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Tatsuo Ohira
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-009 - Metabolomic Analysis in Lung Cancer (ID 8521)
09:30 - 09:30 | Author(s): Tatsuo Ohira
- Abstract
Background:
Metabolomics measures low weight molecules, generally called metabolites, and it is an effective technique to understand how metabolism is changed by various factors, including environment and disease, particularly malignant disease. Body fluids, for example sputum or urine, harvested non-invasively havebeen used in remarkable recent developments of omics analysis technology, yielding highly precise results for diagnosis of oral cancer, breast cancer, and pancreatic cancer. Metabolomic analysis has begun to be reported based on the pattern information of metabolites. It can be used for practical clinical early detection of carcinoma of various organs. However, practical metabolomic analysis regarding lung cancer has not been repored yet. We used surgically resected specimen of lung cancer to analyze and clarify metabolomics as an aspect of lung cancer.
Method:
We obtained resected specimens from patients with lung cancer after obtaining informed consent for this study, and compared the metabolism profile of the normal tissue portion with carcinoma tissue in 80 patients in terms of various clinical aspects. Metabolomic analysis was performed by capillary electrophoresis / time-of-flight mass spectrometry (CE-TOFMS) of metabolites of the lung tissue and analysed ionized tissue which contained the most main metabolites.
Result:
Analysis of serum and metabolite organization by CE-TOFMS revealed that the intermediate metabolite levels of several pathways changed markedly in lung cancer tissue. We can identify a characteristic metabolic marker in advanced lung cancer tissue with metabolomic clinical information by analysing the association with the overall metabolism profile.
Conclusion:
We identified metabolomic biomarkers which were characteristic of lung cancer using resected tissue in this study. At present, we are analysing various body fluids for analysis of lung cancer cases including prognostic implications. Applications to non-invasive, simple, easy and cheap cancer screening are expected in the future.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-019 - Sizing Capillary Electrophoresis with PCR to Detect Various EGFR Exon 19 Deletions in Non-Small Cell Lung Cancer (ID 8614)
09:30 - 09:30 | Author(s): Tatsuo Ohira
- Abstract
Background:
This study points out an issue of PCR-based methods to detect exon 19 deletions. PCR methods are used for clinical examination, because they are useful, rapid and cost-effective to detect EGFR mutations. Exon 19 deletions are most important among EGFR mutations to dictate EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy in non-small cell lung cancer (NSCLC), and have various species. The sensitive PCR methods select major exon 19 deletions, but cannot detect unusual variants. We investigated the clinical significance of minority exon 19 deletions.
Method:
A series of 73 NSCLC patients, which were treated with EGFR-TKI for recurrent disease after they had undergone surgery from 1992 to 2004. In all cases, Microdissenction and direct sequence were performed. Scorpion Amplification Refractory Mutation System (ARMS) and cobas version 2.0, as sensitive PCR methods, were performed in 47 patients along with sizing capillary electrophoresis for the exhaustive detection of exon 19 deletions.
Result:
EGFR mutations were detected from 35 patients (47.9%), which were one exon 18 mutation, 23 exon 19 deletions, and 11 exon 21 mutations in all 73 cases. The catalog of somatic mutation in cancer (COSMIC) database included 174 different exon 19 deletions in 4190 submitted cases at December 2014. E746_A750 deletion was most common deletion of exon 19, accounting for 70% of the total exon 19 deletions (2931/4190). Predicted frequency of exon 19 tested by Scorpion-ARMS was 81.6% (3419/4190), and that of cobas version 2.0 had 82.5% (3457/4190) in the detection of various exon 19 deletions. In clinical samples of this study, Scorpion-ARMS and cobas version 2.0 failed to detect four exon 19 deletions, in two squamous cell carcinomas (EGFR-TKI effects were stable disease and no assessable patient) and two papillary adenocarcinomas (EGFR-TKI effects were stable disease and no assessable patient). One of papillary adenocarcinoma had minority deletion ‘T751_I759 deletion and insertion S’, which had long stable disease for 43.4 months in EGFR-TKI therapy. Sizing capillary electrophoresis was able to detect this deletion.
Conclusion:
This study suggests sizing capillary electrophoresis is necessary for the exhaustive detection of exon 19 deletions, and may identify tumors responsive to EGFR-TKIs therapy, especially those with unusual deletions.
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P2.05 - Early Stage NSCLC (ID 706)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.05-012 - Prognostic Factors for Surgically Resected Non-Small Cell Lung Cancer with Cavity Formation (ID 8763)
09:30 - 09:30 | Author(s): Tatsuo Ohira
- Abstract
Background:
Small pulmonary nodules have been detected frequently by computed tomography (CT). Lung cancers with cavity formation are also easily detected. There are a few reports focused on the cavity wall, although cancer cells exist along the cavity wall, not inside. We evaluated the impact of cavity wall thickness on prognosis and assessed the clinicopathological features in non-small cell lung cancer (NSCLC) with cavity formation.
Method:
Between 2005 and 2011, 1313 patients underwent complete resection for NSCLC. Of these cases, we reviewed 65 patients (5.0%) diagnosed with NSCLC with cavity formation by chest CT. We classified the patients into three groups based on the maximum cavity wall thickness, namely, ≤ 4 mm (Group 1, 8 patients), > 4 mm and ≤ 15 mm (Group 2, 33 patients), and > 15 mm (Group 3, 24 patients).
