Peripheral neurotoxicity is a frequent dose-limiting side effect of the chemotherapeutic agent cisplatin. This study was conducted to investigate the preventive effect of oxytocin (OT) on ...cisplatin-induced neurotoxicity in rats. Forty-four adult female rats were included in the study. Thirty-six rats were administered intraperitoneally (i.p.) single dose cisplatin 10 mg/kg and divided in to 3 groups. The first group (n=12) received saline i.p., whereas the second group (n=12) and the third group (n=12) were injected with 80 µg/kg and 160 µg/kg OT, respectively, for 10 days. The remaining 8 rats served as the control group. Electromyography (EMG) studies were recorded and blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA), tumor necrosis factor (TNF)-α, and glutathione (GSH) levels. EMG findings revealed that compound muscle action potential amplitude was significantly decreased and distal latency was prolonged in the nontreated cisplatin-injected rats compared with the control group (P<0.005). Also, nontreated cisplatin-injected rats showed significantly higher TNF-α and MDA levels and lower GSH level than control group. The administration of OT significantly ameliorated the EMG alterations, suppressed oxidative stress and inflammatory parameters, and increased antioxidative capacity. We suggest that oxytocin may have beneficial effects against cisplatin-induced neurotoxicity.
Obesity is associated with increased mortality among ovarian cancer and is a poor prognostic factor. There are significant links between the leptin hormone, a product of the obesity gene, and the ...development of ovarian cancer. Leptin is a vital hormone-like cytokine secreted from adipose tissue and is mainly involved in the maintenance of energy homeostasis. It regulates several intracellular signaling pathways and also interacts with various hormones and energy regulators. It acts as a growth factor by stimulating cell proliferation and differentiation and in this way contributes to cancer cell development. The aim of the study was to investigate the effects of leptin on human ovarian cancer cells.
In this study, the effects of increasing the concentration of leptin were investigated on the cell viability of OVCAR-3 and MDAH-2774 ovarian cancer lines by MTT assay. Moreover, to elucidate the molecular mechanisms of leptin in ovarian cancer cells, changes in the expression levels of 80 cytokines were evaluated after leptin treatment
a human cytokine antibody array.
Leptin increases the proliferation of both ovarian cancer cell lines. IL-1 level was increased in OVCAR-3 cells and TGF-β level was increased in MDAH-2774 cells after leptin treatment. A decrease in IL-2, MCP-2/CCL8 and MCP-3/CCL7 levels was detected in both ovarian cancer cell lines with leptin administration. An increase in IL-3 and IL-10 expressions, insulin-like growth factor binding proteins (IGFBP) IGFBP-1, IGFBP-2 and IGFBP-3 levels were detected in both ovarian cancer cell lines with leptin administration. In conclusion; leptin has a proliferative effect on human ovarian cancer cell lines and affects different cytokines in different types of ovarian cancer cells.
Lapatinib-(LPT) is a dual tyrosine kinase inhibitor that has important effects on the targeted therapy of various tumours. The current study is aimed to use a novel tracer strategy including ...Technetium-99 m-(
99m
Tc) radiolabeled LPT and its poly(lactic-co-glycolic acid)-(PLGA) encapsulated formulation-(LPT-PLGA). In vitro bioaffinity of the
99m
TcTc-LPT and
99m
TcTc-LPT-PLGA was evaluated by using cell culture methods on human breast adenocarcinoma (MDA-MB-231), cervix adenocarcinoma and human ovarian (MDAH-2774) cancer cell lines. Radiochemical yield were over 95% and both compounds were examined high incorporation values on HeLa and MDAH cell lines. Current results may contribute to develope as the encapculated agents including radiotracer.
Background
Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen ...citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS.
Methods and results
Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05).
Conclusions
In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.
mTOR inhibitors are recently important tools for cancer treatment. They act on cell growth regulation, proliferation, and survival. Pharmacological therapy with mTOR inhibitors such as everolimus is ...emerging as an alternate approach. Meanwhile, early diagnosis is a hot target in cancer research. Conversely, it can be a novel diagnosis approach to monitor mTOR inhibitors during their pathway. From this point of view, radiolabeling of everolimus and its nanoformulation (EVE-PLGA nanoparticles) in high yields (95%) with an important diagnostic radionuclide (technetium-99m) is described. Besides, in vitro incorporation assays of radiolabeled everolimus and its nanoformulation against the cervix and ovarian cancer cells were demonstrated 8- and 12-times high values than control group. In conclusion, radiolabeled everolimus and its nanoformulation have a promise to improve on monitoring mTOR inhibitors.
