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Article ; Online: Plasma Biomarkers to Monitor Bronchopulmonary Carcinoids-Are We There Yet?

Roden, Anja C / Molina, Julian R

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2023 Volume 18, Issue 3, Page(s) 257–259

MeSH term(s)	Humans ; Lung Neoplasms ; Carcinoid Tumor/diagnosis ; Biomarkers ; Bronchi ; Biomarkers, Tumor
Chemical Substances	Biomarkers ; Biomarkers, Tumor
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2022.12.008
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Zs.A 6664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 652: Show issues

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Article ; Online: Surveillance after pediatric thymoma resection.

Wee, Christopher E / Molina, Julian R

Mediastinum (Hong Kong, China)

2019 Volume 3, Page(s) 19

Language	English
Publishing date	2019-05-30
Publishing country	China
Document type	Editorial
ISSN	2522-6711
ISSN (online)	2522-6711
DOI	10.21037/med.2019.04.08
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Article: Immunotherapy in patients with autoimmune disease.

Rakshit, Sagar / Molina, Julian R

Journal of thoracic disease

2020 Volume 12, Issue 11, Page(s) 7032–7038

Abstract: Immune checkpoint inhibitors (ICIs) such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors are widely used for the treatment of multiple cancers. ... ...

Abstract	Immune checkpoint inhibitors (ICIs) such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors are widely used for the treatment of multiple cancers. Seven of these agents are currently FDA approved in the US as first or second line options for solid tumors and hematologic malignancies. These agents work by downregulating pathways that suppress T-cell activation and thereby mounting an immune response to the tumor. In general, ICI are well tolerated with only mild to moderate toxicity. However, in some patients severe immune-related adverse events (irAEs) that mimic the presentation of autoimmune diseases (AID) may occur. It is believed that irAEs occur due to disruption of immunologic self-tolerance, a mechanism that also seems to explain AID. Patients with pre-existing AID are usually excluded from prospective clinical trials due to concerns for flares of the underline AID. There is limited retrospective evidence supporting the use of ICI in patients with some pre-existing AID. These patients have an increased risk of malignancy and there is an unmet need to study ICIs in this population. This manuscript intends to review the current available evidence for the safety and activity of ICIs in patients with pre-existing AID. We summarize the reported use of ICI in patients with pre-existing AID according to the primary tumor site and type of ICI used.
Language	English
Publishing date	2020-11-24
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd-2019-cptn-10
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Article: EZH2 and POU2F3 Can Aid in the Distinction of Thymic Carcinoma from Thymoma.

Naso, Julia R / Vrana, Julie A / Koepplin, Justin W / Molina, Julian R / Roden, Anja C

Cancers

2023 Volume 15, Issue 8

Abstract: Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these entities, EZH2 and POU2F3, and compared them with conventional immunostains. Whole slide ... ...

Abstract	Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these entities, EZH2 and POU2F3, and compared them with conventional immunostains. Whole slide sections of 37 thymic carcinomas, 23 type A thymomas, 13 type B3 thymomas, and 8 micronodular thymomas with lymphoid stroma (MNTLS) were immunostained for EZH2, POU2F3, CD117, CD5, TdT, BAP1, and MTAP. POU2F3 (≥10% hotspot staining), CD117, and CD5 showed 100% specificity for thymic carcinoma versus thymoma with 51%, 86%, and 35% sensitivity, respectively, for thymic carcinoma. All POU2F3 positive cases were also positive for CD117. All thymic carcinomas showed >10% EZH2 staining. EZH2 (≥80% staining) had a sensitivity of 81% for thymic carcinoma and a specificity of 100% for thymic carcinoma versus type A thymoma and MNTLS but had poor specificity (46%) for thymic carcinoma versus B3 thymoma. Adding EZH2 to a panel of CD117, TdT, BAP1, and MTAP increased cases with informative results from 67/81 (83%) to 77/81 (95%). Overall, absent EZH2 staining may be useful for excluding thymic carcinoma, diffuse EZH2 staining may help to exclude type A thymoma and MNTLS, and ≥10% POU2F3 staining has excellent specificity for thymic carcinoma versus thymoma.
Language	English
Publishing date	2023-04-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15082274
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Article: Editorial: pleural recurrence of thymoma-what is the value of intra-thoracic chemo-hyperthermia?

Roden, Anja C / Molina, Julian R

Journal of thoracic disease

2017 Volume 9, Issue 10, Page(s) 3583–3586

Language	English
Publishing date	2017-12-05
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd.2017.09.44
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Article ; Online: Correction to: PFKFB3 regulates cancer stemness through the hippo pathway in small cell lung carcinoma.

