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1. Single-cell characterization of pulmonary nodules implicates suppression of immunosurveillance across early stages of lung adenocarcinoma

Author

Yanagawa, Jane, Tran, Linh M, Salehi-Rad, Ramin, Lim, Raymond J, Dumitras, Camelia, Fung, Eileen, Wallace, William D, Prosper, Ashley E, Fishbein, Gregory, Shea, Conor, Hong, Rui, Kahangi, Bitta, Deng, John J, Gower, Adam C, Liu, Bin, Campbell, Joshua D, Mazzilli, Sarah A, Beane, Jennifer E, Kadara, Humam, Lenburg, Marc E, Spira, Avrum E, Aberle, Denise R, Krysan, Kostyantyn, and Dubinett, Steven M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Lung Cancer, Rare Diseases, Cancer Genomics, Genetics, Cancer, Immunotherapy, Lung, Human Genome, Biotechnology, Women's Health, 2.1 Biological and endogenous factors, Humans, Monitoring, Immunologic, Tomography, X-Ray Computed, Adenocarcinoma of Lung, Lung Neoplasms, Multiple Pulmonary Nodules, Adenocarcinoma, Tumor Microenvironment, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues using single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence (MIF). Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells. This was accompanied by a reduction in effector T cells and an increase of CD4+ regulatory T cells (Treg) in subsolid nodules. An independent set of resected pulmonary nodules consisting of both adenocarcinomas and associated premalignant lesions corroborated the early increment of Tregs in premalignant lesions compared with the associated normal lung tissues by MIF. Gene expression analysis indicated that cancer-associated alveolar type 2 cells and fibroblasts may contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid nodules through ligand-receptor interactions. These findings suggest that there is a suppression of immune surveillance across the spectrum of early-stage lung adenocarcinoma.SignificanceAnalysis of a spectrum of subsolid pulmonary nodules by single-cell RNA sequencing provides insights into the immune regulation and cell-cell interactions in the tumor microenvironment during early lung tumor development.

Published
2023

2. Predictors of Invasiveness in Adenocarcinoma of Lung with Lepidic Growth Pattern.

Author

Young, Timothy J, Salehi-Rad, Ramin, Ronaghi, Reza, Yanagawa, Jane, Shahrouki, Puja, Villegas, Bianca E, Cone, Brian, Fishbein, Gregory A, Wallace, William D, Abtin, Fereidoun, and Barjaktarevic, Igor

Subjects
Lung, Humans, Adenocarcinoma, Lung Neoplasms, Neoplasm Invasiveness, Neoplasm Staging, Adenocarcinoma in Situ, Adenocarcinoma of Lung, adenocarcinoma in situ, ground-glass, lepidic pattern, lung biopsy, lung cancer, Lung Cancer, Rare Diseases, Cancer, Clinical Research, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis
Abstract

Lung adenocarcinoma with lepidic growth pattern (LPA) is characterized by tumor cell proliferation along intact alveolar walls, and further classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic predominant adenocarcinoma (iLPA). Accurate diagnosis of lepidic lesions is critical for appropriate prognostication and management as five-year survival in patients with iLPA is lower than in those with AIS and MIA. We aimed to evaluate the accuracy of CT-guided core needle lung biopsy classifying LPA lesions and identify clinical and radiologic predictors of invasive disease in biopsied lesions. Thirty-four cases of adenocarcinoma with non-invasive lepidic growth pattern on core biopsy pathology that subsequently were resected between 2011 and 2018 were identified. Invasive LPA vs. non-invasive LPA (AIS or MIA) was defined based on explant pathology. Histopathology of core biopsy and resected tumor specimens was compared for concordance, and clinical, radiologic and pathologic variables were analyzed to assess for correlation with invasive disease. The majority of explanted tumors (70.6%) revealed invasive disease. Asian race (p = 0.03), history of extrathoracic malignancy (p = 0.02) and absence of smoking history (p = 0.03) were associated with invasive disease. CT-measured tumor size was not associated with invasiveness (p = 0.15). CT appearance of density (p = 0.61), shape (p = 0.78), and margin (p = 0.24) did not demonstrate a significant difference between the two subgroups. Invasiveness of tumors with lepidic growth patterns can be underestimated on transthoracic core needle biopsies. Asian race, absence of smoking, and history of extrathoracic malignancy were associated with invasive disease.

Published
2022

3. Development of human alveolar epithelial cell models to study distal lung biology and disease

Author

Tran, Evelyn, Shi, Tuo, Li, Xiuwen, Chowdhury, Adnan Y, Jiang, Du, Liu, Yixin, Wang, Hongjun, Yan, Chunli, Wallace, William D, Lu, Rong, Ryan, Amy L, Marconett, Crystal N, Zhou, Beiyun, Borok, Zea, and Offringa, Ite A

Subjects
Biomedical and Clinical Sciences, Engineering, Biomedical Engineering, Stem Cell Research, Lung, Respiratory, Cell biology, Developmental biology, Stem cells research, Transcriptomics
Abstract

Many acute and chronic diseases affect the distal lung alveoli. Alveolar epithelial cell (AEC) lines are needed to better model these diseases. We used de-identified human remnant transplant lungs to develop a method to establish AEC lines. The lines grow well in 2-dimensional (2D) culture as epithelial monolayers expressing lung progenitor markers. In 3-dimensional (3D) culture with fibroblasts, Matrigel, and specific media conditions, the cells form alveolar-like organoids expressing mature AEC markers including aquaporin 5 (AQP5), G-protein-coupled receptor class C group 5 member A (GPRC5A), and surface marker HTII280. Single-cell RNA sequencing of an AEC line in 2D versus 3D culture revealed increased cellular heterogeneity and induction of cytokine and lipoprotein signaling in 3D organoids. Our approach yields lung progenitor lines that retain the ability to differentiate along the alveolar cell lineage despite long-term expansion and provides a valuable system to model and study the distal lung in vitro.

Published
2022

4. Organoids Model Transcriptional Hallmarks of Oncogenic KRAS Activation in Lung Epithelial Progenitor Cells

Author

Dost, Antonella FM, Moye, Aaron L, Vedaie, Marall, Tran, Linh M, Fung, Eileen, Heinze, Dar, Villacorta-Martin, Carlos, Huang, Jessie, Hekman, Ryan, Kwan, Julian H, Blum, Benjamin C, Louie, Sharon M, Rowbotham, Samuel P, Sainz de Aja, Julio, Piper, Mary E, Bhetariya, Preetida J, Bronson, Roderick T, Emili, Andrew, Mostoslavsky, Gustavo, Fishbein, Gregory A, Wallace, William D, Krysan, Kostyantyn, Dubinett, Steven M, Yanagawa, Jane, Kotton, Darrell N, and Kim, Carla F

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Rare Diseases, Stem Cell Research - Induced Pluripotent Stem Cell, Lung Cancer, Cancer, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Lung, Biotechnology, 2.1 Biological and endogenous factors, Animals, Humans, Induced Pluripotent Stem Cells, Mice, Organoids, Proteomics, Proto-Oncogene Proteins p21(ras), KRAS, alveolar, developmental programs, early-stage lung cancer, iPSC, loss of differentiation, organoid, single-cell RNA sequencing, stage IA lung adenocarcinoma, tumor progression, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Mutant KRAS is a common driver in epithelial cancers. Nevertheless, molecular changes occurring early after activation of oncogenic KRAS in epithelial cells remain poorly understood. We compared transcriptional changes at single-cell resolution after KRAS activation in four sample sets. In addition to patient samples and genetically engineered mouse models, we developed organoid systems from primary mouse and human induced pluripotent stem cell-derived lung epithelial cells to model early-stage lung adenocarcinoma. In all four settings, alveolar epithelial progenitor (AT2) cells expressing oncogenic KRAS had reduced expression of mature lineage identity genes. These findings demonstrate the utility of our in vitro organoid approaches for uncovering the early consequences of oncogenic KRAS expression. This resource provides an extensive collection of datasets and describes organoid tools to study the transcriptional and proteomic changes that distinguish normal epithelial progenitor cells from early-stage lung cancer, facilitating the search for targets for KRAS-driven tumors.

Published
2020

5. FRA1 contributes to MEK-ERK pathway-dependent PD-L1 upregulation by KRAS mutation in premalignant human bronchial epithelial cells.

Author

Lee, Mi-Heon, Yanagawa, Jane, Tran, Linh, Walser, Tonya C, Bisht, Bharti, Fung, Eileen, Park, Stacy J, Zeng, Gang, Krysan, Kostyantyn, Wallace, William D, Paul, Manash K, Girard, Luc, Gao, Boning, Minna, John D, Dubinett, Steven M, and Lee, Jay M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Lung Cancer, Genetics, Lung, Cancer, 2.1 Biological and endogenous factors, FRA1, MEK-ERK pathway, PD-L1, KRAS, premalignant human bronchial epithelial cells, Clinical sciences, Neurosciences, Pharmacology and pharmaceutical sciences
Abstract

Oncogenic KRAS mutations are frequently found in non-small cell lung carcinoma (NSCLC) and cause constitutive activation of the MEK-ERK pathway. Many cancer types have been shown to overexpress PD-L1 to escape immune surveillance. FRA1 is a MEK/ERK-dependent oncogenic transcription factor and a member of the AP-1 transcriptional factor superfamily. This study assesses the hypothesis that KRAS mutation directly regulates PD-L1 expression through the MEK-ERK pathway mediated by FRA1. Premalignant human bronchial epithelial cell (HBEC) lines harboring the KRAS mutationV12, EGFR mutation, p53 knock-down, or both KRAS mutation and p53 knock-down were tested for levels of PD-L1, FRA1, and ERK activation (pERK). Our results showed that KRAS mutation alone, but not other genetic alterations, induced significantly higher expression of PD-L1 compared to its vector counterparts. The increased PD-L1 expression in the KRAS mutated cells was dramatically reduced by inhibition of ERK activation. Furthermore, the MEK-ERK pathway-dependent PD-L1 expression was markedly reduced by FRA1 silencing. Interestingly, FRA1 silencing led to inhibition of ERK activation, indicating that FRA1 plays a role in PD-L1 regulation via positive feedback of ERK activation. Correlation of PD-L1 and FRA1 mRNA expression was validated using human lung cancer specimens from The Cancer Genome Atlas (TCGA) and established NSCLC cell lines from Cancer Cell Line Encyclopedia (CCLE). FRA1 expression was significantly associated with PD-L1 expression, and high FRA1 expression was correlated with poor overall survival. Our findings suggest that oncogenic KRAS-driven PD-L1 expression is dependent on MEK-ERK and FRA1 in high risk, premalignant HBEC.

