Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory University
Reporter: Aviva Lev-Ari, PhD, RN
Van Andel, Emory to Develop Early Pancreatic Cancer Dx
NEW YORK (GenomeWeb News) – Van Andel Institute and Emory University researchers will use a $2.3 million grant from the National Cancer Institute to fund an effort to develop new biomarker tools that can aid in the early diagnosis of pancreatic cancer.
The Van Andel and Emory team plan to use gene expression studies and a shotgun glycomics approach to try to develop useful diagnostic tests for a certain carbohydrate structure that is prevalent in most, but not all, pancreatic cancer tumors.
In a shotgun glycomics approach, all of the glycans from a sample are tagged with a fluorescent tag and separated from each other to create a tagged glycolipid library. This library will be developed through gene expression studies on the tumor tissue.
“One of the most common features of pancreatic cancers is the increased abundance of a carbohydrate structure called the CA 19-9 antigen,” Brian Haab, head of Van Andel’s Laboratory of Cancer Immunodiagnostics, said in a statement.
Because CA 19-9 is attached to many different proteins that the tumor secretes into the blood it is used to confirm diagnosis of and to manage disease progression of pancreatic cancer. Tests for this structure have not yet been useful for early detection or diagnosis, however, because around 20 to 30 percent off incipient tumors produce low levels of CA 19-9.
“The low levels are usually due to inherited genetic mutations in the genes responsible for the synthesis of CA 19-9,” Haab explained. “However, patients who produce low CA 19-9 produce alternate carbohydrate structures that are abnormally elevated in cancer.”
This study aims to characterize and identify these glycans to improve the ability to detect cancer in patients with low CA 19-9 levels.
The research will integrate the use affinity reagents, a type of proteins called lectins, as well as shotgun glycomics, to detect these glycan structures and develop a diagnostic test for pancreatic cancer.
Because pancreatic cancer tends to spread before it is diagnosed and because of its resistance to chemotherapy, it has one of the lowest survival rates of any major cancer. It will affect more than 43,000 Americans in 2012 and will kill more than 37,000, according to NCI.
“We anticipate these new approaches advancing pancreatic cancer diagnostics as well as benefiting other glycobiology research in cancer,” Haab said.
Researchers from the Fred Hutchinson Cancer Research Center, Palo Alto Research Center, the University of Georgia, and the University of Pittsburgh Medical Center also are participating in the project.
Related Stories
- MSU to Use $1.5M Award to Study Spread of HER2 Breast Cancers
September 21, 2012 / GenomeWeb Daily News
- Trovagene, MD Anderson Team on KRAS Mutation Research
July 3, 2012 / GenomeWeb Daily News
- Multiplicom Receives $250K Grant to Develop Genetic Fetal Aneuploidy Test
June 6, 2012 / GenomeWeb Daily News
- DiaGenic Gets $1.3M Grant for Alzheimer’s Dx Project
May 16, 2012 / GenomeWeb Daily News
- PROOF Centre Uses Genome BC Funds for COPD Dx
April 17, 2012 / GenomeWeb Daily NewsSOURCE:
[…] Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory … […]
[…] Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory … […]
[…] Pancreatic cancer genomes: Axon guidance pathway genes – aberrations revealed Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory … […]
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette