Molecular Diagnostics
Cancer “signature” is a first step toward a blood test for lung cancer patients. A discovery by Australia-based researchers could help to identify patients with a particularly aggressive type of lung cancer who are likely to respond to immunotherapies currently used to treat other cancers. Their research also revealed a unique molecular signature in the blood that could, in the future, be used to detect these aggressive lung cancers with a simple blood test.
Walter and Eliza Hall Institute cancer researchers Dr. Sarah Best and Dr. Kate Sutherland led the research, working with colleagues at Metabolomics Australia at the Bio21 Institute, University of Melbourne. The study was published in Cell Metabolism.
The study focused on the role of two cell signaling pathways—KEAP1/NRF2 and PI3K—which are known to be involved in adenocarcinomas.
“More than one in five lung adenocarcinomas have alterations in the KEAP1/NRF2 pathway, suggesting it is a major cancer driver,” Sutherland says.“ These cancers are very aggressive, are resistant to standard therapies, and have a poor prognosis, so new therapies are urgently needed.”
Best says that the study revealed that the tumors had characteristics indicating they were likely to respond well to immunotherapy: “Using preclinical models, we showed for the first time that these tumors have the ‘markers’ that respond to anti-PD-1 and anti-CTLA-4 immunotherapies, which are some of the most exciting new cancer therapies being investigated in the clinic.
“But more importantly, we showed that these immunotherapies were effective in fighting the tumors and leading to tumor regression in our preclinical models.”
Best says the research showed that non-stop signaling caused by mutations in the KEAP1/NRF2 and PI3K pathways caused lung adenocarcinomas to develop. “This is the first time anyone has shown that these alterations directly cause lung adenocarcinomas. With this knowledge, we can further investigate how targeting those pathways could lead to therapies for these aggressive and hard-to-treat cancers,” she adds.
Sutherland says the unique molecular signatures found in the blood could be a tool to identify patients who would respond to immunotherapies, or even as the basis of an early detection test for those cancers.
Oncology
Blood cancer precursor is found in 9/11 firefighters. A study published in JAMA Oncology reports that New York City firefighters exposed to the 9/11 World Trade Center disaster site face an increased risk for developing MGUS (monoclonal gammopathy of undetermined significance), which can lead to the blood cancer multiple myeloma. The study was conducted by researchers at Albert Einstein College of Medicine, Montefiore Health System, the Fire Department of the City of New York (FDNY), and Memorial Sloan Kettering Cancer Center.
In MGUS, the blood’s plasma cells produce an abnormal protein called monoclonal protein that can be detected with blood tests. MGUS generally causes no problems but can progress to multiple myeloma, a blood cancer diagnosed in about 30,000 Americans each year. In multiple myeloma, rapidly proliferating plasma cells can crowd out the bone marrow’s normal blood-forming cells, leading to problems including anemia (shortage of red cells) and leukopenia (shortage of white cells). Most multiple myeloma cases are diagnosed in people older than 65.
Previous studies suggest that MGUS and multiple myeloma tend to develop after exposure to toxic chemicals. The aerosolized dust from the collapsed towers exposed FDNY and other first responders to unprecedented levels of polychlorinated biphenyls, polycyclic aromatic hydrocarbons, dioxins, asbestos, and other potential carcinogens, as well as diesel smoke from heavy machinery used in the 10-month rescue-and-recovery effort.
The study population was limited to 781 white, male WTC-exposed firefighters aged 50 to 79 whose blood samples were evaluated to assess the prevalence of MGUS in the group. When results were compared with MGUS prevalence in a non-exposed comparison group, the prevalence of MGUS in the firefighters was nearly twice as high (7.63 cases of MGUS per 100 firefighters vs. 4.34 cases per 100 non-exposed persons).
In a separate analysis, the researchers examined the 16 cases of multiple myeloma diagnosed between September 12, 2001, and July 1, 2017, among all white, male WTC-exposed FDNY firefighters. Their average age of diagnosis was 57, or 12 years younger than the average age for multiple myeloma diagnosis nationally.
Chemistry
Stanford scientists find possible autism biomarker in cerebrospinal fluid. Autism diagnosis is slow and cumbersome, but new findings linking the hormone vasopressin to social behavior in monkeys and autism in people may change that. Low vasopressin in cerebrospinal fluid was related to less sociability in both species, indicating the hormone may be a biomarker for autism. A paper describing the research, which was led by scientists at the Stanford University School of Medicine and the University of
California-Davis, will be published in Science Translational Medicine.
Autism, a developmental disorder characterized by impaired social abilities, affects 1 in 68 U.S. children. Research has shown that early, intensive behavioral treatment is beneficial. Yet many children don’t receive a timely diagnosis. A biological test, with a specific lab measurement indicating autism, could make diagnosis faster.
The current researchers looked for autism biomarkers in rhesus monkeys, a species whose social capabilities are reasonably comparable to those of humans. From 222 male animals, the scientists selected 15 with naturally low sociability and compared them with 15 monkeys with naturally high sociability on several biological parameters.
The scientists measured levels of two hormones, oxytocin and vasopressin, in the monkeys’ blood and in their cerebrospinal fluid, which bathes the brain. Both hormones are peptides implicated in a variety of social roles, including parental care and bonds between mates. Some prior studies have hinted that these hormones may also be involved in autism.
Monkeys in the less social group had significantly less vasopressin in their cerebrospinal fluid than monkeys in the more social group. These vasopressin levels accurately predicted the frequency with which individual monkeys participated in social grooming, an important social activity for rhesus monkeys. Vasopressin blood levels were not different between the two groups. In a group of 10 monkeys, whose cerebrospinal fluid was sampled four times over four months, the scientists showed that vasopressin levels in the fluid were stable over time.
The researchers also compared vasopressin levels in cerebrospinal fluid of 14 boys with autism and seven age-matched children without autism. Children with autism had lower vasopressin levels than children without autism, the study found.
Hematology
Blood type O patients may have higher risk of death from severe trauma. Blood type O is associated with high death rates in severe trauma patients, according to a study published in the open access journal Critical Care. The study involved 901 Japanese emergency care patients with severe trauma who were transported to either of two tertiary emergency critical care medical centers in Japan during 2013 to 2016.
Researchers at Tokyo Medical and Dental University Hospital found that severe trauma patients (those with an injury that has the potential to cause long-term disability or death) with blood type O had a death rate of 28 percent, compared to 11 percent in patients with other blood types.
Dr. Wataru Takayama, the corresponding author, says: “Recent studies suggest that blood type O could be a potential risk factor for hemorrhage. Loss of blood is the leading cause of death in patients with severe trauma, but studies on the association between different blood types and the risk of trauma death have been scarce. We wanted to test the hypothesis that trauma survival is affected by differences in blood types.”
Patients with blood type O have been shown to have lower levels of von Willebrand factor (vWF), a blood clotting agent, than those with other blood types. Lower levels of vWF may be linked to higher levels of hemorrhage. The authors suggest that a lower level of vWF may explain the higher death rate in trauma patients with blood type O. Takayama says that the results also raise questions about how emergency transfusion of O type red blood cells to a severe trauma patient could affect homeostasis and whether type O is different from other blood types in that regard.
The authors caution that all the patients whose data was analyzed in this study were Japanese and that therefore there is a need for further research to understand whether the findings apply to other ethnic groups. Additionally, there was no evaluation of the impact of the individual blood types A, AB, or B, on severe trauma death rates. Instead, the authors compared type O to non-O blood type, which may have diluted the effect of individual blood types on patient survival.
Infectious Diseases
New Lyme disease tests could offer quicker, more accurate detection. New tests to detect early Lyme disease—which has been increasing beyond the summer months—could replace existing tests that often do not clearly identify the infection before health problems occur.
In an analysis published in Clinical Infectious Diseases, scientists from Rutgers University, Harvard University, Yale University, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, and other academic centers, industry, and public health agencies say that new diagnostic methods offer a better chance for more accurate detection of infection from the Lyme bacteria.
Lyme disease is the most common tick-borne infection in North America and Europe. There are currently more than 300,000 cases of Lyme disease annually in the United States alone, and the disease is increasing and spreading into new regions. Lyme disease frequently, but not always, presents with a bull’s-eye rash. When the rash is absent, a laboratory test is needed.
The only FDA-approved Lyme disease tests, based on technology developed more than two decades ago, rely on detecting antibodies that the body’s immune system makes in response to the disease. These antibody-based tests are the most commonly used tests for Lyme disease and are the current standard.
One problem, however, is that many people produce similar—called “cross-reactive”—antibodies in response to other bacteria not associated with Lyme disease. This can reduce assay specificity. Researchers say more specific testing would help doctors decide when to prescribe the antibiotics used to clear the infection and help patients avoid severe, long-term health problems.
