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Article ; Online: Liquid Biopsy as an Adjunct to Lung Screening Imaging.

Deboever, Nathaniel / Ostrin, Edwin J / Antonoff, Mara B

2023 Volume 33, Issue 4, Page(s) 411–419

Abstract: Current lung cancer screening protocols use low-dose computed tomography scans in selected high-risk individuals. Unfortunately, utilization is low, and the rate of false-positive screens is high. Peripheral biomarkers carry meaningful promise in ... ...

Abstract	Current lung cancer screening protocols use low-dose computed tomography scans in selected high-risk individuals. Unfortunately, utilization is low, and the rate of false-positive screens is high. Peripheral biomarkers carry meaningful promise in diagnosing and monitoring cancer with added potential advantages reducing invasive procedures and improving turnaround time. Herein, the use of such blood-based assays is considered as an adjunct to further utilization and accuracy of lung cancer screening.
MeSH term(s)	Humans ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/pathology ; Early Detection of Cancer/methods ; Tomography, X-Ray Computed/methods ; Lung/diagnostic imaging ; Lung/pathology ; Liquid Biopsy ; Mass Screening
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2149218-9
ISSN	1558-5069 ; 1547-4127
ISSN (online)	1558-5069
ISSN	1547-4127
DOI	10.1016/j.thorsurg.2023.04.004
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Article: Amino Acid Oncometabolism and Immunomodulation of the Tumor Microenvironment in Lung Cancer.

Fahrmann, Johannes F / Vykoukal, Jody V / Ostrin, Edwin J

Frontiers in oncology

2020 Volume 10, Page(s) 276

Abstract: The observation that cancer acquires significant changes in its metabolism dates back nearly a century, to Otto Warburg noting that cancer cells preferentially utilize glycolysis even when there are no hypoxic conditions in the growth media. Altered ... ...

Abstract	The observation that cancer acquires significant changes in its metabolism dates back nearly a century, to Otto Warburg noting that cancer cells preferentially utilize glycolysis even when there are no hypoxic conditions in the growth media. Altered energetics are thus considered a hallmark of cancer. However, it has become clear that altered metabolism is not limited to cellular energetic pathways. Alterations in amino acid synthesis and catabolism, lipid biogenesis, and other pathways such as polyamine processing are commonly seen in cancer. Additionally, alterations in metabolism do not only have profound effects for cancer cells but also affect their surrounding microenvironment. With new cancer therapeutics targeting the immune microenvironment, these effects may have implications on cancer growth and response to therapy. These interactions are profound in lung cancer, further demonstrating the manifold interactions between developing tumors and the inflammatory microenvironment. Here, we discuss how dysregulation of metabolism in cancer alters its microenvironment and how this newfound knowledge can be exploited for anticancer treatment.
Language	English
Publishing date	2020-03-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.00276
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Article ; Online: Biomarkers for Lung Cancer Screening and Detection.

Ostrin, Edwin J / Sidransky, David / Spira, Avrum / Hanash, Samir M

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2020 Volume 29, Issue 12, Page(s) 2411–2415

Abstract: Lung cancer is the leading worldwide cause of cancer mortality, as it is often detected at an advanced stage. Since 2011, low-dose CT scan-based screening has promised a 20% reduction in lung cancer mortality. However, effectiveness of screening has been ...

Abstract	Lung cancer is the leading worldwide cause of cancer mortality, as it is often detected at an advanced stage. Since 2011, low-dose CT scan-based screening has promised a 20% reduction in lung cancer mortality. However, effectiveness of screening has been limited by eligibility only for a high-risk population of heavy smokers and a large number of false positives generated by CT. Biomarkers have tremendous potential to improve early detection of lung cancer by refining lung cancer risk, stratifying positive CT scans, and categorizing intermediate-risk pulmonary nodules. Three biomarker tests (Early CDT-Lung, Nodify XL2, Percepta) have undergone extensive validation and are available to the clinician. The authors discuss these tests, with their clinical applicability and limitations, current ongoing evaluation, and future directions for biomarkers in lung cancer screening and detection.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Early Detection of Cancer/methods ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/pathology
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2020-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-20-0865
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Article ; Online: Continuous Objective Assessment of Near Work.

Williams, Rachel / Bakshi, Suyash / Ostrin, Edwin J / Ostrin, Lisa A

Scientific reports

2019 Volume 9, Issue 1, Page(s) 6901

Abstract: Evidence regarding the role of near work in myopia is conflicting. We developed the RangeLife, a device for continuous, objective measurement of working distance. Four devices were built, calibrated, and validated. Then, adult subjects wore the device on ...

