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Query: "author" (Roman Bošnjak) .

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1.
Awake craniotomy for operative treatment of brain gliomas - experience from University Medical Centre Ljubljana
Tilen Žele, Tomaž Velnar, Blaž Koritnik, Roman Bošnjak, Jasmina Markovič Božič, 2023, original scientific article

Abstract: Background. Awake craniotomy is a neurosurgical technique that allows neurophysiological testing with patient cooperation during the resection of brain tumour in regional anaesthesia. This allows identification of vital functional (i.e. eloquent) brain areas during surgery and avoidance of their injury. The aim of the study was to present clinical experience with awake craniotomy for the treatment of gliomas at the University Medical Centre Ljubljana from 2015 to 2019.Patients and methods. Awake craniotomy was considered in patients with a gliomas near or within the language brain areas, in all cases of insular lesions and selected patients with lesions near or within primary motor brain cortex. Each patient was assessed before and after surgery.Results. During the 5-year period, 24 awake craniotomies were performed (18 male and 6 female patients; average age 41). The patient’s cooperation, discomfort and perceived pain assessed during the awake craniotomy were in majority of the cases excellent, slight, and moderate, respectively. After surgery, mild neurological worsening was observed in 13% (3/24) of patients. Gross total resection, in cases of malignant gliomas, was feasible in 60% (6/10) and in cases of low-grade gliomas in 29% (4/14). The surgery did not have important negative impact on functional status or quality of life as assessed by Karnofsky score and Short-Form 36 health survey, respectively (p > 0.05). Conclusions. The results suggest that awake craniotomy for treatment of gliomas is feasible and safe neurosurgical technique. The proper selection of patients, preoperative preparation with planning, and cooperation of medical team members are necessary for best treatment outcome.
Keywords: awake craniotomy, surgery of gliomas, intraoperative neurophysiological testing, primary brain tumours, clinical experiences
Published in DiRROS: 25.07.2024; Views: 94; Downloads: 72
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2.
Localization patterns of cathepsins K and X and their predictive value in glioblastoma
Barbara Breznik, Clara Limbaeck Stanic, Andrej Porčnik, Andrej Blejec, Miha Koprivnikar Krajnc, Roman Bošnjak, Janko Kos, Cornelis J. F. van Noorden, Tamara Lah Turnšek, 2018, original scientific article

Abstract: Background Glioblastoma is a highly aggressive central nervous system neoplasm characterized by extensive infiltration of malignant cells into brain parenchyma, thus preventing complete tumor eradication. Cysteine cathepsins B, S, L and K are involved in cancer progression and are overexpressed in glioblastoma. We report here for the first time that cathepsin X mRNA and protein are also abundantly present in malignant glioma. Materials and methods Gene expression of cathepsins K and X was analyzed using publically-available tran-scriptomic datasets and correlated with glioma grade and glioblastoma subtype. Kaplan-Maier survival analysis was performed to evaluate the predictive value of cathepsin K and X mRNA expression. Cathepsin protein expression was localized and semi-quantified in tumor tissues by immunohistochemistry. Results Highest gene expression of cathepsins K and X was found in glioblastoma, in particular in the mesenchymal subtype. Overall, high mRNA expression of cathepsin X, but not that of cathepsin K, correlated with poor patients’ survival. Cathepsin K and X proteins were abundantly and heterogeneously expressed in glioblastoma tissue. Immuno-labeling of cathepsins K and X was observed in areas of CD133-positive glioblastoma stem cells, localized around arterioles in their niches that also expressed SDF-1α and CD68. mRNA levels of both cathepsins K and X correlated with mRNA levels of markers of glioblastoma stem cells and their niches. Conclusions The presence of both cathepsins in glioblastoma stem cell niche regions indicates their possible role in regulation of glioblastoma stem cell homing in their niches. The clinical relevance of this data needs to be elaborated in further prospective studies.
Keywords: cathepsins, glioblastoma, immunohistochemistry, patient survival, cancer stem cell niches
Published in DiRROS: 24.07.2024; Views: 118; Downloads: 95
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3.
Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches
Barbara Breznik, Clara Limbaeck Stanic, Janko Kos, Mohammed Khurshed, Vashendriya V. V. Hira, Roman Bošnjak, Tamara Lah Turnšek, Cornelis J. F. van Noorden, 2018, original scientific article

