1. Long-term survival in glioblastoma : methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factorUroš Smrdel, Mara Popović, Matjaž Zwitter, Emanuela Boštjančič, Andrej Zupan, Viljem Kovač, Damjan Glavač, Drago Bokal, Janja Jerebic, 2016, izvirni znanstveni članek Povzetek: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization). Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p= 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups. Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.
Ključne besede: glioblastoma, long-term survival, methyl guanine methyl transferase, MGMT, prognostic factor
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2. MicroRNAs and long non-coding RNAs : prospects in diagnostics and therapy of cancerNina Hauptman, Damjan Glavač, 2013, objavljeni znanstveni prispevek na konferenci Povzetek: Background. Non-coding RNAs (ncRNAs) are key regulatory molecules in cellular processes, and are potentialbiomarkers in many diseases. Currently, microRNAs and long non-coding RNAs are being pursued as diagnostic andprognostic biomarkers, and as therapeutic tools in cancer, since their expression profiling is able to distinguish differentcancer types and classify their sub-types.Conclusions. There are numerous studies confirming involvement of ncRNAs in cancer initiation, development andprogression, but have only been recently identified as new diagnostic and prognostic tools. This can be beneficialin future medical cancer treatment options, since ncRNAs are natural antisense interactors included in regulationof many genes connected to survival and proliferation. Research is directed in development of useful markers fordiagnosis and prognosis in cancer and in developing new RNA-based cancer therapies, of which some are alreadyin clinical trials.
Ključne besede: microRNAs, long non-coding RNAs, biomarker
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3. Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycinVesna Todorović, Gregor Serša, Vid Mlakar, Damjan Glavač, Maja Čemažar, 2012, izvirni znanstveni članek Povzetek: Background. Electrochemotherapy is a local treatment combining chemotherapy and electroporation and is highly effective treatment approach for subcutaneous tumours of various histologies. Contrary to surgery and radiation, the effect of electrochemotherapy on metastatic potential of tumour cells has not been extensively studied. The aim of the study was to evaluate the effect of electrochemotherapy with bleomycin on the metastatic potential of human melanoma cells in vitro. Materials and methods. Viable cells 48 hours after electrochemotherapy were tested for their ability to migrate and invade through Matrigel coated porous membrane. In addition, microarray analysis and quantitative Real-Time PCR were used to detect changes in gene expression after electrochemotherapy. Results. Cell migration and invasion were not changed in melanoma cells surviving electrochemotherapy.Interestingly, only a low number of tumourigenesis related genes was differentially expressed after electrochemotherapy. Conclusions. Our data suggest that metastatic potential of human melanoma cells is not affected by electrochemotherapy with bleomycin, confirming safe role of electrochemotherapy in the clinics.
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