Annotated lowest relative variance abstracts

22710711

TGF-β stimulates Pyk2 expression as part of an epithelial-mesenchymal transition program required for metastatic outgrowth of breast cancer.
M K Wendt, B J Schiemann, J G Parvani, Y-H Lee, Y Kang, W P Schiemann
(Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.)
Oncogene

metastatic systemic_dissemination tgf-β show_that breast initiation dramatically stimulating epithelial-mesenchymal_transition stabilized upregulated their cancers transforming_growth pulmonary be invasiveness disseminated raising partially_dependent tyrosine_kinase across further activity upregulate murine isolates also ii tumor pyk2 primary compared secondary elevated levels lungs demonstrated from focal_adhesion we that contrast as_well with as cells promoting shared regulated_by e-cadherin necessary metastatic_cascade elements clonal cultures mediating such whether have tumors distinct thus orthotopic during delineated mda-mb-231_breast homolog mice arousing participates human reaction prevented but_not microenvironments was in expression differentially_expressed initiate and recapitulated proliferative of ex_vivo novel emt β1_integrin significantly driving is program on undergo genetic kinase_fak question stark growth cancer its outgrowth produced observed inhibited recurrent 3d-organotypic isolated_from for robustly iii lesions the inversely_related particularly mammary essential invasion pharmacological_inhibition dispensable are response form by programs ability manner fak pyk2-deficiency micrometastases mechanistically protein predictive this stimulated functions

17114358

A comparison of transcriptomic and metabonomic technologies for identifying biomarkers predictive of two-year rodent cancer bioassays.
Russell S Thomas, Thomas M O'Connell, Linda Pluta, Russell D Wolfinger, Longlong Yang, Todd J Page
(CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709-2137, USA. rthomas@ciit.org)
Toxicol. Sci.

when relatively microarray_analysis spectroscopy exposed standard they modes were without time_consuming two potential contaminants genotoxic removed rodent_bioassay discriminating nongenotoxic each rodent carcinogenic bioassays commercial can categories years evaluating animals discovering compare both among complete spectra carcinogen tissue from model reflect we that individual with additional accuracy identified could_discriminate analyzed as added following shared requiring economically million negative chemical-specific environmental expensive performing tumors exhibited subchronically analysis resonance_nmr relatively_low chemical_carcinogens less_than two-year maximum despite these_results positive metabolite carcinogenic_potential treatment showed role changes common efficiently suggesting_that metabonomic was altered in expression number poor lung performed cellular genes serum_samples increased and of action serum endogenous products 1h $2-4 whole liver play_central costing is on toward technologies biomarkers bioassay tissues transition control noncarcinogenic metabolites one for reduced the few chemicals statistical multiple are this_study but nuclear_magnetic between treatments different by classification transcriptomic all neoplasia groups genotoxicity

12820712

Tissue diagnosis of suspected lung cancer: selecting between bronchoscopy, transthoracic needle aspiration, and resectional biopsy.
Rex C W Yung
(Division of Pulmonary & Critical Care Medicine, Johns Hopkins University School of Medicine, Jefferson B1-170, 600 North Wolfe Street, Baltimore, MD 21287-8922, USA. ryung@jhmi.edu)
Respir Care Clin N Am

