Researchers at Okayama demonstrate that injection of a virus solution followed by tumour removal can eradicate cancer metastasis in lymph nodes without the need for preventative surgery.
While early-stage gastrointestinal cancers can be treated non-surgically, once the cancer has invaded to a particular depth, preventative – ‘prophylactic’ – surgery is routine. The frequency of lymph node metastasis increases significantly once the cancer has penetrated the submucosal layers, and as there is no way of determining whether the cancer has metastasized in the lymph nodes they will be surgically removed just in case. Now researchers at Okayama University and the University of California in San Diego have demonstrated that injection of a viral solution can eradicate lymph node metastasis making prophylactic surgery unnecessary.
To treat early stage cancers a saline solution is injected creating a fluid cushion, which raises and isolates the tumour. The tumour is then readily removed by equipment through a standard endoscopic viewing tube inserted in the gastrointestinal tract. However if the cancer has already penetrated the submucosal layer it will be prone to relapse in the lymphatic system.
Toshiyoshi Fujiwara and his colleagues adapted the standard endoscopic treatment by injecting a solution of Telomelysin – a virus known to kill epithelial and mesenchymal malignant cells – instead of saline solution.  They tested the treatment in a mouse model, injecting green-fluorescent-protein-labelled cancer cells into the submucosal layers of the rectum, which developed lymph node metastasis. Fluorescence imaging showed that cancer cells were successfully eliminated by the treatment with virus solution, in contrast to mice treated with saline solution instead. In addition, treated mice showed no relapse four weeks after the treatment
In their report of the results the researchers conclude, “From a clinical view point, this new, simple, and robust strategy is a more realistic and promising bench-to-bedside translation than prophylactic surgery for ablation of potential lymph node metastases in early gastrointestinal cancer patients.”
Early stage gastrointestinal cancers are defined by the level of the cancer invasion reaching no further than the submucosa. Endoscopic treatment removes these tumours by dissecting the submucosal layers.
For esophageal gastric and colorectal submucosally invaded cancers, the frequency at which the cancer is found to metastasize in the lymph nodes is approximately 10 to 20%. The lymphatic system distributes fluids, proteins, chemicals, cells and drugs. This makes it a major pathway for the spread of metastatic cancers so that cancerous invasion of the lymphatic system is particularly problematic. It is very difficult to determine whether the cancer has metastases in the lymph nodes. As a result lymph node surgery just in case is routine when treating esophageal gastric and colorectal submucosal cancers, even though in many cases it may not have been necessary.
Previous research has demonstrated that certain viruses replicate in cancer cells and break them down, and may be developed for cancer treatments. The researchers further exploited the role of the lymph system in mediating proteins and fluids, a function which makes it more prone to exposure to a virus injected in the surrounding area. They experimented with Telomelysin – a telomerase-dependent, tumour-killing replicating adenoviral agent (OBP-301). The virus is known to kill epithelial and mesenchymal malignant cells.  
The researchers first tested the virus on green-fluorescent-protein-labelled colorectal cancer cell lines with. Using fluorescence imaging, they observed rapid cell death in response to injection with the virus while there was no such response in cell lines treated with mutant strains of the virus that had replication deficiencies.
The researchers demonstrated how their treatment exploited the lymph node function using mouse models injected with red-fluorescent-protein-labelled lymph node metastasized cancer cells. After six days the virus labelled with green fluorescent protein was injected and fluorescence images showed the position of the virus coincided with the metastatic foci in the lymph nodes.

Kikuchi S, Kishimoto H, Tazawa H, Hashimoto Y, Kuroda S, Nishizaki M, Nagasaka T, Shirakawa Y, Kagawa S, Urata Y, Hoffman RM, Fujiwara T: Biological Ablation of Sentinel Lymph Node Metastasis in Submucosally Invaded Early Gastrointestinal Cancer. Mol Ther. 2014 Dec 19.

A Dartmouth study suggests that it may be possible to use Diffuse Optical Spectroscopic Tomographic imaging (DOST) to predict which patients will best respond to chemotherapy used to shrink breast cancer tumours before surgery. These findings could eliminate delays in effective early treatment for tumours unlikely to respond to neoadjuvant chemotherapy (NAC).

Breast cancer is the most common non-skin cancer in women worldwide, and the second leading cause of women’s cancer mortality in the United States. A common treatment strategy after diagnosis is to shrink breast cancer tumours larger than 3 centimetres with a 6- to 8-month course of NAC prior to surgery. Clinical studies have shown that patients who respond to NAC have longer disease-free survival rates, but only 20 to 30 percent of patients who receive NAC fit this profile.

