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1.
Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitors
Tanja Jesenko, Lara Prosen, Maja Čemažar, Tjaša Potočnik, Gregor Serša, 2016, izvirni znanstveni članek

Povzetek: The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors. Materials and methods. ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL-28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status. Furthermore, the effectiveness of ECT in concomitant treatment with BRAF inhibitor vemurafenib was also determined in BRAF mutated cells SK-MEL-28 with clonogenic assay. Results. The survival of BRAF V600E mutated melanoma cells was even lower than non-mutated cells, indicating that ECT is effective regardless of the mutational status of melanoma cells. Furthermore, the synergistic interaction between vemurafenib and ECT with bleomycin was demonstrated in the BRAF V600E mutated melanoma cells. Conclusions. The effectiveness of ECT in BRAF mutated melanoma cells as well as potentiation of its effectiveness during the treatment with vemurafenib in vitro implies on clinical applicability of ECT in melanoma patients with BRAF mutation and/or during the treatment with BRAF inhibitors.
Ključne besede: electrochemotherapy, BRAF inhibitors, vemurafenib, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 16; Prenosov: 2
.pdf Celotno besedilo (642,09 KB)

2.
Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer : single center experience
Janja Ocvirk, Maja Ebert Moltara, Tanja Mesti, Marko Boc, Martina Reberšek, Neva Volk, Jernej Benedik, Zvezdana Hlebanja, 2016, izvirni znanstveni članek

Povzetek: Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients% register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. Patients and methods. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Results. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (% 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7%16.2) and 11.3 (95% CI, 10.2%12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4%28.9) and 27.4 (95% CI, 22.7%31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. Conclusions. In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and welltolerated regimen in elderly patients with metastatic colorectal cancer.
Ključne besede: metastatic colorectal cancer, bevacizumab, chemotherapy, elderly
Objavljeno v DiRROS: 30.04.2024; Ogledov: 18; Prenosov: 2
.pdf Celotno besedilo (620,74 KB)

3.
Recurrence rate in regional lymph nodes in 737 patients with follicular or Hürthle cell neoplasms
Andrej Vogrin, Hana Bešič, Nikola Bešić, Maja Marolt-Mušič, 2016, izvirni znanstveni članek

Povzetek: . Preoperative ultrasound (US) evaluation of central and lateral neck compartments is recommended for all patients undergoing a thyroidectomy for malignant or suspicious for malignancy cytologic or molecular findings. Our aim was to find out how frequent was recurrence in regional lymph nodes in patients with follicular or Hürthle cell neoplasm and usefulness of preoperative neck US investigation in patients with neoplasm. Patients and Methods. Altogether 737 patients were surgically treated because of follicular or Hürthle cell neoplasms from 1995 to 2014 at our cancer comprehensive center. Altogether 207 patients (163 females, 44 males; mean age 52 years) had thyroid carcinoma. Results. Carcinoma was diagnosed in follicular and Hürthle cell neoplasm in 143/428 and 64/309 of cases, respectively. A recurrence in regional lymph nodes occurred in 12/207 patients (6%) during a median follow-up of 55 months. Among patients with carcinoma a recurrence in regional lymph nodes was diagnosed in follicular and Hürthle cell neoplasms in 2% and 14%, respectively (p=0.002). Recurrence in regional lymph nodes was diagnosed in 3/428 (0.7%) of all patients with follicular neoplasm and 9/309 (3%) of all patients with Hürthle cell neoplasm. Recurrence in lymph nodes was diagnosed in 0.7% of patients with a preoperative diagnosis of follicular neoplasm and 3% of patients with a Hürthle cell neoplasm. A recurrence in regional lymph nodes is rare in patients with carcinoma and preoperative diagnosis of follicular neoplasm.
Ključne besede: ultrasonography, thyroid neoplasms, diagnosis, pathology
Objavljeno v DiRROS: 30.04.2024; Ogledov: 12; Prenosov: 4
.pdf Celotno besedilo (435,94 KB)
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4.
Effectiveness of electrochemotherapy after IFN-[alpha] adjuvant therapy of melanoma patients
Andrejc Hribernik, Maja Čemažar, Gregor Serša, Maša Omerzel, Marko Snoj, 2016, izvirni znanstveni članek

Povzetek: The combination of electrochemotherapy with immuno-modulatory treatments has already been explored and proven effective. However, the role of interferon alpha (IFN-alpha) adjuvant therapy of melanoma patients and implication on electrochemotherapy effectiveness has not been explored yet. Therefore, the aim of the study was to retrospectively evaluate the effectiveness and safety of electrochemotherapy after the previous adjuvant treatment with IFN-alpha in melanoma patients. Patients and methods. The study was a retrospective single-center observational analysis of the patients with advanced melanoma, treated with electrochemotherapy after previous IFN-alpha adjuvant therapy. Five patients, treated between January 2008 and December 2014, were included into the study, regardless of the time point of IFN-alpha adjuvant therapy. Results. Electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy proved to be a safe and effective treatment. Patients with one or two metastases responded completely. Among patients with multiple metastases, there was a variable response rate. In one patient all 23 metastases responded completely, in second patient more than 85% of all together 80 metastases responded completely and in third patient all 5 metastases had partial response. Taking into account all metastases from all patients together there was an 85% complete response rate. Conclusions. The study showed that electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy is a safe and effective treatment modality, which results in a high complete response rate, not only in single metastasis, but also in multiple metastases. The high complete response rate might be due to an IFN-alpha immune-editing effect, however, further studies with a larger number of patients are needed to support this presumption.
Ključne besede: electrochemotherapy, IFN-alpha, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 13; Prenosov: 2
.pdf Celotno besedilo (898,63 KB)