curative_surgery when helpful relatively spread quality falls new fellow-in-training frozen_section sputum standard pathological benign initiation cytotoxic surgery endobronchial permit obviating lower without even_if induction central_airways finding circumstances more must_be early cancers increasing ebbx safety superior worse open learning does_not pulmonary be refuses often cardiopulmonary_reserve preferably surgical pathologically guidance practitioners resectional there because retrieved detecting using not an collection also educational pneumonectomy diagnostic_yield can lobectomy tests tumor second pathology peripheral-based whenever examined primary diagnosis lesion need tbbx systems complete ib nodal_staging pursuing effusion tissue geared either affect careful_observation from goals least disease likelihood given staging larger improved anatomic_location involvement rate clinically_staged that rose procedural malignant_pleural radiographic_finding although as_well contrast be_helpful with submucosal potentially_resectable additional accuracy invasive as should thin coming then yet intraoperatively radiographic visible_endobronchial yield usually examination generations range bleeding can_be negative nodules maximize hands-on least_costly improve continued unexpected physician where diagnose may_be have getting such most insufficient thus highest similar bronchoscopy diagnostic_material possibly stage radiotherapy available definitive well_as positive treatment missing immediate ebna extrapulmonary smaller sample held extra especially who likelihood_ratio sequence sampling plans morbid autofluorescence_bronchoscopy smaller_than 18-fdg choose procedures in incidental_finding peribronchial suggestive nodal_stations diagnostic_procedures various ia poor lung performed information_about preceding technology intermediate candidate patients and of same will symptoms regional_nodal cases teaching specimen unless false_negative chemotherapy endoscopic if masses radiology-guided safest use comparable limitations cm techniques directed_toward justify unresectable adequate n3_nodal initially is may increases diagnostic which on synchronous greater approach furthermore accurate fellows ideally toward remains ct only including clinician resection_margins clinical biopsy principal confirm provide therefore applications initial lymph_nodes preferred rapid cancer patient such_as hemoptysis physiologic risk reduce staged bb time under suspected therapy for bronchoscopes ttna lymph_node mass at the lesions these appointment goal peripheral immediate_cytology cough severe central intraepithelial_neoplasia airways adequacy invasive_procedure issues supraclavicular good tbna ebus our are radiographic_evidence specificity sputum_cytology npv may_provide improvement limited pneumothoraces by different visible combine thus_avoiding ability all high subsequent type study procedure biopsies cell should_be address

21159143

Improving chemotherapy for patients with advanced non-small cell lung cancer.
Christian von Plessen
(Department of Pulmonary Medicine and Infectious Diseases, Hillerød Hospital, Hillerød, Denmark. cvplessen@gmail.com)
Clin Respir J

quality feedback metastatic optimal side_effects simple domains locally_advanced tools introduces slow were effective balanced efficacy documented describe three equal potential prolongs_survival increase their population found infrastructure only_minority palliative_intention often thesis elderly first perspective qualitative clinicians_need guidance conditions country it randomised_trial over_time reports beneficial amply unfortunately palliative highly not an knowledge_about microsystem investigate also using ii data can process non-small_cell projects while need report compared standardisation led simplifying higher improving populations general finally disease from platinum-based given we outpatient_clinics quality_indicators matrix temporal satisfaction inform health_care that definition spend performance_status as_well duration with aspects as three_courses usually associations_between macro been correlations treatment_option improve six_courses temporary clinically have findings development similar illustrates introduction industrialised_countries treatment microsystems application focus serve registries unselected changes staffing outpatient_clinic iv section established especially who needs used quantitative lot subgroup in geographical norwegian controlled_trials objective lung project patients and increased of explored largest public system-wide utilisation under-represented combines line most_common chemotherapy norway assessing relevant organisation use whole significant describes explore significant_associations strategic has has_been administrators is advanced_nsclc which on meanwhile furthermore approach measuring settings guide_clinicians suboptimal are_needed clinical qol value recruitment group outcomes controlled knowledge cancer patient by_means survival balance research experiences staff systematic time mortal can_serve under main variations third inspire for related improves_quality at the these prognosis achieve iii description be_cured life_qol incurable we_conclude delays beyond processes evaluation example nsclc studies aims our are we_investigated clinicians approaches national platinum-based_chemotherapy response improvement problems limited between through measurements different areas reporting trials logistic registry clinic system front_line results improvements study strategy units care performance oncology_outpatient clinical_trials this establish

