34 results on '"Puja Kachroo"'
Search Results
2. A Unique Case of Orthostasis in a Patient With Testicular Choriocarcinoma
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Douglas Kyrouac, MD, Daniel J. Lenihan, MD, Andrew M. Kates, MD, Puja Kachroo, MD, Gerald R. Fortuna, Jr, MD, Bruce Roth, MD, and Joshua D. Mitchell, MD
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anticoagulation ,atrial thrombus ,brain metastasis ,cardiac mass ,cardiac MRI ,catheter associated thrombus ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2019
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3. Outcomes of Medical Therapy Plus PCI for Multivessel or Left Main CAD Ineligible for Surgery
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Adam C. Salisbury, J. Aaron Grantham, W. Morris Brown, William L. Ballard, Keith B. Allen, Ajay J. Kirtane, Michael Argenziano, Robert W. Yeh, Kamal Khabbaz, John Lasala, Puja Kachroo, Dimitri Karmpaliotis, Jeffrey Moses, William L. Lombardi, Karen Nugent, Ziad Ali, Kensey L. Gosch, John A. Spertus, and David E. Kandzari
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Cardiology and Cardiovascular Medicine - Published
- 2023
4. Commentary: Starting the conversation of race and outcomes in proximal aortic surgery
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Ali J. Khiabani and Puja Kachroo
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Pulmonary and Respiratory Medicine ,Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2022
5. Commentary: Roadmap to improved success with high-risk thoracoabdominal aortic aneurysm patients
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Puja Kachroo
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Pulmonary and Respiratory Medicine ,Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2022
6. Survival after operative repair of acute type A aortic dissection varies according to the presence and type of preoperative malperfusion
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Stanley B. Wolfe, Thoralf M. Sundt, Eric M. Isselbacher, Duke E. Cameron, Santi Trimarchi, Raffi Bekeredjian, Bradley Leshnower, Joseph E. Bavaria, Derek R. Brinster, Ibrahim Sultan, Chih-Wen Pai, Puja Kachroo, Maral Ouzounian, Joseph S. Coselli, Truls Myrmel, Davide Pacini, Kim Eagle, Himanshu J. Patel, and Arminder S. Jassar
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Pulmonary and Respiratory Medicine ,Surgery ,Cardiology and Cardiovascular Medicine - Abstract
Approximately one-quarter of patients with acute type A aortic dissection (TAAD) present with concomitant malperfusion of coronary arteries, mesenteric circulation, lower extremities, kidneys, brain, and/or coma. It is generally accepted that TAAD patients who present with malperfusion experience higher mortality rates than patients without, although how specific malperfusion syndromes, alone or in combination, affect mortality is not well described.The International Registry of Acute Aortic Dissection database was queried for patients who underwent surgical repair of TAAD. Patients were stratified according to the presence/absence of malperfusion at presentation. Multivariable logistic regression was used to evaluate in-hospital mortality according to malperfusion type. Kaplan-Meier estimates were used to estimate 30-day postoperative survival.Six thousand four hundred thirty-seven patients underwent surgical repair of acute TAAD, of whom 2642 (41%) had 1 or more preoperative malperfusion syndromes. Mesenteric malperfusion (adjusted odds ratio [AOR], 4.84; P .001) was associated with the highest odds of in-hospital mortality, followed by coma (AOR, 1.88; P = .007), limb ischemia (AOR, 1.73; P = .008), and coronary malperfusion (AOR, 1.51; P = .02). Renal malperfusion (AOR, 1.37; P = .24) and neurologic deficit (AOR, 1.35; P = .28) were not associated with increased in-hospital mortality. In patients who survived to discharge, there was no difference in 1-year postdischarge survival in the malperfusion and no malperfusion cohorts (P = .36).Survival during the index admission after TAAD repair varies according to the presence and type of malperfusion syndromes, with mesenteric malperfusion being associated with the highest odds of in-hospital death. Not only the presence of malperfusion but rather specific malperfusion syndromes should be considered when assessing a patient's risk of undergoing TAAD repair.
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- 2022
7. Impact of Surgical Experience on Operative Mortality After Reoperative Cardiac Surgery
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Michael K. Pasque, Marc R. Moon, A. Itoh, Matthew C. Henn, Nabil A. Munfakh, Puja Kachroo, Kunal D. Kotkar, Ralph J. Damiano, Muhammad F. Masood, Spencer J. Melby, and Hersh S. Maniar
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Reoperation ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Time Factors ,Bypass grafting ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Statistical significance ,medicine ,Humans ,Hospital Mortality ,Coronary Artery Bypass ,Aged ,Aged, 80 and over ,Heart Valve Prosthesis Implantation ,business.industry ,General surgery ,Operative mortality ,Middle Aged ,Cardiac surgery ,Standardized mortality ratio ,030228 respiratory system ,Surgery ,Clinical Competence ,Cardiology and Cardiovascular Medicine ,business ,Learning Curve - Abstract
Background Learning curves and skill attrition with aging have been reported to impair outcomes in select surgical subspecialties, but their role in complex cardiac surgery remains unknown. Methods From 1986 to 2019, 2314 patients underwent reoperative cardiac surgery: coronary artery bypass grafting (n = 543), valve (n = 1527), or combined coronary artery bypass grafting and valve (n = 244). Thirty-four different surgeons in practice between 1 and 39 years were included. Standardized mortality ratio (observed-to-expected) was determined for all surgeons in each post-training year of experience. Results Risk-adjusted cumulative sum change-point analysis was used to define five distinct career phases: 0 to 4 years, 5 to 8 years, 9 to 17 years, 18 to 28 years, and 29 to 39 years. With 5 to 8 years and 18 to 28 years of experience, standardized mortality ratio was near unity (0.95 and 1.05, respectively) and lowest with 9 to 17 years of experience (0.78, P = .03). In the youngest experience group (0 to 4 years), observed and expected mortality were both highest, and standardized mortality ratio was elevated at 1.29, which approached statistical significance (P = .059). In the oldest experience group (29 to 39 years), expected mortality was low compared with most other groups but observed mortality increased, yielding a significantly elevated standardized mortality ratio at 1.53 (P = .032). Conclusions Standardized mortality ratios with reoperative cardiac surgery were highest early and late in a surgeon’s career and lowest in mid career. As surgeons gain experience, outcomes improve through the first two career decades, then stabilize in the third decade before declining in the fourth decade.
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- 2020
8. Transcatheter Aortic Valve Replacement (TAVR) in Patients with Paradoxical Low-Flow Low-Gradient Aortic Stenosis
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John M. Lasala, Hersh S. Maniar, Brian R. Lindman, Manoj Thangam, Alan Zajarias, Prashanth Thakker, Spencer J. Melby, Marc Sintek, Nishath Quader, Puja Kachroo, and Mustafa Husaini
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medicine.medical_specialty ,animal structures ,Ejection fraction ,Transcatheter aortic ,business.industry ,medicine.medical_treatment ,medicine.disease ,Asymptomatic ,Stenosis ,Aortic valve replacement ,Valve replacement ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,In patient ,cardiovascular diseases ,Low gradient ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aortic valve replacement is recommended in symptomatic patients with severe aortic stenosis (AS) or asymptomatic with reduced left ventricular ejection fraction (LVEF). The treatment algorithm of p...
