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
LGC Clinical Diagnostics

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


Gold Member
Serological Pipet Controller
PIPETBOY GENIUS
Antipsychotic TDM AssaysSaladax Antipsychotic Assays
New
Anti-Secukinumab ELISA
LISA-TRACKER anti-Secukinumab
New
Herpes Virus Test
Human Herpes Virus (HHV-6) Real Time PCR Kit

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

Hematology

view channel
Image: The smartphone technology measures blood hemoglobin levels from a digital photo of the inner eyelid (Photo courtesy of Purdue University)

First-Of-Its-Kind Smartphone Technology Noninvasively Measures Blood Hemoglobin Levels at POC

Blood hemoglobin tests are among the most frequently conducted blood tests, as hemoglobin levels can provide vital insights into various health conditions. However, traditional tests are often underutilized... Read more

Immunology

view channel
Image: Under a microscope, DNA repair is visible as bright green spots (“foci”) in the blue-stained cell DNA. Orange highlights actively growing cancer cells (Photo courtesy of WEHI)

Simple Blood Test Could Detect Drug Resistance in Ovarian Cancer Patients

Every year, hundreds of thousands of women across the world are diagnosed with ovarian and breast cancer. PARP inhibitors (PARPi) therapy has been a major advancement in treating these cancers, particularly... Read more

Microbiology

view channel
Image: HNL Dimer can be a novel and potentially useful clinical tool in antibiotic stewardship in sepsis (Photo courtesy of Shutterstock)

Unique Blood Biomarker Shown to Effectively Monitor Sepsis Treatment

Sepsis remains a growing problem across the world, linked to high rates of mortality and morbidity. Timely and accurate diagnosis, along with effective supportive therapy, is essential in reducing sepsis-related... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.