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Aripiprazole (ARP) is an atypical anti-psychotic drug widely used to treat schizophrenia and bipolar disorder. The pharmacological effects of ARP on cancer cells are still poorly understood. In this study, anti-cancer effects of ARP on various malignant tumor cells and its molecular mechanism were further carefully examined by using cell proliferation assay, xenograft mouse model, immunoblotting analysis, migration assay, luciferase reporter gene assay, kinase assay, and overexpression strategy. Treatment with ARP induced cytotoxicity in U251 glioma cells, MKN-1 gastric adenosquamous carcinoma cells, and CT26 colon carcinoma cells. ARP suppressed cell proliferation of LN428, MDA-MB-231, and HEK293 cells. Pro-apoptotic factors active caspase-3, -8, and -9, as well as p53, were upregulated, whereas the protein and mRNA levels of anti-apoptotic factor B-cell lymphoma 2 (Bcl-2) decreased. In agreement with the in vitro results, ARP compound also significantly suppressed the growth of tumor masses formed by injecting CT26 colon cancer cells into mice. ARP treatment also effectively decreased the migratory ability of U251 glioma cells by downregulating metalloproteinase-9. Levels of phosphorylated Src, phosphorylated phosphatidylinositide 3-kinase (PI3K), and phosphorylated signal transducer and activator of transcription 3 (STAT3) were significantly decreased following ARP treatment. ARP compound reduced the kinase activity of Src. Our studies suggest that Src may be an important target molecule linked to the antitumor effects of ARP., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Serum autoantibodies against tumor-associated antigens (TAAs) have received much attention as potential biomarkers for early detection of cancers, since they can be detected in the early stages of cancers. Autoantibodies against Cancer Antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), Cancer Antigen 19-9 (CA19-9), c-Myc, p53, heat shock protein (Hsp)27 and Hsp70 have been suggested as potential markers for detecting several types of cancer. In the present study, the seven types of antibody listed above were evaluated for detecting cervical lesions. Enzyme-linked immunosorbent assays (ELISAs) were used to measure IgG levels of the autoantibodies in women with normal cytology, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cervical cancer. The increases of anti-CA15-3 and anti-CEA IgG in cervical cancer were more pronounced than the increases of the other markers, and the level of anti-CA19-9 IgG in CIN III stage was higher than in normal CIN I, CIN II or cervical cancer. A combination of ELISAs detecting anti-CA15-3, anti-CEA and anti-CA19-9 IgGs was found to reliably discriminate CINs from normal and to strongly differentiate cancer from normal (90.3% of sensitivity and 82.1% of specificity). We suggest that the combination of three ELISA may be useful for detecting cervical lesions., Competing Interests: CONFLICTS OF INTEREST The authors declared no conflicts of interest.

