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https://www.readbyqxmd.com/read/28230005/current-mechanism-of-acquired-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-updated-therapy-strategies-in-human-nonsmall-cell-lung-cancer
#1
REVIEW
Kaixian Zhang, Qianqian Yuan
Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28228226/-progress-of-pd-1-pd-l1-inhibitors-in-non-small-cell-lung-cancer
#2
Zhansheng Jiang, Zhanyu Pan, Xiubao Ren
Pembrolizumab, an inhibitor target programmed death 1 (PD-1), was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC). It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1) inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR) was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS) with single pembrolizumab in first line was nearly 1 year (10...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28227444/novel-3d-coaxial-flow-focusing-nozzle-device-for-the-production-of-monodispersed-collagen-microspheres
#3
Sravani Jaligama, Po-Jung Huang, Jun Kameoka, Sravani Jaligama, Po-Jung Huang, Jun Kameoka, Jun Kameoka, Sravani Jaligama, Po-Jung Huang
We have developed a 3D coaxial flow-focusing nozzle device for the mass production of monodispersed collagen microspheres and chemically crosslinked them using EDC (1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide) and N-hydroxysuccinimide (NHS). The size of the microspheres was varied between 200 μm and 600 μm by adjusting the ratio of the flow rates of the dispersed and continuous phases. MDA231-GFP cells were attached to the surface of these particles and their viability was investigated. Because they are comprised of a natural biomaterial, these collagen microspheres will have numerous applications, including bone regeneration scaffolds for tissue engineering and analyses of cancer cell interactions in a 3D environment...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226338/opioids-inhibit-angiogenesis-in-a-chorioallantoic-membrane-model
#4
Haktan Karaman, Adnan Tufek, Evren Karaman, Orhan Tokgoz
BACKGROUND: Angiogenesis is an important characteristic of cancer. Switching from the avascular phase to the vascular phase is a necessary process for tumor growth. Therefore, research in cancer treatment has focused on angiogenesis as a drug target. Despite the widespread use of opioids to treat pain in patients with cancer, little is known about the effect of these drugs on vascular endothelium and angiogenesis. OBJECTIVES: We aimed to investigate the efficacies of morphine, codeine, and tramadol in 3 different concentrations on angiogenesis in hens' eggs...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28226332/responsible-safe-and-effective-prescription-of-opioids-for-chronic-non-cancer-pain-american-society-of-interventional-pain-physicians-asipp-guidelines
#5
Laxmaiah Manchikanti, Adam M Kaye, Nebojsa Nick Knezevic, Heath McAnally, Konstantin Slavin, Andrea M Trescot, Susan Blank, Vidyasagar Pampati, Salahadin Abdi, Jay S Grider, Alan D Kaye, Kavita N Manchikanti, Harold Cordner, Christopher G Gharibo, Michael E Harned, Sheri L Albers, Sairam Atluri, Steve M Aydin, Sanjay Bakshi, Robert L Barkin, Ramsin M Benyamin, Mark V Boswell, Ricardo M Buenaventura, Aaron K Calodney, David L Cedeno, Sukdeb Datta, Timothy R Deer, Bert Fellows, Vincent Galan, Vahid Grami, Hans Hansen, Standiford Helm Ii, Rafael Justiz, Dhanalakshmi Koyyalagunta, Yogesh Malla, Annu Navani, Kent H Nouri, Ramarao Pasupuleti, Nalini Sehgal, Sanford M Silverman, Thomas T Simopoulos, Vijay Singh, Daneshvari R Solanki, Peter S Staats, Ricardo Vallejo, Bradley W Wargo, Arthur Watanabe, Joshua A Hirsch
BACKGROUND: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28224367/novel-treatment-with-intraperitoneal-moc31pe-immunotoxin-in-colorectal-peritoneal-metastasis-results-from-the-immunopeca-phase-1-trial
#6
Ida S Frøysnes, Yvonne Andersson, Stein G Larsen, Ben Davidson, Janne-Merete Torset Øien, Kari Hauge Olsen, Karl-Erik Giercksky, Lars Julsrud, Øystein Fodstad, Svein Dueland, Kjersti Flatmark
BACKGROUND: MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC...
