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201. Reduced IL-6 levels and tumor-associated phospho-STAT3 are associated with reduced tumor development in a mouse model of lung cancer chemoprevention with myo- inositol

Author

Unver, Nese, primary, Delgado, Oliver, additional, Zeleke, Kirubel, additional, Cumpian, Amber, additional, Tang, Ximing, additional, Caetano, Mauricio S., additional, Wang, Hong, additional, Katayama, Hiroyuki, additional, Yu, Hua, additional, Szabo, Eva, additional, Wistuba, Ignacio I., additional, Moghaddam, Seyed Javad, additional, Hanash, Samir M., additional, and Ostrin, Edwin J., additional

Published
2017
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203. Distinguishing mechanisms underlying EMT tristability

Author

Jia, Dongya, primary, Jolly, Mohit Kumar, additional, Tripathi, Satyendra C., additional, Den Hollander, Petra, additional, Huang, Bin, additional, Lu, Mingyang, additional, Celiktas, Muge, additional, Ramirez-Peña, Esmeralda, additional, Ben-Jacob, Eshel, additional, Onuchic, José N., additional, Hanash, Samir M., additional, Mani, Sendurai A., additional, and Levine, Herbert, additional

Published
2017
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205. Contribution of a Blood-Based Protein Biomarker Panel to the Classification of Indeterminate Pulmonary Nodules

Author

Ostrin, Edwin J., Bantis, Leonidas E., Wilson, David O., Patel, Nikul, Wang, Renwei, Kundnani, Deepali, Adams-Haduch, Jennifer, Dennison, Jennifer B., Fahrmann, Johannes F., Chiu, Hsienchang Thomas, Gazdar, Adi, Feng, Ziding, Yuan, Jian-Min, and Hanash, Samir M.

Abstract

The workup and longitudinal monitoring for subjects presenting with pulmonary nodules is a pressing clinical problem. A blood-based biomarker panel potentially has utility for identifying subjects at higher risk for harboring a malignant nodule for whom additional workup would be indicated or subjects at reduced risk for whom imaging-based follow-up would be indicated.

Published
2021
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209. YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition

Author

Ajani, Jaffer A, Xu, Yan, Huo, Longfei, Wang, Ruiping, Li, Yuan, Wang, Ying, Pizzi, Melissa Pool, Scott, Ailing, Harada, Kazuto, Ma, Lang, Yao, Xiaodan, Jin, Jiankang, Zhao, Wei, Dong, Xiaochuan, Badgwell, Brian D, Shanbhag, Namita, Tatlonghari, Ghia, Estrella, Jeannelyn Santiano, Roy-Chowdhuri, Sinchita, Kobayashi, Makoto, Vykoukal, Jody V, Hanash, Samir M, Calin, George Adrian, Peng, Guang, Lee, Ju-Seog, Johnson, Randy L, Wang, Zhenning, Wang, Linghua, and Song, Shumei

Abstract

ObjectivePeritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events leading to PC are unknown. The yes-associated protein 1 (YAP1) oncogene has emerged in many tumour types, but its clinical significance in PC is unclear. Here, we investigated the role of YAP1 in PC and its potential as a therapeutic target.MethodsPatient-derived PC cells, patient-derived xenograft (PDX) and patient-derived orthotopic (PDO) models were used to study the function of YAP1 in vitro and in vivo. Immunofluorescence and immunohistochemical staining, RNA sequencing (RNA-Seq) and single-cell RNA-Seq (sc-RNA-Seq) were used to elucidate the expression of YAP1 and PC cell heterogeneity. LentiCRISPR/Cas9 knockout of YAP1 and a YAP1 inhibitor were used to dissect its role in PC metastases.ResultsYAP1 was highly upregulated in PC tumour cells, conferred cancer stem cell (CSC) properties and appeared to be a metastatic driver. Dual staining of YAP1/EpCAM and sc-RNA-Seq revealed that PC tumour cells were highly heterogeneous, YAP1highPC cells had CSC-like properties and easily formed PDX/PDO tumours but also formed PC in mice, while genetic knockout YAP1 significantly slowed tumour growth and eliminated PC in PDO model. Additionally, pharmacologic inhibition of YAP1 specifically reduced CSC-like properties and suppressed tumour growth in YAP1highPC cells especially in combination with cytotoxics in vivo PDX model.ConclusionsYAP1 is essential for PC that is attenuated by YAP1 inhibition. Our data provide a strong rationale to target YAP1 in clinic for GAC patients with PC.

