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Iskalni niz: "avtor" (Kern Izidor) .

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1.
Triple synchronous cancers : a medical and ethical problem
Lučka Debevec, Rok Cesar, Izidor Kern, 2007, izvirni znanstveni članek

Povzetek: Background. In a patient with suspicious synchronous multiple tumours, there are limited possibilities for effective therapy. Therefore, the decision for invasive diagnostics and precise staging of tumours is questionable, especially in elderly patients suitable only for symptomatic therapy. Case report. A 78-year-old man with hypertension and angina pectoris was admitted to the hospital due to syncope. Two primary lung tumours and a kidney tumour were detected by imaging investigation. The patient refused invasive diagnostics and left the hospital. After 19 months he was readmitted in an impaired clinical condition and subsequently died of bronchopneumonia. The autopsy revealed squamous cell carcinoma of the right upper lobe with metastases to regional lymph nodes and to the brain, small-cell carcinoma of the left upper lobe with metastases to regional lymph nodes and to the spleen,and clear-cell kidney carcinoma with multiple metastases to the lungs. All tumours were necrotizing, and therefore we assumed that any attempt at specific therapy would have been ineffective. Conclusions. In an elderly patient with advanced lung tumors and suspicious synchronous triple cancers, the "wait and see" option can be suitable.
Objavljeno v DiRROS: 22.02.2024; Ogledov: 67; Prenosov: 20
.pdf Celotno besedilo (147,54 KB)

2.
Surgical treatment of malignant pleural mesothelioma
Janez Eržen, Stanko Vidmar, Mihael Sok, Andrej Debeljak, Peter Kecelj, Viljem Kovač, Marjeta Stanovnik, Tomaž Rott, Izidor Kern, 2005, izvirni znanstveni članek

Povzetek: Background. The aim of the study was to identify perioperative morbidity and mortality, the category and mode of adjuvant treatment, local recurrence and survival in patients treated by extrapleural pneumonectony (EPP) for malignantpleural mesothelioma (NLPM). Methods. From 2000 to 2003, 18 patients with MPM were referred to the Department of Thoracic Surgery in Ljubljana, and17 of them were operated on. Two patients underwent explorative thoracotomy, and 15 patients were evaluated. Five female and nine male patients (aged 52-68 years) were treated by EPP and one male patient by pleurectomy. Eight patients received both adjuvant chemotherapy (ChT) and radiotherapy (RT), with cisplatin 100 mg/m2 + mitomycin C 6-10 mg/m2 gemcitabine 1000 mg/m2 and external beam radiation with 24 Gy - 58 Gy respectively, three patients received no adjuvant therapy, three patients weretreated by adjuvant ChT, two of them were given cisplatin 100 mg/m2 + mitomycin C 6-10 mg/m2, and one patient cisplatin 100 mg/m2 on the first day and gemcitabine 250 mg/rn2 in prolonged 6 hours infusion on the first and on the eighth day. One patient was treated only by adjuvant RT. Results. There were no perioperative deaths and the postoperative morbidity was 42%. Of the 15 evaluable patients, and in the median follow up of 40 months (28-64), we noticed nine (60.0%) recurrences, seven local and two abdominal. Eight (53.3%)patients died, all because of the local progress of disease. (Abstract truncated at 2000 characters)
Objavljeno v DiRROS: 14.02.2024; Ogledov: 77; Prenosov: 22
.pdf Celotno besedilo (82,10 KB)

3.
Characterization of lung cancer patients, their actual treatment and survival : experience of Slovenia
Lučka Debevec, Andrej Debeljak, Janez Eržen, Viljem Kovač, Izidor Kern, 2005, izvirni znanstveni članek

