[Intraperitoneal invasiveness of ovarian cancer from the cellular and molecular perspective]. / Wewnatrzotrzewnowa inwazyjnosc raka jajnika z perspektywy komórkowej i molekularnej.

Peritoneal cavity is the primary site of ovarian cancer metastases. It is believed that the intraperitoneal invasiveness of the malignancy is determined by interactions between cancer cells and the normal peritoneal mesothelum. The nature of these interactions is, however unclear which is the reason for divergent opinions about the role of mesothelial cells in disease progression. According to some authors, the mesothelium acts as a barrier which prevents the expansion of the tumor cells. However other researchers claim that these cells actively promote various elements of cancer cell invasiveness. The aim of this study was to present both concepts of the role of the mesothelial cells in the intraperitoneal development of ovarian cancer metastases, with particular emphasis on the mechanisms of reciprocal interaction between normal and cancer cells.

[Biological multifunctionality of resveratrol and its derivatives]. / Biologiczna wielofunkcyjnosc resweratrolu i jego pochodnych.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phytoalexin known for its cardioprotective, neuroprotective, anti-inflammatory, anti-cancer and anti-aging properties. Unfortunately, low bioavailability and rapid degradation to less active metabolites limit the use of this compound in a practical medicine. Therefore, lots of attention is paid to synthetic derivatives of resveratrol whose biological properties have repeatedly been recognized to be more pronounced compared with their natural precursor. This paper presents current state of knowledge on the biological activities of resveratrol and its analogues, focusing on so far recognized mechanisms of action of these compounds and their potential applicability.

Hybrid procedure in a patient with symptomatic thoraco-abdominal aneurysm and prior abdominal aortic reconstruction - case report.

Open repair of thoracoabdominal aortic aneurysm is connected with high mortality and morbidity. On the other hand, endovascular treatment of thoraco-abdominal aneurysms, which started 10 years ago, reduced perioperative mortality and morbidity. However, it results in a high level of late complications. It seems that an interesting solution to the problem is a hybrid procedure, which allows late complications to be reduced with acceptable levels of operative mortality and morbidity. This case report presents the use of a hybrid procedure in treatment of symptomatic thoraco-abdominal aneurysm in a patient with prior abdominal aortic reconstruction. In the first stage the patient underwent open revascularization of visceral vessels of the aorta. One week later a thoraco-abdominal stent-graft was implanted. The perioperative and postoperative period was uncomplicated. Two months after the second intervention the patient returned to work. Control imaging conducted 30 and 90 days after the procedure confirmed patency of all revascularized vessels and did not reveal any graft-related complications. The hybrid procedure seems to be an interesting alternative for open and endovascular repair of thoraco-abdominal aneurysms because it combines the advantages of open and endovascular repair. It also gives an opportunity to perform the procedure within a reasonable period of time from diagnosis of symptomatic thoraco-abdominal aneurysm.

Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms.

Resveratrol (3,4',5-trihydroxy-trans-stilbene; RVT) is a natural phytoestrogen known to modulate the rate of senescence in cultured cells. The mechanism by which RVT affects this process is still elusive. In this paper we used human peritoneal mesothelial cells (HPMCs) to examine the effect of RVT (0.5 and 10 µM) on their growth and senescence, with particular emphasis paid to parameters associated with oxidative stress. The results showed that RVT used at a concentration of 0.5 µM (but not at 10 µM) markedly improved HPMC growth capacity, as evidenced by elevated expression of PCNA antigen, augmented fraction of cells in the S phase of the cell cycle, and increased number of divisions achieved before senescence. These effects coincided with diminished expression and activity of senescence-associated ß-galactosidase but were not associated with changes in the telomere length and an incidence of apoptosis. Moreover cells exposed to 0.5 µM RVT were characterized by increased release of reactive oxygen species, which was accompanied by up-regulated biogenesis of mitochondria and collapsed mitochondrial membrane potential. At the same time, they displayed increased activity of superoxide dismutase and reduced DNA damage (8-OH-dG and γ-H2A.X level). The efficiency of 8-OH-dG repair was increased which could be related to increased activity of DNA glycosylase I (hOgg1). As shown using RT-PCR, expression of hOgg1 mRNA in these cells was markedly elevated. Collectively, our results indicate that delayed senescence of HPMCs exposed to RVT may be associated with mobilization of antioxidative and DNA repair mechanisms.

Resveratrol and its synthetic derivatives exert opposite effects on mesothelial cell-dependent angiogenesis via modulating secretion of VEGF and IL-8/CXCL8.

We examined the effect of resveratrol (RVT) and its two derivatives (3,3',4,4'-tetrahydroxy-trans-stilbene and 3,3',4,4',5,5'-hexahydroxy-trans-stilbene) on human peritoneal mesothelial cell (HPMC)-dependent angiogenesis in vitro. To this end, angiogenic activity of endothelial cells (HUVEC, HMVEC, and HMEC-1) was monitored upon their exposure to conditioned medium (CM) from young and senescent HPMCs treated with stilbenes or to stilbenes themselves. Results showed that proliferation and migration of endothelial cells were inhibited in response to indirect (HPMC-dependent) or direct RVT activity. This effect was associated with decreased secretion of VEGF and IL-8/CXCL8 by HPMCs treated with RVT, which confirmed the experiments with recombinant forms of these angiogenic agents. Angiogenic activity of endothelial cells treated with CM from HPMCs exposed to RVT analogues was more effective. Improved migration was particularly evident in cells exposed to CM from senescent HPMCs. Upon direct treatment, RVT derivatives stimulated proliferation (but not migration) of HUVECs, and failed to affect the behaviour of HMVEC and HMEC-1 cells. These compounds stimulated production of VEGF and IL-8/CXCL8 by HPMCs. Studies with neutralizing antibodies against angiogenic factors revealed that augmented angiogenic reactions of endothelial cells exposed to CM from HPMC treated with RVT analogues were related to enhanced production of VEGF and IL-8/CXCL8. Collectively, these findings indicate that RVT and its synthetic analogues divergently alter the secretion of the angiogenic factors by HPMCs, and thus modulate HPMC-dependent angiogenic responses in the opposite directions. This may have implications for the attempts of practical employment of the stilbenes for treatment of pathologies proceeding with abnormal vascularisation of the peritoneal tissue.