PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-7 (7)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
author:("seurati, mosm")
1.  O-6-methylguanine-deoxyribonucleic acid methyltransferase methylation enhances response to temozolomide treatment in esophageal cancer 
Background:
World-wide, esophageal cancer is a growing epidemic and patients frequently present with advanced disease that is surgically inoperable. Hence, chemotherapy is the predominate treatment. Cytotoxic platinum compounds are mostly used, but their efficacy is only moderate. Newer alkylating agents have shown promise in other tumor types, but little is known about their utility in esophageal cancer.
Methods:
We utilized archived human esophageal cancer samples and esophageal cancer cell lines to evaluate O-6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) hypermethylation status and determined sensitivity to the alkylating drug temozolomide (TMZ). Immunoblot analysis was performed to determine MGMT protein expression in cell lines. To assess and confirm the effect of TMZ treatment in a methylated esophageal cancer cell line in vivo, a mouse flank xenograft tumor model was utilized.
Results:
Nearly 71% (12/17) of adenocarcinoma and 38% (3/8) of squamous cell carcinoma (SCC) patient samples were MGMT hypermethylated. Out of four adenocarcinoma and nine SCC cell lines tested, one of each histology was hypermethylated. Immunoblot analyses confirmed that hypermethylated cell lines did not express the MGMT protein. In vitro cell viability assays showed the methylated Kyse-140 and FLO cells to be sensitive to TMZ at an IC50 of 52-420 μM, whereas unmethylated cells Kyse-410 and SKGT-4 did not respond. In an in vivo xenograft tumor model with Kyse-140 cells, which are MGMT hypermethylated, TMZ treatment abrogated tumor growth by more than 60%.
Conclusion:
MGMT methylation may be an important biomarker in subsets of esophageal cancers and targeting by TMZ may be utilized to successfully treat these patients.
doi:10.4103/1477-3163.120632
PMCID: PMC3853796  PMID: 24319345
Alkylating agents; deoxyribonucleic acid repair genes; in vivo pre-clinical; esophageal cancer; O-6-methylguanine-deoxyribonucleic acid methyltransferase hypermethylation; response to treatment; temozolomide
2.  A Web-Based Patient Tool for Preventive Health: Preliminary Report 
Background
The Internet is a promising medium for engaging the community in preventive care and health promotion, particularly among those who do not routinely access health care.
Objective
The authors pilot-tested a novel website that translates evidence-based preventive health guidelines into a patient health education tool. The web-based tool allows individuals to enter their health risk factors and receive a tailored checklist of recommended preventive health services based on up-to-date guidelines from the US Preventive Services Task Force and the Advisory Committee on Immunization Practices.
Methods
The authors conducted surveys and in-depth interviews among a purposive sample of adults from an urban African American community who pilot-tested the website in a standardized setting. Interviews were designed to assess the usability, navigability, and content of the website and capture patient perceptions about its educational value and usefulness. Each interview was audiotaped, transcribed, and examined using the constant comparative method.
Results
Twenty-five participants piloted the tool: 96% found it easy to use and 64% reported learning something new. Many participants reported that, in addition to improving clinical preventive care (the intended purpose), the website could serve as a stand-alone tool to improve self-awareness and motivate behavior change.
Conclusions
A web-based tool designed to translate preventive health guidelines for the community may serve the dual purpose of improving the delivery of preventive health care and encouraging health promotion. The website developed here is publicly available for use by practitioners and the community.
doi:10.1177/2150131911436011
PMCID: PMC3718287  PMID: 23804175
web-based learning; preventive health; evidence based medicine; doctor-patient relationship
3.  Role of MetMAb (OA-5D5) in c-MET active lung malignancies 
Expert Opinion on Biological Therapy  2011;11(12):1655-1662.
