Ovarian Cancer Institute

Atlanta, GA, United States

Ovarian Cancer Institute

Atlanta, GA, United States
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News Article | October 28, 2016
Site: www.prweb.com

A total of 28 Mercy Medical Center physicians were recognized in Baltimore magazine’s November 2016 “Top Docs” issue, representing 23 separate specialties, ranging from breast cancer surgery to varicose veins. They are (as listed in the magazine): Dr. Kelly Alexander, General Surgery Dr. Mark Applefeld, Cardiology: Interventional Dr. Fermin Barrueto, Urogynecology Dr. John Campbell, Orthopedic Surgery: Foot & Ankle Dr. Bernard W. Chang, Plastic Surgery: Reconstructive and Plastic Surgery: Breast Dr. Teresa Diaz-Montes, Gynecologic Oncology Dr. Susan Dulkerian, Neonatology Dr. R. Mark Ellerkmann, Gynecology: General Dr. J. Lawrence Fitzpatrick, General Surgery Dr. Neil B. Friedman, Breast Surgery and Oncology: Breast Dr. Scott Huber, Gastroenterology Dr. Dwight D. Im, Gynecologic Oncology Dr. Maria Jacobs, Radiation Oncology Dr. Clifford Jeng, Orthopedic Surgery: Foot & Ankle Dr. Peter Ledakis, Oncology: General Dr. Paul Lucas, Surgery for Chronic Venous Disease/Varicose Veins Dr. Lynn Ludmer, Rheumatology Dr. David Maine, Pain Management Dr. Andrea Marx, Rheumatology Dr. Albert Polito, Pulmonary Dr. Neil B. Rosenshein, Gynecologic Oncology Dr. John Salkeld, Radiology: Nuclear Medicine Dr. Armando Sardi, Surgical Oncology Dr. David Sill, Interventional Radiology Dr. Amish Sura, Cardiology: Interventional Dr. Thomas Swope, General Surgery Dr. Debra Vachon, ColoRectal Dr. Linda C. Wang, Dermatology (Medical) Mercy’s Dr. Maria C.E. Jacobs, Director of Radiation Oncology, was among several doctors photographed and profiled for the special edition. Dr. Jacobs works in close collaboration with the cancer surgeons, including fellow Baltimore magazine “Top Doc” honoree, Dr. Neil B. Friedman, Director, The Hoffberger Breast Center to coordinate post surgical treatment for breast cancer patients. Dr. Jacobs and Dr. Friedman were the first team of doctors in the state of Maryland to use Intraoperative Radiotherapy (IORT), a state-of-the-art technology that allows patients to get treated in one single radiation therapy session – a notable advantage over the many multiple visits required prior to IORT. Each Mercy physician was recognized as among the best in their respective fields. Other honorees including Dr. Dwight Im, Dwight D. Im, M.D., FACOG, renowned gynecologic cancer surgeon and leader of Mercy Medical Center’s prestigious gynecology and robotic surgery programs, and been named a “Top Doctor" for 2016 earlier this year by Castle Connolly Medical Ltd.; Armando Sardi, M.D., FACS, respected and renowned Surgical Oncologist who has been honored as a Top Doc in Baltimore magazine multiple times, serves as Medical Director of The Institute for Cancer Care at Mercy and as Chief of Division of Surgical Oncology at Mercy and recognized internationally for his work in the field of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to treat late stage, complex cancers of the abdominal region; and Teresa P. Diaz-Montes, M.D., MPH, FACOG, Associate Director of The Lya Segall Ovarian Cancer Institute, the first center in the region specifically designed for the treatment of ovarian cancer. Mercy Medical Center in Baltimore, MD, is a 142-year-old university affiliated medical facility named a "Top Hospital" by U.S. News and World Report with a national reputation for women's health care. For more information about Mercy, visit Mercy online at http://www.mdmercy.com; MDMercyMedia on FACEBOOK and TWITTER; or call 1-800-MD-MERCY.


