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CUL4high lung adenocarcinomas are dependent on the CUL4-p21 ubiquitin signaling for proliferation and survival
Wang, Yannan; Yan, Fan; Nasar, Abu; Chen, Zhe-Sheng; Altorki, Nasser Khaled; Stiles, Brendon; Narula, Navneet; Zhou, Pengbo
Cullin 4A and 4B ubiquitin ligases are often highly accumulated in human malignancies, and are believed to possess oncogenic properties. However, the underlying mechanisms by which CUL4A and CUL4B promote pulmonary tumorigenesis remain largely elusive. In this study, we report that both CUL4A and CUL4B are highly expressed in non-small cell lung cancer (NSCLC) patients, and high expression of both is associated with disease progression, chemotherapy resistance, and poor survival in adenocarcinomas. Depletion of CUL4A (CUL4Ak/d) or CUL4B (CUL4Bk/d) leads to cell cycle arrest at G1 and loss of proliferation and viability of NSCLC cells both in culture and in a lung cancer xenograft model, suggesting that CUL4A and 4B are oncoproteins required for tumor maintenance of certain NSCLC. Mechanistically, increased accumulation of the cell cycle-dependent kinase inhibitor p21/Cip1/WAF1 was observed in lung cancer cells upon CUL4 silencing. Knockdown of p21 rescued the G1 arrest of CUL4Ak/d or CUL4Bk/d NSCLC cells and allowed proliferation to resume. These findings reveal that p21 is the primary downstream effector of lung adenocarcinoma dependence on CUL4, highlight the notion that not all substrates respond equally to abrogation of the CUL4 ubiquitin ligase in NSCLCs, and imply that CUL4Ahigh CUL4Bhigh may serve as a prognostic marker and therapeutic target for NSCLC patients.
PMID: 34119472
ISSN: 1525-2191
CID: 4916652
Lepidic-Like Pattern of Metastasis in Solitary Pulmonary Nodules: A Systematic Review with Radiologic-Pathologic Correlation of a Deceptive Phenomenon [Meeting Abstract]
Amezcua, Jose Manuel Gutierrez; Zhou, Fang; Azour, Leah; Narula, Navneet; Moreira, Andre; Adler, Esther
ISI:000629694102301
ISSN: 0023-6837
CID: 4916742
Lepidic-Like Pattern of Metastasis in Solitary Pulmonary Nodules: A Systematic Review with Radiologic-Pathologic Correlation of a Deceptive Phenomenon [Meeting Abstract]
Amezcua, Jose Manuel Gutierrez; Zhou, Fang; Azour, Leah; Narula, Navneet; Moreira, Andre; Adler, Esther
ISI:000629690900928
ISSN: 0893-3952
CID: 4916722
Considerations for Patients With Peripheral Artery Disease During the COVID-19 Pandemic [Editorial]
Farhan, Serdar; Kamran, Haroon; Vogel, Birgit; Garg, Karan; Rao, Ajit; Narula, Navneet; Jacobowitz, Glenn; Tarricone, Arthur; Kapur, Vishal; Faries, Peter; Marin, Michael; Narula, Jagat; Lookstein, Robert; Olin, Jeffrey W; Krishnan, Prakash
New York City was one of the epicenters of the COVID-19 pandemic. The management of peripheral artery disease (PAD) during this time has been a major challenge for health care systems and medical personnel. This document is based on the experiences of experts from various medical fields involved in the treatment of patients with PAD practicing in hospitals across New York City during the outbreak. The recommendations are based on certain aspects including the COVID-19 infection status as well as the clinical PAD presentation of the patient. Our case-based algorithm aims at guiding the treatment of patients with PAD during the pandemic in a safe and efficient way.
PMCID:8013533
PMID: 33783244
ISSN: 1938-2723
CID: 4862282
Recognizing Cutibacterium acnes as a cause of infectious pericarditis: A case report and review of literature [Case Report]
Li-Geng, Tony; Geraci, Travis C; Narula, Navneet; Zervou, Fainareti N; Prasad, Prithiv J; Decano, Arnold G; Sterling, Stephanie; Zacharioudakis, Ioannis M
Cutibacterium acnes is an anaerobic bacterium commonly thought of as a culture contaminant rather than a pathogen. We present a case of Cutibacterium acnes pericarditis in a 22-year-old immunocompetent woman managed with surgical pericardial window and a 4-week course of penicillin G and review related literature on Cutibacterium acnes pericarditis.
