Characiejus D.,Vilnius University |
Characiejus D.,Center for Innovative Medicine |
Hodzic J.,VU University Amsterdam |
Jacobs J.J.L.,VU University Amsterdam
Present cancer treatment strategies are based on the assumption that a therapy may work ("response") or not work ("no-response"). However, the existing evidence suggests that current cancer treatment modalities may also have a cancer-promoting effect in part of the patients. In this paper, some relevant data are reviewed suggesting that surgery, irradiation, chemotherapy and immunotherapy can stimulate tumor growth / metastatic spread and decrease survival of patients in certain subgroups. Thus, results of cancer treatment may be improved by detection and use of biomarkers that correlate with positive or negative therapeutic effects. Small trials based on groups with differing biomarkers rather than large phase III trials may aid the development and efficacy testing of new anticancer drugs. Moreover, ignoring biomarkers that correlate with positive or negative therapeutic effect may not be compatible anymore with the ethical principle "First Do No Harm". © 2010 The Author(s). Source
Baek J.-H.,Center for Innovative Medicine |
Schmidt E.,Center for Innovative Medicine |
Viceconte N.,Center for Innovative Medicine |
Strandgren C.,Center for Innovative Medicine |
And 10 more authors.
Human Molecular Genetics
Hutchinson-Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin. © The Author 2014. Source
Jacobs J.J.L.,University Medical Center |
Snackey C.,University Medical Center |
Geldof A.A.,University Medical Center |
Geldof A.A.,VU University Amsterdam |
And 4 more authors.
Prophylactic vaccination is arguably the most effective medical preventative method. After local inoculation, vaccines induce antigen-specific systemic immunity, protecting the whole body. Systemic antitumour immunity can cure advanced cancer, but will therapeutic vaccination suffice? A vaccine for castration-refractory prostate cancer (CRPC) was approved by regulatory authority, but its evidence is disputed. We critically reviewed the clinical efficacy of therapeutic cancer vaccines for prostate cancer, including the results of 31 clinical studies employing vaccines-only, and another 10 studies combining vaccines with immune co-stimulation. Vaccinations yielded immunological responses, but no study showed evidence for clinically relevant therapeutic improvement. Clinical failure of therapeutic vaccination is discussed in the light of immunological dogmas and mechanisms of antitumour therapies. We propose that cancer immunotherapy might be improved by immunological danger, i.e. disturbing tumour homeostasis by destroying the tumour tissue or inducing local inflammation. Such danger might override immunological tolerance, and thereby allow clinically relevant anticancer results. Source
Gefenas E.,Vilnius University |
Cekanauskaite A.,Vilnius University |
Tuzaite E.,Vilnius University |
Dranseika V.,Vilnius University |
And 2 more authors.
This paper maps the ethical issues that arise in the context of personalised medicine. First, it highlights the ethical problems related to increased predictive power of modern diagnostic interventions. Such problems emerge because the ability to identify individuals or groups of individuals that can potentially benefit from a particular therapeutic intervention also raises a question of personal responsibility for health-related behaviour and lifestyle. The second major area of ethical concern is related to health prevention and distributive justice. The paper discusses the ethical challenges brought by the personalised medicine in the context of the Additional Protocol to the Convention on Human Rights and Biomedicine concerning Genetic Testing for Health Purposes. Finally, it notes that the issue of consent in the context of biobanks, the need to rethink the prevalent models of research designs and to communicate relevant findings to the donors of biological materials deserve further discussion. © 2011 European Association for Predictive, Preventive and Personalised Medicine. Source
Balevicius Z.,Vilnius University |
Balevicius Z.,Lithuanian Academy of Sciences |
Drevinskas R.,Vilnius University |
Dapkus M.,Vilnius University |
And 3 more authors.
Thin Solid Films
Total internal reflection ellipsometry (TIRE) technique was used to investigate the optical response of different hybrid multilayer systems. It was shown that the optical response was significantly changed by gold nanoparticles, which have been introduced for modification of functional properties of hybrid system. Nevertheless, the dispersion of optical parameters for gold nanoparticles was quite close in various hybrid systems in the case of adequate models used for interpretation of TIRE data. © 2010 Elsevier B.V. All rights reserved. Source