73843 An Andalusian team of researchers led by the University of Granada has demonstrated the efficacy of a new drug against cancerogenic stem cells, which cause the onset and development of cancer, of relapse after chemotherapy and metastasis. This drug, called Bozepinib, has proved to be effective in tests with mice. The results have been published in the prestigious journal Oncotarget.

Cancerogenic stem cells appear in small quantities in tumours, and one of their important features is that they contribute to the formation of metastasis in different places within the original tumour. Cancerogenic stem cells remain dormant under normal conditions (i.e. they do not divide). Conventional chemotherapy and radiotherapy act upon those cancer cells which are clearly differentiated—i.e. which are undergoing processes of division—but they cannot destroy these dormant cancerogenic stem cells. Actually, after a positive initial response to treatment, many cancer patients suffer a relapse because these cancerogenic stem cells have not been destroyed.
During the last few years, research in fight against cancer has focused on the search for new drugs that can selectively attack these cancerogenic stem cells. If they can be eliminated, the tumour will then be eliminated in its entirety, which will lead to the complete curation of patients.
Scientists in the «Advanced therapies: differentiation, regeneration and cancer» research group led by UGR professor Juan Antonio Marchal have collaborated with Joaquín Campos, from the School of Pharmacy, U. of Granada, and María Ángeles García, from Virgen de las Nieves University Hospital in Granada, as well as with the universities of Jaen and Miami (US) to develop the new drug Bozepinib.
Clinical tests on patients
This new drug shows a selective type of activity against cancerogenic stem cells in breast, colon, and skin cancers. «The powerful anti-tumour activity of Bozepinib is due to the inhibition of the HER2 signalling pathway, and to the fact that this drug inhibits the invasiveness and the formation of new vessels in the tumour (angiogenesis)», says prof. Juan Antonio Marchal. Researchers have also revealed the specific mechanism by means of which Bozepinib acts against cancerogenic stem cells
This new drug proved to be nontoxic for healthy mice when it was intraperitoneally or orally administered, and it also inhibited tumoural growth and the formation of lung metastasis in those mice in which the tumour was induced.
Researchers are currently conducting safety tests and they expect that this new drug, as well as its derivatives, can be run through clinical tests with actual patients in the near future.
Explore further: Clumped cancer cells spread more efficiently through the body than lone ones
More information: «HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are targets of Bozepinib.» Alberto Ramírez, Houria Boulaiz, Cynthia Morata-Tarifa, Macarena Perán, Gema Jiménez, Manuel Picon-Ruiz, Ahmad Agil, Olga Cruz-López, Ana Conejo-García, Joaquín M. Campos, Ana Sánchez, María A. García, Juan A. Marchal. Oncotarget, Vol. 5, No. 11

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73810 An international team of scientists which includes researchers from the U. of Granada has demonstrated for the first time that it is possible to establish in an objective way the level of fatigue in physicians after long shifts through their eye movement. 

This research reveals that the speed of saccadic movement (mostly voluntary rapid eye movements which we use to focus our gaze upon an object that attracts our attention) is an excellent index to measure objectively the level of fatigue in the medical profession.
In an article published in Annals of Surgery (the most prestigious journal in the field), scientists evaluated the performance of doctors from the Traumatology Service at St Joseph’s Hospital and Medical Centre, Phoenix (US), before and after their so called ‘call-day’ (a 24-hour shift during which doctors do not get any sleep)
All of them had the speed of their saccadic eye movements measured before and after the shift. Besides, they had to perform simulated laparoscopic tests (also before and after this 24-hour shift)
Subjective fatigue perception
Results proved that after long hours, the speed of saccadic movements effectively diminished, while their subjective perception of fatigue increased. However, in the simulated laparoscopic tests after the shift, the execution was not affected in any significant way by their fatigue.
This means that—fortunately for patients—the previous work hours did not have a negative impact on their surgery practice. This supports the hypothesis that fatigue is not the only source of errors in medical professionals. Although shifts involve restless work, doctors, in their professional practice, always display all the resources available to obtain the best results. There is, for instance, a complex relation between continuous care, patient safety, economic factors, and the level of fatigue in doctors themselves.
«It is also true that those other professional competence resources can do little when there is an excess of working hours, and consequently those results are fundamental to contribute to the regulation of shifts and schedules, based on objective data on fatigue and performance», suggested Leandro Luigi Di Stasi, Fulbright researcher at the Barrow Neurological Institute(Phoenix, AZ, US), and Andrés Catena, director of the Centre for Research on Mind, Brain and Behaviour at the University of Granada.

More than a decade ago, the U.S. Government’s National Institute of Medicine published a report titled «To Err Is Human: Building a Safer Health System», which estimated that medical errors were responsible for between 44.000 and 98.000 deaths in the U.S., and more than a million injuries every year.
Although these estimates are not devoid of controversy, it is obvious that medical errors and accidental damage do occur too frequently. In particular, errors originating in fatigue have been identified as one of the factors that lead to most accidents at work. The costs of such accidents has been recently estimated to amount to 31,1 billion dollars in the U.S.
Avoiding errors
In Spain, around 10% of patients in hospital suffer some type of adverse episode as a result of medical attention, and about 50% of these errors could have been avoided by the application of safer clinical practices.
«For these reasons, all those strategies whose objective is to know the factors that lead to unsafe medical practices, and consequently diminish patient safety, are part of the agenda of several international organizations, including the World Health Organization», according to Di Stasi and Catena.
Since long work shifts and overtime hours are both becoming more frequent, especially among resident doctors, «the study of fatigue as a factor that contributes to the prevention of errors in the health system has become one of the main topics in risk management within this context.»
The results of this research also open to debate the number of hours that doctors can work without affecting patient safety. For instance, in the U.S. residents work almost twice as their Spanish or French counterparts (80 hours a week vs 40)
The results of this study can also be applied to other fields similar to medicine, which also require long hours involving large amounts of sophisticated knowledge and complex decision-making skills coupled with technical complexity—such as civil and military aviation.
Explore further: Reducing residents’ work hours may have unintended consequences
More information: «Saccadic eye movement metrics reflect surgical residents’ fatigue.» Ann Surg. 2014 Apr;259(4):824-9. DOI: 10.1097/SLA.0000000000000260
Journal reference: Annals of Surgery
Provided by University of Granada

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