Povzetek: Background. The aim of the study was to establish characteristics of lung cancer patients diagnosed at the University Clinic of Respiratory and AllergicDiseases Golnik in 1996, their selected and realized therapy, and survival. Methods. The retrospective study comprises 345 patients aged from 37to 90 years (mean 65), 285 males and 60 females. Performance status (Karnofsky): > 80 in 171 patients, 60-80 in 130 and < 60 in 44 patients. Mirroscopically confirmed tumour in 97%: by bronchoscopy 281, transthoracic needle biopsy 23, peripheral lymph nodes biopsy 12, sputum cytology 7, pleural(effusion) cytology 4, distant metastases biopsy 2, mediastinoscopy 1, autopsy 4 patients. Histology and/or cytology: squamous 131, adenocarcinoma 86, large cell 63, small cell 51, non-small cell 1, unclassified 2. Clinical staging of non-small cell lung cancer (NSCLC): stage I 63, stage ll 32, stage IIIA 48, stage IIIB 59, stage IV 77, undeterminable 2 patients. Staging in small cell lung cancer (SCLC): limited disease 24, extended disease 27 patients. Results. The selected primary oncological therapy was changed in 11%. Realized primary therapy: radiotherapy 102 (30%), surgery 77 (23%), chemotherapy 47 (14%), supportive treatment 111 (33%). In resected patients staging was correct in 46%, underestimated in 44%, overestimated in 10%. The overall five-year survival was 7.8% (median 6.2 months) and the five year survival of resected patients was 41.9% (median 33 months). The median survival of irradiated patients was 5.7 months, of supportively treated patients 2.5 months. The survival was significantly different according to theperformance status and stage. (Abstract truncated at 2000 characters)
Objavljeno v DiRROS: 14.02.2024; Ogledov: 69; Prenosov: 16
.pdf Celotno besedilo (88,13 KB)

4.
Cytology of mediastinal tumors
Milivoj Mermolja, Izidor Kern, Marjeta Terčelj-Zorman, Marjan Jereb, 1997, izvirni znanstveni članek

Povzetek: Our experience with cytological examinations of tumorous mediastinal lesions is evaluated. A group of 117 patients with mediastinal tumor have been included into the study. Among them carcinomas prevailed (60,7%), followed by lymphomas (18,8%), other tumors (15.4%) and thymic neoplasms (5.1%). Malignantor suspicious cells were found in 77.4% of patients with carcinoma. The cells indicating a possibility of non-Hodgkin's lymphoma were found in 9 out of 14 patients. In 5 out of 6 thymic neoplasms the cytological pattern wasconsistent with the diagnosis of thymic neoplasm. One case of thymoma was cytologically falsely diagnosed as malignant lymphoma. One case of neurofibroma was falsely diagnosed as adenocarcinoma. The sensitivity of cytological examinations was 67.5%. If 18 patients with diagnostically unsatisfactory material were excluded from the analysis, the sensitivity wouldincrease to 80.8%. Owing to the wide variety of primary and metastatic tumors that can occur in the mediastinum, apart from the routine cytological techniques, additional staining methods should be used. For final cytological diagnosis the integration of cytological findings with clinical and radiological data is often required. Owing to the characteristics of the obtained material and biological behaviour of some mediastinal tumors, some tumors cannot be definitively diagnosed by cytological examinations alone.
Objavljeno v DiRROS: 18.01.2024; Ogledov: 117; Prenosov: 38
.pdf Celotno besedilo (1,10 MB)

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Priporočila za obravnavo bolnikov s pljučnim rakom
Martina Vrankar, Nina Boc, Izidor Kern, Aleš Rozman, Karmen Stanič, Tomaž Štupnik, Mojca Unk, Maja Ebert Moltara, Vesna Zadnik, Katja Adamič, Jernej Benedik, Marko Bitenc, Jasna But-Hadžić, Anton Crnjac, Marina Čakš, Dominik Časar, Eva Ćirić, Tanja Čufer, Ana Demšar, Rok Devjak, Goran Gačevski, Marta Globočnik Kukovica, Kristina Gornik-Kramberger, Maja Ivanetič Pantar, Marija Ivanović, Urška Janžič, Staša Jelerčič, Veronika Kloboves-Prevodnik, Mile Kovačević, Luka Ležaič, Mateja Marc-Malovrh, Katja Mohorčič, Loredana Mrak, Igor Požek, Nina Turnšek, Bogdan Vidmar, Dušanka Vidovič, Gregor Vlačić, Ana Lina Vodušek, Rok Zbačnik, Ivana Žagar, 2023, strokovni članek