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- 2020
9. A Unique Case of Orthostasis in a Patient With Testicular Choriocarcinoma
- Author
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Andrew M. Kates, Gerald R. Fortuna, Puja Kachroo, Douglas Kyrouac, Joshua D. Mitchell, Bruce J. Roth, and Daniel J. Lenihan
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lcsh:Diseases of the circulatory (Cardiovascular) system ,Pathology ,medicine.medical_specialty ,business.industry ,atrial thrombus ,Atrial Thrombus ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,Article ,Oncology ,lcsh:RC666-701 ,Cardiac mass ,cardiac MRI ,catheter associated thrombus ,medicine ,cardiac mass ,brain metastasis ,Testicular Choriocarcinoma ,anticoagulation ,Cardiology and Cardiovascular Medicine ,business ,Brain metastasis - Published
- 2019
10. Surgical options for aortic root aneurysm disease: which procedure, which patient
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Matthew R. Schill and Puja Kachroo
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Surgical repair ,Aortic valve ,Valve-sparing aortic root replacement ,Heart Valve Prosthesis Implantation ,medicine.medical_specialty ,Aortic Aneurysm, Thoracic ,business.industry ,Regurgitation (circulation) ,Disease ,medicine.disease ,Aortic root aneurysm ,Surgery ,Aortic aneurysm ,medicine.anatomical_structure ,Treatment Outcome ,Cardiothoracic surgery ,Aortic Valve ,cardiovascular system ,medicine ,Humans ,Cardiology and Cardiovascular Medicine ,business ,Aorta - Abstract
Purpose of review Several surgical repair strategies are available for patients with aortic root aneurysms. This review summarizes the indications for surgery, surgical treatment options, as well their associated outcomes. Recent findings Despite the development and increasing adoption of valve sparing aortic root replacement, most patients with aortic root aneurysms still undergo placement of a composite valved graft. Valve sparing aortic root replacement may have a lower rate of bleeding and thrombotic complications during long-term follow-up with excellent long-term survival and low rates of aortic valve reintervention. Summary Patients with aortic root aneurysms who are symptomatic or reach the recommended size criteria should undergo surgical repair. Most patients receive composite valve graft conduits with good outcomes. The presence of normal aortic leaflet tissue and minimal regurgitation, including those with connective tissue disorders, should be evaluated for valve sparing aortic root replacement. Valve sparing procedures are durable and obviate the need for lifelong anticoagulation and avoid the risk of structural degeneration of bioprosthetic valves.
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- 2021
11. Association of STS database variables with repair durability in ischemic mitral regurgitation using machine learning
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Puja Kachroo, Hersh S. Maniar, Michael K. Pasque, Ralph J. Damiano, Brian P. Cupps, Marc R. Moon, Aixia Guo, Akinobu Itoh, Randi E. Foraker, and Robert M. MacGregor
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Pulmonary and Respiratory Medicine ,Mitral Valve Annuloplasty ,medicine.medical_treatment ,Myocardial Ischemia ,computer.software_genre ,Logistic regression ,Machine learning ,Coronary artery disease ,Machine Learning ,medicine ,Humans ,Mitral valve repair ,Database ,Receiver operating characteristic ,business.industry ,Deep learning ,Area under the curve ,Mitral Valve Insufficiency ,medicine.disease ,Support vector machine ,Treatment Outcome ,Test set ,Surgery ,Artificial intelligence ,Cardiology and Cardiovascular Medicine ,business ,computer - Abstract
BACKGROUND Machine learning (ML) can identify nonintuitive clinical variable combinations that predict clinical outcomes. To assess the potential predictive contribution of standardized Society of Thoracic Surgeons (STS) Database clinical variables, we used ML to detect their association with repair durability in ischemic mitral regurgitation (IMR) patients in a single institution study. METHODS STS Database variables (n = 53) served as predictors of repair durability in ML modeling of 224 patients who underwent surgical revascularization and mitral valve repair for IMR. Follow-up mortality and echocardiography data allowed 1-year outcome analysis in 173 patients. Supervised ML analyses were performed using recurrence (≥3+ IMR) or death versus nonrecurrence (
- Published
- 2021
12. Impact of aortic valve effective height following valve-sparing root replacement on postoperative insufficiency and reoperation
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Puja Kachroo, Meghan O. Kelly, Nadia H. Bakir, Catherine Cooper, Alan C. Braverman, Nicholas T. Kouchoukos, and Marc R. Moon
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Pulmonary and Respiratory Medicine ,Male ,Adult ,Reoperation ,Heart Valve Prosthesis Implantation ,Aortic Valve Insufficiency ,Middle Aged ,Treatment Outcome ,Aortic Valve ,Humans ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,Retrospective Studies - Abstract
This study evaluated the impact of anatomic aortic root parameters during valve-sparing root replacement on the probability of postoperative aortic insufficiency and freedom from aortic valve reoperation.From 1995 to 2020, 177 patients underwent valve-sparing root replacement (163 reimplantations, 14 remodeling). Preoperative and postoperative echocardiograms were analyzed to measure annulus and sinus diameters, effective height of leaflet coaptation, and degree of aortic insufficiency. Logistic regression was used to evaluate predictors of 2+ or greater late postoperative aortic insufficiency. Fine-Gray regression determined predictors for aortic valve reintervention.The study population included 122 (69%) men with a mean age of 43 ± 15 years. A total of 119 patients (67%) had an identified connective tissue disorder. The cumulative incidence of aortic valve reoperation was estimated as 7% at 5 years and 12% at 10 years. The probability of 2+ or greater late postoperative aortic insufficiency was inversely related to effective height during valve-sparing root replacement (P = .018). As postoperative effective height fell below 11 mm, the probability of 2+ or greater aortic insufficiency exceeded 10%. On multivariable logistic regression, effective height (odds ratio, 0.53; 0.33-0.86; P = .010), preoperative annulus diameter (odds ratio, 1.44; 1.13-1.82; P = .003), and degree of preoperative aortic insufficiency (odds ratio, 2.57; 1.45-4.52; P = .001) were associated with increased incidence of 2+ or greater late postoperative aortic insufficiency. On multivariable Fine-Gray regression, risk factors for aortic valve reintervention included preoperative annulus diameter (subdistribution hazard ratio, 1.28 [1.03-1.59], P = .027), history of 3+ or greater aortic insufficiency (subdistribution hazard ratio, 4.28; 1.60-11.44; P = .004), and 2+ or greater early postoperative aortic insufficiency (subdistribution hazard ratio, 5.22; 2.29-11.90; P lt; .001).Measures to increase effective height during valve-sparing root replacement may decrease the risk of more than mild postoperative aortic insufficiency after repair and the need for aortic valve reoperation.
