Search results

1

Carbon monoxide - a "new" gaseous modulator of gene expression.

100%

Dulak J., Józkowicz A.

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2003

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vol. 50

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issue 1

31-47

EN

Carbon monoxide (CO) is an odorless, tasteless and colorless gas which is generated by heme oxygenase enzymes (HOs). HOs degrade heme releasing equimolar amounts of CO, iron and biliverdin, which is subsequently reduced to bilirubin. CO shares many properties with nitric oxide (NO), an established cellular messenger. Both CO and NO are involved in neural transmission and modulation of blood vessel function, including their relaxation and inhibition of platelet aggregation. CO, like NO, binds to heme proteins, although CO binds only ferrous (FeII) heme, whereas NO binds both ferrous and ferric (FeIII). CO enhances the activity of guanylate cyclase although it is less potent than NO. In contrast, CO inhibits other heme proteins, such as catalase or cytochrome P450. The effects of CO on gene expression can be thus varied, depending on the cellular microenvironment and the metabolic pathway being influenced. In this review the regulation of gene expression by HO/CO in the cardiovascular system is discussed. Recent data, derived also from our studies, indicate that HO/CO are significant modulators of inflammatory reactions, influencing the underlying processes such as cell proliferation and production of cytokines and growth factors.

2

Effects of protoporphyrins on production of nitric oxide and expression of vascular endothelial growth factor in vascular smooth muscle cells and macrophages.

100%

Józkowicz A., Dulak J.

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2003

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vol. 50

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issue 1

69-79

EN

Heme oxygenase-1 (HO-1), an inducible enzyme degrading heme to biliverdin, iron and carbon monoxide, is involved in regulation of inflammation and angiogenesis. Tin protoporphyrin (SnPPIX) and zinc protoporphyrin (ZnPPIX) are commonly used as competitive inhibitors of HO-1. We aimed to compare the effects of SnPPIX and ZnPPIX on the production of vascular endothelial growth factor (VEGF), activity of inducible nitric oxide synthase (iNOS) and cell viability. All experiments were performed on rat vascular smooth muscle cells and murine RAW264.7 macrophages treated with 3-10 μM protoporphyrins. Some cells were additionally stimulated with IL-1β or with lipopolysaccharide. After a 24 h incubation period SnPPIX and ZnPPIX significantly reduced the generation of VEGF in vascular smooth muscle cells and RAW264.7, both in resting and stimulated cells. The inhibitory potentials of both protoporphyrins on VEGF synthesis were very similar. In contrast, analysis of iNOS activity revealed that results obtained with different HO-1 inhibitors are discrepant. Generation of nitric oxide by iNOS was significantly increased by SnPPIX but strongly decreased by ZnPPIX. Similar differences were observed when cell viability was compared. SnPPIX improved the cell survival rate, whereas the same doses of ZnPPIX exerted some cytotoxic effects. In summary, SnPPIX and ZnPPIX can be used as HO-1 inhibitors in some experimental models. However, these compounds produce also HO-independent effects, which can make the interpretation of experiments very uncertain. Thus the involvement of the HO-1 pathway should be always confirmed by more specific methods.

3

Vascular Endothelial Growth Factor and Survivin Immunostaining in Gastric Adenocarcinoma

86%

Bury J., Szumiło J., Dąbrowski A., Ciechański A., Śliwińska J., Wallner G.

Polish Journal of Surgery

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2012

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vol. 84

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issue 7

341-347

EN

Two molecules - vascular endothelial growth factor involved in new vessels formation and survivin - antiapoptotic protein, reported to be associated with worse prognosis in various malignancies have been chosen for the study. Both are potential target for novel therapiesThe aim of the study was to determine the immunostaining of VEGF and survivin in gastric carcinoma and to analyse their relationship to the selected clinicopathological features and survival.Material and methods. Formalin-fixed, paraffin-embedded sections from 41 gastric adenocarcinomas were used for immunohistochemical reaction with monoclonal antibodies against vascular endothelial growth factor and survivin. The results were compared with selected clinicopathological features and survival.Results. Positive immunohistochemical reaction for vascular endothelial growth factor and survivin was revealed in 24 (58,53%) and 30 (73,17%), gastric carcinomas respectively. Vascular endothelial growth factor-negative gastric carcinomas were significantly more common in cases without metastases to regional lymph nodes and distant organs and in less advanced cases. Similar, distant metastases were also statistically less common in survivin-negative carcinomas. The differences in immunohistochemical reactions for survivin between less and more advanced cases almost reach statistical significance. The only factors significantly influenced 1, 2 and 3-year survival were vascular endothelial growth factor and survivin status. Statistically significant higher percentage of survival was noted in patients with vascular endothelial growth factor- and survivin-negative tumors.Conclusions. It seems that vascular endothelial growth factor and survivin play role in local invasion and spread of gastric adenocarcinoma and negatively influences survival. However, further studies are required to assess their true usefulness in the clinical practice.