Povzetek: Leta 2019 so bila objavljena Priporočila za obravnavo bolnikov s pljučnim rakom, ki so v slovenski prostor vnesla prepotrebno poenotenje diagnostike in zdravljenja z namenom izboljšanja preživetja bolnikov s pljučnim rakom. Posodobitev Priporočil tri leta po izidu izvirnika prinaša največ novosti v poglavju o sistemskem zdravljenju bolnikov s pljučnim rakom. To kaže na izjemen napredek na področju razumevanja onkogeneze in biologije pljučnega raka ter s tem razvoja novih zdravil. Breme pljučnega raka ostaja veliko, saj je pljučni rak pri nas in v svetu še vedno najpogostejši vzrok smrti zaradi raka. Za vsako peto smrt zaradi raka je odgovoren pljučni rak. Skoraj tretjina bolnikov s pljučnim rakom ne prejme specifičnega onkološkega zdravljenja, bodisi zaradi slabega stanja zmogljivosti, spremljajočih bolezni ali obsega bolezni. Polovica bolnikov ima ob diagnozi razsejano bolezen, zaradi česar izboljšanje preživetja z malimi koraki sledi napredku v zdravljenju bolnikov s pljučnim rakom. Ti podatki nas opominjajo, da se bomo morali za velike premike v obravnavi bolnikov s pljučnim rakom lotiti drugačnih pristopov. Kot najbolj obetavno se ponuja zgodnje odkrivanje bolezni, ko so možnosti ozdravitve pljučnega raka najboljše. Zapisana Priporočila so usmeritev za obravnavo bolnikov s pljučnim rakom. Le s sodobnim multidisciplinarnim pristopom obravnave lahko bolniku ponudimo zdravljenje, ki mu omogoča najboljši izhod prognostično neugodne bolezni.
Ključne besede: pljučni rak, priporočila
Objavljeno v DiRROS: 27.07.2023; Ogledov: 320; Prenosov: 112
.pdf Celotno besedilo (708,18 KB)
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P14/ARF-positive malignant pleural mesothelioma : ǂa ǂphenotype with distinct immune microenvironment
Federica Pezzuto, Francesca Lunardi, Luca Vedovelli, Francesco Fortarezza, Loredana Urso, Federica Grosso, Giovanni Luca Ceresoli, Izidor Kern, Gregor Vlačić, Fiorella Calabrese, 2022, izvirni znanstveni članek