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- 2021
13. SVEP1 is a human coronary artery disease locus that promotes atherosclerosis
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Erica P. Young, Robert P. Mecham, Puja Kachroo, In Hyuk Jung, Katherine Santana, Arturo Alisio, Jared S. Elenbaas, Kory J. Lavine, Babak Razani, Chul Joo Kang, and Nathan O. Stitziel
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0301 basic medicine ,Vascular smooth muscle ,Myocytes, Smooth Muscle ,Integrin ,Notch signaling pathway ,Inflammation ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Muscle, Smooth, Vascular ,Article ,Coronary artery disease ,Extracellular matrix ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Animals ,Humans ,Medicine ,Cells, Cultured ,Cell Proliferation ,biology ,business.industry ,General Medicine ,Atherosclerosis ,medicine.disease ,Plaque, Atherosclerotic ,Mice, Inbred C57BL ,030104 developmental biology ,Fibroblast growth factor receptor ,biology.protein ,Cancer research ,medicine.symptom ,business ,Cell Adhesion Molecules - Abstract
A low-frequency variant of sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1), an extracellular matrix protein, is associated with risk of coronary disease in humans independent of plasma lipids. Despite a robust statistical association, if and how SVEP1 might contribute to atherosclerosis remained unclear. Here, using Mendelian randomization and complementary mouse models, we provide evidence that SVEP1 promotes atherosclerosis in humans and mice and is expressed by vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque. VSMCs also interact with SVEP1, causing proliferation and dysregulation of key differentiation pathways, including integrin and Notch signaling. Fibroblast growth factor receptor transcription increases in VSMCs interacting with SVEP1, and is further increased by the coronary disease-associated SVEP1 variant p.D2702G. These effects ultimately drive inflammation and promote atherosclerosis. Taken together, our results suggest that VSMC-derived SVEP1 is a pro-atherogenic factor, and support the concept that pharmacological inhibition of SVEP1 should protect against atherosclerosis in humans.
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- 2021
14. Gender-Based Outcomes After Surgical Revascularization in Stable Coronary Disease Patients: Decades Later and Questions Remain
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Puja Kachroo
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Text mining ,business.industry ,General surgery ,Medicine ,Humans ,Surgery ,Coronary Artery Disease ,Coronary disease ,Cardiology and Cardiovascular Medicine ,business ,Surgical revascularization - Published
- 2021
15. IMPACT OF OBESITY ON CLINICAL OUTCOMES IN MARFAN SYNDROME
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Andrew Lai, Tarun Ramayya, Leslie Boyer, John Ohman, Puja Kachroo, and Alan C. Braverman
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Cardiology and Cardiovascular Medicine - Published
- 2022
16. SVEP1, a novel human coronary artery disease locus, promotes atherosclerosis
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Arturo Alisio, In-Hyuk Jung, Nathan O. Stitziel, Puja Kachroo, Robert P. Mecham, Erica P. Young, Jared S. Elenbaas, Kory J. Lavine, Babak Razani, Katherine Santana, and Chul Joo Kang
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Vascular smooth muscle ,biology ,business.industry ,Integrin ,Notch signaling pathway ,Inflammation ,medicine.disease ,Extracellular matrix ,Coronary artery disease ,Fibroblast growth factor receptor ,Mendelian randomization ,Cancer research ,biology.protein ,Medicine ,medicine.symptom ,business - Abstract
SummaryA low-frequency variant of SVEP1, an extracellular matrix protein, is associated with risk of coronary disease in humans independent of plasma lipids. Despite a robust statistical association, however, it was unclear if and how SVEP1 might contribute to atherosclerosis. Here, using Mendelian randomization and complementary mouse models, we provide evidence that SVEP1 promotes atherosclerosis in humans and mice. We find that SVEP1 is expressed by vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque. VSMCs also interact with SVEP1, causing proliferation and dysregulation of key differentiation pathways, including integrin and Notch signaling. Fibroblast growth factor receptor transcription increases in VSMCs interacting with SVEP1, and is further increased by the coronary disease-associated SVEP1 variant. These effects ultimately drive inflammation and promote atherosclerosis. Taken together, our results suggest that VSMC-derived SVEP1 is a pro-atherogenic factor, and support the concept that pharmacological inhibition of SVEP1 should protect against atherosclerosis in humans.
- Published
- 2020
17. Radiation Exposure During Transcatheter Valve Replacement: What Cardiac Surgeons Need to Know
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Matthew C. Henn, Alan Zajarias, John M. Lasala, Hersh S. Maniar, Puja Kachroo, Ali J. Khiabani, Eric Novak, Alejandro Aquino, Marc Sintek, and Spencer J. Melby
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Placebo ,Radiation Dosage ,law.invention ,Transcatheter Aortic Valve Replacement ,03 medical and health sciences ,0302 clinical medicine ,Radiation Protection ,Valve replacement ,Randomized controlled trial ,Interquartile range ,law ,Occupational Exposure ,Medicine ,Humans ,Single-Blind Method ,business.industry ,Mitral valve replacement ,Thoracic Surgery ,Radiation Exposure ,Femoral Artery ,030228 respiratory system ,Cardiothoracic surgery ,Hybrid operating room ,Surgery ,Radiation protection ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine - Abstract
Transcatheter aortic valve replacement (TAVR) and transcatheter mitral valve replacement expose operators to radiation. These procedures differ primarily in whether they are performed via a transfemoral (TF) or an alternative access (AA) approach. This study compared operator radiation exposure during transcatheter valve implantation when performed via a TF vs an AA approach, when performed in a catheterization lab vs a hybrid operating room (OR), and investigated the potential benefit of disposable shielding.Dosimeters were worn during TAVR-TF (n = 50) and TAVR-AA (n = 31) procedures by operators. All TAVR-AA procedures were performed in a hybrid OR and TF procedures were performed in either catheterization labs (n = 16) or a hybrid OR (n = 34). Disposable radiation shielding pads (RADPAD; Worldwide Innovations and Technologies, Inc, Kansas City) or a placebo were added in a randomized, blinded fashion.Team radiation exposure was higher after TAVR-AA vs TAVR-TF (median 15.1 mRad [interquartile range: IQR 8.6, 32.4] vs 5.5 mRad [IQR 2.4, 9.8], P.001). TAVR-TF procedures required the same amount of fluoroscopy time regardless of where they were performed (20.3 ± 7.4 min in hybrid OR vs 19.0 ± 6.4 min in catheterization lab, P = .55). However, radiation exposure for TAVR-TF remained higher when performed in a hybrid OR (median 9.0 mRad [IQR 4.5, 11.9] vs 2.2 mRad [IQR 1.3, 2.8], P.001). Radiation exposure was greatest for TAVR-AA (median 15.1 mRad [IQR 8.6, 32.4]). The use of RADPAD did not decrease radiation exposure (median 9.0 mRad [IQR 4.5, 14.7] vs 9.4 mRad [IQR 2.8, 19.5], P = .82).Procedures performed in the hybrid OR were associated with higher operator radiation exposure. In comparison with the TF approach, AA cases had the highest levels of operator radiation. This is particularly important in cases of transcatheter mitral valve replacement that can only be done via an AA approach. The use of disposable radiation shielding in this series did not attenuate operator radiation exposure. Radiation shielding within hybrid ORs should be scrutinized in an effort to remain on par with that found within catheterization labs.
