optimized in vegetables matrices such as lettuce (Lactuca sativa)...
February 1, 2018: Toxins
https://www.readbyqxmd.com/read/29381751/molecular-mechanism-of-inhibitory-effects-of-bovine-lactoferrin-on-the-growth-of-oral-squamous-cell-carcinoma
#14
Chanbora Chea, Mutsumi Miyauchi, Toshihiro Inubushi, Nurina Febriyanti Ayuningtyas, Ajiravudh Subarnbhesaj, Phuong Thao Nguyen, Madhu Shrestha, Sivmeng Haing, Kouji Ohta, Takashi Takata
BACKGROUND: Lactoferrin (LF), a member of the transferrin family, recently has been demonstrated to have anticancer effects on various cancers including oral squamous cell carcinoma (OSCC). However, little is known about the underlying mechanisms of its effects on OSCC. Therefore, we aimed to investigate the mechanism of the suppressive effects of bovine LF (bLF) on the growth of OSCC cells. METHODS: In the current study, HSC2, HSC3, HSC4 and normal human oral keratinocytes (RT7) cell lines were tested with bLF 1, 10, and 100 μg/ml...
2018: PloS One
https://www.readbyqxmd.com/read/29374719/phase-ii-study-of-s-1-plus-trastuzumab-for-her2-positive-metastatic-breast-cancer-gbccsg-01
#15
Takaaki Fujii, Jun Horiguchi, Yasuhiro Yanagita, Yukio Koibuchi, Fumihiro Ikeda, Nobuyuki Uchida, Morihiko Kimura
AIM: Treatment strategies for patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) have significantly progressed. The use of trastuzumab, a monoclonal antibody targeting the HER2 (human epidermal growth factor 2) protein, in combination with chemotherapy improves survival in patients with HER2-positive breast cancer. S-1, an oral combination of fluorouracil derivatives, is widely used in Japan and is more convenient than intravenous drugs. However, little is known about the combination of S-1 and trastuzumab in patients with HER2-positive MBC...
February 2018: Anticancer Research
https://www.readbyqxmd.com/read/29366976/synergistic-interplay-between-the-two-major-bone-minerals-hydroxyapatite-and-whitlockite-nanoparticles-for-osteogenic-differentiation-of-mesenchymal-stem-cells
#16
Hao Cheng, Rosa Chabok, Xiaofei Guan, Aditya Chawla, Yuxiao Li, Ali Khademhosseini, Hae Lin Jang
The inorganic part of human bone is mainly composed of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) minerals, where the WH phase occupies up to 20-35% of total weight. These two bone minerals have different crystal structures and physicochemical properties, implying their distinguished role in bone physiology. However, until now, the biological significance of the presence of a certain ratio between HAP and WH in bone is unclear. To address this fundamental question, bone mimetic scaffolds are designed to encapsulate human mesenchymal stem cells (MSCs) for assessing their osteogenic activity depending on different ratios of HAP and WH...
January 20, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29364886/safety-and-pharmacokinetics-of-the-fc-modified-hiv-1-human-monoclonal-antibody-vrc01ls-a-phase-1-open-label-clinical-trial-in-healthy-adults
#17
Martin R Gaudinski, Emily E Coates, Katherine V Houser, Grace L Chen, Galina Yamshchikov, Jamie G Saunders, LaSonji A Holman, Ingelise Gordon, Sarah Plummer, Cynthia S Hendel, Michelle Conan-Cibotti, Margarita Gomez Lorenzo, Sandra Sitar, Kevin Carlton, Carolyn Laurencot, Robert T Bailer, Sandeep Narpala, Adrian B McDermott, Aryan M Namboodiri, Janardan P Pandey, Richard M Schwartz, Zonghui Hu, Richard A Koup, Edmund Capparelli, Barney S Graham, John R Mascola, Julie E Ledgerwood
BACKGROUND: VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb) against the CD4-binding site of the HIV-1 envelope glycoprotein (Env) that is currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial. VRC01LS is a modified version of VRC01, designed for extended serum half-life by increased binding affinity to the neonatal Fc receptor. METHODS AND FINDINGS: This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was conducted by the Vaccine Research Center (VRC) at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD)...
January 2018: PLoS Medicine
https://www.readbyqxmd.com/read/29357948/development-of-pd-1-and-pd-l1-inhibitors-as-a-form-of-cancer-immunotherapy-a-comprehensive-review-of-registration-trials-and-future-considerations
#18
REVIEW
Jun Gong, Alexander Chehrazi-Raffle, Srikanth Reddi, Ravi Salgia
Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014...
January 23, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29353766/development-and-validation-of-image-stimuli-for-emotion-elicitation-isee-a-novel-affective-pictorial-system-with-test-retest-repeatability
#19
Hanjoo Kim, Xin Lu, Michael Costa, Baris Kandemir, Reginald B Adams, Jia Li, James Z Wang, Michelle G Newman
The aim of this study was to develop a novel set of pictorial stimuli for emotion elicitation. The Image Stimuli for Emotion Elicitation (ISEE), are the first set of stimuli for which there was an unbiased initial selection method and with images specifically selected for high retest correlation coefficients and high agreement across time. In order to protect against a researcher's subjective bias in screening initial pictures, we crawled 10,696 images from the biggest image hosting website (Flickr.com) based on a computational selection method...
January 11, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29353042/ginkgolic-acid-induces-interplay-between-apoptosis-and-autophagy-regulated-by-ros-generation-in-colon-cancer
#20
Yuxia Liu, Bin Yang, Lirong Zhang, Xianling Cong, Zhen Liu, Yu Hu, Jing Zhang, Haixia Hu
Presently, developing effective anti-colon cancer drugs still remains to be important. Ginkgolic acids (GA), as a botanical drug extracted from the seed coat of Ginkgo biloba L., possess various bioactive properties. Our findings, for the first time, indicated that GA suppressed colon cancer cell proliferation, migration and invasion. GA led to cell death through G0/G1 phase arrest. In addition, apoptosis was significantly induced by GA treatment. The intrinsic apoptosis pathway was included, proved by the release of cytochrome c (Cyto-c) from the mitochondria into the cytosol...
January 15, 2018: Biochemical and Biophysical Research Communications
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