February 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28224267/selection-of-dna-aptamers-for-extra-cellular-domain-of-human-epidermal-growth-factor-receptor-2-to-detect-her2-positive-carcinomas
#7
A Sett, B B Borthakur, U Bora
BACKGROUND: Human epidermal growth factor receptor 2 (Her2, an orphan receptor of ErbB family) is considered as an important biomarker as it plays a key role in the development and progression of aggressive types of breast, ovarian, stomach and gastric cancer. In the present study, we developed novel DNA aptamers against the extra-cellular domain (ECD) of Her2 protein for detection of Her2-positive carcinomas. METHODS: We cloned and expressed Her2-ECD protein in E...
February 21, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28223274/long-term-responders-on-olaparib-maintenance-in-high-grade-serous-ovarian-cancer-clinical-and-molecular-characterization
#8
Stephanie Lheureux, Zhongwu Lai, Brian A Dougherty, Sarah Runswick, Darren Hodgson, Kirsten M Timms, Jerry S Lanchbury, Stanley B Kaye, Charlie Gourley, David D L Bowtell, Elise C Kohn, Clare L Scott, Ursula A Matulonis, Tony Panzarella, Katherine Karakasis, Julia V Burnier, Blake Gilks, Mark J O'Connor, Jane D Robertson, Jonathan Ledermann, J Carl Barrett, Tony W Ho, Amit M Oza
PURPOSE: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. EXPERIMENTAL DESIGN: A comparative molecular analysis of Study 19 (NCT00753545), a randomized Phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28223142/glucose-capped-silver-nanoparticles-induce-cell-cycle-arrest-in-hela-cells
#9
Elisa Panzarini, Stefania Mariano, Cristian Vergallo, Elisabetta Carata, Gian Maria Fimia, Francesco Mura, Marco Rossi, Viviana Vergaro, Giuseppe Ciccarella, Marco Corazzari, Luciana Dini
This study aims to determine the interaction (uptake and biological effects on cell viability and cell cycle progression) of glucose capped silver nanoparticles (AgNPs-G) on human epithelioid cervix carcinoma (HeLa) cells, in relation to amount, 2×10(3) or 2×10(4) NPs/cell, and exposure time, up to 48h. The spherical and well dispersed AgNPs (30±5nm) were obtained by using glucose as reducing agent in a green synthesis method that ensures to stabilize AgNPs avoiding cytotoxic soluble silver ions Ag(+) release...
February 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28223062/nivolumab-for-previously-treated-unresectable-metastatic-anal-cancer-nci9673-a-multicentre-single-arm-phase-2-study
#10
Van K Morris, Mohamed E Salem, Halla Nimeiri, Syma Iqbal, Preet Singh, Kristen Ciombor, Blase Polite, Dustin Deming, Emily Chan, James L Wade, Lianchun Xiao, Tanios Bekaii-Saab, Luis Vence, Jorge Blando, Armeen Mahvash, Wai Chin Foo, Chimela Ohaji, Manolo Pasia, Gail Bland, Aki Ohinata, Jane Rogers, Amir Mehdizadeh, Kimberly Banks, Richard Lanman, Robert A Wolff, Howard Streicher, James Allison, Padmanee Sharma, Cathy Eng
BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. METHODS: We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA...
