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1.
Oral treatment with etoposide in small cell lung cancer - dilemmas and solution
Renata Režonja, Lea Knez, Tanja Čufer, Aleš Mrhar, 2013, review article

Abstract: Background. Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be atrisk for excess toxicity. Conclusions. The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.
Keywords: oral etoposide, bioavailability, pharmacokinetic variability, small cell lung cancer, treatment
Published in DiRROS: 22.03.2024; Views: 31; Downloads: 8
.pdf Full text (465,72 KB)

2.
Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting
Mirko Lekić, Viljem Kovač, Nadja Triller, Lea Knez, Aleksander Sadikov, Tanja Čufer, 2012, original scientific article

Abstract: Background. Small cell lung cancer (SCLC) represents approximately 13 tomediansurvival of SCLC patients treated by specific therapy (chemotherapy andžor radiotherapy) with regard to the 18%months in patients treated with standard chemotherapy and radiotherapy. Inpresence or absence of brain metastases at the time of diagnosis. Patients and methods. All SCLC patients have been treated in a routine clinical practice and followed up at theUniversity Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. Results. We found 251 patients eligible for the study. The median age of them was 65 years, majoritywere male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients(25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmedby a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. (Abstract truncated at 2000 characters)
Keywords: pljuča, rak (medicina), drobnocelični rak, metastaze, možgani
Published in DiRROS: 22.03.2024; Views: 42; Downloads: 22
.pdf Full text (552,38 KB)

3.
Effects of electrochemotherapy on immunologically important modifications in tumor cells
Urša Kešar, Boštjan Markelc, Tanja Jesenko, Katja Uršič Valentinuzzi, Maja Čemažar, Primož Strojan, Gregor Serša, 2023, original scientific article

Abstract: Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies.
Keywords: electrochemotherapy, cisplatin, immune response
Published in DiRROS: 21.03.2024; Views: 49; Downloads: 26
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4.
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 trial
Ana 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, original scientific article

Abstract: 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.
Keywords: gastrointestinal microbiome, mRNA expression of PD-L1 and IFNγ, immune checkpoint inhibitors, metastatic melanoma
Published in DiRROS: 21.03.2024; Views: 56; Downloads: 26
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6.
Triple negative breast cancer : prognostic factors and survival
Tanja Ovčariček, Snježana Frković-Grazio, Erika Matos, Barbara Možina, Simona Borštnar, 2011, original scientific article

Abstract: 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)
Published in DiRROS: 19.03.2024; Views: 66; Downloads: 25
.pdf Full text (536,99 KB)

7.
Lymphedema following cancer therapy in Slovenia : a frequently overlooked condition?
Tanja Planinšek Ručigaj, Nada Kecelj, Vesna Tlaker Žunter, 2010, original scientific article

Abstract: 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.
Keywords: rak (medicina), zdravljenje, limfedem
Published in DiRROS: 18.03.2024; Views: 50; Downloads: 21
.pdf Full text (416,52 KB)

8.
Digital ischemic events related to gemcitabine : report of two cases and a systematic review
Cvetka Grašič-Kuhar, Tanja Mesti, Branko Zakotnik, 2010, original scientific article

Published in DiRROS: 15.03.2024; Views: 65; Downloads: 26
.pdf Full text (621,57 KB)

9.
Cisplatin-induced non-convulsive posterior reversible encephalopathy syndrome in a 41-year-old woman with metastatic malignant melanoma
Janja Ocvirk, Marko Boc, Martina Reberšek, Tanja Roš-Opaškar, 2009, original scientific article

Abstract: 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.
Published in DiRROS: 08.03.2024; Views: 58; Downloads: 25
.pdf Full text (343,74 KB)

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