- Published
- 2018
18. Developing a machine learning model using isolated Society of Thoracic Surgeons database variables to predict the presence of clinically-significant ischemic mitral regurgitation
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Marci S. Damiano, Spencer Melby, Brian P. Cupps, Linda Schulte, Ralph J. Damiano, Tina Burmeister, Hersh S. Maniar, Michael K. Pasque, Muhammad F. Masood, Marc R. Moon, Robert M. MacGregor, Akinobu Itoh, Puja Kachroo, Randi E. Foraker, Kunal D. Kotkar, and Aixia Guo
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medicine.medical_specialty ,Ischemic mitral regurgitation ,business.industry ,Internal medicine ,Cardiology ,medicine ,business - Published
- 2021
19. Cardiothoracic Organ Procurement for Transplantation: How I Teach It
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Sharven Taghavi, Christina C. Pasque, Michael K. Pasque, Jessica Y. Rove, Puja Kachroo, and Alejandro Bribriesco
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pathology ,Tissue and Organ Procurement ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Intensive care medicine ,business.industry ,Teaching ,Internship and Residency ,Thoracic Surgery ,Organ Transplantation ,United States ,Transplantation ,Organ procurement ,030228 respiratory system ,Education, Medical, Graduate ,Female ,Surgery ,Clinical Competence ,Educational Measurement ,Cardiology and Cardiovascular Medicine ,business - Published
- 2016
20. Sex-Related Differences in Aortic Dissection in Marfan Syndrome
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Puja Kachroo, Matthew A. Henn, Tarun Ramayya, Jason R. Cook, J. Westley Ohman, Rahul R. Handa, and Alan C. Braverman
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Marfan syndrome ,Aortic dissection ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,Surgery ,Sex related ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business - Published
- 2019
21. OUTCOMES ASSOCIATED WITH PERCUTANEOUS CORONARY INTERVENTION PRIOR TO TRANSCATHETER AORTIC VALVE IMPLANTATION
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Hersh S. Maniar, Mustafa Husaini, Prashanth Thakker, Alan Zajarias, Manoj Thangam, Howard I. Kurz, Nishath Quader, Jasvindar Singh, Puja Kachroo, Spencer J. Melby, John M. Lasala, John Posenau, Richard G. Bach, Amit P. Amin, and Marc Sintek
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medicine.medical_specialty ,Transcatheter aortic ,business.industry ,medicine.medical_treatment ,Percutaneous coronary intervention ,medicine.disease ,Coronary artery disease ,Valve replacement ,Internal medicine ,Conventional PCI ,medicine ,Retrospective analysis ,Cardiology ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business - Abstract
Coronary artery disease (CAD) is encountered in 40-75% of those undergoing transcatheter aortic valve replacement (TAVR). However, the safety of percutaneous coronary intervention (PCI) prior to TAVR is unclear. A retrospective analysis of patients with PCI < 6 months prior to TAVR from 1/1/2013- 1
- Published
- 2019
22. Observed to expected 30-day mortality as a benchmark for transcatheter aortic valve replacement
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Marc Sintek, D. Craig Miller, Hersh S. Maniar, Marci S. Damiano, John M. Lasala, Nishath Quader, Kelly Koogler, C. Ryan King, Ralph J. Damiano, Alan Zajarias, Marc R. Moon, Matthew C. Henn, Puja Kachroo, and Spencer J. Melby
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Transcatheter aortic ,business.industry ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,medicine.disease ,Confidence interval ,03 medical and health sciences ,0302 clinical medicine ,Standardized mortality ratio ,030228 respiratory system ,Valve replacement ,Aortic valve replacement ,30 day mortality ,Cardiothoracic surgery ,Internal medicine ,medicine ,Cardiology ,Risk of mortality ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
The observed-to-expected 30-day mortality ratio (O:E ratio) is a standard metric by which transcatheter aortic valve replacement (TAVR) trials have been evaluated. Early TAVR trials consistently demonstrated O:E ratio less than 0.6 after TAVR when based on the Society for Thoracic Surgery Predicted Risk of Mortality (STS-PROM) for surgical aortic valve replacement. Recent published results from the Transcatheter Valve Therapy (TVT) Registry have demonstrated O:E ratios of 1.0. We evaluated our own O:E ratios for TAVR to investigate this discordance.Data were collected prospectively for TAVR patients from 2008 through 2015 (N = 546) and were reviewed retrospectively. The observed mortality and STS-PROM were calculated to formulate O:E ratios and were compared over a variety of subgroups.Overall, the O:E ratio for 30-day mortality was 0.4 and significantly less than 1 (P .001; 95% confidence interval, 0.25-0.63). The O:E ratio relationship remained less than 0.5 for patients with low (STS-PROM 4), moderate (STS-PROM = 4-8) and high risk (STS-PROM 8). The O:E ratio was significantly higher for transapical patients (O:E ratio = 0.8) when compared with transfemoral patients (O:E ratio = 0.2). Lastly, O:E ratios for both commercial (O:E ratio = 0.5) and research (O:E ratio = 0.3) patients were similar (P = .337), and both were significantly less than 1 (P = .007 and P .001, respectively).The STS-PROM consistently overestimated 30-day mortality after TAVR. Achieving an O:E ratio less than 0.6 may be a realistic goal for all TAVR programs. While an accurate and specific risk calculator for 30-day mortality after TAVR remains to be established, our data suggest that current TVT results are not acceptable for commercial TAVR and that programs with an O:E ratio greater than 0.6, based on the STS-PROM, should reevaluate internal processes to improve their results.
