Biopeer

RNA can largely coordinate gene activity

Researchers at the Stanford University School of Medicine have discovered that RNA can coordinate gene activity across vast portions of the human genome – a cell’s genetic blueprint. The study also suggests that RNA may play an important role in cancer development and stem cell maintenance. The researchers used a new type of gene chip called a tiling array in their study. “We were surprised to find that at least one of these molecules can suppress genes on a completely different chromosome. This opens up the whole genome to potential regulation by ncRNAs,” said Howard Chang, M.D., Ph.D., assistant professor of dermatology at Stanford University School of Medicine. “I like to think of it as genomic scuba diving," said John Rinn, a postdoctoral scholar in Chang's laboratory. "It gives us an up-close, unbiased view of what's actually happening at the chromosomal level." The findings of this study will have important implications for cancer therapies and stem cell research.

Scientists at the Rockefeller University, Howard Hughes Medical Institute and the National Cancer Institute found that the protein, ATM, which is vital for helping repair double-stranded breaks in DNA of immune cells, is also a part of a system that prevents damage from being passed on during cell division. The findings of the study show that in the absence of ATM protein, the chromosomal breaks created during a process immune cells undergo called V(D)J recombination go unrepaired, and checkpoints that normally prevent the damaged cell from replicating are lost. “I think it's important to understand them because eventually we might be able to prevent these dangerous chromosome fusions,” said Michel Nussenzweig, Sherman Fairchild Professor and head of the Laboratory in Molecular Immunology.

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Medipattern’s B-CAD to improve breast cancer diagnosis

Mammography and Ultrasound Specialists (MUS) of Texas announce the installation of Medipattern’s B-CAD. According to MUS, the B-CAD is capable of generating a more thorough record of the diagnostic breast ultrasound procedure, which would improve consistency from reader to reader. During a typical examination, the saved images are sent via DICOM to a CAD module located on a network, where they are analyzed. CAD uses standard imaging techniques to determine the shape, size, and orientation of each lesion at a deeper level than can be displayed on screen. The software analyzes images of lesions from the breast ultrasound, segments them, and generates BI-RADS scores. The software can compile all the information into a natural language report, including the physician’s findings.

Researchers at the Seattle Cancer Care Alliance (SCCA) and the University of Washington Medical Center found that using breast scan software to enhance magnetic resonance imaging (MRI) reduces the number of false positive identifications of malignant tumors. The team examined 154 breast lesions that were deemed suspicious by radiologists and visible only on MRI. The findings were compared to the new findings using computer-aided enhancement (CAE) software. According to the study, false positives were reduced by 23% when CAE was used at its highest enhancement level. “In summary, our findings suggest that CAE has the potential to improve the discrimination of benign and malignant breast MRI lesions,” said Teresa Williams, M.D., of the Seattle Cancer Care Alliance. The software is already commercially available and has been shown useful in reducing the false positive rate of breast MRI.

A study conducted by Russell N. Low, medical director of the Sharp and Children’s MRI Center in San Diego, found that diffusion-weighted imaging (DWI) could help radiologists significantly improve the accuracy of conventional MR imaging of peritoneal metastases (cancer in the membrane that lines the abdominal wall). The study was conducted on 24 oncology patients who underwent preoperative abdominal MRI to affirm Dr. Low's suspicions about the diagnostic benefit of adding DWI to the protocol. Based on 153 sites of confirmed peritoneal tumor, DWI/MRI identified 141 sites with 14 false positives. Its sensitivity, specificity, and accuracy were 92%, 92%, and 93%, respectively. MRI alone was 78% sensitive, 86% specific, and 82% accurate.

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Gene therapy for Parkinson's disease set for clinical trials

A study, recently published in The Lancet, found that a gene-bearing virus injected into the midbrains of 12 patients suffering from Parkinson's disease showed motor function improvements. “The safety and effectiveness clearly indicate that this is something worth pursuing,” said Michael Kaplitt, neurological surgeon at New York-Presbyterian Hospital. The researchers used a harmless virus to transport a gene that codes for an enzyme, called glutamic acid decarboxylase, into neurons in the area of the brain called the subthalamic nucleus. The gene prompted the subthalamic cells to produce gamma-aminobutyric acid, which made the neurons settle down and restore motor function. The 12 subjects were monitored for a period of one year and their motor function showed up to 65% improvement. The researchers are hoping to have a full scale clinical trial for the gene therapy set by the year's end.

Peregrine Pharmaceuticals, a clinical stage biopharmaceutical company, recently announced the initiation of a new Phase II clinical trial designed to evaluate the safety and efficacy of its tumor necrosis therapy (TNT) agent – Cotara – in patients with glioblastoma multiforme (GBM), a deadly form of brain cancer. In a pilot study, Cotara has demonstrated a 58% increase in the expected median survival time in a group of 28 patients suffering from recurrent late stage glioblastoma multiforme. “We anticipate that positive data from this study, together with dosimetry and dosing data being collected in ongoing U.S. Cotara trials, will help us determine the optimal design of Phase III product registration trials,” said Steven W. King, president and CEO of Peregrine.

