Tezacitabine blocks tumor cells in G1 and S phases of the cell cycle and induces apoptotic cell death

Tezacitabine (FMdC) is a new cytostatic/cytotoxic agent widely investigated in clinical trials and on the cellular level. In a previous paper (3) we worked on human and murine leukemia (L-1210, HL-60, and MOLT-4) cells, and in this paper we investigated the influence of FMdC on the cell cycle and apoptosis in vitro of three other leukemias (CCRF-SB, KG-1, and Jurkat), and human solid tumor (carcinoma) cell lines (COLO-205, MCF-7, and PC-3). We found that FMdC induces the G1 (at concentrations higher than 10 nM). and S-phase (at low concentration) leaky block of the cell cycle. FMdC also effectively induces apoptotic death of cells by the caspase 3/7 pathway. We found also that FMdC induces intensive changes in the protein metabolism. These changes are correlated with the cell death.     

Parachute mitral valve in a young adult with recurrent pulmonary oedema

A parachute mitral valve is a rare congenital malformation resulting from fusion of the mitral chordae tendineae and their attachment to the one prominent papillary muscle. It can be found either as an isolated lesion or, more often, associated with left heart obstructive lesions, patent ductus arteriosus or ventricular septal defect. Congenital mitral stenosis usually presents with severe symptoms in early childhood, otherwise remains stable and hardly ever requires surgical intervention. We present a case of a young adult with severe stenosis of a parachute mitral valve and history of recurrent pulmonary oedema treated by mitral commissurotomy.     

Heterotopic pancreas in the stomach (type II according to Heinrich) - literature review and case report

Heterotopic pancreas is a rare congenital disorder characterized by the presence of normal pancreatic tissue located outside the pancreas. The most common locations include the duodenum, stomach, and jejunum. Most cases of heterotopic pancreas are asymptomatic. However, the development of clinical symptoms depends on the size, location and pathological changes similar to those observed in case of the normal pancreas. The Authors presented a case of multiple stomach heterotopic pancreatic lesions in an adult male patient. The atypical clinical presentation including non-specific endoscopic and CT images were responsible for the misdiagnosis before surgery. The patient underwent surgery. The tumor located in the posterior wall of the body of the stomach was excised by wedge resection. The postoperative course proved uneventful. Proper diagnosis was established on the basis of the histopathological examination of the resected tumor: heterotopic pancreas-multiple lesions, type II, according to Heinrich. The presented case report demonstrated that heterotopic pancreas should always be considered in the differential diagnosis of gastric tumors.     

Synthesis and proapoptotic properties of new casein kinase II inhibitors

Casein kinase II (CK2) is the most pleiotropic of all protein kinases with more than 300 substrates implicated in a wide variety of cellular functions as signal transduction, proliferation and cell survival. Increased levels of CK2 has been demonstrated in a number of cancers, where it regulates the activity of various oncoproteins and tumor suppressor proteins. Therefore, CK2 inhibitors could be considered as potential anticancer drugs in monotherapy or in combination with known cytostatics. In this study, we examined proapoptotic activity of new strong CK2 inhibitor - 4,5,6,7-tetraiodobenzimidazole (TIBI) (IC50 = 38 nM) as well as new derivatives of 4,5,6,7-tetrabromobenzimidazole and 4,5,6,7-tetraiodobenzimidazole. All the tested compounds induced apoptosis and cytostatic effects in the promyelocytic leukemia cell line (HL-60). The proapoptotic effect was concentration and time dependent. The changes of the mitochondrial membrane potential and cell cycle progression were also observed.     