4

Cardiovascular complications of selected antibodies used in oncological immunotherapy

86%

Kufel-Grabowska J.

OncoReview

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2017

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vol. 7

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issue 2

78-82

EN

Immunotherapy supports other therapeutic methods and is an important element in the fight against cancer. Its main tasks include stimulation and guidance of the immune system to fight cancer, inhibition of the mechanisms that block the immune system, and direct destruction of neoplastic cells. Different from chemotherapy or hormonal therapy, its mechanism of action is associated with a different profile of adverse events. HER2 receptor inhibitors may cause symptoms of heart failure, which usually recede, once the treatment has been discontinued. Bevacizumab, an anti-VEGF antibody, induces numerous cardiovascular complications, including arterial hypertension, arterial embolism, haemorrhage and haemoptysis as well as venous thromboembolism.

5

Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis.

86%

Kimura H., Esumi H.

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2003

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vol. 50

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issue 1

49-59

EN

Physiologically, angiogenesis is tightly regulated, or otherwise it leads to pathological processes, such as tumors, inflammatory diseases, gynecological diseases and diabetic retinopathy. The vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis. The VEGF gene expression is regulated by a variety of stimuli. Hypoxia is one of the most potent inducers of the VEGF expression. The hypoxia inducible factor 1 (HIF-1) plays as a key transcription factor in hypoxia-mediated VEGF gene upregulation. Nitric oxide (NO) as well as hypoxia is reported to upregulate the VEGF gene by enhancing HIF-1 activity. The Akt/protein kinase B (PKB) pathway may be involved in NO-mediated HIF-1 activation in limited cell lines. There are some reports of negative effects of NO on HIF-1 and VEGF activity. These conflicting data of NO effects may be attributed mainly to the amount of released NO. Indeed, NO can be a positive or negative modulator of the VEGF gene under the same conditions simply by changing its amounts. The VEGF-mediated angiogenesis requires NO production from activated endothelial NO synthase (eNOS). Activation of eNOS by VEGF involves several pathways including Akt/PKB, Ca2+/calmodulin, and protein kinase C. The NO-mediated VEGF expression can be regulated by HIF-1 and heme oxygenase 1 (HO-1) activity, and the VEGF-mediated NO production by eNOS can be also modulated by HIF-1 and HO-1 activity, depending upon the amount of produced NO. These reciprocal relations between NO and VEGF may contribute to regulated angiogenesis in normal tissues.

6

Ligands of peroxisome proliferator-activated receptor-γ increase the generation of vascular endothelial growth factor in vascular smooth muscle cells and in macrophages.

86%

Jozkowicz A., Dulak J., Piatkowska E., Placha W., Dembinska-Kiec A.

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2000

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vol. 47

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issue 4

1147-1157

EN

Peroxisome proliferator-activated receptors-γ (PPARγ) are ligand-inducible transcription factors of the nuclear hormone receptor superfamily. We examined the effect of PPARγ activation on the generation of vascular endothelial growth factor (VEGF), one of the major angiogenic agents. Rat vascular smooth muscle cells (VSMC) and murine macrophages RAW264.7 were incubated for 24 h with PPARγ activators: prostaglandin J2 and ciglitazone. PPARγ were expressed in VSMC and RAW cells and their activity was upregulated in the presence of PGJ2 and ciglitazone. Incubation of the cells with PPARγ activators significantly augmented the release of VEGF protein into the media, both in resting and in IL-1β- or LPS-stimulated cultures. The higher protein generation was connected with the increased expression of mRNA and transcriptional activation of VEGF promoter. We conclude that the activation of PPARγ upregulates the generation of VEGF and may be involved in the regulation of angiogenesis.

7

Bevacizumab in age-related macular degeneration – comparison of subjective estimation of vision with objective test results

86%

Piotrowska-Gwóźdź A., Piotrowska-Seweryn A., Mazur-Piotrowska G.