Published
2021
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210. Integrated genomic profiling and modelling for risk stratification in patients with advanced oesophagogastric adenocarcinoma

Author

Hao, Dapeng, He, Siyuan, Harada, Kazuto, Pizzi, Melissa Pool, Lu, Yang, Guan, Pujun, Chen, Lu, Wang, Ruiping, Zhang, Shaojun, Sewastjanow-Silva, Matheus, Abdelhakeem, Ahmed, Shanbhag, Namita, Bhutani, Manoop, Han, Guangchun, Lee, Jeffrey H, Zhao, Shuangtao, Weston, Brian, Blum Murphy, Mariela, Waters, Rebecca, Estrella, Jeannelyn Santiano, Roy-Chowdhuri, Sinchita, Gan, Qiong, Lee, Ju-Seog, Peng, Guang, Hanash, Samir M, Calin, George Adrian, Song, Xingzhi, Zhang, Jianhua, Song, Shumei, Wang, Linghua, and Ajani, Jaffer A

Abstract

ObjectivePrognosis of patients with advanced oesophagogastric adenocarcinoma (mEGAC) is poor and molecular determinants of shorter or longer overall survivors are lacking. Our objective was to identify molecular features and develop a prognostic model by profiling the genomic features of patients with mEGAC with widely varying outcomes.DesignWe profiled 40 untreated mEGACs (20 shorter survivors <13 months and 20 longer survivors >36 months) with whole-exome sequencing (WES) and RNA sequencing and performed an integrated analysis of exome, transcriptome, immune profile and pathological phenotypes to identify the molecular determinants, developing an integrated model for prognosis and comparison with The Cancer Genome Atlas (TCGA) cohorts.ResultsKMT2Calterations were exclusively observed in shorter survivors together with high level of intratumour heterogeneity and complex clonal architectures, whereas the APOBEC mutational signatures were significantly enriched in longer survivors. Notably, the loss of heterozygosity in chromosome 4 (Chr4) was associated with shorter survival and ‘cold’ immune phenotype characterised by decreased B, CD8, natural killer cells and interferon-gamma responses. Unsupervised transcriptomic clustering revealed a shorter survivor subtype with distinct expression features (eg, upregulated druggable targets JAK2, MAP3K13and MECOM). An integrated model was then built based on clinical variables and the identified molecular determinants, which significantly segregated shorter and longer survivors. All the above features and the integrated model have been validated independently in multiple TCGA cohorts.ConclusionThis study discovered novel molecular features prognosticating overall survival in patients with mEGAC and identified potential novel targets in shorter survivors.

Published
2021
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211. Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung adenocarcinoma

Author

Vykoukal, Jody, primary, Sun, Nan, additional, Aguilar-Bonavides, Clemente, additional, Katayama, Hiroyuki, additional, Tanaka, Ichidai, additional, Fahrmann, Johannes F., additional, Capello, Michela, additional, Fujimoto, Junya, additional, Aguilar, Mitzi, additional, Wistuba, Ignacio I., additional, Taguchi, Ayumu, additional, Ostrin, Edwin J., additional, and Hanash, Samir M., additional

Published
2017
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212. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers

