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Pan-Chyr Yang
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-41 - Identification of Novel Blood-Brain Barrier Penetrating DNA Aptamers (ID 2303)
10:15 - 18:15 | Author(s): Pan-Chyr Yang
- Abstract
Background
A significant portion of lung cancer patients develops central nervous system (CNS) metastasis at certain time points in their disease courses. The structure of blood-brain barrier (BBB) strictly regulates brain homeostasis and protects the brain from exogenous damage. At the same time, these features impede effective drug delivery in to CNS, including antibody-based molecular probes. Therefore, detection of small CNS lesions and effective drug delivery across the BBB can be very challenging. Aptamers, also known as chemical antibodies, are small synthetic DNA or RNA oligonucleotides. With its inborn nature of low molecular weight, aptamers may possess better tissue penetrating ability comparing to antibodies. The current study aims to develop BBB-penetrating aptamers for CNS metastatic lung tumor targeting.
Method
In vivo SELEX (Systematic Evolution of Ligands by Exponential enrichment) was used for aptamer identification in the current study. In brief, we established CNS lung cancer mouse models by intra-ventricular inoculation of lung cancer cells. The single-stranded DNA oligonucleotide library was then intraperitoneally injected to the tumor-bearing mice. The mouse was perfused with SELEX buffer and the CNS tissues were carefully isolated. Tissue/tumor-binding oligonucleotide sequences were extracted and amplified by PCR. The procedure was repeated for several rounds and the products of the final SELEX round was subjected for sequencing.
Result
Our data showed that the CNS lung cancer mouse model was nicely established. The growth of tumors was in vivo monitored by IVIS imaging system and confirmed by immunohistochemistry staining. Through in vivo SELEX using the well-established mouse model, a group of potential BBB-penetrating aptamers was identified. By sequence analyses and secondary structure prediction, we further categorized a subset of aptamers that may possess CNS lung tumors targeting ability. Aptamer signals were in vivo captured by IVIS imaging system and was confirmed by confocal microscopy images showing the colocalization of aptamer and lung cancer cell signals.
Conclusion
We have identified BBB-penetrating aptamers that may possess CNS lung tumor targeting ability. The aptamers may serve as guiding molecules for drug delivery and/or probes for molecular imaging. Further studies are required to determine their translational potential.
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P2.03-58 - Double Primary Lung Cancer and Breast Cancer Is a Distinct Disease Entity (ID 2005)
10:15 - 18:15 | Author(s): Pan-Chyr Yang
- Abstract
Background
Double primary lung cancer (LC) and breast cancer (BC) is occasionally observed in clinic. Prior knowledge often attributes increased risks for second primary BC/LC in LC/BC patients to radiation exposure. Our previous study showed that in a 128-patient female Taiwanese double primary LC/BC cohort, 77 (60%) had both cancers diagnosed within 5 years of each other, suggesting the existence of other contributing risk factors. The current study aims to identify characteristics of female double primary LC/BC patients in western-based population.
Method
The double primary LC/BC cohort was identified from the Vanderbilt BioVU database. Vanderbilt BioVU is a de-identified electronic medical record (EMR)-based biorepository that enables longitudinal EMR study and paired genetic data assessment.
