BACKGROUND: Lymphedema is a chronic condition characterized by progressive edema with complicated treatment. Recently, new treatment strategies inducing lymphangiogenesis were proposed. The aim of our study was to examine the effect of vascular endothelial growth factor C (VEGF-C) and adipose-derived stem cells (ADSCs) on lymphatic regeneration and drainage re-establishment in vascularized lymph node transfer (VLNT) model using a pedicled vascularized lymph node (VLN) groin flap. METHODS: Female Lewis rats with groin VLN flaps were utilized as a lymphedema model. Group A served as the control. Group B received VEGF-C. Group C received both VEGF-C and ADSCs. Group D received ADSCs only. Lymphatic drainage re-establishment was evaluated by ultrasound-photoacoustic imaging (US-PAI) after indocyanine green (ICG) injection. RESULTS: The fastest regeneration of elevated flaps was observed in Groups B and C in all monitored periods. After the first month, ICG positivity was detected in 14.3% of animals in Group A, 71.43% of animals in Group B (odds ratio [OR] = 15; p = 0.048), and 83.33% in Group C (OR = 30; p = 0.027). On the contrary, the difference between control group and Group D (16.67%; p = 0.905) was statistically insignificant. Administration of VEGF-C, ADSC + VEGF-C, and ADSC led to full flap regeneration after 6 months. The control group had the lowest percentage of ICG positivity at all monitored time points. CONCLUSION: We found that the fastest regeneration occurred with the combination of the VLN flap and VEGF-C. The addition of ADSC had an insignificant effect in our study. Furthermore, we proved the feasibility of PAI as an assessment tool of the lymphatic drainage recovery in a VLNT model.

• MeSH
• indokyanová zeleň MeSH
• kmenové buňky MeSH
• krysa rodu rattus MeSH
• lymfatické uzliny krevní zásobení   MeSH
• lymfedém * chirurgie   etiologie   MeSH
• potkani inbrední LEW MeSH
• regenerace MeSH
• vaskulární endoteliální růstový faktor C * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Intradialytic hypotension is a major complication during hemodialysis session, associated with increased risk of cardiovascular events and mortality. Its pathophysiology is believed to be multifactorial and remains not well elucidated. The aim of this study is to put forward new mechanisms behind the development of intradialytic hypotension. The study included sixty-five subjects on chronic hemodialysis, divided into two groups: intradialytic hypotensive (n=12) and normotensive (n=53), according to the variation of systolic blood pressure between post-dialysis and pre-dialysis measurements. Renin and angiotensin converting enzyme I plasma concentrations increased in both groups but more likely in normotensive group. Aldosterone plasma concentration is increased in the normotensive group while it decreased in the intradialytic hypotension group. Plasma endothelin concentrations showed higher values in intradialytic hypotension group. Post-dialysis asymmetric dimethylarginine and angiotensin converting enzyme 2 plasma concentrations were significantly higher in intradialytic hypotension group as compared to normotensive one. Collectrin plasma concentrations were significantly lower in intradialytic hypotension group. Finally, post-dialysis vascular endothelial growth factor C plasma concentration significantly increased in intradialytic hypotension group. In conclusion, endothelial dysfunction characterized by a lower level of vasoactive molecule seems to play a critical role in intradialytic hypotension development.

