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1.
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: 18; Prenosov: 12
.pdf Celotno besedilo (16,83 MB)
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Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer : correlation with traditional prognostic factors
Maja Lampelj, Darja Arko, Nina Čas-Sikošek, Rajko Kavalar, Maja Ravnik, Barbara Jezeršek Novaković, Sarah Dobnik, Nina Fokter Dovnik, Iztok Takač, 2015, izvirni znanstveni članek

Povzetek: Background. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. Patients and methods. 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman%s rank correlation, Mann Whitney U test and X2 test for statistical analysis. Results. Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). Conclusions. Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated.
Ključne besede: urokinase plasminogen activator, plasminogen activator inhibitor, breast cancer
Objavljeno v DiRROS: 17.04.2024; Ogledov: 42; Prenosov: 22
.pdf Celotno besedilo (571,67 KB)
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Adjuvant TNF-a therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectiveness
Maja Čemažar, Vesna Todorović, Janez Ščančar, Urša Lampreht Tratar, Monika Savarin, Urška Kamenšek, Simona Kranjc Brezar, Andrej Cör, Gregor Serša, 2015, izvirni znanstveni članek

Povzetek: Background. Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor % (TNF-%) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. Materials and methods. In vivo study was designed to evaluate the effect of TNF-% applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-% on electrochemotherapy with different cisplatin doses. Results. A synergistic interaction between TNF-% and electrochemotherapy was observed. Administration of TNF-% before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-% administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-% induced blood vessel damage and increased tumour necrosis after combination of TNF-% and electrochemotherapy, indicating an anti-vascular action of TNF-%. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Conclusion. Adjuvant intratumoural TNF-% therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.
Ključne besede: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Objavljeno v DiRROS: 17.04.2024; Ogledov: 46; Prenosov: 5
.pdf Celotno besedilo (978,26 KB)

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Higher levels of total pepsin and bile acids in the saliva as a possible risk factor for early laryngeal cancer
Maja Šereg Bahar, Aleš Jerin, Irena Hočevar-Boltežar, 2015, izvirni znanstveni članek

Povzetek: Background. Gastroesophageal reflux is suspected to be an etiological factor in laryngeal and pharyngeal cancer. The aim of this study was to establish, using a non-invasive method, whether laryngopharyngeal reflux (LPR) appears more often in patients with early laryngeal cancer than in a control group. Patients and methods. We compared the pH, the level of bile acids, the total pepsin and the pepsin enzymatic activity in saliva in a group of 30 patients with T1 laryngeal carcinoma and a group of 34 healthy volunteers. Results. The groups differed significantly in terms of levels of total pepsin and bile acids in the saliva sample. Higher levels of total pepsin and bile acids were detected in the group of cancer patients. No significant impact of other known factors influencing laryngeal mucosa (e.g. smoking, alcohol consumption, and the presence of irritating substances in the workplace) on the results of saliva analysis was found. Conclusions. A higher level of typical components of LPR in the saliva of patients with early laryngeal cancer than in the controls suggests the possibility that LPR, especially biliary reflux, has a role in the development of laryngeal carcinoma.
Ključne besede: laryngopharyngeal reflux, gastric acid, pepsin, bile acids, laryngeal carcinoma
Objavljeno v DiRROS: 17.04.2024; Ogledov: 46; Prenosov: 9
.pdf Celotno besedilo (558,42 KB)

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Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experience
Tanja Mesti, Maja Ebert Moltara, Marko Boc, Martina Reberšek, Janja Ocvirk, 2015, izvirni znanstveni članek

Povzetek: Treatment options of recurrent malignant gliomas are very limited and with a poor survival benefit. The results from phase II trials suggest that the combination of bevacizumab and irinotecan is beneficial. Patients and methods. The medical documentation of 19 adult patients with recurrent malignant gliomas was retrospectively reviewed. All patients received bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 or 125 mg/m2) every two weeks. Patient clinical characteristics, drug toxicities, response rate, progression free survival (PFS) and overall survival (OS) were evaluated. Results. Between August 2008 and November 2011, 19 patients with recurrent malignant gliomas (median age 44.7, male 73.7%, WHO performance status 0%2) were treated with bevacizumab/irinotecan regimen. Thirteen patients had glioblastoma, 5 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. With exception of one patient, all patients had initially a standard therapy with primary resection followed by postoperative chemoradiotherapy. Radiological response was confirmed after 3 months in 9 patients (1 complete response, 8 partial responses), seven patients had stable disease and three patients have progressed. The median PFS was 6.8 months (95% confidence interval [CI]: 5.3-8.3) with six-month PFS rate 52.6%. The median OS was 7.7 months (95% CI: 6.6-8.7), while six-month and twelve-month survival rates were 68.4% and 31.6%, respectively. There were 16 cases of hematopoietic toxicity grade (G) 1-2. Non-hematopoietic toxicity was present in 14 cases, all G1-2, except for one patient with proteinuria G3. No grade 4 toxicities, no thromboembolic event and no intracranial hemorrhage were observed. Conclusions. In recurrent malignant gliomas combination of bevacizumab and irinotecan might be an active regimen with acceptable toxicity.
Ključne besede: recurrent malignant glioma, systemic therapy, bevacizumab
Objavljeno v DiRROS: 17.04.2024; Ogledov: 45; Prenosov: 6
.pdf Celotno besedilo (534,06 KB)

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Mediastinal teratoma with hydrops fetalis in a newborn and development of chronic respiratory insufficiency
Milanka Simončič, Silvester Kopriva, Živa Zupančič, Maja Jerše, Janez Babnik, Matevž Srpčič, Štefan Grosek, 2014, pregledni znanstveni članek