Generex Biotechnology Corporation recently announced at the 67th Scientific Sessions of the American Diabetes Association, that the company is initiating a Phase III clinical trial of Generex Oral-lyn, an oral insulin spray product. The six month trial would include 750 type 1 diabetes mellitus patients. “We enter this trial with a great deal of confidence that the results will validate the successful outcomes that patients have experienced in previous clinical trials,” said Anna Gluskin, president and CEO of Generex.

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Renewed hope for treating type 1 diabetes

Biotechnologists at the Norwegian University of Science and Technology (NTNU) developed a new alginate capsule that may keep the body’s immune system from recognizing and attacking insulin-producing cells implanted into diabetic patients. The new gel capsule, called Trondheim Alginate Microcapsule (TAM), is designed to camouflage the alien insulin-producing cells from cells in the body's immune system. "If the capsule is to function well, it needs to be suitably porous so that it allows nutrients to enter the insulin cells while insulin is transported out," said Yrr Morch, research fellow at NTNU. "It must be suitably small, and it must be stable so it doesn’t swell and gradually break. We seem to be in the process of solving all these challenges." If the gel capsule becomes a medical reality, it could prevent some diabetes patients from having to take immunosuppressants, which carry a high risk of infections and cancer.

A study conducted by Amylin Pharmaceuticals, and Eli Lilly and Company, found that the BYETTA (exenatide) Treatment sustained improvements in patients' blood sugar levels and progressive weight loss through three and a half years of injection therapy. In this study, 151 people with type 2 diabetes took part in a 30-week placebo-controlled trial. After three and a half years, participants using BYETTA (10 mcg) along with oral medication showed reductions in blood sugar. The drug also showed improvements in the cardiovascular risk factors associated with type 2 diabetes, and associations with weight loss.

Researchers at Malmo University Hospital in Sweden, found that adding a teaspoon of cinnamon to a bowl of rice pudding lowered the post-meal blood sugar rise in a group of 14 healthy people. Joanna Hlebowicz, main author of the study, also found that people with type 2 diabetes who added cinnamon in their diet for 40 days tended to show a dip in blood sugar and cholesterol. The findings, published in the American Journal of Clinical Nutrition, suggest that cinnamon may have the potential to help control blood sugar surges in diabetics.

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Sea-squirt derived drug shows potent anti-tumor activity

A study at the Instituto Nazionale Tumori in Milan, Italy, found that a sea-squirt derived drug called trabectedin (ecteinascidinin-743) shows anti-tumor activity in more than half of the patients with a specific type of cancer. The researchers studied the effect of trabectedin on 51 patients with advanced pre-treated myxoid liposarcomas. They found two patients' tumors disappeared completely and 24 patients showed a partial response. According to the researchers,  “If the results of this analysis are reproduced in ongoing prospective studies, myxoid sarcoma would represent a uniquely sensitive subgroup to trabectedin treatment in the heterogeneous family of soft-tissue sarcoma.” The scientists are now studying the selective mechanism of the action of trabectedin and forming prospective studies to assess the drug in preoperative and metastatic conditions.

Leire García Navarro, a researcher in the School of Pharmacy at the University of Navarra, discovered a new treatment which slows the growth of colon and liver cancers. The researcher used genetic therapy with non-viral vectors to transfer genetic material to cancerous cells. Because it's non-viral, the treatment can be applied repeatedly as it does not generate immunity. Ms. Navarro prepared a new pharmaceutical format called 'lipopolyplex,' which aids the genetic material in penetrating damaged cells and allows drug release in tumorous organs. Experimentation with this new drug in mice showed a slower rate of tumor growth than in animals subjected to other procedures.

Dr. John Maris, of The Children's Hospital of Philadelphia, reviewed new approaches to treatments for children whose neuroblastoma has relapsed in an aggressive form in the June 23 issue of the Lancet. Neuroblastoma can range from a relatively easy cancer to treat, to a very aggressive cancer. Dr. Maris argues that pre-defining a patient's risk level could help oncologists design the best treatment, avoiding the twin pitfalls of under-treating or over-treating any given child. “Our goal is to match the most appropriate treatment with precise molecular targets in biological pathways, so we can intervene to stop neuroblastoma in its tracks,” said Maris.

