The –553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women

Introduction

Fibroblast growth factor-2 (FGF2) is an important signalling molecule contributing to angiogenesis, tumour growth and progression and its expression is implicated in breast cancer (BC) development. We investigated whether –553 T/A FGF2 gene polymorphism is associated with the risk and progression of BC in Polish women.

Material and methods

The –553 T/A polymorphism was genotyped in 230 breast cancer patients and 245 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples.

Results

The T/A genotypes (OR = 2.12, 95% CI: 1.20–3.74) (p = 0.08) and the combined heterozygotes T/A and homozygote A/A (OR = 2.18, 95% CI: 1.24–3.83) (p = 0.006) had an increased risk of BC. The median FGF2 levels in the tumours of A allele carriers were significantly increased compared to T/T patients, whereas in serum FGF2 levels were hardly altered among different genotype carriers. Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23–5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49–6.99) (p = 0.002). Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients.

Conclusions

Our study shows for the first time that the –553 T/A FGF2 gene polymorphism may be associated with a risk of BC developing and progression in Polish women and may have prognostic value for the assessment of BC high-risk groups.     

Antitumor Effects of Recombinant Antivascular Protein ABRaA-VEGF121 Combined with IL-12 Gene Therapy

Development and neoplastic progression strongly rely on tumor microenvironment cells. Various kinds of cells that form such tumor milieu play substantial roles in angiogenesis and immunosuppression. Attempts to inhibit tumor vascularization alter tumor milieu and enhance immune response against the tumor. Anticancer therapeutic strategy bringing together antiangiogenic and immunostimulating agents has emerged as a promising approach. We here investigated whether therapy directed against preexisting vessels, combined with an immunomodulatory factor would be equally effective in arresting tumor growth. To this goal, we investigated the effectiveness of ABRaA-vascular endothelial growth factor isoform 121 (VEGF₁₂₁), an antivascular drug constructed by us. It is a fusion protein composed of VEGF₁₂₁, and abrin A chain (translation-inhibiting toxin). We used it in combination with interleukin (IL-12) gene therapy and tried to inhibit B16-F10 melanoma tumor growth. ABRaA-VEGF₁₂₁ is a chimeric recombinant protein capable of destroying tumor vasculature and triggering necrosis in the vicinity of damaged vessels. IL-12 cytokine, in turn, activates both specific and non-specific immune responses. Our results demonstrate that combination of ABRaA-VEGF₁₂₁ antivascular agent with immunostimulatory cytokine IL-12 indeed inhibits tumor growth more effectively than either agent alone, leading to complete cure of ca. 20 % mice. Post-therapeutic analysis of tumors excised from mice treated with combination therapy showed decreased numbers of blood microvessels in the tumor microenvironment, lowered numbers of regulatory T lymphocytes, as well as showed higher levels of CD4⁺ and CD8⁺ as compared to control mice. It seems that bringing together antivascular strategy and the action of immunostimulating agents indeed inhibits growth of tumors.     

Influenza vaccination coverage in children with inflammatory bowel disease

The aim of this study was to evaluate the influenza vaccination status among paediatric patients with inflammatory bowel disease (IBD) in Poland. This was a questionnaire‐based study. 242 patients with IBD and 142 controls were enrolled in the study. Of patients with IBD, 7·8% received an influenza vaccine, compared to 18·3% of controls (P = 0·0013). There were no statistically significant differences in time from IBD diagnosis, disease activity and in drugs, between vaccinated and non‐vaccinated IBD children. In conclusion, the data of our study demonstrate an alarmingly poor influenza vaccination status in the majority of children with IBD. Therefore, there is an unmet need to implement better influenza vaccination strategies for this group of patients.     

Diagnostic validity Polish language version of the questionnaire MINI-KID (Mini International Neuropsychiatry Interview for Children and Adolescent)

Objective

Since over forty years structuralized interviews for clinical and epidemiological research in child and adolescent psychiatry are being developed that should increase validity and reliability of diagnoses according to classification systems (DSM and ICD). The aim of the study is to assess the validity of the Polish version of MINI-KID (Mini International Neuropsychiatric Interview for Children and Adolescents) in comparison to clinical diagnosis made by a specialist in the field of child and adolescent psychiatry.

Materials and methods

There were 140 patients included in the study (93 boys, 66.4%, mean age 11.8 ± 3.0 and 47 girls 33.5%, mean age 14.0 ± 2.9). All the patients were diagnosed by the specialist in the field of child and adolescent psychiatry according to ICD-10 criteria and by the independent interviewer with the Polish version of MINI-KID (version 2.0, 2001).

Results

There was higher agreement between clinical diagnoses and diagnoses based on MINI-KID interview with respect to eating disorders and externalizing disorders (κ 0.43–0.56) and lower in internalizing disorders (κ 0.13–0.45). In the clinical interview, there was smaller number of diagnostic categories (maximum 3 diagnoses per one patient) in comparison to MINI-KID (maximum 10 diagnoses per one patient), and the smaller percentage of patients with one diagnosis (65,7%) in comparison to MINI-KID interview (72%).

Conclusion

Our study has shown satisfactory validity parameters of MINI-KID questionnaire, promoting its use for clinical and epidemiological settings.

Implications and contribution

The Mini International Neuropsychiatry Interview for Children and Adolescent (MINI-KID) is the first structuralized diagnostic interview for assessing mental status in children and adolescents, which has been translated into Polish language. Our validation study demonstrated satisfactory psychometric properties of the questionnaire, enabling its use in clinical practice and in research projects.     

ST segment elevation typical for Brugada syndrome after intracoronary acetylocholine injection with retrosternal pain in history

Chest pain is mainly linked with acute coronary syndrome, but sometimes it can be the only manifestation of ventricular tachycardia. We present a case of a young man who was diagnosed with Brugada syndrome after intracoronary acetylocholine injection, with negative test with flecanaide. First manifestation of a disease was a chest pain.