Annotated high citation abstracts

11879110

Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution.
C Arden Pope, Richard T Burnett, Michael J Thun, Eugenia E Calle, Daniel Krewski, Kazuhiko Ito, George D Thurston
(Department of Economics, Brigham Young University, 142 FOB, Provo, UT 84602, USA. cap3@email.byu.edu)
JAMA

cardiopulmonary questionnaire diet fraction were united_states found cause ongoing_prospective exposure adults less increased_risk each pollution society oxide--related smoking_history data an not ii an_important conclusive detailing prevention particles particle effects elevation mortality all-cause day-to-day individual with as coarse approximately_million death throughout assess weight through_december sulfur environmental have_been adverse health race however measures air_pollution was various in total_suspended associated 10-microg/m lung and long-term of linked metropolitan_areas combined education enrolled consistently marital_status combustion-related is which part respectively including alcohol_consumption age_sex relationship_between outcomes vital_status cancer risk for the approximately associations american studies height particulate_air between by occupational_exposures factor participants_completed

11784875

Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
Joan H Schiller, David Harrington, Chandra P Belani, Corey Langer, Alan Sandler, James Krook, Junming Zhu, David H Johnson
(University of Wisconsin Hospital and Clinics, Madison, USA.)
N. Engl. J. Med.

cisplatin we_conducted reference 1-year_survival toxicity cancer survival experimental did_not renal time gemcitabine one receive disease for was any in were the docetaxel regimen rate 2-year_survival associated lung confidence_interval months significantly_longer percent_confidence performance_status three advantage_over patients and with of regimens interval total response_rate cause grade cisplatin_plus offered randomized randomly_assigned treated determine_whether superior percent_percent assigned advanced_non-small-cell but vs between than eligible significant progression all median_survival paclitaxel significantly_lower study differ_significantly chemotherapy_regimens those carboplatin more_likely others percent none four to did or treatment had

12748244

Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected].
Masahiro Fukuoka, Seiji Yano, Giuseppe Giaccone, Tomohide Tamura, Kazuhiko Nakagawa, Jean-Yves Douillard, Yutaka Nishiwaki, Johan Vansteenkiste, Shinzoh Kudoh, Danny Rischin, Richard Eek, Takeshi Hora ...
(Fourth Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohnohigashi Osakasayama, Osaka 589, Japan. mfukuoka@med.kindai.ac.jp)
J. Clin. Oncol.

third-line_treatment ci provided multicenter_phase symptom_improvement ten were containing aes had efficacy two due receiving advanced_non-small-cell median tyrosine_kinase diarrhea tumor an_important second gefitinib among both clinically_meaningful response_rates wilmington_de 500-mg/d evaluable levels parallel-group withdrawal median_progression-free doses months grade with dose as tolerability adverse_events receive_either factor_receptor treatment_option similar once_daily two_hundred randomized_double-blind oral showed rates corrected mg/d who was in objective antitumor_activity lung confidence_interval patients and of novel drug-related platinum 250-mg drug-related_toxicities ii_trial skin_reactions zd1839_astrazeneca generally_mild consisted_mainly is chemotherapy_regimens advanced_nsclc respectively higher-dose_group 500-mg pretreated cancer survival one ae for symptom_relief at the more_frequent these profile times recorded nsclc overall_survival inhibitor randomly_assigned response epidermal_growth groups improvements gefitinib_iressa at_least symptom gefitinib_mg/d favorable this to

15329413

EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.
William Pao, Vincent Miller, Maureen Zakowski, Jennifer Doherty, Katerina Politi, Inderpal Sarkaria, Bhuvanesh Singh, Robert Heelan, Valerie Rusch, Lucinda Fulton, Elaine Mardis, Doris Kupfer, Richard ...
(Program in Cancer Biology and Genetics and Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. paow@mskcc.org)
Proc. Natl. Acad. Sci. U.S.A.

