Effect of the farnesyl transferase inhibitor L-744,832 on the colon cancer cell line DLD-1 and its combined use with radiation and 5-FU

BACKGROUND: Ras oncogenes are found in 25% of human tumors and they significantly affect prognosis. One of the major fields studied to improve anticancer drugs is blockade of the oncogenic ras protein function. One of the mechanisms to block the function of these proteins is to block farnesylation using a farnesyl transferase inhibitor (FTI) and thus to prevent the ras from anchoring to the cell membrane. METHODS: In this study, we investigated the effects of FTI L-744,832 either alone or in combination with 5-fluorouracil (5-FU; 1 microM/l) and radiotherapy (2, 6, and 10 Gy) on the colon cancer cell line DLD-1 with mutations in K-, N- and H-ras, c-myb, c-myc, p53, fos, sis and DNA repair genes. Drugs were added 3 h after cultivation. Radiotherapy was performed on the 3rd day of the study. On the 3rd day, medium and drugs were changed. Evaluations were performed on the 6th day. RESULTS: Administration of L-744,832, neither alone nor its combination with 5-FU and radiation, affected the number of DLD-1 cells and apoptosis rates. Regarding its effects on the cell cycle, L-744,832 was shown to lead to G(0)/G(1) and G(2)/M accumulation in a dose-dependent manner when administered alone. However, in combination with 5-FU, only a G(0)/G(1) accumulation was observed. CONCLUSION: Our study showed that FTI L-744,832 does not effect the cell number and apoptosis rate of DLD-1 cells and it cannot overcome 5-FU and radiation resistance, although it is able to modify some phases of the cell cycle.     

Transvaginal Route for Kidney Extraction in Laparoscopic Donor Nephrectomy

Background and Objectives:

The aim of this retrospective study was to compare conventional laparoscopic living-donor nephrectomy with transvaginal natural orifice transluminal endoscopic surgery–assisted living-donor nephrectomy in terms of feasibility and reproducibility.

Methods:

A total of 115 consecutive female patients who underwent laparoscopic living-donor nephrectomy (n = 70) or transvaginal natural orifice transluminal endoscopic surgery–assisted living-donor nephrectomy (n = 45) were included and compared in terms of operative characteristics, as well as donor and recipient outcomes.

Results:

No significant difference was observed between the laparoscopic living-donor nephrectomy and transvaginal natural orifice transluminal endoscopic surgery–assisted living-donor nephrectomy groups in terms of mean duration of warm and cold ischemia, operation time, length of hospital stay, arterial anastomoses, visual analog scale pain scores, serum creatinine levels, and receiver outcomes, whereas a significantly higher number of venous anastomoses was noted in the laparoscopic living-donor nephrectomy group than in the transvaginal natural orifice transluminal endoscopic surgery–assisted living-donor nephrectomy group (P = .029).

Conclusions:

Transvaginal natural orifice transluminal endoscopic surgery–assisted living-donor nephrectomy seems to be a feasible and reproducible alternative to conventional laparoscopic living-donor nephrectomy in female donors provided the viability of the vagina as an organ retrieval route.     

Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet

Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low‐density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium‐dependent relaxations in cholesterol‐fed rats. For this purpose, rats were fed by 2% cholesterol‐enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium‐dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL‐cholesterol levels were found to be increased in cholesterol‐fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.     

Depression and anxiety status of patients with implantable cardioverter defibrillator and precipitating factors

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are life-saving devices in treatment of life-threatening arrhythmia. We evaluate the emotional status of Turkish patients with ICD and try to explain factors that affect emotional status of the patients. METHODS: Ninety-one patients with previously implanted ICD were included in the study. Follow-up periods, presence of ICD shock, shock frequency, time of the recent shock, age, and gender were noted. Depression and anxiety scores were evaluated according to Hospital Anxiety and Depression (HAD) chart. RESULTS: Mean anxiety and depression scores were found as 9.1 +/- 5.3 and 7.2 +/- 5.1, respectively. According to HAD charts, 42 patients (46%) had anxiety and 37 patients (41%) had depression. Depression scores indicated significant difference between subgroups divided on the basis of follow-up periods (P = 0.026) and on the basis of time of recent shock (P = 0.028). There was significant difference in anxiety scores (P = 0.016) between patients with ICD shocks and patients with no shocks. When the patients were divided into subgroups according to shock frequency, both depression (P = 0.024) and anxiety (P = 0.016) scores presented significant difference. In female patients, depression and anxiety scores were found significantly higher compared to male patients (P = 0.046 and P = 0.016, respectively). In multivariate analysis, gender and shock frequency were found as predictors for anxiety scores (P = 0.019 and P = 0.044, respectively). However same analysis revealed no predictive factor for depression score. CONCLUSION: Our study indicates presence of depression and anxiety in nearly half of the patients with ICD. Consultation with psychiatry should be a part of the treatment for patients with ICD, especially for those who constitute high-risk groups.     