News Article | November 7, 2016
Site: www.eurekalert.org

Ovarian cancer growth inhibited by nanoparticle delivery of EGFR siRNA, allowing chemotherapy to starkly shrink or eliminate tumors in mice In the fight against cancer, doctors dish out combination-blows of surgery, chemotherapy and other drugs to beat back a merciless foe. Now, scientists have taken early steps toward adding a stinging punch to clinicians' repertoire. A novel targeted therapy using nanoparticles has enabled researchers at the Georgia Institute of Technology to purge ovarian tumors in limited, in vivo tests in mice. "The dramatic effect we see is the massive reduction or complete eradication of the tumor, when the 'nanohydrogel' treatment is given in combination with existing chemotherapy," said chief researcher John McDonald. That nanohydrogel is a minute gel pellet that honed in on malignant cells with a payload of an RNA strand. The RNA entered the cell, where it knocked down a protein gone awry that is involved in many forms of cancer. In trials on mice, it put the brakes on ovarian cancer growth and broke down resistance to chemotherapy. That allowed a common chemotherapy drug, cisplatin, to drastically reduce or eliminate large carcinomas with very similar speed and manner. The successful results in treatment of four mice with the combination of siRNA and cisplatin showed little variance. The therapeutic short interfering RNA (siRNA) developed by McDonald and Georgia Tech researchers Minati Satpathy and Roman Mezencev, thwarted cancer-causing overproduction of cell structures called epidermal growth factor receptors (EGFRs), which extend out of the wall of certain cell types. EGFR overproduction is associated with aggressive cancers. The researchers from Georgia Tech's School of Biological Sciences published their results on Monday, November 7, 2016, in the journal Scientific Reports. Research was funded by the National Institutes of Health's IMAT Program, the Ovarian Cancer Institute, the Deborah Nash Endowment Fund, the Curci Foundation and the Markel Foundation. The new treatment has not been tested on humans, and research would be required by science and by law to demonstrate consistent results - efficacy - among other things, before preliminary human trials could become possible. The current in vivo success strengthens the idea that knocking out EGFR at the RNA level may be a worthy goal to explore in the fight against carcinomas in general. The same patented nanohydrogel packed with other types of therapeutic RNA is currently being tested for the treatment of other types cancers. EGFRs are receptors found in epithelial cells, which line organs throughout the body: Lungs, mouth, throat, intestines and others. In women, it also lines reproductive organs: Ovaries, uterus and cervix. They are long proteins that poke through the cell membrane, connecting the cell's interior with the outside. They look like squiggly worms with tiny mouths on the outside that take up a messenger protein. In a healthy cell, those messenger molecules cause EGFRs to trigger long chains of biochemical reactions that lead to the activation of genes involved in a variety of cellular functions. In carcinoma cells, the number of EGFRs present typically skyrockets. "In many cancers, EGFR is overexpressed," McDonald said. "The problem is that because of this overexpression, many cellular functions, including cell replication and resistance to certain chemotherapy drugs, are dramatically cranked up." The cell goes haywire, metabolizes too much sugar, divides too much, and resists chemotherapy. The cancer grows into a tumor and can spread through the body. An overabundance of EGFRs found in a biopsy is usually a sign the cancer is aggressive, and that patient prognosis is poor. "In 70 percent of ovarian cancer patients, EGFR is overexpressed at very high levels," McDonald said. EGFR overexpression also