Search results

1

Construction of a bicistronic proangiogenic expression vector and its application in experimental angiogenesis in vivo.

100%

Małecki M., Przybyszewska M., Janik P.

Acta Biochimica Polonica

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2003

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vol. 50

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issue 3

875-882

EN

Manipulation of angiogenesis in vivo is an example of successful gene therapy strategies. Overexpression of angiogenic genes like VEGF, FGF or PDGF causes new vessel formation and improves the clinical state of patients. Gene therapy is a very promising procedure but requires large amounts of pharmaceutical-grade plasmid DNA. In this regard we have constructed a bicistronic plasmid DNA vector encoding two proangiogenic factors, VEGF165 and FGF-2. The construct (pVIF) contains the internal ribosome entry site (IRES) of the encephalomyocarditis virus (ECMV) which permits both genes to be translated from a single bicistronic mRNA. The IRES sequence allows for a high efficiency of gene expression in vivo. The pVIF vector was characterized in vitro and in vivo. In vivo angiogenesis studies showed that the bicistronic vector encoding two proangiogenic factors induces the formation of new vessels significantly more than pVEGF165 or pFGF-2 alone. In our opinion the combined proangiogenic approach with VEGF165 and FGF-2 is more powerful and efficient than single gene therapy. We also postulate that IRES sequence can serve as a useful device improving efficiency of gene therapy.

2

Ovarian cancer: early detection, angiogenesis, lymphangiogenesis and current prospects for therapy

100%

Wertel I., Bednarek W., Czekierdowski A., Kotarski J.

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issue 1

24-28

EN

I Chair and Department of Gynecological Oncology and Gynecology is a specialist research center providing help in diagnostics and treatment of gynecological malignancies. The research work is focused on the processes of angiogenesis and lymphangiogenesis. Development of blood and lymphatic vessels is subject to research in a wide range of malignancies, including ovarian cancer, endometrial cancer and uterine sarcomas. Angiogenesis in malignancies of the female genital tract is investigated by using some modern 3D sonography that uses high-definition blood flow imaging. Ovarian Tumors and Early Ovarian Cancer Detection unit was established in 2002 and since that time more than 3500 patients with difficult to diagnose tumors have been consulted and treated in the Department. Ovarian cancer immunology studies are the second leading research fiekld in the 1st Chair Department of Gynecological Oncology and Gynecology. The Department is well equipped with diagnostic devices as well as a scientific laboratory. This allows for studies in the fields of imaging of masses, their immunology, biochemistry and molecular biology. Understanding immunological response in patients with ovarian cancer is the key to develop new, effective therapies, including immunological vaccines. In this area we are cooperating with prominent international research centers: Department of Surgery, University of Michigan and Department of Microbiology and Immunology, University of Arkansas. Results of our research are published in both Polish and international journals specializing in fields of gynecology, oncology, immunology and basic science.

3

Proangiogenic activity of plant extracts in accelerating wound healing - a new face of old phytomedicines

100%

Majewska I., Gendaszewska-Darmach E.

Acta Biochimica Polonica

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2011

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vol. 58

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issue 4

449-460

EN

Angiogenesis, the formation of new capillaries from pre-existing vascular network, plays an important role in physiological and pathological processes such as embryonic development, wound healing, and development of atherosclerosis. Extension of the circulatory network is also considered to be one the most important factors during cancerogenesis. Inhibition of angiogenesis may lead to inhibition of tumor growth whereas stimulation may improve wound healing. Research achievements suggest the use of plants and their extracts as potential therapeutic agents with pro- or antiangiogenic activity. Since the anticancer and antiangiogenic properties of many phytomedicines have been amply reviewed elsewhere this paper will focus on the treatment of vascular insufficiency in wound healing. Globally accepted herbal drugs are thought to be safe and effective, however, there is a need for more evidence-based confirmation in controlled and validated trials. Among the most frequently studied proangiogenic phytochemicals are ginsenosides from Panax ginseng, beta-sitosterol from Aloe vera, calycosin from Radix Astragali, and extracts from Hippophae rhamnoides L. and Angelica sinensis.

4

Combined delivery of an antiangiogenic protein (angiostatin) and an immunomodulatory gene (interleukin-12) in the treatment of murine cancer.

100%

Wilczyńska U., Kucharska A., Szary J., Szala S.