wild-type screened show_that gefitinib-refractory were containing exon_deletion point phosphotyrosine drug found cancers former egfr occur_frequently tyrosine_kinase because five concentrations phosphorylation data an related non-small_cell resected collectively_these distinct_subset gefitinib sequencing compared gene lifetime_never as_opposed levels from adenocarcinomas demonstrated tk_domain we that contrast 10-fold_lower with constructs cells whereas target occur diminished codon factor_receptor sensitive induced eight tumors analogous immunoblotting erlotinib-refractory similar most frequently mutation-positive egfr_tk 2-28 lysates was in various associated lung patients and of transiently_transfected tyrosine cigarettes reportedly who_smoked domain is which alterations gefitinib-sensitive comprise point_mutations kinase_inhibitor clinically_relevant mutations untreated current_smokers inhibited for at the smokers exon somatic_mutations within egfr_exons are types epidermal_growth undocumented seven no gefitinib_iressa erlotinib in-frame_deletions erlotinib_tarceva protein never_smokers none mutant to sensitivity or

15210113

Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis.
Jing Yang, Sendurai A Mani, Joana Liu Donaher, Sridhar Ramaswamy, Raphael A Itzykson, Christophe Come, Pierre Savagner, Inna Gitelman, Andrea Richardson, Robert A Weinberg
(Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.)
Cell

cell-cell_adhesion metastasis twist key_regulators cancer secondary e-cadherin-mediated mesenchymal_markers cell_motility search human metastasize breast mechanistic_link transcription_factor suggesting_that from model for site we in the activation associated that expression contributes lung epithelial-mesenchymal_transition induction master_regulator with and of found level invasive cells promoting cancers emt e-cadherin highly_metastatic disseminate lobular morphogenesis their_ability loss between carcinoma by mammary_gland high specifically_inhibits suppression mammary_carcinoma murine results have highly an is tumors correlated type which embryonic tumor essential_role ectopic_expression multistep_process establish during distant_organs plays_an to these_results primary infiltrating

15118073

Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
Thomas J Lynch, Daphne W Bell, Raffaella Sordella, Sarada Gurubhagavatula, Ross A Okimoto, Brian W Brannigan, Patricia L Harris, Sara M Haserlat, Jeffrey G Supko, Frank G Haluska, David N Louis, David ...
(Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston 02129, USA.)
N. Engl. J. Med.

vitro exposed were cultured lead molecular_mechanisms dramatic after small cancers those_who egfr often pocket tyrosine_kinase who_had activity substitutions not an enhanced primary gefitinib gain compared functional_consequences additive gene either inhibition from demonstrated screening with identified as cells been factor_receptor function such have eight most tumors responsiveness similar percent detected clustered_around targets heterozygous who however subgroup in atp-binding lung suggesting evaluated patients and increased of will nine gefitinib-responsive about proteins amino_acid correlate domain may which clinical rapid cancer mutations did_not identical observed for the these unknown confer_susceptibility somatic_mutations egfr_mutants multiple inhibitor expressed are response epidermal_growth by all seven we_searched growth_factor no factor specific signaling underlying in-frame_deletions identify none mutant to sensitivity or non-small-cell_lung

16014882

Erlotinib in previously treated non-small-cell lung cancer.
Frances A Shepherd, José Rodrigues Pereira, Tudor Ciuleanu, Eng Huat Tan, Vera Hirsh, Sumitra Thongprasert, Daniel Campos, Savitree Maoleekoonpiroj, Michael Smylie, Renato Martins, Maximiliano van Koo ...
(Department of Medical Oncology, University Health Network, Princess Margaret Hospital Site, University of Toronto, Canada.)
N. Engl. J. Med.

group we_conducted cancer survival iv they mg_daily double-blind_trial eligible_if placebo_group one from therapy receive for stratification stratified_according was in at the were failure number who_underwent prior_platinum-based months two performance_status toxic_effects second-line_chemotherapy patients with regimens of prolongs_survival and after dose response_rate inhibitor overall_survival randomly_assigned adjusted determine_whether chemotherapy received platinum-based_chemotherapy response prior center epidermal_growth factor_receptor randomized_placebo-controlled ratio first-line median_duration stage_iiib five because can_prolong placebo erlotinib chemotherapy_regimens median_age randomization respectively categories years percent less_than favor to hazard_ratio oral or progression-free_survival non-small-cell_lung discontinued had

16199517

Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.
Aravind Subramanian, Pablo Tamayo, Vamsi K Mootha, Sayan Mukherjee, Benjamin L Ebert, Michael A Gillette, Amanda Paulovich, Scott L Pomeroy, Todd R Golub, Eric S Lander, Jill P Mesirov
(Broad Institute of Massachusetts Institute of Technology and Harvard, 320 Charles Street, Cambridge, MA 02141, USA.)
Proc. Natl. Acad. Sci. U.S.A.