makes cancer cells resistant to chemotherapy by thwarting a natural defense mechanism. "The platinum-based chemotherapies used to treat ovarian cancers cause DNA damage, which switches on apoptosis," McDonald said. Apoptosis is cell suicide. When cells can't repair DNA damage, they're programmed to kill themselves to keep the damaged cells from spreading. The primary chemotherapy used to treat ovarian cancer works by coaxing cancer cells to trigger the suicide program, but having too many epidermal growth factor receptors gets in the way. "EGFR overexpression hinders apoptosis; they won't die. By knocking down EGRF, we make the cell hypersensitive to the drug. Apoptosis is reactivated," McDonald said. Existing EGFR targeted drugs called tyrosine-kinase inhibitors disrupt an EGFR function, but their success in treating ovarian cancer has been limited. "Clinicians have tried EGFR inhibitors to treat ovarian cancers for some years, and they only get about 20% of patients responding to it," McDonald said. "Apparently, the particular EGFR function inhibited by these drugs is not critical to ovarian cancer." The short interfering (si) RNA designed by the Georgia Tech researchers attacks the cancer much closer to its root. To make the protein for EGFR, RNA has to transfer its genetic code from DNA. The researchers' siRNA binds to the cell's RNA and stops it from working. "We're knocking down EGFR at the RNA level," McDonald said. "Since EGFR is multi-functional, it's not exactly clear which malfunctions contribute to ovarian cancer growth. By completely knocking out its production in ovarian cancer cells, all EGFR functions are blocked." The nanohydrogel that delivers the siRNA to the cancer cells is a colloid ball of a common, compact organic molecule and about 98 percent water. Another molecule is added to the surface of the nanohydrogel as a guide. It makes the pellets adhere to the cancer cells like sticky cluster bombs. Cancerous tissue may also be aiding the nanohydrogel in targeting it. "When you get into a tumor, there are a lot of blood vessels, and many are broken," McDonald said. "This may help the nanoparticles get passively trapped in the neighborhood of tumorous tissues." In the in vivo trials, the siRNA, which contained a fluorescent tag, allowed researchers to observe nanoparticles successfully honing in on the cancer cells. "We originally selected to target the EGFR gene because its activity is easily measured, and we wanted to use it simply as an indicator that our nanoparticle siRNA delivery system was working," McDonald said. "The fact that the EGFR knockdown so dramatically sensitized the cells to standard chemotherapy came as a bit of a surprise." At first, his team observed how the tumors responded to chemotherapy alone. Then they combined it with the nanoparticle treatment. "When we gave the chemotherapy alone, the response was moderate, but with the addition of the nanoparticles, the tumor was either significantly reduced or completely gone," McDonald said. But he tempered enthusiasm with caution. "Further work will be required to see if the treatment completely destroyed every trace of cancer cells in the tumors that disappeared, or if future recurrence is possible." If the researchers' continuing studies further prove to be consistent, the combination of the nanohydrogel with other therapeutic RNAs could represent a significant advancement in the treatment of a wide spectrum of cancers. Georgia Tech's Lijuan Wang and Dr. Benedict Benigno from Atlanta's Northside Hospital coauthored the paper. Research was funded by the National Institutes of Health's Program for Innovative Molecular Analysis Technologies Program (grant 1R21CA155479-01), the Ovarian Cancer Institute at Northside Hospital, the Deborah Nash Endowment Fund, the Curci Foundation, and the Markel Foundation. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsoring agencies.


