David M Hwang

University Health Network, Toronto, Ontario, Canada

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Publications (78)237.92 Total impact

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    ABSTRACT: The contribution of bone marrow cells (BMC) in lung repair is controversial. We previously reported a subpopulation of BMC that express Clara cell secretory protein (CCSP). To determine the contribution of endogenous CCSP(+) BMC to airway regeneration we performed bone marrow transplantation studies using the CCtk mouse, which expresses a thymidine kinase suicide gene under regulation of the CCSP promoter. Mice were transplanted with wild type or CCtk BMC and treated with ganciclovir to eliminate CCSP(+) cells. After airway injury using naphthalene, mice depleted of CCSP(+) BMC had more inflammatory cells in lung and decreased levels of oxygen in arterial blood. They also had reduced expression of airway epithelial genes and less Clara cells compared to control mice that had intact CCSP(+) BMC and bone marrow derived CCSP(+) cells in the airways. After naphthalene injury, administration of CCSP reproduced the beneficial effect of CCSP(+) BMC by improving recovery of airway epithelium, reducing lung inflammation and increasing oxygen in arterial blood from mice depleted of CCSP(+) BMC. Our data demonstrates that ablation of CCSP(+) BMC delays airway recovery and suggests the beneficial effect of CCSP(+) BMC in lung recovery is in part due to production of CCSP itself.Molecular Therapy (2014); doi:10.1038/mt.2014.223.
    Molecular therapy : the journal of the American Society of Gene Therapy. 11/2014;
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    ABSTRACT: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals. Methods: Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis’ ALK break-apart FISH kit. Initial IHC results were used to optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays. Results: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH. Conclusions: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers.
    Journal of Thoracic Oncology 09/2014; 9(9):1255-1263. · 4.47 Impact Factor
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    ABSTRACT: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2014; · 4.55 Impact Factor
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    ABSTRACT: To determine long-term outcome and risk factors for recurrence after thymectomy.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2014; 9(7):1018-22. · 4.55 Impact Factor
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    ABSTRACT: Epidermal growth factor receptor (EGFR) mutation testing has become critical in the treatment of patients with advanced non-small-cell lung cancer. This study involves a large cohort and epidemiologically unselected series of EGFR mutation testing for patients with nonsquamous non-small-cell lung cancer in a North American population to determine sample-related factors that influence success in clinical EGFR testing.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2014; · 4.55 Impact Factor
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    ABSTRACT: The aim of this work was to establish a novel orthotopic human non-small cell lung cancer (NSCLC) murine xenograft model by a nonsurgical, transbronchial approach. Male athymic nude mice and human NSCLC cell lines, including A549, H460, and H520 were used. Under direct visualization of the vocal cords, a 23-gauge blunt-tip slightly curved metal catheter was introduced into the trachea to the bronchus, and 2.5 × 10(5) tumor cells mixed with Matrigel (BD Biosciences, Mississauga, Ontario, Canada) were administered into the lung. Mice were monitored using weekly microcomputed tomography scans for tumor formation. When the tumor size reached more than 4 mm in diameter, the animals were euthanized, and the tumor tissue was evaluated histopathologically. Of 37 mice studied, 34 were confirmed to have tumor formation: 29 developed solitary tumors and 5 had multifocal lesions. There was no evidence of extrapleural dissemination or effusion. Transbronchial delivery of tumor cells enabled the establishment of a novel orthotopic human NSCLC murine xenograft model. This clinically relevant preclinical model bearing a solitary nodule is of value for a variety of in vivo research studies.
    The Annals of thoracic surgery 05/2014; 97(5):1771-5. · 3.45 Impact Factor
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    ABSTRACT: The long-term success of lung transplantation is limited by chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the alveolar alarmin profiles in CLAD subtypes, restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). Bronchoalveolar lavage (BAL) samples were collected from 53 recipients who underwent double lung or heart-lung transplantation, including patients with RAS (n = 10), BOS (n = 18) and No CLAD (n = 25). Protein levels of alarmins such as S100A8, S100A9, S100A8/A9, S100A12, S100P, high-mobility group box 1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in BAL fluid were measured. RAS and BOS showed higher expressions of S100A8, S100A8/A9 and S100A12 compared with No CLAD (p < 0.0001, p < 0.0001, p < 0.0001 in RAS vs. No CLAD, p = 0.0006, p = 0.0044, p = 0.0086 in BOS vs. No CLAD, respectively). Moreover, RAS showed greater up-regulation of S100A9, S100A8/A9, S100A12, S100P and HMGB1 compared with BOS (p = 0.0094, p = 0.038, p = 0.041, p = 0.035 and p = 0.010, respectively). sRAGE did not show significant difference among the three groups (p = 0.174). Our results demonstrate distinct expression patterns of alveolar alarmins in RAS and BOS, suggesting that RAS and BOS may represent biologically different subtypes. Further refinements in biologic profiling will lead to a better understanding of CLAD.