Published
2020

6. Capillary Proliferation in Systemic‐Sclerosis‐Related Pulmonary Fibrosis: Association with Pulmonary Hypertension

Author

Seki, Atsuko, Anklesaria, Zafia, Saggar, Rajeev, Dodson, Mark W, Schwab, Kristin, Liu, Ming‐Chang, Ashana, Deepshikha Charan, Miller, William D, Vangala, Sitaram, DerHovanessian, Ariss, Channick, Richard, Shaikh, Faisal, Belperio, John A, Weigt, Stephen S, Lynch, Joseph P, Ross, David J, Sullivan, Lauren, Khanna, Dinesh, Shapiro, Shelley S, Sager, Jeffrey, Gargani, Luna, Stanziola, Anna, Bossone, Eduardo, Schraufnagel, Dean E, Fishbein, Gregory, Xu, Haodong, Fishbein, Michael C, Wallace, William D, and Saggar, Rajan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Lung, Scleroderma, Rare Diseases, Autoimmune Disease, Respiratory, Clinical sciences
Abstract

ObjectiveWe sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH).MethodsTwo pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc-PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquantitatively assessed in areas of preserved lung architecture. Capillary proliferation (CP) within the alveolar walls was measured by its distribution, extent (CP % involvement), and maximum number of layers (maximum CP). These measures were then evaluated to determine the strength of their association with right heart catheterization-proven PH.ResultsUsing consensus measures, all measures of CP were significantly associated with PH. Maximum CP had the strongest association with PH (P = 0.013; C statistic 0.869). Maximum CP 2 or more layers and CP % involvement 10% or greater were the optimal thresholds that predicted PH, both with a sensitivity of 56% and specificity of 91%. The CP was typically multifocal rather than focal or diffuse and was associated with a background pattern of usual interstitial pneumonia. There was a significant but weaker relationship between the presence of abnormal small arteries and veins and PH.ConclusionIn the setting of advanced SSc-PF, the histopathologic feature of the pulmonary microcirculation best associated with PH was capillary proliferation in architecturally preserved lung areas.

Published
2019

8. Insights on pulmonary tumor thrombotic microangiopathy: a seven‐patient case series

Author

Godbole, Rohit, Saggar, Rajan, Zider, Alexander, Betancourt, Jamie, Wallace, William D, Suh, Robert D, and Kamangar, Nader

Subjects
Lung, Hematology, Cardiovascular, Rare Diseases, Cancer, Heart Disease, pulmonary pathology, chest imaging, pulmonary arterial hypertension, Cardiorespiratory Medicine and Haematology
Abstract

Pulmonary tumor thrombotic microangiopathy (PTTM) is a disease process wherein tumor cells are thought to embolize to the pulmonary circulation causing pulmonary hypertension (PH) and death from right heart failure. Presented herein are clinical, laboratory, radiographic, and histologic features across seven cases of PTTM. Highlighted in this publication are also involvement of pulmonary venules and clinical features distinguishing PTTM from clinical mimics. We conducted a retrospective chart review of seven cases of PTTM from hospitals in the greater Los Angeles metropolitan area. Patients in this series exhibited: symptoms of cough and progressive dyspnea; PH and/or heart failure on physical exam; laboratory abnormalities of anemia, thrombocytopenia, elevated LDH, and elevated D-dimer; chest computed tomography (CT) showing diffuse septal thickening, mediastinal and hilar lymphadenopathy and nodules; elevated pulmonary artery pressures on transthoracic echocardiogram and/or right heart catheterization; and presence of malignancy. Tumor emboli and fibrocellular intimal proliferation were seen in pulmonary arterioles, while two patients had pulmonary venopathy. PTTM is a devastating disease occurring in patients with metastatic carcinoma. An early diagnosis is challenging. Understanding the clinical presentation of PTTM and distinguishing PTTM from clinical mimics may help achieve an early diagnosis and allow time for initiation of treatment.

Published
2017

9. Phase I Trial of Intratumoral Injection of CCL21 Gene–Modified Dendritic Cells in Lung Cancer Elicits Tumor-Specific Immune Responses and CD8+ T-cell Infiltration

Author

Lee, Jay M, Lee, Mi-Heon, Garon, Edward, Goldman, Jonathan W, Salehi-Rad, Ramin, Baratelli, Felicita E, Schaue, Dörthe, Wang, Gerald, Rosen, Fran, Yanagawa, Jane, Walser, Tonya C, Lin, Ying, Park, Stacy J, Adams, Sharon, Marincola, Francesco M, Tumeh, Paul C, Abtin, Fereidoun, Suh, Robert, Reckamp, Karen L, Lee, Gina, Wallace, William D, Lee, Sarah, Zeng, Gang, Elashoff, David A, Sharma, Sherven, and Dubinett, Steven M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Biotechnology, Immunotherapy, Vaccine Related, Cancer, Lung, Clinical Research, Immunization, Lung Cancer, 6.1 Pharmaceuticals, Good Health and Well Being, Adult, Aged, B7-H1 Antigen, CD8-Positive T-Lymphocytes, Cancer Vaccines, Carcinoma, Non-Small-Cell Lung, Chemokine CCL21, Cohort Studies, Dendritic Cells, Dyspnea, Female, Humans, Immunotherapy, Adoptive, Injections, Intralesional, Interferon-gamma, Lung Neoplasms, Male, Middle Aged, Muscle Weakness, Pain, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

Purpose: A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following in situ vaccination (ClinicalTrials.gov: NCT01574222).Experimental Design: Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 × 106, 5 × 106, 1 × 107, or 3 × 107 DCs/injection) by CT- or bronchoscopic-guided intratumoral injections (days 0 and 7). Immune responses were assessed by tumor antigen-specific peripheral blood lymphocyte induction of IFNγ in ELISPOT assays. Tumor biopsies were evaluated for CD8+ T cells by IHC and for PD-L1 expression by IHC and real-time PCR (RT-PCR).Results: Twenty-five percent (4/16) of patients had stable disease at day 56. Median survival was 3.9 months. ELISPOT assays revealed 6 of 16 patients had systemic responses against tumor-associated antigens (TAA). Tumor CD8+ T-cell infiltration was induced in 54% of subjects (7/13; 3.4-fold average increase in the number of CD8+ T cells per mm2). Patients with increased CD8+ T cells following vaccination showed significantly increased PD-L1 mRNA expression.Conclusions: Intratumoral vaccination with Ad-CCL21-DC resulted in (i) induction of systemic tumor antigen-specific immune responses; (ii) enhanced tumor CD8+ T-cell infiltration; and (iii) increased tumor PD-L1 expression. Future studies will evaluate the role of combination therapies with PD-1/PD-L1 checkpoint inhibition combined with DC-CCL21 in situ vaccination. Clin Cancer Res; 23(16); 4556-68. ©2017 AACR.

Published
2017

10. Dynamic Changes in Intracellular ROS Levels Regulate Airway Basal Stem Cell Homeostasis through Nrf2-Dependent Notch Signaling

Author

Paul, Manash K, Bisht, Bharti, Darmawan, Daphne O, Chiou, Richard, Ha, Vi L, Wallace, William D, Chon, Andrew T, Hegab, Ahmed E, Grogan, Tristan, Elashoff, David A, Alva-Ornelas, Jackelyn A, and Gomperts, Brigitte N

Subjects
Medical Biotechnology, Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Lung, Regenerative Medicine, 1.1 Normal biological development and functioning, Respiratory, Generic health relevance, Animals, Antioxidants, Cell Cycle, Cell Differentiation, Cell Proliferation, Homeostasis, Humans, Mice, NF-E2-Related Factor 2, Oxidation-Reduction, Polidocanol, Polyethylene Glycols, Reactive Oxygen Species, Receptors, Notch, Signal Transduction, Stem Cells, Trachea, Wound Healing, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Airways are exposed to myriad environmental and damaging agents such as reactive oxygen species (ROS), which also have physiological roles as signaling molecules that regulate stem cell function. However, the functional significance of both steady and dynamically changing ROS levels in different stem cell populations, as well as downstream mechanisms that integrate ROS sensing into decisions regarding stem cell homeostasis, are unclear. Here, we show in mouse and human airway basal stem cells (ABSCs) that intracellular flux from low to moderate ROS levels is required for stem cell self-renewal and proliferation. Changing ROS levels activate Nrf2, which activates the Notch pathway to stimulate ABSC self-renewal and an antioxidant program that scavenges intracellular ROS, returning overall ROS levels to a low state to maintain homeostatic balance. This redox-mediated regulation of lung stem cell function has significant implications for stem cell biology, repair of lung injuries, and diseases such as cancer.