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Predklinične raziskave v onkologiji
Maja Čemažar, 2024, samostojni znanstveni sestavek ali poglavje v monografski publikaciji

Ključne besede: onkologija, predklinične raziskave, klinične raziskave
Objavljeno v DiRROS: 24.04.2024; Ogledov: 65; Prenosov: 12
.pdf Celotno besedilo (130,79 KB)

7.
Financiranje akademskih kliničnih raziskav
Maja Čemažar, 2024, samostojni znanstveni sestavek ali poglavje v monografski publikaciji

Ključne besede: onkologija, financiranje, klinične raziskave
Objavljeno v DiRROS: 24.04.2024; Ogledov: 55; Prenosov: 13
.pdf Celotno besedilo (119,53 KB)

8.
Release of growth factors after mechanical and chemical pleurodesis for treatment of malignant pleural effusion : a randomized control study
Aljaž Hojski, Maja Leitgeb, Anton Crnjac, 2015, izvirni znanstveni članek

Povzetek: Growth factors are key inducers of fibrosis but can also mediate inflammatory responses resulting in increasing pleural effusion and acute respiratory distress syndrome. The primary aim of the study was to analyse growth factors release after performing chemical and mechanical pleurodesis in the first 48 hours at the patients with malignant pleural effusion. The secondary endpoints were to evaluate the effectiveness of the both pleurodeses, symptoms release and the quality of life of patients after the treatment. Patients and methods. A prospective randomized study included 36 consecutive female patients with breast carcinoma and malignant pleural effusion in an intention-to-treat analysis. We treated 18 patients by means of thoracoscopic mechanical pleurodesis and 18 patients by chemical pleurodesis with talcum applied over a chest tube. We gathered the pleural fluid and serum samples in the following 48 hours under a dedicated protocol and tested them for growth factors levels. A quality of life and visual analogue pain score surveys were also performed. Results. Median measured serum vascular endothelial growth factor (VEGF) level after chemical pleurodesis was 930.68 pg/ml (95% CI: 388.22-4656.65) and after mechanical pleurodesis 808.54 pg/ml. (95% CI: 463.20-1235.13) (p = 0.103). Median pleural levels of transforming growth factor (TGF) ß1 were higher after performing mechanical pleurodesis (4814.00 pg/ml [95% CI: 2726.51-7292.94]) when compared to those after performing chemical pleurodesis (1976.50 pg/ml [95% CI: 1659.82-5136.26]) (p = 0.078). We observed similar results for fibroblast growth factor (FGF) ß; the serum level was higher after mechanical pleurodesis (30.45 pg/ml [95% CI: 20.40-59.42]), compared to those after chemical pleurodesis (13.39 pg/ml [95% CI: 5.04-74.60]) (p = 0.076). Mechanical pleurodesis was equally effective as chemical pleurodesis in terms of hospital stay, pleural effusion re-accumulation, requiring of additional thoracentesis, median overall survival, but, it shortened the mean thoracic drainage duration (p = 0.030) and resulted in a higher symptoms release and in a better quality of life (p = 0.047). Conclusions. We recorded an increase in serum VEGF levels after chemical pleurodesis, however on the contrary, an increase in the pleural fluid level of TGF%1 and FGF%] after mechanical pleurodesis with respect to compared group. Although the differences did not reach statistical significance, VEGF, TGFß1 and FGFß remain the most interesting parameters for future research. Considering the mechanisms of growth factors action, we conclude that in our study group mechanical pleurodesis might be more efficient in terms of growth factors release, thoracic drainage duration and resulted in a higher symptoms release and in a better quality of life than chemical pleurodesis.
Ključne besede: malignant pleural effusion, pleurodesis, growth factors, quality of life
Objavljeno v DiRROS: 23.04.2024; Ogledov: 45; Prenosov: 25
.pdf Celotno besedilo (663,37 KB)
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9.
Safety and efficacy of IL-12 plasmid DNA transfection into pig skin : supportive data for human clinical trials on gene therapy and vaccination
Urša Lampreht Tratar, Tanja Jesenko, Maša Omerzel, Alenka Seliškar, Urban Stupan, Mihajlo Djokić, Jerneja Sredenšek, Blaž Trotovšek, Gregor Serša, Maja Čemažar, 2024, izvirni znanstveni članek

Povzetek: Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment of various types of tumors in human oncology and as an adjuvant in DNA vaccines. In recent years, we have developed a plasmid encoding human IL-12 (phIL12) that is currently in a phase I clinical study. The aim was to confirm the results of a non-clinical study in mice on pharmacokinetic characteristics and safety in a porcine model that better resembled human skin. The GET of phIL12 in the skin was performed on nine pigs using different concentrations of plasmid phIL12 and invasive (needle) or noninvasive (plate) types of electrodes. The results of our study demonstrate that the GET of phIL-12 with needle electrodes induced the highest expression of IL-12 at the protein level on day 7 after the procedure. The plasmid was distributed to all tested organs; however, its amount decreased over time and was at a minimum 28 days after GET. Based on plasmid copy number and expression results, together with blood analysis, we showed that IL-12 GET is safe in a porcine animal model. Furthermore, we demonstrated that pigs are a valuable model for human gene therapy safety studies.
Ključne besede: interleukin 12, gene electrotransfer, immunotherapy
Objavljeno v DiRROS: 18.04.2024; Ogledov: 51; Prenosov: 29
.pdf Celotno besedilo (16,83 MB)
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