rna software_package location analysis_gsea two describe genomewide cancer-related sets yields here_we data an powerful method pathways focusing_on biological gene finds chromosomal from we embodied independent that although set_enrichment with where function such analysis notably extracting common gsea share_common in demonstrate expression lung genes single-gene and of freely_available information biologically little routine insights_into how biomedical_research database called analytical_method is leukemia several remains tool similarity data_sets including its cancer patient has_become survival for reveals together the studies defined major_challenge between regulation by interpreting groups power derives insight many initial or

15728811

EGFR mutation and resistance of non-small-cell lung cancer to gefitinib.
Susumu Kobayashi, Titus J Boggon, Tajhal Dayaram, Pasi A Jänne, Olivier Kocher, Matthew Meyerson, Bruce E Johnson, Michael J Eck, Daniel G Tenen, Balázs Halmos
(Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.)
N. Engl. J. Med.

report dramatic_responses gefitinib threonine-to-methionine showed his cancer patient mutations have_been structural gene relapse led who presence from in at the change that unknown lung anilinoquinazoline two case point_mutation patients with ultimately of and identified after dna studies gefitinib-responsive resulting resistance egfr complete_remission position drug_resistance advanced_non-small-cell specimens response epidermal_growth factor_receptor mutation revealed biochemical who_had amino_acid here_we inhibitors such have mechanism is most this tumor years second during to despite sequence biopsy_specimen egfr-mutant treatment non-small-cell_lung modeling

15766527

RAS is regulated by the let-7 microRNA family.
Steven M Johnson, Helge Grosshans, Jaclyn Shingara, Mike Byrom, Rich Jarvis, Angie Cheng, Emmanuel Labourier, Kristy L Reinert, David Brown, Frank J Slack
(Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.)
Cell

possible_mechanism seam regulate restricting multivulva where_they cancer mutations regulatory_rnas tissue human show_that time for implicated degrees let-7 in terminal_differentiation the utr p6 expression absent at that ras lower let-7_mirna lung genes times and contains of found multiple mir-84 humans let-60/ras sites overexpression are utrs tumors reporter_gene significantly_higher phenotype suppresses loss precursor micrornas_mirnas than largely manner here_we cell is contain allowing negatively_regulates member multicellular vulval lcss specifies activating fate normal protein complementary including

17167137

Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.
Alan Sandler, Robert Gray, Michael C Perry, Julie Brahmer, Joan H Schiller, Afshin Dowlati, Rogerio Lilenbaum, David H Johnson
(Vanderbilt University, Nashville, TN, USA. sandler@vanderbilt.edu)
N. Engl. J. Med.

were disease_progression point intolerable benefit cancers ecog_performance advanced_non-small-cell selected organ_function chemotherapy-plus-bevacizumab there median_survival paclitaxel brain_metastases treatment-related_deaths until carboplatin clinicaltrials_gov hazard_ratio bevacizumab_monoclonal nct00021060 evident compared response_rates oncology_group pulmonary_hemorrhage median_progression-free shown from vascular_endothelial months eastern_cooperative performance_status with administered_every as corresponding two_groups death bleeding ecog clinically tumors variety excluded antibody_against treatment rates iv was in number lung toxic_effects status patients and increased of chemotherapy squamous-cell significant addition six_cycles has_been has which between_july conducted respectively including group chemotherapy-alone cancer risk hemoptysis survival primary_end plus_bevacizumab bevacizumab recurrent for weeks the overall_survival randomized carboplatin_plus assigned alone paclitaxel_plus inadequate growth_factor stage_iiib study to or