Rationale for bisphosphonate use in patients with endoprosthesis

Total joint replacement is accompanied by dramatic changes in the biomechanics of the adjacent bone. Under these conditions the phenomenon of stress-shielding is responsible for localized but significant bone atrophy. Another important and inevitable result of total joint arthroplasty is the production of wear debris particles, which recruit macrophages. These cells are present in abundance in osteolytic lacunae filled with pseudo-membranes, which are the cause of aseptic loosening of the implants. Bisphosphonates are an osteotrophic class of drugs that have been demonstrated to inhibit osteoclast-induced osteolysis. They are widely applied in bone pathologies in which osteoclastosis plays an important role, e. g. osteoporosis, Sudeck's bone dystrophy, Paget's bone disease, and many others. The routine administration of bisphosphonates in patients recovering from joint replacements seems to be fully justified. There is considerable evidence from both animal and human studies supporting the view that the suppression of osteoclastic activity is beneficial for the bone adjacent to metal implants. We have observed decreased joint pain in the early stages of aseptic loosening and stabilization of the x-ray picture of the bone adjacent to joint replacements after prolonged bisphosphonate treatment.     

Epstein-Barr virus (EBV) infection and p53 protein expression in gastric carcinoma

In the presented studies p53 protein expression was evaluated in samples of gastric carcinoma originating from 32 selected adult patients (with documented diagnosis of adenocarcinoma of the stomach and without the presence of Helicobacter pylori infection). Among the patients 14 individuals carried EBV-positive gastric carcinoma (group 1) while the 18 remaining patients carried EBV-negative gastric carcinoma (group 2). EBV infection was detected testing the tissue material for the presence of EBER by RNA in situ hybridization (ISH) and testing sera of the patients for EBV-specific antibodies. Expression of p53 protein was analysed using immunohistochemistry. Presence of p53 protein was noted in 9 (64.3%) cases of EBV-positive gastric cancer (group 1) and in 10 (55.5%) cases of EBV-negative gastric cancer (group 2). No significant differences were detected in the frequencies of p53 protein expression in the two studied groups. The results permit to conclude that abnormalities in p53 in gastric cancer are independent of EBV infection, even if EBV may participate in development of the tumour.     

Posturography as objective evaluation of the balance system in Parkinson's disease patients after neurosurgical treatment. A preliminary report

BACKGROUND AND PURPOSE: In advanced stages of Parkinson's disease (PD) beside resting tremor, rigidity, and bradykinesia, most patients reveal severe balance instability. The goal of this study is to determine objectively postural control changes using static posturography after neurosurgical treatment (unilateral posteroventrolateral pallidotomy). MATERIAL AND METHODS: 15 patients with advanced idiopathic PD underwent unilateral posteroventrolateral pallidotomy. The study group was composed of 8 men and 7 women. The mean disease duration until operation was 12.5+/-3.5 years, and the mean age of the patients at the time of surgery was 65.8+/-4.1 years. Postural control changes were assessed objectively by static computerized posturography and subjectively according to items of posture, gait and postural stability derived from Part III (motor examination) UPDRS. All evaluations of the balance system were performed preoperatively in the off and on condition, and also two weeks postoperatively in the same conditions. RESULTS: It was found that the majority of posturographic parameters in the off condition were improved after neurosurgical treatment. The improvement in the on condition was less pronounced. For example, the mean path length in the off condition during eyes opened was 318+/-159 mm before pallidotomy, and after surgery it was 240.9+/-119.2 mm in off. The difference was statistically significant (p < 0.005, t=3.11). CONCLUSIONS: Pallidotomy improves postural control changes in the early postoperative period, which can be proved by static computerized posturography.     

Parthenolide Inhibits Proliferation of Fibroblast-Like Synoviocytes In Vitro

Parthenolide is a bioactive constituent of an aromatic herb Feverfew (Tanacetum parthenium). It has been found that both parthenolide and extract of feverfew have anti-inflammatory and antinociceptive properties. Moreover, they demonstrate antiproliferative activities on different human tumour cells. The massive hyperplasia of synovial fibroblasts is the one of the most striking features of rheumatoid arthritis. It is not known whether this is due to the proliferation of synovial fibroblasts or to defective apoptosis. We investigated the effect of parthenolide on the proliferation of rabbit synoviocytes cell line HIG-82, rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and human skin fibroblasts (HSF) in vitro. Cell proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5'-bromo-2'-deoxy-uridine methods. Parthenolide inhibited proliferation of HIG-82 and human RA-FLS. The proliferation of HSF was inhibited less effectively. The antiproliferative potential of parthenolide was demonstrated.