11. The prognostic and predictive value of human gastrointestinal microbiome and exosomal mRNA expression of PD-L1 and IFNγ for immune checkpoint inhibitors response in metastatic melanoma patients : protocol trialAna Erman, Marija Ignjatović, Katja Leskovšek, Simona Miceska, Urša Lampreht Tratar, Maša Omerzel, Veronika Kloboves-Prevodnik, Maja Čemažar, Lidija Kandolf Sekulović, Gorazd Avguštin, Janja Ocvirk, Tanja Mesti, 2023, izvirni znanstveni članek Povzetek: Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study. Stool samples are submitted before the start of treatment, at the 12th (+/−2) week and 28th (+/−2) week, and at the occurrence of event (suspected disease progression/hyperprogression, immune-related adverse event (irAE), deterioration). Peripheral venous blood samples are taken additionally at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether the human gastrointestinal microbiome (bacterial and viral) and the exosomal mRNA expression of PD-L1 and IFNγ and its dynamics predicts the response to treatment with PD-1 and CTLA-4 inhibitors and its association with the occurrence of irAE. The response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclusions: This is the first study to combine and investigate multiple potential predictive and prognostic biomarkers and their dynamics in first line ICI in metastatic melanoma patients.
Ključne besede: gastrointestinal microbiome, mRNA expression of PD-L1 and IFNγ, immune checkpoint inhibitors, metastatic melanoma
Objavljeno v DiRROS: 21.03.2024; Ogledov: 71; Prenosov: 36
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12. Potentiation of electrochemotherapy by intramuscular IL-12 gene electrotransfer in murine sarcoma and carcinoma with different immunogenicityAleš Sedlar, Tanja Jesenko, Boštjan Markelc, Lara Prosen, Simona Kranjc Brezar, Maša Omerzel, Tanja Blagus, Maja Čemažar, Gregor Serša, 2012, izvirni znanstveni članek Objavljeno v DiRROS: 21.03.2024; Ogledov: 73; Prenosov: 28
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13. Triple negative breast cancer : prognostic factors and survivalTanja Ovčariček, Snježana Frković-Grazio, Erika Matos, Barbara Možina, Simona Borštnar, 2011, izvirni znanstveni članek Povzetek: Background. Triple negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesteron(PgR) receptors as well as human epidermal growth factor receptor 2 (HER2). Our retrospective analysis addressed prognostic factors for short- and long-term outcomes of patients (pts) with TNBC pts treated in routine clinical practice. Patient and methods.Our retrospective study included 269 TNBC treated at Institute of Oncology Ljubljana between March 2000 and December 2006. The collected data included patientsć, tumoursć and treatmentsć characteristics. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model was used in the multivariate analysis. Results. The median age ofour patients was 55.3 yrs (23-88.5) and the median follow-up was 5.9 yrs (0.3-9.6). Six (2%) pts experienced local only, 79 (92%) pts distal recurrenceand 66 (24%) died. The predominant localisation of the first relapsewas in visceral organs (70.4%). The 5-year disease-free survival (DFS) for the entire group was 68.2% and the 5-year overall survival (OS) was 74.5%.We found a pattern of high recurrence rate in the first 3 years following the diagnosis and a clear decline in recurrence rate over the next 3years. In the univariate analysis age, nodal status, size and lymphovascular invasion (LVI) were found to have a significant impact on DFS as well as on OS. In the multivariate analysis only age (HR=1.79; 95%CI=1.14-2.82; p=0.012) and nodal status (HR=2.71; 95%CI=1.64-4.46; p<0.001) retained their independent prognostic value for DFS and for OS only the nodal status (HR=2.96; 95%CI=1.51-5.82; p=0.002). (Abstract truncated at 2000 characters)
Objavljeno v DiRROS: 19.03.2024; Ogledov: 91; Prenosov: 30
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14. Lymphedema following cancer therapy in Slovenia : a frequently overlooked condition?Tanja Planinšek Ručigaj, Nada Kecelj, Vesna Tlaker Žunter, 2010, izvirni znanstveni članek Povzetek: Introduction. Secondary lymphedema following cancer therapy is a frequent, often painful, quality of life disturbing condition, reducing the patients' mobility and predisposing them to complications, e.g. infections and malignancies. The critical aspect of lymphedema therapy is to start as soon aspossible to prevent the irreversible tissue damage. Patients and methods. Weperformed a retrospective study of patients with lymphedema, treated at the Department of Dermatovenereology, University Medical Center Ljubljana, from January 2002 to June 2010. The patientsć demographic and medical data were collected, including type of cancer, type and stage of lymphedema, and time tofirst therapy of lymphedema. The number of referred patients with lymphedema following the therapy of melanoma, breast cancer, and uterine/cervical cancer, was compared to the number of patients expected to experience lymphedema following cancer therapy, calculated from the incidence reported in the literature. Results. In the period of 8.5 years, 543 patients (432 females, 112 males) with lymphedema were treated. The results show that probably many Slovenian patients with secondary lymphedema following cancer therapy remain unrecognized and untreated or undertreated. In the majority of our patients, the management of lymphedema was delayedč on average, the patients first received therapy for lymphedema 3.6 years after the first signsof lymphedema. Conclusions. To avoid a delay in diagnosis and therapy, and the complications of lymphedema following cancer therapy, the physician should actively look for signs or symptoms of lymphedema during the follow-up period, and promptly manage or refer the patients developing problems.