Introduction
MetMAb (OA-5D5) is a one-armed monoclonal antibody developed to bind to and inhibit c-MET receptor tyrosine kinase. Though early in clinical testing, this agent holds great promise in diseases thought to be driven by c-MET activation, as evidenced by the phase II results in non-small cell lung cancer, (NSCLC) where a benefit in overall survival was observed in patients with MET diagnostic positive disease. Thus far, both alone and in combination with other targeted agents, this drug has been well tolerated and no new significant safety signals have been identified.
Areas covered
The review summarizes the structure and function of the c-MET receptor and its ligand HGF, provides an overview of select targeted monotherapies developed to interfere in the MET-HGF signaling pathway, discusses pre-clinical and clinical data surrounding MetMAb, and concludes with an expert opinion regarding this novel agent.
Expert opinion
MetMAb has been well tolerated and based on phase II data testing it, in combination with erlotinib in advanced NSCLC, may have a role in improving survival in patients with disease driven by c-MET activation. However, phase III validation is underway and the results of these studies will help elucidate which patients will benefit most from this novel agent.
doi:10.1517/14712598.2011.626762
PMCID: PMC3258451  PMID: 22047509
MetMAb; c-MET; HGF; targeted therapy; monoclonal antibody; personalized medicine; non-small cell lung cancer
4.  Utilisation of a thoracic oncology database to capture radiological and pathological images for evaluation of response to chemotherapy in patients with malignant pleural mesothelioma 
BMJ Open  2012;2(5):e001620.
Objective
An area of need in cancer informatics is the ability to store images in a comprehensive database as part of translational cancer research. To meet this need, we have implemented a novel tandem database infrastructure that facilitates image storage and utilisation.
Background
We had previously implemented the Thoracic Oncology Program Database Project (TOPDP) database for our translational cancer research needs. While useful for many research endeavours, it is unable to store images, hence our need to implement an imaging database which could communicate easily with the TOPDP database.
Methods
The Thoracic Oncology Research Program (TORP) imaging database was designed using the Research Electronic Data Capture (REDCap) platform, which was developed by Vanderbilt University. To demonstrate proof of principle and evaluate utility, we performed a retrospective investigation into tumour response for malignant pleural mesothelioma (MPM) patients treated at the University of Chicago Medical Center with either of two analogous chemotherapy regimens and consented to at least one of two UCMC IRB protocols, 9571 and 13473A.
Results
A cohort of 22 MPM patients was identified using clinical data in the TOPDP database. After measurements were acquired, two representative CT images and 0–35 histological images per patient were successfully stored in the TORP database, along with clinical and demographic data.
Discussion
We implemented the TORP imaging database to be used in conjunction with our comprehensive TOPDP database. While it requires an additional effort to use two databases, our database infrastructure facilitates more comprehensive translational research.
Conclusions
The investigation described herein demonstrates the successful implementation of this novel tandem imaging database infrastructure, as well as the potential utility of investigations enabled by it. The data model presented here can be utilised as the basis for further development of other larger, more streamlined databases in the future.
doi:10.1136/bmjopen-2012-001620
PMCID: PMC3488720  PMID: 23103606
Basic Sciences
5.  Proteomic characterization of non-small cell lung cancer in a comprehensive translational thoracic oncology database 
Background
In recent years, there has been tremendous growth and interest in translational research, particularly in cancer biology. This area of study clearly establishes the connection between laboratory experimentation and practical human application. Though it is common for laboratory and clinical data regarding patient specimens to be maintained separately, the storage of such heterogeneous data in one database offers many benefits as it may facilitate more rapid accession of data and provide researchers access to greater numbers of tissue samples.
Description
The Thoracic Oncology Program Database Project was developed to serve as a repository for well-annotated cancer specimen, clinical, genomic, and proteomic data obtained from tumor tissue studies. The TOPDP is not merely a library—it is a dynamic tool that may be used for data mining and exploratory analysis. Using the example of non-small cell lung cancer cases within the database, this study will demonstrate how clinical data may be combined with proteomic analyses of patient tissue samples in determining the functional relevance of protein over and under expression in this disease.
