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Blood test supports use of potential new treatment for patients with stomach cancer

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By measuring the number of copies of just one gene from cancer DNA circulating in the bloodstream, scientists were able to identify the patients with stomach cancer who were most likely to respond to treatment.

Stomach cancers with many copies of the FGFR2 gene were found to be particularly susceptible to the experimental drug, an FGFR inhibitor, because the tumours had become reliant on, or ‘addicted’ to, the gene in order to grow.

The new test, described in the prestigious journal Cancer Discovery this week, could be used in future to direct treatment, by identifying a subset of patients who could benefit from an FGFR2 inhibitor.

A team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust assessed the potency of the FGFR inhibitor AZD4547 in patients with stomach and breast cancer in a phase II clinical trial that screened 341 patients.

The study was funded by Cancer Research UK and AstraZeneca, with some additional funding from the charity Breast Cancer Now and the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (ICR).

Initially using tumour biopsies, researchers found many copies of the FGFR2 gene in 9 per cent of cancers among the 135 stomach cancer patients on the trial. Cancer cells often undergo changes in their DNA that can result in multiple copies of genes that help cancers grow and spread.

Tumours with multiple copies of the gene FGFR2 responded well to the treatment, with three out of nine patients having a response to treatment, and in those patients the drug worked for an average of 6.6 months.

Some 18 per cent of breast cancers were found to have multiple copies of a sister gene, known as FGFR1, and not FGFR2 – but tumours with multiple FGFR1 genes did not have the same susceptibility to the drug.

Interrogating the reason for their observations, the researchers took samples back to the laboratory to pick apart the reasons why the drug worked well in FGFR2 tumours and not in other FGFR genes.

Through painstaking experiments, they found that FGFR2 hijacks molecular pathways that help cancer grow and spread, and some stomach tumours become addicted to high levels of the gene’s protein product.

This phenomenon is known as cancer gene ‘addiction’, and is a weakness that can be exploited by modern targeted therapies.

Study co-leader Dr Nicholas Turner, Team Leader in Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“Our study has identified a potential new treatment for a subset of patients with gastric cancer, and has explained why some gastric cancers were responding to treatment while others did not. We were able to design a blood test to screen for patients who were most likely to benefit from an FGFR2 inhibitor, helping us to target drug therapy at those patients who were most likely to benefit.

“The research helps shed light on how tumours can become addicted to certain cancer genes, and shows how we can treat the disease effectively by taking advantage of these weak points in cancer’s armoury.”

Professor David Cunningham, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Honorary Professor of Cancer Medicine at The Institute of Cancer Research, London, who was Chief Investigator of the clinical trial associated with the study, said:

“This is a great example of a faster, smarter treatment being delivered to a relatively small but important group of patients with gastric cancer, made possible through the support of our NIHR Biomedical Research Centre.”

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

“This is an important study, which shows how new targeted treatments can exploit cancer’s genetic addictions, and acts as a proof of principle that cancer DNA detected in the bloodstream can be used to guide treatment.

“This is a perfect example of not just bench to bedside but back again – showing the value in taking clinical findings and scrutinising them back in the lab.”

Dr Emma Smith, Cancer Research UK’s science information manager, said:

“Developing ways to identify people who are most likely to benefit from drugs targeting particular genetic faults is vital to help ensure each patient gets the most effective treatment. The next steps will be larger clinical trials to see if testing for this genetic abnormality can spot people whose stomach cancer will respond well to this treatment.”

Dr Carl Barrett, VP Translational Science, Oncology iMed, Innovative Medicines & Early Development, AstraZeneca, said:

“This collaboration illustrates the importance of carefully analysing patient tissue samples to develop an understanding of markers of sensitivity and resistance. This knowledge will help future development of FGFR inhibitors and the understanding of the genomic response to treatment. The development of a blood-based biomarker assay, which will detect circulating tumour DNA, will help identify patients whose tumour is addicted to FGFR2 gene amplification events. AstraZeneca already uses this approach for several targeted therapies across our oncology portfolio.”