Objective: This prospective randomized controlled pilot study aimed to find whether gelatin-thrombin matrix used as a tissue sealant (FloSeal) can prevent the occurrence of pelvic lymphocele in patients with gynecologic cancer who has undergone pelvic lymphadenectomy., Methods: Each patient, who undergo a laparotomic pelvic lymph node dissection on both sides, was randomly assigned for FloSeal application on 1 side of the pelvis. The other side of the pelvis without any product application being the control side. The amount of lymph drainage at each side of the pelvis was measured for 3 days, and computed tomography scans were obtained 7 days and 6 months after surgery for detection of pelvic lymphocele., Results: Among 37 cases, the median amount of lymph drainage was significantly decreased in the hemi-pelvis treated with FloSeal compared to the control hemi-pelvis (p=0.025). The occurrence of lymphocele was considerably reduced in treated hemi-pelvis (8/37, 21.6%) compared with control hemi-pelvis (12/37, 32.4%) after 7 post-operative days (p=0.219), and more decreased in the treated hemi-pelvis (5/37, 13.5%) compared with control hemi-pelvis (9/37, 24.3%) after postoperative 6 months (p=0.344)., Conclusion: The application of FloSeal as a tissue sealant in lymph nodes resected tissues can reduce the incidence of pelvic lymphocele in gynecologic cancer patients. A large randomized controlled study could confirm these preliminary results., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Human papillomavirus (HPV) E6 protein is an oncoprotein with a pivotal role in cervical carcinogenesis. Expression and purification of HPV E6 from Escherichia coli (E. coli) has been difficult because of its strong hydrophobicity even when expressed as a fusion protein with glutathione S-transferase (GST). There has been no protocol suggested for purifying GST-tagged HPV E6 protein with high purity so far. Herein, we provide efficient protocol for purifying GST-HPV16 E6 protein for the first time. In the current study, the GST-tagged protein was expressed in E. coli and a purification method was designed using cation-exchange chromatography followed by GST-affinity chromatography. Using physiological pH buffer during cell lysis and first cation-exchange chromatography significantly reduced yield of full-length GST-HPV16 E6 protein. It was found that using an alkaline buffer during cation-exchange chromatography was needed to obtain full length GST-HPV16 E6 protein. GST-HPV16 E6 protein recovered from the purification using alkaline condition retained its inherent p53-binding ability. Moreover, we were able to detect anti-HPV16 E6 antibodies with high sensitivity in sera from patients with cervical cancer using the GST-HPV16 E6 protein. It was found that the GST-HPV16 E6 protein could be used as a coating agent to enhance the sensitivity of detection of serum anti-HPV16 E6 antibodies when treated with ethylene glycol-bis (β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). These results indicate that the two-step chromatographic purification allows obtaining high purity of GST-HPV16 E6 protein and the GST-HPV16 E6 is suitable to be used as an antigen of serology assay., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Autophagy is the process of lysosome-mediated degradation and recycling that functions as an adaptive survival mechanism during anti-cancer therapy. Aberrant activation of the phosphoinositide-3-kinase (PI3K) pathway frequently occurs in solid tumors, including cervical cancer. However, single-agent PI3K inhibitors show modest anti-tumor efficacy in clinics. To see whether autophagy inhibition improves the efficacy of PI3K inhibitor in PIK3CA-mutant cancer cells, cells were treated with BKM120, a pan-PI3K inhibitor, and the autophagy inhibitor hydroxychloroquine (HCQ). Autophagy inhibition augmented the efficacy of BKM120 depending on PIK3CA-mutant cancer cell type. BKM120 treatment led to the nuclear accumulation of forkhead box O3 (FOXO3a) in Caski and T47D cells, which showed a synergistic effect of BKM120 and HCQ and the strong induction of autophagy. However, most FOXO3a remained in cytoplasm in C33A and ME180 cells, which did not exhibit synergy. These data suggest that BKM120-induced nuclear translocation of FOXO3a might elicit autophagy and be a critical factor determining the synergistic activity of BKM120 and HCQ in PIK3CA-mutant cancer cells. The release of FOXO3a from 14-3-3 by BV02 or 14-3-3 knockdown induced autophagy by BKM120 in C33A cells and sensitized the cells to the combined BKM120 and HCQ treatment, suggesting that cytoplasmic retention of FOXO3a by 14-3-3 even in the presence of BKM120 inhibit autophagy induction and synergistic effect of BKM120 and HCQ combination. Taken together, our study shows that subcellular localization of FOXO3a might be a potential biomarker for predicting response to the combination treatment with PI3K and autophagy inhibitors in PIK3CA-mutant cervical cancer patients.

