The effectiveness of chemotherapy and electrochemotherapy on ovarian cell lines in vitro.

The presented study aimed to evaluate in vitro the effectiveness of improvement standard chemotherapy with bleomycin by electroporation in two various ovarian cancer cell lines. Two human ovarian cell lines OvBH-1 and SKOV-3 were used. The lines were selected because of their resistance to several therapeutic methods. As anticancer drug we use range of concentrations of bleomycin. In EP and ECT experiments different voltage values: from 0 to 1200 V/cm, 8 pulses with duration of 100µs and intervals between pulses 1s long were used. The cells viability after applied treatments was evaluated by MTT assay. The expression of heat shock proteins - HSP27 was examined by immunocytochemical ABC method.The cytotoxicity with different concentrations of bleomycin alone was not significantly decrease in both cell lines. It confirms resistance of these cells to conventional chemotherapy. The highest decrease of cell proliferation was observed after EP with bleomycin after 48h of incubation for 1000 V/cm. The intensity of expression of small heat shock proteins HSP27 slightly increased after ECT in both treated cell lines, in particular in OvBH-1. The presented study indicated that application of electroporation may effectively enhance chemotherapy with bleomycin, particularly in the case of treating ovarian cancer resistant to standard therapy.

Gene expression profiles in three histologic types, clear-cell, endometrioid and serous ovarian carcinomas.

Ovarian carcinoma is the most lethal type of gynecologic malignancy in the Western world. Majority of early stage ovarian cancers are asymptomatic and this is the main reason that more than two-thirds of patients are diagnosed with advanced disease. Ovarian tumors are heterogeneous and the different histologic subtypes are further classified as benign, borderline (low-grade) and malignant (high-grade) to reflect their behavior. The aim of the study was to analyze gene expression profiles in three histologic types of ovarian carcinoma in an attempt to find the molecular differences among serous, endometrioid and clear cell subtypes. The analysis of gene expression was performed on 57 samples of ovarian carcinoma. RNA was isolated from the ovarian cancer tissues. The gene expression changes were determined by microarray analysis and quantitative real time polymerase chain reaction (qRT-PCR). Measurement of relative gene expression levels was used to identify molecular differences among three histologic types of ovarian carcinoma (clear-cell, endometrioid and serous). Unsupervised statistical analysis revealed four biological subtypes among three histotypes under study. The endometrioid ovarian carcinoma was divided into two molecular subtypes. The biggest molecular differences were observed between clear-cell and serous carcinomas (1070 genes, FDR 0.05), the smallest between endometrioid and serous carcinomas (81 genes, FDR 0.05). The biggest group of differentially expressed genes was involved in transport and metabolism. This finding can explain the differences in the response to chemotherapy observed among different histologic types of ovarian carcinomas. In conclusion, we found TCF2 (HNF1B) gene as a suitable marker for ovarian clear cell carcinoma. Gene expression profiling also shed light on the molecular mechanisms of different chemoresistance among the analyzed histotypes.

Iraq and the future of nuclear nonproliferation: the roles of inspections and treaties.

In the aftermath of the GulfWar, revelations about Iraq's extensive program to develop nuclear weapons challenge the future of the international nuclear nonproliferation regime. Until inspections sanctioned by the U.N. Security Council began, Iraq's violations of its obligations under the Treaty on the Nonproliferation of Nuclear Weapons and its related safeguards agreement with the International Atomic Energy Agency went undetected. The ultimate impact of Iraq's behavior on the regime cannot yet be determined, but there is now an opportunity to improve safeguards and other aspects of the regime, including strengthening export controls and proliferation intelligence collection and sharing and the development of appropriate response capabilities.

Monitoring of photodynamic therapy results in age-related macular degeneration by means of preferential hyperacuity perimeter.

PURPOSE: To describe changes revealed by Zeiss Preferential Hyperacuity Perimeter (PreView PHP) in age-related macular degeneration (AMD), before and after photodynamic therapy (PDT), and determine usefulness of such monitoring. METHODS: Forty patients (40 eyes) with subfoveolar choroidal neovascularization (CNV) and 20 volunteers with cataract (40 eyes) were examined in a prospective study. Control group was screened for false positive results to evaluate reliability of the test. Subfoveolar CNV was confirmed by fluorescein angiography and optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and macular visual field in the PHP (area and intensity of distortion) were assessed 1 day before and 1 week and 4 weeks after PDT. RESULTS: Four weeks after PDT there was improvement in PHP results in 20 eyes (50%), stabilization in 15 eyes (37.5%) and progression in 5 eyes (12.5%). At this time there was BCVA improvement in 9 eyes (22.5%), stabilization in 28 eyes (70%), and worsening in 3 eyes (7.5%). 1 week after PDT 30 eyes (75%) presented temporary progression in PHP but only 3 patients (7.5%) presented temporary decrease of visual acuity and progression in OCT. Correlation coefficient of BCVA and PHP results was low during whole study. There was no significant change in control group during observation. 17.5% false positive PHP results were obtained at baseline. In the PDT group no false negative results were noted. CONCLUSIONS: Visual outcome after PDT cannot be predicted with use of PreView PHP. Temporary progression of changes in PHP 1 week after PDT can be expected in most cases.