Acta Biochimica Polonica

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2001

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vol. 48

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issue 4

1077-1084

EN

We investigated the feasibility of a novel therapeutic approach to treat neoplastic diseases in mice. This novel strategy consists in delivering a protein (angiostatin) with strong antiangiogenic properties, followed by administration of the interleukin 12 gene that is strongly immunomodulatory and has also some antiangiogenic effects. When angiostatin-mediated antiangiogenic therapy was used in combination with intratumor delivery of the IL-12 gene (a strategy much safer than IL-12 protein administration), this produced a synergistic therapeutic effect.

5

Design of vascular endothelium-specific drug-targeting strategies for the treatment of cancer.

100%

Molema G.

Acta Biochimica Polonica

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2005

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vol. 52

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issue 2

301-310

EN

Tumor endothelial cells are actively involved in the neovascularization processes that accompany tumor growth. Their easy accessibility for systemically applied therapeutics makes them interesting targets for therapeutic intervention. Especially for drug targeting-based therapeutics that often consist of macromolecular moieties, the tumor endothelium is considered a much better target than the tumor cells located behind the vascular wall barrier. In this review, the general principles underlying the development and choices in the development of vascular drug-targeting strategies are discussed. An overview of target epitopes identified in the past two decades is followed by a summary of those strategies that directly or indirectly induced tumor blood flow blockade in vivo. The demonstrated therapeutic success in pre-clinical animal models in debulking large tumor masses and inhibiting tumor outgrowth warrant further development of these therapeutic approaches. Yet, more effort should be put in studies in which the efficacy of different effector activities aimed at the same target, of one effector activity aimed at different targets, and of multiple target strategies are be compared. Combining these data with proper inventories on the molecular basis of tumor endothelial heterogeneity in general will make possible the development of tumor vascular drug-targeting strategies towards clinical application.

6

The effect of hydrazine derivatives of 3-formylchromones on angiogenic basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanoma cell line WM-115

88%

Łazarenkow A., Michalska M., Mirowski M., Słomiak K., Nawrot-Modranka J.

Acta Biochimica Polonica

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2017

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vol. 64

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issue 3

585-590

EN

The hydrazine derivatives of benzopyrones remain an unexplored group of chemical compounds. This preliminary study investigates the influence of A-5, CH-3 and K-2 derivatives at concentrations of 1, 10, 100 nM and 1 μM on selected biochemical factors of a melanoma cell line WM-115, with regard to their potential angiogenic properties. The studied compounds were found to influence cell proliferation, as well as total protein, bFGF and FGFR1 concentration.

7

Combination of vasostatin gene therapy with cyclophosphamide inhibits growth of B16(F10) melanoma tumours

88%

Jazowiecka-Rakus J., Jarosz M., Szala S.

Acta Biochimica Polonica

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2006

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vol. 53

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issue 1

199-202

EN

Angiogenesis, i.e. formation of new blood vessels out of pre-existing capillaries, is essential to the development of tumour vasculature. The discovery of specific antiangiogenic inhibitors has important therapeutic implications for the development of novel cancer treatments. Vasostatin, the N-terminal domain of calreticulin, is a potent endogenous inhibitor of angiogenesis and tumour growth. In our study, using B16(F10) murine melanoma model and electroporation we attempted intramuscular transfer of human vasostatin gene. The gene therapy was combined with antiangiogenic drug dosing schedule of a known chemotherapeutic (cyclophosphamide). The combination of vasostatin gene therapy and cyclophosphamide administration improved therapeutic effects in melanoma tumours. We observed both significant inhibition of tumour growth and extended survival of treated mice. To our knowledge, this is one of the first reports showing antitumour efficacy of electroporation-mediated vasostatin gene therapy combined with antiangiogenic chemotherapy.

8

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

88%

Dulak J., Józkowicz A.

Acta Biochimica Polonica

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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.

9

Antigen levels of urokinase-type plasminogen activator receptor and its gene polymorphism related to microvessel density in colorectal cancer

75%

Przybylowska K., Szemraj J., Kulig A., Dziki A., Ulanska J., Blasiak J.

Acta Biochimica Polonica

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2008

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vol. 55

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issue 2

357-363

EN

We determined the distribution of genotypes and frequencies of alleles of the (CA)n repeat polymorphism in intron 3 of the urokinase plasminogen activator receptor (uPAR) gene, uPAR antigen levels and microvessel density (MVD) in tumour and distant mucosa samples from 52 patients with colorectal cancer. The uPAR level was higher for patients with high MVD comparing to patients with lower MVD which may suggest that uPAR can be correlated with progression of colorectal cancer. The significant relationship between the high MVD and uPAR antigen level appeared to be independent of the (CA)n repeat polymorphism because no differences in the level of uPAR antigen between carriers of alleles were found. The received results, indicate that uPAR might be considered as a target in colorectal cancer patients' therapy.

