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358 results on '"Dragnev, Konstantin H"'

2. Efficacy and safety of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in combination with pembrolizumab in patients with KRAS G12C-mutant advanced NSCLC.

Author

Fujiwara, Yutaka, Burns, Timothy F., Dragnev, Konstantin H., Murciano-Goroff, Yonina R., Lee, Dae Ho, Hollebecque, Antoine, Koyama, Takafumi, Cassier, Philippe Alexandre, Italiano, Antoine, Heist, Rebecca Suk, Han, Ji-Youn, Deming, Dustin A., Spira, Alexander I., Sabari, Joshua K., Chisamore, Michael Jon, Fink, Aaron Alan, Chen, Aaron, Willard, Melinda D., Oxnard, Geoffrey R., and Ammakkanavar, Natraj Reddy

Published
2024
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3. Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor response in metastatic renal cell carcinoma

Author

Brown, Landon C, Zhu, Jason, Desai, Kunal, Kinsey, Emily, Kao, Chester, Lee, Yong Hee, Pabla, Sarabjot, Labriola, Matthew K, Tran, Jennifer, Dragnev, Konstantin H, Tafe, Laura J, Dayyani, Farshid, Gupta, Rajan T, McCall, Shannon, George, Daniel J, Glenn, Sean T, Nesline, Mary K, George, Saby, Zibelman, Matthew, Morrison, Carl, Ornstein, Moshe C, and Zhang, Tian

Subjects
Cancer, Clinical Research, Immunization, Kidney Disease, Vaccine Related, Prevention, Genetics, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Humans, B7-H1 Antigen, Carcinoma, Renal Cell, CTLA-4 Antigen, Forkhead Transcription Factors, Immune Checkpoint Inhibitors, Ipilimumab, Kidney Neoplasms, Nivolumab, Retrospective Studies, Tumor Microenvironment, Immunotherapy, Tumor Biomarkers, Gene Expression Profiling
Abstract

BackgroundImmunotherapy combinations including ipilimumab and nivolumab are now the standard of care for untreated metastatic renal cell carcinoma (mRCC). Biomarkers of response are lacking to predict patients who will have a favorable or unfavorable response to immunotherapy. This study aimed to use the OmniSeq transcriptome-based platform to develop biomarkers of response to immunotherapy.MethodsTwo cohorts of patients were retrospectively collected. These included an investigational cohort of patients with mRCC treated with immune checkpoint inhibitor therapy from five institutions, and a subsequent validation cohort of patients with mRCC treated with combination ipilimumab and nivolumab from two institutions (Duke Cancer Institute and Cleveland Clinic Taussig Cancer Center). Tissue-based RNA sequencing was performed using the OmniSeq Immune Report Card on banked specimens to identify gene signatures and immune checkpoints associated with differential clinical outcomes. A 5-gene expression panel was developed based on the investigational cohort and was subsequently evaluated in the validation cohort. Clinical outcomes including progression-free survival (PFS) and overall survival (OS) were extracted by retrospective chart review. Objective response rate (ORR) was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1.ResultsThe initial investigation cohort identified 86 patients with mRCC who received nivolumab (80%, 69/86), ipilimumab/nivolumab (14%, 12/86), or pembrolizumab (6%, 5/86). A gene expression score was created using the top five genes found in responders versus non-responders (FOXP3, CCR4, KLRK1, ITK, TIGIT). The ORR in patients with high gene expression (GEhigh) on the 5-gene panel was 29% (14/48), compared with low gene expression (GElow) 3% (1/38, χ2 p=0.001). The validation cohort was comprised of 62 patients who received ipilimumab/nivolumab. There was no difference between GEhigh and GElow in terms of ORR (44% vs 38.5%), PFS (HR 1.5, 95% CI 0.58 to 3.89), or OS (HR 0.96, 95% CI 0.51 to 1.83). Similarly, no differences in ORR, PFS or OS were observed when patients were stratified by tumor mutational burden (high=top 20%), PD-L1 (programmed death-ligand 1) expression by immunohistochemistry or RNA expression, or CTLA-4 (cytotoxic T-lymphocytes-associated protein 4) RNA expression. The International Metastatic RCC Database Consortium (IMDC) risk score was prognostic for OS but not PFS.ConclusionA 5-gene panel that was associated with improved ORR in a predominantly nivolumab monotherapy population of patients with mRCC was not predictive for radiographic response, PFS, or OS among patients with mRCC treated with ipilimumab and nivolumab.