17625570

Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
Manabu Soda, Young Lim Choi, Munehiro Enomoto, Shuji Takada, Yoshihiro Yamashita, Shunpei Ishikawa, Shin-ichiro Fujiwara, Hideki Watanabe, Kentaro Kurashina, Hisashi Hatanaka, Masashi Bando, Shoji Ohn ...
(Division of Functional Genomics, Jichi Medical University, Tochigi 329-0498, Japan.)
Nature

cancer its formation express fusion underlie comprising gene show_that kinase_alk human tumours harbouring subset from forced eml4-alk_fusion for was in molecular_events the these were that kinase echinoderm_microtubule-associated subcutaneous lung nude_mice promising_candidate foci generated as_well clinical_outcome portions within and of nsclc 3t3_fibroblasts patients cells mutations small achieved as protein-like_eml4 be improvement epidermal_growth likely by identification factor_receptor transcript molecular tyrosine_kinase out results culture here_we therapeutic_target is pathogenesis distinct transformed anaplastic_lymphoma chromosome_2p those our_data this may examined demonstrate_that diagnostic individuals marker to mouse inversion fusion_gene non-small-cell_lung transforming detected

17463250

MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling.
Jeffrey A Engelman, Kreshnik Zejnullahu, Tetsuya Mitsudomi, Youngchul Song, Courtney Hyland, Joon Oh Park, Neal Lindeman, Christopher-Michael Gale, Xiaojun Zhao, James Christensen, Takayuki Kosaka, Al ...
(Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.)
Science

gefitinib her3 cancer invariably_develop met inhibition for we was in the these effective that amplification activation lung had cell_line find describe thought as_well with and of resistance as cells their family promote cancers are egfr focal_amplification drug_resistance but specimens be receptors we_propose erbb-driven epidermal_growth factor_receptor treatments developed met_proto-oncogene activating_mutations causes by pi3k_pathway here_we driving specific signaling dependent tumors kinase_inhibitors erlotinib result thus restored may other erbb3 egfr/erbb met_amplification to gefitinib-sensitive sensitivity

19692680

Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
Tony S Mok, Yi-Long Wu, Sumitra Thongprasert, Chih-Hsin Yang, Da-Tong Chu, Nagahiro Saijo, Patrapim Sunpaweravong, Baohui Han, Benjamin Margono, Yukito Ichinose, Yutaka Nishiwaki, Yuichiro Ohe, Jin-Ji ...
(State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong. tony@clo.cuhk.edu.hk)
N. Engl. J. Med.

produce ci suggested_that acne were point significantly_longer open-label former those_who egfr superior selected pulmonary alopecia who_had noninferiority diarrhea area_under an also carboplatin tumor uncontrolled clinicaltrials_gov body-surface_area hazard_ratio primary progression-free_survival adenocarcinoma gefitinib among compared gene square_meter calculated we effects with dose as advanced whereas death adverse_events received intention-to-treat_population negative than factor_receptor nct00322452 neurotoxic have curve egfr_mutation among_nonsmokers superiority positive treatment previously_untreated showed rates who nonsmokers showing 12-month outcome carboplatin-paclitaxel was subgroup in number objective gefitinib_mg confidence_interval patients and of most_common strong_predictor east_asia mutation progression milliliter is plus_paclitaxel efficacious group mg_per first-line_treatment cancer its primary_end met receive presence for better at the phase would_be previous per_minute respect studies randomly_assigned per_day epidermal_growth rash study light_smokers this to initial

20573926

Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
Makoto Maemondo, Akira Inoue, Kunihiko Kobayashi, Shunichi Sugawara, Satoshi Oizumi, Hiroshi Isobe, Akihiko Gemma, Masao Harada, Hirohisa Yoshizawa, Ichiro Kinoshita, Yuka Fujita, Shoji Okinaga, Harut ...
(Miyagi Cancer Center, Miyagi, Japan.)
N. Engl. J. Med.

metastatic standard were disease_progression point significantly_longer efficacy safety_profile appetite_loss response_rate resulting egfr receiving highly_responsive advanced_non-small-cell selected first median who_had basis data not kinase_inhibitors known_about secondary_end hazard_ratio progression-free_survival gefitinib compared elevated levels higher median_progression-free from disease we improved that months as_well compares with as sensory_neuropathy death adverse_events received than sensitive factor_receptor first-line planned_interim analysis one_patient previously aminotransferase standard-chemotherapy points_included who c000000376 carboplatin-paclitaxel was in number confidence_interval lung toxic_effects patients and of interstitial little chemotherapy most_common vs how umin-ctr is neutropenia_anemia on group early_termination cancer egfr_tyrosine mutations such_as its survival primary_end receive for the overall_survival randomly_assigned but epidermal_growth rash study egfr_mutations acceptable_toxicity to died or

