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Cocaine Addiction Leads to Build-up of Iron in Brain

Cocaine addiction may affect how the body processes iron, leading to a build-up of the mineral in the brain, according to new research from the University of Cambridge. The study, published today in Translational Psychiatry, raises hopes that there may be a biomarker – a biological measure of addiction – that could be used as a target for future treatments.

Quest Diagnostics Introduces Comprehensive Opioid Therapy Genetic Test Based on CYP450 Biomarker License with Transgenomic

Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, recently announced the availability of a new lab-developed genetic test to aid the delivery of personalized opioid pain-relieving treatment. It is believed to be the first clinical lab to offer testing for variants in all cytochrome P450 (CYP450) genes known to influence the CYP450 enzyme system, which affects metabolism of opioids and other medications.

Researchers Identify Biomarkers for Possible Blood Test to Predict Suicide Risk

Indiana University School of Medicine researchers have found a series of RNA biomarkers in blood that may help identify who is at risk for committing suicide.

In a study reported Aug. 20 in the advance online edition of the Nature Publishing Group journal Molecular Psychiatry, the researchers said the biomarkers were found at significantly higher levels in the blood of both bipolar disorder patients with thoughts of suicide as well in a group of people who had committed suicide.

Principal investigator Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine and attending psychiatrist and research and development investigator at the Richard L. Roudebush Veterans Affairs Medical Center in Indianapolis, said he believes the results provide a first “proof of principle” for a test that could provide an early warning of somebody being at higher risk for an impulsive suicide act.

“Suicide is a big problem in psychiatry. It’s a big problem in the civilian realm, it’s a big problem in the military realm and there are no objective markers,” said Dr. Niculescu, director of the Laboratory of Neurophenomics at the Institute of Psychiatric Research at the IU School of Medicine.

“There are people who will not reveal they are having suicidal thoughts when you ask them, who then commit it and there’s nothing you can do about it. We need better ways to identify, intervene and prevent these tragic cases,” he said.

Over a three-year period, Niculescu and his colleagues followed a large group of patients diagnosed with bipolar disorder, completing interviews and taking blood samples every three to six months. The researchers conducted a variety of analyses of the blood of a subset of participants who reported a dramatic shift from no suicidal thoughts to strong suicidal ideation. They identified differences in gene expression between the “low” and “high” states of suicidal thoughts and subjected those findings to a system of genetic and genomic analysis called Convergent Functional Genomics that identified and prioritized the best markers by cross-validation with other lines of evidence.

The researchers found that the marker SAT1 and a series of other markers provided the strongest biological “signal” associated with suicidal thoughts.

Next, to validate their findings, working with the local coroner’s office, they analyzed blood samples from suicide victims and found that some of same top markers were significantly elevated.

Finally, the researchers analyzed blood test results from two additional groups of patients and found that high blood levels of the biomarkers were correlated with future suicide-related hospitalizations, as well as hospitalizations that had occurred before the blood tests.

“This suggests that these markers reflect more than just a current state of high risk, but could be trait markers that correlate with long term risk,” said Dr. Niculescu.

Although confident in the biomarkers validity, Dr. Niculescu noted that a limitation is that the research subjects were all male.
“There could be gender differences,” he said. “We would also like to conduct more extensive, normative studies, in the population at large.”

In addition to extending the research to females to see if the same or other markers come into play, Dr. Niculescu and colleagues plan to conduct research among other groups, such as persons who have less impulsive, more deliberate and planned subtypes of suicide.

Nonetheless, Dr. Niculescu said, “These seem to be good markers for suicidal behavior in males who have bipolar mood disorders or males in the general population who commit impulsive violent suicide. In the future we want to study and assemble clinical and socio-demographic risk factors, along with our blood tests, to increase our ability to predict risk.

“Suicide is complex: in addition to psychiatric and addiction issues that make people more vulnerable, there are existential issues related to lack of satisfaction with one’s life, lack of hope for the future, not feeling needed, and cultural factors that make suicide seem like an option.”