Clinical data for 1323 patients with non-small cell lung cancer has been captured to date. Proteomic studies have been performed on tissue samples from 105 of these patients. These tissues have been analyzed for the expression of 33 different protein biomarkers using tissue microarrays. The expression of 15 potential biomarkers was found to be significantly higher in tumor versus matched normal tissue. Proteins belonging to the receptor tyrosine kinase family were particularly likely to be over expressed in tumor tissues. There was no difference in protein expression across various histologies or stages of non-small cell lung cancer. Though not differentially expressed between tumor and non-tumor tissues, the over expression of the glucocorticoid receptor (GR) was associated improved overall survival. However, this finding is preliminary and warrants further investigation.
Conclusion
Though the database project is still under development, the application of such a database has the potential to enhance our understanding of cancer biology and will help researchers to identify targets to modify the course of thoracic malignancies.
doi:10.1186/2043-9113-1-8
PMCID: PMC3097094  PMID: 21884620
6.  Proteomic characterization of non-small cell lung cancer in a comprehensive translational thoracic oncology database 
Background
In recent years, there has been tremendous growth and interest in translational research, particularly in cancer biology. This area of study clearly establishes the connection between laboratory experimentation and practical human application. Though it is common for laboratory and clinical data regarding patient specimens to be maintained separately, the storage of such heterogeneous data in one database offers many benefits as it may facilitate more rapid accession of data and provide researchers access to greater numbers of tissue samples.
Description
The Thoracic Oncology Program Database Project was developed to serve as a repository for well-annotated cancer specimen, clinical, genomic, and proteomic data obtained from tumor tissue studies. The TOPDP is not merely a library--it is a dynamic tool that may be used for data mining and exploratory analysis. Using the example of non-small cell lung cancer cases within the database, this study will demonstrate how clinical data may be combined with proteomic analyses of patient tissue samples in determining the functional relevance of protein over and under expression in this disease.
Clinical data for 1323 patients with non-small cell lung cancer has been captured to date. Proteomic studies have been performed on tissue samples from 105 of these patients. These tissues have been analyzed for the expression of 33 different protein biomarkers using tissue microarrays. The expression of 15 potential biomarkers was found to be significantly higher in tumor versus matched normal tissue. Proteins belonging to the receptor tyrosine kinase family were particularly likely to be over expressed in tumor tissues. There was no difference in protein expression across various histologies or stages of non-small cell lung cancer. Though not differentially expressed between tumor and non-tumor tissues, the over expression of the glucocorticoid receptor (GR) was associated improved overall survival. However, this finding is preliminary and warrants further investigation.
Conclusion
Though the database project is still under development, the application of such a database has the potential to enhance our understanding of cancer biology and will help researchers to identify targets to modify the course of thoracic malignancies.
doi:10.1186/2043-9113-1-8
PMCID: PMC3164615  PMID: 21603121
7.  Generation of Comprehensive Thoracic Oncology Database - Tool for Translational Research 
The Thoracic Oncology Program Database Project was created to serve as a comprehensive, verified, and accessible repository for well-annotated cancer specimens and clinical data to be available to researchers within the Thoracic Oncology Research Program. This database also captures a large volume of genomic and proteomic data obtained from various tumor tissue studies. A team of clinical and basic science researchers, a biostatistician, and a bioinformatics expert was convened to design the database. Variables of interest were clearly defined and their descriptions were written within a standard operating manual to ensure consistency of data annotation. Using a protocol for prospective tissue banking and another protocol for retrospective banking, tumor and normal tissue samples from patients consented to these protocols were collected. Clinical information such as demographics, cancer characterization, and treatment plans for these patients were abstracted and entered into an Access database. Proteomic and genomic data have been included in the database and have been linked to clinical information for patients described within the database. The data from each table were linked using the relationships function in Microsoft Access to allow the database manager to connect clinical and laboratory information during a query. The queried data can then be exported for statistical analysis and hypothesis generation.
doi:10.3791/2414
PMCID: PMC3182654  PMID: 21304468

Results 1-7 (7)