Author

Cohen, Joshua D., primary, Javed, Ammar A., additional, Thoburn, Christopher, additional, Wong, Fay, additional, Tie, Jeanne, additional, Gibbs, Peter, additional, Schmidt, C. Max, additional, Yip-Schneider, Michele T., additional, Allen, Peter J., additional, Schattner, Mark, additional, Brand, Randall E., additional, Singhi, Aatur D., additional, Petersen, Gloria M., additional, Hong, Seung-Mo, additional, Kim, Song Cheol, additional, Falconi, Massimo, additional, Doglioni, Claudio, additional, Weiss, Matthew J., additional, Ahuja, Nita, additional, He, Jin, additional, Makary, Martin A., additional, Maitra, Anirban, additional, Hanash, Samir M., additional, Dal Molin, Marco, additional, Wang, Yuxuan, additional, Li, Lu, additional, Ptak, Janine, additional, Dobbyn, Lisa, additional, Schaefer, Joy, additional, Silliman, Natalie, additional, Popoli, Maria, additional, Goggins, Michael G., additional, Hruban, Ralph H., additional, Wolfgang, Christopher L., additional, Klein, Alison P., additional, Tomasetti, Cristian, additional, Papadopoulos, Nickolas, additional, Kinzler, Kenneth W., additional, Vogelstein, Bert, additional, and Lennon, Anne Marie, additional

Published
2017
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214. In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer

Author

Kodama, Michiko, primary, Kodama, Takahiro, additional, Newberg, Justin Y., additional, Katayama, Hiroyuki, additional, Kobayashi, Makoto, additional, Hanash, Samir M., additional, Yoshihara, Kosuke, additional, Wei, Zhubo, additional, Tien, Jean C., additional, Rangel, Roberto, additional, Hashimoto, Kae, additional, Mabuchi, Seiji, additional, Sawada, Kenjiro, additional, Kimura, Tadashi, additional, Copeland, Neal G., additional, and Jenkins, Nancy A., additional

Published
2017
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215. MCAM Mediates Chemoresistance in Small-Cell Lung Cancer via the PI3K/AKT/SOX2 Signaling Pathway

Author

Tripathi, Satyendra C., primary, Fahrmann, Johannes F., additional, Celiktas, Muge, additional, Aguilar, Mitzi, additional, Marini, Kieren D., additional, Jolly, Mohit K., additional, Katayama, Hiroyuki, additional, Wang, Hong, additional, Murage, Eunice N., additional, Dennison, Jennifer B., additional, Watkins, D. Neil, additional, Levine, Herbert, additional, Ostrin, Edwin J., additional, Taguchi, Ayumu, additional, and Hanash, Samir M., additional

Published
2017
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216. Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis

Author

Schliekelman, Mark J., primary, Creighton, Chad J., additional, Baird, Brandi N., additional, Chen, Yulong, additional, Banerjee, Priyam, additional, Bota-Rabassedas, Neus, additional, Ahn, Young-Ho, additional, Roybal, Jonathon D., additional, Chen, Fengju, additional, Zhang, Yiqun, additional, Mishra, Dhruva K., additional, Kim, Min P., additional, Liu, Xin, additional, Mino, Barbara, additional, Villalobos, Pamela, additional, Rodriguez-Canales, Jaime, additional, Behrens, Carmen, additional, Wistuba, Ignacio I., additional, Hanash, Samir M., additional, and Kurie, Jonathan M., additional

Published
2017
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217. Abstract 2775: CPS1 as a therapeutic target and prognostic indicator in LKB1-inactivated lung adenocarcinoma

Author

Celiktas, Muge, primary, Tanaka, Ichidai, additional, Tripathi, Satyendra Chandra, additional, Fahrmann, Johannes F., additional, Aguilar-Bonavides, Clemente, additional, Villalobos, Pamela, additional, Delgado, Oliver, additional, Dhillon, Dilsher, additional, Dennison, Jennifer B., additional, Ostrin, Edwin J., additional, Wang, Hong, additional, Behrens, Carmen, additional, Do, Kim-Anh, additional, Gazdar, Adi F., additional, Hanash, Samir M., additional, and Taguchi, Ayumu, additional

Published
2017
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219. Abstract 238: Evidence of early colorectal cancer risk and prevention pathways in the fecal microbiome of colonoscopy patients: associations with diet and circulating adipocytokines