Published
2014

11. The utility of next‐generation sequencing in distinguishing between separate primary lung carcinomas and intrapulmonary metastasis: A case report.

Author

Mantri, Shilpa S., Wallace, William D., and Nieva, Jorge J.

Subjects
*DIFFERENTIAL diagnosis, *TUMOR markers, *DECISION making in clinical medicine, *METASTASIS, *LUNG tumors, *GENETIC mutation, *GENETIC testing, *SEQUENCE analysis, *MOLECULAR diagnosis
Abstract

The distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is crucial to accurate cancer staging. Histopathology‐based classification cannot always determine the relatedness of multiple tumors taken from the lung. Recently, next‐generation sequencing (NGS) has been used for biomarker determination, but it also has the potential to inform clonality determination among multiple tumors. Here we present a patient with three lung tumors, each diagnosed as adenocarcinoma by histopathology with a differential diagnosis of SPLC versus IPM. We pursued molecular profiling by NGS, which revealed three unique mutational patterns ruling out the possibility of clonal relatedness among the cancers. Our case supports the utility of NGS in supplementing histopathological methods to distinguish between SPLCs and IPMs and to guide treatment decisions. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Leukocyte chemotactic factor 2 (LECT2) amyloidosis presenting as pulmonary-renal syndrome: a case report and review of the literature.

Author

Khalighi, Mazdak A, Yue, Andrew, Hwang, Mei-Tsuey, and Wallace, William D

Subjects
amyloid, lect2, pulmonary-renal syndrome
Abstract

Leukocyte chemotactic factor-2 (LECT2) amyloidosis has been described as being associated with kidney disease; however, no clinical manifestations outside of the kidney have been previously reported. We describe a patient presenting with pulmonary-renal syndrome found to have deposition of amyloidogenic LECT2 (ALECT2) within both the lung and the kidney. This case is unique in regard to both the patient's clinical presentation of pulmonary-renal syndrome in the setting of amyloidosis and the biopsy finding of ALECT2 deposition within the lung. It also emphasizes the importance of tissue diagnosis in such cases, given that amyloidosis was not initially considered in the differential diagnosis.

Published
2013

13. Predictors of survival in portopulmonary hypertension: a 20-year experience

Author

Aggarwal, Manik, Li, Manshi, Bhardwaj, Abhishek, Wallace, William D., Wang, Xiaofeng, Carey, William D., Dweik, Raed A., Heresi, Gustavo A., and Tonelli, Adriano R.

Subjects
Adult, End Stage Liver Disease, Male, Pulmonary Arterial Hypertension, Hepatology, Hypertension, Pulmonary, Hypertension, Portal, Gastroenterology, Humans, Female, Middle Aged, Severity of Illness Index, Article
Abstract

BACKGROUND AND OBJECTIVES: Portopulmonary hypertension (PoPH) is a rare complication of portal hypertension associated with poor survival. Scarce data is available on predictors of survival in PoPH with conflicting results. We sought to characterize the outcomes and variables associated with survival in a large cohort of patients with PoPH in an American population of patients. STUDY DESIGN AND METHODS: We identified PoPH patients from the Cleveland Clinic Pulmonary Hypertension Registry between 1998–2019. We collected prespecified data, particularly focusing on hepatic and cardiopulmonary assessments and tested their effect on long-term survival. RESULTS: Eighty patients with PoPH with a mean ± standard deviation age of 54 ±10 years, (54% females) were included in the analysis. The median Model for End Stage Liver disease with sodium (MELD-Na) score was 13.0 (10.0–18.0) at PoPH diagnosis. World Health Association functional class III-IV was noted in 57%. Mean pulmonary arterial pressure was 47 ±10 mmHg and pulmonary vascular resistance 6.0 ±2.8 Woods units. A total of 63 (78.5%) patients were started on pulmonary arterial hypertension (PAH)-specific treatment during the first 6 months of diagnosis. Survival rates at 1-, 3- and 5-year were 77%, 52% and 34%, respectively. Cardiopulmonary hemodynamics as well as PAH-specific treatment did not affect survival. In multivariable model, MELD-Na, resting heart rate and the presence of hepatic encephalopathy were independent predictors of survival. CONCLUSIONS: PoPH patients have poor 5-year survival which is strongly associated to the severity of underlying liver disease and not to the hemodynamic severity of PoPH; therefore efforts should be focused in facilitating liver transplantation for these patients.

Published
2021
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14. Coxiella burnetii Endocarditis and Meningitis, California, USA, 2017

Author

Allan-Blitz, Lao-Tzu, Sakona, Ashyln, Wallace, William D., and Klausner, Jeffrey D.

Subjects
University of California, Health aspects, Meningitis -- Health aspects, Endocarditis -- Health aspects, Epidemiology -- Health aspects, RNA -- Health aspects
Abstract

Coxiella burnetii is the bacterium responsible for Q fever. The epidemiology of C. burnetii infection in the United States is not well characterized. Chronic infection can result in endocarditis or [...]

Published
2018
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20. A conflict of interest?

Author

Patterson, James A, Neill, Adrian K, Mulholland, Keith, and Wallace, William D

Published
2004

23. The Immune Contexture Associates with the Genomic Landscape in Lung Adenomatous Premalignancy

Author

Krysan, Kostyantyn, primary, Tran, Linh M., additional, Grimes, Brandon S., additional, Fishbein, Gregory A., additional, Seki, Atsuko, additional, Gardner, Brian K., additional, Walser, Tonya C., additional, Salehi-Rad, Ramin, additional, Yanagawa, Jane, additional, Lee, Jay M., additional, Sharma, Sherven, additional, Aberle, Denise R., additional, Spira, Arum E., additional, Elashoff, David A., additional, Wallace, William D., additional, Fishbein, Michael C., additional, and Dubinett, Steven M., additional

Published
2019
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25. Pitfalls and Artifacts of 123I-Ioflupane SPECT in Parkinsonian Syndromes: A Quality Improvement Teaching Tool.

Author

Santos, Cristiane A. Tuma, Wallace, William David, Sanghun Kim, Vijayakumar, Vani, Santos, Cristiane Araujo Tuma, Wallace, William D, Kim, Sanghun, and Tuma Santos, Cristiane A

Abstract

The aim of the current article is to describe how to improve the quality of imaging with 123I-ioflupane SPECT and to serve as a teaching tool on this topic. The radiopharmaceutical 123I-ioflupane is used to visualize the nigrostriatal pathway. Parkinson disease and parkinsonian syndromes are movement disorders that exhibit nigrostriatal degeneration, with a decreased dopamine transporter level in the pathway and thus a decreased 123I-ioflupane distribution. Other nonparkinsonian movement disorders, such as essential tremor, will have intact dopaminergic neurons and exhibit a normal distribution of the radiopharmaceutical throughout the striata. Parkinsonian disorders are usually diagnosed clinically. However, 123I-ioflupane SPECT can be a valuable tool when the clinical features are not sufficiently clear. 123I-ioflupane SPECT image interpretation is not always straightforward. Many pitfalls, including biologic factors, technical factors, medications, and factors such as age, race, ethnicity, and body habitus, can make the interpretation challenging. The technologist and nuclear radiologist must identify the expected imaging findings to avoid the most common mistakes related to artifacts. This article reviews the usual pitfalls and artifacts of 123I-ioflupane SPECT that can compromise an accurate diagnosis and lead to misinterpretation of image findings. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Taxpayers face diversity in state appeals procedures.

Author

Wells, Steven C., Barney, Doug, and Wallace, William D.

Subjects
State taxation -- Research -- Analysis, Tax accounting -- Analysis -- Research, Tax appeals -- Research -- Analysis
Abstract

EXECUTIVE SUMMARY * MULTISTATE TAXPAYERS face a variety of tax appeals procedures in the 50 states. Until uniform procedures are adopted, CPAs must make certain they understand current rules to [...]

Published
1992

31. PD-L1 expression correlates with immune response in a Phase I trial of CCL21 gene modified dendritic cell therapy in lung cancer

Author

Lee, Jay M, primary, Garon, Edward B, additional, Lee, Mi-Heon, additional, Wang, Gerald, additional, Schaue, Dörthe, additional, Baratelli, Felicita, additional, Abtin, Fereidoun, additional, Suh, Robert, additional, Wallace, William D, additional, Zeng, Gang, additional, Sharma, Sherven, additional, and Dubinett, Steven M, additional

Published
2014
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32. Presence of a Putative Tumor-Initiating Progenitor Cell Population Predicts Poor Prognosis in Smokers with Non–Small Cell Lung Cancer

Author

Ooi, Aik T., primary, Mah, Vei, additional, Nickerson, Derek W., additional, Gilbert, Jennifer L., additional, Ha, Vi Luan, additional, Hegab, Ahmed E., additional, Horvath, Steve, additional, Alavi, Mohammad, additional, Maresh, Erin L., additional, Chia, David, additional, Gower, Adam C., additional, Lenburg, Marc E., additional, Spira, Avrum, additional, Solis, Luisa M., additional, Wistuba, Ignacio I., additional, Walser, Tonya C., additional, Wallace, William D., additional, Dubinett, Steven M., additional, Goodglick, Lee, additional, and Gomperts, Brigitte N., additional

Published
2010
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33. Abstract 4299: Poor prognosis in smokers with non-small cell lung cancer correlates with the presence of a reparative progenitor cell population

Author

Ooi, Aik T., primary, Mah, Vei H., additional, Nickerson, Derek W., additional, Gilbert, Jennifer L., additional, Ha, Vi L., additional, Hegab, Ahmed E., additional, Horvath, Steve, additional, Alavi, Mohammad, additional, Maresh, Erin, additional, Chia, David, additional, Gower, Adam C., additional, Lenburg, Marc E., additional, Spira, Avrum, additional, Walser, Tonya, additional, Wallace, William D., additional, Dubinett, Steven M., additional, Goodglick, Lee, additional, and Gomperts, Brigitte N., additional

Published
2010
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34. Constructive dividends; taxpayers beware

Author

Wallace, William D. and Scribner, Michael

Subjects
Dividends -- Accounting and auditing, Securities -- Taxation, Tax shelters -- Methods, Banking, finance and accounting industries, Business
Published
1989

35. Computers and the tax professional

Author

Throneberry, Mary Beth, Malley, John C., and Wallace, William D.