Depressive symptoms, cognitive decline, and risk of AD in older persons.

BACKGROUND: Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD, but there have been few prospective studies and their results have been inconsistent. METHODS: Participants are Catholic clergy members who were aged > or =65 years and who did not have clinical evidence of AD. During a 7-year period, they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived. Number of depressive symptoms was assessed at baseline with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The association of CES-D score with incident AD, using proportional hazards models, and cognitive decline, using random effects models, was examined. RESULTS: At baseline, participants reported an average of about one depressive symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108 persons developed AD. In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function, CES-D score was associated with both risk of AD and rate of cognitive decline. For each depressive symptom, risk of developing AD increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. CONCLUSIONS: The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD.

Association between intra-abdominal pressure and jugular bulb saturation in critically ill patients.

BACKGROUND: Disorders in cerebral circulation following elevated intra-abdominal pressure (IAP) may lead to silent brain ischemia, which can be serious problem in sedated critically ill patients. The aim of the present study was to analyse the possible association between jugular venous bulb pressure (JVBP) and jugular venous bulb saturation (SjO2) to IAP in critically ill patients. METHODS: Adult septic shock patients with acute kidney injury were studied just after the admission to Intensive Care Unit and after 24 and 48 hours of treatment. Patients were divided into: CVVH group (patients treated with continuous veno-venous haemofiltration) and furosemide group (patients treated with furosemide infusion). The IAP was measured via the bladder. The right jugular vein was retrogradely cannulated for JVBP and SjO2 measurement. Intra-abdominal hypertension was defined as a sustained increase of IAP equal to or above 12 mmHg. RESULTS: Forty patients (25 male and 15 female patients) were studied. In all participants, IAP strongly correlated with JVBP (P<0.001, r=0.73). This correlation was stronger in the furosemide group than the CVVH group. Moreover, an increase in IAP was related to an increase in JVBP and a decrease in SjO2. There was an inverse correlation between IAP and SjO2 (P<0.001, r=-0.55). This correlation was stronger in furosemide group than CVVH group. CONCLUSION: IAP is correlated to JVBP and inversely correlated to SjO2. Increase in IAP leads to elevation in JVBP and decrease in SjO2. Renal replacement therapy disturbs the correlation between IAP, JVBP and SjO2.

Organ retrieval in donors suspected of cancer: single-center experience.

BACKGROUND: The transmission of cancerous cells with a transplanted organ is among the most serious complications of transplant surgery. Detailed preoperative tests seek to reduce the risk of transmission of viral and bacterial infections as well as to prevent donor-derived malignancy following organ transplantation. The objective of this study was to report our experience among cadaveric donors who we suspected of cancer. MATERIALS AND METHODS: We performed a retrospective search of the medical records of 75 potential cadaveric donors referred to our unit between January 2007 and December 2010. Our focus, however, was on donors suspected of cancer. RESULTS: Among 75 potential cadaveric donors 22 (29%) revealed features suggestive of cancer: physical signs of tumor pre- or intraoperatively: elevation of serum levels of a cancer marker; or an abnormal finding on radiological imaging. Among the latter group, 15 donors necessitated urgent histopathologic examination to rule out or confirm cancer. In four cases, organ transplantation was abandoned following the examination, including three cases in which a tissue diagnosis of cancer was evident and in one case, the examination was inconclusive to exclude cancer. In the remaining 14 cases, the histopathologic examination did not reveal cancer; thus transplantation was performed. CONCLUSIONS: Thorough histopathologic examination is essential in all potential donors who are suspected of cancer to prevent donor-derived malignancy following transplantation. In some cases, however, the tissue sampling is not conclusive; hence, transplantation must be abandoned. Even the most precise examination of the donor does not protect the recipient from the risk of transmission of cancer.

Successful kidney transplantation in a patient with multiple endocrine neoplasia type 2A syndrome: case study.

We present the case of a 37-year-old patient diagnosed with multiple endocrine neoplasia type 2A (MEN 2A) syndrome, as confirmed by genetic tests, who underwent the transplantation of a kidney from a cadaveric donor. MEN 2A, a hereditary autosomal dominant syndrome, is caused by the mutation of the RET proto-oncogene. In almost all patients this syndrome, is characterized by the occurrence of medullary thyroid cancer and pheochromocytoma; in some individuals also hyperparathyroidism. The available literature has not documented a kidney transplantation performed in Poland for this indication.