Endovenous Laser Ablation of Varicose Veins Preserves Biological Properties of Vascular Endothelium and Modulates Proinflammatory Agent Profile More Favorably Than Classic Vein Stripping.

Here we compared effect of serum from varicose patients undergoing endovenous laser ablation (EVLA) and classic vein stripping (CVS) on biological properties of endothelial cells and on the local and systemic profiles of proinflammatory agents. Results showed that serum from EVLA patients improved proliferation and reduced senescence and oxidative stress in the endothelial cells, as compared with the serum from CVS patients. These effects were related to a suppressed activity of TGF-1, the level of which in the serum from the EVLA patients was decreased.

Inhibition of NF-kappaB with Dehydroxymethylepoxyquinomicin modifies the function of human peritoneal mesothelial cells.

Peritoneal mesothelial cells exposed to bioincompatible dialysis fluids contribute to damage of the peritoneum during chronic dialysis. Inflammatory response triggered in the mesothelium leading to neovascularization and fibrosis plays an important role in that process. We studied the effects of Dehydroxymethyepoxyquinmicin (DHMEQ)-an NF-κB inhibitor on function of human peritoneal mesothelial cells (HPMC) in culture.

Senescent peritoneal mesothelium creates a niche for ovarian cancer metastases.

Although both incidence and aggressiveness of ovarian malignancy rise with age, the exact reason for this tendency, in particular the contribution of senescent cells, remains elusive. In this project we found that the patient's age determines the frequency of intraperitoneal metastases of ovarian cancer. Moreover, we documented that senescent human peritoneal mesothelial cells (HPMCs) stimulate proliferation, migration and invasion of ovarian cancer cells in vitro, and that this effect is related to both the activity of soluble agents released to the environment by these cells and direct cell-cell contact.

Serum from Varicose Patients Induces Senescence-Related Dysfunction of Vascular Endothelium Generating Local and Systemic Proinflammatory Conditions.

Although the role of endothelium in varicose vein development is indisputable, the effect of the pathology on biological properties of endothelial cells remains unclear. Here we examined if the presence of varicose veins affects senescence of endothelial cells (HUVECs) and, if so, what will be the local and systemic outcome of this effect. Experiments showed that HUVECs subjected to serum from varicose patients display improved proliferation, increased expression of senescence marker, SA--Gal, and increased generation of reactive oxygen species (ROS), as compared with serum from healthy donors.

Sulodexide Reduces the Proinflammatory Effect of Serum from Patients with Peripheral Artery Disease in Human Arterial Endothelial Cells.

Background/aims: Dysfunction of the arterial endothelial cells promotes the progression of atherosclerosis. We studied how exposure of human arterial endothelial cells to atherosclerotic serum from patients with peripheral artery disease changes the secretory activity of these cells, and whether that reaction is modified by sulodexide.

Methods: Endothelial cells in in vitro culture were exposed to standard culture medium ± 100pg/mL Interleukin-1(IL-1) or to medium supplemented with 20% atherosclerotic serum.

Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines.

Background: Multiple drug resistance (MDR) of cancer cells is the main reason of intrinsic or acquired insensitivity to chemotherapy in many cancers. In this study we used ovarian cancer model of acquired drug resistance to study development of MDR. We have developed eight drug resistant cell lines from A2780 ovarian cancer cell line: two cell lines resistant to each drug commonly used in ovarian cancer chemotherapy: cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX) and topotecan (TOP).

COPD promotes migration of A549 lung cancer cells: the role of chemokine CCL21.

Patients with COPD develop lung cancer more frequently than healthy smokers. At the same time, molecular mediators promoting various aspects of cancer cell progression are still elusive. In this report, we examined whether COPD can be coupled with increased migration of non-small-cell lung cancer cells A549 and, if so, whether this effect may be related to altered production and activity of chemokines CCL21, CXCL5, and CXCL12.