Author

Daniel, Carrie R., primary, Hoffman, Kristi L., additional, Raju, G S., additional, Hanash, Samir M., additional, Hutchinson, Diane S., additional, Ajami, Nadim J., additional, Fowler, Richard G., additional, Browman, Gladys J., additional, Sood, Akhil, additional, Scheet, Paul, additional, Wu, Xifeng, additional, and Petrosino, Joseph F., additional

Published
2017
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220. Abstract 3170: MCAM modulates small cell lung cancer chemoresistance via PI3k/Akt/Sox2 signaling pathway

Author

Tripathi, Satyendra C., primary, Fahrmann, Johannes F., additional, Celiktas, Muge, additional, Aguilar, Mitzi, additional, Marini, Kieren D., additional, Jolly, Mohit K., additional, Katayama, Hiroyuki, additional, Wang, Hong, additional, Murage, Eunice N., additional, Dennison, Jennifer B., additional, Watkins, D. Neil, additional, Levine, Herbert, additional, Ostrin, Edwin J., additional, Taguchi, Ayumu, additional, and Hanash, Samir M., additional

Published
2017
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221. Deubiquitinase USP18 Loss Mislocalizes and Destabilizes KRAS in Lung Cancer

Author

Mustachio, Lisa Maria, primary, Lu, Yun, additional, Tafe, Laura J., additional, Memoli, Vincent, additional, Rodriguez-Canales, Jaime, additional, Mino, Barbara, additional, Villalobos, Pamela Andrea, additional, Wistuba, Ignacio, additional, Katayama, Hiroyuki, additional, Hanash, Samir M., additional, Roszik, Jason, additional, Kawakami, Masanori, additional, Cho, Kwang-jin, additional, Hancock, John F., additional, Chinyengetere, Fadzai, additional, Hu, Shanhu, additional, Liu, Xi, additional, Freemantle, Sarah J., additional, and Dmitrovsky, Ethan, additional

Published
2017
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222. Abstract 3984: Neuropilin-1 mediates neutrophil elastase uptake and antigen cross-presentation in breast cancer cells

Author

Kerros, Celine, primary, Tripathi, Satyendra C., additional, Zha, Dongxing, additional, Anna, Sergeeva, additional, Peters, Haley L., additional, Katayama, Hiroyuki, additional, Sukhumalchandra, Pariya, additional, Cox, Kathryn R., additional, Perakis, Alexander A., additional, John, Lisa S. St, additional, Alatrash, Gheath, additional, Mittendorf, Elizabeth A., additional, Dwyer, Karen C., additional, Hanash, Samir M., additional, and Molldrem, Jeffrey J., additional

Published
2017
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224. Neuropilin-1 mediates neutrophil elastase uptake and cross-presentation in breast cancer cells

Author

Kerros, Celine, primary, Tripathi, Satyendra C., additional, Zha, Dongxing, additional, Mehrens, Jennifer M., additional, Sergeeva, Anna, additional, Philips, Anne V., additional, Qiao, Na, additional, Peters, Haley L., additional, Katayama, Hiroyuki, additional, Sukhumalchandra, Pariya, additional, Ruisaard, Kathryn E., additional, Perakis, Alexander A., additional, St. John, Lisa S., additional, Lu, Sijie, additional, Mittendorf, Elizabeth A., additional, Clise-Dwyer, Karen, additional, Herrmann, Amanda C., additional, Alatrash, Gheath, additional, Toniatti, Carlo, additional, Hanash, Samir M., additional, Ma, Qing, additional, and Molldrem, Jeffrey J., additional

Published
2017
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227. Role of CPS1 in Cell Growth, Metabolism, and Prognosis in LKB1-Inactivated Lung Adenocarcinoma

Author

Çeliktaş, Müge, primary, Tanaka, Ichidai, additional, Chandra Tripathi, Satyendra, additional, Fahrmann, Johannes F., additional, Aguilar-Bonavides, Clemente, additional, Villalobos, Pamela, additional, Delgado, Oliver, additional, Dhillon, Dilsher, additional, Dennison, Jennifer B., additional, Ostrin, Edwin J., additional, Wang, Hong, additional, Behrens, Carmen, additional, Do, Kim-Anh, additional, Gazdar, Adi F., additional, Hanash, Samir M., additional, and Taguchi, Ayumu, additional

