Author Interviews, Biomarkers, Cancer Research, Genetic Research, Ovarian Cancer / 07.08.2023
Ovarian Cancer: Proteomics Study Allows Identification of Subtype Resistant to Chemotherapy
MedicalResearch.com Interview with:
Pei Wang, PhD
Professor, Department of Genetics and Genomic Sciences
Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Michael J. Birrer MD PhD
Director, Winthrop P. Rockefeller Cancer Institute
University of Arkansas for Medical Sciences
Little Rock, AR 72205
Amanda G. Paulovich MD PhD
Translational Science and Therapeutics Division
Fred Hutchinson Cancer Center
Seattle WA 98109
MedicalResearch.com: What is the background for this study? How common is serous ovarian cancer?
Response: Epithelial ovarian cancer accounts for >185,000 deaths/year worldwide. The most common subtype, high-grade serous ovarian cancer (HGSOC), accounts for 60% of deaths. Despite improvements in surgical and chemotherapeutic approaches, HGSOC mortality has not changed in decades. Five-year survival remains ~30% for the majority of patients.
Standard of care involves surgical debulking combined with adjuvant or neoadjuvant chemotherapy with carbo- or cisplatin in combination with a taxane. At diagnosis, HGSOC is among the most chemo-sensitive of all epithelial malignancies, with initial response rates of ~85%, presumably related to DNA repair defects. Platinum is thought primarily to drive the response rate, due to the lower single-agent response rate for taxanes.
Unfortunately, 10-20% of HGSOC patients have treatment-refractory disease at diagnosis, fail to respond to initial chemotherapy, and have a dismal prognosis. The poor response to subsequent therapy and median overall survival of ~12 months for these patients has not changed in 40 years.
Despite >30 years of literature studying platinum resistance in cancer, there currently is no way to distinguish refractory from sensitive HGSOCs prior to therapy. Consequently, patients with refractory disease experience the toxicity of platinum-based chemotherapy without benefit. Due to their rapid progression, they are commonly excluded from participating in clinical trials. Consequently, there is no ongoing clinical research that could identify effective therapeutic agents for these patients or provide insights into molecular mechanisms of refractory disease. “Right now, we can’t identify drug-resistant ovarian cancer patients up front,” said co-senior author Michael Birrer, MD, PhD, who directs UAMS’ Winthrop J. Rockefeller Cancer Institute. “We find them by default: They get sick and pass away so quickly that they can’t even be put on new clinical trials.”
To address this unmet clinical need, we performed proteogenomic analysis of treatment-naïve HGSOCs (chemo-sensitive and chemo-refractory) to identify molecular signatures of refractory HGSOC and to identify potential treatment targets.
Lone Star Tick Nymph-CDC image[/caption]
MedicalResearch.com: What is the background for this study? Would you briefly describe Alpha-gal Syndrome?
Response: Alpha-gal syndrome is an emerging and potentially life-threatening allergic condition that is associated with a tick bite. It is also called alpha-gal allergy, red meat allergy, or tick bite meat allergy.
Increasing case studies and anecdotal reports suggested that AGS was a growing concern, but, prior to these studies, information on clinician awareness and the number of people impacted was not available at a national level.
Mytien Nguyen[/caption]
Mytien Nguyen, MS
Department of Immunobiology,
Yale School of Medicine
New Haven, Connecticut
MedicalResearch.com: What is the background for this study?
Response: Physician-scientists are critical for innovative translational research. 
Dr. Li Li[/caption]
Li Li, M.D., Ph.D., M.P.H
Walter M. Seward Professor
Chair of Family Medicine
Director of population health
University of Virginia School of Medicine
Editor-in-chief of The BMJ Family Medicine
Dr. Li joined the U.S. Preventive Services Task Force in January 2021
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Task Force reviewed the latest available evidence to evaluate whether screening all children and adolescents who are 20 years old or younger for high cholesterol improves their heart health into adulthood.