10

HIF-1: the knowns and unknowns of hypoxia sensing.

75%

Zagórska A., Dulak J.

Acta Biochimica Polonica

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2004

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vol. 51

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issue 3

563-585

EN

Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that functions as a master regulator of cellular and systemic oxygen homeostasis. It consists of two constitutively produced subunits: HIF-1α and HIF-1β. Under normoxic conditions HIF-1α undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the α subunit. Additionally, hydroxylation of an asparaginyl residue blocks the transcriptional activity of HIF-1 due to inhibition of its interaction with co-activators. In contrast, under hypoxic conditions, abolition of prolyl hydroxylation results in HIF-1α stabilization, whereas the lack of asparaginyl hydroxylation allows the transcriptional activity. Additionally, the transcriptional activity may be modulated by phosphorylation or redox modification of HIF-1. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, various growth factors, or direct inhibitors of prolyl and asparaginyl hydroxylases. Therefore, it seems to be a crucial transcription factor elicited by a wide range of stresses such as impaired oxygenation, inflammation, energy deprivation, or intensive proliferation. However, the mechanisms of normoxic activation, as well as of oxygen sensing, are not yet fully known. Further understanding of the processes that control HIF-1 activity will be crucial for the development of new diagnostic and therapeutic strategies.

11

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

75%

Kimura H., Esumi H.

Acta Biochimica Polonica

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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.

12

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

75%

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

Acta Biochimica Polonica

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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.

13

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

63%

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.

14

Capillaroscopic patterns in patients with systemic sclerosis, psoriasis and alopecia and their correlations with serum concentrations of several angiogenic markers

63%

Chodorowska G., Michalska-Jakubus M., Bartosińska J., Gerkowicz A., Adamczyk M., Krasowska D.

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issue 1

49-54

EN

Introduction. Capillaroscopy is a non-invasive imaging method that allows cutaneous microcirculation to be analyzed. During the last decades, a diagnostic and prognostic potential of nailfold capillaroscopy (NVC) has been gaining increasing appreciation. The main indications include Raynaud phenomenon and scleroderma spectrum diseases, however the usefulness of this technique is also suggested in a variety of non-rheumatic diseases. Aim. To assess capillaroscopic patterns in systemic scleroderma (SSc), psoriasis (PV), psoriatic arthritis (PsA), alopecia areata (AA) and androgenetic alopecia. To evaluate serum levels of several endothelial and angiogenic markers, and their relation to capillaroscopic pattern. Material and methods. There were evaluated 295 patients with systemic scleroderma (SSc), psoriasis (PV), psoriatic arthritis (PsA), alopecia areata (AA) and androgenetic alopecia, as well as age- and sex-matched controls, were examined. In each subject, NVC was performed and serum concentration levels of several angiogenic markers. Results. In SSc three NVC patterns: early, active and late were distinguished. Angiopoietin-2 concentrations were higher and andothelial microparticles were lower in patients with late NVC pattern. We found several differences between the NVC pattern in PV and PsA. No correlations between NVC pattern and serum levels of angiogenic markers were revealed. In AA, we distinguished both normal and abnormal NVC patterns, although the normal patterns were more frequent. Branching capillaries and features of neoformation were often present in patients with the abnormal pattern. In androgenetic alopecia, the normal NVC pattern was most frequently present, however, we found several statistically significant capillarosopic alterations, like branching capillaries, features of neoformation and altered distribution of capillaries. Discussion and Conclusions. Serum levels of Ang-2 and EMPs may reflect capillary damage in SSc. NVC pattern varies between PV and PsA patients. The presence of abnormal NVC patterns in alopecia patients might show the role of disturbances in microcirculation in the diseases. Further studies are required to confirm the hypothesis.

15

Terapia bewacizumabem w raku jajnika – przegląd badań klinicznych

63%

Lubin J., Markowska A., Markowska J.

