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Article ; Online: Circulating tumor DNA: Solid data from liquid biopsies.

Schrump, David S

The Journal of thoracic and cardiovascular surgery

2017 Volume 154, Issue 3, Page(s) 1132–1133

MeSH term(s)	Carcinoma, Non-Small-Cell Lung ; Circulating Tumor DNA ; Humans ; Liquid Biopsy ; Lung Neoplasms ; Mutation ; Neoplastic Cells, Circulating
Chemical Substances	Circulating Tumor DNA
Language	English
Publishing date	2017-05-25
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	3104-5
ISSN	1097-685X ; 0022-5223
ISSN (online)	1097-685X
ISSN	0022-5223
DOI	10.1016/j.jtcvs.2017.05.059
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Article ; Online: Commentary: Keeping the target painted for precision cancer therapy.

Schrump, David S / Hoang, Chuong D

The Journal of thoracic and cardiovascular surgery

2020 Volume 162, Issue 2, Page(s) 475–476

MeSH term(s)	Humans ; Neoplasms/therapy
Language	English
Publishing date	2020-05-04
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	3104-5
ISSN	1097-685X ; 0022-5223
ISSN (online)	1097-685X
ISSN	0022-5223
DOI	10.1016/j.jtcvs.2020.04.095
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Article ; Online: Invited commentary.

Schrump, David S

The Annals of thoracic surgery

2014 Volume 97, Issue 3, Page(s) 1045

MeSH term(s)	Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Esophageal Neoplasms/genetics ; Esophageal Neoplasms/metabolism ; Esophageal Squamous Cell Carcinoma ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/biosynthesis
Chemical Substances	MIRN17 microRNA, human ; MIRN18A microRNA, human ; MIRN19 microRNA, human ; MicroRNAs
Language	English
Publishing date	2014-02-28
Publishing country	Netherlands
Document type	Journal Article ; Comment
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2013.12.031
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Article ; Online: Analysis of circulating tumor DNA: The next paradigm shift in detection and treatment of lung cancer.

Schrump, David S / Hong, Julie A

The Journal of thoracic and cardiovascular surgery

2018 Volume 155, Issue 6, Page(s) 2632–2633

MeSH term(s)	Biomarkers ; Carcinoma, Non-Small-Cell Lung ; Circulating Tumor DNA ; Humans ; Lung Neoplasms ; Neoplastic Cells, Circulating
Chemical Substances	Biomarkers ; Circulating Tumor DNA
Language	English
Publishing date	2018-02-08
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	3104-5
ISSN	1097-685X ; 0022-5223
ISSN (online)	1097-685X
ISSN	0022-5223
DOI	10.1016/j.jtcvs.2018.01.060
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Article ; Online: Targeting FAcilitates Chromatin Transcription complex inhibits pleural mesothelioma and enhances immunotherapy.

Singh, Anand / Pruett, Nathanael / Dixit, Shivani / Gara, Sudheer K / Wang, Haitao / Pahwa, Roma / Schrump, David S / Hoang, Chuong D

Journal of experimental & clinical cancer research : CR

2023 Volume 42, Issue 1, Page(s) 304

Abstract: Background: Diffuse pleural mesothelioma (DPM) is an aggressive therapy-resistant cancer with unique molecular features. Numerous agents have been tested, but clinically effective ones remain elusive. Herein, we propose to use a small molecule CBL0137 ( ... ...

Abstract	Background: Diffuse pleural mesothelioma (DPM) is an aggressive therapy-resistant cancer with unique molecular features. Numerous agents have been tested, but clinically effective ones remain elusive. Herein, we propose to use a small molecule CBL0137 (curaxin) that simultaneously suppresses nuclear factor-κB (NF-κB) and activates tumor suppressor p53 via targeting FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone critical for DNA repair. Methods: We used DPM cell lines, murine models (xeno- and allo-grafts), plus DPM patient samples to characterize anti-tumor effects of CBL0137 and to delineate specific molecular mechanisms. Results: We verified that CBL0137 induced cell cycle arrest and apoptosis. We also discovered that DPM is a FACT-dependent cancer with overexpression of both subunits structure-specific recognition protein 1 (SSRP1), a poor prognosis indicator, and suppressor of Ty 16 (SUPT16H). We defined several novel uses of CBL0137 in DPM therapy. In combination with cisplatin, CBL0137 exhibited additive anti-tumor activity compared to monotherapy. Similarly, CBL0137 (systemic) could be combined with other novel agents like microRNA-215 (intrapleural) as a more effective regimen. Importantly, we established that CBL0137 induces immunogenic cell death that contributes to activating immune response pathways in DPM. Therefore, when CBL0137 is combined with dual immune checkpoint inhibitors DPM tumor growth is significantly suppressed. Conclusions: We identified an unrecognized molecular vulnerability of DPM based on FACT dependency. CBL0137 alone and in several combinations with different therapeutics showed promising efficacy, including that of improved anti-tumor immunity. Overall, these preclinical findings suggest that CBL0137 could be ideally suited for use in DPM clinical trials.
MeSH term(s)	Humans ; Mice ; Animals ; Chromatin ; Cisplatin ; Mesothelioma, Malignant ; Mesothelioma/drug therapy ; Mesothelioma/genetics ; Immunotherapy ; DNA-Binding Proteins ; High Mobility Group Proteins ; Transcriptional Elongation Factors ; Transcription Factors ; Cell Cycle Proteins ; MicroRNAs/genetics
Chemical Substances	Chromatin ; Cisplatin (Q20Q21Q62J) ; SSRP1 protein, human ; DNA-Binding Proteins ; High Mobility Group Proteins ; Transcriptional Elongation Factors ; SUPT16H protein, human ; Transcription Factors ; Cell Cycle Proteins ; MIRN215 microRNA, human ; MicroRNAs
Language	English
Publishing date	2023-11-16
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-023-02889-6
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Zs.A 2065: Show issues