February 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28222395/technetium-99m-radiolabeled-paclitaxel-as-an-imaging-probe-for-breast-cancer-in-vivo
#11
Liziane O F Monteiro, Renata S Fernandes, Luciano C Castro, Valbert N Cardoso, Mônica C Oliveira, Danyelle M Townsend, Alice Ferretti, Domenico Rubello, Elaine A Leite, André L B de Barros
The high incidence and mortality of breast cancer supports efforts to develop innovative imaging probes to effectively diagnose, evaluate the extent of the tumor, and predict the efficacy of tumor treatments while concurrently and selectively delivering anticancer agents to the cancer tissue. In the present study we described the preparation of technetium-99m ((99m)Tc)-labeled paclitaxel (PTX) and evaluated its feasibility as a radiotracer for breast tumors (4T1) in BALB/c mice. Thin Layer Chromatography (TLC) was used to determine the radiochemical purity and in vitro stability of (99m)Tc-PTX...
February 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28222318/design-synthesis-biological-evaluation-and-molecular-modeling-study-of-novel-macrocyclic-bisbibenzyl-analogues-as-antitubulin-agents
#12
Bin Sun, Lin Li, Qing-Wen Hu, Hong-Bo Zheng, Hui Tang, Huan-Min Niu, Hui-Qing Yuan, Hong-Xiang Lou
A series of macrocyclic bisbibenzyls with novel skeletons was designed, synthesized, and evaluated for antiproliferative activity against five anthropic cancer cell lines. Among these novel molecules, compound 47 displayed excellent anticancer activity against HeLa, k562, HCC1428, HT29 and PC-3/Doc cell lines, with IC50 values ranging from of 1.51 μM-5.51 μM, which were more potent than the parent compound, marchantin C. Compounds 44 and 55 with novel bisbibenzyl skeletons also exhibited significantly improved antiproliferative potency...
February 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28222309/gemcitabine-erlotinib-versus-gemcitabine-erlotinib-capecitabine-in-the-first-line-treatment-of-patients-with-metastatic-pancreatic-cancer-efficacy-and-safety-results-of-a-phase-iib-randomised-study-from-the-spanish-ttd-collaborative-group
#13
Antonio Irigoyen, Javier Gallego, Carmen Guillén Ponce, Ruth Vera, Vega Iranzo, Inmaculada Ales, Sara Arévalo, Aleydis Pisa, Marta Martín, Antonieta Salud, Esther Falcó, Alberto Sáenz, José Luis Manzano Mozo, Gema Pulido, Joaquina Martínez Galán, Roberto Pazo-Cid, Fernando Rivera, Teresa García García, Olbia Serra, Eva Ma Fernández Parra, Alicia Hurtado, Ma José Gómez Reina, Luis Jesús López Gomez, Esther Martínez Ortega, Manuel Benavides, Enrique Aranda
BACKGROUND: Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC. PATIENTS AND METHODS: Previously untreated mPC patients were randomised to receive G (1000 mg/m(2), days 1, 8, 15) + E (100 mg/day, days 1-28) + C (1660 mg/m(2), days 1-21) or GE, q4 weeks, until progression or unacceptable toxicity...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28222251/prognostic-methylation-markers-for-overall-survival-in-cytogenetically-normal-patients-with-acute-myeloid-leukemia-treated-on-swog-trials
#14
Xiaoyu Qu, Megan Othus, Jerry Davison, Yu Wu, Liying Yan, Soheil Meshinchi, Fabiana Ostronoff, Elihu H Estey, Jerry P Radich, Harry P Erba, Frederick R Appelbaum, Min Fang
BACKGROUND: Aberrant DNA methylation is known to occur in patients with acute myeloid leukemia (AML), whereas methylation signatures and prognostic markers have been proposed. The objective of the current study was to evaluate all CpG sites of the genome and identify prognostic methylation markers for overall survival in patients with AML with normal karyotype (AML-NK). METHODS: AML-NK samples from 7 SWOG trials were analyzed using a novel genome-wide approach called "CHARMcox" (comprehensive high-throughput array-based relative methylation analysis combined with the Cox proportional hazards model) controlling for known clinical covariates...
