Podcast
Questions and Answers
What is a primary goal of the PhD thesis related to ATRA?
What is a primary goal of the PhD thesis related to ATRA?
- To develop traditional chemotherapy methods for Gastric Cancer.
- To provide pre-clinical data for ATRA's potential in treating Gastric Cancer. (correct)
- To analyze the dietary impacts on Gastric Cancer progression.
- To study the history of Gastric Cancer treatment.
What methodologies will be used to define the genomic profiles in the research?
What methodologies will be used to define the genomic profiles in the research?
- Microarray analysis followed by Western blotting.
- Whole exome sequencing combined with CRISPR technology.
- SNP genotyping associated with classical genetic mapping.
- RNA-sequencing based on non-oriented gene-expression approaches. (correct)
How does the project aim to classify Gastric Cancer cell lines?
How does the project aim to classify Gastric Cancer cell lines?
- Based on their geographical location.
- Relating them to patient demographics and symptoms.
- Using molecular profiles to identify different sub-groups. (correct)
- According to their response to various drug treatments.
Which RNA-Sequencing tool is mentioned for analyzing Gastric Cancer cell lines?
Which RNA-Sequencing tool is mentioned for analyzing Gastric Cancer cell lines?
What is one of the short-term goals related to ATRA in the project?
What is one of the short-term goals related to ATRA in the project?
What aspect of Gastric Cancer does the research identify as heterogeneous?
What aspect of Gastric Cancer does the research identify as heterogeneous?
What is a long-term objective related to ATRA therapies proposed in the research?
What is a long-term objective related to ATRA therapies proposed in the research?
What is one method used in the experimental design of Aim 1?
What is one method used in the experimental design of Aim 1?
What does the differential analysis in Aim 1 seek to evaluate?
What does the differential analysis in Aim 1 seek to evaluate?
What aspect of Gastric Cancer treatment is being explored in relation to ATRA?
What aspect of Gastric Cancer treatment is being explored in relation to ATRA?
What is a major limitation noted regarding ATRA's application in Gastric Cancer?
What is a major limitation noted regarding ATRA's application in Gastric Cancer?
Which innovative strategy may be considered if ATRA is found to promote Gastric Cancer cell proliferation?
Which innovative strategy may be considered if ATRA is found to promote Gastric Cancer cell proliferation?
What is the purpose of developing diagnostic tools in the context of ATRA therapies?
What is the purpose of developing diagnostic tools in the context of ATRA therapies?
What type of studies does the proposed research not foresee any technical problems with?
What type of studies does the proposed research not foresee any technical problems with?
What emerging theme in medicine is highlighted as relevant to the ongoing research?
What emerging theme in medicine is highlighted as relevant to the ongoing research?
What characteristic distinguishes ATRA from conventional chemotherapeutics?
What characteristic distinguishes ATRA from conventional chemotherapeutics?
Why is the exploration of ATRA's therapeutic potential in Gastric Cancer considered limited?
Why is the exploration of ATRA's therapeutic potential in Gastric Cancer considered limited?
What is a potential outcome of completing the project exploring ATRA in Gastric Cancer?
What is a potential outcome of completing the project exploring ATRA in Gastric Cancer?
What type of data is being collected through high-throughput genomic studies?
What type of data is being collected through high-throughput genomic studies?
What is the primary focus of the tissue-slice culture model developed in the study?
What is the primary focus of the tissue-slice culture model developed in the study?
Which technique is used to validate the gene-networks modulated by ATRA in Gastric Cancer tissue slices?
Which technique is used to validate the gene-networks modulated by ATRA in Gastric Cancer tissue slices?
What is the required time frame for processing surgical samples after collection?
What is the required time frame for processing surgical samples after collection?
What measurement technique is employed to assess cell growth inhibition and apoptosis in the study?
What measurement technique is employed to assess cell growth inhibition and apoptosis in the study?
In the context of ATRA sensitivity, what main outcome does the study aim to correlate with in vitro responses?
In the context of ATRA sensitivity, what main outcome does the study aim to correlate with in vitro responses?
What is the primary focus of the study regarding ATRA in Gastric Cancer?
What is the primary focus of the study regarding ATRA in Gastric Cancer?
Which biomarker is used to assess apoptosis in the study?
Which biomarker is used to assess apoptosis in the study?
What technique is employed to measure gene expression changes in the treated tissue slices?
What technique is employed to measure gene expression changes in the treated tissue slices?
What is the significance of evaluating Ki67 levels in this study?
What is the significance of evaluating Ki67 levels in this study?
What is the role of the computational model mentioned in the study?
What is the role of the computational model mentioned in the study?
What type of culture medium is used for incubating tissue slices with ATRA?
What type of culture medium is used for incubating tissue slices with ATRA?
Which gene expression technology is utilized in the evaluation of proliferation associated genes?
Which gene expression technology is utilized in the evaluation of proliferation associated genes?
What is the consequence of ATRA treatment that the study aims to explore?
What is the consequence of ATRA treatment that the study aims to explore?
What kind of samples are prioritized for confirming the predictive model?
What kind of samples are prioritized for confirming the predictive model?
What is the expected outcome regarding ATRA's effect on Ki67 levels?
What is the expected outcome regarding ATRA's effect on Ki67 levels?
What is the primary purpose of developing a new gene-expression model in the context of Gastric Cancer?
What is the primary purpose of developing a new gene-expression model in the context of Gastric Cancer?
Which methodology is emphasized for clustering and subgroup identification according to molecular profiles?
Which methodology is emphasized for clustering and subgroup identification according to molecular profiles?
What does the AUC/ATRA-score reflect in the context of the study?
What does the AUC/ATRA-score reflect in the context of the study?
How many Gastric Cancer cell lines are utilized in the experimental design for predicting ATRA sensitivity?
How many Gastric Cancer cell lines are utilized in the experimental design for predicting ATRA sensitivity?
What is the main goal of using bioinformatics methodologies in the study?
What is the main goal of using bioinformatics methodologies in the study?
What is the significance of optimizing and validating the new gene-expression model?
What is the significance of optimizing and validating the new gene-expression model?
Which approach enables the retrieval of transcriptomic expression data for the Gastric Cancer cell lines?
Which approach enables the retrieval of transcriptomic expression data for the Gastric Cancer cell lines?
Why is there a focus on selecting Gastric Cancer patients who may benefit from ATRA-based treatments?
Why is there a focus on selecting Gastric Cancer patients who may benefit from ATRA-based treatments?
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Study Notes
Study Objectives and Aims
- Primary goal: Provide pre-clinical data on all-trans retinoic acid (ATRA) for personalized treatment of Gastric Cancer.
- Define molecular mechanisms and gene-networks linked to ATRA's anti-tumor activity in specific subgroups of Gastric Cancer.
- Develop a diagnostic tool for selecting Gastric Cancer patients suitable for ATRA-based therapies.
- Long-term aim: Create rationale for therapeutic combinations of ATRA with agents targeting specific gene-networks.
Specific Aim 1: ATRA-Sensitivity and Genomic Profiles
- Objective: Assess ATRA-sensitivity of Gastric Cancer cell lines and classify molecular profiles to identify sub-groups.
- Perform RNA-Sequencing on a panel of 15 Gastric Cancer cell lines (NextSeq-500 Illumina) to investigate transcriptomic profiles.
- Characterize gene transcription effects induced by ATRA treatment.
Specific Aim 2: Gene-Expression Model Development
- Utilize a larger panel of 27 Gastric Cancer cell lines to establish a predictive gene-expression model for ATRA sensitivity.
- Evaluate response to ATRA using an in vitro sensitivity scoring system (AUC/ATRA-score).
- Profile gene-expression data retrieved from the Cancer Cell Line Encyclopedia (CCLE) for model validation and optimization.
Specific Aim 3: Validation Using Primary Tumor Samples
- Transition from cell line studies to short-term tissue-slice cultures of primary Gastric Cancer specimens.
- Test ATRA's anti-tumor activity on fresh surgical samples from patients while monitoring cell growth inhibition and apoptosis.
- Establish correlation between in vitro ATRA responses and genomic profiles to refine predictive capacity of the gene-expression model.
Materials & Methods Overview
- Apply comprehensive bioinformatics and computational techniques for data analysis and gene expression profiling.
- Assess growth inhibition through quantitative Ki67 expression and apoptosis using activated caspase-3 markers.
- Implement RNA extraction from treated tissue slices for subsequent RNA-sequencing.
Risk Analysis
- Anticipated technical feasibility for genomic studies, with no major challenges expected.
- Lack of systematic literature on ATRA’s anti-tumor effects in Gastric Cancer may influence the study direction.
- If ATRA promotes rather than inhibits Gastric Cancer cell proliferation, future research may shift towards retinoid receptor inverse-agonists.
Significance and Innovation
- ATRA presents a non-traditional cancer treatment contrasting typical chemotherapeutics, with limited studies on its efficacy in Gastric Cancer.
- Project aims to elucidate the therapeutic potential of ATRA, promoting insights into novel anti-cancer agents, particularly in personalized medicine.
- Development of precise diagnostic tools to predict patient sensitivity to ATRA-based therapies is essential for tailoring treatment plans.
- Completion of the project could establish justification for Phase I/II clinical trials involving ATRA and related retinoids in Gastric Cancer patients.
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