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P. Yang



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    O11 - Symptom Management (ID 137)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Supportive Care
    • Presentations: 1
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      O11.04 - Patterns of Quality of Life, Their Characteristics and Relationship to Symptoms -- 12 Months Follow-up in Newly Diagnosed Advanced Lung Cancer Patients (ID 3359)

      16:35 - 16:45  |  Author(s): P. Yang

      • Abstract
      • Presentation
      • Slides

      Background
      Patients with newly diagnosed advanced lung cancer may experience severe impacts on their quality of life (QOL). However, relatively few studies have examined the longitudinal patterns of QOL and their relationship to patients’ symptoms during the first 12 months of cancer diagnosis. Thus, the purposes of this study were to (1) examine the overall pattern and the potential sub-patterns (if any) of QOL in these patients during the first 12 months of cancer diagnosis; and (2) identify those important characteristics of each QOL sub-pattern and their relationship to patients’ symptoms.

      Methods
      This is a 12-month prospective longitudinal study. Newly diagnosed advanced lung cancer patients (Stage IIIB & IV) were eligible to be recruited and followed for 12 months on 5 time points (Pre-treatment, 1, 3, 6 and 12 months since treatments). The overall QOL was measured by the overall QOL item in the EORTC QLQ-C30 (0-100 scoring, higher is better). The QOL patterns and factors related to the patterns were analyzed by Latent Class Growth Analysis (LCGA). Potential factors (independent variables) used to predict the overall QOL change and each QOL sub-pattern (dependent variables) included: physical function, selected symptoms, emotion distress, self-efficacy (on coping with cancer) and important demographic and treatment related variables.

      Results
      A total of 200 subjects completed the 5 follow-up assessments. Generally, patients had moderate level of QOL across the 12 months. There were three QOL sub-patterns were identified. In the pattern I (around 50% of subjects), patients reported moderate to relatively good levels of QOL (scoring around 70-80) across the 12 months. In the pattern II (around 45% of subjects), patients reported moderate levels of QOL (scoring around 50-70 QOL). In the pattern III (<10% subjects), patients reported poor level of QOL (scoring around 40 or less). Overall, symptoms including fatigue, pain, lack of appetite and dyspnea were significantly related to the changes of QOL. Other factors also included psychological distress, uncertainty and self-efficacy (level of confidence) in coping well with lung cancer.

      Conclusion
      The results provide a relatively comprehensive picture about the overall QOL and the sub-patterns of QOL for those newly diagnosed advanced lung cancer patients. The results further support the giving timing and tailoring interventions are needed to better improve lung cancer patients’ QOL. (Acknowledgement: National Health Research Institute,NHRI,Taiwan).

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    P1.05 - Poster Session 1 - Preclinical Models of Therapeutics/Imaging (ID 156)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 2
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      P1.05-011 - Antitumor agent KNG-I-484C causes cell death through inducing cell cycle arrest (ID 1754)

      09:30 - 09:30  |  Author(s): P. Yang

      • Abstract

      Background
      Lung cancer is the leading cause of cancer deaths in the world, and is classified into two major groups, non-small cell lung cancer (NSCLC, ~85%) and small-cell lung cancer (SCLC, ~15%). EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma. However, secondary EGFR mutation may cause drug resistant and cancer relapse. Further investigation and drug development is necessary for lung cancer therapy. KNG-I-484C is an analog of Desmosdumotin B compound, isolated and modified from the roots of Desmos dumosus. Previous studies showed that KNG-I-484C can inhibit cell proliferation of multidrug resistant (MDR) cancer cell line, KB-V, as well as multiple non-MDR cancer cell lines. Therefore, KNG-I-484C may act as a potential antitumor agent to inhibit drug-resistant cancer cells.

      Methods
      KNG-I-484C anti-tumorigenesis activity is estimated in non-small cell lung cancer cell lines by SRB assay and by the soft agar colony formation assay. Flow cytometry is used for cell cycle progression and cell apoptosis evaluation. The centrosomes observation is by the IF staining. The gene expression affected by the compound is by DNA microarray. Nude mice are subcutaneously injected with non-small cell lung cancer cell lines. When the tumor volume reaches about 2 mm[3], KNG-I-484C is administered by intra-peritoneal injection. The body weight of mice will be monitored. Before tumor volume reaches 1 cm[3], the mice will be sacrificed for the measurement of the tumor volume and blood.

      Results
      KNG-I-484C can inhibit cell proliferation and colonies formation in the soft agar in NSCLC cell lines. The compound induces G2/M arrest by flow cytometry and the G2/M markers, cyclin B1 and phospho-histone H3, are upregulated at the early stage. And it then causes cell apoptosis by annexin-V staining assay, and the apoptotic markers, caspase 3 and cleaved PARP increases by the treatment. KNG-I-484C treatment causes abnormal formation of centrosomes in NSCLC cell lines. The microarray results showed that EGR1 (early growth response protein 1) may be one of the target candidate. In the animal model, KNG-I-484C tends to inhibit the tumor growth.

