Maja Sirotković-Skerlev

University Hospital Centre Zagreb

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Ana Kulić

University Hospital Centre Zagreb

Damir Vrbanec

Juraj Dobrila University of Pula

Natalija Dedić Plavetić

University Hospital Centre Zagreb

Zdenko Kovač

University of Zagreb

Mihael Skerlev

University of Zagreb

Jasminka Jakić‐Razumović

University of Zagreb

Sanja Kapitanović

Rudjer Boskovic Institute

M. Skerlev

University Hospital Centre Zagreb

Suzana Ljubojević Hadžavdić

University of Zagreb

ŠK

Šimun Križanac

University Hospital Dubrava

Cooperative Institutions

University Hospital Centre Zagreb

University of Zagreb

University Hospital Dubrava

Rudjer Boskovic Institute

Klinički Bolnički Centar Rijeka

Croatian Academy of Sciences and Arts

University of Antwerp

VIB-UAntwerp Center for Molecular Neurology

Antwerp University Hospital

Klinički bolnički centar Osijek

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Low serum MMP-1 in breast cancer: a negative prognostic factor?

Biomarkers (2012)

Ana Kulić Natalija Dedić Plavetić Jurica Vrbanec Maja Sirotković-Skerlev

In this study we investigated the prognostic significance of serum matrix metalloproteinase (MMP)-1 levels in early-stage breast cancer patients and correlated these levels with various clinicopathologic parameters. MMP-1 levels were determined by enzyme-linked immunosorbent assay. MMP-1 serum levels in patients (n = 60) were significantly lower than in healthy subjects (n = 20, p < 0.0001). We found significant negative correlation between serum levels of MMP-1 and several negative prognostic factors of breast cancer. Kaplan–Meier analysis showed significantly shorter 5-year survival in patients with lower values of MMP-1 compared to those with high levels of MMP-1 (p = 0.0147). Our results suggest a negative prognostic role of low serum MMP-1.

Clinical Significance

10.3109/1354750x.2012.678885

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Long-term outcome of patients with luminal A breast cancer surrogate subtype according to chromosomal instability measured by securin expression

The Breast (2019)

Natalija Dedić Plavetić MM Lovric Mirna Majzec Ana Kulić Maja Sirotković-Skerlev

Securin

Surrogate endpoint

Chromosome instability

10.1016/s0960-9776(19)30351-0

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301P Epigenetic modifications of IL-17 gene in patients with early breast cancer and healthy controls

Annals of Oncology (2023)

Ljubica Radmilović Varga Tihana Marić Ana Katušić Bojanac K. Horvatović Marina Popović

CpG site

Bisulfite sequencing

10.1016/j.annonc.2023.09.497

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Long Term Outcome of Surrogate Subtypes of Primary Operable Breast Cancer According to Securin Expression

Research Square (Research Square) (2023)

Marko Lovrić Natalija Dedić Plavetić Mirna Majzec Ana Kulić Maja Sirotković-Skerlev

Abstract Background: Despite dramatic advances in cancer research, breast cancer remains a major health problem. In this heterogeneous disease, patients with different molecular subtypes have a different therapeutic approach and prognosis. Securin is known to participate in maintaining chromosomal integrity during the cell cycle through regulation of metaphase-anaphase transition, DNA damage repair and apoptosis. The aim of this study was to evaluate the prognostic role of securin expression as a measure of chromosomal instability in different surrogate subtypes of breast cancer in order to discriminate patients with worse prognosis. Materials and methods: Breast cancer paraffin-embedded tissue specimens were obtained from a consecutive series of 215 patients with primary operable invasive breast carcinomas referred to the University Hospital Centre Zagreb, Croatia, from 2002 to 2003. Immunohistochemical (IHC) staining for securin was performed, and all relevant clinical and histopathological data were collected. Surrogate subtypes were defined according to St Gallen's consensus criteria. All patients were followed-up prospectively according to standard institutional practise for local and distant reccurence and death to collect data on disease-free (DFS) and overall survival (OS). Results: In this patient cohort, median securin expression was 7 % of positive cells, ranging from 1 % to 42 %. Statistically significant correlation between tumor size and securin expression (p = 0.0272) and securin and Ki 67% expression (p = 0.0065) was shown. Securin expression differs among surrogate subtypes of breast cancer with highest expression in HER2+ subtype (median= 12). Univariate analysis has shown that in luminal A subtype and triple negative subtype there is statistically significant correlation between securin expression and DFS as well as OS. According to logistic regression analysis, it has also been shown that securin expression was independent prognostic factor for ten-year overall survival (OS). Conclusion: Our study has shown that patients with BC overexpressing securin have a worse long-term prognosis in comparison with those without overexpression but only in luminal A like and triple negative like surrogate subtypes.