News Article | November 8, 2016
Site: www.rdmag.com

In the fight against cancer, doctors dish out combination-blows of surgery, chemotherapy and other drugs to beat back a merciless foe. Now, scientists have taken early steps toward adding a stinging punch to clinicians' repertoire. A novel targeted therapy using nanoparticles has enabled researchers at the Georgia Institute of Technology to purge ovarian tumors in limited, in vivo tests in mice. "The dramatic effect we see is the massive reduction or complete eradication of the tumor, when the 'nanohydrogel' treatment is given in combination with existing chemotherapy," said chief researcher John McDonald. That nanohydrogel is a minute gel pellet that honed in on malignant cells with a payload of an RNA strand. The RNA entered the cell, where it knocked down a protein gone awry that is involved in many forms of cancer. In trials on mice, it put the brakes on ovarian cancer growth and broke down resistance to chemotherapy. That allowed a common chemotherapy drug, cisplatin, to drastically reduce or eliminate large carcinomas with very similar speed and manner. The successful results in treatment of four mice with the combination of siRNA and cisplatin showed little variance. The therapeutic short interfering RNA (siRNA) developed by McDonald and Georgia Tech researchers Minati Satpathy and Roman Mezencev, thwarted cancer-causing overproduction of cell structures called epidermal growth factor receptors (EGFRs), which extend out of the wall of certain cell types. EGFR overproduction is associated with aggressive cancers. The researchers from Georgia Tech's School of Biological Sciences published their results on Monday, November 7, 2016, in the journal Scientific Reports. Research was funded by the National Institutes of Health's IMAT Program, the Ovarian Cancer Institute, the Deborah Nash Endowment Fund, the Curci Foundation and the Markel Foundation. The new treatment has not been tested on humans, and research would be required by science and by law to demonstrate consistent results - efficacy - among other things, before preliminary human trials could become possible. The current in vivo success strengthens the idea that knocking out EGFR at the RNA level may be a worthy goal to explore in the fight against carcinomas in general. The same patented nanohydrogel packed with other types of therapeutic RNA is currently being tested for the treatment of other types cancers. EGFRs are receptors found in epithelial cells, which line organs throughout the body: Lungs, mouth, throat, intestines and others. In women, it also lines reproductive organs: Ovaries, uterus and cervix. They are long proteins that poke through the cell membrane, connecting the cell's interior with the outside. They look like squiggly worms with tiny mouths on the outside that take up a messenger protein. In a healthy cell, those messenger molecules cause EGFRs to trigger long chains of biochemical reactions that lead to the activation of genes involved in a variety of cellular functions. In carcinoma cells, the number of EGFRs present typically skyrockets. "In many cancers, EGFR is overexpressed," McDonald said. "The problem is that because of this overexpression, many cellular functions, including cell replication and resistance to certain chemotherapy drugs, are dramatically cranked up." The cell goes haywire, metabolizes too much sugar, divides too much, and resists chemotherapy. The cancer grows into a tumor and can spread through the body. An overabundance of EGFRs found in a biopsy is usually a sign the cancer is aggressive, and that patient prognosis is poor. "In 70 percent of ovarian cancer patients, EGFR is overexpressed at very high levels," McDonald said. EGFR overexpression also makes cancer cells resistant to chemotherapy by thwarting a natural defense mechanism. "The platinum-based chemotherapies used to treat ovarian cancers cause DNA damage, which switches on apoptosis," McDonald said. Apoptosis is cell suicide. When cells can't repair DNA damage, they're programmed to kill themselves to keep the damaged cells from spreading. The primary chemotherapy used to treat ovarian cancer works by coaxing cancer cells to trigger the suicide program, but having too many epidermal growth factor receptors gets in the way. "EGFR overexpression hinders apoptosis; they won't die. By knocking down EGRF, we make the cell hypersensitive to the drug. Apoptosis is reactivated," McDonald said. Existing EGFR targeted drugs called tyrosine-kinase inhibitors disrupt an EGFR function, but their success in treating ovarian cancer has been limited. "Clinicians have tried EGFR inhibitors to treat ovarian cancers for some years, and they only get about 20% of patients responding to it," McDonald said. "Apparently, the particular EGFR function inhibited by these drugs is not critical to ovarian cancer." The short interfering (si) RNA designed by the Georgia Tech researchers attacks the cancer much closer to its root. To make the protein for EGFR, RNA has to transfer its genetic code from DNA. The researchers' siRNA binds to the cell's RNA and stops it from working. "We're knocking down EGFR at the RNA level," McDonald said. "Since EGFR is multi-functional, it's not exactly clear which malfunctions contribute to ovarian cancer growth. By completely knocking out its production in ovarian cancer cells, all EGFR functions are blocked." The nanohydrogel that delivers the siRNA to the cancer cells is a colloid ball of a common, compact organic molecule and about 98 percent water. Another molecule is added to the surface of the nanohydrogel as a guide. It makes the pellets adhere to the cancer cells like sticky cluster bombs. Cancerous tissue may also be aiding the nanohydrogel in targeting it. "When you get into a tumor, there are a lot of blood vessels, and many are broken," McDonald said. "This may help the nanoparticles get passively trapped in the neighborhood of tumorous tissues." In the in vivo trials, the siRNA, which contained a fluorescent tag, allowed researchers to observe nanoparticles successfully honing in on the cancer cells. "We originally selected to target the EGFR gene because its activity is easily measured, and we wanted to use it simply as an indicator that our nanoparticle siRNA delivery system was working," McDonald said. "The fact that the EGFR knockdown so dramatically sensitized the cells to standard chemotherapy came as a bit of a surprise." At first, his team observed how the tumors responded to chemotherapy alone. Then they combined it with the nanoparticle treatment. "When we gave the chemotherapy alone, the response was moderate, but with the addition of the nanoparticles, the tumor was either significantly reduced or completely gone," McDonald said. But he tempered enthusiasm with caution. "Further work will be required to see if the treatment completely destroyed every trace of cancer cells in the tumors that disappeared, or if future recurrence is possible." If the researchers' continuing studies further prove to be consistent, the combination of the nanohydrogel with other therapeutic RNAs could represent a significant advancement in the treatment of a wide spectrum of cancers.