Abstract	Evidence regarding the role of near work in myopia is conflicting. We developed the RangeLife, a device for continuous, objective measurement of working distance. Four devices were built, calibrated, and validated. Then, adult subjects wore the device on weekdays and weekend days, while simultaneously wearing an actigraph device for objective measurements of light exposure and activity. Subjects maintained an activity log and answered a visual activity questionnaire. RangeLife data were downloaded and binned into 0.10 m intervals. Objective diopter hours (dh), a weighted measure of near work, were calculated. Diopter hours for all subjects were significantly higher on weekdays (14.73 ± 4.67 dh) compared to weekends (11.90 ± 4.84 dh, p = 0.05). 94 ± 1.85% of near and intermediate viewing distances were recorded when the subjects were exposed to mesopic and indoor photopic light levels (<1000 lux), and 80.03 ± 2.11% during periods of sedentary physical activity (<320 counts per minute). Subjective reports of time viewing near and intermediate distances significantly overestimated objective measures (p = 0.002). The RangeLife was shown to provide reliable measures of viewing distance, and can be further utilized to understand potential influences of viewing behaviors on refractive error.
MeSH term(s)	Adult ; Case-Control Studies ; Female ; Humans ; Male ; Monitoring, Physiologic ; Myopia/etiology ; Myopia/physiopathology ; Surveys and Questionnaires ; Time Factors ; Wearable Electronic Devices ; Young Adult
Language	English
Publishing date	2019-05-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-43408-y
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Article ; Online: Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma.

Tai, Mei-Chee / Bantis, Leonidas E / Parhy, Gargy / Kato, Taketo / Tanaka, Ichidai / Chow, Chi-Wan / Fujimoto, Junya / Behrens, Carmen / Hase, Tetsunari / Kawaguchi, Koji / Fahrmann, Johannes F / Ostrin, Edwin J / Yokoi, Kohei / Chen-Yoshikawa, Toyofumi F / Hasegawa, Yoshinori / Hanash, Samir M / Wistuba, Ignacio I / Taguchi, Ayumu

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identification of those in an early stage who would likely benefit from ... ...

Abstract	Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identification of those in an early stage who would likely benefit from adjuvant chemotherapy. To identify circulating miRNAs useful for predicting recurrence in early-stage LUAD, we performed miRNA microarray analysis with pools of pretreatment plasma samples from patients with stage I LUAD who developed recurrence or remained recurrence-free during the follow-up period. Subsequent validation in 85 patients with stage I LUAD resulted in the development of a circulating miRNA panel comprising miR-23a-3p, miR-320c, and miR-125b-5p and yielding an area under the curve (AUC) of 0.776 in predicting recurrence. Furthermore, the three-miRNA panel yielded an AUC of 0.804, with a sensitivity of 45.8% at 95% specificity in the independent test set of 57 stage I and II LUAD patients. The miRNA panel score was a significant and independent factor for predicting disease-free survival (
MeSH term(s)	Humans ; Circulating MicroRNA/genetics ; Biomarkers, Tumor/genetics ; Adenocarcinoma of Lung/genetics ; MicroRNAs ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics
Chemical Substances	Circulating MicroRNA ; Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2024-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042331
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Article: Kynureninase Upregulation Is a Prominent Feature of NFR2-Activated Cancers and Is Associated with Tumor Immunosuppression and Poor Prognosis.

León-Letelier, Ricardo A / Abdel Sater, Ali H / Chen, Yihui / Park, Soyoung / Wu, Ranran / Irajizad, Ehsan / Dennison, Jennifer B / Katayama, Hiroyuki / Vykoukal, Jody V / Hanash, Samir / Ostrin, Edwin J / Fahrmann, Johannes F

Cancers

2023 Volume 15, Issue 3

Abstract: The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is frequently activated in various cancer types. Aberrant activation of NRF2 in cancer is attributed to gain-of-function mutations in the NRF2-encoding ... ...

Abstract	The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is frequently activated in various cancer types. Aberrant activation of NRF2 in cancer is attributed to gain-of-function mutations in the NRF2-encoding gene
Language	English
Publishing date	2023-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15030834
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Article ; Online: Mortality Benefit of a Blood-Based Biomarker Panel for Lung Cancer on the Basis of the Prostate, Lung, Colorectal, and Ovarian Cohort.

Irajizad, Ehsan / Fahrmann, Johannes F / Marsh, Tracey / Vykoukal, Jody / Dennison, Jennifer B / Long, James P / Do, Kim-Anh / Feng, Ziding / Hanash, Samir / Ostrin, Edwin J

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2023 Volume 41, Issue 27, Page(s) 4360–4368

Abstract: Purpose: To investigate the utility of integrating a panel of circulating protein biomarkers in combination with a risk model on the basis of subject characteristics to identify individuals at high risk of harboring a lethal lung cancer.: Methods: ... ...

Abstract	Purpose: To investigate the utility of integrating a panel of circulating protein biomarkers in combination with a risk model on the basis of subject characteristics to identify individuals at high risk of harboring a lethal lung cancer. Methods: Data from an established logistic regression model that combines four-marker protein panel (4MP) together with the Prostate, Lung, Colorectal, and Ovarian (PLCO) risk model (PLCO Results: When considering cases diagnosed within 1 year of blood draw and all noncases, the area under receiver operation characteristics curve estimate of the 4MP + PLCO Conclusion: The blood-based biomarker panel in combination with PLCO
MeSH term(s)	Male ; Humans ; Risk Assessment ; Prostate ; Lung Neoplasms/diagnosis ; Lung Neoplasms/epidemiology ; Lung ; Biomarkers ; Colorectal Neoplasms/diagnosis ; Early Detection of Cancer
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.22.02424
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Article ; Online: Transcriptomic profiles of retinal ganglion cells are defined by the magnitude of intraocular pressure elevation in adult mice.