Subjects
Tax returns -- Technology application, Automation -- Planning, Accounting firms -- Technology application, Tax consultants -- Planning, Computers -- Purchasing, Banking, finance and accounting industries, Business
Published
1987

38. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one: National Harbor, MD, USA. 9-13 November 2016

Author

Lundqvist, Andreas, van Hoef, Vincent, Zhang, Xiaonan, Wennerberg, Erik, Lorent, Julie, Witt, Kristina, Sanz, Laia Masvidal, Liang, Shuo, Murray, Shannon, Larsson, Ola, Kiessling, Rolf, Mao, Yumeng, Sidhom, John-William, Bessell, Catherine A., Havel, Jonathan, Schneck, Jonathan, Chan, Timothy A., Sachsenmeier, Eliot, Woods, David, Berglund, Anders, Ramakrishnan, Rupal, Sodre, Andressa, Weber, Jeffrey, Zappasodi, Roberta, Li, Yanyun, Qi, Jingjing, Wong, Philip, Sirard, Cynthia, Postow, Michael, Newman, Walter, Koon, Henry, Velcheti, Vamsidhar, Callahan, Margaret K., Wolchok, Jedd D., Merghoub, Taha, Lum, Lawrence G., Choi, Minsig, Thakur, Archana, Deol, Abhinav, Dyson, Gregory, Shields, Anthony, Haymaker, Cara, Uemura, Marc, Murthy, Ravi, James, Marihella, Wang, Daqing, Brevard, Julie, Monaghan, Catherine, Swann, Suzanne, Geib, James, Cornfeld, Mark, Chunduru, Srinivas, Agrawal, Sudhir, Yee, Cassian, Wargo, Jennifer, Patel, Sapna P., Amaria, Rodabe, Tawbi, Hussein, Glitza, Isabella, Woodman, Scott, Hwu, Wen-Jen, Davies, Michael A., Hwu, Patrick, Overwijk, Willem W., Bernatchez, Chantale, Diab, Adi, Massarelli, Erminia, Segal, Neil H., Ribrag, Vincent, Melero, Ignacio, Gangadhar, Tara C., Urba, Walter, Schadendorf, Dirk, Ferris, Robert L., Houot, Roch, Morschhauser, Franck, Logan, Theodore, Luke, Jason J., Sharfman, William, Barlesi, Fabrice, Ott, Patrick A., Mansi, Laura, Kummar, Shivaani, Salles, Gilles, Carpio, Cecilia, Meier, Roland, Krishnan, Suba, McDonald, Dan, Maurer, Matthew, Gu, Xuemin, Neely, Jaclyn, Suryawanshi, Satyendra, Levy, Ronald, Khushalani, Nikhil, Wu, Jennifer, Zhang, Jinyu, Basher, Fahmin, Rubinstein, Mark, Bucsek, Mark, Qiao, Guanxi, MacDonald, Cameron, Hylander, Bonnie, Repasky, Elizabeth, Chatterjee, Shilpak, Daenthanasanmak, Anusara, Chakraborty, Paramita, Toth, Kyle, Meek, Megan, Garrett-Mayer, Elizabeth, Nishimura, Michael, Paulos, Chrystal, Beeson, Craig, Yu, Xuezhong, Mehrotra, Shikhar, Zhao, Fei, Evans, Kathy, Xiao, Christine, Holtzhausen, Alisha, Hanks, Brent A., Scharping, Nicole, Menk, Ashley V., Moreci, Rebecca, Whetstone, Ryan, Dadey, Rebekah, Watkins, Simon, Ferris, Robert, Delgoffe, Greg M., Peled, Jonathan, Devlin, Sean, Staffas, Anna, Lumish, Melissa, Rodriguez, Kori Porosnicu, Ahr, Katya, Perales, Miguel, Giralt, Sergio, Taur, Ying, Pamer, Eric, van den Brink, Marcel R. M., Jenq, Robert, Annels, Nicola, Pandha, Hardev, Simpson, Guy, Mostafid, Hugh, Harrington, Kevin, Melcher, Alan, Grose, Mark, Davies, Bronwyn, Au, Gough, Karpathy, Roberta, Shafren, Darren, Ricca, Jacob, Zamarin, Dmitriy, Batista, Luciana, Marliot, Florence, Vasaturo, Angela, Carpentier, Sabrina, Poggionovo, Cécile, Frayssinet, Véronique, Fieschi, Jacques, Van den Eynde, Marc, Pagès, Franck, Galon, Jérôme, Hermitte, Fabienne, Smith, Sean G., Nguyen, Khue, Ravindranathan, Sruthi, Koppolu, Bhanu, Zaharoff, David, Schvartsman, Gustavo, Bassett, Roland, McQuade, Jennifer L., Haydu, Lauren E., Kline, Douglas, Chen, Xiufen, Fosco, Dominick, Kline, Justin, Overacre, Abigail, Chikina, Maria, Brunazzi, Erin, Shayan, Gulidanna, Horne, William, Kolls, Jay, Bruno, Tullia C., Workman, Creg, Vignali, Dario, Adusumilli, Prasad S., Ansa-Addo, Ephraim A, Li, Zihai, Gerry, Andrew, Sanderson, Joseph P., Howe, Karen, Docta, Roslin, Gao, Qian, Bagg, Eleanor A. L., Tribble, Nicholas, Maroto, Miguel, Betts, Gareth, Bath, Natalie, Melchiori, Luca, Lowther, Daniel E., Ramachandran, Indu, Kari, Gabor, Basu, Samik, Binder-Scholl, Gwendolyn, Chagin, Karen, Pandite, Lini, Holdich, Tom, Amado, Rafael, Zhang, Hua, Glod, John, Bernstein, Donna, Jakobsen, Bent, Mackall, Crystal, Wong, Ryan, Silk, Jonathan D., Adams, Katherine, Hamilton, Garth, Bennett, Alan D., Brett, Sara, Jing, Junping, Quattrini, Adriano, Saini, Manoj, Wiedermann, Guy, Brewer, Joanna, Duong, MyLinh, Lu, An, Chang, Peter, Mahendravada, Aruna, Shinners, Nicholas, Slawin, Kevin, Spencer, David M., Foster, Aaron E., Bayle, J. Henri, Bergamaschi, Cristina, Ng, Sinnie Sin Man, Nagy, Bethany, Jensen, Shawn, Hu, Xintao, Alicea, Candido, Fox, Bernard, Felber, Barbara, Pavlakis, George, Chacon, Jessica, Yamamoto, Tori, Garrabrant, Thomas, Cortina, Luis, Powell, Daniel J., Donia, Marco, Kjeldsen, Julie Westerlin, Andersen, Rikke, Westergaard, Marie Christine Wulff, Bianchi, Valentina, Legut, Mateusz, Attaf, Meriem, Dolton, Garry, Szomolay, Barbara, Ott, Sascha, Lyngaa, Rikke, Hadrup, Sine Reker, Sewell, Andrew Kelvin, Svane, Inge Marie, Fan, Aaron, Kumai, Takumi, Celis, Esteban, Frank, Ian, Stramer, Amanda, Blaskovich, Michelle A., Wardell, Seth, Fardis, Maria, Bender, James, Lotze, Michael T., Goff, Stephanie L., Zacharakis, Nikolaos, Assadipour, Yasmine, Prickett, Todd D., Gartner, Jared J., Somerville, Robert, Black, Mary, Xu, Hui, Chinnasamy, Harshini, Kriley, Isaac, Lu, Lily, Wunderlich, John, Robbins, Paul F., Rosenberg, Steven, Feldman, Steven A., Trebska-McGowan, Kasia, Malekzadeh, Parisa, Payabyab, Eden, Sherry, Richard, Gokuldass, Aishwarya, Kopits, Charlene, Rabinovich, Brian, Green, Daniel S., Kamenyeva, Olena, Zoon, Kathryn C., Annunziata, Christina M., Hammill, Joanne, Helsen, Christopher, Aarts, Craig, Bramson, Jonathan, Harada, Yui, Yonemitsu, Yoshikazu, Mwawasi, Kenneth, Denisova, Galina, Giri, Rajanish, Jin, Benjamin, Campbell, Tracy, Draper, Lindsey M., Stevanovic, Sanja, Yu, Zhiya, Weissbrich, Bianca, Restifo, Nicholas P., Trimble, Cornelia L., Hinrichs, Christian S., Tsang, Kwong, Fantini, Massimo, Hodge, James W., Fujii, Rika, Fernando, Ingrid, Jochems, Caroline, Heery, Christopher, Gulley, James, Soon-Shiong, Patrick, Schlom, Jeffrey, Jing, Weiqing, Gershan, Jill, Blitzer, Grace, Weber, James, McOlash, Laura, Johnson, Bryon D., Kiany, Simin, Gangxiong, Huang, Kleinerman, Eugenie S., Klichinsky, Michael, Ruella, Marco, Shestova, Olga, Kenderian, Saad, Kim, Miriam, Scholler, John, June, Carl H., Gill, Saar, Moogk, Duane, Zhong, Shi, Liadi, Ivan, Rittase, William, Fang, Victoria, Dougherty, Janna, Perez-Garcia, Arianne, Osman, Iman, Zhu, Cheng, Varadarajan, Navin, Frey, Alan, Krogsgaard, Michelle, Landi, Daniel, Fousek, Kristen, Mukherjee, Malini, Shree, Ankita, Joseph, Sujith, Bielamowicz, Kevin, Byrd, Tiara, Ahmed, Nabil, Hegde, Meenakshi, Lee, Sylvia, Byrd, David, Thompson, John, Bhatia, Shailender, Tykodi, Scott, Delismon, Judy, Chu, Liz, Abdul-Alim, Siddiq, Ohanian, Arpy, DeVito, Anna