News Article | November 7, 2016
Site: www.sciencedaily.com

In the fight against cancer, doctors dish out combination-blows of surgery, chemotherapy and other drugs to beat back a merciless foe. Now, scientists have taken early steps toward adding a stinging punch to clinicians' repertoire. A novel targeted therapy using nanoparticles has enabled researchers at the Georgia Institute of Technology to purge ovarian tumors in limited, in vivo tests in mice. "The dramatic effect we see is the massive reduction or complete eradication of the tumor, when the 'nanohydrogel' treatment is given in combination with existing chemotherapy," said chief researcher John McDonald. That nanohydrogel is a minute gel pellet that honed in on malignant cells with a payload of an RNA strand. The RNA entered the cell, where it knocked down a protein gone awry that is involved in many forms of cancer. In trials on mice, it put the brakes on ovarian cancer growth and broke down resistance to chemotherapy. That allowed a common chemotherapy drug, cisplatin, to drastically reduce or eliminate large carcinomas, with very similar speed and manner. The successful results treating four mice with the combination of siRNA and cisplatin showed little variance. The therapeutic short interfering RNA (siRNA) developed by McDonald and Georgia Tech researchers Minati Satpathy and Roman Mezencev, thwarted cancer-causing overproduction of cell structures called epidermal growth factor receptors (EGFRs), which extend out of the wall of certain cell types. EGFR overproduction is associated with aggressive cancers. The researchers from Georgia Tech's School of Biological Sciences published their results in the journal Scientific Reports. Research was funded by the National Institutes of Health's IMAT Program, the Ovarian Cancer Institute, the Deborah Nash Endowment Fund, the Curci Foundation and the Markel Foundation. The new treatment has not been tested on humans, and research would be required by science and by law to demonstrate consistent results -- efficacy -- among other things, before preliminary human trials could become possible. The current in vivo success strengthens the idea that knocking out EGFR at the RNA level may be a worthy goal to explore in the fight against carcinomas in general. The same patented nanohydrogel packed with other types of therapeutic RNA is currently being tested for the treatment of other types cancers. EGFRs are receptors found in epithelial cells, which line organs throughout the body: Lungs, mouth, throat, intestines and others. In women, it also lines reproductive organs: Ovaries, uterus and cervix. They are long proteins that poke through the cell membrane, connecting the cell's interior with the outside. They look like squiggly worms with tiny mouths on the outside that take up a messenger protein. In a healthy cell, those messenger molecules cause EGFRs to trigger long chains of biochemical reactions that lead to the activation of genes involved in a variety of cellular functions. In carcinoma cells, the number of EGFRs present typically skyrockets. "In many cancers, EGFR is overexpressed," McDonald said. "The problem is that because of this overexpression, many cellular functions, including cell replication and resistance to certain chemotherapy drugs, are dramatically cranked up." The cell goes haywire, metabolizes too much sugar, divides too much, and resists chemotherapy. The cancer grows into a tumor and can spread through the body. An overabundance of EGFRs found in a biopsy is usually a sign the cancer is aggressive, and that patient prognosis is poor. "In 70 percent of ovarian cancer patients, EGFR is overexpressed at very high levels," McDonald said. EGFR overexpression also makes cancer cells resistant to chemotherapy by thwarting a natural defense mechanism. "The platinum-based chemotherapies used to treat ovarian cancers cause DNA damage, which switches on apoptosis," McDonald said. Apoptosis is cell suicide. When cells can't repair DNA damage, they're programmed to kill themselves to keep the damaged cells from spreading. The primary chemotherapy used to treat ovarian cancer works by coaxing cancer cells to trigger the suicide program, but having too many epidermal growth factor receptors gets in the way. "EGFR overexpression hinders apoptosis; they won't die. By knocking down EGRF, we make the cell hypersensitive to the drug. Apoptosis is reactivated," McDonald said. Existing EGFR targeted drugs called tyrosine-kinase inhibitors disrupt an EGFR function, but their success in treating ovarian cancer has been limited. "Clinicians have tried EGFR inhibitors to treat ovarian cancers for some years, and they only get about 20% of patients responding to it," McDonald said. "Apparently, the particular EGFR function inhibited by these drugs is not critical to ovarian cancer." The short interfering (si) RNA designed by the Georgia Tech researchers attacks the cancer much closer to its root. To make the protein for EGFR, RNA has to transfer its genetic code from DNA. The researchers' siRNA binds to the cell's RNA and stops it from working. "We're knocking down EGFR at the RNA level," he said. "Since EGFR is multi-functional, it's not exactly clear which malfunctions contribute to ovarian cancer growth. By completely knocking out its production in ovarian cancer cells, all EGFR functions are blocked." The nanohydrogel that delivers the siRNA to the cancer cells is a colloid ball of a common, compact organic molecule and about 98 percent water. Another molecule is added to the surface of the nanohydrogel as a guide. It makes the pellets adhere to the cancer cells like sticky cluster bombs. Cancerous tissue may also be aiding the nanohydrogel in targeting it. "When you get into a tumor, there are a lot of blood vessels, and many are broken," McDonald said. "This may help the nanoparticles get passively trapped in the neighborhood of tumorous tissues." In the in vivo trials, the siRNA, which contained a fluorescent tag, allowed researchers to observe nanoparticles successfully honing in on the cancer cells. "We originally selected to target the EGFR gene because its activity is easily measured, and we wanted to use it simply as an indicator that our nanoparticle siRNA delivery system was working," McDonald said. "The fact that the EGFR knockdown so dramatically sensitized the cells to standard chemotherapy came as a bit of a surprise." At first, his team observed how the tumors responded to chemotherapy alone. Then they combined it with the nanoparticle treatment. "When we gave the chemotherapy alone, the response was moderate, but with the addition of the nanoparticles, the tumor was either significantly reduced or completely gone," McDonald said. But he tempered enthusiasm with caution. "Further work will be required to see if the treatment completely destroyed every trace of cancer cells in the tumors that disappeared, or if future recurrence is possible." If the researchers' continuing studies further prove to be consistent, the combination of the nanohydrogel with other therapeutic RNAs could represent a significant advancement in the treatment of a wide spectrum of cancers.