Source: ICR

 

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Urine tests not reliable for dehydration in older adults

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Water-loss dehydration happens when people don’t drink enough fluid. Urine tests are widely used by medics, nurses and other health professionals to screen for water-loss dehydration among older people.

But new research published today reveals that the diagnostic accuracy of urine tests is too low to be useful and that the tests should not be used to indicate hydration status in older people.

Lead researcher Dr Lee Hooper from UEA’s Norwich Medical School said: “Around 20 per cent of older people living in residential care don’t drink enough fluid, so are dehydrated. This figure rises to around 40 per cent among older adults admitted to hospital.

“Dehydration often goes unnoticed by carers, but it can lead to increased risk of hospital admission, urinary tract infections, disability and even death.

“Early identification, prevention and treatment of dehydration would likely improve the health of older people and reduce healthcare costs.

“Dark urine and high urine specific gravity have long been described as clinical indicators of dehydration – with nursing and medical text books, reviews, guidelines and public websites all advocating their use.

“We wanted to test their accuracy.” The team assessed 383 men and women aged over 65 living in residential care, nursing homes, or in their own homes in Norfolk and Suffolk.

They tested participants’ blood (measured serum osmolality) to assess whether they were drinking enough to stay hydrated – and compared the results with urine samples taken at the same time. They tested urine for colour, cloudiness, specific gravity, osmolality, volume, glucose, and pH.

Dr Hooper said: “Assessing a urine sample is simple and cheap. But our research shows that urine tests for dehydration are not fit for purpose – either alone or as part of a wider tranche of tests. They are not sensitive or specific enough. Urine tests will indicate that some people are dehydrated when they are not, but the urine tests also miss some older adults who really are dehydrated.

“Urine colour for example can be altered by medical conditions, medications such as warfarin and by eating certain foods such as beetroot or blackberries.

“Urinary tests rely on normal kidney function. While urine tests do seem to be able to indicate hydration status in children and younger adults, ageing is associated with impaired kidney function. As we get older we cannot concentrate our urine as well as younger people – so urine tests are not useful in older adults for indicating hydration.

“There is a great need to develop simple, inexpensive and non-invasive tools for the assessment of dehydration in older people.”

Source: UEA

 

Interview: Ronald Van Rij (Holland)

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Ronald Van Rij (Holland). Radboud Institute for Molecular Life Sciences (RIMLS),Radboud University Medical Center, Nijmegen, the Netherlands.

Interview about dengue virus.

Interview: Graham Beastall (United Kingdom)

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Graham Beastall. Past President at International Federation of Clinical Chemistry & Laboratory Medicine (IFCC). Laboratory Medicine Consulting Glasgow, UK

Click on the link below to enjoy the webinar:

 

Shaping the Future of Laboratory Medicine (2014/05/28)

 

Interview about the IFCC (2012/06/06)

 

Interview: Prof. José Eduardo Levi (Brazil)

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Prof. José Eduardo Levi (Brazil). PhD in Biological Sciences. Cell Biology. Genetics. Albert Einstein Hospital. Sao Paulo, Brazil.

Interview about latest findings in Zika virus.

IFCC’s Forthcoming Congresses – June Issue

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Calendar of IFCC Congresses/Conferences and Regional Federation’s Congresses

Nov 26 – 29, 2016 14th Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine Congress Taipei, TW
Jun 11 – 15, 2017 IFCC-EFLM EuroMedLab 2017 Athens, GR
Sep 17 – 22, 2017 XXIII COLABLIOCLI Congress 2017 and XI Uruguayan Congress of Clinical Biochemistry Punta del Este, UY
Oct 22 – 25, 2017 XXIII IFCC WorldLab 2017 Durban, ZA
May 18 – 23, 2019 IFCC-EFLM EuroMedLab 2019 Barcelona, ES
May 24 – 28, 2020 XXIV IFCC WorldLab 2020 Seoul Seoul, KR