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Article: Pulmonary Metastasectomy for Adrenocortical Carcinoma-Not If, but When.

Carr, Shamus R / Villa Hernandez, Frank / Varghese, Diana Grace / Choo-Wosoba, Hyoyoung / Steinberg, Seth M / Teke, Martha E / Del Rivero, Jaydira / Schrump, David S / Hoang, Chuong D

Cancers

2024 Volume 16, Issue 4

Abstract: Background: Adrenocortical carcinoma (ACC) commonly metastasizes to the lungs, and pulmonary metastasectomy (PM) is utilized due to limited systemic options.: Methods: All ACC patients with initially only lung metastases (LM) from a single ... ...

Abstract	Background: Adrenocortical carcinoma (ACC) commonly metastasizes to the lungs, and pulmonary metastasectomy (PM) is utilized due to limited systemic options. Methods: All ACC patients with initially only lung metastases (LM) from a single institution constituted this observational case series. Kaplan-Meier and Cox proportional hazard analyses evaluated the association with potential prognostic factors and outcomes. Overall survival (OS) was calculated from the date of the PM or, in those patients who did not undergo surgery, from the development of LM. Results: A total of 75 ACC patients over a 45-year period met the criteria; 52 underwent PM, and 23 did not. The patients undergoing PM had a median OS of 3.1 years (95% CI: 2.4, 4.7 years) with the 5- and 10-year OS being 35.5% and 32.8%, respectively. The total resected LM did not impact the OS nor the DFS. The patients who developed LM after 11 months from the initial ACC resection had an improved OS (4.2 years; 95% CI: 3.2, NR; Conclusions: PM appears to have a role in ACC patients. The number of nodules should not be an exclusion factor. Patients developing LM within a year of primary tumor resection may benefit from waiting before further surgeries, which may provide additional insight into who may benefit from PM.
Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16040702
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Article ; Online: Clinical utility of immunohistochemical subtyping in patients with small cell lung cancer.

Chiang, Chi-Lu / Huang, Hsu-Ching / Luo, Yung-Hung / Shen, Chia-I / Chao, Heng-Sheng / Tseng, Yen-Han / Chou, Teh-Ying / Schrump, David S / Yeh, Yi-Chen / Chen, Yuh-Min

Lung cancer (Amsterdam, Netherlands)

2024 Volume 188, Page(s) 107473

Abstract: Objectives: Molecular subtyping of small cell lung cancer (SCLC) tumors based on the expression of four transcription factors (ASCL1, NEUROD1, POU2F3, and YAP1) using immunohistochemical (IHC) staining has recently emerged as a proposed approach. This ... ...

Abstract	Objectives: Molecular subtyping of small cell lung cancer (SCLC) tumors based on the expression of four transcription factors (ASCL1, NEUROD1, POU2F3, and YAP1) using immunohistochemical (IHC) staining has recently emerged as a proposed approach. This study was aimed to examine this subtyping method in Asian patients with SCLC and investigate its correlation with treatment efficacy. Materials and methods: Seventy-two tumor samples from patients with SCLC, including de novo cases and those transformed from EGFR-mutant tumors, were analyzed. IHC staining was used to measure the expression of the four transcription factors and conventional SCLC markers. Subtypes were defined based on relative expression levels. The treatment response and outcome of patients receiving immune checkpoint inhibitors and chemotherapy were also reviewed. Results: ASCL1 was the most common subtype, observed in 55.2 % of the samples, followed by NEUROD1 (26.9 %) and POU2F3 (9 %). No tumor exhibited predominant YAP1 positivity, while 41.8 % of the samples demonstrated positivity for two subtype markers. Approximately 50 % of the patients experienced a subtype switch after disease progression. Patients with the ASCL1/NEUROD1 (SCLC-A/N) subtype had similar progression-free survival (PFS) compared to non-SCLC-A/N patients after treatment with immune checkpoint inhibitors plus chemotherapy. Transformed SCLC patients had significantly worse PFS than de novo SCLC patients after chemoimmunotherapy. (2.1 vs. 5.4 months, P = 0.023) CONCLUSIONS: This study revealed the challenges associated with using IHC alone for molecular subtyping, highlighting the frequent co-expression of subtypes and temporal changes following treatment. Further research is warranted to explore the prognostic and therapeutic implications of IHC subtyping in patients with SCLC.
MeSH term(s)	Humans ; Small Cell Lung Carcinoma/drug therapy ; Lung Neoplasms/drug therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Transcription Factors/metabolism
Chemical Substances	Immune Checkpoint Inhibitors ; Transcription Factors
Language	English
Publishing date	2024-01-13
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2024.107473
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Targeting epigenetic mediators of gene expression in thoracic malignancies.

Schrump, David S

Biochimica et biophysica acta

2012 Volume 1819, Issue 7, Page(s) 836–845

Abstract: Lung and esophageal cancers and malignant pleural mesotheliomas are highly lethal neoplasms that are leading causes of cancer-related deaths worldwide. Presently, limited information is available pertaining to epigenetic mechanisms mediating initiation ... ...

Abstract	Lung and esophageal cancers and malignant pleural mesotheliomas are highly lethal neoplasms that are leading causes of cancer-related deaths worldwide. Presently, limited information is available pertaining to epigenetic mechanisms mediating initiation and progression of these neoplasms. The following presentation will focus on the potential clinical relevance of epigenomic alterations in thoracic malignancies mediated by DNA methylation, perturbations in the histone code, and polycomb group proteins, as well as ongoing translational efforts to target epigenetic regulators of gene expression for treatment of these neoplasms. This article is part of a Special Issue entitled: Chromatin in time and space.
MeSH term(s)	Animals ; Chromatin/genetics ; Chromatin/metabolism ; DNA Methylation ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/physiology ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Molecular Targeted Therapy ; Polycomb-Group Proteins/metabolism ; Polycomb-Group Proteins/physiology ; Protein Processing, Post-Translational ; Thoracic Neoplasms/drug therapy ; Thoracic Neoplasms/genetics ; Thoracic Neoplasms/metabolism
Chemical Substances	Chromatin ; DNA-Binding Proteins ; Polycomb-Group Proteins
Language	English
Publishing date	2012-04-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagrm.2012.03.009
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Article: MicroRNA-206 suppresses mesothelioma progression via the Ras signaling axis.

Singh, Anand / Pruett, Nathanael / Pahwa, Roma / Mahajan, Arushi P / Schrump, David S / Hoang, Chuong D

Molecular therapy. Nucleic acids

2021 Volume 24, Page(s) 669–681

Abstract: ... therapeutic target, there are no standard agent(s) specifically inhibiting Ras signaling adopted in clinical ...

Abstract	Malignant pleural mesothelioma (MPM) is an incurable surface neoplasm with peculiar pathobiology. MPM proliferates by using the tyrosine-kinase-Ras pathway. Despite representing an attractive therapeutic target, there are no standard agent(s) specifically inhibiting Ras signaling adopted in clinical settings. We posited that biologic effects of microRNA (miRNA) can disrupt this molecular network. Using patient samples, cell lines, and murine tumor xenograft models, we confirmed specific genes in the Ras pathway are targeted by an MPM-associated miRNA and then examined its therapeutic effects. We verified significant and consistent downregulation of miR-206 in MPM tissues. When miR-206 is ectopically re-expressed in MPM cells and delivered to tumor xenografts in mice, it exerted significant cell killing by suppressing multiple components of the receptor-tyrosine-kinase-Ras-cell-cycle-signaling network; some of which were prognostic when overexpressed and/or have not been druggable. Of note, we validated
Language	English
Publishing date	2021-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2021.04.001
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Article ; Online: Characterization of pleural mesothelioma by hierarchical clustering analyses using immune cells within tumor microenvironment.

Inaguma, Shingo / Wang, Chengbo / Ito, Sunao / Ueki, Akane / Lasota, Jerzy / Czapiewski, Piotr / Langfort, Renata / Rys, Janusz / Szpor, Joanna / Waloszczyk, Piotr / Okoń, Krzysztof / Biernat, Wojciech / Takiguchi, Shuji / Schrump, David S / Miettinen, Markku / Takahashi, Satoru

Pathobiology : journal of immunopathology, molecular and cellular biology

2024

Abstract: Introduction: Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated.: Methods: In this study, 60 well-characterized pleural ... ...

Abstract	Introduction: Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated. Methods: In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1 and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed. Results: Among the immune cell markers, CD3 (P < 0.0001), CD4 (P = 0.0016), CD8 (P = 0.00094), CD163+ (P = 0.042) and FOXP3+ (P = 0.025) were significantly associated with unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (P = 0.050), CD27 (P = 0.014) and TIM-3 (P = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (P = 0.011): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (P = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04) and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients. Conclusion: Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.
Language	English
Publishing date	2024-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1022703-9
ISSN	1423-0291 ; 1015-2008
ISSN (online)	1423-0291
ISSN	1015-2008
DOI	10.1159/000538520
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