Wang L.,Georgia Institute of Technology | Mezencev R.,Georgia Institute of Technology | Svajdler M.,R.Ø.S.A. | Svajdler M.,University of Strasbourg | And 3 more authors.
Gynecologic Oncology | Year: 2014

Objective We recently determined that the ectopic over-expression of miR-429 and other members of the miR-200 family of microRNAs in ovarian cancer (OC) mesenchymal-like cell lines induces mesenchymal-to-epithelial transition (MET) with a concomitant increase in sensitivity to platinum drugs. We sought to determine if metastasizing OC cells isolated from an OC patient could also be induced by miR-429 to undergo MET and become sensitized to established first-line platinum-based therapies. Methods We established and characterized a new primary cell line (OCI-984) from free-floating OC cells isolated from the ascites fluid of an advanced stage OC patient. miR-429 was ectopically over-expressed in these cells. Results The over-expression of miR-429 in OCI-984 cells induced morphological, functional and molecular changes consistent with MET and a concomitant significant increase in the sensitivity of the converted cells to cisplatin. Conclusions Our findings indicate that the miR-200 family of microRNAs, and miR-429 in particular, play a critical role in the functioning of OC metastasizing cells and that targeted delivery of miR-429, and perhaps other miR-200 family members, in combination with platinum-based chemotherapies may be an effective strategy in reducing OC metastasis and tumor recurrence. © 2014 Elsevier Inc. All rights reserved.