12065068

A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer.
A Clegg, D A Scott, M Sidhu, P Hewitson, N Waugh
(Southampton Health Technology Assessments Centre, Wessex Institute for Health Research and Development, University of Southampton, UK.)
Health Technol Assess

cisplatin quality not_yet stopped they gbp problem omitted gentler mean three depend_on modest found increase pooling_data vinorelbine_plus early newer_drugs economic prolong_life insufficient_evidence median quality-adjusted_life-year it median_survival deaths systematic_literature costly being estimates among judgement from least reliant_on would_allow improved that cost-effectiveness next_few with drop extend following per_annum death range vinorelbine randomised_trials nhs have available older previously welcome comparisons single centres used calculations especially pound rather_than any models assumed patients and vary increased declining chemotherapy single-agent_gemcitabine constraints do_so pessimistic protocols treat benefits only lyg clinical supplemented balance gemcitabine_plus gemcitabine for better real-life reviewed newer different_scenarios these few side-effects pairwise_comparisons would_be well some might_be palliative_radiotherapy are response likely pooling study probably estimate effectiveness many or overcome when review_examines new comparator newer_agents without gives per_cent equal regimens best made each across an detrimental_effect years subject six need calculated viewed docetaxel effects regimen remain individual figures total treated loss life-year_gained comparators already implications applied others net have_been common assumptions pharmacists involves per_life-year however was in number poor lung direct_comparisons explored symptoms routine platinum would about less_expensive limitations making participation appear may strengthen which on several derive cancer cost_per patient research did_not staff untreated one wake condition only_few modelling shift vinorelbine_gemcitabine particularly beds generally incidence good care_bsc studies aims approaches through inpatient results summary hospital_admissions this cost-effective cost-saving sensitivity year costs_per practice surgery changing availability were apply second-line_chemotherapy be nearly_all depending_on there basis expenditure not related again everywhere very uncontrolled further_research lack diagnosis report single-agent_vinorelbine uk compared saved model greater_proportion failed forms european_community months duration variable because_they appearing than much_lower most indirect_comparisons order absence bsc wide_range cycles advent rates antiemetics staffing aided scenario costs lower-dose of fall continuation achieved smoking assessing most_common if government use gave gains conventionally provide outcomes first-line_treatment rest people such_as control under main therapy oncologists usa previous within example extensive expressed entirely published_data but non-financial between varied_depending all an_outpatient gained_lyg type treating care should_be workload their_respective versus non-small-cell_lung ways had needed spread caution referral efficacy will_be more drug recent_advances after their small infrastructure combinations overall life accepted stay less first satisfactory non-responders based_on because five paclitaxel data using generic activities still also incremental_cost choice likelihood given present admissions as proportion nurses first-line_chemotherapy million usually effect drugs leading_cause factors survive analysis relatively_low cured maximum particular treatment baseline modern much_more per_lyg cited cost against fortuitously giving but_not having announced performed conclusions attitudes reasonable reported trial has is other review best_supportive wales choosing involved survival might worthwhile receive england at the scottish impact known averaging into paclitaxel_plus by different trials diminution outpatient_visits

24128285

Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis.
Wen-guo Jiang, Xin-an Lu, Bo-yang Shang, Yan Fu, Sheng-hua Zhang, Daifu Zhou, Liang Li, Yi Li, Yongzhang Luo, Yong-su Zhen
(Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P, R, China. yluo@tsinghua.edu.cn.)
BMC Cancer

metastasis new vitro breast endostatin-ldp modality promising two efficacy drug endostatin-lidamycin 4t1-luc their share_similar obtained specimens es-ldm athymic_mice it further tumor_vasculature pg-be1 an also member extremely cytotoxicity tumor antiangiogenic es-based apo-protein lidamycin_ldm both es-ldp-ae binding_affinity consists assay moiety tissue higher fusion_protein respective demonstrated model potent we that structures show fundamental with inhibits cells tube enediyne energizing migration_invasion effect active carcinoma than upon tissue_microarray ldp-endostatin specifically designed development cell_proliferation targets we_reasoned evidently ldm experimental human chromophore antiangiogenesis used accumulated wound_healing vivo against was in provides es lung endostatin evaluated tube_formation chromoprotein and of block endothelial information ldp combined xenograft significant migration addition endostatin_es is may obtain which several disrupted furthermore antibiotics analogs enediyne-energized therefore capability endostatin-based growth non-covalently cancer formation antitumor es-ldp inhibited ae therapy for the animal_models some family antitumor_activities