Abstract: Glioblastoma (GBM) is the most lethal brain tumor also due to malignant and therapy-resistant GBM stem cells (GSCs) that are localized in protecting hypoxic GSC niches. Some members of the cysteine cathepsin family of proteases have been found to be upregulated in GBM. Cathepsin K gene expression is highly elevated in GBM tissue versus normal brain and it has been suggested to regulate GSC migration out of the niches. Here, we investigated the cellular distribution of cathepsins B, X and K in GBM tissue and whether these cathepsins are co-localized in GSC niches. Therefore, we determined expression of these cathepsins in serial paraffin sections of 14 human GBM samples and serial cryostat sections of two samples using immunohistochemistry and metabolic mapping of cathepsin activity using selective fluorogenic substrates. We detected cathepsins B, X and K in peri-arteriolar GSC niches in 9 out of 16 GBM samples, which were defined by co-expression of the GSC marker CD133, the niche marker stromal-derived factor-1α (SDF-1α) and smooth muscle actin as a marker for arterioles. The expression of cathepsin B and X was detected in stromal cells and cancer cells throughout the GBM sections, whereas cathepsin K expression was more restricted to arteriole-rich regions in the GBM sections. Metabolic mapping showed that cathepsin B, but not cathepsin K is active in GSC niches. On the basis of these findings, it is concluded that cathepsins B, X and K have distinct functions in GBM and that cathepsin K is the most likely GSC niche-related cathepsin of the three cathepsins investigated.
Keywords: cysteine cathepsins, glioblastoma stem cells, niches, stroma, proteolytic activity
Published in DiRROS: 24.07.2024; Views: 104; Downloads: 105
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4.
The cytotoxic effects of cannabidiol and cannabigerol on glioblastoma stem cells may mostly involve GPR55 and TRPV1 signalling
Tamara Lah Turnšek, Bernarda Majc, Metka Novak, Ajda Sušnik, Barbara Breznik, Andrej Porčnik, Roman Bošnjak, Aleksander Sadikov, Marta Malavolta, Selma Halilčević, Jernej Mlakar, Roby Zomer, 2022, original scientific article

Abstract: Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60–70% of all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and non-specific ion receptor protein transporters TRPs. First, we found up-regulated CNR1, GPR55, and TRPV1 expression in glioma patient-derived tissue samples and cell lines compared with non-malignant brain samples. CNR1 and GPR55 did not correlate with glioma grade, whereas TRPV1 negatively correlated with grade and positively correlated with longer overall survival. This suggests a tumour-suppressor role of TRPV1. With respect to markers of GBM stem cells, preferred targets of therapy, TRPV1 and GPR55, but not CNR1, strongly correlated with different sets of stemness gene markers: NOTCH, OLIG2, CD9, TRIM28, and TUFM and CD15, SOX2, OCT4, and ID1, respectively. This is in line with the higher expression of TRPV1 and GPR55 genes in GSCs compared with differentiated GBM cells. Second, in a panel of patient-derived GSCs, we found that CBG and CBD exhibited the highest cytotoxicity at a molar ratio of 3:1. We suggest that this mixture should be tested in experimental animals and clinical studies, in which currently used Δ9-tetrahydrocannabinol (THC) is replaced with efficient and non-psychoactive CBG in adjuvant standard-of-care therapy.
Keywords: glioblastoma, glioma, cannabigerol, cannabidiol, cannabinoid receptors, stem cells
Published in DiRROS: 18.07.2024; Views: 116; Downloads: 101
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5.
Advances in the management of craniopharyngioma in children and adults
Mojca Jensterle Sever, Sončka Jazbinšek, Roman Bošnjak, Mara Popović, Lorna Zadravec-Zaletel, Tina Vipotnik-Vesnaver, Barbara Faganel Kotnik, Primož Kotnik, 2019, review article

