An independent academic study provides a detailed analysis of deep well microplates and the significant levels of contamination found in more than 50% of the commercially available plates tested.
The study gives data on a large range of microplates from numerous manufacturers based in Europe, USA and China. Mass spectral data shows that persistent contamination from a range of compounds found in the raw polymer master batch continues to be evident in many of the microplates tested. The effect of extractables leached out of the deep well plates identified in this report depends on the exact application for which the plate was designed but is highly likely to significantly affect their performance and contaminate samples stored in them.
The authors of the report conclude it is likely that a low grade polypropylene was used in the production of a significant proportion of the deep well microplates that leached extractables when tested.

http://tinyurl.com/qaxn89a

A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas (PTC) – the most common form of thyroid cancer – has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive disease development. The findings also may help improve diagnosis and treatment. Investigators with The Cancer Genome Atlas (TCGA) Research Network identified new molecular subtypes that will help clinicians determine which tumours are more aggressive and which are more likely to respond to certain treatments. Their findings confirmed that PTCs are driven primarily by mutations in one of two cancer-associated genes: BRAF (and a particular mutation, V600E) or RAS. The work also detailed many differences between the two genetic types, particularly in signalling pathways that promote tumour development and growth.

The researchers developed a scoring system to reflect gene expression in the two PTC types, allowing them to characterize tumours and determine both the pathway a tumour uses to send signals and its relative aggressiveness. Where a tumour lies on a scale – called its thyroid differentiation score – can have important treatment implications because different tumor signaling properties can mean the cancer responds differently to particular therapies.

The study also showed that BRAF-driven tumors have a broader range of genetic complexity than previously thought, with distinct subtypes. The results suggest a need for a new classification system that more accurately reflects underlying genetic characteristics of the cancer.

Thyroid cancer is the fastest growing cancer in the United States, with more than 20,000 new PTC cases each year. Most thyroid cancers are slow-growing and treatable with surgery, hormone therapy and radioactive iodine. National Human Genome Research Institute

A study combining tumour cells from patients with breast cancer with a laboratory model of blood vessel lining provides the most compelling evidence so far that a specific trio of cells is required for the spread of breast cancer. The findings could lead to better tests for predicting whether a woman’s breast cancer will spread and to new anti-cancer therapies. The study was led by researchers at the NCI-designated Albert Einstein Cancer Center and Montefiore Einstein Center for Cancer Care (MECCC).

Maja Oktay, M.D., Ph.D.According to the National Cancer Institute, more than 232,000 American women developed breast cancer last year and nearly 40,000 women died from the disease. It is the most common cancer among women in the United States. Most breast cancer deaths occur because the cancer has spread, or metastasized, which means that cells in the primary tumour have invaded blood vessels and travelled via the bloodstream to form tumours elsewhere in the body.

In earlier studies involving animal models and human cancer cell lines, researchers found that breast cancer spreads when three specific cells are in direct contact: an endothelial cell (a type of cell that lines the blood vessels), a perivascular macrophage (a type of immune cell found near blood vessels), and a tumour cell that produces high levels of Mena, a protein that enhances a cancer cell’s ability to spread. Where these three cells come in contact is where tumour cells can enter blood vessels—a site called a tumour microenvironment of metastasis, or TMEM. Tumours with high numbers of TMEM sites (i.e., they have a high TMEM ‘score’) were more likely to metastasize than were tumours with lower TMEM scores. In addition, the researchers found that cancer tissues high in a form of Mena called MenaINV were especially likely to metastasize. (MenaINV refers to the invasive form of Mena.)

‘Those studies revealed new insights into how cancer might spread, but they didn’t necessarily show what is happening in patients,’ said study leader Maja Oktay, M.D., Ph.D., associate professor of pathology at Albert Einstein College of Medicine of Yeshiva University and attending cytopathologist at Montefiore.

Since then, the scientists have extended their research to include patients with breast cancer. In 2011, they published findings on 40 patients showing a correlation between high MenaINV levels and high TMEM scores. The present study combines results from those 40 patients plus an additional 60 patients. All 100 patients had been diagnosed with invasive ductal carcinoma and were being treated at MECCC. Invasive ductal carcinoma is the most common type of invasive breast cancer, accounting for 80 percent of cases. In this disease, the cancer has grown through the duct walls and into the surrounding breast tissue.
For the subset of more recent patients, the researchers assessed tumour cell behaviour—in particular, cancer cells’ ability to cross the endothelium (inner layer) of blood vessels. They obtained tumour cells using fine needle aspiration and placed them in a novel engineered tissue assay designed to replicate the endothelium of a blood vessel—the barrier that cells must cross so they can spread from a primary tumour to distant sites. Biopsied tumour tissue from all 60 new patients was fixed in formalin and embedded in paraffin so that TMEM sites in the tissue could be counted.
‘It’s critically important to learn more about the metastatic process so we can develop new ways to predict whether cancer will spread and identify new treatments.’

Breast cancer cells able to cross the endothelial layer in this assay were found to have higher MenaINV levels compared with the total population of patients’ aspirated cells. In addition, finding high levels of MenaINV correlated with finding high numbers of TMEM sites in paraffin biopsy specimens from the same patients. The TMEM ‘score’ for each biopsy specimen was calculated by counting the total number of TMEM sites observed within ten 400x magnification fields. Combining the results from all 100 patients showed that the findings were consistent across the three most common clinical subtypes of invasive ductal carcinoma.

