Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma

Aim: To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL). Materials and Methods: Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LLbearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals. Results: As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD-2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered. Conclusion: The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo

Дослідження змін потенціалів спинного мозку тварин у залежності від віку

Research of changes of cord dorsum potentials (CDP) of spinal cord (SC) of depending on age in cats. Is shown, that the first negative component of CDP is most stable on amplitude and dynamic characteristic for all age-group. Components of CDP, which were connected to work of polysynaptic neurones and especially with presynaptic inhibition showed large variables and instability at a repeated or long-term stimulation for very young or old animals. We assume, that the specified character of changes of potentials is connected to change of an effective performance of neurones in a brainНа кішках вивчали потенціали дорсальної поверхні (ПДП) спинного мозку (CM) у залежності від віку тварини. З’ясовано, що перший негативний (Nj) комнонент ПДП є найбільш стабільним по амплітуді та динамічних характеристиках для усіх вікових груп. Компоненти, пов’язані з роботою полісинаптичних нейронів, та особливо з пресинаптичним гальмуванням, були більш варіабельні та нестійки при повторних та тривалих подразненнях для дуже молодих або старих тварин. Робиться припущення, що такий характер змін потеніалів пов’язаний зі зменшенням кількості нейронів при старінні та розбудовою синаптичних утворень при дорослішанні. Вірогідно, що по формі ПДП можливо оцінити ступінь старіння мозку або його окремих ланокНа кішках вивчали потенціали дорсальної поверхні (ПДП) спинного мозку (CM) у залежності від віку тварини. З’ясовано, що перший негативний (Nj) комнонент ПДП є найбільш стабільним по амплітуді та динамічних характеристиках для усіх вікових груп. Компоненти, пов’язані з роботою полісинаптичних нейронів, та особливо з пресинаптичним гальмуванням, були більш варіабельні та нестійки при повторних та тривалих подразненнях для дуже молодих або старих тварин. Робиться припущення, що такий характер змін потеніалів пов’язаний зі зменшенням кількості нейронів при старінні та розбудовою синаптичних утворень при дорослішанні. Вірогідно, що по формі ПДП можливо оцінити ступінь старіння мозку або його окремих ланок

Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study

Aim: In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. Materials and Methods: The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution has been performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct cell counting. To study intracellular localization of hBD-2 immunocytofluorescent and immunocytochemical analyses were applied, and effect of hBD-2 on signal cascades involved in cell cycle regulation has been studied by Western blotting. Results: According to our data, rec-hBD-2 exerts a concentration-dependent effect on the viability of cultured A549 and A431 cells. It causes proproliferative effect at concentrations below 1 nM, significant suppression of cell proliferation at concentration range from 10 nM to 1 µM (p<0.05), and cell death at higher concentrations. Using flow cytometry we have demonstrated that hBD-2 dependent growth suppression is realized via cell cycle arrest at G1/S phase (p<0.05). Also, we have registered significant activation of pRB and decreased expression of Cyclin D1 in cells treated with the defensin compared to untreated control cells, while the expression of p53 remains unaffected. The study of intracellular localization of hBD-2 in these cells has revealed that exogeneously added defensin molecules enter the cells, are distributed throughout the cytoplasm and could be detected in cell nuclei. The model study using A549 cells treated with 1,25-(OH)2D3 has shown similar cell growth suppression effect of native endogenously produced hBD-2. Conclusion: The results of our study suggest that in malignant epithelial cells hBD-2 may control cell growth via arrest of G1/S transition and activation of pRB

Polymorphisms of the GCLC Gene Are Novel Genetic Markers for Susceptibility to Psoriasis Associated with Alcohol Abuse and Cigarette Smoking

The aim of this pilot study was to investigate whether single nucleotide polymorphisms in the gene encoding the catalytic subunit of glutamate cysteine ligase are associated with the risk and clinical features of psoriasi

Immunohistochemical analysis of beta-defensin-2 expression in human lung tumors

The aim of this paper is to present research was directed on analysis of the expression patterns of human beta-defensin-2 (hBD-2) in human lung tumors

Polysemy of greek suffix -os- in the formation of derivative clinical terms

The aim of the study - to analyze the meanings of the suffix -os- in the formation of derivative clinical terms.Цель исследования - анализ значений суффикса -os- при формировании производных клинических термино