We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Antiangiogenic Treatment Improves Survival of Mice Models of Ovarian Cancer

By LabMedica International staff writers
Posted on 08 Dec 2014
Print article
A new antiangiogenic treatment with 3TSR has been shown to shrink tumors and improves effectiveness of chemotherapy.

Epithelial ovarian cancer is the most lethal cancer of the female reproductive organs, with more than 200,000 new cases and more than 125,000 deaths each year worldwide. Because symptoms tend to be vague, 80% of these tumors are not recognized until the disease has metastasized to other region of the body. The conventional treatment for advanced ovarian cancer includes high-dose chemotherapy, which frequently results in debilitating side effects and for which the five-year survival rate is only 35%.

Now new research in an animal model finds that a novel combination therapy, which couples low-dose chemotherapy with an antiangiogenic treatment, resulted in better survival rates compared with standard therapy. Led by investigators from Beth Israel Deaconess Medical Center (BIDMC; Boston, MA, USA) and the University of Guelph (Guelph, ON, Canada), the findings show that the agent, 3TSR (type-1-repeat), not only led to tumor regression, but also improved tumor blood flow and enabled more efficient delivery of much smaller and less toxic doses of chemotherapy.

The study was published online November 2014 in the Journal of the Federation of American Societies for Experimental Biology (FASEB) and will be published in the February 2015 print issue. “The five-year survival rate for ovarian cancer has changed very little over the past 20 years and new treatment options are urgently needed,” said co-senior author Jack Lawler, PhD, an investigator in BIDMC’s Center for Vascular Biology Research and professor of pathology at Harvard Medical School (Boston, MA, USA). “High-dose chemotherapy is usually required for the treatment of advanced ovarian cancer because the vascular supply to the tumor is inefficient and the cells inside the tumor have limited exposure to the chemotherapy drugs. Our results showed that when pretreated with an antiangiogenic agent, the animals responded to smaller, more frequent doses of chemotherapy, while still deriving more clinical benefit compared to current therapy protocols.”

Similar to many other types of cancer, ovarian cancer obtains nutrients and oxygen by inducing the growth of new blood vessels, a process known as angiogenesis. Antiangiogenic approaches to treat cancers attempt to disrupt the balance between promoters and inhibitors of angiogenesis, either by inhibiting proangiogenic factors or by increasing antiangiogenic molecules.

The Lawler laboratory at BIDMC investigates thrombospondin-1 (TSP-1), the first naturally occurring protein to be identified as an angiogenesis inhibitor. “What we’re trying to do is to boost the antiangiogenic side of the balance in order to deprive the tumor of blood supply and halt growth,” he stated.

Earlier research by Dr. Lawler and others had revealed that a portion of TSP-1 known as 3TSR interacts with another protein, CD36, which is found on the surface of endothelial cells that line the blood vessels. Combined, the two molecules cause endothelial cells to block growing and die, reducing blood vessel growth and disrupting the tumor’s ability to survive. The new findings revealed that 3TSR was acting on more than just endothelial cells and was directly inhibiting growth of ovarian tumor cells. “We think this might be occurring because, like endothelial cells, ovarian cancer cells contain CD36,” said Dr. Lawler. “The sensitivity of the tumor cells to 3TSR means that both endothelial and tumor cells can be targeted with a single reagent.”

Many of the blood vessels in tumors do not function correctly to distribute blood because they are not correctly formed; these blood vessels are destroyed during the early phase of antiangiogenic treatment, resulting in a period of time when blood flow to the tumor improves. In this new study, Dr. Lawler, and co-senior author Jim Petrik, PhD, of the University of Guelph, wanted to find out if 3TSR would enhance uptake of chemotherapy drugs delivered through lower-dose “metronomic” regimen.

The scientists performed a series of experiments in which mouse ovarian cancer cells were injected into an animal model and allowed to grow until they demonstrated features similar to patients with advanced disease, specifically, the spread of small tumors throughout the abdomen and the accumulation of fluid called ascites. “This is the advanced stage at which most women are first diagnosed with ovarian cancer,” explained Dr. Lawler. The investigators then treated the mice with either intermittent doses of standard high-dose chemotherapy or with more frequent doses of low-dose chemotherapy. In each case, the chemotherapy was either administered on its own or in combination with pretreatment with 3TSR.

The end result for the pretreated mice receiving the smaller chemotherapy doses was a smaller tumor, with improved blood supply. “We were able to exploit this enhanced blood supply to improve chemotherapy drug delivery to the tumor, with excellent clinical effect,” added Dr. Lawler. “The benefit of this approach is that we can create an environment that increases the efficiency of drug delivery, enabling the use of significantly lower doses of the chemotherapeutic agents and thereby reducing the side effects associated with the treatment. The clinical implications are significant. With this approach, patients could receive significantly smaller doses of chemotherapy drug while deriving greater clinical benefit, compared to current therapy protocols. We hope that this will soon be tested in clinical trials.”

Related Links:

Beth Israel Deaconess Medical Center 
University of Guelph


New
Gold Member
Pneumocystis Jirovecii Detection Kit
Pneumocystis Jirovecii Real Time RT-PCR Kit
Antipsychotic TDM Assays
Saladax Antipsychotic Assays
New
Urine Bone Markers Control
Lyphochek Urine Bone Markers Control
New
Urine Collection Container
Urine Monovette

Print article

Channels

Clinical Chemistry

view channel
Image: The new saliva-based test for heart failure measures two biomarkers in about 15 minutes (Photo courtesy of Trey Pittman)

POC Saliva Testing Device Predicts Heart Failure in 15 Minutes

Heart failure is a serious condition where the heart muscle is unable to pump sufficient oxygen-rich blood throughout the body. It ranks as a major cause of death globally and is particularly fatal for... Read more

Molecular Diagnostics

view channel
Image: Schematic overview of maternal biomarker discovery using cell-free RNA during pregnancy (Photo courtesy of Circulation Research (2024). DOI: 10.1161/CIRCRESAHA.124.325024)

Maternal Blood Test Identifies Congenital Heart Diseases in Fetus

Each year, around 1,000 children are born with a single ventricle heart defect (SVHD), a condition where one of the heart's lower chambers is underdeveloped, too small, or missing a valve.... Read more

Hematology

view channel
Image: QScout CBC will give a complete blood count in 2 minutes from fingerstick or venous blood (Photo courtesy of Ad Astra Diagnostics)

Next Gen CBC and Sepsis Diagnostic System Targets Faster, Earlier, Easier Results

Every hour is critical in protecting patients from infections, yet there are currently limited tools to assist in early diagnosis before patients reach a hospital. The complete blood count (CBC) is a common... Read more

Microbiology

view channel
Image: The InfectoSynovia test has the potential to revolutionize the diagnosis of periprosthetic joint infection (Photo courtesy of 123RF)

High-Accuracy Bedside Test to Diagnose Periprosthetic Joint Infection in Five Minutes

Periprosthetic joint infection (PJI) represents a significant global issue that is worsening as the number of joint replacements increases due to aging populations. In the United States alone, the anticipated... Read more

Pathology

view channel
Image

AI-Based Method Shows Promise for Pathological Diagnosis of Hereditary Kidney Diseases

Alport syndrome is a hereditary kidney disorder characterized by kidney dysfunction, sensorineural hearing loss, and ocular abnormalities. Early in the disease, patients experience hematuria, which is... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.