Targeting Antioxidant Enzymes With Novel Therapeutics May Selectively Kill Off Metastasizing Cancer Cells

Main Category: Cancer / Oncology
Article Date: 25 Jun 2013 - 0:00 PDT Current ratings for:
Targeting Antioxidant Enzymes With Novel Therapeutics May Selectively Kill Off Metastasizing Cancer Cells

A new study by a team of researchers from the University of Notre Dame provides an important new insight into how cancer cells are able to avoid the cell death process. The findings may suggest a chemotherapeutic approach to prevent the spread of cancers.

Metastasis, the spread of cancer from one organ to other parts of the body, relies on cancer cells ability to evade a cell death process called anoikis, according to Zachary T. Schafer, Coleman Assistant Professor of Cancer Biology at Notre Dame. Metalizing cancer cells are able to survive anoikis, which normally results from detachment from the extracellular matrix. However, Schafer notes that the molecular mechanisms cancer cells detached from the extracellular matrix use to survive has not been well understood.

"This paper reveals that cancer cells that are detached from their normal environment, as they would be during metastasis, relay on the activity of antioxidant enzymes to facilitate their survival," Schafer said. "This class of enzymes is critical for neutralizing oxidative stress and function much like the compounds that are present in a variety of foods."

The paper describes a prominent role for antioxidant enzymes in facilitating the survival of breast cancer cells after detachment from the extracellular matrix. Conversely, the researchers report, silencing antioxidant enzyme expression reduced tumor formation.

"The results in this paper suggest that targeting antioxidant enzymes with novel therapeutics may selectively kill off metastasizing cancer cells," Schafer said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. The paper appears in the journal Cancer Research, which is the most frequently cited cancer journal in the world.

The researchers collaborated with Matthew Leevy in Notre Dame's in vivo imaging facility.

Other authors of the paper include doctoral student Calli Davison, rising junior Sienna Durbin, 2011 alum Matthew Thau, graduate student Victoria Zellmer, and Sarah Chapman, Justin Diner and Connor Wathen from the Notre Dame Integrated Imaging Facility.

University of Notre Dame

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Novel Therapeutic Approach To Treating Inflammation In Cardiovascular Disease

Main Category: Heart Disease
Also Included In: Immune System / Vaccines;??Cancer / Oncology
Article Date: 07 May 2013 - 1:00 PDT Current ratings for:
Novel Therapeutic Approach To Treating Inflammation In Cardiovascular Disease

Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs, an established treatment for cancer patients, could offer a novel therapeutic approach to decrease levels of inflammation in the atherosclerotic plaques of patients with cardiovascular disease (CVD), reported an abstract1 study at the International Conference on Nuclear Cardiology and Cardiac CT, May 5 to 8 in Berlin, Germany.

"Our results should act as a stimulus for further exploration of radionuclide based interventions in atherosclerosis. Ultimately such therapies might be used to lower the degree of inflammation in atherosclerosis which has the potential to reduce the occurrence of heart attacks," said Imke Schatka, the first author of the study from the Department of Nuclear Medicine at Hannover Medical School, Germany.

PRRT is a technique currently used to treat patients with metastatic neuroendocrine tumours (NETS), a diverse group of malignancies deriving from the neuroendocrine cell system (the most frequent locations being pancreas, small intestine and lung).

The discovery of over expression of somatostatin receptors (SSTR) on NET tumours first opened the way for development of radiolabelled somatostatin analogs to image tumours during PET/CT scans. DOTATATE is a somatostatin receptor (SSTR) ligand targeting SSTR-2, a receptor known to be expressed on 70% of NET tumours. Once tumours have been visualized, it is possible to target therapy by attaching the beta-emitter 1?? Lutetium (1??Lu) to the ligand.

Active inflammation has been widely implicated in the initiation, progression and disruption of vulnerable plaques, and consequently offers an emerging target for the imaging and treatment of atherosclerosis. "Since SSTR-2 receptors are also expressed on macrophages we speculated that DOTATATE-PET/CT might be used to detect vulnerable plaques and that a PRRT procedure could reduce inflammation in the arterial wall," explained Schatka.

For the current study, 11 patients (from a group of 165 undergoing PRRT for NET tumours) were retrospectively identified because they met the criteria of only receiving the beta emitter1??Lu treatment after undergoing two consecutive scans, with a third scan following treatment.

For each of the three scans, vessel wall uptake of the DOTATATE ligand was measured in six arterial segments of PET images (carotid, aortic arch, ascending, descending, abdominal aorta, and iliac arteries) and then the overall vessel uptake was determined for each individual patient.

Results showed that for the first scan the overall vessel uptake of the ligand correlated with the age of the patient (P<0.01), the number of calcified plaques (P<0.001) and furthermore was higher in subjects with hypercholesterolemia (p=0.04). No significant differences in overall vessel uptakes were found between scans 1 and 2, confirming reproducibility in the absence of treatment.

However, when treatment with the beta-emitter 1?? Lu-DOTATATE was delivered following scan 2, scan 3 showed significant reductions in the overall vessel uptake of the ligand when compared with both scan 1 (p=0.001) and scan 2 (p=0.004).

"Uptake of the ligand can be considered to be a measure of the quantity of SSTR receptors, which in turn is likely to correlate with the number of activated macrophages and the extent of the inflammatory process," explained Schatka. "Our results suggest that treatment has had a beneficial effect in reducing inflammation."

The next step, said Schatka, would be to get histological proof that reductions in inflammation really had been imaged with DOTATATE-PET/CT by looking at carotid artery samples removed from patients during routine surgery.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our heart disease section for the latest news on this subject. 1. I Schatka, T Wollenweber, C Haense, et al. Peptide receptor radionuclide therapy decreases inflammation in atherosclerotic plaques, as quantified by 68Ga-DOTATATE PET/CT. Abstract no 70100.
European Society of Cardiology Please use one of the following formats to cite this article in your essay, paper or report:

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Identification Of Inhibitors Of Human Proteins That Promote Tumor Formation May Lead To Novel Anti-Cancer Therapeutics

Main Category: Cancer / Oncology
Also Included In: Genetics
Article Date: 07 May 2013 - 1:00 PDT Current ratings for:
Identification Of Inhibitors Of Human Proteins That Promote Tumor Formation May Lead To Novel Anti-Cancer Therapeutics

Tumor repressor genes, which inhibit tumor formation, can be "turned off" due to undesirable molecular changes affecting the chromosomes on which the genes reside. Understanding and being able to control these alterations could lead to new approaches for activating or inactivating genes linked to cancer. A novel, high-throughput screening method used to identify agents that can block one chemical modifier that plays a key role in some forms of cancer is described in ASSAY and Drug Development Technologies, a peer-reviewed journal published from Mary Ann Liebert, Inc., publishers. The article is available on the ASSAY and Drug Development Technologies website.*

Jeffrey Simard, Matthew Plant, Renee Emkey, and Violeta Yu, Amgen, Inc. (Cambridge, MA) present an optimized, robust assay for screening large numbers of chemical compounds against EZH2 methyltransferase. This enzyme is part of a multi-protein complex which can alter the methylation state of chromosomal proteins. Increased EZH2 methyltransferase activity has been associated with reduced expression of tumor repressor genes.

In the article "Development and Implementation of a High-Throughput AlphaLISA Assay for Identifying Inhibitors of EZH2 Methyltransferase" the authors describe the use of AlphaLisa technology to detect methylation by EZH2 and emphasize that this approach should accelerate the identification of small molecule inhibitors for use as research tools and for development as novel anti-cancer therapeutics.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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