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Article ; Online: Single Center Experience Study with Pembrolizumab in Patients with BRAF Mutant Negative Metastatic Melanoma

Pejčić Ivica / Petković Ivan / Cvetanović Ana / Conić Irena

Acta Facultatis Medicae Naissensis, Vol 35, Iss 4, Pp 267-

2018 Volume 272

Abstract: The aim of the paper was to determine the efficacy, toxicity and progression free survival with anti-PD-1 immunotherapy pembrolizumab in BRAF wild type metastatic melanoma patients with good performance status (ECOG PS 0-1). From February 2017 to April ... ...

Abstract	The aim of the paper was to determine the efficacy, toxicity and progression free survival with anti-PD-1 immunotherapy pembrolizumab in BRAF wild type metastatic melanoma patients with good performance status (ECOG PS 0-1). From February 2017 to April 2018, 17 patients with BRAF mutant wild type metastatic melanoma were enrolled in the study. Only 3/17 patient had received chemotherapy previously. The aim of the study was to confirm the efficacy of pembrolizumab immunotherapy in patients with good performance status (ECOG 0-1). Treatment consisted of pembrolizumab 2 mg/kg Q3 weeks continued until disease progression or intolerable toxicity. Secondary end points included toxicity and progression-free survival (defined as the time from randomization to documented disease progression according to RECIST). The overall response rate (ORR) was 11/17 (53.0 %), with complete response (CR) 0, partial response (PR) 3 (18 %), stable disease (SD) 8 (47%), and progressive disease (PD) 6 (35%). A total number of 97 consecutive cycles were administered. Adverse effects were mild. The most common toxicity was pneumonitis grade 1. None of the patients in the study demonstrated grade 2, 3 and 4 toxicity. No treatment-related deaths occurred. The median time to disease progression was 5.8 months. Anti-PD-1 pembrolizumab immunotherapy appeared to be a beneficial therapeutic approach with less toxicity for metastatic BRAF wild type melanoma patients with good PS.
Keywords	immunotherapy ; pembrolizumab ; metastatic melanoma ; Medicine ; R
Subject code	610
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Risk Factors and Predictive Value of Depression and Anxiety in Cervical Cancer Patients.

Tosic Golubovic, Suzana / Binic, Iva / Krtinic, Dane / Djordjevic, Vladimir / Conic, Irena / Gugleta, Uros / Andjelkovic Apostolovic, Marija / Stanojevic, Marko / Kostic, Jelena

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 4

Abstract: Background and ... ...

Abstract	Background and Objectives
MeSH term(s)	Anxiety/diagnosis ; Anxiety/epidemiology ; Anxiety/etiology ; Depression/diagnosis ; Depression/epidemiology ; Depression/etiology ; Female ; Humans ; Quality of Life ; Risk Factors ; Uterine Cervical Neoplasms/complications ; Uterine Cervical Neoplasms/epidemiology
Language	English
Publishing date	2022-04-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58040507
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Article ; Online: Bevacizumab with Chemotherapy as a First-Line Treatment for Advanced Ovarian Cancer in a Serbian Cohort.

Conic, Irena / Nedovic, Bojan / Stojnev, Slavica / Todorovska, Ilinka / Dimitrijevic, Aleksandra / Krstic, Miljan / Djordjevic, Ivana / Djordjevic, Biljana

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 5

Abstract: Background and ... ...

Abstract	Background and Objectives
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/therapeutic use ; Carboplatin/therapeutic use ; Female ; Humans ; Ovarian Neoplasms/drug therapy ; Paclitaxel/therapeutic use ; Serbia
Chemical Substances	Antibodies, Monoclonal, Humanized ; Bevacizumab (2S9ZZM9Q9V) ; Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58050607
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Article ; Online: Prognostic Impact of Canonical TGF-β Signaling in Urothelial Bladder Cancer.

Stojnev, Slavica / Krstić, Miljan / Čukuranović Kokoris, Jovana / Conić, Irena / Petković, Ivan / Ilić, Sonja / Milosević-Stevanović, Jelena / Veličković, Ljubinka Janković

Medicina (Kaunas, Lithuania)

2019 Volume 55, Issue 6

Abstract: Background and ... ...