At this time, there is not enough evidence to determine whether or not screening all kids is beneficial, so we are calling for additional research on the effectiveness of screening and treatment of high cholesterol in kids and teens.
Dr. Callaghan[/caption]
Bridget Callaghan Ph.D.
Assistant Professor of Psychology
UCLA
Dr. Callahan studies interactions between mental and physical health across development.
MedicalResearch.com: What is the background for this study?
Response: A growing body of evidence links the gut microbiome to brain and immune functioning, and changes to that community of microorganisms is likely among the ways that hardship affects children’s socioemotional development.
Limited evidence in humans has demonstrated the adversities experienced prenatally and during early life influence the composition of the gut microbiome, but no studies had examined whether stress experienced in a mother's own childhood could influence the microbiome of the next generation of children.
Kazi Albab Hussain[/caption]
Kazi Albab Hussain
Graduate Student (PhD)
Specialization: Water Resources
Advisor: Professor Yusong Li, PhD
Associate Dean for Faculty and Inclusion
MedicalResearch.com: What is the background for this study?
Response: Microplastics have been detected in various food items and beverages, including table salt, bottled water, fish, and mussels. The extensive use of plastic-based products in food preparation, storage, and handling has raised concerns about the direct release of microplastics. Interestingly, we often discuss microplastics but overlook nanoplastics in the conversation. Due to their smaller size, nanoplastics are harder to be detected.
In our study, we wanted to see the release of both microplastics and nanoplastics, as nanoplastics may be even more toxic than microplastics.
Unfortunately, infants and toddlers are particularly vulnerable to the potential health impacts of micro- and nanoplastics. Studies have shown significant ingestion of these particles from polypropylene feeding bottles and silicone-rubber baby teats. We aimed to investigate the release of of micro- and nanoplastics, estimated their exposure for infants and toddlers, and evaluated their cytotoxicity to human embryonic kidney cells.
MedicalResearch.com: What is the background for this study?
Response: I became interested in dog's sense of smell several years ago while doing therapy dog demonstrations at the California Science Center in Los Angeles during a special traveling exhibit "Dogs! A Science Tail." (Now at the Orlando Science Center). I did a lot of research on this topic and taught children about it through the Los Angeles Public Library using my Great Pyrenees therapy dogs. Then, COVID broke out and I expanded my research into any work being done to possibly utilize scent dogs for screening and testing for COVID. I found only a few such studies. However, I fortuitously met Heather Junqueira of BioScent, Inc. (in Florida) online and she was beginning to successfully teach her beagles to detect COVID-related odors. She agreed to co-author a peer-reviewed review paper with me. That led to our first paper -
Dickey, T, Junqueira, H. Toward the use of medical scent dogs for COVID-19 screening. J Osteopath Med 2021;1(2): 141-148. 
Dr. Davis[/caption]
Prof. Jonathan Davis, MD,
Chief of Newborn Medicine
Tufts Medical Center and
[caption id="attachment_60599" align="alignleft" width="125"]
Dr. Kruger[/caption]
Jessica Kruger PhD
Clinical Associate Professor of Community Health and Health Behavior
University at Buffalo School of Public Health and Health Professions
MedicalResearch.com: What is the background for this study?
Response: The 2018 Farm Bill authorizing hemp production led to new cannabinoids in the consumer marketplace. As the market becomes increasingly saturated with suppliers, companies continually diversify available products.
The rapid emergence of novel cannabinoids outpaces systematic research necessary to inform regulations and harm reduction. Empirical evidence is needed to guide policies, practices, and education of consumers. Product manufacturers, social media participants, and cannabis oriented on-line news sources have claimed that THC-O-acetate is a "psychedelic" cannabinoid, producing experiences similar to those associated with LSD, psilocybin, mescaline, and DMT.