Lili L.N.,H Petit Institute Of Bioengineering And Biosciences | Matyunina L.V.,H Petit Institute Of Bioengineering And Biosciences | Walker L.D.,H Petit Institute Of Bioengineering And Biosciences | Wells S.L.,Northside Hospital | And 4 more authors.
Journal of Ovarian Research | Year: 2013

Background: While metastasis ranks among the most lethal of all cancer-associated processes, on the molecular level, it remains one of the least well understood. One model that has gained credibility in recent years is that metastasizing cells at least partially recapitulate the developmental process of epithelial-to-mesenchymal transition (EMT) in their transit from primary to metastatic sites. While experimentally supported by cell culture and animal model studies, the lack of unambiguous confirmatory evidence in cancer patients has led to persistent challenges to the model's relevance in humans. Methods. Gene expression profiling (Affymetrix, U133) was carried out on 14 matched sets of primary (ovary) and metastatic (omentum) ovarian cancer (serous adenocarcinoma) patient samples. Hierarchical clustering and functional pathway algorithms were used in the data analysis. Results: While histological examination reveled no morphological distinction between the matched sets of primary and metastatic samples, gene expression profiling clearly distinguished two classes of metastatic samples. One class displayed expression patterns statistically indistinguishable from primary samples isolated from the same patients while a second class displayed expression patterns significantly different from primary samples. Further analyses focusing on genes previously associated with EMT clearly distinguished the primary from metastatic samples in all but one patient. Conclusion: Our results are consistent with a role of EMT in most if not all ovarian cancer metastases and demonstrate that identical morphologies between primary and metastatic cancer samples is insufficient evidence to negate a role of EMT in the metastatic process. © 2013 Lili et al.; licensee BioMed Central Ltd.


Mittal V.K.,Georgia Institute of Technology | McDonald J.F.,Georgia Institute of Technology | McDonald J.F.,Ovarian Cancer Institute
Nucleic Acids Research | Year: 2012

The rapid expansion in the quantity and quality of RNA-Seq data requires the development of sophisticated high-performance bioinformatics tools capable of rapidly transforming this data into meaningful information that is easily interpretable by biologists. Currently available analysis tools are often not easily installed by the general biologist and most of them lack inherent parallel processing capabilities widely recognized as an essential feature of next-generation bioinformatics tools. We present here a user-friendly and fully automated RNA-Seq analysis pipeline (R-SAP) with built-in multi-threading capability to analyze and quantitate high-throughput RNA-Seq datasets. R-SAP follows a hierarchical decision making procedure to accurately characterize various classes of transcripts and achieves a near linear decrease in data processing time as a result of increased multi-threading. In addition, RNA expression level estimates obtained using R-SAP display high concordance with levels measured by microarrays. © 2012 The Author(s).


Hill C.G.,Georgia Institute of Technology | Matyunina L.V.,Georgia Institute of Technology | Walker D.,Georgia Institute of Technology | Benigno B.B.,Ovarian Cancer Institute | And 2 more authors.
BMC Systems Biology | Year: 2014