- Published
- 2019
23. Chest Wall Sarcomas are Accurately Diagnosed by Image-Guided Core Needle Biopsy
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Peter S. Pak, Harpavan S. Sandha, Puja Kachroo, Robert B. Cameron, Jay M. Lee, Leanne L. Seeger, Fritz C. Eilber, and Scott D. Nelson
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Male ,Core needle ,Sternum ,Chest wall ,Biopsy ,Cardiorespiratory Medicine and Haematology ,Radiography, Interventional ,Needle ,80 and over ,Tomography ,Ultrasonography ,Cancer ,Aged, 80 and over ,screening and diagnosis ,Rib cage ,Interventional ,medicine.diagnostic_test ,Biopsy, Needle ,Soft tissue ,Sarcoma ,Middle Aged ,X-Ray Computed ,Detection ,Oncology ,Female ,Radiology ,4.2 Evaluation of markers and technologies ,Adult ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Clinical Sciences ,Oncology and Carcinogenesis ,Ribs ,and over ,Malignancy ,Young Adult ,Rare Diseases ,Predictive Value of Tests ,Clinical Research ,medicine ,Humans ,Oncology & Carcinogenesis ,Thoracic Wall ,Ultrasonography, Interventional ,Retrospective Studies ,Aged ,business.industry ,Histology ,Thoracic Neoplasms ,medicine.disease ,Radiography ,Core needle biopsy ,Neoplasm Grading ,Tomography, X-Ray Computed ,Digestive Diseases ,business - Abstract
OBJECTIVE:: Sarcomas are rare mesenchymal malignancies. Accurate preoperative diagnosis is a prerequisite in considering investigational or institutional management algorithms that include neoadjuvant treatment. We reviewed our experience using core needle biopsy for chest wall sarcomas. Methods: A retrospective review of our sarcoma databases revealed that 40 core needle biopsies and 35 tumor resections were performed in 34 patients, with chest wall musculoskeletal tumors, referred to the University of California, Los Angeles from 1991 to 2010. Primary, metastatic, or recurrent sarcomas involving the sternum, ribs, and soft tissues of the chest wall were evaluated for (1) adequacy of tissue from image-guided core needle biopsies and (2) accuracy in determining malignancy, histological subtype, and sarcoma grade. Results: Twenty-eight of the 40 needle biopsy samples (70%) were adequate for histopathological analysis. Forty-two percent of nondiagnostic findings occurred due to insufficient tissue, whereas the remainder had sufficient tissue, but the pathologist was unable to determine specific histology. Excluding the nondiagnostic samples, the accuracy in determining malignancy, histological subtype, and grade in sarcomas was 100, 92, and 87%, respectively. The sensitivity and specificity of determining malignancy and high-grade sarcomas were 100, 100, 77, and 100%, respectively. There were no complications from the image-guided biopsies. Conclusions: We demonstrated that image-guided core needle biopsy when performed and reviewed by experienced radiologists and musculoskeletal pathologists is a safe and accurate diagnostic technique for chest wall sarcomas. Core needle biopsy should be considered in the multidisciplinary approach to chest wall musculoskeletal tumors, especially when induction therapy is considered. Copyright © 2011 by the International Association for the Study of Lung Cancer.
- Published
- 2012
24. Combination Treatment with Apricoxib and IL-27 Enhances Inhibition of Epithelial-Mesenchymal Transition in Human Lung Cancer Cells through a STAT1 Dominant Pathway
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Sherven Sharma, Paul Pagano, Kostyantyn Krysan, Steven M. Dubinett, Gerald Wang, Mi-Heon Lee, Jane Yanagawa, Jay M. Lee, Maie A. St. John, Tonya C. Walser, and Puja Kachroo
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Cancer Research ,Epithelial-Mesenchymal Transition ,Apricoxib ,Vimentin ,medicine.disease_cause ,Article ,IL-27 ,STAT3 ,chemistry.chemical_compound ,A549 ,STAT1 ,Non-small cell lung cancer ,2.1 Biological and endogenous factors ,Medicine ,Epithelial–mesenchymal transition ,Aetiology ,Lung ,Cancer ,Tumor microenvironment ,biology ,business.industry ,Lung Cancer ,Cell migration ,COX-2 ,Oncology ,chemistry ,Immunology ,biology.protein ,Cancer research ,Signal transduction ,business ,Carcinogenesis - Abstract
BackgroundThe cyclooxygenase 2 (COX-2) pathway has been implicated in the molecular pathogenesis of many malignancies, including lung cancer. Apricoxib, a selective COX-2 inhibitor, has been described to inhibit epithelial-mesenchymal transition (EMT) in human malignancies. The mechanism by which apricoxib may alter the tumor microenvironment by affecting EMT through other important signaling pathways is poorly defined. IL-27 has been shown to have anti-tumor activity and our recent study showed that IL-27 inhibited EMT through a STAT1 dominant pathway.ObjectiveThe purpose of this study is to investigate the role of apricoxib combined with IL-27 in inhibiting lung carcinogenesis by modulation of EMT through STAT signaling.Methods and resultsWestern blot analysis revealed that IL-27 stimulation of human non-small cell lung cancer (NSCLC) cell lines results in STAT1 and STAT3 activation, decreased Snail protein and mesenchymal markers (N-cadherin and vimentin) and a concomitant increase in expression of epithelial markers (E-cadherin, β-and γ-catenins), and inhibition of cell migration. The combination of apricoxib and IL-27 resulted in augmentation of STAT1 activation. However, IL-27 mediated STAT3 activation was decreased by the addition of apricoxib. STAT1 siRNA was used to determine the involvement of STAT1 pathway in the enhanced inhibition of EMT and cell migration by the combined IL-27 and apricoxib treatment. Pretreatment of cells with STAT1 siRNA inhibited the effect of combined IL-27 and apricoxib in the activation of STAT1 and STAT3. In addition, the augmented expression of epithelial markers, decreased expression mesenchymal markers, and inhibited cell migration by the combination treatment were also inhibited by STAT1 siRNA, suggesting that the STAT1 pathway is important in the enhanced effect from the combination treatment.ConclusionCombined apricoxib and IL-27 has an enhanced effect in inhibition of epithelial-mesenchymal transition and cell migration in human lung cancer cells through a STAT1 dominant pathway.
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- 2014
25. IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer
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Gerald Wang, Mi Heon Lee, Felicita Baratelli, Ling Zhang, Steven M. Dubinett, Sherven Sharma, Tonya C. Walser, Puja Kachroo, Gina Lee, Jay M. Lee, Minu K. Srivastava, and Kostyantyn Krysan
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Interleukin-27 ,Cancer Research ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Angiogenesis ,Cell ,Transfection ,medicine.disease_cause ,IL-27 ,STAT3 ,03 medical and health sciences ,STAT1 ,0302 clinical medicine ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Epithelial–mesenchymal transition ,Angiogenic Proteins ,RNA, Small Interfering ,Lung cancer ,Cytokine ,030304 developmental biology ,0303 health sciences ,biology ,Research ,Cancer ,medicine.disease ,STAT1 Transcription Factor ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Carcinogenesis ,Signal Transduction - Abstract
Background Interleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial–mesenchymal transition (EMT) and angiogenesis are key processes in carcinogenesis. Although IL-27 has been shown to have potent anti-tumor activity in various cancer models, the role of IL-27 in EMT and angiogenesis is poorly understood. In this study, we investigated the role of IL-27 in regulating EMT and angiogenesis through modulation of the STAT pathways in human non-small cell lung carcinoma (NSCLC) cells. Methods STAT activation following IL-27 exposure was measured in human NSCLC cell lines. Expression of epithelial (E-cadherin, γ-catenin) and mesenchymal (N-cadherin, vimentin) markers were assessed by Western blot analysis. Production of pro-angiogenic factors (VEGF, IL-8/CXCL8, CXCL5) were examined by ELISA. Cell motility was examined by an in vitro scratch and transwell migration assays. Selective inhibitors of STAT1 (STAT1 siRNAs) and STAT3 (Stattic) were used to determine whether both STAT1 and STAT3 are required for IL-27 mediated inhibition of EMT and secretion of angiogenic factors. Results Our results demonstrate that IL-27 stimulation in NSCLC resulted in 1) STAT1 and STAT3 activation in a JAK-dependent manner, 2) development of epithelial phenotypes, including a decrease in the expression of a transcriptional repressor for E-cadherin (SNAIL), and mesenchymal marker (vimentin) with a reciprocal increase in the expression of epithelial markers, 3) inhibition of cell migration, and 4) reduced production of pro-angiogenic factors. STAT1 inhibition in IL-27–treated cells reversed the IL-27 effect with resultant increased expression of Snail, vimentin and the pro-angiogenic factors. The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. Conclusion IL-27 induces mesenchymal to epithelial transition and inhibits the production of pro-angiogenic factors in a STAT1–dominant pathway. These findings highlight the importance of STAT1 in repressing lung carcinogenesis and describe a new anti-tumor mechanism of IL-27.
