Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

Q. Le



Author of

  • +

    MO03 - Thymic Malignancies (ID 123)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO03.08 - Increased Galectin-1 Expression in a Thymic Epithelial Tumor Tissue Microarray (TMA) and Galectin-1 Knockdown Studies in a Thymoma Cell Line (ID 1238)

      10:30 - 12:00  |  Author(s): Q. Le

      • Abstract
      • Presentation
      • Slides

      Background
      Thymoma is a rare malignancy with a paucity of data on biology. Thymic epithelial tumors are often admixed with developing T-lymphocytes in the microenvironment. Galectin-1 (gal-1) is a beta-galactosidase binding protein involved in T-cell development via thymic stromal and thymocyte interaction as well as thymocyte development through negative selection. Gal-1 also induces apoptosis of effector T-lymphocytes, promotes angiogenesis, and is a poor prognostic indicator when overexpressed in several tumor types. To our knowledge expression of gal-1 has not been examined in thymic epithelial tumors.

      Methods
      A TMA was constructed from 68 patients with thymic malignancies and 8 benign thymic controls at Stanford University School of Medicine (Stanford, CA). Immunohistochemical stains for galectin-1 (1:200 dilution; citrate pre-treatment; mouse monoclonal; Novocastra) were performed on 4 µM-thick TMA sections. Galectin-1 cytoplasmic staining of the epithelial cell component was scored as negative (0), focal positive (1+), or strong positive (2+) by a Stanford pathologist, who was blinded to the clinical data. Gal-1 expression was averaged for each patient sample. Statistical analysis was performed using SAS Enterprise Guide v5.0 (Cary, NC). Non-parametric statistical analyses were used to compare average patient gal-1 expression between thymic tumors and benign thymic controls. Stable gal-1 knockdown was achieved in IU-TAB1, a human thymoma WHO type AB cell line, using the pLKo.1 vector with gal-1 shRNA (Open Biosystems). Lentivirus was produced using the Trans-Lentiviral Packaging System (Thermo Scientific). In vitro proliferation cell counts were performed by hemocytometer. After hypoxia exposure (0.5% O~2~), apoptotic cells were labeled using the APO-Direct kit and quantified by flow cytometry (BD Biosciences).

      Results
      Demographics for 68 patients: M:F (53%/47%), Mean age at diagnosis: 55 years, WHO Histology: A (10%), B (57%), AB (24%), C (4%), unclassified (4%), Pathologic Maseoka Stage: I (46%), IIa (18%), IIb (4%), III (18%), IVa (9%) IVb (6%). Gal-1 expression was increased among thymic tumor tissue compared to unpaired controls (mean avg gal-1 expression 1.5 vs. 0.125, p=0.0012, Kruskal-Wallis test). Logistic regression of tumor vs. control thymus by gal-1 generated a C-statistic of 0.845. A significant increase in gal-1 expression was noted across all WHO thymoma subtypes except thymic carcinoma (type C) (p < 0.05, non-parametric ANOVA with post-hoc ranked Dunnett’s t-test). Among 11 thymic tumors analyzed with paired adjacent resected benign thymus tissue from the same patient, a significant increase was noted in gal-1 expression among tumor compared with adjacent resected normal benign thymus (mean avg gal-1 1.82 vs. 0.35, p=0.004, sign-rank test). In vitro, gal-1 knockdown did not affect IU-TAB1 proliferation. Preliminary results showed gal-1 knockdown increased apoptosis under hypoxia compared to scramble control.

      Conclusion
      Gal1 expression was increased among thymoma compared with benign thymus controls and paired adjacent resected benign thymus. A robust C-statistic of 0.845 indicates that gal-1 expression may discriminate tumor from benign thymus. Increased gal-1 expression was conserved across WHO histologic subtype except for thymic carcinoma—whose analysis was limited due to small sample size. Gal-1 knockdown might increase apoptosis under hypoxia. We are continuing to investigate the biologic and clinical significance of increased gal-1 expression in thymoma.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MS01 - Radiation as a Systemic Therapy (ID 18)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
    • +

      MS01.1 - Immunomodulation with Radiotherapy (ID 457)

      14:00 - 15:30  |  Author(s): Q. Le

      • Abstract
      • Slides

      Abstract
      Non-small cell lung cancer (NSCLC) is a highly lethal disease. Despite dose escalation with conformal radiotherapy (RT) in combination with modern chemotherapy, there is still a significantly high rate of intrathoracic failure and poor overall survival in patients with locally advanced disease. Recently, clinical studies have shown that blocking the immune check points such as CTLA4 and PD1 is effective in patients with metastatic NSCLC, resulting in a high response rate and improved both progression-free and overall survival. This generates enthusiasm for further studying the effect of immunomodulation with radiation therapy in earlier stage tumors. However, radiation can cause lymphodepletion, and persistently profound radiation-associated lymphopenia has been linked to poorer tumor control and survival in several solid tumors, including NSCLC. Radiation-induce lymphopenia can potentially counteract the effect of immunotherapy, making it less effective in patients treated with radiotherapy. Unfortunately the mechanism of radiation-induced lymphopenia is poorly understood, and unless we can overcome such effect, it will be difficult to integrate immunotherapy with radiotherapy. Galectin-1 (Gal-1) is a secreted carbohydrate binding lectin that is well known for its role in modulating T-cell homeostasis. More recently, it has been shown to play a major role in cancer progression. It is expressed in many cancers, including NSCLC, where increased Gal-1 expression is closely associated with larger tumors, more nodal metastasis and lower overall survival. In human head and neck cancer, expression of Galectin-1 was inversely related to intratumoral T-cell level and correlated with prognosis. We have previously showed that Gal-1’s secretion is enhanced by both hypoxia and radiation in NSCLC. Using an immunocompetent mouse model, we have also shown that tumor-derived Gal-1 is important for promoting tumor growth and spontaneous metastasis in NSCLC. Further mechanistic studies suggested that Gal-1 mediates its tumor promoting function by enhancing intratumoral T-cell death while protecting hypoxic tumor cells from apoptosis. More recently, using the same mouse model, we found that circulating plasma tumor Gal-1, which is elevated after tumor irradiation, appears to mediate the phenomenon of lymphopenia in mice. In addition, in vitro and in vivo studies indicate that down regulation of Gal-1 expression or blocking its function result in enhanced radiation sensitivity in NSCLC, resulting in more cell kill and tumor shrinkage. Based on these data, we believe that the poor outcome associated with radiation-induced lymphopenia is due to Gal-1’s effect on tumor infiltrating lymphocytes, and it is therefore logical to target Gal-1 in combination with radiation in NSCLC.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.