Calendar of events with IFCC auspices

May 09- Dec 09, 2016 Course Quality Management and Good Laboratory Practice, Third Edition, 2015 PAHO/WHO online course
Jun 04-July 17, 2016  High Speciality QC Training Mexico City, MX
Aug 11 – 13, 2016  9th Palestinian Conference of Laboratory Medicine  Ramallah, Palestine
Sep 03 – 08, 2016  41st FEBS Congress/FEBS 2016 Kusadasi/Ephesus,TR 
Sep 13 – 15, 2016  AACB AIMS 2016 Combined Scientific Meeting Brisbane, AU
Sep 16, 2016 AACB Chromatography Mass Spectometry Satellite Meeting  Brisbane, AU
Sep 21 – 24, 2016  4th Joint EFLM-UEMS Congress “Laboratory Medicine at the Clinical Interface” Warsaw, PL 
Sep 21 – 24, 2016 The Benefits and Challenges of Point-of-Care Testing across the Clinical Spectrum. 26th International CPOCT Symposium  Copenhagen, DK
Sep 28 – 30, 2016 2nd German Congress on Laboratory Medicine DKLM 2016 and 13th Annual Congress of the German Society for Clinical Chemistry and Laboratory Medicine e.V.  Mannheim, DE
Sep 29, 2016  SBPC/ML&IFCC Joint Symposium Rio de Janeiro, BR 
Sep 30 – 01, 2016 5th Slovenian Congress of Clinical Chemistry and Laboratory Medicine  Portoroz, SI
Oct 04 – 08, 2016  First Scientific and Professional Congress of Biochemistry 2016 Cordoba, AR 
Oct 19 – 21, 2016  X National Congress of Clinical Laboratory Zaragoza, ES 
Oct 20 – 22, 2016 Joint Meeting of the “3rd Congress on Controversies in Thrombosis & Hemostasis” and the “8th Russian Conference on Clinical Hemostasiology and Hermorheology”  Moscow, RU
Oct 26 – 28, 2016 LMCE 2016 & KSLM 57th Annual Meeting  Seoul, KR
Oct 27, 2016 International Conference on Laboratory Medicine “Towards performance specifications for the extra-analytical phases of laboratory testing”  Padova, IT
Nov 09 – 11, 2016 EFLM Course “Developing medical tests that improve patient outcomes”  Leiden, NL
Nov 17 – 18, 2016  10th International Scientific Meeting of the Centre of Metrological Traceability in Laboratory Medicine (CIRME) “Ten years after” Milan, IT 
Dec 02 – 03, 2016  Journée de Biologie Praticienne 50 Paris, FR
Feb 09 – 10, 2017 International Congress on Quality in Laboratory Medicine  Helsinki, FI
Oct 20 – 22, 2017 XIV International Congress of Pediatric Laboratory Medicine  Durban, ZA

New material developed that quickly kills Escherichia coli

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ntegrated into the membrane, thinning the outer leaflet, resulting in strain within the bilayer (jagged arrows) c) Phase transition and pore formation d) Transport of lipids and peptides into the inner leaflet e) Diffusion of peptides onto intracellular targets (in some cases) f) Membrane collapses into fragments, physically disrupting the target cell's membrane Image: Nature

One area being explored is host defense peptides, also known as antimicrobial peptides or AMPs, natural parts of innate immune response found in every classification of life. AMPs are broad spectrum and have been demonstrated to kill everything from viruses to gram-negative bacteria with a variety of modes of action.

This new work, published in the journal Small, new developments in antimicrobial peptides are described. Scientists at the Institute of Bioengineering and Nanotechnology (IBN) at Agency for Science, Technology and Research (A*STAR) Singapore, led by Yugen Zhang, have made a molecule from a linked chain of chemicals, called imidazolium oligomers. They’ve demonstrated that it can kill E. coli bacteria by penetrating the cell membrane due in part to the chain structure. That is of particular benefit; traditional antibiotics leave the cell membrane intact, which can allow antibiotic resistance material to grow.

“Our unique material can kill bacteria rapidly and inhibit the development of antibiotic-resistant bacteria. Computational chemistry studies supported our experimental findings that the chain-like compound works by attacking the cell membrane. This material is also safe for use because it carries a positive charge that targets the more negatively charged bacteria, without destroying red blood cells,” explains Dr Zhang.

The imidazolium oligomers are simply a white powder that is soluble in water. The research team determined that if the powder was dissolved in alcohol, gels spontaneously formed. This stuff could be used in alcohol sprays that sterilize hospitals or homes.