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- 2013
26. Single-institution, multidisciplinary experience with surgical resection of primary chest wall sarcomas
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Michael T. Selch, David Elashoff, Catherine Lee, Bartosz Chmielowski, Jay M. Lee, Harpavan S. Sandha, Puja Kachroo, Peter S. Pak, E. Carmack Holmes, Scott D. Nelson, Fritz C. Eilber, and Robert B. Cameron
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Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Prognostic variable ,Chest wall ,Adolescent ,medicine.medical_treatment ,Metastasis ,Young Adult ,medicine ,Humans ,Prospective Studies ,Survival rate ,Neoadjuvant therapy ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Primary chest wall sarcomas ,business.industry ,Soft tissue sarcoma ,Sarcomas ,Soft tissue ,Sarcoma ,Perioperative ,Middle Aged ,Thoracic Neoplasms ,Thoracic Surgical Procedures ,medicine.disease ,Surgery ,Survival Rate ,Treatment Outcome ,Oncology ,Female ,Radiology ,Chondrosarcoma ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Introduction Primary chest wall sarcomas are rare mesenchymal tumors and their mainstay of therapy is wide surgical resection. We report our single-institution, multidisciplinary experience with full-thickness resection for primary chest wall sarcomas. Methods A retrospective review of our prospectively maintained databases revealed that 51 patients were referred for primary chest wall sarcomas from 1990 to 2009. Results All patients required resections that included rib and/or sternum. Twenty-nine patients (57%) had extended resections beyond the chest wall. Forty-two patients (82%) required prosthetic reconstruction and 17 patients (33%) had muscle flap coverage. Overall, 51% (26/51) of patients received neoadjuvant therapy. Seventy-three percent (11/15) of high-grade soft tissue sarcomas, 77% (10/13) of high-risk bony sarcomas, and 67% (4/6) of desmoid tumors were treated with induction therapy. Negative margins were obtained in 46 patients (90%). There were no perioperative mortalities. Eight patients (16%) experienced complications. Local recurrence and metastasis was detected in 14 and 23%. Five-year overall and disease-free survivals were 66% and 47%, respectively. Favorable prognostic variables for survival included age ⩽50 years, tumor volume ⩽200 cm 3 , desmoid tumor, bony tumor, chondrosarcoma, and low-grade soft tissue sarcoma. Conclusions We report our multidisciplinary experience with primary chest wall sarcomas that included induction therapy in the majority of high-risk soft tissue and bony sarcomas and desmoid tumors. Despite aggressive preoperative treatments, acceptable surgical results with low morbidity and mortality can be achieved. Neoadjuvant systemic therapy may reduce local and distant recurrence and improve overall survival.
- Published
- 2012
27. Ossicular motion related to middle ear transmission delay in gerbil
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Puja Kachroo, Elizabeth S. Olson, and Ombeline de La Rochefoucauld
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Time Factors ,Umbo ,Acoustics ,Incus ,Ear, Middle ,Mechanotransduction, Cellular ,Article ,Hearing ,medicine ,otorhinolaryngologic diseases ,Pressure ,Animals ,Ear canal ,Cochlea ,Group delay and phase delay ,Stapes ,Ear Ossicles ,Physics ,Ossicles ,Sensory Systems ,Biomechanical Phenomena ,medicine.anatomical_structure ,Acoustic Stimulation ,Middle ear ,sense organs ,Gerbillinae - Abstract
The middle ear transmits sound efficiently from the air in the ear canal (EC) to the fluid filled cochlea. In gerbil, middle ear transmission produces a constant pressure gain between the EC and the cochlea of ~ 25 dB from 2 to 40 kHz, and a delay-like phase corresponding to a ~25 – 30 μs delay. The mechanisms by which the air-born signal is collected and delivered to the cochlea are not thoroughly understood, and the source of the delay is controversial. We investigated these issues by observing ossicular motion along a single line of sight, roughly parallel to the EC and perpendicular to the stapes footplate. Measurements were made at the umbo, the lateral process of the manubrium, across the malleus-incus joint, at the long process of the incus, and the stapes head. While the overall delay between EC pressure and stapes velocity was fairly constant with frequency, subcomponents of the delay were frequency dependent. Up to ~ 17 kHz, most of the overall delay was between the EC and umbo with a much smaller contribution along the ossicles, whereas in the range from ~17 to 30 kHz, more of the overall delay was along the ossicles.