Abstract	Background and objectives
MeSH term(s)	Biomarkers, Tumor/analysis ; Biomarkers, Tumor/blood ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Serbia ; Smad2 Protein/analysis ; Smad2 Protein/blood ; Smad4 Protein/analysis ; Smad4 Protein/blood ; Transforming Growth Factor beta1/analysis ; Transforming Growth Factor beta1/blood ; Urinary Bladder Neoplasms/blood
Chemical Substances	Biomarkers, Tumor ; SMAD2 protein, human ; SMAD4 protein, human ; Smad2 Protein ; Smad4 Protein ; Transforming Growth Factor beta1
Language	English
Publishing date	2019-06-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina55060302
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Article ; Online: Bevacizumab with Chemotherapy as a First-Line Treatment for Advanced Ovarian Cancer in a Serbian Cohort

Irena Conic / Bojan Nedovic / Slavica Stojnev / Ilinka Todorovska / Aleksandra Dimitrijevic / Miljan Krstic / Ivana Djordjevic / Biljana Djordjevic

Medicina, Vol 58, Iss 607, p

2022 Volume 607

Abstract: Background and Objectives : For stage IIIb–IV ovarian cancer, bevacizumab-containing treatment is considered the standard of care. The purpose of this study was to evaluate the efficacy of bevacizumab in combination with carboplatin and paclitaxel as a ... ...

Abstract	Background and Objectives : For stage IIIb–IV ovarian cancer, bevacizumab-containing treatment is considered the standard of care. The purpose of this study was to evaluate the efficacy of bevacizumab in combination with carboplatin and paclitaxel as a first-line treatment for advanced ovarian cancer. Materials and Methods : Eligible patients had stage IIIc–IV ovarian cancer according to the International Federation of Gynecology and Obstetrics with no clinical signs or symptoms of gastrointestinal obstruction or a history of abdominal fistulae, gastrointestinal perforation, or intra-abdominal abscess or evidence of rectosigmoid involvement by pelvic examination, bowel involvement on computed tomography, or clinical symptoms of bowel obstruction in the previous 6 months. After debulking surgery, the patients received 175 mg/m 2 paclitaxel and carboplatin (AUC 6) for the first six cycles and 7.5 mg/kg bevacizumab every three weeks up to 17 cycles until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was progression-free survival. The secondary endpoint was overall survival. Results : Between April 2017 and March 2020, 35 patients began study treatment. Bevacizumab was administered at 7.5 mg/kg in all the patients and for more than 7.5 months in 70% of them. The median progression-free survival was 20 months (95% CI: 16–23). The median overall survival was not reached. Conclusions : This was, to our knowledge, the first trial in Serbia to show progression-free survival and overall survival of combination regimens in advanced ovarian cancer. Based on the observed progression-free survival, bevacizumab combined with chemotherapy should be considered as a standard option in advanced ovarian cancer.
Keywords	bevacizumab ; ovarian cancer ; progression-free survival ; overall survival ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Risk Factors and Predictive Value of Depression and Anxiety in Cervical Cancer Patients

Suzana Tosic Golubovic / Iva Binic / Dane Krtinic / Vladimir Djordjevic / Irena Conic / Uros Gugleta / Marija Andjelkovic Apostolovic / Marko Stanojevic / Jelena Kostic

Medicina, Vol 58, Iss 4, p

2022 Volume 507

Abstract: Background and Objectives : Women with cervical cancer may experience depression or anxiety, influencing their quality of life and even their adherence to cancer treatments. This study aimed to explore and measure the levels of anxiety and depression in ... ...

Abstract	Background and Objectives : Women with cervical cancer may experience depression or anxiety, influencing their quality of life and even their adherence to cancer treatments. This study aimed to explore and measure the levels of anxiety and depression in patients suffering from cervical cancer and to identify the possible predictors among known risk factors such as age, cancer stage, smoking status, number of partners, use of contraceptives, and annual gynecological visits. Materials and Methods : In total, 59 patients with cervical cancer were included. A consecutive sampling method was used to select participants in this research. Depression and anxiety were assessed using the Zung Anxiety Scale (SAS) and Zung Depression Scale (SDS). The subjects were divided into three groups, according to the stage of cancer. Results : Scores of depression and anxiety were increased in all recruited cervical cancer patients. A significant correlation was found between disease stage and the scores of depression ( p = 0.002) and anxiety ( p = 0.016). More severe depressive symptoms correlated to a more advanced stage of the disease. A multiple linear regression showed that disease stage and annual visits to the gynecologist are the risk factors associated with higher depression scores. Conclusions : Patients diagnosed with cervical cancer are a vulnerable group for the development of the psychiatric disorders and they require screening programs, which could potentially detect candidates for co-psychiatric and/or psychotherapeutic treatment. They demand particular attention because anxiety and depression are associated with the significant burden of the underlying disease and unfavorable survival rates.
Keywords	anxiety ; depression ; cervical cancer ; Medicine (General) ; R5-920
Subject code	610 ; 150
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prognostic Impact of Canonical TGF-β Signaling in Urothelial Bladder Cancer

Slavica Stojnev / Miljan Krstić / Jovana Čukuranović Kokoris / Irena Conić / Ivan Petković / Sonja Ilić / Jelena Milosević-Stevanović / Ljubinka Janković Veličković

Medicina, Vol 55, Iss 6, p

2019 Volume 302

Abstract: Background and objectives : Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal ... ...