Ključne besede: rak (medicina), zdravljenje, limfedem
Objavljeno v DiRROS: 18.03.2024; Ogledov: 79; Prenosov: 28
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16. Cisplatin-induced non-convulsive posterior reversible encephalopathy syndrome in a 41-year-old woman with metastatic malignant melanomaJanja Ocvirk, Marko Boc, Martina Reberšek, Tanja Roš-Opaškar, 2009, izvirni znanstveni članek Povzetek: Background. Cisplatin, a widely used antineoplastic agent usually induces peripheral neuropathy, but can rarely also complicate with encephalopathy, with or without seizures. Case report. We report a case of a young patient with metastatic malignant melanoma with signs and symptoms of cisplatin-induced non-convulsive posterior reversible encephalopaty syndrome. Within the days shortly after the first cycle of cisplatin based chemotherapy the patient suffered from nausea, vomitus, headache, severe pain at the site of sub-cutaneous metastases and confusion. She later experienced somnolence, cortical blindness and aphasia, but without epileptic seizures. Conclusions. Cisplatin is an effective chemotherapeutic drug but also very toxic one and physicians using it must also be aware of possible encephalopathy.
Objavljeno v DiRROS: 08.03.2024; Ogledov: 112; Prenosov: 34
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18. Adjuvant treatment of breast cancer patients with trastuzumabErika Matos, Tanja Čufer, 2007, pregledni znanstveni članek Povzetek: Background. Trastuzumab is a monoclone antibody directed against HER2 receptors that are overexpressed in approximately 20% of breast cancer patients. The present paper presents five clinical trials in which trastuzumabwas applied in breast cancer patients in adjuvant setting. The results of all the trials consistently demonstrate a high efficacy of this target drug in the patients with HER2 positive tumours. So far, no formal guidelines for using trastuzumab in adjuvant setting for breast cancer have been approved. The reasons are many: (i) mean observation time in the studies done so far was considerably short; (ii) the drug was used according to different schedules, (iii) the overall time of treatment with trastuzumab was different in each trial, (iv) late side effects of treatment with trastuzumab are inadequately investigated, and (v) nobody can so far say for sure for which HER2 status patients therapy with trastuzumab is really beneficial. Conclusions. Trastuzumab is definitely very helpful in the treatment of the HER2-positive breast cancer patients that are hormone-independent and of anatomically larger tumours; but, what the absolute benefit of trastuzumab therapy in the treatment of small hormone-dependent tumours is remains a mystery. Incidentally, it must be borne in mind that cardiotoxicity, the well known side effect, may put particularly elderly patients at risk of death, thus beating any treatment advantages down. It has also not been yet resolved at what time it would be most appropriate to start with the therapy with trastuzumab, what would be the optimal duration of the therapy and whether trastuzumab is to be administered concurrently with chemotherapy or immediately after it? What is the optimal treatment duration, one or two yearsor only a few months? In addition there is still a question of optimal HER2 status determination and which HER2 status predicts for trastuzumab benefit. (Abstract truncated at 2000 characters)
Objavljeno v DiRROS: 22.02.2024; Ogledov: 177; Prenosov: 29
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19. Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphomaBarbara Jezeršek Novaković, Vladimir Kotnik, Tanja Južnič Šetina, Marjeta Vovk, Srdjan Novaković, 2007, izvirni znanstveni članek Povzetek: Background. Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study wastherefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemoimmunotherapy in high-risk patients with aggressive CD20 lymphomas. Patients, materials and methods. The activity of rituximab was tested in vitroon Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Results. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease free at 18.5 months median observation period. Conclusions. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 micro g/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high- risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results.
Objavljeno v DiRROS: 22.02.2024; Ogledov: 133; Prenosov: 33
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