“The global threat of drug-resistant bacteria has given rise to the urgent need for new materials that can kill and prevent the growth of harmful bacteria. Our new antimicrobial material could be used in consumer and personal care products to support good personal hygiene practices and prevent the spread of infectious diseases,” said the Executive Director of IBN, Professor Jackie Y. Ying.

While E. coli is normally found in the intestines of humans and animals, there are some strains that can cause serious illness and even death. That kind of bacterial infection is also contagious and can spread easily through contaminated food or water, or just from contact with people or animals. Good hygiene practices like hand washing can help prevent E. coli infections.

Other than E. coli, the team also tested IBN’s new material against other common strains of antibiotic-resistant bacteria and fungi, such as Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa. These pathogens can cause conditions ranging from skin infections to pneumonia and toxic shock syndrome. The material killed 99.9% of those microbes within just two minutes.

This rapid bacteria-killing material might just be a powerful new weapon against drug-resistant microbes.

Source: LabRoots

Dual Autism-Intellectual Disability From Maternal Inflammation

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Cytokines and chemokines are inflammatory chemicals that cells of the immune system produce and respond to in order to communicate with each other. In their study of approximately one thousand pregnant women, researchers from the University of California Davis Health System were able to provide evidence that increased levels of cytokines and chemokines increased the likelihood that a mother would give birth to a child that would eventually develop a condition consisting of both autism and intellectual disability.

Chemokines are involved in the regulation of migration, proliferation, and differentiation of neuronal cells, while cytokines influence neurogenesis, neuronal and glial cell migration, proliferation, differentiation, and synaptic maturation and pruning.

The inflammatory levels in mothers of children with this dual condition appeared different from mothers of children with autism only, mothers of children with intellectual disability only, and mothers of children with neither of these disorders.

“Their profiles are distinct from all of the other groups that we studied, based on their cytokine and chemokine profiles,” said Judy Van de Water, professor of Internal Medicine in the Division of Rheumatology, Allergy and Clinical Immunology and a researcher affiliated with the UC Davis MIND Institute.

The elevated levels of cytokines and chemokines during the second trimester of these women were especially surprising for researchers because these chemicals are usually down-regulated during this time. The researchers believe their findings indicate a disturbance in immune regulation as compared to healthy pregnancies of women who give birth to children without autism and/or intellectual disability.

The researchers arrived at their conclusion after conducting a population-based study with blood serum samples from mothers in the Kaiser Permanente Early Markers for Autism Study, obtained from the California Department of Public Health. All of the samples they used for analysis came from mothers who delivered their children between July 2000 and September 2003.

Out of nearly 1,000 mothers, 18.4 percent had children who developed both autism and intellectual disability, 20.1 percent had children who developed just autism, and 18.8 percent developed just intellectual disability. 42.8 percent of mothers had children with none of these conditions. Throughout the study, researchers measured mid-gestational blood serum levels of 22 different cytokines and chemokines, including M-CSF, IL-1Alpha, Il-6, IFN-Gamma.

“This study is incredibly valuable because it helps us understand more about the sources of variability within autism spectrum disorder, providing important insights into the different neurobiological mechanisms underlying important subtypes of the disorder,” said Leonard Abbeduto, director of the MIND Institute.

Scientists are beginning to hypothesize the cause behind cases of elevated second trimester inflammation. One idea is that changes in the immune environment during pregnancy disrupts the “neurodevelopmental trajectory” of fetal development. This series of interactions is then thought to result in the behavior phenotype that develops some time after birth referred to as “autism with intellectual disability.”

“Most importantly,” Abbeduto said, “This study brings us closer to knowing how to prevent adverse developmental outcomes.”

The study was recently published in Molecular Psychiatry.

Source: LabRoots

El Microscopio – Program 21

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  • Graham Beastall, IFCC’s Past President. Webinar “Medical Laboratory accreditation: What is it and why is it important”.
  • Ronald Van Rij. Dengue.
  • José Eduardo Levi. Latest findings in Zika virus
  • Agenda.
  • News and events about clinical chemistry.
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