    American Journal of Transplantation 04/2014; · 6.19 Impact Factor
  • Photodiagnosis and photodynamic therapy 02/2014;
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    ABSTRACT: We developed an innovative approach for malignant pleural mesothelioma (MPM) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP). This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy (SMART). All resectable clinical T1-3N0M0 histologically proven, previously untreated MPMs were eligible. Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT. Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings. The primary end point was treatment-related mortality and secondary end points were overall survival, disease-free survival, treatment-related morbidity, and patterns of failure. Targeted accrual of 25 patients was completed between November 2008 and October 2012. All patients completed SMART. IMRT was well tolerated with no grade 3+ toxicities. EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality. Thirteen patients developed grade 3+ surgical complications. One patient (4%) died from treatment-related toxicity (empyema) during follow-up. All but one patient had stage III or IV disease on final pathologic findings. Five of 13 ypN2 patients received adjuvant chemotherapy. After a median follow-up of 23 months (range, 6-51), the cumulative 3-year survival reached 84% in epithelial subtypes compared with 13% in biphasic subtypes (p = 0.0002). SMART is feasible in resectable MPM patients. This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2014; · 4.55 Impact Factor
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    ABSTRACT: Context.-Surgical removal and pathologic handling of lung tissue has a compressive effect upon its architecture. The effect of surgical atelectasis on morphology has not been examined in depth, especially with respect to lung adenocarcinomas. Objective.-To examine the influence of surgical atelectasis on morphologic lepidic growth pattern, mimicking papillary adenocarcinoma pattern. Design.-In 2 cases serial sections of resected pulmonary adenocarcinoma were used, as was a 3-dimensional reconstruction. Elastin stains were performed on primary and metastatic adenocarcinomas. Results.-Perfusion fixation of another case showed marked morphologic differences of less compressed peripheral lung tissue, emphasizing the preexisting alveolar structure. An elastic stain may help identify true lesional architecture. Conclusions.-We demonstrate that microscopic sections of adenocarcinoma in situ in compressed/collapsed tissue may give rise to a pseudopapillary pattern mimicking invasive adenocarcinoma. Accurate appreciation of different tumor architecture in lung adenocarcinoma has important biologic and clinical implications. Pathologists should be aware of the possibility of misclassification of adenocarcinoma pattern due to tissue artifacts caused by lung tissue handling.
    Archives of pathology & laboratory medicine 12/2013; 137(12):1792-1797. · 2.78 Impact Factor
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    ABSTRACT: In vivo lung perfusion (IVLP) is an emergent strategy to treat lung metastases because it allows localized delivery of chemotherapy with minimal systemic exposure. Previously, short-term (±30 minutes) IVLP resulted in variable efficacy and significant lung toxicity. We hypothesize that a modified IVLP strategy derived from an ex vivo lung perfusion technique could minimize lung injury. Our objective was to demonstrate the feasibility and safety of a modified prolonged (4 hours) IVLP. Six Yorkshire pigs were used for the experiments. A thoracotomy was performed, the left pulmonary artery and pulmonary veins were cannulated, and the left lung was isolated in situ. IVLP was performed at normothermia for 4 hours using Steen Solution (XVIVO Perfusion, Göteburg, Sweden) as perfusate. The flow rate was 16% of estimated cardiac output and left atrial pressure was maintained between 3 and 5 mm Hg. Perfusate was deoxygenated and supplied with CO2 to physiologic levels before entering the lungs. A protective mode of ventilation was used. After IVLP, the left lung was allowed to reperfuse for additional 4 hours. Airway dynamics, gas exchange, and pulmonary vascular resistance were used to assess left lung physiology. Histologic signs of lung injury were assessed before and after IVLP, and 4 hours after reperfusion. Lung function parameters were stable throughout the 4-hour IVLP and during reperfusion. No significant histologic evidence of acute lung injury was observed. Four hours of IVLP is feasible without adding significant lung injury. Prolonged perfusion time and a protective protocol might provide safer and more efficacious treatment of pulmonary metastases.
