Clinical significance of lymph node size in locally advanced cervical cancer treated with concurrent chemoradiotherapy.

Background: This study aimed to assess the in-field lymph node (LN) failure rate according to LN size and to investigate effect of LN size on the survival outcome of patients with locally advanced cervical carcinoma treated with concurrent chemoradiotherapy (CCRT). Methods: A total of 310 patients with locally advanced cervical carcinoma treated with CCRT were enrolled in retrospective study. LN status was evaluated by magnetic resonance imaging. All patients received conventional external beam irradiation and high-dose rate brachytherapy, and concurrent cisplatin-based chemotherapy. In-field LN failure rate according to LN size was analyzed. Results: The median follow-up period was 83 months (range, 3-201 months). In-field LN failure rate in patients with pelvic LN size more than 10 mm was significantly higher than that in patients with pelvic LN size less than 10 mm (p<0.001). A similar finding was observed in the in-field para-aortic LN (PALN) failure rate (p=0.024). The pelvic and PALN size (≥10 mm) was a significant prognostic factor of overall-survival (OS) and disease-free survival rate in univariate and multivariate analyses. The OS rate was significantly different between groups according to LN size (<10 mm vs. ≥10 mm). Conclusion: A LN of less than 10 mm in size in an imaging study is controlled by CCRT. On the other hand, in LN of more than 10 mm in size, the in-field LN failure rate increase and the prognosis deteriorate. Therefore, a more aggressive treatment strategy is needed.

Optimal cutoff level of serum squamous cell carcinoma antigen to detect recurrent cervical squamous cell carcinoma during post-treatment surveillance.

OBJECTIVE: The objective of this study was to determine the optimal cutoff level of serum squamous cell carcinoma antigen (SCC-Ag) to detect recurrent cervical squamous cell carcinoma during post-treatment surveillance. METHODS: Between January 2000 and July 2014, a total of 158 women with cervical squamous cell carcinoma were treated with radiotherapy with or without concurrent chemotherapy at our department. A total of 1,550 serum SCC-Ag tests performed during post-treatment surveillance of the 158 patients were included in this retrospective study. RESULTS: During post-treatment surveillance, 53 patients were diagnosed as having recurrent cervical cancer based on biopsy or a radiological test showing progression of a lesion. Receiver operating characteristic (ROC) curve for serum SCC-Ag to diagnose recurrent cervical squamous cell carcinoma showed that the area under the ROC curve was 0.914 (95% confidence interval, 0.887-0.942; P<0.001). The best cutoff value for serum SCC-Ag to obtain the highest Youden's index was ≥2 ng/mL (sensitivity, 80.2%; specificity, 94.6%). CONCLUSION: Serum SCC-Ag test was helpful in detecting recurrent cervical squamous cell carcinoma during post-treatment surveillance, and the optimal cutoff value was ≥2 ng/mL. The researchers recommend active imaging studies, when serum SCC-Ag level ≥2 ng/mL during post-treatment surveillance.

Prophylactic extended-field irradiation with concurrent chemotherapy for pelvic lymph node-positive cervical cancer.

PURPOSE: This study aimed to evaluate whether prophylactic extended-field pelvic radiotherapy (EF-PRT) yields better results than standard whole pelvic radiotherapy (WPRT) in patients with pelvic lymph node-positive cervical cancer treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 126 cases of stage IB-IVA cervical cancer that had pelvic lymph node involvement in magnetic resonance imaging and were treated with CCRT between 2000 and 2016 were reviewed. None of the patients had paraaortic lymph node (PALN) metastases. The patients were classified to two groups, namely, those treated with EF-PRT, including prophylactic para-aortic radiotherapy, and those treated only with WPRT. The median dose to the PALN area in patients treated with EF-PRT was 45 Gy. All patients received concurrent cisplatin-based chemotherapy. RESULTS: Overall, 52 and 74 patients underwent EF-PRT and WPRT, respectively. Patient characteristics and irradiated dose were not significantly different, except the dose to the para-aortic area, between the two groups. The median follow-up period was 75.5 months (range, 5 to 195 months). The 10-year cumulative recurrence rate of PALN for EF-PRT vs. WPRT was 6.9% and 10.1% (p = 0.421), respectively. The 10-year disease-free survival and overall survival for EF-PRT vs. WPRT were 69.7% vs. 66.1% (p = 0.748) and 71.7% vs. 72.3% (p = 0.845), respectively. Acute gastrointestinal complications were significantly higher in EF-PRT (n = 21; 40.4%) than WPRT (n = 26; 35.1%) (p = 0.046). Late toxicities were not significantly different in both groups. CONCLUSION: In this study, prophylactic radiotherapy for PALN does not have an additional benefit in patients with pelvic lymph node-positive cervical cancer treated with CCRT.

