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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: 99; Downloads: 20
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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: 73; Downloads: 15
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Abstract: 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.
Keywords: mediastinal teratoma, non-immune hydrops fetalis, diaphragm paralysis, chronic respiratory insufficiency, novorojenčki, mediastinalni teratom, kronična respiratorna insuficienca
Published in DiRROS: 11.04.2024; Views: 95; Downloads: 43
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Abstract: 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
Keywords: autonomic nervous system, diving, parasympathicus, cardiovascular risk
Published in DiRROS: 09.04.2024; Views: 76; Downloads: 32
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Abstract: Plant viruses pose a significant threat to agriculture. Several are stable outside their hosts, can enter water bodies and remain infective for prolonged periods of time. Even though the quality of irrigation water is of increasing importance in the context of plant health, the presence of plant viruses in irrigation waters is understudied. In this study, we conducted a large-scale high-throughput sequencing (HTS)-based virome analysis of irrigation and surface water sources to obtain complete information about the abundance and diversity of plant viruses in such waters. We detected nucleic acids of plant viruses from 20 families, discovered several novel plant viruses from economically important taxa, like Tobamovirus and observed the influence of the water source on the present virome. By comparing viromes of water and surrounding plants, we observed presence of plant viruses in both compartments, especially in cases of large-scale outbreaks, such as that of tomato mosaic virus. Moreover, we demonstrated that water virome data can extensively inform us about the distribution and diversity of plant viruses for which only limited information is available from plants. Overall, the results of the study provided extensive insights into the virome of irrigation waters from the perspective of plant health. It also suggested that an HTS-based water virome surveillance system could be used to detect potential plant disease outbreaks and to survey the distribution and diversity of plant viruses in the ecosystem.
Keywords: plant viruses, environmental water testing, high-throughput sequencing, agroecosystems, irrigation water, virome
Published in DiRROS: 29.03.2024; Views: 125; Downloads: 52
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