    The Journal of thoracic and cardiovascular surgery 11/2013; · 3.41 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 10/2013; 188(7):878-880. · 11.04 Impact Factor
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    ABSTRACT: We have previously reported a subpopulation of bone marrow cells (BMC) that express Clara cell secretory protein (CCSP), generally felt to be specific to lung Clara cells. Ablation of lung Clara cells has been reported using a transgenic mouse that expresses thymidine kinase under control of the CCSP promoter. Treatment with ganciclovir results in permanent elimination of CCSP(+) cells, failure of airway regeneration, and death. To determine if transtracheal delivery of wild-type bone marrow CCSP(+) cells is beneficial after ablation of lung CCSP(+) cells, transgenic mice were treated with ganciclovir followed by transtracheal administration of CCSP(+) or CCSP(-) BMC. Compared with mice administered CCSP(-) cells, mice treated with CCSP(+) cells had more donor cells lining the airway epithelium, where they expressed epithelial markers including CCSP. Although donor CCSP(+) cells did not substantially repopulate the airway, their administration resulted in increased host ciliated cells, better preservation of airway epithelium, reduction of inflammatory cells, and an increase in animal survival time. Administration of CCSP(+) BMC is beneficial after permanent ablation of lung Clara cells by increasing bronchial epithelial repair. Therefore, CCSP(+) BMC could be important for treatment of lung diseases where airways re-epithelialization is compromised.Molecular Therapy (2013); doi:10.1038/mt.2013.53.
    Molecular Therapy 04/2013; · 7.04 Impact Factor
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    ABSTRACT: The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation.
    American Journal of Transplantation 04/2013; · 6.19 Impact Factor
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    ABSTRACT: BACKGROUND: The timing of disease onset may affect the prognosis in chronic lung allograft dysfunction (CLAD). The relationship between the timing of disease onset and the prognosis of CLAD and its sub-types, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), was examined. METHODS: Clinical records and pulmonary function data of 597 patients who underwent bilateral lung transplantation from 1996 to 2010 and survived for >3 months were examined. RESULTS: Among 155 patients with a final diagnosis of BOS, patient survival after disease onset was significantly different according to disease-onset timing (BOS onset/post-BOS median survival: overall/1,438 days; <1 year/511 days; 1-2 years/1,199 days; 2-3 years/1,403 days; >3 years/did not reach median survival; p < 0.0001). The prognosis of RAS was generally poorer than that of BOS (overall post-RAS median survival, 377 days). Treating non-CLAD, CLAD, BOS, and RAS as time-dependent covariates, recipient sex-adjusted and age-adjusted Cox regression analysis demonstrated an overall mortality risk of BOS (reference: no CLAD) of 6.7 (95% confidence interval, 4.6-9.9). However, when patients survived 3 years without CLAD, the mortality risk of subsequent BOS was only 1.9 (95% confidence interval, 0.8-4.4) compared with no CLAD. The number of RAS patients was too small to obtain sufficient power to estimate time-dependent mortality risk. CONCLUSION: Late-onset BOS showed a better prognosis than early-onset BOS. Studies that do not distinguish BOS from RAS may overestimate the mortality risk of BOS. Multicenter studies will be required to further elucidate risk factors toward the development of better management strategies for CLAD.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2013; · 3.54 Impact Factor
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    ABSTRACT: Restrictive allograft syndrome (RAS) is a novel form of chronic lung allograft dysfunction after lung transplantation. RAS is characterized by restrictive physiology and peripheral lung fibrosis. The purpose of the study is to analyze progression patterns of RAS. Clinical information, pulmonary function test results and radiographic findings were reviewed for 25 RAS patients who received bilateral lung or heart-lung transplantation between January 2004 and December 2009. Average time from transplantation to RAS onset was 647±544 (mean±SD) days; RAS onset to end of observation (death or re-transplantation) was 490±417 days. RAS patients had 1 to 4 episodes of acute exacerbation (2.48±0.82 episodes/patient) that accompanied acute respiratory deterioration or distress, a sudden drop in pulmonary function, evidence of diffuse alveolar damage (DAD) on biopsies, and patchy or diffuse ground-glass opacities (GGO) with occasional consolidation on computed tomography scan. Patients were most frequently managed by high-dose steroid in combination with empirical antibiotics, with uncertain efficacy. Acute exacerbation was followed by an interval during which resolution of GGO and progression of consolidation, interstitial reticular shadows and traction bronchiectasis were frequently observed. The interval between episodes of acute exacerbation was 238±165 days. In 21 patients, the last episode of acute exacerbation led to death or urgent retransplantation. RAS shows a "stair-step" pattern of progression. Acute lung injury represented by DAD and GGO is followed by an interval period during which graft fibrosis often progresses.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2013; 32(1):23-30. · 3.54 Impact Factor