Abstract: Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient%s quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor%s molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity. Conclusions. Craniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.
Keywords: craniopharyngioma, hypopituitarism, metabolic syndrome
Published in DiRROS: 09.07.2024; Views: 133; Downloads: 70
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6.
7.
Early outcome in endoscopic extended endonasal approach for removal of supradiaphragmatic craniopharyngiomas : a case series and a comprehensive review
Roman Bošnjak, Mitja Benedičič, Alenka Vittori, 2013, original scientific article

Abstract: Background. The choice of endoscopic expanded endonasal approach introduces the possibility of improved gross total resection of craniopharyngioma while minimizing surgical morbidity in a significant subset of patients. Methods. From our trans-sphenoidal surgical series of 331 cases, we retrospectively reviewed visual, endocrine and neuro-cognitive outcomes in the first consecutive eight patients (median age 63 years; range 4773 years) with newly diagnosed supradiaphragmatic craniopharyngioma (median tumour height 23 mm; range 1534 mm), removed by expanded endonasal approach (median follow-up 27 months; range 1069 months). Gross total resection was attempted in all patients. Results. Gross total resection was achieved in 6 of 8 patients. Visual improvement was present in 6 of 8 patients of patients or in 14 of 16 eyes. New endocrinopathy, including diabetes insipidus, appeared in 5 of 8 patients. Stalk was preserved in 4 patients. Cognitive decline was present in 2 cases. Five of 8 patients retained previous quality of life. Conclusions. Our early outcome results are comparable to the recent few expanded endonasal approach series, except for the incidence of new endocrinopathy and cerebrospinal fluid leak rate. This was influenced by higher number of transinfundibular tumours in our series, where stalk preservation is less likely, and not using nasoseptal flap or gasket closure in the first half of cases. Including data from the literature and ours, expanded endonasal approach shows a trend for improved gross total resection rate with less morbidity, more obviously for visual outcome and quality of life than for endocrine outcome. However, validity of expanded endonasal approach should be confirmed in a larger number of patients with a longer follow-up period.
Published in DiRROS: 22.03.2024; Views: 220; Downloads: 68
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8.
9.
Odpornost glioblastoma na radioterapijo : vpliv rakavih matičnih celic in mikroo[ko]lja tumorja
Barbara Breznik, Bernarda Majc, Anamarija Habič, Urška Ušeničnik, Andrej Porčnik, Roman Bošnjak, Jernej Mlakar, Marija Skoblar Vidmar, Tanja Jesenko, Maja Čemažar, Tamara Lah Turnšek, Metka Novak, 2022, published scientific conference contribution (invited lecture)

Abstract: Glioblastom je najpogostejši možganski tumor pri odraslih z zelo slabo prognozo preživetja bolnikov. Ta je posledica odpornosti glioblastoma na standardno zdravljenje, ki vključuje radioterapijo in kemoterapijo. Z namenom načrtovanja učinkovitejših pristopov zdravljenja preučujemo biološke mehanizme odpornosti glioblastoma na radioterapijo s poudarkom na mikrookolju tumorja in rakavih matičnih celicah. V predkliničnih raziskavah uporabljamo napredne in personalizirane celične modele, ki posnemajo mikrookolje tumorja v bolnikih in z večjo natančnostjo napovedo odziv bolnika na zdravljenje. Hkrati so takšni modeli pomembni za testiranje novih pristopov za zdravljenje kot je imunoterapija.
Keywords: glioblastom, mikrookolje, organoidi, možganski rak, možganski tumor, onkologija
Published in DiRROS: 16.06.2022; Views: 806; Downloads: 239
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10.
Nevrokirurško zdravljenje zasevkov v centralnem živčevju
Roman Bošnjak, 2000, review article

Published in DiRROS: 31.08.2018; Views: 2453; Downloads: 605
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