Purpose: The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma., Materials and Methods: The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0-50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week., Results: The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture., Conclusion: Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: The Pap test has been used for over 50 years for primary screening of cervical cancer. There has been no study of glycosylation changes in Pap test samples despite considerable potential of the glycosylation changes as biomarkers for detecting cancerous lesions. In this study, we developed a 96-well platform for enzyme-linked lectin assays (ELLAs) to evaluate glycosylation levels in cervical cells., Methods: A total of 117 samples of exfoliated cervical cells (ECCs) from 37 individuals with normal cytology, 20 with cervical intraepithelial neoplasia (CIN) 1, 19 with CIN 2, 26 with CIN 3 and 15 with cervical cancer were analyzed by ELLAs. The wells of 96-well plates were coated with lysates of the cervical cells, and sialylation and fucosylation levels were compared between the groups., Results: Sialylation levels increased and fucosylation levels decreased with increasing grade of cervical dysplasia. ELLAs for sialylation [ELLA-Sambucus nigra (SNAs)] and fucosylation [ELLA-Aleuria aurantia lectin (AAL)] discriminated not only CIN 2 and worse (CIN 2+: CIN 2, CIN 3, and cancer) from normal cytology but also CIN 3 and worse (CIN 3+: CIN3 and cancer) from normal cytology. ELLA-SNAs and ELLA-AALs distinguished cancer from normal cytology with a high true-positive rate (TPR) (ELLA-SNAs: 87%; ELLA-AALs: 87%) and low false-positive rate (FPR) (ELLA-SNAs: 19%; ELLA-AALs: 11%)., Conclusions: The sialylation and fucosylation levels of ECCs as measured by ELLAs have great potential as biomarkers for primary screening of cervical cancer.

Background: A low-mass-ion discriminant equation (LOME) was constructed to investigate whether systematic low-mass-ion (LMI) profiling could be applied to ovarian cancer (OVC) screening., Results: Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry was performed to obtain mass spectral data on metabolites detected as LMIs up to a mass-to-charge ratio ( m/z ) of 2500 for 1184 serum samples collected from healthy individuals and patients with OVC, other types of cancer, or several types of benign tumor. Principal component analysis-based discriminant analysis and two search algorithms were employed to identify discriminative low-mass ions for distinguishing OVC from non-OVC cases. OVC LOME with 13 discriminative LMIs produced excellent classification results in a validation set (sensitivity, 93.10 %; specificity, 100.0 %). Among 13 LMIs showing differential mass intensities in OVC, 3 metabolic compounds were identified and semi-quantitated. The relative amount of LPC 16:0 was somewhat decreased in OVC, but not significantly so. In contrast, D,L - glutamine and fibrinogen alpha chain fragment were significantly increased in OVC compared to the control group ( p  = 0.001 and 0.002, respectively)., Conclusion: The present study suggested that OVC LOME might be a useful non-invasive tool with high sensitivity and specificity for OVC screening. The LOME approach could enable screening for multiple diseases, including various types of cancer, based on a single blood sample. Furthermore, the serum levels of three metabolic compounds- D,L - glutamine, LPC 16:0 and fibrinogen alpha chain fragment-might facilitate screening for OVC.

Objective: Decreased adiponectin and increased leptin plasma concentrations are believed to be associated with the occurrence and progression of cancers such as endometrial cancer and breast cancer. The aim of this study was to explore the association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer., Methods: For patients with ovarian cancer and the control group, adiponectin and leptin levels were measured; anthropometric data were obtained during a chart review. Statistical comparisons between groups were analyzed using the Student's t-test; correlations were confirmed using the Pearson correlation., Results: The mean adiponectin and leptin concentrations in patients with ovarian cancer were lower than those of the control group (8.25 vs. 11.44 µg/mL, respectively; P=0.026) (7.09 vs. 15.4 ng/mL, respectively; P=0.001). However, there was no significant difference in adiponectin and leptin levels between early-stage (I/II) and advanced-stage (III/IV) disease (P=0.078)., Conclusion: Compared with other gynecological cancers, the level of adiponectin and leptin were decreased in ovarian cancer that may have some diagnostic value; additional study to elucidate the function of these two hormones in the development of ovarian carcinogenesis is necessitated.