‘Our work represents the first clinical evidence that tumour total haemoglobin (estimated from DOST images) is different in the women with locally advanced breast cancer who respond to neoadjuvant chemotherapy,’ said lead author Shudong Jiang, associate professor of Engineering at the Thayer School of Engineering at Dartmouth. ‘We were able to predict breast tumour response to NAC based on image data acquired before the initiation of therapy.’
DOST imaging is used to measure tumour tissue for haemoglobin and oxygen saturation levels—key indicators of the presence the tiny blood vessels cancer tumours need to grow. This study suggests that biomarkers obtained through DOST imaging could help physicians determine the best treatment strategy for patients.
‘The implication of this information is that certain tumours are pre-disposed to responding to neoadjuvant chemotherapy, and that this predisposition could be known prior to choosing the therapy,’ says Jiang. ‘The study also could dramatically accelerate future randomized clinical trials on optimal NAC regimes. By using a validated imaging surrogate as an outcome measure, we could potentially reduce the number of patients required, and the length of time they need to be followed.’
Jiang says the next step will be to develop a portable and compact system to more accurately measure changes in the breast prior or/and during neoadjuvant chemotherapy. This system could be integrated into the workflow of clinical oncology practice to maximize patient participation, and determine whether additional prognostic information could be obtained that would influence patient management. Norris Cotton Cancer Center at Dartmouth-Hitchcock

New Penn Medicine research has found that elevated levels in the blood of the brain-enriched protein calpain-cleaved αII-spectrin N-terminal fragment, known as SNTF, shortly after sports-related concussion can predict the severity of post-concussion symptoms in professional athletes.

This new study builds on previous research from this group showing that elevated blood levels of SNTF on the day of a mild traumatic brain injury treated in the emergency room predicted those patients who would go on to suffer diffuse axonal injury and long-term cognitive dysfunction.

“We extended this biomarker research to the domain of professional sports to test its merit as an objective and rapid way to determine players’ severity of brain injury,” says lead author, Robert Siman, PhD, Research Professor of Neurosurgery at Penn. “This blood test may aid neurobiologically-informed decisions on suitability for return to play following a sports-related concussion.”

The study, conducted in collaboration with Henrik Zetterberg, MD, PhD and Kai Blennow, MD, PhD, of the Sahgrenska Academy at University of Gothenburg, Sweden, and their colleagues, enrolled 288 players in the top Swedish professional ice hockey league.  Each of the 28 players who suffered a concussion during the first half of the 2012-2013 season received serial blood draws and was evaluated daily for symptom resolution using the latest guidelines for treatment of sports concussions. Eight of the concussed players were symptom-free within a few days of their injury, but 20 of the players had persistent post-concussion symptoms requiring they be withheld from play six days or longer.  An additional 45 players were evaluated during the preseason, 17 of whom were also tested before and after a concussion-free training game.

Compared to those players who were not concussed, or whose concussion symptoms resolved rapidly, the researchers found an increase in the blood SNTF concentration from one hour up to 144 hours post-concussion in those players experiencing persisting post-concussion symptoms.  SNTF is a protein that is present at undetectable levels in healthy human brains, but is produced under conditions where nerve cells are traumatized and begin to die.  Concussions that lead to lasting brain dysfunction cause SNTF to accumulate in vulnerable long axon tracts of the brain, and its blood elevation is a measure of this diffuse axonal injury.

“These results show that SNTF has promise as a blood biomarker for sports-related concussion and beyond. High blood levels of SNTF appear to identify acute brain damage that corresponds with persisting symptoms after concussion.  These observations lend further support to the growing awareness that concussion is not trivial, since it can induce permanent brain damage in some individuals,” agree Siman and senior author, Douglas H. Smith, MD, professor of Neurosurgery and director of the Center for Brain Injury and Repair at Penn. Penn Medicine

A new test from Washington University’s Genomic Pathology Services will help physicians quickly zero in on genetic mutations that may be contributing to kidney disease.
Many kidney disorders are difficult to diagnose. To address this problem, scientists and clinicians have developed a diagnostic test that identifies genetic changes linked to inherited kidney disorders. This testing is now available nationwide through Genomic Pathology Services (GPS) at Washington University School of Medicine in St. Louis.

“For many kidney diseases, diagnosis can be an odyssey in which you sequence one gene after another over a long period of time to learn what’s going wrong and what the best options are for treatment,” said GPS chief medical officer and Washington University pathologist Jonathan Heusel, MD, PhD. “It makes more sense to screen all the possible contributing genes at once with a single test and consider options for treatment.”
To make this possible, the GPS team developed the test with kidney disease specialists, including Joseph Gaut, MD, PhD, a renal pathologist.

The test employs next-generation sequencing technology to decode genes associated with kidney disease. Using software developed at the university, clinical genomics specialists analyse and interpret the observed genetic alterations to identify disease-related genetic changes, or variants. They then must determine whether a given variant poses clinical risks based on available medical knowledge.

“The variants have to be evaluated on a case-by-case basis, which can be time-consuming and labour-intensive,” Heusel said.

GPS continues to update the kidney test as new links between kidney problems and DNA are identified.

“We stay abreast of the literature, and as new genes become clinically meaningful, we will incorporate those into the test,” said Catherine Cottrell, PhD, medical director for GPS.

The kidney test will check for:
•          Alport syndrome, which is characterized by progressive loss of kidney function, hearing loss and eye abnormalities;
•          Nephrotic syndrome, which includes symptoms such as protein in the urine, low blood-protein levels, high levels of cholesterol and triglycerides, and swelling;
•          Metabolic disorders associated with renal disease and including other systemic abnormalities such as diabetes, amyloidosis and others;
•          Complement (immune system) defects related to kidney disease, including atypical hemolytic uremic syndrome. Washington University