Current Gynecologic Oncology

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2013

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vol. 11

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issue 4

286-294

EN

Angiogenesis is a process which has been in the focus in the last decade due to its role in the development of cancers. The identification of vascular endothelial growth factor (VEGF) in the beginning of the 80’s became the new objective of therapies of cancers. The finding of angiogenesis inhibitors has brought the therapy of cancers including ovarian cancer in a new era. Apart from the “golden standard” such as the taxans and platinum components, the treatment of ovarian cancer has not introduced any new front-line drugs for many years. The registration of bevacizumab has changed data regarding in particular the progression-free survival (PFS), which was confirmed by GOG-0218 and ICON-7 clinical trials. The aim of the article was to put clinical trials that pointed to the efficiency of bevacizumab in order as well as presenting those whose results may allow in the nearest future for a wider use of bevacizumab – not only in the front-line chemotherapy of ovarian cancer, but also in neoadjuvant therapy and the treatment of a recurrent neoplasm, both platinum-sensitive and platinum-resistant. Studies of predictive factors, which allow for a group of patients who benefit most from anti-angiogenic drugs treatment to be singled out, are also important. At present, clinical trials and scientific studies are under way and maybe they will help identify patients whose PFS and the overall survival (OS) time is be prolonged as a result of treatment with bevacizumab.

PL

Angiogeneza to proces, na którym w ciągu ostatnich dekad skupiono szczególną uwagę, ponieważ odgrywa on istotną rolę w rozwoju nowotworów. Identyfikacja czynnika wzrostu śródbłonka naczyniowego VEGF (vascular endothelial growth factor) na początku lat 80. ubiegłego stulecia stała się niewątpliwie nowym celem terapii nowotworów, a stworzenie leków hamujących angiogenezę umożliwiło wprowadzenie leczenia nowotworów, w tym raka jajnika, w nową erę. Od wielu lat w terapii tego nowotworu, oprócz „złotego standardu”, jakim jest stosowanie taksanów i pochodnych platyny, nie wdrożono nowych leków w pierwszej linii leczenia. Rejestracja bewacizumabu zmieniła dane dotyczące szczególnie czasu wolnego do progresji (progression-free survival, PFS), co potwierdziły badania rejestracyjne tego preparatu (GOG-0218 i ICON-7). Celem pracy było usystematyzowanie badań klinicznych, które dowiodły skuteczności bewacizumabu, a także przedstawienie tych, których wyniki w najbliższej przyszłości mogą pozwolić na szersze zastosowanie leku – nie tylko w terapii pierwszej linii chemioterapii raka jajnika, ale także w terapii neoadiuwantowej oraz w leczeniu wznowy raka jajnika zarówno u pacjentek z nowotworem platynowrażliwym, jak i platynoopornym. Dużej uwagi wymagają też badania nad czynnikami predykcyjnymi, umożliwiającymi wyłonienie grupy pacjentów, którzy mogą uzyskać największą korzyść z leczenia lekami antyangiogennymi. Obecnie trwają badania naukowe i kliniczne, które być może pozwolą zidentyfikować chorych, u których terapia bewacizumabem wydłuży PFS i czas całkowitego przeżycia (overall survival, OS).

16

Znaczenie kliniczne ekspresji neuropiliny-1 u chorych na raka jajnika

63%

Klasa-Mazurkiewicz D., Narkiewicz J., Milczek T., Lipińska B., Emerich J., Wydra D.

Current Gynecologic Oncology

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2009

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vol. 7

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issue 4

237-247

EN

Background: Angiogenesis is a key process in the development of a malignant tumor, enabling both growth of primary lesion and spread of metastases. Most potent stimulators of normal and pathological angiogenesis are proteins of the vascular endothelial growth factor (VEGF) family. Regulation of angiogenesis process is also mediated by neuropilin- 1 (NP-1), as coreceptor VEGFR-2. NP-1 plays a crucial role controlling both normal angiogenesis during embryonal development and pathological angiogenesis in malignant tumors. The aim of this paper was to assess NP-1 expression in ovarian cancer and to analyze correlations between NP-1 expression and selected clinical-pathological factors in a group of ovarian cancer patients. Material and method: Analyzed was the relative level of NP-1 in 168 surgical specimens collected during surgical procedures performed at the Department of Oncologic Gynecology of Medical University in Gdańsk. Tissue samples included: 32 healthy tissues, 42 benign tumors, 10 borderline tumors, 76 ovarian cancers, 8 metastatic tumors. Relative NP-1 level was assessed using Western blotting technology. Results: Overexpression of NP-1 was seen significantly more often in early clinical stages of ovarian cancer (p=0.01), in cancers other than serous (p=0.04) and in patients with peritoneal exudate (p=0.03). Log-rank test did not reveal any significant correlation between NP-1 expression and favorable response to chemotherapy, disease-free survival or total survival time. Conclusions. Elevated NP-1 level seen in initial clinical stages of ovarian cancer may indicate crucial role of neoangiogenesis in the early phase of tumor development.

17

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

63%

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.

18

Ekspresja czynnika VEGF i receptora R1 w mięśniakach macicy kobiet w różnym wieku

63%

Bogunia E., Morek M., Plewka A., Plewka D., Miśkiewicz A., Wittek P., Kurpas P., Bilski R., Madej P.

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EN

Uterine myomas are the most common benign neoplasms of female reproductive organs. These neoplasms depend upon the impact of steroidal sex hormones – estrogen and progesterone. In uterine myoma cells a disturbed expression of some cytokines and factors is found, including angiogenic factors. The aim of the study was to evaluate the VEGF factor and VEGF-R1 receptor expression in uterine myomas. In the study there were 20 women with myomatous alterations in the uterus, including 10 women in reproductive age and 10 women in perimenopausal age. The study material consisted of tissue specimens taken from the myoma and specimens taken from normal myometrium. Evaluation of the VEGF factor and R1 receptor expression was conducted by means of immunohistochemical staining, using the ABC technique. In the evaluated cells with uterine myoma, both in young women and those in perimenopausal age, a significant increase in VEGF expression was found. This expression was independent of the myoma size. Moreover, a significantly higher VEGF-R1 expression was found in large myomas compared to small ones. The high VEGF factor expression level in women in perimenopausal age may indicate an additional local process of estrogen synthesis. The high VEGF-R1 expression in large myomas may suggest a direct stimulation of myoma growth affected by VEGF.

PL

Mięśniaki macicy należą do najczęstszych łagodnych nowotworów żeńskich narządów płciowych. Są to nowotwory zależne od wpływu steroidowych hormonów płciowych – estrogenów i progesteronu. W komórkach mięśniaków macicy stwierdza się zaburzoną ekspresję niektórych cytokin i czynników, w tym czynników angiogennych. Celem badań była ocena ekspresji naczyniowo-śródbłonkowego czynnika wzrostu VEGF (vascular endothelial growth factor) i receptora VEGF-R1 (vascular endothelial growth factor receptor 1) w mięśniakach macicy. Badaniem objęto 20 kobiet ze zmianami mięśniakowatymi w macicy, w tym 10 w wieku rozrodczym i 10 w wieku okołomenopauzalnym. Materiał do badań stanowiły wycinki tkankowe pobrane z mięśniaka oraz próbki pobrane z prawidłowego miometrium. Ekspresję czynnika VEGF i receptora R1 oceniano na podstawie barwienia immunohistochemicznego, wykorzystując technikę ABC. W ocenianych typach komórek macicy z mięśniakami, zarówno u kobiet młodych, jak i w wieku okołomenopauzalnym stwierdzono wyraźny wzrost ekspresji VEGF. Ekspresja ta była niezależna od wielkości mięśniaka. Stwierdzono także wyraźnie wyższą ekspresję VEGF-R1 w mięśniakach dużych niż w małych. Wysoki poziom ekspresji czynnika VEGF u kobiet w wieku okołomenopauzalnym może wskazywać na dodatkowy lokalny proces syntezy estrogenów. Wysoka ekspresja VEGF-R1 w mięśniakach dużych może świadczyć

19

Molecular mechanisms of neoplasia

63%

Derkacz A., Komosińska-Vassev K.

Annales Academiae Medicae Silesiensis

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2017

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vol. 71

225-245

EN

The evolution of normal cells into neoplastic cells involves many stages. This paper describes six characteristics of tumour cells: maintenance of cell division-promoting signals, resistance to exogenous growth inhibitors, avoidance of apoptosis, acquisition of the ability to undergo an infinite number of divisions, induction of angiogenesis as well as activation of the ability to invade and metastasise. The listed and described characteristics of tumor cells are associated with genomic instability and the production of inflammation. Genomic instability protes the formation of a diverse pool of cells, and the accumulation of traits of tumor cells leads to inflammation. The progress of science has enabled the addition of two further features acquired by cells during the process of neoplasia – modification of cellular metabolism and avoidance of recognition by the immune system.