Park, Yong H / Snook, Joshua D / Ostrin, Edwin J / Kim, Sangbae / Chen, Rui / Frankfort, Benjamin J

Scientific reports

2019 Volume 9, Issue 1, Page(s) 2594

Abstract: Elevated intraocular pressure (IOP) is the major risk factor for glaucoma, a sight threatening disease of retinal ganglion cells (RGCs) and their axons. Despite the central importance of IOP, details of the impact of IOP elevation on RGC gene expression ... ...

Abstract	Elevated intraocular pressure (IOP) is the major risk factor for glaucoma, a sight threatening disease of retinal ganglion cells (RGCs) and their axons. Despite the central importance of IOP, details of the impact of IOP elevation on RGC gene expression remain elusive. We developed a 4-step immunopanning protocol to extract adult mouse RGCs with high fidelity and used it to isolate RGCs from wild type mice exposed to 2 weeks of IOP elevation generated by the microbead model. IOP was elevated to 2 distinct levels which were defined as Mild (IOP increase >1 mmHg and <4 mmHg) and Moderate (IOP increase ≥4 mmHg). RNA sequencing was used to compare the transcriptional environment at each IOP level. Differentially expressed genes were markedly different between the 2 groups, and pathway analysis revealed frequently opposed responses between the IOP levels. These results suggest that the magnitude of IOP elevation has a critical impact on RGC transcriptional changes. Furthermore, it is possible that IOP-based set points exist within RGCs to impact the direction of transcriptional change. It is possible that this improved understanding of changes in RGC gene expression can ultimately lead to novel diagnostics and therapeutics for glaucoma.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Disease Models, Animal ; Female ; Glaucoma/diagnosis ; Glaucoma/metabolism ; Intraocular Pressure ; Male ; Mice ; Mice, Inbred C57BL ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/pathology ; Sequence Analysis, RNA/methods ; Transcriptome
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-02-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-39141-1
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Article: Contributions of Circulating microRNAs for Early Detection of Lung Cancer.

Vykoukal, Jody / Fahrmann, Johannes F / Patel, Nikul / Shimizu, Masayoshi / Ostrin, Edwin J / Dennison, Jennifer B / Ivan, Cristina / Goodman, Gary E / Thornquist, Mark D / Barnett, Matt J / Feng, Ziding / Calin, George A / Hanash, Samir M

Cancers

2022 Volume 14, Issue 17

Abstract: There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed ... ...

Abstract	There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed for their predictive performance in identifying lung cancer cases in the pre-diagnostic setting. The 30 miRNAs were assayed using sera collected from 102 individuals diagnosed with lung cancer within one year following blood draw and 212 controls matched for age, sex, and smoking status. The additive performance of top-performing miRNA candidates in combination with a previously validated four-protein marker panel (4MP) consisting of the precursor form of surfactant protein B (Pro-SFTPB), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA21-1) was additionally assessed. Of the 30 miRNAs evaluated, five (miR-320a-3p, miR-210-3p, miR-92a-3p, miR-21-5p, and miR-140-3p) were statistically significantly (Wilcoxon rank sum test p < 0.05) elevated in case sera compared to controls, with individual AUCs ranging from 0.57−0.62. Compared to the 4MP alone, the combination of 3-miRNAs + 4MP improved sensitivity at 95% specificity by 19.1% ((95% CI of difference 0.0−28.6); two-sided p: 0.006). Our findings demonstrate utility for miRNAs for early detection of lung cancer in combination with a four-protein marker panel.
Language	English
Publishing date	2022-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14174221
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Article ; Online: The Emerging Role of B Cells in Tumor Immunity.

Tsou, Peiling / Katayama, Hiroyuki / Ostrin, Edwin J / Hanash, Samir M

Cancer research

2016 Volume 76, Issue 19, Page(s) 5597–5601

Abstract: There is increasing evidence supporting a role for B cells in tumor immunology. Paraneoplastic syndromes occurring before a cancer diagnosis have pointed to the potential for harnessing the humoral immune response for early cancer detection. The presence ...

Abstract	There is increasing evidence supporting a role for B cells in tumor immunology. Paraneoplastic syndromes occurring before a cancer diagnosis have pointed to the potential for harnessing the humoral immune response for early cancer detection. The presence of tumor-infiltrating B lymphocytes has been linked to a favorable clinical outcome in many types of cancers. However, B cells represent a heterogeneous population with functionally distinct subsets, and the balance among subtypes impacts tumor development. Here, we review recent findings related to B cells and to the humoral immune response in cancer and their translational significance. Cancer Res; 76(19); 5597-601. ©2016 AACR.
MeSH term(s)	Autoantibodies/analysis ; Autoantibodies/therapeutic use ; Autoimmunity ; B-Lymphocytes/immunology ; Biomarkers ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Neoplasms/immunology ; Tumor Microenvironment
Chemical Substances	Autoantibodies ; Biomarkers
Language	English
Publishing date	2016-10-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-16-0431
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