Published
2022

5. SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.

Author

Reckamp, Karen L., primary, Redman, Mary Weber, additional, Dragnev, Konstantin H., additional, Iams, Wade Thomas, additional, Henick, Brian S., additional, Miao, Jieling, additional, LeBlanc, Michael Leo, additional, Carrizosa, Daniel R., additional, Herbst, Roy S., additional, Blanke, Charles D., additional, and Gray, Jhanelle E., additional

Published
2024
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6. Pragmaticism in Cancer Clinical Trials

Author

Sankar, Kamya, primary, Redman, Mary W., additional, Dragnev, Konstantin H., additional, Henick, Brian S., additional, Iams, Wade T., additional, Blanke, Charles D., additional, Herbst, Roy S., additional, Gray, Jhanelle E., additional, and Reckamp, Karen L., additional

Published
2024
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10. Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.

Author

Bouley, Stephanie J., Grassetti, Andrew V., Allaway, Robert J., Wood, Matthew D., Hou, Helen W., Burdon Dasbach, India R., Seibel, William, Wu, Jimmy, Gerber, Scott A., Dragnev, Konstantin H., Walker, James A., and Sanchez, Yolanda

Subjects
SCHWANNOMAS, BREAST, GENETIC testing, GENETIC disorders
Abstract

Neurofibromatosis type 1, a genetic disorder caused by pathogenic germline variations in NF1, predisposes individuals to the development of tumors, including cutaneous and plexiform neurofibromas (CNs and PNs), optic gliomas, astrocytomas, juvenile myelomonocytic leukemia, high-grade gliomas and malignant peripheral nerve sheath tumors (MPNSTs), which are chemotherapy- and radiation-resistant sarcomas with poor survival. Loss of NF1 also occurs in sporadic tumors, such as glioblastoma (GBM), melanoma, breast, ovarian and lung cancers. We performed a high-throughput screen for compounds that were synthetic lethal with NF1 loss, which identified several leads, including the small molecule Y102. Treatment of cells with Y102 perturbed autophagy, mitophagy and lysosome positioning in NF1-deficient cells. A dual proteomics approach identified BLOC-one-related complex (BORC), which is required for lysosome positioning and trafficking, as a potential target of Y102. Knockdown of a BORC subunit using siRNA recapitulated the phenotypes observed with Y102 treatment. Our findings demonstrate that BORC might be a promising therapeutic target for NF1-deficient tumors. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Supplementary Table S2 from Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non–Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042)

Author

Gadgeel, Shirish M., primary, Miao, Jieling, primary, Riess, Jonathan W., primary, Moon, James, primary, Mack, Philip C., primary, Gerstner, Gregory J., primary, Burns, Timothy F., primary, Taj, Asma, primary, Akerley, Wallace L., primary, Dragnev, Konstantin H., primary, Laudi, Noel, primary, Redman, Mary W., primary, Gray, Jhanelle E., primary, Gandara, David R., primary, and Kelly, Karen, primary

Published
2023
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19. Data from Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non–Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042)

Author

Gadgeel, Shirish M., primary, Miao, Jieling, primary, Riess, Jonathan W., primary, Moon, James, primary, Mack, Philip C., primary, Gerstner, Gregory J., primary, Burns, Timothy F., primary, Taj, Asma, primary, Akerley, Wallace L., primary, Dragnev, Konstantin H., primary, Laudi, Noel, primary, Redman, Mary W., primary, Gray, Jhanelle E., primary, Gandara, David R., primary, and Kelly, Karen, primary

Published
2023
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20. Supplementary Figure S1 from Phase II Study of Docetaxel and Trametinib in Patients with KRAS Mutation Positive Recurrent Non–Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042)

Author

Gadgeel, Shirish M., primary, Miao, Jieling, primary, Riess, Jonathan W., primary, Moon, James, primary, Mack, Philip C., primary, Gerstner, Gregory J., primary, Burns, Timothy F., primary, Taj, Asma, primary, Akerley, Wallace L., primary, Dragnev, Konstantin H., primary, Laudi, Noel, primary, Redman, Mary W., primary, Gray, Jhanelle E., primary, Gandara, David R., primary, and Kelly, Karen, primary

Published
2023
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21. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author

Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus FA., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Heijden, Erik H. F. M. van der, Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma’en, Timens, Wim, Artigas, María Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher I.