20979469

Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.
Eunice L Kwak, Yung-Jue Bang, D Ross Camidge, Alice T Shaw, Benjamin Solomon, Robert G Maki, Sai-Hong I Ou, Bruce J Dezube, Pasi A Jänne, Daniel B Costa, Marileila Varella-Garcia, Woo-Ho Kim, Thomas J ...
(Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. ekwak@partners.org)
N. Engl. J. Med.

continuing side_effects 6-month_progression-free confirmed were without mean fusion_genes drug after response_rate cancers tumor_shrinkage therapeutic_efficacy overall be exposure crizotinib_pf-02341066 cohort eligible median tyrosine_kinase data an eml4 tumor complete_response recommended alk_rearrangements instituted nct00585195 samples mild inhibition from disease adenocarcinomas we screening present small-molecule_inhibitor months early-phase_clinical duration with grade dose identified total alk_rearrangement inhibiting expanded adverse_events received advanced_alk-positive such oncogenic tumors most others_clinicaltrials treatment daily crizotinib probability kinase_alk established who had_stable was subgroup in dose_escalation mg_twice lung patients and explored of little gastrointestinal tended pfizer funded_by enrolled reached trial rearrangements cutoff alk those gov_number consisting cancer survival time representing presence therapy receive for estimated at the these orally_available approximately phase previous tobacco stable_disease are response partial_responses 28-day_cycles no younger_than study assessed resulted anaplastic_lymphoma clinical_trial to or non-small-cell_lung

22658128

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
Julie R Brahmer, Scott S Tykodi, Laura Q M Chow, Wen-Jen Hwu, Suzanne L Topalian, Patrick Hwu, Charles G Drake, Luis H Camacho, John Kauh, Kunle Odunsi, Henry C Pitot, Omid Hamid, Shailender Bhatia, R ...
(Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.)
N. Engl. J. Med.

mediates year vitro breast multicenter_phase confirmed ligands disease_progression investigators blockade more prolonged pancreatic cancers escalating_doses melanoma selected antibody-mediated be pd-l1 durable an related until tumor complete_response cancer--had among complete receptor preclinical_models disease we rate that with grade administered_every cells as total advanced death received programmed range could_be kilogram induced renal-cell administered ovarian others_clinicaltrials up treatment ranging_from patients--75 cycles role rates host_immune responses was bristol-myers_squibb in intravenous 6-week_cycles antitumor_activity evaluated toxic_effects patients and of pd-1 lasted immune_function funded_by regression median_duration trial body_weight enhances gov_number considered anti-pd-l1 including interactions_between days mg_per its patient cancer observed one therapy for coinhibitory weeks follow-up at the gastric partial_response stabilization occurred nct00729664 evade response antibody ability system at_least t-cell protein this february

22658127

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, Julie R Brahmer, Scott N Gettinger, David C Smith, David F McDermott, John D Powderly, Richard D Carvajal, Jeffrey A Sosman, Michael B Atkins, Philip D Leming, Davi ...
(Department of Surgery, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA. stopali1@jhmi.edu)
N. Engl. J. Med.

pd-l1-negative pd-l1_expression year castration-resistant_prostate were preliminary_data disease_progression blockade objective_responses three blocks more inhibitory after safety immune ligand_pd-l1 does_not melanoma pulmonary events_occurred causes each there five durable every_weeks an until can tumor complete_response deaths immunohistochemical_analysis nct00730639 pathway among toxicity complete response_rates receptor modulation from we four that doses grade with dose resistance total cells advanced death adverse_events overcome cumulative received adverse-event programmed assess pretreatment could_be kilogram renal-cell tumors specifically preclude others_clinicaltrials up treatment cycles role responses was bristol-myers_squibb in expression antitumor_activity performed evaluated patients consistent and of intratumoral pd-1 lasted drug-related_adverse cycle use funded_by enrolled pd-1-pd-l1 bms-936558 body_weight whom pd-l1-positive appear those gov_number on suggest anti-pd-1 relationship_between 8-week specimens_obtained mg_per cancer its produced observed receive one follow-up at the approximately profile occurred defined expressed response partial_responses through by antibody maximum_tolerated all immune-related no assessed