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.
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.
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.
The purpose of this study is to evaluate the prognostic role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the need for para-aortic lymphadectomy in ...patients with primary fallopian tube carcinoma (PFTC).
Ninety-one patients with a diagnosis of PFTC were identified through the gynecologic oncology service database of six academic centers. Clinicopathological, surgical, and complete blood count data were collected.
In univariate analysis, advanced stage, suboptimal surgery, and NLR > 2.7 were significant prognostic factors for progression-free survival, whereas in multivariate analysis, only advanced stage and suboptimal surgery were significant. In addition, in univariate analysis, cancer antigen 125 ≥ 35 U/mL, ascites, advanced stage, suboptimal surgery, NLR > 2.7, PLR > 233.3, platelet count ≥ 400,000 cells/mm(3), staging type, and histological subtype were significant prognostic factors for overall survival (OS); however, in multivariate analysis, only advanced stage, suboptimal surgery, NLR > 2.7, and staging type were significant. Inclusion of pelvic and para-aortic lymphadenectomy in surgery showed significant association with longer OS, with a mean and median OS of 42.0 months and 35.5 months (range, 22 to 78 months), respectively, vs. 33.5 months and 27.5 months (range, 14 to 76 months), respectively, for patients who underwent surgery without para-aortic lymphadenectomy (hazard ratio, 3.1; 95% confidence interval, 1.4 to 5.7; p=0.002).
NLR (in both univariate and multivariate analysis) and PLR (only in univariate analysis) were prognostic factors in PFTC. NLR and PLR are inexpensive and easy tests to perform. In addition, patients with PFTC who underwent bilateral pelvic and para-aortic lymphadenectomy had longer OS.
Aim: To determine the effect of paclitaxel and cisplatin in the reduction of primordial follicular reserve in rat.
Material and methods: Thirty young female rats were divided randomly into three ...groups of 10 rats each. Paclitaxel 7.5 mg/kg and cisplatin 5 mg/kg were administered intraperitoneally in a single dose sterile technique to paclitaxel (n = 10), and cisplatin (n = 10) groups, and sterile saline solution was given to a control group (n = 10). To assess the effects of chemotherapeutic agents on the primordial follicles, the rats were oophorectomised 7 days after the administration of chemotherapeutic agents. Haematoxylin and eosin staining was used to determine the number of primordial follicles. Primordial follicles were identified by the presence of an oocyte encapsulated partially or completely by a single layer of flattened follicular cells without a theca layer at the ovarian cortex.
Results: The number of primordial follicles in the control group was 23.1 ± 16.1 follicles. The number of primordial follicles were decreased significantly in both paclitaxel and cisplatin groups compared to control group (10.3 ± 13.0 and 13.9 ± 15.2 follicles, respectively) (P = 0.001 and P = 0.01, respectively). The difference in the number of primordial follicles between the paclitaxel and cisplatin groups was insignificant (P = 0.465).
Conclusion: The administration of high dose paclitaxel and cisplatin to young rats causes the depletion of primordial follicles. However, no significant difference was observed between the two agents.
To investigate the decisive role of preoperative serum thrombopoietin levels in the discrimination of benign and malignant ovarian pathologies and its value in the evaluation of treatment response.
...Fifty patients with diagnoses of adnexal masses (25 benign, 25 malignant) were included in the study. Blood samples were collected from all cases preoperatively. Age, menopausal status, adnexal mass size, preoperative CA-125 level, platelet count, the stage of the disease (FIGO stage), tumor grade, histologic subgroup, the residual tumor mass, ascites cytology, surgical procedures, and postoperative treatments were recorded for the malignant group. Response to treatment was evaluated based on the revised RECIST guideline.
The preoperative serum thrombopoietin levels of the malignant cases (median, 98; range, 7 to 768) were significantly higher when compared with those of benign cases (median, 27; range, 13 to 131; p=0.004). The positive predictive value of CA-125 was found to be 79%, when it was used as a single marker; however it had risen to 85% when both CA-125 and thrombopoietin levels were used. There was no significant relationship between preoperative serum thrombopoietin levels and tumor grade, ascites cytology, presence of residual mass, and response to treatment. The preoperative serum thrombopoietin levels were significantly higher in stage III-IV cases and cases with serous histology. The post-treatment serum thrombopoietin levels in the malignant group were significantly lower as compared with the preoperative thrombopoietin levels.