PMID: 33771686
ISSN: 1095-8274
CID: 4830272
A novel approach to percutaneous aortic thrombectomy [Case Report]
Silverglate, Quinn; Maldonado, Thomas S; Narula, Navneet; Garg, Karan
Aortic mural thrombus in the absence of underlying aortic disease is rare and results in a risk of distant arterial embolization that can result in limb loss or other end organ damage. Current management involves open surgery, anticoagulation, and systemic thrombolysis; however, each carries inherent risks. We report the case of aortic thrombus with distal emboli in two patients, a 56-year-old man and a 68-year-old man, neither with underlying aortic pathology and both presenting with limb threatening ischemia. We performed percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, Calif) with successful removal of the aortic thrombus in both patients.
PMCID:7921181
PMID: 33718682
ISSN: 2468-4287
CID: 4815172
Lobectomy for Hemorrhagic Lobar Infarction in a Patient With COVID-19 [Case Report]
Geraci, Travis C; Narula, Navneet; Smith, Deane E; Moreira, Andre L; Kon, Zachary N; Chang, Stephanie H
Patients with severe coronavirus disease 2019 from infection with severe acute respiratory syndrome coronavirus 2 mount a profound inflammatory response and are predisposed to thrombotic complications. Pulmonary vein thrombosis is a rare disease process resulting in pulmonary congestion, infarction, and potential mortality. This report describes a patient with coronavirus disease 2019 requiring venovenous extracorporeal membrane oxygenation for hypoxic respiratory failure who developed hemorrhagic infarction of the right lower lobe. During emergency exploration the patient was found to have a right inferior vein thrombosis and marked lobar hemorrhage mandating lobectomy.
PMCID:7518229
PMID: 32987023
ISSN: 1552-6259
CID: 4798372
Robotic Resection of a Combined Capillary and Arteriovenous Malformation in the Mediastinum [Case Report]
Sasankan, Prabhu; Geraci, Travis C; Narula, Navneet; Cerfolio, Robert
The adult presentation of a mediastinal arteriovenous malformation is rare. Resection of these lesions are commonly performed via open thoracotomy, with a risk of bleeding from multiple feeding vessels. This report describes a robotic resection of a mediastinal arteriovenous malformation in a 55-year-old man.
PMID: 32835753
ISSN: 1552-6259
CID: 4798332
Bronchiolar Adenoma/Pulmonary Ciliated Muconodular Papillary Tumor
Shirsat, Hemlata; Zhou, Fang; Chang, Jason C; Rekhtman, Natasha; Saqi, Anjali; Argyropoulos, Kimon; Azour, Lea; Simms, Anthony; Melamed, Jonathan; Hung, Yin P; Roden, Anja C; Mino-Kenudson, Mari; Moreira, Andre L; Narula, Navneet
OBJECTIVES/OBJECTIVE:To describe the histologic features that are helpful in the diagnosis of the rare bronchiolar adenomas/ciliated muconodular papillary tumors (BAs/CMPTs) during intraoperative consultation. METHODS:Multi-institutional retrospective review of frozen sections of 18 BAs/CMPTs. RESULTS:In 14 of 18 cases, BA/CMPT was the primary reason for sublobar lung resection, and in 4 cases, BA/CMPT was an incidental finding intraoperatively for resections performed for carcinoma in other lobes. There were 11 proximal-type/classic BAs/CMPTs and 7 distal-type/nonclassic BAs/CMPTs. Only 3 (16.7%) of 18 were correctly diagnosed at the time of frozen section, all of which were proximal type/classic. The remainder were diagnosed as adenocarcinoma (n = 7); invasive mucinous adenocarcinoma (n = 1); non-small cell lung carcinoma (n = 1); cystic mucinous neoplasm, favor adenocarcinoma (either mucinous or colloid type) (n = 1); favor adenocarcinoma, cannot exclude CMPT (n = 1); atypical proliferation (n = 2); mucinous epithelial proliferation (n = 1); and mucous gland adenoma (n = 1). CONCLUSIONS:BA/CMPT can potentially be misdiagnosed as carcinoma during intraoperative consultation. On retrospective review of the frozen sections, the presence of the following may help to avoid misdiagnosis: a mixture of bland ciliated columnar cells, mucinous cells, and, most important, a basal cell layer, as well as a lack of necrosis, significant atypia, and mitoses.
PMID: 33313677
ISSN: 1943-7722
CID: 4717512
Somatostatin receptor imaging in active cardiac sarcoidosis: Would less be enough? [Editorial]
Zubin Maslov, Petra; Narula, Navneet; Narula, Jagat
PMID: 31332660
ISSN: 1532-6551
CID: 3987962