Abstract	Background and objectives : Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients’ outcome. Materials and Methods : Immunohistochemical analysis of TGF-β1, Smad2, and Smad4 expression was performed on 404 urothelial bladder cancer samples, incorporated in tissue microarrays. Expression status was correlated with clinicopathological and follow-up data. The median follow-up was 61 months. Results : High expression of TGF-β1, Smad2, and Smad4 was detected in 68.1%, 31.7% and 45.2% of the tumors, respectively. TGF-β1 overexpression was significantly associated with high tumor grade, and advanced pathologic stage ( p < 0.001, respectively). Conversely, high Smad2 and Smad4 expression was linked to low tumor grade ( p = 0,003, p = 0.048, respectively), and low tumor stage ( p < 0.001, p = 0.003, respectively). Smad2 showed an inverse correlation with variant morphology and divergent differentiation of urothelial tumors ( p = 0.014). High TGF-β1 correlated directly, while Smad2 and Smad4 correlated inversely to cancer-specific death ( p = 0.043, p = 0.003, and p = 0.022, respectively). There was a strong relationship between Smad2 and Smad4 expression ( p < 0.001). Survival analyses showed that high Smad2 and Smad4 expression was associated with longer overall survival ( p = 0.003, p = 0.034, respectively), while in multivariate regression analysis TGF-β1 manifested as an independent predictor of poor outcome. Conclusions : Unraveling the complex roles and significance of TGF-β signaling in urothelial bladder cancer might have important implications for therapy of this ...
Keywords	urothelial bladder cancer ; TGF-β ; Smad2 ; Smad4 ; immunohistochemistry ; prognosis ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Glioblastoma multiforme stem cells.

Dimov, Irena / Tasić-Dimov, Deasanka / Conić, Irena / Stefanovic, Vladisav

TheScientificWorldJournal

2011 Volume 11, Page(s) 930–958

Abstract: Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while ... ...

Abstract	Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Epigenesis, Genetic ; Glioblastoma/genetics ; Glioblastoma/immunology ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Immunosuppression ; Mice ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Signal Transduction
Chemical Substances	Biomarkers
Language	English
Publishing date	2011-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2075968-X
ISSN	1537-744X ; 1537-744X
ISSN (online)	1537-744X
ISSN	1537-744X
DOI	10.1100/tsw.2011.42
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Glioblastoma Multiforme Stem Cells

Irena Dimov / Deasanka Tasic-Dimov / Irena Conic / Vladisav Stefanovic

The Scientific World Journal, Vol 11, Pp 930-

2011 Volume 958

Abstract	Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies.
Keywords	Technology ; T ; Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ovarian epithelial cancer stem cells.

Conic, Irena / Dimov, Irena / Tasic-Dimov, Desanka / Djordjevic, Biljana / Stefanovic, Vladisav

TheScientificWorldJournal

2011 Volume 11, Page(s) 1243–1269

Abstract: The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. ... ...

Abstract	The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies. Compared to the CSCs of other cancer types, the identification and study of EOC stem cells (EOCSCs) is rather difficult due to several major obstacles: the heterogeneity of tumors comprising EOCs, unknown cells of origin, and lack of knowledge considering the normal ovarian stem cells. This poses a major challenge for urgent development in this research field. This review summarizes and evaluates the current evidence for the existence of candidate normal ovarian epithelial stem cells as well as EOCSCs, emphasizing the requirement for a more definitive laboratory approach for the isolation, identification, and enrichment of EOCSCs. The present review also revisits the ongoing debate regarding other cells and tissues of origin of EOCs, and discusses early events in the pathogenesis of this disease. Finally, this review discusses the signaling pathways that are important regulators of candidate EOCSC maintenance and function, their potential role in the distinct pathogenesis of different EOC subtypes, as well as potential mechanisms and clinical relevance of EOCSC involvement in drug resistance.
MeSH term(s)	Drug Resistance, Neoplasm ; Epithelium/metabolism ; Epithelium/pathology ; Female ; Hedgehog Proteins/metabolism ; Hedgehog Proteins/physiology ; Humans ; MicroRNAs/metabolism ; MicroRNAs/physiology ; Neoplastic Stem Cells/pathology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; PTEN Phosphohydrolase/metabolism ; PTEN Phosphohydrolase/physiology ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-akt/physiology ; Receptors, Notch/metabolism ; Receptors, Notch/physiology ; Signal Transduction
Chemical Substances	Hedgehog Proteins ; MicroRNAs ; Receptors, Notch ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2011-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2075968-X
ISSN	1537-744X ; 1537-744X
ISSN (online)	1537-744X
ISSN	1537-744X
DOI	10.1100/tsw.2011.112
Database	MEDical Literature Analysis and Retrieval System OnLINE

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