<Emphasis Type="Italic">In Vivo</Emphasis> Fluorescence Imaging is Well-Suited for the Monitoring of Adenovirus Directed Transgene Expression in Living Organisms

Purpose  

We tested a new light detection cooled charge-coupled device (CCD) for in vivo assessment of noninvasive, whole-body fluorescence optical imaging of adenovirus directed enhanced green fluorescent protein (AdEGFP) expression.     

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer

INTRODUCTION: YKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer. METHODS: YKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10-96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths. RESULTS: The median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 mug/l (range, 25.0-1021.3 mug/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05). CONCLUSION: Our results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.     

Implantation of a permanent pacemaker in a patient with severe Parkinson's disease and a preexisting bilateral deep brain stimulator

Cardiac pacemakers and implantable defibrillators are commonly used therapeutic modalities in cardiac arrhythmias. Thalamic deep brain stimulation has also become an important modality in the treatment of drug-refractory tremors and other complications in advanced Parkinson's disease. Concerns exist about the potential electrical interaction and interference between these 2 devices in the same patient. There are only a limited number of reports that have investigated this issue. We describe a patient with advanced Parkinson's disease and a previously implanted deep brain stimulator, who subsequently needed a permanent cardiac pacemaker due to severe bradyarrhythmia. Despite the probability of interference between the devices, there were no problems during implantation of the cardiac pacemaker; both the deep brain stimulator and cardiac pacemaker functioned appropriately afterwards.     

Induction of apoptosis and inhibition of growth of human hepatoma HepG2 cells by heparin

BACKGROUND/AIMS: Apoptotic and anti-proliferative effects of heparin on a number of cancers have been described. There have been no studies analyzing the effect of heparin on human hepatoma cells. The aim of this study was to investigate the effect of heparin on human hepatoma cell line, HepG2. METHODOLOGY: HepG2 cell line was cultured with different concentrations of heparin. Colony count, viability assay, percentage of the apoptosis and proliferative index were assessed at the end of the 7th day. Trypan blue was used to assess viability. Apoptosis and proliferative indexes were assessed by flow-cytometry. RESULTS: Hepatoma cells were arrested at the G0/G1 phase with heparin incubation and proliferative indexes decreased significantly in 20, 40 and 80 U/mL of heparin concentrations in comparison with the control (36 +/- 1%, 30 +/- 5% and 29 +/- 8% vs. 44 +/- 1%, p < 0.01). Flow cytometry revealed a statistically significant increase in apoptosis in groups incubated with 40 and 80 U/mL of heparin in comparison with the control (39 +/- 26% and 58 +/- 18% vs. 0.83 +/- 1.3%, p < 0.01). Colony counts per well and viable cells per microL decreased significantly in 80 U/mL of heparin. CONCLUSIONS: Heparin leads to a significant anti-proliferative and an apoptotic effect on human hepatoma cells in vitro.     

Relationship between the serum sCD40L level and aspirin-resistant platelet aggregation in patients with stable coronary artery disease

BACKGROUND: Current evidence supports the central role of inflammation in all phases of the atherosclerotic process, including its thrombotic complications. Increased serum sCD40L may trigger platelet activation, so the aim of the present study was to determine the relation between sCD40L levels and aspirin-resistant platelet aggregation in patients with coronary atherosclerosis. METHODS AND RESULTS: A total of 167 consecutive patients (39-85 years old, 35.9% women) with stable coronary artery disease was enrolled in the study. Platelet function was evaluated by a Platelet Function Analyzer 100 device (PFA-100) with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (ADP) (Col/ADP) cartridges. Aspirin resistance was defined as a closure time (CT) <186 s with Col/Epi cartridges, despite regular aspirin therapy. Serum sCD40L level was determined quantitatively with an ELISA method. Fifty-seven (34.1%) patients had aspirin resistance according to the PFA-100. Mean CT measured with the Col/ADP cartridges was 83+/-18 s (65-101 s). Mean serum sCD40L was 157 pg/ml (6-700 pg/ml) in the entire cohort. Patients with aspirin resistance had a mean serum sCD40L level of 166 pg/ml and patients with aspirin-sensitive platelet aggregation had an sCD40L level of 152 pg/ml (p=0.582). CONCLUSION: The sCD40L level is similar in patients with aspirin-resistant and aspirin-sensitive platelet aggregation according to the PFA-100. There is still need for further studies to elucidate the relationship between aspirin-resistant platelet aggregation and sCD40L, which is now known to be prothrombotic, proinflammatory and to be a risk factor for cardiovascular events.