The Snippet: Delay in hiring science advisers intensifies Brexit worries

Two government departments charged with managing the United Kingdom’s departure from the European Union have not yet appointed chief scientific advisers (CSAs) — and might not do so. That is starting to concern science-policy experts, who worry that scientists won’t be at the table when government makes key decisions on issues such as environmental protection and membership of international collaborations. The United Kingdom has for years embraced the CSA model, in which highly qualified researchers are appointed to senior advisory roles and then embedded in government departments. But neither the Department for Exiting the European Union (DExEU) nor the Department for International Trade (DIT), both of which were created in the wake of the United Kingdom’s decision to leave the EU, has yet appointed, or committed to appointing, a CSA.

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The Snippet : OncoTrack conducts largest academic-industry research to develop new biomarkers for colon cancer

OncoTrack, a public-private consortium supported by the Innovative Medicines Initiative (IMI) joint undertaking, has conducted one of Europe’s largest collaborative academic-industry research projects to develop and assess novel approaches for identification of new markers for colon cancer. Scientists from the OncoTrack Consortium, including researchers from the Max Planck Institute for Molecular Genetics in Berlin and the company Alacris Theranostics, have analyzed tumor samples from cancer patients in a preclinical study. In particular, the scientists looked for biomarkers, i.e. molecules that are typical of the different tumor subgroups and provide valuable information for diagnosis and potential treatment. Among other things, the research team discovered molecules that can predict the effectiveness of two drugs commonly used to treat this disease: Cetuximab and the chemotherapy drug 5FU. The scientists identified the genetic composition of the tumors and analyzed their so-called transcriptome, namely the set of all RNA molecules synthesized in a given tissue. Based on this analysis, they were able to produce a definite molecular fingerprint for all of the tumors. The consortium team identified two such biomarkers, which predict whether either the EGFR inhibitors Cetuximab or the chemotherapy 5FU could trigger a successful response in colorectal cancer.

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The Snippet: Clinical trials need to assess drug efficacy before first-in-human trials

On 17 January 2016, a healthy man was declared brain-dead after receiving an experimental drug in a first-in-human trial in France. Four of five other subjects receiving the same dose have serious, ongoing neurological complications. Investigations into the trial described many troubling safety practices, such as steep increases in dose levels delivered to sequential subjects without sufficient delays to check for safety. In the wake of the tragedies, the French medicines safety agency (ANSM) ordered an examination of the information that the drug developer, Bial, based in Trofa, Portugal, had supplied to ethics committees and potential researchers before the trial. The report notes that the 63-page Investigator Brochure describing the trial included fewer than two pages of evidence that the drug had the desired pharmacological activity. It identified only two studies presented as evidence for efficacy, both problematic. A lack of emphasis on evidence for the efficacy of drug candidates is all too common in decisions about whether an experimental medicine can be tested in humans. There is a need to call for infrastructure, resources and better methods to rigorously evaluate the clinical promise of new interventions before testing them on humans for the first time, to ensure safety from bogus medicines.

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The Snippet : Can the brain detect Addictive cravings even after death?

The scientists from the Department of Forensic Medicine, of the Medical University of Vienna, surprisingly found that addictive cravings can be detectable even after death.
This is due to a protein known as FosB, which is present in the reward centre of the brain. The protein gets altered in chronically ill people who are suffering from an addictive disorder such as heroin addiction. The protein then is genetically modified, split off and shortened. When under the stimulus of a drug, this type of modification results in the protein being more stable leading it to remain longer in this part of the brain than in its original form. This can be as long as several weeks even after withdrawal of the drug. Thus, craving for this stimulus persists which leads to this addictive craving getting stored in a sort of “memory” function and can still be detected after death.

Read more at :

https://www.sciencedaily.com/releases/2016/12/161221090114.htm

The Snippet : Sub types of cervical cancer identified

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. A recent publication in nature reported the extensive molecular characterization of 228 primary cervical cancers, and has been dubbed as the largest comprehensive genomic study of cervical cancer to date. The authors observed striking APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2 as novel significantly mutated genes in cervical cancer. They also discovered novel amplifications in immune targets CD274/PD-L1 and PDCD1LG2/PD-L2, and the BCAR4 lncRNA that has been associated with response to lapatinib. The authors were also able to identify a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumors with high frequencies of KRAS, ARID1A, and PTEN mutations. Integrative clustering of 178 samples identified Keratin-low Squamous, Keratin-high Squamous, and Adenocarcinoma-rich subgroups. These molecular analyses, thus, revealed new potential therapeutic targets for cervical cancers.