Result:
The number of patients with pathological whole tumor size > 3 cm was 2 (25%) in Group 1, 17 (52%) in Group 2, and 23 (96%) in Group 3 (p < 0.001). Cases with lymph node metastasis were 0 (0%) in Group 1, 5 (15%) in Group 2, and 10 (42%) in Group 3 (p = 0.016). The 5-year overall survival (OS) rates were 100% in Group 1, 84.0% in Group 2, and 52.0% in Group 3, with significant differences between Group 1 and Group 3 (p = 0.044) and between Group 2 and Group 3 (p = 0.034). In univariate analysis, neither whole tumor size nor lymph node metastasis was a prognostic factor for OS (p = 0.505, p = 0.274). Only cavity wall thickness was a significant prognostic factor by multivariate analysis (p = 0.009).Figure 1
Conclusion:
Maximum cavity wall thickness was an important prognostic factor in NSCLCs with cavity formation, comparable with other established prognostic factors.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-012 - Liquid Based Cytology (LBC) Specimens Were Useful for EGFR Mutation Test (ID 10305)
09:30 - 09:30 | Presenting Author(s): Tatsuo Ohira
- Abstract
Background:
Reliable EGFR mutation testing techniques are required to identify eligible patients for EGFR-TKI treatment. Nowadays, surgically resected tissues or biopsy specimens are mainly used for the molecular testing. However, the biopsy samples sometimes have a certain limitation and so the cytology specimens are chosen for EGFR testing instead. Plasma sample has also become an option in EGFR-TKI resistant cases in which often have difficulties to obtain the inadequate tumor yield. In this study, we evaluated the feasibilities of using cytology samples and plasma specimens the EGFR molecular testing.
Method:
Cytology samples were obtained from biopsy and cells were suspended into liquid-based cytology (LBC) media. Tumor contents in the samples were confirmed with Papanicolaou stained slides. Plasma samples were also collected from patients shortly before the tissue biopsy. EGFR mutations in these samples were analyzed by cobas EGFR Mutation Test v2. Also, EGFR testing result of tissue specimens of the patients corresponded were collected from the medical records measured by cobas EGFR Mutation Test v2 as references.The feasibilities of both cytology and plasma specimen were evaluated comparing the results with the tissue samples.
Result:EGFR mutation rate of tissue, plasma and LBC
One-hundred seven patients were registered to this study. 60 patients were enrolled to this study. EGFR mutation rates in tissue, cytology, and plasma were 30.0, 23.3 and 15.0 %, respectively. Concordance analysis was performed comparing cytology specimens and plasma specimens to the tissue samples. Overall concordance EGFR mutation status was 85.0 and 81.7%, respectively. A total 7 cytology specimens had discordances and 3 were invalid results. For plasma samples, discordants were found in11 samples but no invalids.Tissue Plasma LBC EGFR mutation + 18 9 14 EGFR mutation - 42 51 43 Invalid 0 0 3 Total 60 60 60 Positive rate (%) 30.0 15.0 23.3
Conclusion:
Plasma was easy to obtain sample, but rate of detection was low. If a cancer cell is detected enough, LBC is useful for the examination for EGFR. Preservation of sample is easy, and re-useful for the examination, repeatedly.
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-003 - Analysis of Dendritic Cell Derived Exosomes That Suppressed Tumor Growth (ID 8062)
09:30 - 09:30 | Author(s): Tatsuo Ohira
- Abstract
Background:
Because dendritic cells (DCs) play a key role in immune reactions to activate T cells against cancer cells by cancer antigen presentation at cellular membrane, DCs have been used in clinical trials as cellular mediators for therapeutic vaccination. It has reported that the exosomes released from vaccinated DCs are responsible for the persistence of antigen presentation. Cancer cells derived exosomes play an immunosuppressive. We considered that whether DCs-derived exosomes could induce suppress cancer cells and more effective response of immune system against cancer with control for the cancer cells-derived exosomes. Because dendritic cells (DCs) play a key role in immune reactions to activate T cells against cancer cells by cancer antigen presentation at cellular membrane, DCs have been used in clinical trials as cellular mediators for therapeutic vaccination. It has reported that the exosomes released from vaccinated DCs are responsible for the persistence of antigen presentation. Cancer cells derived exosomes play an immunosuppressive. We considered that whether DCs-derived exosomes could induce suppress cancer cells and more effective response of immune system against cancer with control for the cancer cells-derived exosomes.
Method:
DCs were generated from bone marrow cells in C57BL/6J by stimulation with GM-CSF and IL-4 mice for 6 days. Murine lung cancer cell line (3LL) was cultured in RPMI1640 medium containing 10%FCS. 3LL cells-derived exosomes and DCs-derived ones were isolated by ultracentrifugation methods and exosomes purification kit (Qiagen). 3LL cells were injected to C57BL/6J mice by intraperitoneal administration. DCs, DCs-exosomes or 3LL-exosmes were weekly administrated to cancer bearing mice. Tumor growth inhibition by exosomes was evaluated measurement of luciferase activity by in vivo image analyzing system.
Result:
DCs and DCs-derived exosomes inhibited lung cancer cell growth, on the other hand, lung cancer derived-exosomes increased in compared with DCs, DCs-exosomes and non-treated.
Conclusion:
For cancer immunotherapy, DC-exosomes and cancer-exosomes play important roles in cancer immune reactions. Further examination, we are going on analyze immunosuppressive molecules possessing cancer cell-derived exosomes, and immune activation molecules in DCs-exosomes.