Povzetek: Background. Mediastinal fetal teratoma can be detected as a mass in the chest during a routine prenatal ultrasound screening. Because of the pressure on mediastinal structures it can be the cause of non-immune hydrops fetalis and polyhydramnion. The development of hydrops fetalis leads to fetal death or premature delivery in most reported cases. Early surgical removal is important, but, the result of treatment depends on the stage of development of mediastinal organs and complications in the postoperative period. Case report. A 31-year-old gravida carrying twins, with spontaneous membrane rupture at 32 weeks gestation underwent urgent caesarean section after antenatal ultrasound revealed severe polyhydramnion and hydrops fetalis in geminus A. The child was intubated immediately after birth due to severe respiratory distress. Ultrasound and X-ray revealed a tumour mass in the right hemithorax. Tumour resection was performed at the age of 7 days. Histology examination revealed an encapsulated immature teratoma. The postoperative course was complicated with respiratory insufficiency which turned into chronic at the age of eight months. Conclusion. This is the fifth reported child with fetal mediastinal teratoma and severe hydrops fetalis that survived the neonatal period. Additional diagnostic search revealed abnormal course of both pulmonary arteries, which was probably one of the main causes of respiratory insufficiency.
Ključne besede: mediastinal teratoma, non-immune hydrops fetalis, diaphragm paralysis, chronic respiratory insufficiency, novorojenčki, mediastinalni teratom, kronična respiratorna insuficienca
Objavljeno v DiRROS: 11.04.2024; Ogledov: 77; Prenosov: 35
.pdf Celotno besedilo (1,29 MB)
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Microinvasive cervical squamous cell carcinoma in Slovenia during the period 2001-2007
Helena Gutnik, Jasenka P. Matišić, Maja Primic-Žakelj, Margareta Strojan Fležar, 2014, izvirni znanstveni članek

Povzetek: Background. Microinvasive squamous cell carcinoma (MISCC) comprises a significant portion of all cervical cancers in Slovenia. Criteria of carcinomatous invasion are well described in the literature, however histopathological assessment of MISCC is difficult, because morphological characteristics can overlap with cervical intraepithelial neoplasia grade 3 (CIN 3) and other pathological changes. The aim of our study was to evaluate the reliability of the histopathological diagnosis of MISCC in Slovenia during the period from 2001 to 2007. Materials and methods. Data on patients with a histopathological diagnosis of cervical MISCC (FIGO stage IA) in the period of 2001 to 2007 were obtained from the Cancer Registry of Slovenia. Histological slides were obtained from the majority of pathology laboratories in Slovenia. We received 250 cases (69% of all MISCC) for the review; 30 control cases with CIN 3 and invasive squamous cell carcinoma FIGO stage IB were intermixed. The slides were coded and reviewed. Results. Among 250 cases originally diagnosed as MISCC, there was an agreement with MISCC diagnosis in 184 (73.6%) cases (of these 179/184 (97.3%) cases were FIGO stage IA1 and 5/184 (2.7%) cases were FIGO stage IA2). Among 179 FIGO stage IA1 cases 117 (65.4%) showed only early stromal invasion. Conclusions. The retrospective review of cases diagnosed as MISCC during the period 2001- 2007 in Slovenia showed a considerable number of overdiagnosed cases. Amongst cases with MISCC confirmed on review, there was a significant proportion with early stromal invasion (depth of invasion less than 1 mm).
Ključne besede: cervical cancer, cervical squamous cell carcinoma, microinvasive squamous cell carcinoma, intraepithelial neoplasia
Objavljeno v DiRROS: 11.04.2024; Ogledov: 86; Prenosov: 19
.pdf Celotno besedilo (969,61 KB)

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Depth of SCUBA diving affects cardiac autonomic nervous system
Marina Vulić, Branislav Milovanovic, Ante Obad, Duška Glavaš, Igor Glavičič, Damir Zubac, Maja Valic, Zoran Valić, 2024, pregledni znanstveni članek

Povzetek: The present study investigated the influence of SCUBA dives with compressed air at depths of 10 and 20 m on ECG-derived HRV parameters in apparently healthy individuals. We hypothesized that cardiac sympathetic activity (measured by HRV parameters) adapts proportionally to diving depth, and that both time- and frequency-domain parameters are sensitive enough to track changes in cardiac ANS function during diving activities and subsequently during the recovery period. Eleven healthy middle-aged recreational divers (nine men and two women, age 43 ± 8, all nonsmokers) volunteered to participate in the present study. The participants (all open-circuit divers) were equipped with dry suits and ECG Holter devices and were later randomly assigned to dive pairs and depths (10 m vs. 20 m), and each participant served as his or her own control. No interaction effects (diving depth x time epoch) were found for the most commonly used HRV markers. More precisely, in response to two different diving protocols, a significant post hoc effect of time was observed for HR and SDNN, as these parameters transiently decreased during the dives and returned to baseline after ascent (p < 0.001). The ULF, VLF (p < 0.003), TP, and LF parameters decreased significantly during the dives, while HF significantly increased (p < 0.003). SCUBA diving apparently challenges the cardiac ANS, even in healthy individuals. The observed changes reveal possible underwater methods of influencing the parasympathetic activity of the heart depending on the depth of the dive. These results identify autonomic nervous system markers to track the cardiovascular risk related to diving and point to the possibility of tracking cardiovascular system benefits during underwater activities in selected patients
Ključne besede: autonomic nervous system, diving, parasympathicus, cardiovascular risk
Objavljeno v DiRROS: 09.04.2024; Ogledov: 62; Prenosov: 27
.pdf Celotno besedilo (456,62 KB)
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