Blood Bank
Study suggests donated blood should not be stored for more than three weeks. A new study of hospital patients indicates that transfusion of donated blood more than three weeks old can result in impaired blood vessel function. The research also suggests why older blood might be detrimental to patient health: a deficiency in nitric oxide, a chemical messenger that relaxes blood vessels.
In the study, 43 Emory University Hospital patients were set to receive cross-matched red blood cells for clinical indications. Members of the group were randomly chosen to receive either fresh (<10 days old) or aged (>three weeks old) red blood cells. On average, they received the equivalent of two units (900 milliliters).Researchers tested blood vessel function by measuring flow-mediated dilation (FMD). Using ultrasound, they tested how much a blood vessel in the arm opens up after a blood pressure cuff is first tightened, and then removed. FMD is an indicator of the health of the endothelial lining of the blood vessels and is dependent on the sufficient production of N2O, which is generated by the blood vessels’ endothelial lining and causes them to relax.
Healthy individuals can have flow-mediated dilation of up to 10%; the average for the hospitalized group was 5%. Patients receiving aged blood saw their FMD halved to 2.4% 24 hours after transfusion; patients receiving fresh blood saw no significant change.
Although blood banks tend to use a “first-in, first-out” policy, limiting storage time could reduce the blood supply. One alternative: reserve fresh blood for patients at highest risk for cardiovascular problems.
HIV
Investigators report toddler “functionally cured” of HIV. A two-year-old child born with HIV and treated with antiretroviral drugs beginning in the first days of life no longer has detectable levels of virus despite not taking HIV medication for 10 months, according to findings presented at the Conference on Retroviruses and Opportunistic Infections (CROI). The case study was presented by researchers from the Johns Hopkins Children’s Center and the University of Massachusetts Medical School. It is the first well-documented case of an HIV-infected child who appears to have been functionally cured of HIV—determined to be without detectable levels of virus and any signs of disease.
In July 2010, the child was born to an HIV-infected mother who had not received antiretroviral therapy. Because of the high risk of HIV exposure, the infant was started at 30 hours of age on liquid antiretroviral treatment, a combination of three anti-HIV drugs: zidovudine, lamivudine, and nevirapine. HIV infection was confirmed through blood samples obtained on the second day of life.
The infant was discharged from the hospital at one week old and placed on liquid antiretroviral therapy. Additional plasma viral load tests performed on blood from the infant over the first three weeks of life again indicated HIV infection. However, by Day 29, viral load was less than 50 copies of HIV per milliliter of blood.
The baby remained on the prescribed antiretroviral treatment regimen until 18 months of age, in January 2012. When the child was seen by medical professionals in fall 2012, blood samples revealed undetectable HIV levels and no HIV-specific antibodies. Further research is needed to understand whether the outcome can be replicated in clinical trials.
Cancer
NIH scientists identify molecular link between metabolism and breast cancer. A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer, according to new findings by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and their colleagues. Metabolic imbalance is often caused by elevated carbohydrate intake, which can lead to over-activating a molecule called C-terminal binding protein (CtBP). This over-activation, in turn, can increase the risk of breast cancer.
It has been known that there is a strong link between obesity and cancer, but the mechanism behind this link has been uncertain. A previous study had suggested that obesity and weight gain may contribute to breast cancer by decreasing the level of the BRCA1 tumor suppressor gene expression in response to high carbohydrate intake.
The new study analyzed prior gene expression studies to determine if gene pathways, repressed by CtBP, were diminished in breast cancer patients who suffered from more aggressive clinical outcomes. Researchers found that, under conditions where they decreased the levels of CtBP, DNA repair increased and the cells developed stability and growth control. They determined that gene pathways targeted by CtBP were also disrupted in more aggressive breast cancers. They also showed that a small molecular inhibitor previously shown to bind to CtBP was able to reverse the gene-repressive effects of CtBP in breast cancer cells even under conditions of high carbohydrate feeding.
Industry News
Ventana and Biocare Medical sign p63 license agreement to aid in the differential diagnosis of benign and malignant prostate lesions. Ventana Medical Systems, Inc., a member of the Roche Group, and Biocare Medical, LLC, have entered into a non-exclusive license agreement to allow Biocare access to certain patents and materials related to p63 diagnostics in the research and IVD field. In parallel, Biocare and AsymmetRx Medical, Inc., have settled a dispute related to the p63 technology. As part of the settlement, Biocare has gained a worldwide license through Ventana to distribute p63 (4A4) mouse monoclonal primary antibody in both the research and IVD market, and AsymmetRx has agreed to terminate all patent infringement litigation. AsymmetRx holds the exclusive, worldwide license under the Harvard Medical School patent filings for the use of the p63 antibody as an aid in the diagnosis of prostate and other cancers.
The p63 gene was discovered in the Harvard lab of Frank McKeon, PhD, and the p63 cancer diagnostic test was invented by a collaboration of labs at Harvard Medical School, Dana Farber Cancer Institute, and the Brigham and Women’s Hospital. p63 protein is highly expressed in prostate, breast, bladder, and lung tissue, and the p63 (4A4) mouse monoclonal antibody has been useful in the differentiation of benign and malignant lesions in conjunction with morphological findings.