Published
2016
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228. Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer

Author

Capello, Michela, primary, Bantis, Leonidas E., additional, Scelo, Ghislaine, additional, Zhao, Yang, additional, Li, Peng, additional, Dhillon, Dilsher S., additional, Patel, Nikul J., additional, Kundnani, Deepali L., additional, Wang, Hong, additional, Abbruzzese, James L., additional, Maitra, Anirban, additional, Tempero, Margaret A., additional, Brand, Randall, additional, Brennan, Lenka, additional, Feng, Eleonora, additional, Taguchi, Ivana, additional, Janout, Vladimir, additional, Firpo, Matthew A., additional, Mulvihill, Sean J., additional, Katz, Matthew H., additional, and Hanash, Samir M., additional

Published
2016
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229. Lysyl Hydroxylase 2 Is Secreted by Tumor Cells and Can Modify Collagen in the Extracellular Space

Author

Chen, Yulong, primary, Guo, Houfu, additional, Terajima, Masahiko, additional, Banerjee, Priyam, additional, Liu, Xin, additional, Yu, Jiang, additional, Momin, Amin A., additional, Katayama, Hiroyuki, additional, Hanash, Samir M., additional, Burns, Alan R., additional, Fields, Gregg B., additional, Yamauchi, Mitsuo, additional, and Kurie, Jonathan M., additional

Published
2016
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230. Protein and glycomic plasma markers for early detection of adenoma and colon cancer

Author

Rho, Jung-hyun, primary, Ladd, Jon J, additional, Li, Christopher I, additional, Potter, John D, additional, Zhang, Yuzheng, additional, Shelley, David, additional, Shibata, David, additional, Coppola, Domenico, additional, Yamada, Hiroyuki, additional, Toyoda, Hidenori, additional, Tada, Toshifumi, additional, Kumada, Takashi, additional, Brenner, Dean E, additional, Hanash, Samir M, additional, and Lampe, Paul D, additional

Published
2016
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231. Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response

Author

Wang, Ruiping, Song, Shumei, Harada, Kazuto, Ghazanfari Amlashi, Fatemeh, Badgwell, Brian, Pizzi, Melissa Pool, Xu, Yan, Zhao, Wei, Dong, Xiaochuan, Jin, Jiangkang, Wang, Ying, Scott, Ailing, Ma, Lang, Huo, Longfei, Vicente, Diego, Blum Murphy, Mariela, Shanbhag, Namita, Tatlonghari, Ghia, Thomas, Irene, Rogers, Jane, Kobayashi, Makoto, Vykoukal, Jody, Estrella, Jeannelyn Santiano, Roy-Chowdhuri, Sinchita, Han, Guangchun, Zhang, Shaojun, Mao, Xizeng, Song, Xingzhi, Zhang, Jianhua, Gu, Jian, Johnson, Randy L, Calin, George Adrian, Peng, Guang, Lee, Ju-Seog, Hanash, Samir M, Futreal, Andrew, Wang, Zhenning, Wang, Linghua, and Ajani, Jaffer A

Abstract

ObjectivePeritoneal carcinomatosis (PC) occurs frequently in patients with gastric adenocarcinoma (GAC) and confers a poor prognosis. Multiplex profiling of primary GACs has been insightful but the underpinnings of PC’s development/progression remain largely unknown. We characterised exome/transcriptome/immune landscapes of PC cells from patients with GAC aiming to identify novel therapeutic targets.DesignWe performed whole-exome sequencing (WES) and whole transcriptome sequencing (RNA-seq) on 44 PC specimens (43 patients with PC) including an integrative analysis of WES, RNA-seq, immune profile, clinical and pathological phenotypes to dissect the molecular pathogenesis, identifying actionable targets and/or biomarkers and comparison with TCGA primary GACs.ResultsWe identified distinct alterations in PC versus primary GACs, such as more frequent CDH1 and TAF1mutations, 6q loss and chr19 gain. Alterations associated with aggressive PC phenotypes emerged with increased mutations in TP53, CDH1, TAF1and KMT2C, higher level of ‘clock-like’ mutational signature, increase in whole-genome doublings, chromosomal instability (particularly, copy number losses), reprogrammed microenvironment, enriched cell cycle pathways, MYC activation and impaired immune response. Integrated analysis identified two main molecular subtypes: ‘mesenchymal-like’ and ‘epithelial-like’ with discriminating response to chemotherapy (31% vs 71%). Patients with the less responsive ‘mesenchymal-like’ subtype had high expression of immune checkpoint T-Cell Immunoglobulin And Mucin Domain-Containing Protein 3 (TIM-3), its ligand galectin-9, V-domain Ig suppressor of T cell activation (VISTA) and transforming growth factor-β as potential therapeutic immune targets.ConclusionsWe have uncovered the unique mutational landscape, copy number alteration and gene expression profile of PC cells and defined PC molecular subtypes, which correlated with PC therapy resistance/response. Novel targets and immune checkpoint proteins have been identified with a potential to be translated into clinics.

Published
2020
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232. An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

Author

Brichory, Franck M., Misek, David E., Yim, Anne-Marie, Krause, Melissa C., Giordano, Thomas J., Beer, David G., and Hanash, Samir M.

Subjects
Immune response -- Physiological aspects, Autoantibodies -- Physiological aspects, Lung cancer -- Diagnosis, Tumor antigens -- Physiological aspects, Science and technology
Abstract

The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and/or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and/or II in sera from patients with lung cancer.

Published
2001

237. Abstract LB-134: Sequential validation of blood-based protein biomarker candidates for early-stage pancreatic cancer

Author

Capello, Michela, primary, Bantis, Leonidas E., additional, Scelo, Ghislaine, additional, Zhao, Yang, additional, Dhillon, Dilsher S., additional, Wang, Hong, additional, Abbruzzese, James L., additional, Maitra, Anirban, additional, Tempero, Margaret A., additional, Brand, Randall, additional, Firpo, Matthew A., additional, Mulvihill, Sean, additional, Katz, Matthew H., additional, Brennan, Paul, additional, Feng, Ziding, additional, Hanash, Samir M., additional, and Taguchi, Ayumu, additional

Published
2016
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239. Stability of the hybrid epithelial/mesenchymal phenotype

Author

Jolly, Mohit Kumar, primary, Tripathi, Satyendra C., additional, Jia, Dongya, additional, Mooney, Steven M., additional, Celiktas, Muge, additional, Hanash, Samir M., additional, Mani, Sendurai A., additional, Pienta, Kenneth J., additional, Ben-Jacob, Eshel, additional, and Levine, Herbert, additional

Published
2016
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240. Cancer-Associated Fibroblasts Induce a Collagen Cross-link Switch in Tumor Stroma

Author

Pankova, Daniela, primary, Chen, Yulong, additional, Terajima, Masahiko, additional, Schliekelman, Mark J., additional, Baird, Brandi N., additional, Fahrenholtz, Monica, additional, Sun, Li, additional, Gill, Bartley J., additional, Vadakkan, Tegy J., additional, Kim, Min P., additional, Ahn, Young-Ho, additional, Roybal, Jonathon D., additional, Liu, Xin, additional, Parra Cuentas, Edwin Roger, additional, Rodriguez, Jaime, additional, Wistuba, Ignacio I., additional, Creighton, Chad J., additional, Gibbons, Don L., additional, Hicks, John M., additional, Dickinson, Mary E., additional, West, Jennifer L., additional, Grande-Allen, K. Jane, additional, Hanash, Samir M., additional, Yamauchi, Mitsuo, additional, and Kurie, Jonathan M., additional

Published
2016
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241. EGFR Signaling Enhances Aerobic Glycolysis in Triple-Negative Breast Cancer Cells to Promote Tumor Growth and Immune Escape