Securin

Surrogate endpoint

10.21203/rs.3.rs-2986797/v1

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[Gastrointestinal stromal tumors (GIST)--a paradigm of successful targeted therapy of solid tumors].

PubMed (2006)

Borislav Belev Damir Vrbanec Marko Kralik Stjepko Pleština Branka Petričević

Gastrointestinal stromal tumors (GIST) have attracted basic scientists as well as clinicians in the last 10 years. The reason for this is explanation of the pathogenetic mechanism of tumor growth by activation of c-Kit protein, followed by a rationally designed suppressor, a drug named imatinib. It is the first successful therapy for solid tumors to date, although there are other ongoing studies of agents with targeted action on different molecules in different tumors. In 80% of patients there is a clinical benefit from imatinib trreatment. GIST shows great diversity in clinical presentation and some questions still remain, such as malignant potential and prognostic criteria in these tumors. Imatinib therapy demonstrates many favorable effects such as acceptable toxicity and relative mild side effects, excellent quality of life, good patient compliance, etc. There are ongoing trials of new agents designated for target molecules, which would hopefully show benefit after developing resistance to imatinib.

Targeted Therapy

Stromal tumor

Imatinib Mesylate

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Charcot‐Marie‐Tooth Disease: A Clinico‐genetic Confrontation

Annals of Human Genetics (2008)

Nina Barišić Kristl G. Claeys Maja Sirotković-Skerlev A. Löfgren Eva Nelis

Summary Charcot‐Marie‐Tooth disease (CMT) is the most common neuromuscular disorder. It represents a group of clinically and genetically heterogeneous inherited neuropathies. Here, we review the results of molecular genetic investigations and the clinical and neurophysiological features of the different CMT subtypes. The products of genes associated with CMT phenotypes are important for the neuronal structure maintenance, axonal transport, nerve signal transduction and functions related to the cellular integrity. Identifying the molecular basis of CMT and studying the relevant genes and their functions is important to understand the pathophysiological mechanisms of these neurodegenerative disorders , and the processes involved in the normal development and function of the peripheral nervous system. The results of molecular genetic investigations have impact on the appropriate diagnosis, genetic counselling and possible new therapeutic options for CMT patients.

Tooth disease

Molecular Genetics

Clinical phenotype

Pathophysiology

10.1111/j.1469-1809.2007.00412.x

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Citations (160)

WHAT SHOULD THE DERMATOVENEREOLOGIST KNOW ABOUT HPV

Mihael Skerlev Maja Sirotković-Skerlev Suzana Ljubojević Hadžavdić

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Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years)

Cancer Biomarkers (2020)

Maja Sirotković-Skerlev Natalija Dedić Plavetić Filip Sedlić Sanja Kusačić Kuna Damir Vrbanec

Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis.This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness.Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty individuals without malignancy.Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200 U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters.Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up.

10.3233/cbm-201497

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Povezanost citosolnih koncentracija katepsina D i stope preživljenja bolesnicas primarnim rakom dojke

Sanda Jelisavac Ćosić Ana Kulić Zdenko Kovač Damir Vrbanec Maja Sirotković-Skerlev

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P2.185 HPV and Pregnancy: The Controversial Role of Maternal-Fetal Transmission

Sexually Transmitted Infections (2013)

M. Skerlev Maja Sirotković-Skerlev Suzana Ljubojević

Background and open questions

Human papillomavirus (HPV) - associated pathology represents one of the major problems among STIs mostly due to the high recurrence rate, difficult eradication and oncogenic potential. Young, sexually active population in the generative period is mostly affected. Pregnancy may definitely foster the development of latent or manifest HPV infections and may enhance the development of the pathology which then often recedes in the postpartum. The data reported in the literature on the relationship between HPV and pregnancy are highly controversial. A number of different opinions emerge regarding the possibility of maternal-fetal virus transmission. This discrepancy depends on the diagnostic techniques, the clinical history and the period of pregnancy when the sample is collected. The possible maternal-fetal transmission of the virus might be considered, for example, the main factor responsible for juvenile laryngeal papillomatosis, and the onset of the genital warts in children’s age (apparently more often than the child’s sexual abuse which should not be neglected either!). Many authors report an initial presence of HPV in newborns which often disappears within 6 months after birth.

Conclusion

According to the most recent vaccination recommendations, HPV vaccines are not recommended for use in pregnant women. However, pregnancy testing is not needed before vaccination. If a woman is found to be pregnant after initiating the vaccination series, no intervention is needed; the remainder of the 3-dose series should be delayed until completion of pregnancy. Providing the controversies that still exist, modes of HPV transmission in pregnancy should be investigated more detailfully in order to get clearer picture and a fuller awareness of the preventive measures. It can be concluded that, in this very moment, there is a need for a coordinated effort of health professionals and policymakers to ensure successful implementation of vaccination programmes for both women and men.

Genital warts

Sex organ

Sexual transmission

10.1136/sextrans-2013-051184.0449

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