PL

Ewolucja komórki prawidłowej w nowotworową obejmuje wiele etapów. W pracy opisano sześć cech charakteryzujących komórki nowotworowe: utrzymanie sygnałów stymulujących podziały komórkowe, oporność na egzogenne inhibitory wzrostu, unikanie apoptozy, nabywanie zdolności do nieskończonej liczby podziałów, indukcję angiogenezy oraz aktywację zdolności do inwazji i przerzutowania. U podłoża wymienionych cech leży nie tylko niestabilność genomu promująca wytworzenie zróżnicowanej genetycznie puli komórek, ale także stan zapalny, który wymaga wystąpienia wielu cech charakterystycznych dla komórek nowotworowych. Postęp badań pozwolił dodać dwie kolejne cechy nabyte przez komórki w czasie nowotworzenia – modyfikację metabolizmu komórkowego oraz unikanie rozpoznania przez system immunologiczny.

20

Stress and cancer

51%

Jośko-Ochojska J., Brus R.

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issue 74

166-180

EN

Scientific research has shown that during stress, the secretion of hormones and neurotransmitters in the brain, etc. is definitely stronger and longer lasting when persons are convinced that they cannot cope with the requirements of a stressful situation, i.e. they are in a state of uncontrolled stress. The main indicator of this condition is a long-term increase in the concentration of stress hormones in the blood. The higher the catecholamine concentration, the more DNA damage, the more cells undergoing tumour transformation, the larger the tumour and the more advanced the disease. Catecholamines also narrow blood vessels, which leads to an increase in VEGF expression, responsible for an increase in angiogenesis, and hence tumour growth and tumour metastasis. Cortisol contributes to inhibition of the immune system and changes in the central nervous system. Under uncontrolled stress, telomeres are shortened, which is another reason for shortening life expectancy. It has also been proven that stress and trauma are inherited in subsequent generations in the mechanism of epigenetic inheritance. Despite epigenetic predispositions to develop various malignancies, including ovarian, stomach and colorectal cancer, people can move from uncontrolled to controlled stress in a particular situation, even though the situation itself does not change. This is a breakthrough message. During cancer, the transition to controlled stress definitely supports therapy, increasing your chances of survival or even recovery. The most common condition for taking control of stress is to change your current lifestyle.

PL

Badania naukowe dowiodły, że w czasie stresu wydzielanie hormonów, neuroprzekaźników w mózgu itp. jest zdecydowanie silniejsze i trwa dłużej, zwłaszcza jeśli człowiek jest przekonany, że nie będzie w stanie sprostać wymaganiom sytuacji stresowej, czyli pozostaje w stanie stresu niekontrolowanego. Głównym wskaźnikiem tego stanu jest długo trwający przyrost stężenia hormonów stresu we krwi. Im większe stężenie katecholamin, tym więcej uszkodzeń DNA, więcej komórek ulegających transformacji nowotworowej, większy guz i bardziej zaawansowana choroba. Katecholaminy ponadto zwężają naczynia krwionośne, co przyczynia się do wzrostu ekspresji czynnika VEGF, który zwiększa angiogenezę, wzrost guza i przerzuty nowotworowe. Kortyzol przyczynia się do hamowania układu immunologicznego i zmian w ośrodkowym układzie nerwowym. W stresie niekontrolowanym skróceniu ulegają telomery, które są kolejną przyczyną skrócenia długości życia. Dowiedziono także, że stres i trauma są dziedziczone w kolejnych pokoleniach w mechanizmie dziedziczenia epigenetycznego. Pojawiają się wtedy predyspozycje epigenetyczne do zachorowania na różne nowotwory złośliwe, w tym raka jajnika, żołądka, jelita grubego. W konkretnej sytuacji można jednak przejść ze stresu niekontrolowanego do kontrolowanego, mimo że sama sytuacja się nie zmienia, i to jest wiadomość przełomowa. W trakcie choroby nowotworowej wejście w stan stresu kontrolowanego zdecydowanie wspomaga terapię, zwiększając szansę na przeżycie lub nawet wyzdrowienie. Najczęściej warunkiem przejęcia kontroli nad stresem jest zmiana dotychczasowego stylu życia. Radzenie sobie ze stresem, aktywność ruchowa i zdrowe odżywianie się są w stanie nawet doprowadzić do zmian na poziomie epigenomu, a badania naukowe dowodzą, że możemy wtedy uporać się z licznymi odziedziczonymi predyspozycjami, zmniejszając prawdopodobieństwo zachorowania na nowotwory złośliwe.

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

Ekspresja czynnika VEGF i receptora R1 w mięśniakach macicy kobiet w różnym wieku

Molecular mechanisms of neoplasia

Stress and cancer