Role of ghrelin in the pancreatic exocrine secretion via mitogen-activated protein kinase signaling in rats.

BACKGROUND: This study was performed to investigate the impact of exogenous ghrelin on the pancreatic α-amylase outputs and responses of pancreatic proteins to ghrelin that may relate to pancreatic exocrine. METHODS: Sprague-Dawley male rats (9 weeks old, 300 ± 10 g) were injected with ghrelin via intraperitoneal (i.p.) infusion at dosage of 0, 0.1, 1.0 and 10.0 µg/kg body weight (BW), respectively. The plasma ghrelin and cholecystokinin (CCK) level were determined using enzyme immunoassay kit; the mRNA expression of ghrelin receptor (GHSR-1α) and growth hormone (GH) receptor were assessed by reverse transcription PCR; the expressions of pancreatic α-amylase activity, extracellular-signal-regulated kinases (ERK), phosphorylated extracellular-signal-regulated kinases (pERK) and c-Jun N-terminal kinase (JNK) were evaluated by western blotting; moreover the responses of pancreatic proteins to ghrelin were analyzed using the two-dimensional gel electrophoresis system. RESULTS: The exogenous ghrelin (1.0 and 10.0 µg/kg BW) elevated the level of plasma ghrelin (p < 0.05), and suppressed the expression of pancreatic α-amylase at a dose of 10.0 µg/kg BW (p < 0.05). No difference in the level of plasma CCK was observed, even though rats were exposed to any dose of exogenous ghrelin. In addition, a combination of western blot and proteomic analysis revealed exogenous ghrelin (10.0 µg/kg BW) induced increasing the JNK and ERK expressions (p < 0.05) and four proteins such as Destrin, Anionic trypsin-1, Trypsinogen, and especially eukaryotic translation initiation factor 3 in rat pancreas. CONCLUSIONS: Taken together, exogenous ghrelin by i.p. infusion plays a role in the pancreatic exocrine secretion via mitogen-activated protein kinase signaling pathway.

Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation.

OBJECTIVE: The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. METHODS: A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. RESULTS: Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). CONCLUSION: Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival.

High expression of epidermal growth factor-like domain 7 is correlated with poor differentiation and poor prognosis in patients with epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to evaluate the expression of epidermal growth factor-like domain 7 (EGFL7) in epithelial ovarian cancer, and to assess its relevance to clinicopathological characteristics and patients' survival. METHODS: A total of 177 patients with epithelial ovarian cancer were enrolled in the current study. For each patient, a retrospective review of medical records was conducted. Immunohistochemical staining for EGFL7 was performed using tissue microarrays made with paraffin-embedded tissue block. EGFL7 expression levels were graded on a grade of 0 to 3 based on the percentage of positive cancer cells. We analyzed the correlations between the expression of EGFL7 and various clinical parameters, and also analyzed the survival outcome according to the EGFL7 expression. RESULTS: The expression of EGFL7 in ovarian cancer tissues was observed in 98 patients (55.4%). High expression of EGFL7 (grade 2 or 3) was significantly correlated with pathologic type, differentiation, stage, residual tumor after debulking surgery, lymphovascular space involvement, lymph node metastasis, high cancer antigen 125, peritoneal cytology, and ascites. Among these clinicopathologic factors, differentiation was significantly correlated with EGFL7 expression in multivariate analysis (p<0.05). Survival analysis showed that the patients with high EGFL7 expression had a poorer disease free survival than those with low EGFL7 expression (p=0.002). CONCLUSION: Our data suggest that EGFL7 expression is a novel predictive factor for the clinical progression of epithelial ovarian cancer, and may constitute a therapeutic target for antiangiogenesis therapy in patients with epithelial ovarian cancer.

trans-11 18:1 vaccenic acid (TVA) has a direct anti-carcinogenic effect on MCF-7 human mammary adenocarcinoma cells.

Trans vaccenic acid (TVA; trans-11 18:1) is a positional and geometric isomer of oleic acid and it is the predominant trans isomer found in ruminant fats. TVA can be converted into cis-9, trans-11 conjugated linoleic acid (c9, t11-CLA), a CLA isomer that has many beneficial effects, by stearoyl CoA desaturase 1 (SCD1) in the mammary gland. The health benefits associated with CLA are well documented, but it is unclear whether trans fatty acids (TFAs) from ruminant products have healthy effects. Therefore, the effects of TVA on the proliferation of MCF-7 human breast adenocarcinoma cells and MCF-10A human breast epithelial cells were investigated in the present study. Results showed that TVA inhibited the proliferation of MCF-7 cells but not MCF-10A cells by down-regulating the expression of Bcl-2 as well as procaspase-9. In addition, the suppressive effect of TVA was confirmed in SCD1-depleted MCF-7 cells. Our results suggested that TVA exerts a direct anti-carcinogenic effect on MCF-7 cells. These findings provided a better understanding of the research on the anti-carcinogenic effects of TVA and this may facilitate the manufacture of TVA/c9, t11-CLA fortified ruminant products.

Identification of proteins involved in the pancreatic exocrine by exogenous ghrelin administration in Sprague-Dawley rats.

The aims of study were to investigate the effects of intraperitoneal (i.p.) infusion of ghrelin on pancreatic α-amylase outputs and the responses of pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control group (C, n = 3) and a treatment group (T, 10.0µg/kg BW, n = 3). Blood samples were collected from rat caudal vein once time after one hour injection. The concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel electrophoresis (2-DE) analysis was conducted to separate the proteins in pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of 10.0 µg/kg body weight (BW) increased the plasma ghrelin concentrations (p = 0.07) and elevated the plasma CCK level significantly (p < 0.05). Although there was no statistically significant, the α-amylase activity tended to increase. The proteomics analysis indicated that some pancreatic proteins with various functions were up- or down- regulated compared with control group. In conclusion, ghrelin may have role in the pancreatic exocrine, but the signaling pathway was still not clear. Therefore, much more functional studies focus on these found proteins are needed in the near future.

Identification of biomarkers for endometriosis in eutopic endometrial cells from patients with endometriosis using a proteomics approach.

Endometriosis is a gynecological disease defined as the presence of endometrial tissue outside the uterine cavity, which is caused by various factors. Proteomic analysis of two sets of eutopic endometrial cells collected from the menstrual blood of females with (n=6; n=3) or without (n=6; n=3) endometriosis was performed to identify novel potential biomarkers for endometriosis. The data revealed that samples from endometriosis patients had stem cell characteristics, as they had higher mRNA expression levels of octamer-binding transcription factor 4 (Oct-4), C-X-C chemokine receptor type 4 (CXCR4), SRY-box containing gene 2 (SOX2) and mesenchymal-epithelial transition factor (MET) compared with that of the normal controls. Three proteins, collapsin response mediator protein 2 (CRMP2), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) and myosin regulatory light polypeptide 9 (MYL9), were simultaneously identified from the two sets of samples from females with or without endometriosis by two-dimensional electrophoresis (2-DE). A difference in CRMP2 expression was confirmed with western blotting. Taken together, the results suggest that CRMP2 plays a role in the pathogenesis of endometriosis.