Published
2020
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23. Phase II study of docetaxel and trametinib in patients with KRAS mutation positive recurrent non-small cell lung cancer (NSCLC) (SWOG S1507, NCT-02642042)

Author

Gadgeel, Shirish M., primary, Miao, Jieling, additional, Riess, Jonathan W., additional, Moon, James, additional, Mack, Philip C., additional, Gerstner, Gregory J., additional, Burns, Timothy F., additional, Taj, Asma, additional, Akerley, Wallace L., additional, Dragnev, Konstantin H., additional, Laudi, Noel, additional, Redman, Mary W., additional, Gray, Jhanelle E., additional, Gandara, David R., additional, and Kelly, Karen, additional

Published
2023
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24. Clinical Genotyping of Non–Small Cell Lung Cancers Using Targeted Next-Generation Sequencing: Utility of Identifying Rare and Co-mutations in Oncogenic Driver Genes

Author

Tafe, Laura J., Pierce, Kirsten J., Peterson, Jason D., de Abreu, Francine, Memoli, Vincent A., Black, Candice C., Pettus, Jason R., Marotti, Jonathan D., Gutmann, Edward J., Liu, Xiaoying, Shirai, Keisuke, Dragnev, Konstantin H., Amos, Christopher I., and Tsongalis, Gregory J.

Published
2016
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28. Data from Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models

Author

Dragnev, Konstantin H., primary, Ma, Tian, primary, Cyrus, Jobin, primary, Galimberti, Fabrizio, primary, Memoli, Vincent, primary, Busch, Alexander M., primary, Tsongalis, Gregory J., primary, Seltzer, Marc, primary, Johnstone, David, primary, Erkmen, Cherie P., primary, Nugent, William, primary, Rigas, James R., primary, Liu, Xi, primary, Freemantle, Sarah J., primary, Kurie, Jonathan M., primary, Waxman, Samuel, primary, and Dmitrovsky, Ethan, primary

Published
2023
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29. Data from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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30. Supplementary Figure S1 from Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models

Author

Dragnev, Konstantin H., primary, Ma, Tian, primary, Cyrus, Jobin, primary, Galimberti, Fabrizio, primary, Memoli, Vincent, primary, Busch, Alexander M., primary, Tsongalis, Gregory J., primary, Seltzer, Marc, primary, Johnstone, David, primary, Erkmen, Cherie P., primary, Nugent, William, primary, Rigas, James R., primary, Liu, Xi, primary, Freemantle, Sarah J., primary, Kurie, Jonathan M., primary, Waxman, Samuel, primary, and Dmitrovsky, Ethan, primary

Published
2023
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31. Supplementary Figure 2 from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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32. Supplementary Figure 1 from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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33. Supplementary Figure Legend from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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34. Supplementary Figure 3 from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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36. Supplementary Data from Uncovering Growth-Suppressive MicroRNAs in Lung Cancer

Author

Liu, Xi, primary, Sempere, Lorenzo F., primary, Galimberti, Fabrizio, primary, Freemantle, Sarah J., primary, Black, Candice, primary, Dragnev, Konstantin H., primary, Ma, Yan, primary, Fiering, Steven, primary, Memoli, Vincent, primary, Li, Hua, primary, DiRenzo, James, primary, Korc, Murray, primary, Cole, Charles N., primary, Bak, Mads, primary, Kauppinen, Sakari, primary, and Dmitrovsky, Ethan, primary

Published
2023
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38. Uncovering Novel Targets for Cancer Chemoprevention

Author

Dragnev, Konstantin H., Feng, Qing, Ma, Yan, Shah, Sumit J., Black, Candice, Memoli, Vincent, Nugent, William, Rigas, James R., Kitareewan, Sutisak, Freemantle, Sarah, Dmitrovsky, Ethan, Schlag, P. M., editor, Senn, H. -J., editor, Kleihues, P., editor, Stiefel, F., editor, Groner, B., editor, Wallgren, A., editor, Rentchnik, P., editor, Senn, Hans-Jörg, editor, and Kapp, Ursula, editor

Published
2007
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43. Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non–Small-Cell Lung Cancer Previously Treated With Immunotherapy—Lung-MAP S1800A

Author

Reckamp, Karen L., primary, Redman, Mary W., additional, Dragnev, Konstantin H., additional, Minichiello, Katherine, additional, Villaruz, Liza C., additional, Faller, Bryan, additional, Al Baghdadi, Tareq, additional, Hines, Susan, additional, Everhart, Leah, additional, Highleyman, Louise, additional, Papadimitrakopoulou, Vassiliki, additional, Neal, Joel W., additional, Waqar, Saiama N., additional, Patel, Jyoti D., additional, Gray, Jhanelle E., additional, Gandara, David R., additional, Kelly, Karen, additional, and Herbst, Roy S., additional

Published
2022
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45. Representativeness of patients enrolled in the Lung Cancer Master Protocol (Lung-MAP).