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- 2010
28. GITR agonist enhances vaccination responses in lung cancer
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Jay M. Lee, Steven M. Dubinett, Marni E. Harris-White, Michael Davoodi, Min Huang, Li X. Zhu, Maie A. St. John, Puja Kachroo, Minu K Srivastava, Sherven Sharma, and Robert M. Strieter
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glucocorticoid‐induced TNFR‐related gene ,regulatory T cell ,mitogen-activated protein kinase ,MDSC ,tumor necrosis factor receptor ,bone marrow adherent ,cytotoxic T lymphocyte ,DC ,NF-κB ,Immune tolerance ,nuclear factor kappa-light-chain-enhancer of activated B cells ,antibody ,PD-1 ,TNFα ,2.1 Biological and endogenous factors ,Immunology and Allergy ,Interferon Alpha ,Aetiology ,extracellular signal-regulated kinase ,Lung ,Original Research ,Cancer ,T cell activation ,Lung Cancer ,P38 ,programmed cell death protein 1 ,Treg ,ERK ,myeloid derived suppressor cell ,Oncology ,5.1 Pharmaceuticals ,anti-GITR antibody ,TNFR ,Tumor necrosis factor alpha ,Development of treatments and therapeutic interventions ,Antibody ,TCR ,Biotechnology ,PD-L1 ,NK ,dendritic cell ,Oncology and Carcinogenesis ,Immunology ,BMA ,Biology ,Ab ,Vaccine Related ,Immune system ,Antigen ,medicine ,GITR ,Antigen-presenting cell ,p38 mitogen-activated protein kinase(s) ,Tumor microenvironment ,interferon γ ,Inflammatory and immune system ,programmed cell death ligand 1 ,vaccination responses ,janus kinase ,natural killer ,medicine.disease ,MAPK ,APC ,antigen presenting cell ,CTL ,Cancer research ,biology.protein ,Immunization ,JNK ,T cell receptor ,DTA-1 ,IFNγ - Abstract
An immune tolerant tumor microenvironment promotes immune evasion of lung cancer. Agents that antagonize immune tolerance will thus aid the fight against this devastating disease. Members of the tumor necrosis factor receptor (TNFR) family modulate the magnitude, duration and phenotype of immune responsiveness to antigens. Among these, GITR expressed on immune cells functions as a key regulator in inflammatory and immune responses. Here, we evaluate the GITR agonistic antibody (DTA-1) as a mono-therapy and in combination with therapeutic vaccination in murine lung cancer models. We found that DTA-1 treatment of tumor-bearing mice increased: (i) the frequency and activation of intratumoral natural killer (NK) cells and T lymphocytes, (ii) the antigen presenting cell (APC) activity in the tumor, and (iii) systemic T-cell specific tumor cell cytolysis. DTA-1 treatment enhanced tumor cell apoptosis as quantified by cleaved caspase-3 staining in the tumors. DTA-1 treatment increased expression of IFNγ, TNFα and IL-12 but reduced IL-10 levels in tumors. Furthermore, increased anti-angiogenic chemokines corresponding with decreased pro-angiogenic chemokine levels correlated with reduced expression of the endothelial cell marker Meca 32 in the tumors of DTA-1 treated mice. In accordance, there was reduced tumor growth (8-fold by weight) in the DTA-1 treatment group. NK cell depletion markedly inhibited the antitumor response elicited by DTA-1. DTA-1 combined with therapeutic vaccination caused tumor rejection in 38% of mice and a 20-fold reduction in tumor burden in the remaining mice relative to control. Mice that rejected tumors following therapy developed immunological memory against subsequent re-challenge. Our data demonstrates GITR agonist antibody activated NK cell and T lymphocyte activity, and enhanced therapeutic vaccination responses against lung cancer.
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- 2015
29. Combination Treatment with Apricoxib and IL-27 Enhances Inhibition of Epithelial-Mesenchymal Transition in Human Lung Cancer Cells through a STAT1 Dominant Pathway
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Puja Kachroo, Mi Heon Lee, primary
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- 2014
- Full Text
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30. Abstract 339: Apricoxib, a selective COX-2 inhibitor, suppresses IL-27-mediated STAT3 activation and potentiates its inhibition of epithelial to mesenchymal transition in human non-small cell lung cancer
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Puja Kachroo, Sherven Sharma, Gina Lee, Jay M. Lee, Kostyantyn Krysan, Sara Zaknoen, Tonya C. Walser, Mi-Heon Lee, and Steven M. Dubinett
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Cancer Research ,Tumor microenvironment ,Oncogene ,biology ,JAK-STAT signaling pathway ,Vimentin ,medicine.disease_cause ,Apricoxib ,chemistry.chemical_compound ,Oncology ,chemistry ,medicine ,Cancer research ,biology.protein ,Epithelial–mesenchymal transition ,Carcinogenesis ,STAT3 - Abstract
Introduction The cyclooxygenase 2 (COX-2) pathway has been implicated in the molecular pathogenesis of many cancers. Apricoxib, a selective COX-2 inhibitor, has recently been demonstrated to inhibit epithelial to mesenchymal transition (EMT) in human malignancies. EMT is a critical process in cancer progression and metastasis whereby epithelial cells undergo changes to a migratory, mesenchymal phenotype. The mechanism by which apricoxib may alter the tumor microenvironment by impacting other important pathways in EMT is poorly defined. To investigate this concept, we utilized Interleukin-27 (IL-27), a member of the IL-12 family, which signals through the JAK-STAT pathway and activates transcriptional factors with opposing roles in carcinogenesis, STAT1 (tumor suppressor) and STAT3 (oncogene). IL-27 has been shown to have anti-tumor activity, but understanding of its mechanism is limited. We previously demonstrated that IL-27 activates both STAT1 and STAT3 pathways in human non-small cell lung cancer (NSCLC) and that the balance in STAT1 and STAT3 activation is important in inhibiting EMT. Here, we studied the effect of apricoxib on IL-27-mediated STAT activation and EMT inhibition. We hypothesize that apricoxib modulates STAT1 and STAT3 activation and regulates EMT. Methods A human NSCLC cell line, A549, was pre-treated with apricoxib (80nM-10µM) for up to 24 hours prior to IL-27 stimulation (50ng/mL). Activation of STAT1 and STAT3 proteins, demonstrated by tyrosine phosphorylation, was measured by Western Blot analysis. Additionally, epithelial markers (E-cadherin, γ-catenin, β-catenin) and mesenchymal markers (N-cadherin, vimentin, snail) were evaluated also by Western blotting. Results IL-27 alone induced phosphorylation of STAT1 and STAT3 proteins compared to untreated control. Pre-treatment with apricoxib resulted in decreased levels of IL-27-mediated STAT1 and STAT3 phosphorylation compared to the IL-27 alone group. Apricoxib alone did not cause STAT1 or STAT3 activation. IL-27 treatment alone increased the levels of E-cadherin, γ-catenin, and β-catenin and decreased the levels of N-cadherin, vimentin, and snail compared to untreated control. Pre-treatment with apricoxib for 24 hours prior to IL-27 exposure resulted in potentiation of IL-27-mediated reduction of N-cadherin, vimentin, and snail and further increased the levels of E-cadherin when compared to the IL-27 alone group. There appeared to be no impact on the expression of γ-catenin or β-catenin with the addition of apricoxib to IL-27. Conclusions Apricoxib inhibits IL-27-mediated activation of STAT1 and STAT3, and potentiates the IL-27-mediated inhibition of epithelial to mesenchymal transition. These findings suggest that apricoxib may regulate EMT through modulation of the STAT pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 339. doi:1538-7445.AM2012-339
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- 2012
31. Abstract 2558: VEGF-dependent suppression of prostaglandin transporter (PGT) expression in Kras mutant human bronchial epithelial cells