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    ABSTRACT: SESSION TYPE: Lung Cancer IIPRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PMPURPOSE: Currently available orthotopic human non-small cell lung cancer (NSCLC) xenograft models utilize percutaneous delivery of tumor cells, which may result in pneumothorax, pleural dissemination and multifocal lesions. A clinically relevant preclinical model bearing a solitary nodule would be of value for a variety of research studies. The aim of the present work is to establish an ultra-minimally invasive orthotopic human NSCLC xenograft model in immunodeficient mice.METHODS: Male athymic nude mice (NCr-Foxn1nu) and human NSCLC cell lines, including A549 (adenocarcinoma), H460 (large cell carcinoma) and H520 (squamous cell carcinoma), were used. Mice were anesthetized and placed in the supine recumbent position. Pulling the tongue laterally using a Mosquito-pean forcep allowed us to lift the lower jaw and expose the glottis. Under direct visualization of the vocal cords using a surgical microscope, a 23G blunt-tip slightly curved metal catheter was introduced into the trachea. A total of 50-70 µl of the tumor cell suspension (2.5x105 tumor cells) was mixed with MatrigelTM and administered into the lung. Mice were monitored using weekly microCT scans for tumor formation. When the tumor size reached more than 4 mm in diameter, the animals were sacrificed and the tumor tissue was evaluated histopathologically.RESULTS: Of 26 mice (A549, n=17, H460, n=6, H520, n=3) studied, 23 were confirmed to have tumor formation. 19 developed solitary tumors and 4 mice had multifocal lesions. There was no evidence of extra-pleural dissemination or effusion. On examination of hematoxylin-eosin, elastic trichrome and CD31 stained sections, tumor cells were observed growing primarily within the alveolar structures. H460 tumors exhibited invasion into the bronchioles and visceral pleura. Differential EGFR expressions were also observed between each cell type by immunohistochemistry.CONCLUSIONS: Transbronchial delivery of tumor cells enabled the establishment of a novel minimally invasive orthotopic human lung cancer xenograft model in mice.CLINICAL IMPLICATIONS: This model will provide a clinically relevant in-vivo platform suitable for studies of imaging, tumor biology and novel therapeutic interventions in lung cancer.DISCLOSURE: The following authors have nothing to disclose: Takahiro Nakajima, Takashi Anayama, Yasushi Matsuda, David Hwang, Patrick McVeigh, Brian Wilson, Gang Zheng, Shaf Keshavjee, Kazuhiro YasufukuNo Product/Research Disclosure InformationDivision of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
    Chest 10/2012; 142(4_MeetingAbstracts):594A. · 7.13 Impact Factor
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    ABSTRACT: We previously described restrictive allograft syndrome as a form of chronic lung allograft dysfunction, demonstrating restrictive pulmonary function decline. However, the histopathological correlates of restrictive allograft syndrome have yet to be satisfactorily described. We hypothesized that pulmonary pleuroparenchymal fibroelastosis, as has recently been described in bone marrow transplant recipients, may also be present in the lungs of patients with restrictive allograft syndrome. Retrospective review of 493 patients who underwent lung transplantation between 1 January 1996 and 30 June 2009, was conducted. Out of 47 patients with clinical features of restrictive allograft syndrome, 16 had wedge biopsy, re-transplant lung explant, or autopsy lung specimens available for review. All lungs showed varying degrees of pleural fibrosis. Fifteen of 16 showed parenchymal fibroelastosis, characterized by hypocellular collagen deposition with preservation and thickening of the underlying alveolar septal elastic network. The fibroelastosis was predominantly subpleural in distribution, with some cases also showing centrilobular and paraseptal distribution. A sharp demarcation was often seen between areas of fibroelastosis and unaffected lung parenchyma, with fibroblastic foci often present at this interface. Concurrent features of obliterative bronchiolitis were present in 14 cases. Another common finding was the presence of diffuse alveolar damage (13 cases), usually in specimens obtained <1 year after clinical onset of restrictive allograft syndrome. The single specimen in which fibroelastosis was not identified was obtained before the clinical onset of chronic lung allograft dysfunction, and showed features of diffuse alveolar damage. In conclusion, pleuroparenchymal fibroelastosis is a major histopathologic correlate of restrictive allograft syndrome, and was often found concurrently with diffuse alveolar damage. Our findings support a temporal sequence of diffuse alveolar damage followed by the development of pleuroparenchymal fibroelastosis in the histopathologic evolution of restrictive allograft syndrome.Modern Pathology advance online publication, 28 September 2012; doi:10.1038/modpathol.2012.171.