Povzetek: Introduction: The CDKN2A gene plays a central role in the pathogenesis of malignant pleural mesothelioma (MPM). The gene encodes for two tumor suppressor proteins, p16/INK4A and p14/ARF, frequently lost in MPM tumors. The exact role of p14/ARF in MPM and overall its correlation with the immune microenvironment is unknown. We aimed to determine whether there is a relationship between p14/ARF expression, tumor morphological features, and the inflammatory tumor microenvironment. Methods: Diagnostic biopsies from 76 chemo-naive MPMs were evaluated. Pathological assessments of histotype, necrosis, inflammation, grading, and mitosis were performed. We evaluated p14/ARF, PD-L1 (tumor proportion score, TPS), and Ki-67 (percentage) by immunohistochemistry. Inflammatory cell components (CD3+, CD4+, CD8+ T lymphocytes; CD20+ B-lymphocytes; CD68+ and CD163+ macrophages) were quantified as percentages of positive cells, distinguishing between intratumoral and peritumoral areas. The expression of p14/ARF was associated with several clinical and pathological characteristics. A random forest-based machine-learning algorithm (Boruta) was implemented to identify which variables were associated with p14/ARF expression. Results: p14/ARF was evaluated in 68 patients who had a sufficient number of tumor cells. Strong positivity was detected in 14 patients (21%) (11 epithelioid and 3 biphasic MPMs). At univariate analysis, p14/ARF-positive epithelioid mesotheliomas showed higher nuclear grade (G3) (p = 0.023) and higher PD-L1 expression (≥50%) (p = 0.042). The percentages of CD4 and CD163 in peritumoral areas were respectively higher and lower in p14/ARF positive tumors but did not reach statistical significance with our sample size (both p = 0.066). The Boruta algorithm confirmed the predictive value of PD-L1 percentage for p14/ARF expression in all histotypes. Conclusions: p14/ARF-positive epithelioid mesotheliomas may mark a more aggressive pathological phenotype (higher nuclear grade and PD-L1 expression). Considering the results regarding the tumor immune microenvironment, p14/ARF-negative tumors seem to have an immune microenvironment less sensitive to immune checkpoint inhibitors, being associated with low PD-L1 and CD4 expression, and high CD163 percentage. The association between p14/ARF-positive MPMs and PD-L1 expression suggests a possible interaction of the two pathways. Confirmation of our preliminary results could be important for patient selection and recruitment in future clinical trials with anticancer immunotherapy.
Ključne besede: lung -- cytology -- pathology, neoplasms, malignant mesothelioma, malignant pleural mesothelioma, tumor microenvironment
Objavljeno v DiRROS: 30.05.2022; Ogledov: 722; Prenosov: 471
.pdf Celotno besedilo (13,14 MB)
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9.
Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small cell lung cancer : an international multicenter study
Zsolt Megyesfalvi, Nandor Barany, Andras Lantos, Zsuzsanna Valko, Orsolya Pipek, Christian Lang, Anna Schwendenwein, Felicitas Oberndorfer, Sandor Paku, Bence Ferencz, Izidor Kern, Mile Kovačević, Viktoria Laszlo, Balazs Dome, 2022, izvirni znanstveni članek

Povzetek: The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we have investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1 and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines reveal distinct vulnerability profiles defined by transcription regulators.
Ključne besede: Non-small-cell lung carcinoma, immunohistochemistry, molecular subtypes, prognostic relevance, expression pattern, neuroendocrine subtypes
Objavljeno v DiRROS: 27.05.2022; Ogledov: 781; Prenosov: 1181
.pdf Celotno besedilo (4,37 MB)
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10.
Utility of telomerase gene mutation testing in patients with idiopathic pulmonary fibrosis in routine practice
Julij Šelb, Katarina Osolnik, Izidor Kern, Peter Korošec, Matija Rijavec, 2022, izvirni znanstveni članek

Povzetek: Recent studies have suggested that causative variants in telomerase complex genes (TCGs) are present in around 10% of individuals with idiopathic pulmonary fibrosis (IPF) regardless of family history of the disease. However, the studies used a case-control rare variant enrichment study design which is not directly translatable to routine practice. To validate the prevalence results and to establish the individual level, routine clinical practice, and utility of those results we performed next generation sequencing of TCGs on a cohort of well-characterized consecutive individuals with IPF (diagnosis established according to ATS/ERS/JRS/ALAT guidelines). Of 27 IPF patients, three had a family history of idiopathic interstitial pneumonia (familial IPF) and 24 did not (sporadic IPF). Pathogenic/likely-pathogenic variants (according to American College of Medical Genetics criteria) in TCG were found in three individuals (11.1%) of the whole cohort; specifically, they were present in 2 out of 24 (8.3%) of the sporadic and in 1 out of 3 (33.3%) of the patients with familial IPF. Our results, which were established on an individual-patient level study design and in routine clinical practice (as opposed to the case-control study design), are roughly in line with the around 10% prevalence of causative TCG variants in patients with IPF.
Ključne besede: telomerase, idiopathic pulmonary fibrosis, genetic variation, telomerase complex
Objavljeno v DiRROS: 07.02.2022; Ogledov: 743; Prenosov: 342
.pdf Celotno besedilo (236,11 KB)

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