Dr. Potnuru[/caption]
Paul Potnuru, MD
Assistant Professor
Anesthesiology, Critical Care and Pain Medicine
The John P. and Kathrine G. McGovern Medical School
The University of Texas Health Science Center at Houston
Dr. Miller[/caption]
Alex P. Miller, PhD
TranSTAR T32 Postdoctoral Fellow
Department of Psychiatry
Washington University School of Medicine
St. Louis, MO
MedicalResearch.com: What is the background for this study?
Response: Adolescent cannabis use is increasing in the United States. Prior research suggests that people who start using cannabis earlier are more likely to engage in problematic use and also experience greater mental health challenges and socioeconomic disadvantages overall. For example, children who begin using cannabis early are more likely to have behavioral problems and disorders and are more less likely to complete school.
In our study, we used data from the Adolescent Brain Cognitive Development (ABCD) Study, which is following nearly 12,000 kids across the nation to track behavior and brain development as well as health from middle childhood to young adulthood. We looked at what factors are associated with the initiation of cannabis use by age 12-14.
Dr. Hafezi-Moghadam[/caption]
Ali Hafezi-Moghadam, Ph.D., M.D
Director, Molecular Biomarkers Nano-Imaging Laboratory (MBNI)
Associate Professor of Radiology, Harvard Medical School
Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?
Response: “It is very easy to answer many fundamental biological questions” said Richard Feynman in his 1959 address, where he also offered his simple and ingenious solution: “you just look at the thing!”
Dr. Thomas[/caption]
Dr. Daniel Thomas MD PhD FRACP FRCPA
Program Leader, Blood Cancer
Precision Medicine Theme at the South Australia Health Medical Research Institute
Clinical Hematologist, Royal Adelaide Hospital
Associate Professor, Adelaide Medical School, The University of Adelaide
MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of CMML?
Response: Chronic myelomonocytic leukemia (CMML) is a rare, but increasingly frequent, clonal stem cell disorder that results in hyperproliferation of inflammatory monocytes, a form of white blood cells. It features both myelodysplasia and myeloproliferation. CMML is most often found in older adults and leads to anemia, decreased quality of life, and an increased risk of acute myeloid leukemia (AML).
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that stimulates production, growth, differentiation, activation, and function of myeloid cells (monocytes, neutrophils, and eosinophils). In the presence of RAS-pathway mutations, a greater sensitivity to GM-CSF contributes to the hyperproliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML). In CMML, greater sensitivity to GM-CSF stimulates excessive monocytic precursor proliferation.
The PREACH-M Trial, which stands for PREcision Approach to CHronic Myelomonocytic Leukemia, assesses the efficacy of lenzilumab in addition to azacitidine in treatment-naïve CMML participants with RAS-pathway mutations (KRAS, NRAS, CBL) and separately high dose ascorbate in participants with TET2 mutations who do not have RAS-pathway mutations. The study is currently underway and actively enrolling. It is being conducted and funded by the South Australian Health and Medical Research Institute (SAHMRI). 
Dr. Kamath[/caption]
Dr. Suneel Kamath MD
Gastrointestinal Oncologist
Cleveland Clinic
Senior Author on this research
MedicalResearch.com: What is the background for this study?
Response: Colorectal cancer rates in young people under age 50 are skyrocketing and have been for the last 3-4 decades. We really don’t understand why because most cases (probably around 70%) are not genetic or hereditary, just random, unfortunate events. We suspect that it is some exposure(s) like excess consumption of red meat, processed foods, sugar-sweetened beverages, excess antibiotic use altering the microbiome, rising incidence of obesity or some other factors. We really don’t know why yet.
Our study used a technology called metabolomics, the study of breakdown products and production building blocks for our bodies, to look for differences in colorectal cancer in young people versus people that are older that developed colorectal cancer. Because metabolomics measures how each individual interacts with the exposures in our environment like diet, air quality, etc., it is a way to bridge the gap between our nature (determined by genetics) and nurture (determined by our exposures).
Dr. Nowell[/caption]
W. Benjamin Nowell PhD
Director of Patient-Centered Research at Global Healthy Living Foundation
Columbia University in the City of New York