• MeSH
• aldosteron krev   MeSH
• arginin analogy a deriváty   krev   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• cévní endotel metabolismus   patofyziologie   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• endotelin-1 krev   MeSH
• hypotenze etiologie   krev   patofyziologie   MeSH
• inhibitory ACE krev   MeSH
• krevní tlak * MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny krev   MeSH
• nemoci ledvin krev   patofyziologie   terapie   MeSH
• renin krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor C krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: To compare the density of lymphatic vessels and VEGF-C and VEGF-D expression in Warthin's tumours (WTs) and oncocytic adenomas (OCAs). METHODS: Twenty three WTs and 13 OCAs of the parotid gland were analyzed. Lymphatic vessels were detected using the D2-40 antibody. For evaluation of the intratumour and peritumour lymphatic vessel density (iLVD and pLVD, respectively) the area of greatest vascularisation (hot spots) was chosen, using a ×40 field, and the number of vessels per square millimeter was counted in a ×200 field. The staining intensity for VEGF-C and VEGF-D immunoreaction in the tumour cells was graded from 0 to 3. RESULTS: The mean iLVD and pLVD values in WTs was 4.7 (range 1-8) and 6.9 (range 3-10), those in the OCAs 1.0 (range 0-3) and 5.8 (range 2-8), respectively. The differences in the iLVD, but not pLVD between the two tumour groups were statistically significant. In both entities, the pLVD markedly outnumbered the iLVD. The intratumour vessels in the WTs were present exclusively in the lymphoid stroma. In the group of 23 WTs, 13 (56.6%), 17 (73.9%) and 10 (43.4%) samples revealed positive VEGF-C, VEGF-D and both immunoreactions, respectively. 10 of 13 (77%) cases revealed VEGF-D immunoreaction and in none of them was the VEGF-C reaction present. CONCLUSION: The tumours had a comparable high density of peritumorous lymphatic network. However, WTs markedly differed from OCAs in the number of the intratumorous vessels. These were abundant solely in the stroma of WT, while practically lacking in the neoplastic epithelium of the WT and relatively rare in OCAs. We suggest that homeostasis in both entities is mediated mainly by peritumorous lymphatics. The lymphatic drainage in WTs is also fostered exclusively by stromal lymphatics, whereas in stroma poor OCAs by the vessels present in their neoplastic epithelium. We also believe that WTs stimulate proliferation of pre-existing lymphatic capillaries by means of the paracrine secretion of VEGF-C and VEGF-D in the neoplastic as well as reactive stromal cells, while in the OCAs only the latter factor takes part in their lymphangiogenesis.

• MeSH
• adenolymfom patologie   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfangiogeneze MeSH
• lymfatické cévy patologie   MeSH
• oxyfilní adenom patologie   MeSH
• patologická angiogeneze MeSH
• regulace genové exprese u nádorů fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor C metabolismus   MeSH
• vaskulární endoteliální růstový faktor D metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The project deals with the VEGF-C/D gene alteration and oncoprotein expression and its significance for lymphangionegenesis, lymphatic metastases and prognosis of salivary carcinomas. In a retrospective study 100 tumors, that had been treated surgically along with the lymph nodes, will be enrolled. VEGF-C/D gene alteration and oncoprotein expression in primary lesions will be correlated with tumor stromal lymphatic vessel microdensity, detected by D2-40 antibody, selectively marking lymphatic endothelial cells. All the above parameters will be statistically correlated with the histopathological status of lymph nodes, locoregional recurrence and survival rates. The project is expected to confirm the relationship between VEGF-C/D gene and oncoprotein expression and lymphangioneogenesis, nodal metastases and prognosis of salivary carcinomas.

Projekt zkoumá alteraci a expresi genů VEGF-C/D a jejich význam pro neolymfangiogenezu, lymfogenní metastázování a prognózu karcinomů slinných žláz. V retrospektivní studii bude hodnoceno 100 tumorů, jejichž chirurgická léčba byla spojena s disekcí krčních uzlin. Alterace a exprese VEGF-C/D genů v primárních lézích bude korelována s denzitou nádorových lymfatických cév, stanovenou protilátkou D2-40. Všechny výše uvedené parametry pak budou statistickými metodami porovnány s histopatologickým stavem krčních uzlin, vznikem lokoregionálních recidiv a s přežíváním. Očekáváme, že projekt potvrdí korelaci alterace a exprese genů VEGF-C/D s novotvorbou lymfatických cév, s výskytem uzlinových metastáz a s horší prognózou.

• MeSH
• karcinom MeSH
• lymfatické uzliny MeSH
• metastázy nádorů MeSH
• nádory slinných žláz diagnóza   terapie   MeSH
• patologická angiogeneze MeSH
• prognóza MeSH
• vaskulární endoteliální růstový faktor C analýza   MeSH
• vaskulární endoteliální růstový faktor D analýza   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• otorinolaryngologie
• onkologie
• molekulární biologie, molekulární medicína
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