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

Objective: Digital cervicography systems would be expected to reduce the costs of film cervicography, and provide the opportunity for "telemedicine-based" screening. We aimed to develop web-based digital cervicography system, and validate it compared with conventional film cervicography., Methods: A hundred cases from five centers were prospectively included, and cervical images (analogue, digitalized by scanning analogue, and digital) were taken separately using both analogue (Cerviscope) and digital camera (Dr. Cervicam) in each patient. Nine specialists evaluated the three kinds of images of each case with time interval between evaluations of each image. To validate novel digitalized system, we analyzed intra-observer variance among evaluation results of three kinds of images., Results: Sixty-three cases were finally analyzed after excluding technically defective cases that cannot be evaluable on analogue images. The generalized kappa for analogue versus digital image was 0.83, for analogue versus scanned image 0.72, and for digital versus scanned image was 0.71; all were in excellent consensus., Conclusion: Digitalized cervicography system can be substituted for the film cervicography very reliably, and can be used as a promising telemedicine tool for cervical cancer screening.

Ovarian cancer is recognized with high mortality due to asymptomatic nature of the disease and difficulties in diagnosing early stage of the cancer. The present study evaluates the use of differential scanning calorimetry (DSC) in differentiating the severity of ovarian cancer from healthy women. 47 diseased women were subdivided into four stages with respect to clinical relevance and severity. Stages I-II were regarded as early stages and stages III-IV were regarded as advanced stages. The two average transition temperatures (T m ) increased with disease severity from 64.84 and 70.32 °C (healthy) to 68.46 and 75.24 °C (stage IV), respectively. T m were increased depending on clinical groups. In addition, the change in heat capacity was also dependent on the disease severity. To further support and investigate the nature of the proposed interactions, matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis is employed. The results suggest the differences in peptide expression between early and advanced stage of ovarian cancer, affected abundant proteins in plasma. The combined DSC and MS approach was supportive in identifying a unique signature of ovarian cancer stages, and demonstrates the potential of DSC as a complementary diagnostic tool in the evaluation of early stage ovarian cancer.

A new slim-type electro-floating display system based on the polarization-controlled optical path is proposed. In the proposed system, the optical path between the input plane and Fresnel lens can be made recursive by repetitive transmission and reflection of the input beam by employing a new polarization-based optical path controller (P-OPC), which is composed of two quaterwave plates, a half mirror and a reflective polarizer. Based on this P-OPC, the absolute optical path between the input plane and Fresnel lens, virtually representing the physical depth of the display system, can be reduced down to one third of its original path, which results in the same rate of decrease in the volume size of the display system. The operational principle of the proposed system is analyzed with the Jones matrix. In addition, to confirm the feasibility of the proposed system, experiments with test prototypes are carried out, and the results are comparatively discussed with those of the conventional system.

In the present study, the correlation between the antibody response against human endogenous retrovirus K (HERV-K) envelope and human age was investigated. Antibody levels were compared in groups in their 20s (n = 25), 30s (n = 39), 40s (n = 68), 50s (n = 32), and 60s and over (n = 25), which included healthy individuals and breast cancer and/or cervical cancer patients. It appeared that both IgM and IgG responses against the HERV-K envelope fell with increasing age. There were no differences in anti-HERV-K envelope antibody levels between healthy individuals and cancer patients. Therefore, our results indicated that the anti-HERV-K antibody levels cannot be considered as cancer-specific marker. Also, IgG1 appeared to be the predominant subtype in the reduction of the IgG response by age. Receiver operating characteristic curves of anti-HERV-K envelope IgM levels indicated that the groups of people in their 20s or 30s could be distinguished from those in their 40s, 50s or 60s and over with satisfactory sensitivity and specificity. These findings indicate that the serum antibody level of HERV-K envelope is a critical parameter reflecting person's age.