Thrombopoietin can play an additive role for prediction of ovarian cancer.
After revealing the anti-cancer properties of boron, which is included in the category of essential elements for human health by the World Health Organization, the therapeutic potential of boron ...compounds has been begun to be evaluated, and its molecular effect mechanisms have still been among the research subjects. In ovarian cancer, mutations or amplifications frequently occur in the PI3K/Akt/mTOR pathway components, and dysregulation of this pathway is shown among the causes of treatment failure. In the present study, it was aimed to investigate the anti-cancer properties of boron-containing DPD in SKOV3 cells, which is an epithelial ovarian cancer model, through PI3K/AKT/mTOR pathway. The cytotoxic activity of DPD in SKOV3 cells was evaluated by WST-1 test, apoptotic effect by Annexin V and JC-1 test. The gene expressions associated with PI3K/AKT/mTOR pathway were determined by real-time qRT-PCR. In SKOV3 cells, the IC
50
value of DPD was found to be 6.7 mM, 5.6 mM, and 5.2 mM at 24th, 48th and 72nd hour, respectively. Compared with the untreated control group, DPD treatment was found to induce apoptosis 2.6-fold and increase mitochondrial membrane depolarization 4.5-fold. DPD treatment was found to downregulate
PIK3CA
,
PIK3CG
,
AKT2
,
IGF1
,
IRS1
,
MAPK3
,
HIF-1
,
VEGFC
,
CAB39
,
CAB39L
,
STRADB
,
PRKAB2
,
PRKAG3
,
TELO2
,
RICTOR
,
MLST8
, and
EIF4B
genes and upregulate
TP53
,
GSK3B
,
FKBP8
,
TSC2
,
ULK1
, and
ULK2
genes. These results draw attention to the therapeutic potential of DPD, which is frequently exposed in daily life, in epithelial ovarian cancer and show that it can be a candidate compound in combination with chemotherapeutics.
This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification ...system, with particular focus on the high-intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high-intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high-intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high-intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high-intermediate- and high-risk endometrial cancer cases.
Objectives: To evaluate differences in ascitic fluid trace element concentrations which might be useful in discrimination between benign and malignant ascites.
Design and Methods: The concentrations ...of copper, zinc, magnesium and iron in ascitic fluid and venous blood in 17 patients were investigated. The relationship between these trace elements and type of disease were examined. Investigations were carried out in a group of 5 males and 5 females aged 54 to 77 yr who had cirrhosis ascites and in a group of 7 females aged 41 to 76 yr with ascites due to gynecologic neoplasms.
Results: The mean ascitic fluid and serum concentrations of copper were significantly higher in neoplastic diseases compared to benign disease states (118,43 vs. 97,50, 91,14 vs. 26.90) (
p < 0,05 and
p < 0,01 respectively). The zinc levels in ascitic fluid and serum were significantly different between the groups (
p < 0,01). Neoplastic patients had significantly higher ascitic fluid magnesium levels than the benign disease group (2,17 vs. 1,55,
p < 0,001). The serum levels of iron were significantly lower in the neoplastic diseases group (92, 28 vs. 255,
p < 0, 01). In benign diseases the concentration of zinc in ascitic fluid correlated positively with ascitic fluid copper concentrations. The concentrations of zinc and iron in malignant ascites correlate positively with the magnesium concentrations. Statistically significant negative correlations were found between ascites zinc and magnesium and magnesium and copper in cirrhotic patients and magnesium and copper in malignant diseases.
Conclusions: The results showed that zinc, magnesium and iron levels were significantly different between cirrhotic and neoplastic illness. Analysis of serum and ascitic fluid trace element composition may be helpful in identifying and distinguishing the malignant and nonmalignant ascites and provides useful information on processes regulating passage of blood components into the peritoneal cavity.
Large cell neuroendocrine carcinoma is a rare aggressive cervical neoplasm, considerably rarer than the well-recognized small cell neuroendocrine carcinoma of the cervix. Cervical large cell ...neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have an unfavorable outcome, similar to that of small cell carcinoma.
We report a 45-year-old woman with large cell neuroendocrine uterine cervical carcinoma.
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