AIMS: Some human neoplasms stimulate lymphangiogenesis through the over-production of vascular endothelial growth factors C/D (VEGF-C/D). Previously little attention has been paid to the mechanisms of lymphogenous spread of salivary adenoid cystic carcinoma (SACC). The current study investigates the presence of lymphatic network and the role of VEGF-C and VEGF-D in its formation. METHODS: The retrospective study was performed in 20 (12 females and 8 males) patients diagnosed with SACC. For the evaluation of VEGF-C/D immunoreactivity, semiquantitative histoscore was calculated as a sum of positive tumor cell score (range 0-3) and staining intensity (range 0-3). Lymphatic vessel density (LVD) was determined as the number of D2-40 positive lymphatic capillaries present at "hot spots". Moreover, the values of histoscores were calculated in surrounding normal parotid parenchyma and compared to those counted in tumors. LVD in the tumor center (iLVD), in its periphery (pLVD), and in healthy gland were identified. RESULTS: VEGF-C/D expression, iLVD and pLVD were higher in SACC than in normal gland. The VEGF-C/D score correlated neither with pLVD nor with iLVD. High iLVD values were associated with poor survival. CONCLUSIONS: The authors present the first study demonstrating the existence of lymphatic vessels in SACC.

• MeSH
• adenoidně cystický karcinom diagnóza   metabolismus   MeSH
• dospělí MeSH
• imunohistochemie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfangiogeneze imunologie   MeSH
• lymfatické cévy metabolismus   MeSH
• lymfatické metastázy MeSH
• mladý dospělý MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• slinné žlázy metabolismus   MeSH
• vaskulární endoteliální růstový faktor C metabolismus   MeSH
• vaskulární endoteliální růstový faktor D metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Recent research suggests that multinodular recurrent pleomorphic adenoma (PA) might result from cell migration through lymphatics. Lymphangiogenesis in malignancies is mediated by vascular endothelial growth factors C and D (VEGF-C/D). We studied the expression of VEGF-C/D in PA by immunohistochemistry as well as lymphatic vessel density (LVD). In 6 non-recurrent, 4 primary-to-recur, and 10 recurrent PAs, VEGF-C/D expression was assessed by immunohistochemistry. Staining was scored in terms of staining intensity (0 = absent to 3 = strong), and the percentage of positive tumor cells (scored as 0 (0-19 %), 1 (20-39 %), 2 (40-50 %), and 3 (60-100 %)) and a sum score were calculated. Intra- and peritumoral LVD was assessed by counting of LV after immunostaining, using the D2-40 antibody. All but one sample were VEGF-C negative. The differences in VEGF-D expression between non-recurrent, primary-to-recur, and recurrent PAs were not significant (p>0.05). VEGF-D expression did not correlate with peritumoral LVD (p>0.05). Our study revealed a significant difference between intra- and peritumoral LVD values when comparing individual and all sample groups (p=0.01). The lack of VEGF-C expression and of significant differences in VEGF-D expression and peritumoral LVD between patients with non-recurrent, primary-to-recur, and recurrent PAs does not support the lymphangiogenic local spread hypothesis

• MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * patologie   MeSH
• lymfatické cévy * patologie   MeSH
• lymfatické metastázy MeSH
• nádory slinných žláz * chemie   patologie   MeSH
• pleomorfní adenom chemie   patologie   MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor C * analýza   MeSH
• vaskulární endoteliální růstový faktor D * analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

Lymfangiogenéza – tvorba lymfatických kapilár – v malígnom melanóme a v jeho blízkom okolí zohráva dôležitú úlohu pri metastázovaní tumoróznych buniek z malígneho melanómu do organizmu. Malígny melanóm produkuje epidermálny rastový faktor EGF, ktorý indukuje tvorbu cievneho rastového endotelového faktora VEGF-C, a tým spúšťa lymfangiogenézu. Je veľmi pravdepodobné, že malígne bunky z melanómu vstupujú do lymfatických kapilár aj cez špecializované inter-endotelové spojenia (endotelové mikrochlopne, primárne chlopne) situované v ich stenách. Po vstupe malígnych buniek do lymfatických kapilár putujú tieto bunky v lymfe do sentinelovej lymfatickej uzliny. Malígne bunky môžu pravdepodobne lymfogénne metastázovať priamo aj do distálnych spádových lymfatických uzlín. Vo včasnom štádiu malígneho melanómu sa nevylučuje ani hematogénna cesta metastázovania.

Lymphangiogenesis – proliferation of lymphatic capillaries – in melanoma and in its vicinity plays an important role in metastatic process of malign melanoma cells in organism. Melanoma produces epidermal growth factor EGF which induces vascular endothelial growth factor VEGF-C and thereby starts lymphangiogenesis. It is very probable that malignant melanoma cells enter lymphatic capillaries also through specialized inter-endothelial junctions (endothelial microvalves, primary valves) situated in their walls. After entry of malign cells into lymphatic capilla­ries, these cells travel in lymph to the sentinel lymph node. Malign cells metastasize through lymphatic vessels probably also directly into distal regional lymphatic nodes. Metastasizing through blood vessels is suggestible also in early stage melanoma.

• MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• endoteliální buňky metabolismus   MeSH
• epidermální růstový faktor MeSH
• lidé MeSH
• lymfangiogeneze * MeSH
• lymfatické cévy * metabolismus   ultrastruktura   MeSH
• lymfatické metastázy * patologie   ultrastruktura   MeSH
• lymfatické uzliny metabolismus   patologie   MeSH
• melanom * metabolismus   patologie   MeSH
• pohyb buněk MeSH
• sentinelová uzlina MeSH
• vaskulární endoteliální růstový faktor C biosyntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain normal blood pressure in states of interstitial Na(+) and Cl(-) accumulation. Failure of this physiological extrarenal regulatory mechanism leads to a salt-sensitive blood pressure response.

• MeSH
• chlorid sodný farmakologie   MeSH
• deoxykortikosteron farmakologie   MeSH
• dichlormethylendifosfonát farmakologie   MeSH
• exprese genu fyziologie   MeSH
• fagocyty cytologie   fyziologie   MeSH
• financování organizované MeSH
• hypertenze metabolismus   patofyziologie   MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl farmakokinetika   MeSH
• kůže metabolismus   MeSH
• lymfangiogeneze fyziologie   MeSH
• lymfatické cévy cytologie   fyziologie   MeSH
• mineralokortikoidy farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• proteinurie metabolismus   patofyziologie   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• TNF-alfa genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vaskulární endoteliální růstový faktor C genetika   metabolismus   MeSH
• vodní a elektrolytová rovnováha fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

Vascular endothelial growth factors (VEGFs) have a leading role among variety of angiogenic factors. Together with their receptors, they play an important role in endothelial cell proliferation and/or elongation, migration and vascular morphogenesis. In order to determine their possible role in malignant melanoma progression, VEGF (representing VEGFA), VEGF-C and VEGFR-1, -2, -3 immunohistochemical expression on formalin-fixed, paraffin-embedded tissue sections were evaluated. A total of 196 tissue samples consisting of 130 malignant melanomas (MM) with various vertical depth of invasion, 15 metastatic melanomas, and 66 nevi including dysplastic nevi and melanocytic nevi were analysed. Production of both VEGFs were common in benign melanocytic tumors while MM exhibited significant upregulation of VEGF (p<0.0027) and VEGF-C (p<0.0001). The proteins were also detected within stromal cells surrounding tumors, particularly in fibrocytes/ fibroblasts, macrophages and endothelial cells. They also exhibited significant increase in malignant lesions (p<0.0001). VEGFRs were localized in tumor, as well in stromal cells. Although expression of VEGF receptors was significantly higher in MM versus nevi (p<0.002 for VEGFR-1, p<0.004 for VEGFR-2 and p<0.0001 for VEGFR-3), a considerable percentage of MM were negative. There were no correlations between sentinel node positivity and all investigated proteins. When clinical outcome was evaluated, progression of the disease positively correlated with VEGF (p<0,007) and VEGF-C (p<0,008) expression VEGF (p<0.001) and VEGF-C (p<0.0001) positively correlated with nestin expression in the capillary endothelium, which was used for angiogenesis detection. Our work demonstrated that upregulation of VEGFs is associated with progression of malignant melanomas. The protein expression in the tumor microenvironment highlights their importance in malignant stromal phenotype which may serve as a potential target for the anticancer therapy.

• MeSH
• cévní endotel metabolismus   MeSH
• financování organizované MeSH
• lidé MeSH
• melanom metabolismus   patologie   MeSH
• nádory kůže metabolismus   patologie   MeSH
• prognóza MeSH
• proteiny intermediálních filament metabolismus   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptor 3 pro vaskulární endoteliální růstový faktor metabolismus   MeSH
• receptory vaskulárního endoteliálního růstového faktoru metabolismus   MeSH
• vaskulární endoteliální růstové faktory metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• vaskulární endoteliální růstový faktor C metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• antigen CA-125 krev   terapeutické užití   MeSH
• lidé MeSH
• nádorové biomarkery krev   terapeutické užití   MeSH
• nádory vaječníků diagnóza   krev   MeSH
• receptory lysofosfatidových kyselin fyziologie   chemie   krev   MeSH
• vaskulární endoteliální růstový faktor C škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH