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1992. The influence of folate pathway polymorphisms on high-dose methotrexaterelated toxicity and survival in children with non-Hodgkin malignant lymphomaNina 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
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1993. Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approachKlemen Zupančič, Andrej Blejec, Ana Herman, Matija Veber, Urška Verbovšek, Marjan Koršič, Miomir Knežević, Primož Rožman, Tamara Lah Turnšek, Kristina Gruden, Helena Motaln, 2014, original scientific article Abstract: Background. Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. Materials and methods. We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM. Results. We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM. Conclusions. Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.
Keywords: glioblastoma, proteomics, biomarker
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1994. Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesotheliomaKatja Goričar, Viljem Kovač, Vita Dolžan, 2014, original scientific article Abstract: Introduction. A combination of pemetrexed and cisplatin has been shown to improve the outcome in patients with malignant pleural mesothelioma (MPM), however, there is a great heterogeneity in treatment response among patients. The aim of our study was to evaluate the influence of polymorphisms in folate pathway and transporter genes on pemetrexed treatment outcome in Slovenian patients with MPM. Methods. MPM patients treated with pemetrexed in the course of a prospective randomized clinical trial were genotyped for nineteen polymorphisms in five genes of folate pathway and six transporter genes. Logistic regression was used to assess the influence of polymorphisms on treatment efficacy and toxicity, while Cox regression was used to determine their influence on progression-free and overall survival. Results. Patients with at least one polymorphic MTHFD 1 rs2236225 allele had a significantly lower response rate (p = 0.005: odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.03-0.54) and shorter progression-free survival (p = 0.032: hazard ratio [HR) = 3.10: 95% CI = 1.10-8.74) than non-carriers. Polymorphisms in transporter genes did not influence survival; however, several were associated with toxicity. Liver toxicity was significantly lower in carriers of polymorphic ABCC2 rs2273697 (p = 0.028: OR = 0.23; 95% CI = 0.06-0.85). SLC01Bl rs4149056 (p = 0.028: OR = 0.23: 95% CI = 0.06-0.85) and rsll045879 (p = 0.014: OR = 0.18; 95% CI = 0.05-0.71) alleles compared to non-carriers, as well as in patients with SLC01Bl GCAC haplotype (p = 0.048; OR = 0.17; 95% CI = 0.03-0.98). Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004: OR = 10.67; 95% CI = 2.15-52.85) and ABCC2 CAG haplotype (p = 0.006: OR = 5.67: 95% CI = 1.64-19.66). Conclusions. MTHFD 1 polymorphism affected treatment response and survival. while polymorphisms in ABCC2 and SLC01Bl transporter genes influenced the risk for toxicity. These polymorphisms could serve as potential markers of pemetrexed treatment outcome in patients with MPM.
Keywords: polymorphisms, folate pathway, mesothelioma
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1996. Balloon aortic valvuloplasty (BAV) as a bridge to aortic valve replacement in cancer patients who require urgent non-cardiac surgeryPolonca Kogoj, Rok Devjak, Matjaž Bunc, 2014, original scientific article Abstract: Balloon aortic valvuloplasty (BAV) is a percutaneous treatment option for severe, symptomatic aortic stenosis. Due to early restenosis and failure to improve long term survival, BAV is considered a palliative measure in patients who are not suitable for open heart surgery due to increased perioperative risk. BAV can be used also as a bridge to surgical or transcatheter aortic valve implantation (TAVI) in hemodinamically unstable patients or in patients who require urgent major non-cardiac surgery.We reported 6 oncologic patients with severe aortic stenosis that required a major abdominal and gynecological surgery. In 5 cases we performed BAV procedure alone, in one patients with concomitant coronary artery disease we combined BAV and PCI. With angioplasty and BAV we achieved a good coronary artery flow and an increase in aortic valve area without any periprocedural complications. After the successful procedure, we observed a hemodynamic and symptomatic improvement. As a consequence the operative risk for non-cardiac surgery decreased and the surgical treatment was done without complications in all the 6 cases.We conclude that BAV can be utilized as a part of a complex therapy in severe aortic stenosis aimed to improve the quality of life, decrease the surgical risk for major non-cardiac surgery or as a bridge to surgical or transcatheter aortic valve implantation.
Keywords: aortic valve stenosis, elderly comorbidities, coronary artery disease
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1997. Circulating serum sVCAM-1 concentration inadvanced ovarian cancer patients : correlation with concentration in ascitesMarina Jakimovska, Katarina Černe, Ivan Verdenik, Borut Kobal, 2014, original scientific article Abstract: Background. Vascular cell adhesion molecule-1 (VCAM-1) is associated with ovarian cancer progression but theorigin of its soluble form (sVCAM-1) in serum is not well investigated. The purpose of this study was to elucidate whetherthe concentration of sVCAM-1 in serum correlates with the concentration in ascites, that represents local tumour environment,and with systemic inflammation, various clinicopathological characteristics, and patient outcome.Patients and methods. Thirty-six patients with advanced ovarian cancer were included in the study. Serum forsVCAM-1 analysis was obtained prior to surgery. Ascites samples were collected at the beginning of the operation.Clinical data were collected from patients medical records. sVCAM-1 in samples was analysed by flow cytometricbead-based assay. The mean follow-up period was 11 months (range 0-23) from the time of surgery.Results. Serum sVCAM-1 concentrations are positively correlated to ascites sVCAM-1 concentrations. There was aweakly positive correlation of serum sVCAM-1 with tumour size and no correlation with inflammatory tumour markers,FIGO stage or grade. Higher concentrations of sVCAM-1 were associated with poor disease outcome (death fromovarian cancer) in almost all cases before chemotherapy was started.Conclusion. This is the first study demonstrating that serum concentrations of sVCAM-1 in advanced ovarian cancerpatients correlate with sVCAM-1 concentrations in ascites, thus expressing the biologic potential of malignant diseaseto metastasis, rather than systemic inflammation. Higher serum and ascites sVCAM-1 concentrations might have predictivepotential for different biologic behaviour.
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1998. Segmentation of hepatic vessels from MRI images for planning of electroporation-based treatments in the liverMarija Marčan, Denis Pavliha, Maja Marolt-Mušič, Igor Fučkan, Ratko Magjarević, Damijan Miklavčič, 2014, original scientific article Keywords: electrochemotherapy, non-thermal irreversible electroporation, treatment planning, hepatic vessel segmentation, non-invasive tumor treatments, MRI of liver
Published in DiRROS: 16.04.2024; Views: 464; Downloads: 231
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