      Conclusion
      KNG-I-484C can inhibit cell proliferation and induce cell apoptosis in lung cancer cell lines by directly inhibiting tubulin polymerization. Additional mechanisms of action may go through the centrosome abnormality. Therefore, KNG-I-484C may serve as a new and potential antitumor agent against NSCLC.

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      P1.05-018 - Inhibition of Non-small-cell Lung Cancer Growth by pH Control Release Nanoparticle Carrying miR-135b Antagomir (ID 2707)

      09:30 - 09:30  |  Author(s): P. Yang

      • Abstract

      Background
      We identified an intronic miRNA, miR-135b, up-regulated in aggressive non-small-cell lung cancer(NSCLC). Ectopically delivering mir-135b enhanced cell invasive and migratory ability in vitro and in vivo; whereas specific inhibition of miR-135b by miR-135b-specific molecular sponge and antagomirs suppressed cancer cell invasion, orthotopic lung tumor growth and metastasis in mouse model. We showed that miR-135b could directly repress the expression of Hippo pathway components. In this study, we design a tunable pH-responsive hydrogels to enhance the bioactivity of chemically modified antisense RNA oligonucleotide and SPION in tumor microenvironment for acidosis-related tumor therapy.

      Methods
      pH-responsive matrix of PEG-imidazole hydrogel releases chemically modified oligonucleotides (antagomir) and positively charged superparamagnetic iron oxide nanoparticles (SPION) were prepared. NOD-SCID mice were subcutaneously injected with CL1-5 cells and control antagomiR or antagomir-135b was intra-tumoural injected for 3 weeks. Body weight was determined. Blood was collected before euthanasia. Total tumor volume, metastatic nodules, and miR-135b expression are measured.

      Results
      By using pH-responsive release of SPION from hydrogels to release antagomiR, we found the hydrogel administered to natural physiology had a rate of slower release at pH6.7 than at pH7.4, which is sufficient to restrain cellular uptake of antagomir and the rate of release in acidic environments can be manipulated via the imidazole content. .In addition, systematic administrated antagomiR-135b through I.V. injection inhibited the orthotopic lung tumor growth and decreased the volume of lung metastases. Both results trigger us to examine the possibility of in vivo placing the antagomiR-containing hydrogels by the side of tumor, to evaluate the effect of localized releasing antagomiR on tumor growth.

      Conclusion
      Our results support that inhibition of miR-135b by pH control release nanoparticle may be promising to develop a new therapeutic strategy for NSCLC.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-047 - Clinical Factors Associated with the Efficacy of Pemetrexed as Continuation Maintenance Chemotherapy in Patients with Advanced Lung Adenocarcinoma (ID 2859)

      09:30 - 09:30  |  Author(s): P. Yang

      • Abstract

      Background
      Pemetrexed maintenance therapy significantly improved survival in patients with advanced nonsquamous non-small cell lung cancer. This study was to investigate the clinical characteristics and to identify the prognostic factors of pemetrexed as continuation maintenance chemotherapy for patients with advanced lung adenocarcinoma.

      Methods
      Patients with advanced lung adenocarcinoma treated with pemetrexed for continuation maintenance therapy after platinum-based doublet frontline treatment without disease progression were enrolled. The medical records were analyzed for basic characteristics, epidermal growth factor receptor (EGFR) mutation analysis, treatment responses, progression-free survival (PFS) and overall survival (OS).

      Results
      From September 2009 to September 2012, the medical records of 121 patients with advanced lung adenocarcinoma treated with pemetrexed and platinum as first line chemotherapy were reviewed. Sixty-nine patients treated with pemetrexed for continuation maintenance therapy after 6 cycles platinum-based doublet frontline treatment were included. Thirty-five patients (50.7%) were male. The mean of age was 66 ± 13 years old. Twenty-one patients (30.4%) were current or former smoker. The median cycles of pemetrexed as maintenance therapy was 6 cycles (range from 1 to 36 cycles). Elderly patients (age ≥ 70 years old v.s. age < 70 years old, median PFS: 9.6 months v.s. 4.0 months, p=0.002) and patients with lower glomerular filtration rate (GFR) (GFR ≥ 60 ml/min vs. GFR < 60 ml/min, median PFS: 4.0 months vs. 7.9 months, p=0.03) had longer PFS in maintenance phase of pemetrexed treatment. Other clinical factors, including EGFR mutation status, use of cisplatin or carboplatin, gender, smoking history, and treatment response to first-line chemotherapy, had no eventful effect on PFS. However, there was no significant association between OS and these clinical factors.

      Conclusion
      Pemetrexed continuation maintenance therapy may be more beneficial for elderly patients and patients who had lower renal function.