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Ultra deep sequencing identifies previously undetectable HIV drug-resistant variants

Researchers at the Yale School of Medicine have identified previously undetectable, rare drug-resistant HIV variants using an innovative genome sequencing technology. The study analyzed 258 blood samples taken from HIV infected individuals before treating them with the drug. “We found that the fraction of HIV patients that harbored resistance mutations is at least twice as high as previously thought,” said Michael Kozal, M.D., Yale University School of Medicine. These low frequency resistant viral strains were not detectable by resistance testing methods currently used in the clinic. “Ultra Deep Sequencing provides an essential tool for research on viral diseases and their treatments," said Egholm Michael, vice president of research and development at 454 Life Sciences. "The ability to use 454 Sequencing to detect rare viral mutations is a crucial research tool to better understand the early stages of HIV drug resistance.” This finding will prove useful in the future to better understand the antiretroviral drug combinations that have the ability to suppress these resistant HIV strains, leading to better clinical responses in patients.

According to a study, published in the June 21 issue of the New England Journal of Medicine, patients suffering from both hepatitis B and HIV should not take the hepatitis-fighting drug Baraclude. Baraclude was approved as a drug to fight hepatitis B in early 2005. While Baraclude is very effective in treating hepatitis B, the study revealed that it also undermines the potency of combination drug therapies for HIV. “The active site (of drug action) – a polymerase enzyme – is similar on HIV and hepatitis B,” explained Chloe Thio, associate professor of medicine at Johns Hopkins University School of Medicine. “This means that if you are going to go ahead and treat for hepatitis B, you better be screening for HIV, too,” said. Michael Horberg, director of HIV/AIDS policy at Kaiser Permanente in Santa Clara, Calif.

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Researchers identify key genetic themes that keep stem cells in flexible state

A team of Canadian scientists identified 1,155 genes under the control of a single gene called Oct4, the master regulator of the stem cell state. Researchers developed a comprehensive definition of stem cells on a molecular basis such that stem cells keep their DNA packed in a flexible format, keep cell division tightly controlled, prevent signals that trigger death and repair DNA. “You could call this a 'theory-of-everything' for stem cells,” said Michael Rudnicki, senior scientist at the Ottawa Health Research Institute. To conduct the study, researchers applied rigorous analysis methods using data from Stem Base, the largest stem cell gene expression database in the world. "These findings may help us to understand how the key genes which control cell fate are regulated, and how, when dysregulated, they can lead to disease," said Pearl Campbell, lead author of the study. "This may ultimately allow us to develop targeted therapies to stimulate adult stem cells within our own bodies to repair damaged tissues, and may provide further areas of exploration for the treatment of cancer."

Researchers at Children's Hospital of Boston found a new way to increase stem cell production in blood, which might pave the way for a potential treatment for leukemia patients who undergo chemotherapy or bone marrow transplants. The researchers demonstrated that a stable analog of prostaglandin is capable of enhancing the blood-forming system, both during embryonic development and after the system has been damaged. The prostaglandin, dmPGE2, was discovered after screening more than 2,500 chemicals in zebrafish. “The fact that we confirmed the zebrafish discovery in a mammalian system suggests it may also be applicable in humans,” said Wolfram Goessling, MD, PhD, of the Children's Hospital of Boston. The hospital is planning to begin a clinical trial of this drug in 2008.

Scientists at the University of Rochester are testing a new innovation in biotherapy that alters a common childhood respiratory virus, called the adenovirus, to destroy cancer cells. The researchers designed a new version of the adenovirus to selectively attack cancer cells more frequently than other cells, and it is expected to have powerful potential. "Our concept is very promising and we hope it will open the door to safer and more effective treatments," said Baek Kim, associate professor of Microbiology and Immunology at the University of Rochester Medical Center. "If this works, the most exciting part is that patients would be able to generate their own internal weapons to kill the malignant cells without having to endure a toxic element such as chemotherapy."

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Steroid treatment might reduce risk of rheumatoid arthritis related lymphoma

The findings of a study, presented at the Annual European Congress of Rheumatology (EULAR) 2007, suggest that the risk of rheumatoid arthritis related lymphomas are significantly reduced in patients treated with oral steroid treatment for more than two years. The most pronounced steroidal effect was observed in the diffuse large B-cell lymphoma subtype. "The pros and cons of corticosteroid treatment in rheumatoid arthritis have been a subject of much debate, and long-term steroid treatment is often limited as a result of concerns about various side effects," said Eva Baecklund of the Uppsala University Hospital in Sweden. "Patients with severe rheumatoid arthritis are at increased risk for malignant lymphomas (cancer in the immune system), but long-term steroid treatment may decrease this risk." In this study, the steroid treatment outcome was not associated with the presence of the Epstein-Barr virus in lymphomas.