Background: Documented changes in levels of microRNAs (miRNA) in a variety of diseases including cancer are leading to their development as early indicators of disease, and as a potential new class of therapeutic agents. A significant hurdle to the rational application of miRNAs as therapeutics is our current inability to reliably predict the range of molecular and cellular consequences of perturbations in the levels of specific miRNAs on targeted cells. While the direct gene (mRNA) targets of individual miRNAs can be computationally predicted with reasonable degrees of accuracy, reliable predictions of the indirect molecular effects of perturbations in miRNA levels remain a major challenge in molecular systems biology.Results: Changes in gene (mRNA) and miRNA expression levels between normal precursor and ovarian cancer cells isolated from patient tissue samples were measured by microarray. Expression of 31 miRNAs was significantly elevated in the cancer samples. Consistent with previous reports, the expected decrease in expression of the mRNA targets of upregulated miRNAs was observed in only 20-30% of the cancer samples. We present and provide experimental support for a network model (The Transcriptional Override Model; TOM) to account for the unexpected regulatory consequences of modulations in the expression of miRNAs on expression levels of their target mRNAs in ovarian cancer.Conclusions: The direct and indirect regulatory effects of changes in miRNA expression levels in vivo are interactive and complex but amenable to systems level modeling. Although TOM has been developed and validated within the context of ovarian cancer, it may be applicable in other biological contexts as well, including of potential future use in the rational design of miRNA-based strategies for the treatment of cancers and other diseases. © 2014 Hill et al.; licensee BioMed Central Ltd.


Zhou M.,Georgia Institute of Technology | McDonald J.F.,Georgia Institute of Technology | McDonald J.F.,Ovarian Cancer Institute | Fernandez F.M.,Georgia Institute of Technology
Journal of the American Society for Mass Spectrometry | Year: 2010

Metabolomic fingerprinting of bodily fluids can reveal the underlying causes of metabolic disorders associated with many diseases, and has thus been recognized as a potential tool for disease diagnosis and prognosis following therapy. Here we report a rapid approach in which direct analysis in real time (DART) coupled with time-of-flight (TOF) mass spectrometry (MS) and hybrid quadrupole TOF (Q-TOF) MS is used as a means for metabolomic fingerprinting of human serum. In this approach, serum samples are first treated to precipitate proteins, and the volatility of the remaining metabolites increased by derivatization, followed by DART MS analysis. Maximum DART MS performance was obtained by optimizing instrumental parameters such as ionizing gas temperature and flow rate for the analysis of identical aliquots of a healthy human serum samples. These variables were observed to have a significant effect on the overall mass range of the metabolites detected as well as the signal-to-noise ratios in DART mass spectra. Each DART run requires only 1.2 min, during which more than 1500 different spectral features are observed in a time-dependent fashion. A repeatability of 4.1% to 4.5% was obtained for the total ion signal using a manual sampling arm. With the appealing features of high-throughput, lack of memory effects, and simplicity, DART MS has shown potential to become an invaluable tool for metabolomic fingerprinting. © 2010 American Society for Mass Spectrometry.


Abbott K.L.,University of Georgia | Lim J.-M.,University of Georgia | Wells L.,University of Georgia | Benigno B.B.,Ovarian Cancer Institute | And 3 more authors.
Proteomics | Year: 2010

Epithelial ovarian cancer is diagnosed less than 25% of the time when the cancer is confined to the ovary, leading to 5-year survival rates of less than 30%. Therefore, there is an urgent need for early diagnostics for ovarian cancer. Our study using glycotranscriptome comparative analysis of endometrioid ovarian cancer tissue and normal ovarian tissue led to the identification of distinct differences in the transcripts of a restricted set of glycosyltransferases involved in N-linked glycosylation. Utilizing lectins that bind to glycan structures predicted to show changes, we observed differences in lectin-bound glycoproteins consistent with some of the transcript differences. In this study, we have extended our observations by the use of selected lectins to perform a targeted glycoproteomic analysis of ovarian cancer and normal ovarian tissues. Our results have identified several glycoproteins that display tumor-specific glycosylation changes. We have verified these glycosylation changes on glycoproteins from tissue using immunoprecipitation followed by lectin blot detection. The glycoproteins that were verified were then analyzed further using existing microarray data obtained from benign ovarian adenomas, borderline ovarian adenocarcinomas, and malignant ovarian adenocarcinomas. The verified glycoproteins found to be expressed above control levels in the microarray data sets were then screened for tumor-specific glycan modifications in serum from ovarian cancer patients. Results obtained from two of these glycoprotein markers, periostin and thrombospondin, have confirmed that tumor-specific glycan changes can be used to distinguish ovarian cancer patient serum from normal serum. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA.

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