Marie, Riddell, Stanley, Margolin, Kim, Magalhaes, Isabelle, Mattsson, Jonas, Uhlin, Michael, Nemoto, Satoshi, Villarroel, Patricio Pérez, Nakagawa, Ryosuke, Mule, James J., Mailloux, Adam W., Mata, Melinda, Nguyen, Phuong, Gerken, Claudia, DeRenzo, Christopher, Gottschalk, Stephen, Mathieu, Mélissa, Pelletier, Sandy, Stagg, John, Turcotte, Simon, Minutolo, Nicholas, Sharma, Prannda, Tsourkas, Andrew, Mockel-Tenbrinck, Nadine, Mauer, Daniela, Drechsel, Katharina, Barth, Carola, Freese, Katharina, Kolrep, Ulrike, Schult, Silke, Assenmacher, Mario, Kaiser, Andrew, Mullinax, John, Hall, MacLean, Le, Julie, Kodumudi, Krithika, Royster, Erica, Richards, Allison, Gonzalez, Ricardo, Sarnaik, Amod, Pilon-Thomas, Shari, Nielsen, Morten, Krarup-Hansen, Anders, Hovgaard, Dorrit, Petersen, Michael Mørk, Loya, Anand Chainsukh, Junker, Niels, Rivas, Charlotte, Parihar, Robin, Rooney, Cliona M., Qin, Haiying, Nguyen, Sang, Su, Paul, Burk, Chad, Duncan, Brynn, Kim, Bong-Hyun, Kohler, M. Eric, Fry, Terry, Rao, Arjun A., Teyssier, Noam, Pfeil, Jacob, Sgourakis, Nikolaos, Salama, Sofie, Haussler, David, Richman, Sarah A., Nunez-Cruz, Selene, Gershenson, Zack, Mourelatos, Zissimos, Barrett, David, Grupp, Stephan, Milone, Michael, Rodriguez-Garcia, Alba, Robinson, Matthew K., Adams, Gregory P., Santos, João, Havunen, Riikka, Siurala, Mikko, Cervera-Carrascón, Víctor, Parviainen, Suvi, Antilla, Marjukka, Hemminki, Akseli, Sethuraman, Jyothi, Santiago, Laurelis, Chen, Jie Qing, Dai, Zhimin, Sha, Huizi, Su, Shu, Ding, Naiqing, Liu, Baorui, Pasetto, Anna, Helman, Sarah R., Rosenberg, Steven A., Burgess, Melissa, Zhang, Hui, Lee, Tien, Klingemann, Hans, Nghiem, Paul, Kirkwood, John M., Rossi, John M., Sherman, Marika, Xue, Allen, Shen, Yueh-wei, Navale, Lynn, Kochenderfer, James N., Bot, Adrian, Veerapathran, Anandaraman, Wiener, Doris, Waller, Edmund K., Li, Jian-Ming, Petersen, Christopher, Blazar, Bruce R., Li, Jingxia, Giver, Cynthia R., Wang, Ziming, Grossenbacher, Steven K., Sturgill, Ian, Canter, Robert J., Murphy, William J., Zhang, Congcong, Burger, Michael C., Jennewein, Lukas, Waldmann, Anja, Mittelbronn, Michel, Tonn, Torsten, Steinbach, Joachim P., Wels, Winfried S., Williams, Jason B., Zha, Yuanyuan, Gajewski, Thomas F., Williams, LaTerrica C., Krenciute, Giedre, Kalra, Mamta, Louis, Chrystal, Xin, Gang, Schauder, David, Jiang, Aimin, Joshi, Nikhil, Cui, Weiguo, Zeng, Xue, Zhao, Zeguo, Hamieh, Mohamad, Eyquem, Justin, Gunset, Gertrude, Bander, Neil, Sadelain, Michel, Askmyr, David, Abolhalaj, Milad, Lundberg, Kristina, Greiff, Lennart, Lindstedt, Malin, Angell, Helen K., Kim, Kyoung-Mee, Kim, Seung-Tae, Kim, Sung, Sharpe, Alan D., Ogden, Julia, Davenport, Anna, Hodgson, Darren R., Barrett, Carl, Lee, Jeeyun, Kilgour, Elaine, Hanson, Jodi, Caspell, Richard, Karulin, Alexey, Lehmann, Paul, Ansari, Tameem, Schiller, Annemarie, Sundararaman, Srividya, Roen, Diana, Ayers, Mark, Levitan, Diane, Arreaza, Gladys, Liu, Fang, Mogg, Robin, Bang, Yung-Jue, O’Neil, Bert, Cristescu, Razvan, Friedlander, Philip, Wassman, Karl, Kyi, Chrisann, Oh, William, Bhardwaj, Nina, Bornschlegl, Svetlana, Gustafson, Michael P., Gastineau, Dennis A., Parney, Ian F., Dietz, Allan B., Carvajal-Hausdorf, Daniel, Mani, Nikita, Schalper, Kurt, Rimm, David, Chang, Serena, Kurland, John, Ahlers, Christoph Matthias, Jure-Kunkel, Maria, Cohen, Lewis, Maecker, Holden, Kohrt, Holbrook, Chen, Shuming, Crabill, George, Pritchard, Theresa, McMiller, Tracee, Pardoll, Drew, Pan, Fan, Topalian, Suzanne, Danaher, Patrick, Warren, Sarah, Dennis, Lucas, White, Andrew M., D’Amico, Leonard, Geller, Melissa, Disis, Mary L., Beechem, Joseph, Odunsi, Kunle, Fling, Steven, Derakhshandeh, Roshanak, Webb, Tonya J., Dubois, Sigrid, Conlon, Kevin, Bryant, Bonita, Hsu, Jennifer, Beltran, Nancy, Müller, Jürgen, Waldmann, Thomas, Duhen, Rebekka, Duhen, Thomas, Thompson, Lucas, Montler, Ryan, Weinberg, Andrew, Kates, Max, Early, Brandon, Yusko, Erik, Schreiber, Taylor H., Bivalacqua, Trinity J., Lunceford, Jared, Nebozhyn, Michael, Murphy, Erin, Loboda, Andrey, Kaufman, David R., Albright, Andrew, Cheng, Jonathan, Kang, S. Peter, Shankaran, Veena, Piha-Paul, Sarina A., Yearley, Jennifer, Seiwert, Tanguy, Ribas, Antoni, McClanahan, Terrill K., Sher, Xinwei, Liu, Xiao Qiao, Joe, Andrew, Plimack, Elizabeth, Forrest-Hay, Alex, Guyre, Cheryl A., Narumiya, Kohei, Delcommenne, Marc, Hirsch, Heather A., Deshpande, Amit, Reeves, Jason, Shu, Jenny, Zi, Tong, Michaelson, Jennifer, Law, Debbie, Trehu, Elizabeth, Sathyanaryanan, Sriram, Hodkinson, Brendan P., Hutnick, Natalie A., Schaffer, Michael E., Gormley, Michael, Hulett, Tyler, Ballesteros-Merino, Carmen, Dubay, Christopher, Afentoulis, Michael, Reddy, Ashok, David, Larry, Jayant, Kumar, Agrawal, Swati, Agrawal, Rajendra, Jeyakumar, Ghayathri, Kim, Seongho, Kim, Heejin, Silski, Cynthia, Suisham, Stacey, Heath, Elisabeth, Vaishampayan, Ulka, Vandeven, Natalie, Viller, Natasja Nielsen, O’Connor, Alison, Chen, Hui, Bossen, Bolette, Sievers, Eric, Uger, Robert, Johnson, Lisa, Kao, Hsiang-Fong, Hsiao, Chin-Fu, Lai, Shu-Chuan, Wang, Chun-Wei, Ko, Jenq-Yuh, Lou, Pei-Jen, Lee, Tsai-Jan, Liu, Tsang-Wu, Hong, Ruey-Long, Kearney, Staci J., Black, Joshua C., Landis, Benjamin J., Koegler, Sally, Hirsch, Brooke, Gianani, Roberto, Kim, Jeffrey, He, Ming-Xiao, Zhang, Bingqing, Su, Nan, Luo, Yuling, Ma, Xiao-Jun, Park, Emily, Kim, Dae Won, Copploa, Domenico, Kothari, Nishi, doo Chang, Young, Kim, Richard, Kim, Namyong, Lye, Melvin, Wan, Ee, Knaus, Hanna A., Berglund, Sofia, Hackl, Hubert, Karp, Judith E., Gojo, Ivana, Luznik, Leo, Hong, Henoch S., Koch, Sven D., Scheel, Birgit, Gnad-Vogt, Ulrike, Kallen, Karl-Josef, Wiegand, Volker, Backert, Linus, Kohlbacher, Oliver, Hoerr, Ingmar, Fotin-Mleczek, Mariola, Billingsley, James M., Koguchi, Yoshinobu, Conrad, Valerie, Miller, William, Gonzalez, Iliana, Poplonski, Tomasz, Meeuwsen, Tanisha, Howells-Ferreira, Ana, Rattray, Rogan, Campbell, Mary, Bifulco, Carlo, Bahjat, Keith, Curti, Brendan, Vetsika, E-K, Kallergi, G., Aggouraki, Despoina, Lyristi, Z., Katsarlinos, P., Koinis, Filippos, Georgoulias, V., Kotsakis, Athanasios, Martin, Nathan T., Aeffner, Famke, Cerkovnik, Logan, Pratte, Luke, Kim, Rebecca, Krueger, Joseph, Martínez-Usatorre, Amaia, Jandus, Camilla, Donda, Alena, Carretero-Iglesia, Laura, Speiser, Daniel