    Modern Pathology 09/2012; · 5.25 Impact Factor
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    ABSTRACT: The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infections. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3-deficient mice (129/SvEv/C57BL6/J) and their wild-type (WT) littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. In PTX3 WT mice, MHV-1 induced PTX3 expression in the lung and serum in a time-dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3-deficient mice than that in WT mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity in vitro. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung, attenuated MHV-1-induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection-induced acute lung injury.
    Laboratory Investigation 06/2012; 92(9):1285-96. · 3.96 Impact Factor
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    ABSTRACT: The differential therapeutic efficacy and toxicity of targeted therapies has made subtyping of non-small lung cancer (NSCLC) mandatory. This study aimed to review the accuracy of NSCLC subtyping using lung fine needle aspirates (FNAs) in two periods (before and after the introduction of targeted therapy), checking the reasons for failure and the impact of the use of immunohistochemistry (IHC). An electronic search retrieved all NSCLC FNAs with a corresponding surgical specimen from 2001 to 2009. NSCLC, NOS (not otherwise specified) cases from 2005 to 2009 (after targeted therapy) were reviewed to determine reasons for failure in subtyping and to further subtype based solely on cytomorphology. The number of cases in which IHC was performed and the antibodies used were also recorded. Cytohistological agreement of 602 lung FNAs (341 adenocarcinomas, 93 squamous cell carcinomas and 168 NSCLC, NOS) was achieved in 93.80%. There was a significant decrease in the percentage of cases not subtyped in the period after the introduction of targeted therapy (35.07% versus 24.57%). Final percentage of cases not subtyped after morphological review was 17.03%. IHC was performed in 157 cases, with an increased use in recent years. The number of antibodies did not influence the overall success in subtyping and an average of 3 markers was used. Most frequent antibodies used were TTF-1, CK7, high molecular weight keratin and p63. More than half of cases not subtyped even after IHC corresponded to poorly or undifferentiated neoplasms in the surgical specimens. For the NSCLC, NOS which IHC was not performed, a cell block was produced in 106 cases (75.71%). Review of the cell block slides from 2005 to 2009 showed that the majority (70.7%) had rare, few or no tumor cells. Specific subtyping can be achieved in a high proportion of lung FNAs with high accuracy. The percentage of NSCLC, NOS has significantly decreased in recent years together with a trend for an increased use of IHC as well as increased number of cell blocks produced. An average of 3 IHC markers was used for subtyping and the number of markers did not influence the overall subtyping.
    Lung cancer (Amsterdam, Netherlands) 05/2012; 77(3):501-6. · 3.14 Impact Factor

Publication Stats

467 Citations
237.92 Total Impact Points

Institutions

  • 2010–2014
    • University Health Network
      • • Department of Pathology
      • • Thoracic Surgery Clinic
      Toronto, Ontario, Canada
    • SickKids
      • Division of Pathology
      Toronto, Ontario, Canada
  • 2013
    • Okayama Rosai Hospital
      Okayama, Okayama, Japan
  • 2006–2013
    • University of Toronto
      • • Department of Surgery
      • • Division of Respirology
      Toronto, Ontario, Canada
  • 2011
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2009
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 2008
    • Saint Michael's Medical Center
      Newark, New Jersey, United States