February 21, 2017: Cancer
https://www.readbyqxmd.com/read/28222073/a-phase-i-study-of-intravenous-and-oral-rucaparib-in-combination-with-chemotherapy-in-patients-with-advanced-solid-tumours
#15
Richard H Wilson, Tr Jeffry Evans, Mark R Middleton, L Rhoda Molife, James Spicer, Veronique Dieras, Patricia Roxburgh, Heidi Giordano, Sarah Jaw-Tsai, Sandra Goble, Ruth Plummer
BACKGROUND: This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly(ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours. METHODS: Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide. Subsequently, the study was amended to focus on oral rucaparib (once daily, days 1-14) combined with carboplatin (day 1) in 21-day cycles...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28222072/discrepancies-in-central-review-re-testing-of-patients-with-er-positive-and-her2-negative-breast-cancer-in-the-optima-prelim-randomised-clinical-trial
#16
S E Pinder, A F Campbell, J M S Bartlett, A Marshall, D Allen, M Falzon, J A Dunn, A Makris, L Hughes-Davies, R C Stein
BACKGROUND: There is limited data on results of central re-testing of samples from patients with invasive breast cancer categorised in their local hospital laboratories as oestrogen receptor (ER) positive and human epidermal growth factor receptor homologue 2 (HER2) negative. METHODS: The Optimal Personalised Treatment of early breast cancer usIng Multiparameter Analysis preliminary study (OPTIMA prelim) was the feasibility phase of a randomised controlled trial to validate the use of multiparameter assay-directed chemotherapy decisions in the UK National Health Service (NHS)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28222071/combination-of-the-histone-deacetylase-inhibitor-vorinostat-with-bevacizumab-in-patients-with-clear-cell-renal-cell-carcinoma-a-multicentre-single-arm-phase-i-ii-clinical-trial
#17
Roberto Pili, Glenn Liu, Sreenivasulu Chintala, Hendrick Verheul, Shabnam Rehman, Kristopher Attwood, Martin A Lodge, Richard Wahl, James I Martin, Kiersten Marie Miles, Silvia Paesante, Remi Adelaiye, Alejandro Godoy, Serina King, James Zwiebel, Michael A Carducci
BACKGROUND: Class II histone deacetylase (HDAC) inhibitors induce hypoxia-inducible factor-1 and -2α degradation and have antitumour effects in combination with vascular endothelial growth factor (VEGF) inhibitors. In this study, we tested the safety and efficacy of the HDAC inhibitor vorinostat and the VEGF blocker bevacizumab in metastatic clear-cell renal cell carcinoma (ccRCC) patients previously treated with different drugs including sunitinib, sorafenib, axitinib, interleukin-2, interferon, and temsirolimus...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28221867/osimertinib-in-pretreated-t790m-positive-advanced-non-small-cell-lung-cancer-aura-study-phase-ii-extension-component
#18
James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Suresh S Ramalingam, Lecia V Sequist, Wu-Chou Su, Sang-We Kim, Joo-Hang Kim, David Planchard, Enriqueta Felip, Fiona Blackhall, Daniel Haggstrom, Kiyotaka Yoh, Silvia Novello, Kathryn Gold, Tomonori Hirashima, Chia-Chi Lin, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Pasi A Jänne
Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#19
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28220020/randomized-phase-ii-study-of-ramucirumab-or-icrucumab-in-combination-with-capecitabine-in-patients-with-previously-treated-locally-advanced-or-metastatic-breast-cancer
#20
Linda T Vahdat, Rachel Layman, Denise A Yardley, William Gradishar, Mohamad A Salkeni, Anil Abraham Joy, Agustin A Garcia, Patrick Ward, James Khatcheressian, Joseph Sparano, Gladys Rodriguez, Shande Tang, Ling Gao, Rita P Dalal, John Kauh, Kathy Miller
BACKGROUND: Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and -2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced or metastatic breast cancer. METHODS: Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m(2) orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM + CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR + CAP) every 21 days...
February 20, 2017: Oncologist
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