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1.
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, original scientific article

Abstract: 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.
Keywords: urokinase plasminogen activator, plasminogen activator inhibitor, breast cancer
Published in DiRROS: 17.04.2024; Views: 33; Downloads: 19
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2.
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, original scientific article

Abstract: 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.
Keywords: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Published in DiRROS: 17.04.2024; Views: 36; Downloads: 5
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3.
The cost of systemic therapy for metastatic colorectal carcinoma in Slovenia : discrepancy analysis between cost and reimbursement
Tanja Mesti, Biljana Mileva Boshkoska, Mitja Kos, Metka Tekavčič, Janja Ocvirk, 2015, original scientific article

Abstract: The aim of the study was to estimate the direct medical costs of metastatic colorectal cancer (mCRC) treated at the Institute of Oncology Ljubljana and to question the healthcare payment system in Slovenia. Methods. Using an internal patient database, the costs of mCRC patients were estimated in 2009 by examining (1) mCRC direct medical related costs, and (2) the cost difference between payment received by Slovenian health insurance and actual mCRC costs. Costs were analysed in the treatment phase of the disease by assessing the direct medical costs of hospital treatment with systemic therapy together with hospital treatment of side effects, without assessing radiotherapy or surgical treatment. Follow-up costs, indirect medical costs, and nonmedical costs were not included. Results. A total of 209 mCRC patients met all eligibility criteria. The direct medical costs of mCRC hospitalization with systemic therapy in Slovenia for 2009 were estimated as the cost of medications (cost of systemic therapy + cost of drugs for premedication) + labor cost (the cost of carrying out systemic treatment) + cost of lab tests + cost of imaging tests + KRAS testing cost + cost of hospital treatment due to side effects of mCRC treatment, and amounted to %3,914,697. The difference between the cost paid by health insurance and actual costs, estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009, was %1,900,757.80. Conclusions. The costs paid to the Institute of Oncology Ljubljana by health insurance for treating mCRC with systemic therapy do not match the actual cost of treatment. In fact, the difference between the payment and the actual cost estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009 was %1,900,757.80. The model Australian Refined Diagnosis Related Groups (AR-DRG) for cost assessment in oncology being currently used is probably one of the reasons for the discrepancy between pay-outs and actual costs. We propose new method for more precise cost assessment in oncology.
Keywords: cost of treatment, metastatic colorectal cancer, cost of targeted therapy, monitoring costs
Published in DiRROS: 17.04.2024; Views: 37; Downloads: 5
.pdf Full text (730,95 KB)

4.
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, original scientific article

Abstract: 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.
Keywords: laryngopharyngeal reflux, gastric acid, pepsin, bile acids, laryngeal carcinoma
Published in DiRROS: 17.04.2024; Views: 37; Downloads: 6
.pdf Full text (558,42 KB)

5.
Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experience
Tanja Mesti, Maja Ebert Moltara, Marko Boc, Martina Reberšek, Janja Ocvirk, 2015, original scientific article

Abstract: 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.
Keywords: recurrent malignant glioma, systemic therapy, bevacizumab
Published in DiRROS: 17.04.2024; Views: 38; Downloads: 5
.pdf Full text (534,06 KB)

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The role of PET-CT in radiotherapy planning of solid tumours
Staša Jelerčič, Mirjana Rajer, 2015, review article

Abstract: PET-CT is becoming more and more important in various aspects of oncology. Until recently it was used mainly as part of diagnostic procedures and for evaluation of treatment results. With development of personalized radiotherapy, volumetric and radiobiological characteristics of individual tumour have become integrated in the multistep radiotherapy (RT) planning process. Standard anatomical imaging used to select and delineate RT target volumes can be enriched by the information on tumour biology gained by PET-CT. In this review we explore the current and possible future role of PET-CT in radiotherapy treatment planning. After general explanation, we assess its role in radiotherapy of those solid tumours for which PET-CT is being used most. Conclusions. In the nearby future PET-CT will be an integral part of the most radiotherapy treatment planning procedures in an every-day clinical practice. Apart from a clear role in radiation planning of lung cancer, with forthcoming clinical trials, we will get more evidence of the optimal use of PET-CT in radiotherapy planning of other solid tumours.
Keywords: positron emission therapy, radiotherapy, radiotherapy planning, tumour biology
Published in DiRROS: 16.04.2024; Views: 44; Downloads: 6
.pdf Full text (1,25 MB)

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The influence of folate pathway polymorphisms on high-dose methotrexaterelated toxicity and survival in children with non-Hodgkin malignant lymphoma
Nina Erčulj, Barbara Faganel Kotnik, Maruša Debeljak, Janez Jazbec, Vita Dolžan, 2014, original scientific article

Abstract: Background. We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL). Patients and methods. In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. Results. Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype. Conclusions. Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTXrelated toxicity in children with NHL.
Keywords: childhood, non-Hodgkin lymphoma, polymorphism
Published in DiRROS: 16.04.2024; Views: 33; Downloads: 18
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