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EN

PURPOSE: Anti-VEGF therapy plays a great role in medicine, especially in opthalmology. The aim of the therapy is to inhibit the VEGF-A factors that are responsible for the angiogenesis in diseases such as the wet form of age-related macular degeneration (AMD). One of the monoclonal anti-VEGF antibodies is bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA). The aim of the study was to compare the subjective estimation of visual acuity with objective test results in patients undergoing anti-VEGF therapy using Avastin. MATERIALS AND METHODS: The authors report a study of 57 patients (37 females and 20 males) with exudative AMD whose near and distance visual acuity was examined before the first dose of Avastin and 1 month after the third injection. Additionally, an original questionnaire evaluating the subjective state of vision during the activities of daily routine was performed. RESULTS: When examining distance visual acuity, 29 patients made an improvement, deterioration was reported in 5 cases and in 23 cases the results remained unaltered. The results were correlated with the subjective estimation. CONCLUSIONS 1. Avastin stabilizes the degeneration process of AMD in most patients and sometimes improves visual acuity. 2. There is a positive correlation between the objective test results and subjective opinion in patients undergoing anti-VEGF therapy using Avastin.

PL

WSTĘP: Terapia anti-VEGF odgrywa niezwykle istotną rolę w medycynie, zwłaszcza w okulistyce. Polega na hamowaniu czynnika VEGF-A, który jest odpowiedzialny za angiogenezę w takich chorobach, jak wysiękowa postać zwyrodnienia plamki związanego z wiekiem (age-related macular degeneration – AMD). Jednym z przeciwciał monoklonalnych skierowanych przeciwko VEGF jest bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA). Celem badania jest porównanie subiektywnej oceny widzenia z obiektywnymi wynikami badań u pacjentów poddanych terapii anty-VEGF z zastosowaniem Avastinu. MATERIAŁ I METODY: Badaniem objęto 57 pacjentów (37 kobiet 20 mężczyzn) z wysiękową postacią AMD, u których dokonano oceny ostrości wzorku do bliży i dali przed pierwszą dawką i miesiąc po trzeciej iniekcji doszklistkowej Avastinu. Dodatkowo przeprowadzono autorską ankietą oceniającą widzenie podczas wykonywania czynności życia codziennego. WYNIKI: Analizując wyniki ostrości wzroku dla dali 29 pacjentów wykazało poprawę, 5 pogorszenie widzenia, a w 23 przypadkach ostrość wzroku nie uległa zmianie. Wykazano dodatnią korelację powyższych danych z wynikami subiektywnej oceny. WNIOSKI: 1. Avastin stabilizuje proces chorobowy w wysiękowej postaci AMD, a u niektórych pacjentów obserwowana jest poprawa ostrości widzenia. 2. Istnieje dodatnia korelacja między obiektywnymi wynikami ostrości wzroku a subiektywną oceną widzenia u pacjentów poddanych terapii anty-VEGF z zastosowaniem Avastinu.

8

Serum levels of VEGF-A, sVEGFR-2 and galectin-3 do not correlate with clinical stage, tumor size, or effectiveness of perioperative chemotherapy in patients with non-metastatic breast cancer

72%

Grochoła-Małecka I., Czajka-Francuz P., Owczarek A. J., Wojnar J., Handzlik G., Francuz T., Chudek J.

