Medicine and Health Sciences Commons^™

Phase 1b Trial Of Proteasome Inhibitor Carfilzomib With Irinotecan In Lung Cancer And Other Irinotecan-Sensitive Malignancies That Have Progressed On Prior Therapy (Onyx Ist Reference Number: Car-Ist-553), Susanne M. Arnold, Kari Chansky, Markos Leggas, Michael A. Thompson, John L. Villano, John Hamm, Rachel E. Sanborn, Glen J. Weiss, Gurkamal Chatta, Maria Q. Baggstrom

Markey Cancer Center Faculty Publications

Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function. Patients with stable asymptomatic brain metastases were eligible. Dose escalation utilized a standard 3 …

Obesity, Metabolic Factors And Risk Of Different Histological Types Of Lung Cancer: A Mendelian Randomization Study, Robert Carreras-Torres, Mattias Johansson, Philip C. Haycock, Kaitlin H. Wade, Caroline L. Relton, Richard M. Martin, George Davey Smith, Demetrius Albanes, Melinda C. Aldrich, Angeline Andrew, Susanne M. Arnold, Heike Bickeböller, Stig E. Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E. Caporaso, Chu Chen, David C. Christiani, Warren Jay Christian, Jennifer A. Doherty, Eric J. Duell, John K. Field, Michael P. A. Davies, Michael W. Marcus, Gary E. Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A. Kiemeney

Markey Cancer Center Faculty Publications

Background

Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.

Methods and findings

We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of …

Identification Of Prognostic Genes And Gene Sets For Early-Stage Non-Small Cell Lung Cancer Using Bi-Level Selection Methods, Suyan Tian, Chi Wang, Howard H. Chang, Jianguo Sun

Biostatistics Faculty Publications

In contrast to feature selection and gene set analysis, bi-level selection is a process of selecting not only important gene sets but also important genes within those gene sets. Depending on the order of selections, a bi-level selection method can be classified into three categories – forward selection, which first selects relevant gene sets followed by the selection of relevant individual genes; backward selection which takes the reversed order; and simultaneous selection, which performs the two tasks simultaneously usually with the aids of a penalized regression model. To test the existence of subtype-specific prognostic genes for non-small cell lung cancer …

Lkb1 Inactivation Drives Lung Cancer Lineage Switching Governed By Polycomb Repressive Complex 2, Haikuo Zhang, Christine Fillmore Brainson, Shohei Koyama, Amanda J. Redig, Ting Chen, Shuai Li, Manav Gupta, Carolina Garcia-De-Alba, Margherita Paschini, Grit S. Herter-Sprie, Gang Lu, Xin Zhang, Bryan P. Marsh, Stephanie J. Tuminello, Chunxiao Xu, Zhao Chen, Xiaoen Wang, Esra A. Akbay, Mei Zheng, Sangeetha Palakurthi, Lynette M. Sholl, Anil K. Rustgi, David J. Kwiatkowski, J. Alan Diehl, Adam J. Bass, Norman E. Sharpless, Glenn Dranoff, Peter S. Hammerman, Hongbin Ji, Nabeel Bardeesy, Dieter Saur, Hideo Watanabe, Carla F. Kim, Kwok-Kin Wong

Toxicology and Cancer Biology Faculty Publications

Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but …

Terminate Lung Cancer (Tlc) Study—A Mixed-Methods Population Approach To Increase Lung Cancer Screening Awareness And Low-Dose Computed Tomography In Eastern Kentucky, Roberto Cardarelli, David Reese, Karen L. Roper, Kathryn Cardarelli, Frances J. Feltner, Jamie L. Studts, Jennifer R. Knight, Debra Armstrong, Anthony D. Weaver, Dana Shaffer

Family and Community Medicine Faculty Publications

For low dose CT lung cancer screening to be effective in curbing disease mortality, efforts are needed to overcome barriers to awareness and facilitate uptake of the current evidence-based screening guidelines. A sequential mixed-methods approach was employed to design a screening campaign utilizing messages developed from community focus groups, followed by implementation of the outreach campaign intervention in two high-risk Kentucky regions. This study reports on rates of awareness and screening in intervention regions, as compared to a control region.

Disparities In Stage-Appropriate Therapy For Resectable Non-Small Cell Lung Cancer In Kentucky, Jeremiah T. Martin

Theses and Dissertations--Clinical Research Design

Lung cancer (NSCLC) is the leading cause of cancer related mortality. Lung cancer screening aims to detect treatable cancers, however survival advantage will only be seen with early and appropriate stage-directed therapy. This study aims to understand recent rates of therapy for early-stage lung cancer in Kentucky, and to explore potential sources of disparities in treatment and outcomes. A Kentucky Cancer Registry query was performed of all NSCLC cases treated in the state from 2005-2014. Of 39,763 lung cancer patients, 10,622 were clinically operable. Of these, overall 40% did not receive surgery, while 16% did not receive any stage-appropriate local …