12481412

Inhibition of phosphatidylinositol 3-kinase-Akt signaling blocks growth, promotes apoptosis, and enhances sensitivity of small cell lung cancer cells to chemotherapy.
Geoffrey W Krystal, Geoffrey Sulanke, Julie Litz
(Department of Medicine, Medical College of Virginia/Virginia Commonwealth University, McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA. gkrystal@hsc.vcu.edu)
Mol. Cancer Ther.

promotes stem_cell apoptosis panel igf-i-mediated confirmed bronchial_epithelial scf-mediated pi3k-akt transduction_pathways drug factor_scf inducing_apoptosis sensitivity promote persists akt mrc-5 induce pulmonary be fcs grown pi3k apoptotic activate largely components concentrations potently because it an using pi3k-akt_signaling also can factor_igf six pathway average primary pi3k-akt_pathway low both exogenous albeit kinetics levels be_useful inhibition from prominent we activation that scf as_well with resistance as signals proportion cells inhibiting death reversed rapidly receptors could_potentially very_sensitive effect could cell_lines induced may_be such insulin-like_growth factors inhibitors tumors constitutively_active relatively_low absence within_min alternative sclc fcs-induced its_ability doxycycline-regulated treatment igf-i role especially ld50 suggesting_that was in expression lung cell_line fades data_demonstrate and of inhibit completely_inhibited attained achieved occurs chemotherapy use important fibroblast significant potently_inhibited is promising_therapeutic which approach on respectively allele taken_together only kinase downstream_signal therefore myristolated potentiated growth cancer survival saturating did_not agents scf-induced pi3k_akt inhibited presence under for minimal itself at the ic50 microm these ca stresses enzymes etoposide multiple known phosphatidylinositol_3-kinase suppressed novel_therapeutic augmented determined ly294002 but different by growth_factor pi3k-related akt_signaling selective no mediated_by at_least dead signaling

21271351

Tumor microenvironment is multifaceted.
Catherine Sautès-Fridman, Julien Cherfils-Vicini, Diane Damotte, Sylvain Fisson, Wolf Hervé Fridman, Isabelle Cremer, Marie-Caroline Dieu-Nosjean
(Centre de Recherche des Cordeliers, Team 13, Institut National de la Santé et de la Recherche Médicale U872, 15 rue de l'Ecole de Médecine, Paris 75006, France. catherine.fridman@crc.jussieu.fr)
Cancer Metastasis Rev.

promotes langerhans_cells rna mucosal show_that ti-balt series organization tumor-induced initiation complex were cells--to two dc three after disease-specific_survival immunoprivileged immune cancers view multifaceted bacterial_infections intdc double-stranded host densities induces mature_dc here_we decreases highly data an opposite not also non-small_cell tumor immature_dc lymphoma inflammatory dc--and receptor tlr7/8 immune_response gene finally from fresh bronchus-associated_lymphoid prominent we activation that present structures th1_cytokine and/or with cytokines cells microenvironment occur act contact chemoresistance immunosuppressive_environment cell_lines stroma stimulation where may_allow tlr4 have strongly dynamic tumors early-stage_nsclc illustrates bacterial grow characteristic detected mice impaired follicular directly role work tumoral host_immune growing responses human infiltrated influence especially developing sampling microenvironments microorganisms in progress expression tertiary_lymphoid lung we_summarize patients and of interstitial linked exhibit bacteria immature ex_vivo chemotherapy eyes tlr-stimulated progression chemosensitivity migration tlr may which on suspect respectively derive anti-tumor_immune review only since subsets tissues growth cancer such_as protected survival produced adaptive for viral at the processing find invasion tlr3 some we_hypothesize hosts situ infiltration contains nsclc sites our are but depends_on develop local response cell_viability lc recent by context antigens system infectious cell arising external predictive