He said he hopes such biomarkers, along with other tools, including neuropsychological tests and socio-demographic checklists currently in development by his group, ultimately can help identify people who are at risk, leading to pre-emptive intervention, counseling, and saved lives.

“Over a million people each year world-wide die from suicide and this is a preventable tragedy”.

Study: Discovery and validation of blood biomarkers for suicidality [Molecular Psychiatry]

Source: Indiana University School of Medicine

Unexpected Synergy Between Two Cancer-linked Proteins Offers Hope for Personalised Cancer Therapy

A team of scientists led by Associate Professor Zeng Qi from A*STAR’s Institute of Molecular and Cell Biology (IMCB) have discovered a new biomarker which will help physicians predict how well cancer patients respond to cancer drugs. Having the means to identify patients who are most likely to benefit from currently available cancer drugs not only reduces substantially the healthcare cost for the patient, it could mean saving precious lives by getting the right drugs to the right patient at the onset of the treatment. This study published and featured on August cover of the Journal of Clinical Investigation will boost the development of personalised medicine in cancer care and therapy.

Metastasis is the rapid and uncontrollable spread of cancer cells from the primary tumour to other parts of the body. It is often the leading cause of death in cancer patients. Increasingly, there is evidence to show that in many cancers that have metastasised, a protein called PRL-3 is often found to be present at unusually high levels. Since it was first identified in 1998 by Associate Professor Zeng, several other research groups have found evidence to support the strong link between elevated levels of PRL-3 protein and the metastasis of aggressive cancers in the lung, liver, colon and breast. This cancer-promoting action of PRL-3 makes it an ideal target for cancer diagnostics and treatment.

In this study, the IMCB team discovered a curious synergy between PRL-3 and EGFR, another well-known cancer-linked protein frequently associated with breast and lung cancers in humans. They found that cancer cells with higher levels of PRL-3 not only hyperactivate EGFR, but also develop an ‘addiction’ for it to survive. Consequently, by suppressing EGFR activity with EGFR inhibitor drugs, the scientists observed that cancer cells with higher levels of PRL-3 were more rapidly destroyed. To validate these findings in humans, the team collaborated with Associate Professor Wee Joo Chng from the National University Health System to run an analysis on pre-existing clinical data of colorectal cancer patients. The results confirmed that patients who respond better to EGFR inhibitor drugs were those suffering from cancers with abnormally high levels of PRL-3.

Associate Professor Zeng said, “This unexpected synergy has revealed a vulnerable spot of aggressive cancers and brought new hope of treating PRL-3 driven cancers successfully. The addiction phenomenon we observed in cancer cells is akin to depriving alcohol from an alcoholic, thereby inducing the severe ‘withdrawal effects’. In the same way, by selecting cancer patients with elevated levels of PRL-3 and greater ‘addiction’ of EGFR for anti-EGFR treatment, we can deliver more effective and targeted cancer therapy with the existing EGFR inhibitor cancer drugs.”

Professor Sir David Lane, Chief Scientist of A*STAR said, “This is an excellent example of how years of basic research lay the foundation for advancement in translational and clinical applications. I am pleased that the team is exploring the potentials of developing this new predictive biomarker into a rapid diagnostic kit for identifying patients who will respond favourably to current anti-EGFR treatment. I believe that this study will open new avenues for personalised medicine in cancer therapy.”

Study: Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells [Journal of Clinical Investigation]

Source: Agency for Science, Technology and Research (A*STAR)

Quest Diagnostics Introduces Comprehensive Opioid Therapy Genetic Test Based on CYP450 Biomarker License with Transgenomic

Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, recently announced the availability of a new lab-developed genetic test to aid the delivery of personalized opioid pain-relieving treatment. It is believed to be the first clinical lab to offer testing for variants in all cytochrome P450 (CYP450) genes known to influence the CYP450 enzyme system, which affects metabolism of opioids and other medications.