Annales Academiae Medicae Silesiensis

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2022

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issue 76

96-105

EN

WSTĘP: Angiogeneza nowotworowa jest procesem regulowanym przez wiele cytokin i czynników wzrostu, spośród których znaczącą rolę odgrywają czynnik wzrostu śródbłonka naczyń (vascular endothelial growth factor – VEGF), drugi rozpuszczalny receptor dla śródbłonkowego czynnika wzrostu (soluble vascular endothelial growth factor receptor 2 – sVEGFR-2) i galektyna-3. Dane literaturowe dotyczące oceny zmian stężenia VEGF, sVEGFR-2 oraz galekty-ny-3 w trakcie chemioterapii (chemotherapy – CTH) raka piersi (breast cancer – BC) są niejednoznaczne. Celem niniejszej pracy była analiza stężenia VEGF-A, sVEGFR-2 oraz galektyny-3 w surowicy pacjentek z rakiem piersi, rozpoczynających adjuwantową i neoadjuwantową chemioterapię oraz ocena zmian stężenia tych cytokin w trakcie leczenia. MATERIAŁ I METODY: Jednoośrodkowe badanie objęło 98 pacjentek z miejscowo zaawansowanym rakiem piersi, w tym 56 poddanych adjuwantowej i 42 neoadjuwantowej terapii. Stężenie VEGF-A, sVEGFR-2 i galektyny-3 w surowicy krwi oceniono na początku leczenia oraz po 2 miesiącach terapii. WYNIKI: Nie stwierdzono istotnych różnic pomiędzy stężeniami VEGF-A, sVEGFR-2 oraz galektyny-3 w surowicy pacjentek poddanych adjuwantowej i neoadjuwantowej chemioterapii. Nie wykazano również zależności między stężeniem tych cytokin w surowicy a stopniem zaawansowania klinicznego raka piersi. W trakcie przedoperacyjnej chemio-terapii odnotowano znaczące zwiększenie stężenia VEGF-A, sVEGFR-2 i galektyny-3, jednakże zarówno wyjściowe stężenia cytokin, jak i zmiany w czasie nie miały znaczenia predykcyjnego dla uzyskania całkowitej odpowiedzi patologicznej. WNIOSKI: Stężenia VEGF-A, sVEGFR-2 oraz galektyny-3 w surowicy nie korelują ze stopniem zaawansowania klinicznego ani masą nowotworu u pacjentek z miejscowo zaawansowanym rakiem piersi. Wyjściowe stężenia VEGF-A, sVEGFR-2 i galektyny-3 oraz zaobserwowany wzrost stężeń tych cytokin w surowicy w trakcie chemioterapii nie mają wartości predykcyjnej dla jej skuteczności.

PL

INTRODUCTION: Tumor angiogenesis is regulated by numerous cytokines and growth factors, with vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 2 (sVEGFR-2), and galectin-3, playing a significant role in the process. There are conflicting data concerning changes in serum VEGF, sVEGFR-2 and galectin-3 levels in breast cancer (BC) patients during the course of the disease and chemotherapy (CTH). This study aimed to assess the serum levels of VEGF-A, sVEGFR-2, and galectin-3 in women starting adjuvant and neoadjuvant therapy for BC, and their changes during the treatment. MATERIAL AND METHODS: This single-center study enrolled 98 women with non-metastatic BC, including 56 who started adjuvant therapy and 42 preoperative (neoadjuvant/induction) CTH. The serum levels of VEGF-A, sVEGFR-2, and galectin-3 were assessed at the beginning of CTH and after 2 subsequent months. RESULTS: There were no significant differences in the serum levels of VEGF-A, sVEGFR-2, and galectin-3 between patients starting adjuvant and preoperative therapy. In addition, there was no correlation between the serum levels and the clinical stage of BC. During CTH, a significant increase in VEGF-A, sVEGFR-2, and galectin-3 was noted, however, without a predictive significance for obtaining complete pathological response (pCR) both for the initial levels and changes in the serum levels. CONCLUSIONS: The serum levels of VEGF-A, sVEGFR-2, and galectin-3 do not correlate with the clinical stage or tumor size in patients with non-metastatic BC. The baseline levels of VEGF-A, sVEGFR-2 and galectin-3, and the observed increase in the serum levels of VEGF-A and sVEGFR-2 during CTH do not predict its efficacy.

9

Wpływ 8-miesięcznego treningu sportowego na stężenie naczyniowo-śródbłonkowego czynnika wzrostu u młodych lekkoatletów – udział adaptacyjnej angiogenezy w kształtowaniu wydolności tlenowej

72%

Krenc Z., Mazurowski W., Wosik-Erenbek M., Wiszniewska M.

Pediatria i Medycyna Rodzinna

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2015

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vol. 11

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issue 4

402-409

EN

A long-term sports training induces morphological and functional changes in the cardiovascular system, with the activation of angiogenesis being one of the most significant ones. Aim: The aim of the study was to assess the impact of an 8-month sports training on the serum levels of vascular endothelial growth factor and the physical performance in young athletes. Material and methods: A total of 28 sports middle school students (athletics faculty) aged 13 years, including 14 boys and 14 girls, were included in the study. All participants underwent clinical assessment at each stage of the study. Electrocardiographic and echocardiographic examinations were performed. Furthermore, the levels of vascular endothelial growth factor were measured and a cardiac stress test was performed, the outcome of which was used to calculate the physical working capacity (PWC170). Results: There was a statistically significant decrease (274.3 ± 195.7 vs. 193.8 ± 153.8 ng/ml, p < 0.001) in the serum levels of vascular endothelial growth factor during the 8-month sports training. The levels were significantly lower in male athletes both at baseline (196.2 ± 157.3 vs. 352.4 ± 204.0 ng/ml, p = 0.02), and at the end of the observation period (139.6 ± 110.9 vs. 247.9 ± 174.6 ng/ml, p = 0.003). In the same period, the average PWC170 value increased throughout the study group (108.6 ± 28.1 vs. 119.0 ± 34.1 W, p = 0.02), and sex-related statistically significant changes occurred only on the male group of athletes. No statistically significant correlations were found between the relative changes in the levels of vascular endothelial growth factor and the PWC170 index (Spearman’s rank correlation coefficient – Rs 0.158, p > 0.05). Conclusions: Long-term sports training results in a decrease in the levels of vascular endothelial growth factor. At the same time, physical efficiency improvement is observed, which may suggest the involvement of adaptive, exerciseinduced angiogenesis in the skeletal muscles. However, the observed changes show distinct differences depending on the sex.