Author

Lim, Seung-Oe, primary, Li, Chia-Wei, additional, Xia, Weiya, additional, Lee, Heng-Huan, additional, Chang, Shih-Shin, additional, Shen, Jia, additional, Hsu, Jennifer L., additional, Raftery, Daniel, additional, Djukovic, Danijel, additional, Gu, Haiwei, additional, Chang, Wei-Chao, additional, Wang, Hung-Ling, additional, Chen, Mong-Liang, additional, Huo, Longfei, additional, Chen, Chung-Hsuan, additional, Wu, Yun, additional, Sahin, Aysegul, additional, Hanash, Samir M., additional, Hortobagyi, Gabriel N., additional, and Hung, Mien-Chie, additional

Published
2016
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243. Abstract A060: Immunoproteasome deficiency is a feature of NSCLC with a mesenchymal phenotype and is associated with restricted antigen presentation and poor outcome in patients

Author

Tripathi, Satyendra C., primary, Peters, Haley L., additional, Ostrin, Edwin J., additional, Taguchi, Ayumu, additional, Katayama, Hiroyuki, additional, Wang, Hong, additional, Momin, Amin, additional, Jolly, Mohit K., additional, Celiktas, Muge, additional, Rodriguez, Jaime, additional, Behrens, Carmen, additional, Wistuba, Ignacio I., additional, Jacob, Eshel Ben, additional, Levine, Herbert, additional, Molldrem, Jeffrey J., additional, and Hanash, Samir M., additional

Published
2016
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245. Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry.

Author

Miyamoto, Suzanne, Miyamoto, Suzanne, Taylor, Sandra L, Barupal, Dinesh K, Taguchi, Ayumu, Wohlgemuth, Gert, Wikoff, William R, Yoneda, Ken Y, Gandara, David R, Hanash, Samir M, Kim, Kyoungmi, Fiehn, Oliver, Miyamoto, Suzanne, Miyamoto, Suzanne, Taylor, Sandra L, Barupal, Dinesh K, Taguchi, Ayumu, Wohlgemuth, Gert, Wikoff, William R, Yoneda, Ken Y, Gandara, David R, Hanash, Samir M, Kim, Kyoungmi, and Fiehn, Oliver

Abstract

Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection.

Published
2015

246. MAPRE1 as a Plasma Biomarker for Early-Stage Colorectal Cancer and Adenomas

Author

Taguchi, Ayumu, primary, Rho, Jung-hyun, additional, Yan, Qingxiang, additional, Zhang, Yuzheng, additional, Zhao, Yang, additional, Xu, Hanwen, additional, Tripathi, Satyendra Chandra, additional, Wang, Hong, additional, Brenner, Dean E., additional, Kucherlapati, Melanie, additional, Kucherlapati, Raju, additional, Boutin, Adam T., additional, Wang, Y. Alan, additional, DePinho, Ronald A., additional, Feng, Ziding, additional, Lampe, Paul D., additional, and Hanash, Samir M., additional

Published
2015
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247. Enrichment strategies in glycomics-based lung cancer biomarker development

Author

Ruhaak, L Renee, Nguyen, Uyen Thao, Stroble, Carol, Taylor, Sandra L, Taguchi, Ayumu, Hanash, Samir M, Lebrilla, Carlito B, Kim, Kyoungmi, and Miyamoto, Suzanne

Subjects
Male, Biochemistry & Molecular Biology, Lung Neoplasms, Glycosylation, Pilot Projects, Adenocarcinoma of Lung, Adenocarcinoma, Medical Biochemistry and Metabolomics, Rare Diseases, Polysaccharides, Humans, Glycomics, Lung, Cancer, screening and diagnosis, Tumor, Mass spectrometry, Nonsmall cell lung cancer, Prevention, Lung Cancer, Biomarker, Middle Aged, 4.1 Discovery and preclinical testing of markers and technologies, Detection, Protein enrichment, Case-Control Studies, N-glycan, Female, Biomarkers
Abstract