In the present study, we developed serological strategies using immunoglobulin fractions obtained by protein A chromatography to screen for cervical cancer and cervical intraepithelial neoplasia I (CIN I). The reactivities of the immunoglobulins purified from sera of women with normal cytology, CIN I and cervical cancer were compared in enzyme-linked immunosorbent assays (ELISA) and enzyme-linked lectin assays (ELLAs). To capture the immunoglobulins, ELISAs and ELLAs were performed in protein A immobilized microplates. The reactivity of immunoglobulin in ELISA was in the increasing order normal cytology, CIN I and cervical cancer, while that in ELLAs for detecting fucosylation was in the decreasing order normal cytology, CIN I and cervical cancer. It was confirmed that women with CIN I were distinguishable from women with normal cytology or women with cervical cancer in the ELISA or the ELLA for detecting fucosylation with considerable sensitivity and specificity. Women with cervical cancer were also distinguishable from women with normal cytology with high sensitivity (ELISA: 97%, ELLA: 87%) and specificity (ELISA: 69%, ELLA: 72%). Moreover, the logistic regression model of the ELISA and the ELLA discriminated cervical cancer from normal cytology with 93% sensitivity and 93% specificity. These results indicate that the ELISAs and the ELLAs have great potential as strategies for primary screening of cervical cancer and CIN. It is expected that the ELISA and the ELLA can provide new insights to understand systemic changes of serum immunoglobulins during cervical cancer progression., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs.

Purpose: To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute., Materials and Methods: Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox regression was applied to analyze prognostic factors., Results: The 5-year disease-free survival was 79% and 5-year OS was 91%. In univariate analysis, positive or close PRM, LN metastasis, direct extension of parametrium, lymphovascular invasion, histology of adenocarcinoma, and chemotherapy were related with more DM and poor OS. In multivariate analysis, PRM and LN metastasis remained independent prognostic factors for OS., Conclusion: PORT after radical hysterectomy in uterine cervical cancer showed excellent OS in this study. Positive or close PRM after radical hysterectomy in uterine cervical cancer correlates with poor prognosis even with CCRT. Therefore, additional treatments to improve local control such as radiation boosting need to be considered.

Mycobacterium (M.) bovis, a bacterium in the M. tuberculosis complex, is a causative agent of bovine tuberculosis, a contagious disease of animals. Mycobacterial culture is the gold standard for diagnosing bovine tuberculosis, but this technique is laborious and time-consuming. In the present study, performance of the SD Bioline TB Ag MPT4 Rapid test, an immunochromatographic assay, was evaluated using reference bacterial strains and M. bovis field isolates collected from animals. The SD MPT64 Rapid test produced positive results for 95.5% (63/66) of the M. bovis isolates from cattle and 97.9% (46/47) of the isolates from deer. Additionally, the test had a sensitivity of 96.5% (95% CI, 91.2-99.0), specificity of 100% (95% CI, 96.7-100.0), positive predictive value of 100% (95% CI, 96.7-100.0), and negative predictive value of 92.9% (95% CI, 82.7-98.0) for M. bovis isolates. In conclusion, the SD MPT64 Rapid test is simple to use and may be useful for quickly confirming the presence of M. bovis in animals.

Mature cystic teratoma is a common benign neoplasm of the ovary. Complications occur in approximately 20% of cases. Clinical manifestations, laboratory findings, and imaging studies can assist in making a diagnosis of ovarian torsion of mature cystic teratoma. Furthermore, serum tumor markers may be helpful for diagnosing mature cystic teratoma and its torsion and, thus, can lead to early surgical intervention. A 56-year-old woman presented with a huge pelvic mass and pelvic pain. Serum CA19-9, CA125, and carcinoembryonic antigen levels were abnormally elevated at >700 U/ml, 282.5 U/ml, and 3.94 U/ml, respectively. The tumor was surrounded by extensive adhesions and showed inflammatory changes. The serum levels of these markers returned to normal levels after surgery.