[Molecular bases of cellular senescence: Hayflick phenomenon 50 years later].

Normal human somatic cells have strictly limited proliferative capacity and reach a state of senescence when it becomes exhausted. It is believed that senescence is a response to extensive and irreparable DNA injury, localized in telomeric and/or non-telomeric regions of the genome. Main cause of this damage is oxidative stress, increasing due to deteriorated function of mitochondria.

Effect of brefeldin A and castanospermine on resistant cell lines as supplements in anticancer therapy.

In the present study, we analyzed the influence of brefeldin A (BFA) and castanospermine (CAS) on the activity, stability and localization of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in various resistant cell lines. The impact of BFA and CAS on cell viability was assessed using the MTT test. Western blotting (WB) was performed to assess the effect of the inhibitors on the expression of the investigated proteins.

Levels of hepatocyte growth factor in serum correlate with quality of life in hemodialysis patients.

Purpose: Patients with end stage renal failure (ESRD) report low quality of life and inflammation may be one of the contributing factors. We studied if the hemodialysis induced inflammation correlates with the patients quality of life.

Methods: Study was performed in 76 (35 males and 41 females) ESRD patients treated with hemodialysis.

[Intraperitoneal invasiveness of ovarian cancer from the cellular and molecular perspective].

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.

The double-edged sword of long non-coding RNA: The role of human brain-specific BC200 RNA in translational control, neurodegenerative diseases, and cancer.

The complexity of eukaryotic organisms involves the regulation of gene expression through DNA-protein, RNA-DNA, RNA-RNA, and RNA-protein interactions. The role of RNA molecules in the regulation of genes in higher species has become even more evident with the discovery that about 97% of transcription products are represented by non-protein coding RNAs (ncRNAs) including short ncRNAs and long ncRNAs (lncRNAs). In addition to the well-characterized role of ncRNAs in different physiological cellular processes, numerous studies have also indicated the crucial roles of ncRNAs in neurological diseases and cancer.

Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo.

It is believed that senescent cells contribute to the progression of primary and metastatic tumors, however, the exact mechanisms of this activity remain elusive. In this report we show that senescent human peritoneal mesothelial cells (HPMCs) alter the secretory profile of ovarian cancer cells (A2780, OVCAR-3, SKOV-3) by increasing the release of four angiogenic agents: CXCL1, CXCL8, HGF, and VEGF. Proliferation and migration of endothelial cells subjected to conditioned medium generated by: cancer cells modified by senescent HPMCs; cancer cells co-cultured with senescent HPMCs; and by early-passage HPMCs from aged donors, were markedly intensified.

Colorectal cancer-promoting activity of the senescent peritoneal mesothelium.

Gastrointestinal cancers metastasize into the peritoneal cavity in a process controlled by peritoneal mesothelial cells (HPMCs). In this paper we examined if senescent HPMCs can intensify the progression of colorectal (SW480) and pancreatic (PSN-1) cancers in vitro and in vivo. Experiments showed that senescent HPMCs stimulate proliferation, migration and invasion of SW480 cells, and migration of PSN-1 cells.

High Potency of a Novel Resveratrol Derivative, 3,3',4,4'-Tetrahydroxy-trans-stilbene, against Ovarian Cancer Is Associated with an Oxidative Stress-Mediated Imbalance between DNA Damage Accumulation and Repair.

We explored the effect of a new resveratrol (RVT) derivative, 3,3',4,4'-tetrahydroxy-trans-stilbene (3,3',4,4'-THS), on viability, apoptosis, proliferation, and senescence of three representative lines of ovarian cancer cells, that is, A2780, OVCAR-3, and SKOV-3, in vitro. In addition, the mechanistic aspects of 3,3',4,4'-THS activity, including cell redox homeostasis (the production of reactive oxygen species, activity of enzymatic antioxidants, and magnitude of DNA damage accumulation and repair), and the activity of caspases (3, 8, and 9) and p38 MAPK were examined. The study showed that 3,3',4,4'-THS affects cancer cell viability much more efficiently than its parent drug.