Thirusangu, Prabhu / Ray, Upasana / Sarkar Bhattacharya, Sayantani / Oien, Derek B / Jin, Ling / Staub, Julie / Kannan, Nagarajan / Molina, Julian R / Shridhar, Viji

Oncogene

2022

Language	English
Publishing date	2022-11-28
Publishing country	England
Document type	Published Erratum
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-022-02470-z
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Article ; Online: PFKFB3 works on the FAK-STAT3-SOX2 axis to regulate the stemness in MPM.

Sarkar Bhattacharya, Sayantani / Thirusangu, Prabhu / Jin, Ling / Staub, Julie / Shridhar, Viji / Molina, Julian R

British journal of cancer

2022 Volume 127, Issue 7, Page(s) 1352–1364

Abstract: Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm and often acquires chemoresistance by increasing stemness in tumour tissue, thereby generating cancer stem cells (CSCs). CSCs escape treatment by deploying metabolic pathways to ... ...

Abstract	Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm and often acquires chemoresistance by increasing stemness in tumour tissue, thereby generating cancer stem cells (CSCs). CSCs escape treatment by deploying metabolic pathways to trigger dormancy or proliferation, also gaining the ability to exit and re-enter the cell cycle to hide their cellular identity. Methods: We employed various cellular and biochemical assays to identify the role of the glycolytic enzyme PFKFB3, by knocking it down and pharmacologically inhibiting it with PFK158, to determine its anticancer effects in vitro and in vivo by targeting the CSC population in MPM. Results: Here, we have identified PFKFB3 as a strategic player to target the CSC population in MPM and demonstrated that both pharmacologic (PFK158) and genetic inhibition of PFKFB3 destroy the FAK-Stat3-SOX2 nexus resulting in a decline in conspicuous stem cell markers viz. ALDH, CD133, CD44, SOX2. Inhibition of PFKFB3 accumulates p21 and p27 in the nucleus by decreasing SKP2. Lastly, PFK158 diminishes tumour-initiating cells (TICs) mediated MPM xenograft in vivo. Conclusions: This study confers a comprehensive and mechanistic function of PFKFB3 in CSC maintenance that may foster exceptional opportunities for targeted small molecule blockade of the TICs in MPM.
MeSH term(s)	Cell Line, Tumor ; Cell Proliferation ; Humans ; Mesothelioma, Malignant ; Neoplastic Stem Cells/pathology ; Phosphofructokinase-2/genetics ; Phosphofructokinase-2/metabolism ; Pyridines/pharmacology ; Quinolines/pharmacology ; SOXB1 Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism ; SOXB1 Transcription Factors/pharmacology ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism
Chemical Substances	PFK158 ; Pyridines ; Quinolines ; SOX2 protein, human ; SOXB1 Transcription Factors ; STAT3 Transcription Factor ; STAT3 protein, human ; PFKFB3 protein, human (EC 2.7.1.105) ; Phosphofructokinase-2 (EC 2.7.1.105)
Language	English
Publishing date	2022-07-06
Publishing country	England
Document type	Journal Article
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-022-01867-7
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Article ; Online: Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment.

Duma, Narjust / Santana-Davila, Rafael / Molina, Julian R

Mayo Clinic proceedings

2019 Volume 94, Issue 8, Page(s) 1623–1640

Abstract: Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non-small cell lung cancer (NSCLC). Screening has been introduced with the goal of early detection. The ...

Abstract	Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non-small cell lung cancer (NSCLC). Screening has been introduced with the goal of early detection. The National Lung Screening Trial found a lung cancer mortality benefit of 20% and a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography in high-risk individuals. The treatment of lung cancer has also evolved with the introduction of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of NSCLC treatment. Furthermore, the results of new trials continue to help us understand the role of these novel agents and which patients are more likely to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy, combined with chemotherapy, or after definite chemoradiotherapy in patients with stage III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant cells has been studied as a potential biomarker for response to ICIs. However, important drawbacks exist that limit its discriminatory potential. Identification of accurate predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains essential to select the most appropriate candidates for ICI therapy. Many questions remain unanswered regarding the proper sequence and combinations of these new agents; however, the field is moving rapidly, and the overall direction is optimistic.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/epidemiology ; Carcinoma, Non-Small-Cell Lung/prevention & control ; Carcinoma, Non-Small-Cell Lung/therapy ; Chemoradiotherapy/methods ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Early Detection of Cancer/methods ; Education, Medical, Continuing ; Female ; Humans ; Immunotherapy/methods ; Lung Neoplasms/diagnosis ; Lung Neoplasms/epidemiology ; Lung Neoplasms/prevention & control ; Lung Neoplasms/therapy ; Male ; Molecular Targeted Therapy/methods ; Pneumonectomy/methods ; Prognosis ; Risk Assessment ; Survival Analysis ; United States
Language	English
Publishing date	2019-08-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2019.01.013
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Article ; Online: Pulmonary Neuroendocrine Tumors: Adjuvant and Systemic Treatments.