PurposeThere is a need to identify better glycan biomarkers for diagnosis, early detection, and treatment monitoring in lung cancer using biofluids such as blood. Biofluids are complex mixtures of proteins dominated by a few high abundance proteins that may not have specificity for lung cancer. Therefore, two methods for protein enrichment were evaluated; affinity capturing of IgG and enrichment of medium abundance proteins, thus allowing us to determine which method yields the best candidate glycan biomarkers for lung cancer.Experimental designN-glycans isolated from plasma samples from 20 cases of lung adenocarcinoma and 20 matched controls were analyzed using nLC-PGC-chip-TOF-MS (where PGC is porous-graphitized carbon). N-glycan profiles were obtained for five different fractions: total plasma, isolated IgG, IgG-depleted plasma, and the bound and flow-through fractions of protein enrichment.ResultsFour glycans differed significantly (false discovery rate, FDR < 0.05) between cases and controls in whole unfractionated plasma, while four other glycans differed significantly by cancer status in the IgG fraction. No significant glycan differences were observed in the other fractions.Conclusions and clinical relevanceThese results confirm that the N-glycan profile in plasma of lung cancer patients is different from healthy controls and appears to be dominated by alterations in relatively abundant proteins.

Published
2013

248. Reduced IL‐6 levels and tumor‐associated phospho‐STAT3 are associated with reduced tumor development in a mouse model of lung cancer chemoprevention with <italic>myo‐</italic>inositol.

Author

Unver, Nese, Delgado, Oliver, Zeleke, Kirubel, Cumpian, Amber, Tang, Ximing, Caetano, Mauricio S., Wang, Hong, Katayama, Hiroyuki, Yu, Hua, Szabo, Eva, Wistuba, Ignacio I., Moghaddam, Seyed Javad, Hanash, Samir M., and Ostrin, Edwin J.

Abstract

Several promising chemopreventive agents have for lung cancer emerged in preclinical models and in retrospective trials. These agents have been shown to modulate pathways altered in carcinogenesis and reduce markers of carcinogenesis in animal and cell culture models. Cancer‐prone transgenic mice with oncogenic Kras expressed in the airway epithelium (CcspCre/+; KrasLSL‐G12D/+) were raised on diets compounded with myo‐inositol. These animals form lung premalignant lesions in a stereotypical fashion over the ten weeks following weaning. Mice raised on myo‐inositol containing diets showed potent reduction in the number, size, and stage of lesions as compared to those raised on control diets. myo‐inositol has previously been reported to inhibit phosphoinositide 3‐kinase (PI3K) signaling. However, in mice raised on myo‐inositol, total PI3K signaling was largely unaffected. Proteomic and cytokine analyses revealed large reduction in IL‐6 related pathways, including STAT3 phosphorylation. This effect was not due to direct inhibition of IL‐6 production and autocrine signaling within the tumor cell, but rather through alteration in macrophage recruitment and in phenotype switching, with an increase in antitumoral M1 macrophages. [ABSTRACT FROM AUTHOR]

Published
2018
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250. HIV Infection and Circulating Levels of Prosurfactant Protein B and Surfactant Protein D.

Author

Shiels, Meredith S., Kirk, Gregory D., Drummond, M. Bradley, Dhillon, Dilsher, Hanash, Samir M., Taguchi, Ayumu, and Engels, Eric A.

Subjects
HIV infections, PULMONARY surfactant-associated protein B, PULMONARY surfactant-associated protein D, PNEUMONIA, BLOOD serum analysis, IMMUNOSUPPRESSION, VIREMIA
Abstract

Prosurfactant protein B (pro-SFTPB) and surfactant protein D (SFTPD) are markers of lung inflammation and damage. We estimated geometric mean pro-SFTPB and SFTPD levels in 500 human immunodeficiency virus (HIV)-infected and 300 HIV-uninfected injection drug users, adjusting for smoking and other covariates. Pro-SFTPB levels were significantly higher among people with HIV (PWH) (adjusted geometric mean, 21.4 vs 18.1 ng/mL; P = .03), and were higher with lower CD4 counts (P trend = .001), higher HIV RNA (P trend = .05), and without highly active antiretroviral therapy (P = .03). These associations were not observed for SFTPD. Serum levels of pro-SFTPB are elevated among PWH and are associated with immunosuppression and uncontrolled viremia. [ABSTRACT FROM AUTHOR]

Published
2018
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