‘These results confirm that TMEM sites and MenaINV are essential for the spread of breast cancer in humans,’ said Dr. Oktay. ‘They also imply that MenaINV expression and TMEM score measure related aspects of a commonly used mechanism that human breast cancers use to metastasize.’

Dr. Oktay noted that ‘the outcome for patients with metastatic breast cancer hasn’t improved in the past 30 years despite the development of targeted therapies. It’s critically important to learn more about the metastatic process so we can develop new ways to predict whether cancer will spread and identify new treatments.’ Albert Einstein College of Medicine

An exhaustive hereditary analysis of a large Louisiana family with vision issues has uncovered a new gene tied to an incurable eye disorder called retinitis pigmentosa, according to an examination led by scientists at The University of Texas Health Science Center at Houston (UTHealth). It is a family of eye diseases that affects millions worldwide.

The retina converts images into electrical signals that can be processed by the brain. It acts much like the film in a camera.  Retinitis pigmentosa damages this film (the retina) and its early symptoms include decreased night vision and peripheral vision.  Once it starts, the loss of vision is relentlessly progressive, often ending in blindness.

UTHealth’s Stephen P. Daiger, Ph.D., and his colleagues report their discovery of a new gene tied to retinitis pigmentosa, which brings the total of genes associated with this sight-threatening disease to more than 60. The gene is called hexokinase 1 (HK1).

This information is important because it helps affected families cope with the disorder, helps explain the biologic basis of these diseases and suggests targets for drug treatments and gene therapy, said Daiger, the report’s senior author and holder of the Thomas Stull Matney Ph.D. Endowed Professorship in Environmental and Genetic Sciences at UTHealth School of Public Health.

“The challenge now is to block the activity of these mutations and clinical trials are underway to do just that,” he said.

“Dr. Daiger is trying to make a breakthrough in potentially blinding diseases with no known treatments,” said Richard S. Ruiz, M.D., professor of ophthalmology and holder of the John S. Dunn Distinguished University Chair in Ophthalmology at UTHealth. “Right now, we address the symptoms of the disease and help patients make the most of their existing vision.”  

For approximately three decades, Daiger, a member of the Human Genetics Center at the UTHealth School of Public Health, has been following the progress of hundreds of families across the country with retinitis pigmentosa.  “We’ve found the cause of disease in 80 percent of the families we have studied,” Daiger said.  “Our goal is to find the cause in the remaining 20 percent.”

Equipped with the genetic profiles of family members, Daiger’s team has identified differences in the genetic makeup of those with the disease. The researchers also use family histories and DNA tests to glean information about the condition’s hereditary nature.

There are different types of retinitis pigmentosa and Daiger’s laboratory is focused on the autosomal dominant type. This means that only one parent needs the mutation in order to pass the disease to a child. This type accounts for about a third of all cases and many of its disease-causing genes have been discovered, several by Daiger’s research group.

“The story of the HK1 mutation is itself interesting.  What we found is a mutation present in families from Louisiana, Canada and Sicily.  Our evidence suggests the mutation arose in a common ancestor who lived centuries ago,” Daiger said.  “The mutation spread in Europe and North America, and may be common among Acadians in Louisiana.  This is called a founder mutation.” University of Texas Health Science Center

Scientists at IRB Barcelona in collaboration with researchers at the University of Barcelona observe that aggregates of 20 to 100 units of beta-amyloid have a structure that is the most harmful to neurons.

This is the first time that a method allows scientists to monitor aggregation while simultaneously detect a structural pattern responsible for the toxicity of beta-amyloid aggregation.

The researchers state that these studies are a step towards finding a therapeutic target for a disease which, to date, has no treatment.
The peptide —a small protein— beta-amyloid is strongly associated with Alzheimer’s disease; however, researchers are still looking for unequivocal proof that this peptide is the causal agent of the onset and development of the disease. The main obstacle impeding such confirmation is that beta-amyloid is not harmful when found in isolation but only when it aggregates, that is when it self-assembles to form the so-called amyloid fibrils

“We are not dealing with a single target, beta-amyloid alone, but with multiple ones because each aggregate of peptide, which can go from two units to 3,000 is a potential target. Determining the aggregate responsible for neuronal death is extremely complex and is one of the key issues for confirming or rejecting the hypothesis regarding beta-amyloid,” explains Natàlia Carulla, scientist at the Institute for Research in Biomedicine (IRB Barcelona) and principal investigator of the study. In their latest work, Carulla and collaborators describe a technique that has allowed them, for the first time, to distinguish different types of beta-amyloid aggregates formed during aggregation and in parallel to establish which is most toxic. The study provides further evidence in support of the hypothesis that neuronal death is caused by intermediate aggregates of beta-amyloid and reveals that the development of structure within these aggregates determines their ability to cause neuronal death.

The study shows that the most toxic aggregates are those formed by 20 to 100 units of beta-amyloid, known as intermediate aggregates or precursor aggregates of beta-amyloid fibrils. In contrast, the smaller aggregates of beta-amyloid and the amyloid fibrils, which can contain up to 3,000 units of the peptide, do not cause neuronal death. IRB Barcelona