12414510

Proliferation, but not apoptosis, is associated with distinct beta-catenin expression patterns in non-small-cell lung carcinomas: relationship with adenomatous polyposis coli and G(1)-to S-phase cell-cycle regulators.
Athamassios Kotsinas, Konstantinos Evangelou, Panayotis Zacharatos, Christos Kittas, Vassilis G Gorgoulis
(Department of Histology-Embryology, Molecular Carcinogenesis Group, Medical School, University of Athens, Greece.)
Am. J. Pathol.

mechanisms first_time decreased relation apoptosis improper panel heterozygosity release evidence confirmed beta-cat-associated were advantage relationship three finding expression_profiles subcellular_localization found their best representative kip tightly_regulated be indicating patterns further ploidy_status activity accompanied_by data an western_blot our_data reflects examined cytoplasmic-nuclear aberrant cell-cycle low membranous coli_apc concurrently subcellular correlates kinetics levels apc gene samples nuclear_localization subset from immunohistochemical isoform four activation that effects contrast p27 with major beta-cat aspects functional additional whereas never_been component cytoplasmic loss diminished predominant p53 nuclear_accumulation correlations function regulators have indication may_be analysis_revealed most tumors nuclear analysis absence possibly homotypic cancerous experimental_models correlation gained silencing frequent vivo suggesting_that adhesion however above was in associated expression lung proliferation increased and of carcinomas cases degrade represent destruction e2f1 our_knowledge has is multitude result which on localization indicate_that other mcr taken_together ai pi dependent addressed beta-catenin involved tissues its moreover mutations behavior observed residual interestingly presence main reason most_important for inversely_related the these at exon phase checkpoints issues checkpoint mdm2 fractions have_shown /s-phase 90-kd providing overexpression our are we_investigated depends_on by ability adenomatous_polyposis cytoplasm study cell signaling region protein normal this suggest_that

19731971

A very public death: dying of mesothelioma and asbestos-related lung cancer (M/ARLC) in the Latrobe Valley, Victoria, Australia.
Susan F Lee, Margaret M O'Connor, Ysanne Chapman, Vicki Hamilton, Karen Francis
(School of Nursing and Midwifery, Monash University, Frankston, Victoria, Australia. Susan.Lee@med.monash.edu.au)
Rural Remote Health

brown burdensome barriers relation employer mesothelioma location referral rise m/arlc prevent compensation availability were investigated authority two three metropolitan focussing_on providers participants their dying people_who innovative former employers few_studies discomfort carer be often community continuity perceived wives it there coal_mining five reports because further data using related method indicates_that legal complicate years second their_families recommended fatal six lack average primary yallourn family_carers while historical diagnosis being feelings anger comprising males access female from seek_help anticipated rate that compounded volunteer although with industry major regional total yet identified roles interviewed as media burnout stakeholders been travel improve victoria have most town industries fear particular older illness filled strong treatment contracting station members services have_been common health acknowledgement used who asbestos needs stoic healthcare_providers however was having in latrobe_valley models almost_always number workers contributing associated lung poor health_services and loyalty of same largest ignored cases explored information area mill_workers declining service_provision will_continue at_home characterised reported fourth desire education betrayal addition significantly explore analysed mostly advice burdened warnings content is palliative_care key those which responds_poorly in-depth_interviews isolation only health_professional are_needed seek group locally effort late people cancer over risk experiences daughters experience reluctant required time manage rural for themes diagnosed their_carers at the these particularly communication complicated_by australia asbestos-related enablers issues delayed case some delays next times service comprehensive family aims expressed are die national local but electricity between gaps symptom_control by constant_comparative support unpredictability seven rurality strategies power study