Early events in ovarian oncogenesis

Ovarian cancer represents the most lethal of the gynecological neoplasms. The molecular and genetic events associated with early ovarian oncogenesis are still largely unknown, thus contributing to the lack of reliable biomarkers for disease detection. Since the majority of ovarian tumors are diagnosed at an advanced stage, the availability of early ovarian cancer tissue samples for molecular analyses is very limited. In this review, problems encountered in the study of early ovarian cancer are presented, along with the controversies concerning precursor lesions and stepwise progression towards ovarian malignancy. Experimental modeling in the development of ovarian cancer is also described, as well as genetic and epigenetic alterations associated with early ovarian cancer. Lastly, examples of technological advances in the study of early ovarian cancer are discussed. Hopefully, the increasing knowledge about molecular and genetic events involved in the early stages of ovarian tumorigenesis will provide the basis for management of ovarian cancer in the future

Determination of di(2-ethylhexyl) phthalate in plastic medical devices

The presence of DEHP in dialysis and infusion sets for peritoneal dialysis and parenteral nutrition, which are made of PVC and other plastic polymeric materials, were investigated. Phthalate determination was carried out by gas chromatography–mass spectrometry method (GC–MS). The results showed that the peritoneal dialysis set (bag and tubing) made of PVC contains DEHP in significant amount, about 31–34%. Solution for peritoneal dialysis which was stored in the investigated PVC bag, contains low amount of DEHP, about 3.72 µg dm–3. Infusion bottles which are made of LDPE, also contain DEHP but in lower amount than PVC bags. LDPE bottle for packaging physiological saline solution (0.9 % NaCl) showed higher amount of DEHP than LDPE bottle for packaging Ringer’s solution. In con-trast, solution stored in bottle with lower DEHP level, i.e., Ringer’s solution, contained about three times higher concentration of DEHP than physiological saline solution stored in bottle with higher DEHP level. Concentrations of DEHP in Ringer’s solution and physio-logical saline solution are 17.30 and 5.83 µg dm–3, respectively. The obtained values are under estimated upper-bound dose of DEHP received by adult patients undergoing pro-cedures of peritoneal dialysis and parenteral nutrition

Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer

Objectives: This study investigates (1) local tumor control and (2) normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR) for recurrent lung cancer. Methods: For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1) control (n = 10), (2) conventional radiotherapy (RT; n = 10), and (3) PLDR (n = 10). Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10) or 40 × 0.2 Gy pulses with 3-minute intervals (n = 10). Results: For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P .05). For study 2, the average weight was 20.94 ± 1.68 g and 25.69 ± 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR ( P < .05), respectively. Conclusion: This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. Advances in Knowledge: This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques

How the Duration Period of Erythropoietin Treatment Influences the Oxidative Status of Hemodialysis Patients

Background: End-stage renal disease is a state of enhanced oxidative stress (OS) and hemodialysis (HD) and renal anemia further augment this disbalance. Anemia correction with erythropoietin (EPO) may improve oxidative status. However, there is no evidence of time dependent effects of EPO therapy on redox status of HD patients.Objective: The aim of this study was to evaluate whether the duration of EPO treatment may affect OS parameters in uremic patients.Patients and methods: 104 HD patients and 29 healthy volunteers were included. Patients were divided into 3 groups according to the duration of EPO treatment. Forth group consisted of HD patients without EPO treatment. Plasma and erythrocyte malondialdehyde (MDA, MDArbc), reactive carbonyl groups (RCG), plasma sulfhydryl (-SH) groups and total antioxidative capacity (TAC) levels were evaluated.Results: HD patients both with and without EPO treatment, showed a significant increase in all oxidative parameters without significance between EPO treated and -untreated group. The decrease in MDA and MDArbc levels coincided with the duration of EPO treatment. A negative correlation was observed between the duration of EPO treatment and serum MDA (r=&#727;0.309, p=0.003). Increasing periods of EPO treatment were associated with decrease in RCG, without significance between EPO groups. Increase in TAC accompanied increasing durations of EPO treatment, with EPO treatment for more than 24 months causing the most striking changes (p&#60;0.05). There were no significant differences in &#727;SH levels between EPO subgroups.Conclusion: Our results suggest that long term administration of EPO attenuated the lipid peroxidation process and restored the levels of antioxidants.</p

MR-guided pulsed high intensity focused ultrasound enhancement of docetaxel combined with radiotherapy for prostate cancer treatment

The purpose of this study is to evaluate the efficacy of the enhancement of docetaxel by pulsed focused ultrasound (pFUS) in combination with radiotherapy (RT) for treatment of prostate cancer in vivo. LNCaP cells were grown in the prostates of male nude mice. When the tumors reached a designated volume by MRI, tumor bearing mice were randomly divided into 7 groups (n=5): (1) pFUS alone; (2) RT alone; (3) docetaxel alone; (4) docetaxel + pFUS; (5) docetaxel + RT; (6) docetaxel + pFUS + RT; and (7) control. MR guided pFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner. Animals were treated once with pFUS, docetaxel, RT or their combinations. Docetaxel was given by i.v. injection at 5 mg/kg before pFUS. RT was given 2 Gy after pFUS. Animals were euthanized 4 weeks after treatment. Tumor volumes were measured on MRI at 1 and 4 weeks post-treatment. Results showed that triple combination therapies of docetaxel, pFUS and RT provided the most significant tumor growth inhibition among all groups, which may have a potential for the treatment of prostate cancer due to an improved therapeutic ratio