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Qinghua Zhou
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MS16 - Implementation of Lung Cancer Screening (ID 795)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 206 F
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MS16.02 - NELCIN B3 Screening Program in China (ID 11469)
13:45 - 14:00 | Presenting Author(s): Qinghua Zhou
- Abstract
- Presentation
Abstract not provided
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-122 - Individual Precision Surgery for Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging and Typing : The Chinese Experience. (ID 14483)
16:45 - 18:00 | Presenting Author(s): Qinghua Zhou
- Abstract
Background
Lung cancer is the leading cause of cancer deaths in the world. For patients with advanced non-small cell lung cancer (NSCLC), survival prognosis is very poor with chemotherapy and radiotherapy. However, the possibility of occult metastases may lead to discrepancy between clinical and pathologic staging and under-estimation of the disease severity, and how to individualized choose the appropriate patients with locally advanced non-small cell lung cancer for surgery is controversies. In this study, we presented here the Chinese experience: individual precision surgery for locally advanced non-small cell lung cancer based on molecular staging and molecular typing.
a9ded1e5ce5d75814730bb4caaf49419 Method
We developed several molecular biomarkers and molecular models from Circulation Tumor Cell (CTC ) detection, mi-RNA chip, Gene Chip from 1990. We used these Molecular biomarkers and molecular models for molecular staging, molecular typing, choosing indication of operation and neoadjuvant chemotherapy, predicting postoperative recurrence and prognosis of locally advanced non-small cell lung cancer.
4c3880bb027f159e801041b1021e88e8 Result
We developed two molecular staging model for individualized surgical treatment for locally advanced non-small cell lung cancer involving heart, great vessels or both. 3728 patients with locally advanced non-small cell lung cancer were underwent completely resection of the cancer in the three medical center. The 1-, 3-, 5- and 10 year survival rate were 76.5%,63.7%,32.8% and 23.4%, respectively. We used our molecular staging and typing model for neoadjuvant chemotherapy for 665 patients with locally advanced lung cancer. The 1-, 3-, 5- and 10-year survival rate were 79.35%, 51.46%, 27.39% and 20.34% of the patients, respectively. We used our molecular typing model to divide N2 lung cancer into invasive N2 and Non-invasive N2 group. We used our molecular models adenocarcinoma and squamous carcinoma to divide T4 lung cancer into high recurrence and low recurrence groups, and help postoperative adjuvant therapy.
8eea62084ca7e541d918e823422bd82e Conclusion
Our molecular staging and typing models can help us carry out individual precision surgery, predicting prognosis and cancer recurrence of the cancer for locally advancer no-small cell lung cancer.
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P2.01-123 - Translational Medicine of Lung Cancer Metastasis: From Bench to Bedside (ID 14484)
16:45 - 18:00 | Presenting Author(s): Qinghua Zhou
- Abstract
Background
Cancer invasion and metastasis is not only the malignant marker and characteristics, but also the main cause of failure to cure and lose their life of the patients with lung cancer.30% of the lung cancer patients had distant metastasis diagnosed with lung cancer. 80% to 90% of the patient dead of distant metastasis. In this study, we presented the results of individual translational medicine of lung cancer metastasis: from bench to bedside.
a9ded1e5ce5d75814730bb4caaf49419 Method
A pair of lung cancer cell lines (L9981 and NL9980) with same inherit background, different metastatic potential were screened and identified by Single Cell Limited Dilution Cloning. Several differential mi-RNA and gene profiles were screened and identified by mi-RNA array and gene chips from the cells, and peri-cancerous and cancer tissues of patients. Molecular model for early diagnosis and prediction of lung cancer metastasis, molecular typing model of N2 lung cancer were developed by molecular biostatics. 5 small molecular compounds inhibiting lung cancer metastasis were screened and identified based on the molecular targets related to lung cancer metastasis.
4c3880bb027f159e801041b1021e88e8 Result
We successfully established a pair of lung cancer cell lines with same inherit background, different metastatic potential. High-metastatic cell line L9981 with LOH of gene, deletion of mRNA and protein expression of nm23-H1and high metastasis potential, and low-metastatic cell line NL9980 with normal NM23-H1 and low metastasis potential. After knockdown the nm23-H1 gene in NL9980 cell, the Nl9980 cell was endowed the same biological property as L9981 cell has. We got a differential panel of mi-RNAs and gene signature. We found that the patient with LOH of gene, deletion of mRNA and protein expression of nm23-H1 more likely to have distance metastasis and poor prognosis. Based on these findings, we proposed a hypothesis of “Lung Cancer Metastatic Suppressive Cascade” and translate the hypothesis into clinical use in the patients. We got several molecular model for early diagnosis and prediction of lung cancer metastasis of lung cancer after operation; a molecular typing model of dividing N2 lung cancer into invasive N2 and Non-invasive N2. Finally, we use the molecular targets related to lung cancer metastasis to screen and identify 5 small molecular compound inhibiting lung cancer metastasis.