PL

Długotrwały trening sportowy prowadzi do morfologicznych i czynnościowych zmian w układzie sercowo-naczyniowym, wśród których ważne miejsce zajmuje aktywacja procesów angiogenezy. Cel pracy: Celem pracy była ocena wpływu 8-miesięcznego treningu sportowego na stężenie naczyniowo-śródbłonkowego czynnika wzrostu w surowicy oraz wydolność fizyczną u młodych lekkoatletów. Materiał i metody: Badaniem objęto 28 uczniów gimnazjum sportowego o profilu lekkoatletycznym w wieku 13 lat, w tym 14 chłopców i 14 dziewcząt. Na każdym etapie badania wszyscy uczestnicy zostali poddani ocenie klinicznej. Wykonano u nich badania elektrokardiograficzne oraz echokardiograficzne. Oznaczono także stężenie naczyniowo-śródbłonkowego czynnika wzrostu oraz przeprowadzono próbę wysiłkową, której wynik posłużył do wyliczenia wskaźnika wydolności tlenowej PWC170. Wyniki badań: Podczas 8-miesięcznego treningu stężenie naczyniowo- -śródbłonkowego czynnika wzrostu w surowicy zmniejszyło się istotnie statystycznie (274,3 ± 195,7 vs 193,8 ± 153,8 ng/ml, p < 0,001). Jego stężenie było też istotnie niższe w grupie sportowców płci męskiej, zarówno na początku (196,2 ± 157,3 vs 352,4 ± 204,0 ng/ml, p = 0,02), jak i na końcu okresu obserwacji (139,6 ± 110,9 vs 247,9 ± 174,6 ng/ml, p = 0,003). W tym samym okresie średnia wartość wskaźnika PWC170 zwiększyła się w całej badanej grupie (108,6 ± 28,1 vs 119,0 ± 34,1 W, p = 0,02), a w odniesieniu do płci zmiany istotne statystycznie wystąpiły tylko u sportowców płci męskiej. Nie stwierdzono istotnych statystycznie korelacji pomiędzy względnymi zmianami stężenia naczyniowo-śródbłonkowego czynnika wzrostu i wartości wskaźnika PWC170 (współczynnik korelacji rang Spearmana – Rs 0,158, p > 0,05). Wnioski: Podczas długotrwałego treningu sportowego dochodzi do obniżenia stężenia naczyniowo-śródbłonkowego czynnika wzrostu. Jednocześnie obserwowana poprawa wydolności fizycznej może sugerować, że odbywa się to przy udziale adaptacyjnej, indukowanej wysiłkiem fizycznym angiogenezy w mięśniach szkieletowych. Zmiany te wykazują jednak wyraźne różnice zależne od płci.

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Carbon monoxide - a "new" gaseous modulator of gene expression.

Effects of protoporphyrins on production of nitric oxide and expression of vascular endothelial growth factor in vascular smooth muscle cells and macrophages.

Vascular Endothelial Growth Factor and Survivin Immunostaining in Gastric Adenocarcinoma

Cardiovascular complications of selected antibodies used in oncological immunotherapy

Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis.

Ligands of peroxisome proliferator-activated receptor-γ increase the generation of vascular endothelial growth factor in vascular smooth muscle cells and in macrophages.

Bevacizumab in age-related macular degeneration – comparison of subjective estimation of vision with objective test results

Serum levels of VEGF-A, sVEGFR-2 and galectin-3 do not correlate with clinical stage, tumor size, or effectiveness of perioperative chemotherapy in patients with non-metastatic breast cancer

Wpływ 8-miesięcznego treningu sportowego na stężenie naczyniowo-śródbłonkowego czynnika wzrostu u młodych lekkoatletów – udział adaptacyjnej angiogenezy w kształtowaniu wydolności tlenowej