A study conducted at the Karolinska Institutet in Sweden showed that consuming three alcoholic drinks per week decreases the risk of developing rheumatoid arthritis. The researchers conducted a study of incident rheumatoid arthritis cases among 18 to 70-year-olds in a defined area of Sweden. DNA from 1,204 cases and 871 controls was examined to detect the presence of HLA-DRB1 SE alleles, a marker indicating a genetic risk factor for rheumatoid arthritis. "These are very interesting findings and are the first observation, from epidemiological data, which now should be confirmed by further clinical studies before a firm conclusion can be achieved,” said Tore Kvien, president of EULAR. These findings could prove useful in understanding the effects of lifestyle on the risk of developing rheumatoid arthritis, and prove useful in a potential treatment based on the beneficial effects of alcohol.

A recent study that used data from a study conducted in the early '90s in Spain found that breast feeding for 13 or more months reduced women's risk of developing rheumatoid arthritis compared to those who had never breast fed. "This study specifically highlights the potential of naturally-induced hormones in protecting individuals from developing RA (rheumatoid arthritis) in the future," said Mitra Keshavarz of the Malmö Hospital University in Sweden.

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Fluorescence technology may provide 3-D image of breast cancer tumors

Researchers at the University of Pennsylvania used fluorescence diffuse optical tomography (FDOT) to create 3-D images of breast cancer tumors in patients. The technique depends on the presence of fluorophore molecules in tissue, which re-radiate fluorescent light. The images demonstrated significant tumor contrast in breast tissue, paving the way for improved optical diagnostic tools. FDOT may provide information about tumor physiology like oxygen, pH, and calcium concentrations in tissue. "The potential uses of optical fluorophores bear close resemblance to the use of contrast agents in PET and MRI," said Arjun Yodh, professor in the  Department of Physics and Astronomy, University of Pennsylvania. "Successful FDOT represents a critical first step towards application of molecular imaging probes such as dyes and molecular beacons that bind to tumor-specific receptors in deep tissue, a current direction for biomedical optics research.” 

A study conducted in Korea found that patients under the age of 35 have a worse breast cancer prognosis than those between the ages 35 and 50. The study, published in the Journal of Clinical Oncology, found that young cancer patients were more likely to have larger tumors, and have a higher likelihood of positive lymph nodes and hormone receptor-negative cancer. The data showed that in the case of hormone receptor-positive breast cancer, the survival rate of younger women was less than women older than 35. Adjuvant (post-surgery) tamoxifen appeared less effective among younger women with hormone receptor-positive breast cancer. It is yet to be seen whether the results of the study can be generalized to more heterogeneous populations.

Researchers at the Center for Cellular and Molecular Biology at Deakin University found a rogue cell type that may cause cancer cells to move out of the breast and into surrounding tissue. Stephanie Lebret, a researcher at Deakin University, identified the rogue cells with a model of the breast that used cultured cells grown outside the body. "We found that fibroblasts, a cell type that surrounds the mammary gland, help normal breast cells develop, but when these fibroblasts are abnormal, they cause breast cancer cells to change and migrate," said Ms. Lebret. "With further study, it is possible that targeting of this factor may one day be used to prevent the spread of breast cancer."

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Side effects from smallpox vaccine linked to genetic factors

The findings of a study published in The Journal of Infectious Diseases revealed that certain adverse events related to smallpox vaccination are linked to genetic factors. Dr. Samuel L. Stanley Jr. and colleagues studied 346 individuals who had undergone smallpox vaccination, out of which 94 developed fevers after vaccination. The researchers analyzed 19 gene clusters (called haplotypes) that are linked to different immune responses to viral infections. The study identified the link between fevers after immunization with live virus particles, as in smallpox vaccine, and specific gene clusters in the interleukin-1 (IL-1) gene complex on chromosome 2, and the interleukin-18 gene on chromosome 11. "Vaccines are the safest and most effective way to prevent a number of very important childhood and adult diseases," said Dr. Stanley. "Our work is designed to identify ways we might make vaccines even more acceptable in the future by discovering ways to further reduce the chance of minor adverse events."

The U.K. Joint Committee on Vaccination and Immunisation (JCVI) is expected to endorse Gardasil, a vaccine against the virus that causes most cervical cancer. The decision by the JCVI is considered delayed by some, as the U.S. Food and Drug Administration (FDA) approved Gardasil last summer. The (JCVI) will start administering the vaccine in 12-year old girls, starting next year. The vaccine protects against infections from the human papilloma virus (HPV), of which two strains – HPV-16 and HPV-18 – account for 70% of cervical cancer. Strains HPV- 6 and HPV-11 account for about 90% of genital warts. Hugh McKinney, spokesperson for the National Family Campaign, was of the opinion that vaccination against a sexually transmitted virus would encourage sexual behavior of minor girls. "I don't think girls are thinking about cancer when they decide whether or not to have sex," said Syed Ahmed, member of the JCVI, in response to similar remarks. "They are more concerned about becoming pregnant or catching chlamydia or gonorrhoea."

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