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The Snippet : Prostate Cancer – More metastases leading to increased incidence in the disease in the USA

A study, Analysis of Surveillance, Epidemiology, and End Results (SEER), has shed light on the increased prevalence of incidence of distant metastasis at diagnosis in men aged ≥75 years with prostate cancer. This increase is most probably the result of a recommendation provided by the US Preventative Services Task Force (USPSTF), which was to do away with screening for prostate cancer in men ≥75 years old in 2008 and against screening in men of any age in 2012. From the SEER data, 1,107,111 men ≥40 years old diagnosed between 2004 and 3013 with pathologically confirmed prostate cancer were identified. The incidence of distant metastasis was derived using SEER collaborative staging at quarterly intervals. Between 2004 and 2013, the proportion of men aged ≤75 years presenting with distant metastasis increased from 2.7% to 4.0% and the proportion presenting with intermediate-risk or high-risk disease increased from 46.3% to 56.4%. Over the same time period, the proportion of men aged ≥75 years presenting with distant metastasis increased from 6.6% to 12.0% and the proportion of those presenting with intermediate-risk or high-risk disease increased from 58.1% to 72.0%. The significant increase in the incidence of distant metastasis at prostate cancer diagnosis in men aged ≥75 years between 2011 and 2013 in men in could be an effect of the USPSTF 2008 recommendation against screening for prostate cancer in these men.

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The Snippet: Pulling the apoptotic trigger for necrosis

Apoptosis and necrosis are considered to be distinct modes of cell death; however, apoptosis can progress to secondary necrosis if apoptotic cells are not efficiently removed by phagocytic cells. Secondary necrosis was thought to be unregulated and to occur through passive cell swelling. However, research shows that secondary necrosis is another example of programmed cell death and that it is triggered by apoptotic stimuli. The amino-terminal portion of GSDMD oligomerizes and forms pores in the plasma membrane and thereby mediates necrotic cell death. The research found that a member of the gasdermin superfamily, DFNA5, is also a caspase target, but unlike GSDMD it is cleaved by caspase 3, the executioner caspase of the apoptotic pathway. Akin to GSDMD, this processing occurs at a single site (Asp270) and generates amino-terminal (DFNA5-N) and carboxy-terminal (DFNA5-C) portions of DFNA5. When DFNA5-N was ectopically expressed in human embryonic kidney 293T (HEK293T) cells, which do not express endogenous DFNA5, the cells showed morphological and biochemical features characteristic of necrotic cells. Expression of DFNA5 (but not the non-cleavable mutant) and concomitant induction of apoptosis in HEK293T cells generated DFNA5-N and induced secondary necrosis. The DFNA5-N fragment was also detected when apoptosis was induced in macrophages, which endogenously express DFNA5.

The Snippet: Fatal French clinical trial failed to check data before raising drug dose

Criticism of the drug company at the centre of a disastrous clinical trial that left one participant dead and four with long-term neurological symptoms has intensified following a revelation that the firm did not use certain data when deciding to administer a higher dose that proved deadly. On 15 December, during a conference presentation by a scientist from the Portuguese company, Bial, it emerged that the firm did not use certain readings, called pharmacodynamic (PD) data, on how the drug BIA 10-2474 was acting in participants who had received a lower dose, before taking the decision to increase the dosage. When asked why the company had not included the PD data in its dose-escalation decision, Helena Gama, head of Bial’s pharmacovigilance and drug safety office said, “The evaluation before starting a new drug escalation is based on safety evaluation and pharmacokinetic data” — referring to other data on how the drug is absorbed, distributed, metabolized and excreted by the body. “We did not have any profile that precluded the path to the further dosage.”

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Pharma M&A Rebound May Take a While in 2017

The only word that described 2016’s pharma M&A market was “slow.” Some do predict that new year—and administration—could revive energy in the deal making arena, the changes might not happen that fast. The reasons are aplenty, as shares have been sagging under the weight of investor fears of drug-pricing reform. Companies aren’t all that keen on putting themselves up for sale while valuations are low. Drug pricing is inhibiting M&A in another way, too. Specialty drug makers have drawn unwanted attention since last summer with their buy-and-hike-prices strategy. In the meantime, they’ve been shying away from the deal making table, fearing they’d become the next Valeant, Turing or Mylan in the spotlight. Thus, the new regime under Donald Trump might blow life into the M&A activities, but this might take time and visible results might take a while.

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US drug approvals plummet in 2016

US drug approvals are on track to drop by more than half in 2016 compared to 2015. The agency had approved 19 new drugs this year as of 9 December, putting it on track for its lowest yearly tally since 2007. The decline is made more dramatic by 2015’s bumper crop of approvals. The FDA approved 45 new drugs last year — the highest total in nearly 20 years. The data come as the agency waits to find out who will be its next commissioner under US president-elect Donald Trump, as he has indicated that he wants to speed up drug approvals and cut through “the red tape at the FDA”. And on 13 December, President Barack Obama signed into law the 21st Century Cures Act, which includes measures intended to streamline drug approvals.

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