Result
A total of 65 patients were identified. Among them, 59 (90.8%) were non-Hispanic Caucasians, 5 (7.7%) were African Americans, and one (1.5%) was an Asian. Twelve (18.5%) had their BC and 5 (7.7%) had their LC diagnosed before age 50. Eleven (16.9%) patients were life-long never-smokers, and among them, 4 (36.4%) had their BC and 2 (18.2%) had their LC diagnosed before age 50. Definite disease diagnostic dates were available in 62 patients. Among these, only 18 (29.0%) received radiotherapy for either LC or BC and had two cancers diagnosed beyond 5 years from each other. Among the 50 patients with available data for BC molecular subtypes, 38 (76.0%) were ER/PR-positive and HER2-negative, 4 (8.0%) were ER/PR-positive and HER2-positive, and 6 (12.0%) were triple-negative. All of the HER2-positive patients were never-smokers; one of them had bilateral BC, another had bilateral LC, and the rest two had strong LC family history. Forty-eight (73.9%) patients in this cohort had family cancer history within their first to third-degree relatives. There were BC in 28 (43.1%), LC in 20 (30.8%), colon cancer in 9 (13.9%), hematological malignancies in 9 (13.9%), gynecological cancers in 6 (9.2%), prostate cancer in 5 (7.7%), pancreatic cancer in 4 (6.2%), gastric cancer in 3 (4.7%), esophageal cancer in 2 (3.1%), glioblastoma multiforme in 2 (3.1%) and kidney cancer in 2 (3.1%) patients, respectively.
Conclusion
Our data showed that female double primary LC/BC is a distinct disease entity, of which hereditary genetic factors may play an important role. In line with our previous study results, radiation exposure may not be the major risk factor for double primary LC/BC. Genomic studies will be of particular importance to unravel the mystery of this unique disease entity.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-34 - FCGR2B Expression as a Regulator of Immunity in Non-Small Cell Lung Cancer Patients (Now Available) (ID 458)
10:15 - 18:15 | Author(s): Pan-Chyr Yang
- Abstract
Background
FCGR2B (CD32B), a receptor on the B cell membrane, induces the production of inhibitory messages to maintain the homeostasis of the immune system and prevent excessive activation of B cells to attack their own antigens. Therefore, FCGR2B may cause immune cells to not effectively search and kill for cancer cells.This study examined the level of FCGR2B expression on B cells associated with immunity in non-small cell lung cancer (NSCLC) patients.
Method
Healthy volunteers and lung cancer patients were recruited. All control donors’ and patients’ peripheral blood were collected. 200ul blood with appropriate amount of antibody was incubated for 10-15 min at room temperature in the dark and then lysed with 1ml VersaLyse Lysing Solution for 10-15 min at room temperature in the dark. Resuspend in 1ml PBS+ 1% fix solution then were counted by cytoflex flow cytometer (Beckman Coulter). For surface marker analysis, B cells were collected assessing the levels of CD19, CD32, CD21, CD24, CD27, CD38, and IgM/IgD by flow cytometric assay. T cells subtypes including CD3, CD4, CD8, CD27, CD28, CD45, CD45RA, CD57, CCR7 and PD1 were counted by cytoflex flow cytometer.
Result
In this study, healthy volunteers (n=9 ) were compared with NSCLC patients (n=17) to detect the expression of FCGR2B on B cell. We found that Class Switched Memory Cell in NSCLC patients had lower performance than healthy subjects (NSCLC patients v.s. healthy subjects: 65.10 ± 15.72 v.s. 70.76 ± 7.26, p = 0.013). Class Switched Memory Cell was significant lower in advanced stage than that in early stage NSCLC patients (advanced stage v.s. early stage: 54.68 ± 27.21 v.s. 77.73 ± 7.12, p = 0.044). The expression of FCGR2B (CD19CD32) in NSCLC patients was slightly lower than that in healthy subjects (NSCLC patients v.s. healthy subjects: 19.68 ± 10.07 v.s. 32.98 ± 23.92, p = 0.099), but did not reach statistically significant differences. The expression of FCGR2B (CD19CD32) was significantly positively correlated with CD4 Naïve T cell ( R = 0.789; B = 0.291; p < 0.001) and CD3CD4CD45RA (R = 0.765; B = 0.301; p = 0.001).
Conclusion
NSCLC patients with reduced numbers of Class Switched Memory B Cell are more prone to progress lung cancer disease. The positive correlation between FCGR2 B cells and naive T cells in blood is also observed. Future studies focusing on the presence of these B cell subtypes, antigen specificity and interaction with T cells are necessary to further elucidate in NSCLC patients.