Author

Vaidya, Riha, primary, Unger, Joseph M., additional, Qian, Lu, additional, Minichiello, Katherine, additional, Herbst, Roy S., additional, Gandara, David R., additional, Neal, Joel W., additional, Leal, Ticiana, additional, Patel, Jyoti D., additional, Dragnev, Konstantin H., additional, Waqar, Saiama Naheed, additional, Edelman, Martin Joseph, additional, Sigal, Ellen V., additional, Adam, Stacey, additional, Malik, Shakun M., additional, Blanke, Charles David, additional, LeBlanc, Michael Leo, additional, Kelly, Karen, additional, and Redman, Mary Weber, additional

Published
2022
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46. Overall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously treated with immunotherapy: Lung-MAP nonmatched substudy S1800A.

Author

Reckamp, Karen L., primary, Redman, Mary Weber, additional, Dragnev, Konstantin H., additional, Villaruz, Liza C, additional, Faller, Bryan A., additional, Al Baghdadi, Tareq, additional, Hines, Susan, additional, Qian, Lu, additional, Minichiello, Katherine, additional, Gandara, David R., additional, Kelly, Karen, additional, and Herbst, Roy S., additional

Published
2022
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47. Prioritizing Measures That Matter Within a Person-Centered Oncology Learning Health System

Author

Van Citters, Aricca D., Kennedy, Alice M., Kirkland, Kathryn B., Dragnev, Konstantin H., Leach, Steven D., Buus-Frank, Madge E., Malcolm, Elissa F., Holthoff, Megan M., Holmes, Anne B., Nelson, Eugene C., Reeves, Susan A., Tosteson, Anna N. A., Van Citters, Aricca D., Kennedy, Alice M., Kirkland, Kathryn B., Dragnev, Konstantin H., Leach, Steven D., Buus-Frank, Madge E., Malcolm, Elissa F., Holthoff, Megan M., Holmes, Anne B., Nelson, Eugene C., Reeves, Susan A., and Tosteson, Anna N. A.

Abstract

Background Despite progress in developing learning health systems (LHS) and associated metrics of success, a gap remains in identifying measures to guide the implementation and assessment of the impact of an oncology LHS. Our aim was to identify a balanced set of measures to guide a person-centered oncology LHS. Methods A modified Delphi process and clinical value compass framework were used to prioritize measures for tracking LHS performance. A multidisciplinary group of 77 stakeholders, including people with cancer and family members, participated in 3 rounds of online voting followed by 50-minute discussions. Participants rated metrics on perceived importance to the LHS and discussed priorities. Results Voting was completed by 94% of participants and prioritized 22 measures within 8 domains. Patient and caregiver factors included clinical health (Eastern Cooperative Oncology Group Performance Status, survival by cancer type and stage), functional health and quality of life (Patient Reported Outcomes Measurement Information System [PROMIS] Global-10, Distress Thermometer, Modified Caregiver Strain Index), experience of care (advance care planning, collaboRATE, PROMIS Self-Efficacy Scale, access to care, experience of care, end-of-life quality measures), and cost and resource use (avoidance and delay in accessing care and medications, financial hardship, total cost of care). Contextual factors included team well-being (Well-being Index; voluntary staff turnover); learning culture (Improvement Readiness, compliance with Commission on Cancer quality of care measures); scholarly engagement and productivity (institutional commitment and support for research, academic productivity index); and diversity, equity, inclusion, and belonging (screening and follow-up for social determinants of health, inclusivity of staff and patients). Conclusions The person-centered LHS value compass provides a balanced set of measures that oncology practices can use to monitor and evaluate

Published
2022
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49. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors

Author

Liu, Xi, Sempere, Lorenzo F., Ouyang, Haoxu, Memoli, Vincent A., Andrew, Angeline S., Luo, Yue, Demidenko, Eugene, Korc, Murray, Shi, Wei, Preis, Meir, Dragnev, Konstantin H., Li, Hua, DiRenzo, James, Bak, Mads, Freemantle, Sarah J., Kauppinen, Sakari, and Dmitrovsky, Ethan

Subjects
Gene expression -- Physiological aspects -- Genetic aspects -- Research, MicroRNA -- Properties -- Physiological aspects -- Research -- Genetic aspects, Lung cancer -- Development and progression -- Care and treatment -- Research -- Genetic aspects, Cancer cells -- Genetic aspects -- Physiological aspects -- Research, Oncology -- Research -- Physiological aspects, Health care industry
Abstract

Micro RNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microar-ray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31-mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression., Introduction MicroRNAs (miRNAs) are critical regulators of gene expression (1), (2). Mature miRNAs bind target mRNAs at complementary sites in 3'-untranslated regions (3'-UTRs) or coding sequences and thereby trigger downregulation, [...]

Published
2010
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