Peritoneal mesothelium promotes the progression of ovarian cancer cells in vitro and in a mice xenograft model in vivo.

The role of mesothelial cells in the intraperitoneal spread of ovarian cancer is still elusive. In particular, it is unclear whether these cells constitute a passive barrier preventing cancer cell progression or perhaps act as an active promoter of this process. In this report we show that omental human peritoneal mesothelial cells (HPMCs) stimulate adhesion and proliferation of ovarian cancer cells (A2780, OVCAR-3, SKOV-3).

Resveratrol Derivative, 3,3',4,4'-Tetrahydroxy-trans-Stilbene, Retards Senescence of Mesothelial Cells via Hormetic-Like Prooxidative Mechanism.

There is agreement that the biological properties of additionally hydroxylated analogs of resveratrol (RVT) may be stronger compared with their parent drug. Here we examined the effect of a novel RVT derivative, 3,3',4,4'-tetrahydroxy-trans-stilbene (3,3',4,4'-THS), on the replicative senescence of human peritoneal mesothelial cells. The study showed that 3,3',4,4'-THS improves the cell proliferative capacity and delays their entry into senescence compared with control and RVT-treated cells.

Resveratrol inhibits ovarian cancer cell adhesion to peritoneal mesothelium in vitro by modulating the production of α5β1 integrins and hyaluronic acid.

Objective: Resveratrol (Res) is known to inhibit adhesion of numerous malignancies though its effect on an adherence of ovarian cancer cells to peritoneal mesothelium remains undefined.

Methods: To address this issue, ovarian cancer cells (A2780, OVCAR-3, SKOV-3) were subjected to Res (10, 50, 100 μM), and then their adhesion to omentum-derived human peritoneal mesothelial cells (HPMCs) was assayed.

Results: The study showed that Res inhibits adhesion of all ovarian cancer cell lines investigated.

Specificity of cytochemical and fluorescence methods of senescence-associated β-galactosidase detection for ageing driven by replication and time.

Senescence-associated β-galactosidase (SA-β-Gal) is a widely used marker of senescent cells in vitro and in vivo. In this report, young and senescent human peritoneal mesothelial cells (HPMCs) and fragments of the omentum, from which these cells were isolated, were subjected to simultaneous examination of SA-β-Gal using two methods, i.e.

Synthetic resveratrol analogue, 3,3',4,4',5,5'-hexahydroxy-trans-stilbene, accelerates senescence in peritoneal mesothelium and promotes senescence-dependent growth of gastrointestinal cancers.

3,3',4,4',5,5'-Hexahydroxy-trans-stilbene (M8) is a synthetic resveratrol derivative, advertised as a candidate drug highly effective against numerous malignancies. Because multiple tumors prone to M8 frequently metastasize into the peritoneal cavity, this study was aimed at establishing the effect of M8 on the growth and senescence of human peritoneal mesothelial cells (HPMCs), the largest cell population within the peritoneum, actively involved in the intraperitoneal spread of cancer. The study showed that M8, used at the highest non-toxic dose of 10 μM, impairs proliferation and accelerates senescence in cultured HPMCs via an oxidative stress-dependent mechanism.

Bystander senescence in human peritoneal mesothelium and fibroblasts is related to thrombospondin-1-dependent activation of transforming growth factor-β1.

Senescence bystander effect refers to a phenomenon in which senescent cells elicit the development of senescence phenotype in their nearby young counterparts. In this paper we examined the mechanism of senescence bystander effect triggered by senescent human peritoneal mesothelial cells (HPMCs) in proliferating HPMCs and peritoneal fibroblasts (HPFBs). The results showed that conditioned medium (CM) derived from senescent HPMCs elicited a senescence response (growth inhibition coupled with increased expression of senescence-associated β-galactosidase and accumulation of histone γ-H2A.