E., Zehn, Dietmar, Rufer, Nathalie, Romero, Pedro, Panda, Anshuman, Mehnert, Janice, Hirshfield, Kim M., Riedlinger, Greg, Damare, Sherri, Saunders, Tracie, Sokol, Levi, Stein, Mark, Poplin, Elizabeth, Rodriguez-Rodriguez, Lorna, Silk, Ann, Chan, Nancy, Frankel, Melissa, Kane, Michael, Malhotra, Jyoti, Aisner, Joseph, Kaufman, Howard L., Ali, Siraj, Ross, Jeffrey, White, Eileen, Bhanot, Gyan, Ganesan, Shridar, Monette, Anne, Bergeron, Derek, Amor, Amira Ben, Meunier, Liliane, Caron, Christine, Morou, Antigoni, Kaufmann, Daniel, Liberman, Moishe, Jurisica, Igor, Mes-Masson, Anne-Marie, Hamzaoui, Kamel, Lapointe, Rejean, Mongan, Ann, Ku, Yuan-Chieh, Tom, Warren, Sun, Yongming, Pankov, Alex, Looney, Tim, Au-Young, Janice, Hyland, Fiona, Conroy, Jeff, Morrison, Carl, Glenn, Sean, Burgher, Blake, Ji, He, Gardner, Mark, Omilian, Angela R., Bshara, Wiam, Angela, Omilian, Obeid, Joseph M., Erdag, Gulsun, Smolkin, Mark E., Deacon, Donna H., Patterson, James W., Chen, Lieping, Bullock, Timothy N., Slingluff, Craig L., Loffredo, John T., Vuyyuru, Raja, Beyer, Sophie, Spires, Vanessa M., Fox, Maxine, Ehrmann, Jon M., Taylor, Katrina A., Korman, Alan J., Graziano, Robert F., Page, David, Sanchez, Katherine, Martel, Maritza, De Macedo, Mariana Petaccia, Qin, Yong, Reuben, Alex, Spencer, Christine, Guindani, Michele, Racolta, Adriana, Kelly, Brian, Jones, Tobin, Polaske, Nathan, Theiss, Noah, Robida, Mark, Meridew, Jeffrey, Habensus, Iva, Zhang, Liping, Pestic-Dragovich, Lidija, Tang, Lei, Olencki, Thomas, Hutson, Thomas, Roder, Joanna, Blackmon, Shauna, Roder, Heinrich, Stewart, John, Amin, Asim, Ernstoff, Marc S., Clark, Joseph I., Atkins, Michael B., Sosman, Jeffrey, Kluger, Harriet, Halaban, Ruth, Snzol, Mario, Asmellash, Senait, Steingrimsson, Arni, Wang, Chichung, Roman, Kristin, Clement, Amanda, Downing, Sean, Hoyt, Clifford, Harder, Nathalie, Schmidt, Guenter, Schoenmeyer, Ralf, Brieu, Nicolas, Yigitsoy, Mehmet, Madonna, Gabriele, Botti, Gerardo, Grimaldi, Antonio, Ascierto, Paolo A., Huss, Ralf, Athelogou, Maria, Hessel, Harald, Buchner, Alexander, Stief, Christian, Binnig, Gerd, Kirchner, Thomas, Sellappan, Shankar, Thyparambil, Sheeno, Schwartz, Sarit, Cecchi, Fabiola, Nguyen, Andrew, Vaske, Charles, Hembrough, Todd, Spacek, Jan, Vocka, Michal, Zavadova, Eva, Skalova, Helena, Dundr, Pavel, Petruzelka, Lubos, Francis, Nicole, Tilman, Rau T., Hartmann, Arndt, Netikova, Irena, Stump, Julia, Tufman, Amanda, Berger, Frank, Neuberger, Michael, Hatz, Rudolf, Lindner, Michael, Sanborn, Rachel E., Handy, John, Huber, Rudolf M., Winter, Hauke, Reu, Simone, Sun, Cheng, Xiao, Weihua, Tian, Zhigang, Ting, David, Tsai, Katy, Nosrati, Adi, Goldinger, Simone, Hamid, Omid, Algazi, Alain, Tumeh, Paul, Hwang, Jimmy, Liu, Jacqueline, Chen, Lawrence, Dummer, Reinhard, Rosenblum, Michael, Daud, Adil, Tsao, Tsu-Shuen, Ashworth-Sharpe, Julia, Johnson, Donald, Bhaumik, Srabani, Bieniarz, Christopher, Couto, Joseph, Farrell, Michael, Ghaffari, Mahsa, Hubbard, Antony, Kosmeder, Jerome, Lee, Cleo, Marner, Erin, Uribe, Diana, Zhang, Hongjun, Zhang, Jian, Zhang, Wenjun, Zhu, Yifei, Morrison, Larry, Tsujikawa, Takahiro, Borkar, Rohan N., Azimi, Vahid, Kumar, Sushil, Thibault, Guillaume, Mori, Motomi, El Rassi, Edward, Clayburgh, Daniel R., Kulesz-Martin, Molly F., Flint, Paul W., Coussens, Lisa M., Villabona, Lisa, Masucci, Giuseppe V., Geiss, Gary, Birditt, Brian, Mei, Qian, Huang, Alan, Eagan, Maribeth A., Ignacio, Eduardo, Elliott, Nathan, Dunaway, Dwayne, Jung, Jaemyeong, Merritt, Chris, Sprague, Isaac, Webster, Philippa, Liang, Yan, Wenthe, Jessica, Enblad, Gunilla, Karlsson, Hannah, Essand, Magnus, Savoldo, Barbara, Dotti, Gianpietro, Höglund, Martin, Brenner, Malcolm K., Hagberg, Hans, Loskog, Angelica, Bernett, Matthew J., Moore, Gregory L., Hedvat, Michael, Bonzon, Christine, Chu, Seung, Rashid, Rumana, Avery, Kendra N., Muchhal, Umesh, Desjarlais, John, Kraman, Matthew, Kmiecik, Katarzyna, Allen, Natalie, Faroudi, Mustapha, Zimarino, Carlo, Wydro, Mateusz, Doody, Jacqueline, Srinivasa, Sreesha P., Govindappa, Nagaraja, Reddy, Praveen, Dubey, Aparajita, Periyasamy, Sankar, Adekandi, Madhukara, Dey, Chaitali, Joy, Mary, van Loo, Pieter Fokko, Veninga, Henrike, Shamsili, Setareh, Throsby, Mark, Dolstra, Harry, Bakker, Lex, Alva, Ajjai, Gschwendt, Juergen, Loriot, Yohann, Feng, Dai, Poehlein, Christian, Powles, Thomas, Antonarakis, Emmanuel S., Drake, Charles G., Wu, Haiyan, De Bono, Johann, Bannerji, Rajat, Byrd, John, Gregory, Gareth, Opat, Stephen, Shortt, Jake, Thompson, Seth, Balakumaran, Arun, Kumar, Shaji, Rini, Brian I., Mariani, Mariangela, Albiges, Laurence, Haanen, John B., Larkin, James, Schmidinger, Manuela, Magazzù, Domenico, di Pietro, Alessandra, Motzer, Robert J., Borch, Troels Holz, Kongsted, Per, Pedersen, Magnus, Met, Özcan, Boudadi, Karim, Wang, Hao, Vasselli, James, Baughman, Jan E., Wigginton, Jon, Abdallah, Rehab, Ross, Ashley, Park, Jiwon, Grossenbacher, Steven, Luna, Jesus I., Withers, Sita, Culp, William, Chen, Mingyi, Monjazeb, Arta, Kent, Michael S., Chandran, Smita, Danforth, David, Yang, James, Klebanoff, Christopher, Goff, Stephanie, Paria, Biman, Sabesan, Arvind, Srivastava, Abhishek, Kammula, Udai, Richards, Jon, Faries, Mark, Andtbacka, Robert H. I., Diaz, Luis A., Le, Dung T., Yoshino, Takayuki, André, Thierry, Bendell, Johanna, Koshiji, Minori, Zhang, Yayan, Kang, S Peter, Lam, Bao, Jäger, Dirk, Bauer, Todd M., Wang, Judy S., Lee, Jean K., Manji, Gulam A., Kudchadkar, Ragini, Kauh, John S., Tang, Shande, Laing, Naomi, Falchook, Gerald, Garon, Edward B., Halmos, Balazs, Rina, Hui, Leighl, Natasha, Lee, Sung Sook, Walsh, William, Dragnev, Konstanin, Piperdi, Bilal, Rodriguez, Luis Paz-Ares, Shinwari, Nabeegha, Wei, Ziewn, Maas, Mary L, Deeds, Michael, Armstrong, Adam, Peterson, Tim, Steinmetz, Sue, Herzog, Thomas, Backes, Floor J., Copeland, Larry, Del Pilar Estevez Diz, Maria, Hare, Thomas W., Huh, Warner, Kim, Byoung-Gie, Moore, Kathleen M., Oaknin, Ana, Small, William, Tewari, Krishnansu S., Monk, Bradley J., Kamat, Ashish M., Nam, Kijoeng, De Santis, Maria, Dreicer, Robert, Hahn, Noah M., Perini, Rodolfo, Siefker-Radtke, Arlene, Sonpavde, Guru, de Wit, Ronald, Witjes, J. Alfred, Keefe, Stephen, Bajorin, Dean, Armand, Philippe, Kuruvilla, John, Moskowitz, Craig, Hamadani, Mehdi, Zinzani, Pier Luigi, Chlosta, Sabine, Bartlett, Nancy, Sabado, Rachel, Saenger, Yvonne, William, Loging, Donovan, Michael Joseph, Sacris, Erlinda, Mandeli, John, Salazar, Andres M., Powderly, John, Brody, Joshua, Nemunaitis, John, Emens, Leisha, Patnaik, Amita, McCaffery, Ian, Miller, Richard, Laport, Ginna, Coveler, Andrew L., Smith, David C., Grilley-Olson, Juneko E., Goel, Sanjay, Gardai, Shyra J., Law, Che-Leung, Means, Gary, Manley, Thomas, Marrone, Kristen A., Rosner, Gary, Anagnostou, Valsamo, Riemer, Joanne, Wakefield, Jessica, Zanhow, Cynthia, Baylin, Stephen, Gitlitz, Barbara, Brahmer, Julie, Li, Wenting, Schloss, Charles, Michot, Jean-Marie, Ding, Wei, Christian, Beth, Marinello, Patricia, Shipp, Margaret, Najjar, Yana G., Lin, Butterfield, Lisa H., Tarhini, Ahmad A., Davar, Diwakar, Zarour, Hassane, Rush, Elizabeth, Sander, Cindy, Fu, Siqing, Bauer, Todd, Molineaux, Chris, Bennett, Mark K., Orford, Keith W., Papadopoulos, Kyriakos P., Padda, Sukhmani K., Shah, Sumit A., Colevas, A Dimitrios, Narayanan, Sujata, Fisher, George A., Supan, Dana, Wakelee, Heather A., Aoki, Rhonda, Pegram, Mark D., Villalobos, Victor M., Liu, Jie, Takimoto, Chris H., Chao, Mark, Volkmer, Jens-Peter, Majeti, Ravindra, Weissman, Irving L., Sikic, Branimir I., Yu, Wendy, Conlin, Alison, Ruzich, Janet, Lewis, Stacy, Acheson, Anupama, Kemmer, Kathleen, Perlewitz, Kelly, Moxon, Nicole M., Mellinger, Staci, McArthur, Heather, Juhler-Nøttrup, Trine, Desai, Jayesh, Markman, Ben, Sandhu, Shahneen, Gan, Hui, Friedlander, Michael L., Tran, Ben, Meniawy, Tarek, Lundy, Joanne, Colyer, Duncan, Ameratunga, Malaka, Norris, Christie, Yang, Jason, Li, Kang, Wang, Lai, Luo, Lusong, Qin, Zhen, Mu, Song, Tan, Xuemei, Song, James, Millward, Michael, Katz, Matthew H. G., Bauer, Todd W., Varadhachary, Gauri R., Acquavella, Nicolas, Merchant, Nipun, Petroni, Gina, Rahma, Osama E., Chen, Mei, Song, Yang, Puhlmann, Markus, Khattri, Arun, Brisson, Ryan, Harvey, Christopher, Shah, Jatin, Mateos, Maria Victoria, Matsumoto, Morio, Blacklock, Hilary, Rocafiguera, Albert Oriol, Goldschmidt, Hartmut, Iida, Shinsuke, Yehuda, Dina Ben, Ocio, Enrique, Rodríguez-Otero, Paula, Jagannath, Sundar, Lonial, Sagar, Kher, Uma, San-Miguel, Jesus, de Oliveira, Moacyr Ribeiro, Yimer, Habte, Rifkin, Robert, Schjesvold, Fredrik, Ghori, Razi, Spreafico, Anna, Lee, Victor, Ngan, Roger K. C., To, Ka Fai, Ahn, Myung Ju, Ng, Quan Sing, Lin, Jin-Ching, Swaby, Ramona F., Gause, Christine, Saraf, Sanatan, Chan, Anthony T. C., Lam, Elaine, Tannir, Nizar M., Meric-Bernstam, Funda, Gross, Matt, MacKinnon, Andy, Whiting, Sam, Voss, Martin, Yu, Evan Y., Albertini, Mark R., Ranheim, Erik A., Hank, Jacquelyn A., Zuleger, Cindy, McFarland, Thomas, Collins, Jennifer, Clements, Erin, Weber, Sharon, Weigel, Tracey, Neuman, Heather, Hartig, Greg, Mahvi, David, Henry, MaryBeth, Gan, Jacek, Yang, Richard, Carmichael, Lakeesha, Kim, KyungMann, Gillies, Stephen D., Sondel, Paul M., Subbiah, Vivek, Noffsinger, Lori, Hendricks, Kyle, Bosch, Marnix, Lee, Jay M., Lee, Mi-Heon, Goldman, Jonathan W., Baratelli, Felicita E., Schaue, Dorthe, Wang, Gerald, Rosen, Frances, Yanagawa, Jane, Walser, Tonya C., Lin, Ying Q., Adams, Sharon, Marincola, Franco M., Tumeh, Paul C., Abtin, Fereidoun, Suh, Robert, Reckamp, Karen, Wallace, William D., Zeng, Gang, Elashoff, David A., Sharma, Sherven, Dubinett, Steven M., Pavlick, Anna C., Gastman, Brian, Hanks, Brent, Keler, Tibor, Davis, Tom, Vitale, Laura A., Sharon, Elad, Morishima, Chihiro, Cheever, Martin, Heery, Christopher R., Kim, Joseph W., Lamping, Elizabeth, Marte, Jennifer, McMahon, Sheri, Cordes, Lisa, Fakhrejahani, Farhad, Madan, Ravi, Salazar, Rachel, Zhang, Maggie, Helwig, Christoph, Gulley, James L, Li, Roger, Amrhein, John, Cohen, Zvi, Champagne, Monique, Kamat, Ashish, Aznar, M. Angela, Labiano, Sara, Diaz-Lagares, Angel, Esteller, Manel, Sandoval, Juan, Barbee, Susannah D., Bellovin, David I., Timmer, John C., Wondyfraw, Nebiyu, Johnson, Susan, Park, Johanna, Chen, Amanda, Mkrtichyan, Mikayel, Razai, Amir S., Jones, Kyle S., Hata, Chelsie Y., Gonzalez, Denise, Deveraux, Quinn, Eckelman, Brendan P., Borges, Luis, Bhardwaj, Rukmini, Puri, Raj K., Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Bartkowiak, Todd, Jaiswal, Ashvin, Ager, Casey, Ai, Midan, Budhani, Pratha, Chin, Renee, Hong, David, Curran, Michael, Hastings, William D., Pinzon-Ortiz, Maria, Murakami, Masato, Dobson, Jason R., Quinn, David, Wagner, Joel P., Rong, Xianhui, Shaw, Pamela, Dammassa, Ernesta, Guan, Wei, Dranoff, Glenn, Cao, Alexander, Fulton, Ross B., Leonardo, Steven, Fraser, Kathryn, Kangas, Takashi O., Ottoson, Nadine, Bose, Nandita, Huhn, Richard D., Graff, Jeremy, Lowe, Jamie, Gorden, Keith, Uhlik, Mark, O’Neill, Thomas, Widger, Jenifer, Crocker, Andrea, He, Li-Zhen, Weidlick, Jeffrey, Sundarapandiyan, Karuna, Ramakrishna, Venky, Storey, James, Thomas, Lawrence J., Goldstein, Joel, Marsh, Henry C., Grailer, Jamison, Gilden, Julia, Stecha, Pete, Garvin, Denise, Hartnett, Jim, Fan, Frank, Cong, Mei, Cheng, Zhi-jie Jey, Hinner, Marlon J., Aiba, Rachida-Siham Bel, Schlosser, Corinna, Jaquin, Thomas, Allersdorfer, Andrea, Berger, Sven, Wiedenmann, Alexander, Matschiner, Gabriele, Schüler, Julia, Moebius, Ulrich, Rothe, Christine, Shane, Olwill A., Horton, Brendan, Spranger, Stefani, Moreira, Dayson, Adamus, Tomasz, Zhao, Xingli, Swiderski, Piotr, Pal, Sumanta, Kortylewski, Marcin, Kosmides, Alyssa, Necochea, Kevin, Shukla, Sachet A., Patsoukis, Nikolaos, Chaudhri, Apoorvi, Pham, Hung, Hua, Ping, Bu, Xia, Zhu, Baogong, Hacohen, Nir, Wu, Catherine J., Fritsch, Edward, Freeman, Gordon J., Moran, Amy E., Polesso, Fanny, Lukaesko, Lisa, Rådestad, Emelie, Egevad, Lars, Sundberg, Berit, Henningsohn, Lars, Levitsky, Victor, Rafelson, William, Reagan, John L., Fast, Loren, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Ramachandra, Raghuveer, Gowda, Nagesh, Samiulla, Dodheri, Chandrasekhar, Talapaneni, Adurthi, Sreenivas, Mani, Jiju, Nair, Rashmi, Dhudashia, Amit, Gowda, Nagaraj, Ramachandra, Murali, Sankin, Alexander, Gartrell, Benjamin, Cumberbatch, Kerwin, Huang, Hongying, Stern, Joshua, Schoenberg, Mark, Zang, Xingxing, Swanson, Ryan, Kornacker, Michael, Evans, Lawrence, Rickel, Erika, Wolfson, Martin, Valsesia-Wittmann, Sandrine, Shekarian, Tala, Simard, François, Nailo, Rodrigo, Dutour, Aurélie, Jallas, Anne-Catherine, Caux, Christophe, Marabelle, Aurélien, Sullivan, Ryan, McDermott, David, Arora, Kshitij S., Desai, Niyati, Kulkarni, Anupriya, Rajurkar, Mihir, Rivera, Miguel, Deshpande, Vikram, Bellmunt, Joaquim, Yee, Andrew, Raje, Noopur, Choueiri, Toni, Signoretti, Sabina, Mahoney, Kathleen, and Boussiotis, Vassiliki

Abstract

Version of Record

Published
2016
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39. Case Report Predictors and Risk Factors for Recurrent Scleroderma Renal Crisis in the Kidney Allograft: Case Report and Review of the Literature

Author

Pham, Phuong-Thu T., Pham, Phuong-Chi T., Danovitch, Gabriel M., Gritsch, H. Albin, Singer, Jennifer, Wallace, William D., Hayashi, Rick, and Wilkinson, Alan H.

Abstract

Scleroderma renal crisis (SRC) can lead to end-stage renal disease (ESRD) and subsequent need for dialysis and/or renal transplantation. We review all reported cases of renal transplantations in scleroderma patients from PubMed search, present UNOS data on transplant outcomes, and identify predictors for allograft SRC. Of the five cases with recurrent SRC, all developed ESRD within a year of onset of native kidney SRC, whereas none of those who developed ESRD more than 1–2 years after the onset of SRC developed recurrence. Anemia preceded allograft SRC in two cases, pericardial effusion in one, and skin tightening in two others. UNOS data (October 1987–July 2004) documented 260 transplants performed for the renal diagnosis of scleroderma, with a 5-year graft survival rate of 56.7%. The risk for allograft SRC recurrence appears to correlate with early native renal function loss following the onset of SRC. Recurrent SRC in the allograft may be heralded by multiple clinical markers known to be predictive of severe scleroderma, including progression of diffuse skin thickening, new-onset anemia and cardiac complications.

Published
2005
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41. Concepts for Reducing Crime, Theft, and Destruction of Naval Shore Property.

Author

WESTINGHOUSE NATIONAL ISSUES CENTER ARLINGTON VA, Cunningham,Robert K, Wallace,William D, Haskell,Robert J, Palkovitz,Lynne Helfer, WESTINGHOUSE NATIONAL ISSUES CENTER ARLINGTON VA, Cunningham,Robert K, Wallace,William D, Haskell,Robert J, and Palkovitz,Lynne Helfer

Abstract

Concepts for crime reduction on Navy industrial type environments through control of environmental design are presented. Examples of crime prevention methods used in the public sector are discussed. Various opportunities for input of physical security engineering and crime reduction factors into the planning, design and construction of new facilities are identified with reference to the Navy's Facility acquisition system. (Author)

Published
1977

42. What People Write About

Author

Mitchell, John R., Griffin, Paul A., Wallace, William D., Johnson, W. Bruce, Stanga, Keith G., DeVries, JoAnn S., Mitchell, John R., Griffin, Paul A., Wallace, William D., Johnson, W. Bruce, Stanga, Keith G., and DeVries, JoAnn S.

Abstract

1

43. What People Write About

Author

Mitchell, John R., Griffin, Paul A., Wallace, William D., Johnson, W. Bruce, Stanga, Keith G., DeVries, JoAnn S., Mitchell, John R., Griffin, Paul A., Wallace, William D., Johnson, W. Bruce, Stanga, Keith G., and DeVries, JoAnn S.

Abstract

1

47. What People Write About

Author

Mitchell, John R., Griffin, Paul A., Wallace, William D., Johnson, W. Bruce, Stanga, Keith G., DeVries, JoAnn S., Mitchell, John R., Griffin, Paul A., Wallace, William D., Johnson, W. Bruce, Stanga, Keith G., and DeVries, JoAnn S.

Abstract

1

48. National Housing Policy and the Role of Committees of Inquiry

Author

Wallace, William D. S and Wallace, William D. S

Abstract

The objective is to examine, in relation to national housing policy, the role of committees of inquiry, both government appointed committees, and departmental select committees of the House of Commons first established in 1979, The period involved in the study is from 1945 to about 1985 with the government established inquiries being conducted by statutory advisory committees and departmental/interdepartmental committees in the years prior to the mid 1970s, and the select committee inquiries by the Environment Committee and the Scottish Affairs Committee in the early 1980s.

49. Clinicopathologic Study of 28 Cases of Tubulocystic Renal Cell Carcinoma: Is It Time to Reclassify It as a Tubulocystic Renal Cell Tumor?

Author

Xiao GQ, Karne V, Phan S, Cuber A, Chiu R, and Wallace WD

Abstract

Tubulocystic renal cell carcinoma (TC-RCC) is uncommon and is defined by exclusive tubulocystic growth. Its clinicopathology is still evolving. Twenty-eight cases of so-defined TC-RCC were studied for clinicopathology as well as, in some cases, immunohistochemistry. The study showed the tumor had a male predominance; tumor size ranged from 0.1 cm to 3.5 cm; multifocality and peripheral location were common. More than 1/3 rd of the cases presented with pseudoinvasion into fat; 54% of cases concurred with papillary adenoma(s); 53% of cases concurred with at least one other type of low-grade/indolent renal cell carcinoma. Background kidney displayed end-stage kidney disease in 96% of the cases. The tumor was positive for AMACR, negative for GATA3, and rarely/focally positive or completely negative for CK7 and CAIX. All presented with benign clinical courses. Given its frequent association with end-stage kidney disease and other indolent renal neoplasms as well as its uneventful clinical course, we proposed to reclassify it as a tubulocystic renal cell tumor., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. University of Southern California's Institutional Review Board issued approval (HS23-00373). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Xiao et al.)

Published
2024
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50. Phase I Trial of Intratumoral Injection of CCL21 Gene-Modified Dendritic Cells in Lung Cancer Elicits Tumor-Specific Immune Responses and CD8 + T-cell Infiltration.

Author

Lee JM, Lee MH, Garon E, Goldman JW, Salehi-Rad R, Baratelli FE, Schaue D, Wang G, Rosen F, Yanagawa J, Walser TC, Lin Y, Park SJ, Adams S, Marincola FM, Tumeh PC, Abtin F, Suh R, Reckamp KL, Lee G, Wallace WD, Lee S, Zeng G, Elashoff DA, Sharma S, and Dubinett SM

Subjects
Adult, Aged, B7-H1 Antigen genetics, B7-H1 Antigen immunology, B7-H1 Antigen metabolism, CD8-Positive T-Lymphocytes metabolism, Cancer Vaccines administration & dosage, Cancer Vaccines immunology, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung immunology, Chemokine CCL21 genetics, Cohort Studies, Dendritic Cells metabolism, Dendritic Cells transplantation, Dyspnea etiology, Female, Humans, Immunotherapy, Adoptive adverse effects, Injections, Intralesional, Interferon-gamma immunology, Interferon-gamma metabolism, Lung Neoplasms genetics, Lung Neoplasms immunology, Male, Middle Aged, Muscle Weakness etiology, Pain etiology, CD8-Positive T-Lymphocytes immunology, Carcinoma, Non-Small-Cell Lung therapy, Chemokine CCL21 immunology, Dendritic Cells immunology, Immunotherapy, Adoptive methods, Lung Neoplasms therapy
Abstract

Purpose: A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following in situ vaccination (ClinicalTrials.gov: NCT01574222). Experimental Design: Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 × 10 6 , 5 × 10 6 , 1 × 10 7 , or 3 × 10 7 DCs/injection) by CT- or bronchoscopic-guided intratumoral injections (days 0 and 7). Immune responses were assessed by tumor antigen-specific peripheral blood lymphocyte induction of IFNγ in ELISPOT assays. Tumor biopsies were evaluated for CD8 + T cells by IHC and for PD-L1 expression by IHC and real-time PCR (RT-PCR). Results: Twenty-five percent (4/16) of patients had stable disease at day 56. Median survival was 3.9 months. ELISPOT assays revealed 6 of 16 patients had systemic responses against tumor-associated antigens (TAA). Tumor CD8 + T-cell infiltration was induced in 54% of subjects (7/13; 3.4-fold average increase in the number of CD8 + T cells per mm 2 ). Patients with increased CD8 + T cells following vaccination showed significantly increased PD-L1 mRNA expression. Conclusions: Intratumoral vaccination with Ad-CCL21-DC resulted in (i) induction of systemic tumor antigen-specific immune responses; (ii) enhanced tumor CD8 + T-cell infiltration; and (iii) increased tumor PD-L1 expression. Future studies will evaluate the role of combination therapies with PD-1/PD-L1 checkpoint inhibition combined with DC-CCL21 in situ vaccination. Clin Cancer Res; 23(16); 4556-68. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Published
2017
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