8eea62084ca7e541d918e823422bd82e Conclusion
A pair of lung cancer cell lines with same inherit background, different metastatic potential was successfully established. We established several molecular staging and typing models related to lung cancer metastasis and translated them into clinical application in lung cancer patients.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-41 - A Novel Mitochondria-Based Targeting to Restore Therapeutic Response in Cisplatin- and Gefitinib-Resistant Human Lung Cancer Cells (ID 14480)
16:45 - 18:00 | Presenting Author(s): Qinghua Zhou
- Abstract
Background
Lung cancer is the leading cause of cancer related death accounting for up to 25% of all cancer mortality world-wide, with an estimated 1.2 million deaths each year. The major challenge of lung cancer is that approximately 50% of patients diagnosed present with advanced disease, and are likely resistant to chemo- and targeted tyrosine kinase inhibitor (TKI) therapies upon disease progression or acquired during therapeutic intervention. We devised a new approach to target specifically tumor mitochondria and observed that lung cancer cells, resistant to chemo- and TKI, therapies, Cisplatin (CIS) and Gefitinib (GF), respectively, can be overcome by DZ-191, a Simvastatin (SIM)-heptamethine carbocyanine (DZ) conjugate, or DZ-SIM, but not by the unconjugated SIM.
a9ded1e5ce5d75814730bb4caaf49419 Method
(1) Cell viability assay was used to detect the IC50 of the lung cancer cells treated with DZ or DZ-SIM. (2) flow cytometry was used to determine apoptosis of the lung cancer cells. (3)The mitochondrial membrane potential of DZ-SIM- or SIM- treated cells were assayed by using rhodamine123 staining. (4)The expression of PARP, Cleaved PARP, ProCaspase3, cCaspase3, ProCaspase9, cCaspase9, pH2AX and CHOP were detected by Western blot. (5)The Mitochondrial and lysosome staining was photographed by a Keyence microscope. (5)The tumor sizes and tumor volumes were determined by Nude mouse xenograft of lung cancer cells treated by cells with Tween 80), DZ, DZ-SIM or GF (20 mg/kg) and DZ-SIM plus.
4c3880bb027f159e801041b1021e88e8 Result
(1)DZ-SIM can significantly inhibits lung cancer cell growth of A549, A549-DDP, 95D, 95C, YTMLC and H446 in vitro. (2)DZ-SIM can remarkably sensitizes CIS/TKI-induced lung cancer cell death in vivo and vitro. (2)DZ-SIM induced apoptosis of lung cancer cells via caspase activation and decreased mitochondrial membrane potential. (3)DZ-SIM can remarkably inhibits tumor growth in H1650-xenograft in nude mice. (4)The mechanisms of DZ-SIM restore therapeutic response in cisplatin- and gefitinib-resistant human lung cancer cells was that It co-localizes with mitochondrial and lysosomal subcellular organelles.
8eea62084ca7e541d918e823422bd82e Conclusion
(1)DZ-SIM, but not SIM, kills lung cancer cells in vitro and vivo inhibits lung tumors in vivo by inducing programmed cell death. DZ-SIM also sensitizes anti-tumor responses in CIS- and GF-resistant lung cancer cells in culture and tumors in mice.(2)DZ-SIM accumulates in mitochondrial and lysosomal organelles and interrupts mitochondrial membrane potential, activates caspases, apoptosis and DNA fragmentation in lung cancer cells in culture. (3)DZ-SIM can be employed as a promising targeting agent for killing and sensitizing therapeutically-resistant lung tumors to therapy in patients in the future.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.01-114 - Dissociation of Heart and Great Vessels for Long Tracheal Tumors and Lung Cancer Invaded Trachea: The Chinese Experience. (ID 14478)
12:00 - 13:30 | Presenting Author(s): Qinghua Zhou
- Abstract
Background
The length limit of tracheal resection is less than five centimeters. Up to know, there is no any report about resection of more than five centimeters for tracheal tumors. We created a new technique and successfully remove 124 tracheal tumors more than 5 cm in length and 52 lung cancer invaded trachea through dissociation heart and great vessels. Here, we report the results of 176 patients surgically treated in series.
a9ded1e5ce5d75814730bb4caaf49419 Method
All patients were given general anesthesia and single cavity endotracheal intubation. After thoracotomy, the right pericardium was totally excised, the heart, inferior vena cava, superior vena cava, ascending aorta and innominate artery were dissociated. Then, thoracic trachea, left and right main bronchus were dissociated; the proximal and distal end of trachea, or left and right main bronchus, or left main bronchus and right middle trunk bronchus were cut off. Fallowing, the distal end of trachea was anastomosed to the proximal end of trachea, or anastomosed to the left and right main bronchus, or anastomosed to the left main bronchus and right middle trunk bronchus with 3-0 micro Joe lines. Finally, the pulmonary artery sleeve reconstruction was performed, and resection and reconstruction of SVC was performed.
4c3880bb027f159e801041b1021e88e8 Result
There were 124 patients with tracheal tumor over than 5cm in length and 52 patients with lung cancer invaded trachea. The length of trachea tumor was 5.5 cm to 10.9 cm. 5 tracheal tumor involved SVC and combined with SVCS. The trachea length invaded by the cancer was 4.5cm-7.0cm in the 52 patients with lung cancer. Of the 52 cases, 10 cancer invaded right main pulmonary artery, 22 cancer involved right main pulmonary artery and SVC. The operative procedures included: (1) resection and reconstruction of trachea, or combined with carina in 124 cases, and combined with resection and reconstruction of SVC in 5 cases in the tracheal tumor group; (2) Sleeve right upper lobectomy combined with resection and reconstruction of trachea and carina in 52 cases, combined with sleeve pulmonary artery in 10 cases, combined with sleeve pulmonary artery, and resection and reconstruction of SVC in 32 cases of lung cancer group. There were 5 operative death in this series. The 1-, 3-, 5- and 10-year survival were 71.2%, 54.3%, 33.1% and 22.5%.
8eea62084ca7e541d918e823422bd82e Conclusion
We pioneered a new technique and treated 124 tracheal tumor more than 5 cm in length and 52 lung cancer invaded trachea in the world.
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