Uprety, Dipesh / Halfdanarson, Thorvardur R / Molina, Julian R / Leventakos, Konstantinos

Current treatment options in oncology

2020 Volume 21, Issue 11, Page(s) 86

Abstract: Opinion statement: Bronchial carcinoids are uncommon tumors accounting for 20 to 30% of all neuroendocrine tumors and about 1-2% of all cancers of pulmonary origin. Bronchial carcinoids are well-differentiated neuroendocrine tumors and have a favorable ... ...

Abstract	Opinion statement: Bronchial carcinoids are uncommon tumors accounting for 20 to 30% of all neuroendocrine tumors and about 1-2% of all cancers of pulmonary origin. Bronchial carcinoids are well-differentiated neuroendocrine tumors and have a favorable survival outcome when compared with other subtypes of lung cancers. Treatment of bronchial carcinoids is not simple owing to intricacy of symptom presentation and heterogeneity of disease biology. Successful treatment of patients requires a multimodality approach. Resection is curative in the majority of patients with localized tumors and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced disease. To date, very few randomized clinical trials have been done, partly owing to the relative rarity of this malignancy. Somatostatin analogs (SSAs) are reasonable first-line choice for patients with tumors expressing somatostatin receptors. Everolimus is an appropriate first-line choice for somatostatin receptor negative tumors and for any patients with progressive disease. PRRT can also be considered for progressive tumors expressing somatostatin receptors. Based on retrospective series, cytotoxic chemotherapy can be selected in patients with progressive tumors, primarily when cytoreduction is needed. Herein, we will discuss evidence supporting the role of adjuvant and systemic treatment therapies for those with bronchial carcinoid tumors by focusing on various studies.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bronchial Neoplasms/therapy ; Capecitabine/therapeutic use ; Carcinoid Tumor/therapy ; Chemotherapy, Adjuvant ; Cisplatin/therapeutic use ; Etoposide/therapeutic use ; Everolimus/therapeutic use ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Lung Neoplasms/therapy ; Lymph Node Excision ; Molecular Targeted Therapy ; Neuroendocrine Tumors/therapy ; Octreotide/analogs & derivatives ; Octreotide/therapeutic use ; Organometallic Compounds/therapeutic use ; Pneumonectomy ; Protein Kinase Inhibitors/therapeutic use ; Radiopharmaceuticals/therapeutic use ; Receptors, Somatostatin ; Somatostatin/analogs & derivatives ; Temozolomide/therapeutic use ; Watchful Waiting
Chemical Substances	Antineoplastic Agents ; Immune Checkpoint Inhibitors ; Organometallic Compounds ; Protein Kinase Inhibitors ; Radiopharmaceuticals ; Receptors, Somatostatin ; Somatostatin (51110-01-1) ; Capecitabine (6804DJ8Z9U) ; Etoposide (6PLQ3CP4P3) ; Everolimus (9HW64Q8G6G) ; lutetium Lu 177 dotatate (AE221IM3BB) ; Cisplatin (Q20Q21Q62J) ; Octreotide (RWM8CCW8GP) ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2020-08-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057351-0
ISSN	1534-6277 ; 1527-2729
ISSN (online)	1534-6277
ISSN	1527-2729
DOI	10.1007/s11864-020-00786-0
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Zs.A 5523: Show issues

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Article: Comparative Analysis of Predictive Biomarkers for PD-1/PD-L1 Inhibitors in Cancers: Developments and Challenges.

Yang, Fang / Wang, Jacqueline F / Wang, Yucai / Liu, Baorui / Molina, Julian R

Cancers

2021 Volume 14, Issue 1

Abstract: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with ... ...

Abstract	Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the PD-1/PD-L1 blockade has demonstrated meaningful clinical responses and benefits in only a subset of patients. In addition, several severe and life-threatening adverse events were observed in these patients. Therefore, the identification of predictive biomarkers is urgently needed to select patients who are more likely to benefit from ICI therapy. PD-L1 expression level is the most commonly used biomarker in clinical practice for PD-1/PD-L1 inhibitors. However, negative PD-L1 expression cannot reliably exclude a response to a PD-1/PD-L1 blockade. Other factors, such as tumor microenvironment and other tumor genomic signatures, appear to impact the response to ICIs. In this review, we examine emerging data for novel biomarkers that may have a predictive value for optimizing the benefit from anti-PD-1/PD-L1 immunotherapy.
Language	English
Publishing date	2021-12-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14010109
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