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Gina Lee, Ignacio I. Wistuba, Brian Gardner, John D. Minna, Saswati Hazra, Steven M. Dubinett, Jill E. Larsen, Luc Girard, Kostyantyn Krysan, Tonya C. Walser, Puja Kachroo, and Mi-Heon Lee
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Cancer Research ,medicine.medical_specialty ,PROSTAGLANDIN TRANSPORTER ,VEGF receptors ,Mutant ,Biology ,medicine.disease_cause ,Endocrinology ,Oncology ,Internal medicine ,medicine ,Cancer research ,biology.protein ,KRAS - Abstract
Prostaglandin transporters are expressed in cyclooxygenase-positive cells and provide the dominant mechanisms for transport of prostaglandins (PG) across the cell membrane. Specifically, the prostaglandin transporter PGT, expressed in many cell types including lung epithelia, is responsible for the uptake of prostaglandin E2 (PGE2) for intracellular metabolism and degradation by 15-prostaglandin dehydrogenase (15-PGDH). The regulation of prostaglandin transporters has not been fully explored in lung cancer. We hypothesize that loss of PGT expression is important in lung carcinogenesis and its loss may be enhanced in the presence of common mutations in premalignant bronchial epithelial cells and non-small cell lung cancer (NSCLC). Our preliminary studies show that PGT expression (protein and mRNA) and 15-PGDH are significantly downregulated in Kras mutant human bronchial epithelial cells (HBEC) and in NSCLC. It is well known that Kras mutant cancers are associated with increased production of VEGF, an important factor in tumor angiogenesis. In HBEC, we found significantly higher VEGF levels in Kras mutants compared to vector controls (2242 versus 628 pg/mg, p = 0.04). We proposed that VEGF modulates PGT expression and tested our hypothesis by treating HBEC and NSCLC with human recombinant VEGF. PGT expression is downregulated with exogenous VEGF treatment and neutralizing VEGF production (neutralizing VEGF antibody) prevented the loss of PGT expression. The MEK1/2 inhibitor PD98059 upregulated PGT expression in HBEC Kras. Our results suggest Kras mutation is associated with loss of PGT expression and may be dependent on VEGF production. Modulation of PGT expression may be important in lung carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2558. doi:1538-7445.AM2012-2558
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- 2012
32. IL-27 Mediated Inhibition of Epithelial to Mesenchymal Transition is Augmented by STAT1 Activator, 2-(1,8-naphthyridin-2-yl)phenol (2-NP) in Human Non-small Cell Lung Cancer
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Shivani Sharma, Kostyantyn Krysan, Steven M. Dubinett, Gina Lee, Puja Kachroo, Minna K. Lee, and J.M. Lee
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biology ,Chemistry ,Activator (genetics) ,medicine.disease ,chemistry.chemical_compound ,Cancer research ,medicine ,biology.protein ,Phenol ,Surgery ,Epithelial–mesenchymal transition ,Non small cell ,STAT1 ,Lung cancer - Published
- 2012
33. Abstract 3425: Interleukin-27 inhibits epithelial mesenchymal transition in lung carcinogenesis
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John D. Minna, Saswati Hazra, Xiaoyan Cui, Tonya C. Walser, Jay M. Lee, Steven M. Dubinett, Puja Kachroo, Sherven Sharma, and Ling Zhang
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Cancer Research ,Pathology ,medicine.medical_specialty ,Mesenchymal stem cell ,Cancer ,Cell migration ,Vimentin ,Biology ,medicine.disease ,medicine.disease_cause ,Metastasis ,Oncology ,Cancer research ,medicine ,biology.protein ,Epithelial–mesenchymal transition ,Antigen-presenting cell ,Carcinogenesis - Abstract
Interleukin-27 (IL-27), the newest member of the IL-6/IL-12 family, is secreted by antigen presenting cells and has anti-tumor activity through its activation of the JAK-STAT pathway. Transcriptional factors STAT1 and STAT3 have been implicated in the balance of tumor suppressor and oncogenic functions. Epithelial mesenchymal transition (EMT) is a process whereby cells undergo changes from a highly polarized epithelial phenotype to a mesenchymal, migratory phenotype, which plays an important role in tumor metastasis. The role of IL-27 in EMT was evaluated in lung carcinogenesis. Human bronchial epithelial cells (HBECs), genetically modified HBEC to over-express Snail and K-ras (HBEC-Snail, HBEC-K-ras), and non-small cell lung cancer (NSCLC) lines (A549, H2122) were treated with IL-27 at multiple time points. Phosphorylation of STAT1 and STAT3 measured by Western Blot demonstrated activation of both pathways in these cell lines treated with IL-27. However, the STAT1 pathway was attenuated in HBEC-K-ras cells exposed to IL-27. Western analysis of markers for epithelial to mesenchymal transition (EMT) (E-cadherin, γ-catenin, N-cadherin, Vimentin, and Snail) showed up-regulation of E-cadherin and γ-catenin, important for the epithelial phenotype, which peaked 8 hours after IL-27 exposure, while markers important for the mesenchymal phenotype (N-cadherin, Vimentin, and Snail) were all down-regulated at similar time points. The addition of a STAT3 inhibitor to IL-27 treatment led to continued down-regulation of Vimentin beyond 8 hours. A wound healing functional assay to study cell migration after IL-27 treatment of cancer cell lines for up to 48 hours, demonstrated overall decrease in cell migration. In summary, IL-27 inhibits epithelial mesenchymal transition in NSCLCs and oncogenically manipulated HBECs through the regulation of STAT1 and STAT3 pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3425. doi:10.1158/1538-7445.AM2011-3425
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- 2011
34. Abstract 4268: Interleukin-27 inhibits angiogenesis in non-small cell lung cancer
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Xiaoyan Cui, Tonya C. Walser, Ling Zhang, Qiang Ying Lin, Puja Kachroo, Steven M. Dubinett, John D. Minna, Saswati Hazra, and Jay M. Lee
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Cancer Research ,biology ,Angiogenesis ,business.industry ,Cancer ,medicine.disease ,medicine.disease_cause ,Vascular endothelial growth factor ,chemistry.chemical_compound ,Oncology ,chemistry ,Immunology ,medicine ,biology.protein ,Cancer research ,STAT1 ,Lung cancer ,STAT3 ,Antigen-presenting cell ,business ,Carcinogenesis - Abstract
Interleukin-27 (IL-27), the newest member of the IL-6/IL-12 family, is secreted by antigen presenting cells and has anti-tumor activity through its activation of the JAK-STAT pathway. Transcriptional factors STAT1 and STAT3 have been implicated in the balance of tumor suppressor and oncogenic functions. Angiogenesis is a critical process during carcinogenesis. We investigated the role of IL-27 in tumor angiogenesis in lung cancer. Human bronchial epithelial cells (HBECs), genetically modified HBEC to over express Snail and K-ras (HBEC-Snail, HBEC-K-ras), and human non-small cell lung cancer (NSCLC) lines (A549, H2122) were treated with IL-27 at multiple time points. Phosphorylation of STAT1 and STAT3 measured by Western Blot after IL-27 exposure demonstrated activation of both pathways in these cell lines. Protein production of an important pro-angiogenic factor, vascular endothelial growth factor (VEGF), was measured by ELISA and Western analysis. After exposure to IL-27, there was a 60-80% decrease in VEGF protein expression of VEGF by ELISA (confirmed by Western analysis in the NSCLC lines but not in the HBECs or their genetically modified derivatives). The IL-27 down regulation of VEGF was not increased by the addition of a STAT3 inhibitor. In summary, IL-27 inhibits VEGF production in NSCLC through a mechanism independent of STAT3, suggesting that STAT1 may play a dominant role in IL-27 mediated angiogenesis suppression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4268. doi:10.1158/1538-7445.AM2011-4268
- Published
- 2011
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