Purpose
To identify prognostic predictors and spread patterns in adult ovarian granulosa cell tumors (OGCTs).
Methods
Available retrospective data of 108 OGCT patients managed at three centers ...between January 1, 1991 and December 31, 2010 were abstracted and analyzed.
Results
Stage distributions at diagnosis for stage I, II and III OGCT were 84.3, 5.4, and 9.3 %, respectively. Optimal cytoreduction with no macroscopically visible disease was achieved in 99/108 (91.6 %) patients. The median disease-free interval to first recurrence was 61 months. The overall 5- and 10-year survival rates were 93.3 and 90.9 %, respectively. Disease recurred in 18 (16.6 %) patients, and 8 (7.4 %) patients died of their disease. The first recurrence sites included the pelvic peritoneum (
n
= 10), liver/liver-capsule (
n
= 5), rectosigmoid colon (
n
= 4), retroperitoneal lymph nodes (
n
= 3), omentum (
n
= 3), small bowel mesenterium (
n
= 2), and vaginal cuff (
n
= 2). Multiple-site recurrence was observed in 9/18 (50 %) patients. Secondary cytoreduction requiring extensive surgery was performed in 14 patients with an optimality rate of 71.4 %. The remaining four patients received only chemotherapy. Multivisceral approaches, including pelvic peritonectomy (
n
= 9; 64.2 %), rectosigmoid resection (
n
= 3; 21.4 %), and segmental liver capsule resection (
n
= 2; 14.2 %) were performed more frequently during the secondary surgery. Definitive retroperitoneal lymph node metastasis rates at the initial and recurrent settings were 5.1 % (3/58) and 21.4 % (3/14), respectively. Both stage and residual tumor status were significantly associated with recurrence in univariate and multivariate analyses.
Conclusions
Stage and residual tumor status are predictors of recurrence. Pelvic peritoneal, nodal and hepatic involvement, and multiple-site spread patterns requiring extensive cytoreductive surgery are likely associated with recurrence of OGCTs.
Background: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged ...cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001). Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.
To investigate whether granulocyte-colony stimulating factor (G-CSF) can decrease the extent of ovarian follicle loss caused by cisplatin treatment.
Twenty-one adult female Sprague-Dawley rats were ...used. Fourteen rats were administered 2 mg/kg/day cisplatin by intraperitoneal injection twice per week for five weeks (total of 20 mg/kg). Half of the rats (n=7) were treated with 1 mL/kg/day physiological saline, and the other half (n=7) were treated with 100 μg/kg/day G-CSF. The remaining rats (n=7, control group) received no therapy. The animals were then euthanized, and both ovaries were obtained from all animals, fixed in 10% formalin, and stored at 4°C for paraffin sectioning. Blood samples were collected by cardiac puncture and stored at -30°C for hormone assays.
All follicle counts (primordial, primary, secondary, and tertiary) and serum anti-Müllerian hormone levels were significantly increased in the cisplatin+G-CSF group compared to the cisplatin+physiological saline group.
G-CSF was beneficial in decreasing the severity of follicle loss in an experimental rat model of cisplatin chemotherapy.
The endothelial lipase gene (LIPG) has a major role in regulating high density lipoprotein cholesterol (HDL-C), therefore this study investigated whether LIPG is associated with coronary artery ...disease (CAD) in a Turkish population.
The LIPG (584 C/T) mutation was analyzed in 74 CAD patients and 73 controls.
There was a significant difference between the two groups regarding the mutant T allele frequencies (χ
=0.456, p=0.020; 26.7% and 41.8% in patient and control groups, respectively) for 584 C/T. Even though the TT genotype was not significantly different, it had p=0.054 which supported our results.
The endothelial lipase gene (584 C/T) T allele might be protective in association with coronary artery disease. Therefore, LIPG gene is related to risk for CAD in the Turkish population probably through altering HDL-C metabolism.
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