As a new approach for rapid generation of holographic videos, a so-called compressed novel-look-up-table(C-NLUT), which is composed of only two principal fringe patterns (PFPs) of baseline and depth-compensating PFPs (B-PFP, DC-PFP), is proposed. Here, the hologram pattern for a 3-D video frame are generated by calculating the fringe patterns for all depth layers only by using the B-PFP, and then transforming them into those for their depth layers by being multiplied with corresponding DC-PFPs. With this one-step calculation process, the computational speed (CS) of the proposed method can be greatly enhanced. Experimental results show that the CS of the proposed method has been improved by 30.2% on the average compared to that of the conventional method. Furthermore, the average calculation time of a new hybrid MC/C-NLUT method, in which both of motion-compensation (MC) and one-step calculation schemes are employed, has been reduced by 99.7%, 65.4%, 60.2% and 30.2%, respectively compared to each of the conventional ray-tracing, LUT, NLUT, and MC-NLUT methods. In addition, the memory size of the proposed method has been also reduced by 82 × 10(6)-fold and 128-fold compared to those of the conventional LUT and NLUT methods, respectively.

Ovarian cancer (OVC) is one of the most difficult types of cancer to detect in the early stages of its development. There have been numerous attempts to identify a biomarker for OVC; however, an accurate diagnostic marker has yet to be identified. The present study profiled OVC candidate metabolites from the serum to identify potential diagnostic markers for OVC. Data regarding low-mass ions (LMIs) in the serum were obtained using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight analysis. MALDI-mass spectrometry (MS) analysis of each serum sample was repeated six times in order to reduce the likelihood of experimental errors. The intensity of the LMI mass peaks were normalized using total peak area sums. The normalized intensity of LMI was used in principal component analysis-discriminant analysis to differentiate between 142 patients with OVC and 100 healthy control participants. Liquid chromatography-MS/MS was used to identify the selected LMIs. Extracted ion chromatogram analysis was used to measure the relative quantity of candidate metabolites from the LMI mass peak areas. The concentration of common metabolites in the serum was determined using ELISA. The top 20 LMI mass peaks with a weigh factor over 0.05 were selected to distinguish between the patients with OVC and the controls. Among the LMIs, two with 184.05 and 496.30 m/z were identified as L-homocysteic acid (HCA) and lysophosphatidylcholine (LPC) (16:0), respectively. The relative quantity of LPC (16:0) was found to be decreased in the OVC serum (P=0.05), while the quantity of HCA was observed to be significantly higher in the OVC serum (P<0.001). HCA was not detected in 59 cases out of the 63 control participants; however, the majority of the cases of OVC (16/25) exhibited significantly higher quantities of HCA. When the cutoff was 10 nmol/ml, the sensitivity and specificity of HCA were 64.0 and 96.9%, respectively. The level of LPC (16:0) was significantly correlated with tumor grade (P=0.045). HCA and LPC (16:0) showed correlation with stage and tumor histology, but the limited sample size resulted in a lack of statistical significance. The findings of the present study suggest that HCA may have potential to be a biomarker for OVC. The stratified screening including LPC (16:0) did not significantly increase the power for OVC screening; however, the present study showed that profiling LMIs in serum may be useful for identifying candidate metabolites for OVC screening.

A new three-directional motion compensation-based novel-look-up-table (3DMC-NLUT) based on its shift-invariance and thin-lens properties, is proposed for video hologram generation of three-dimensional (3-D) objects moving with large depth variations in space. The input 3-D video frames are grouped into a set of eight in sequence, where the first and remaining seven frames in each set become the reference frame (RF) and general frames (GFs), respectively. Hence, each 3-D video frame is segmented into a set of depth-sliced object images (DOIs). Then x, y, and z-directional motion vectors are estimated from blocks and DOIs between the RF and each of the GFs, respectively. With these motion vectors, object motions in space are compensated. Then, only the difference images between the 3-directionally motion-compensated RF and each of the GFs are applied to the NLUT for hologram calculation. Experimental results reveal that the average number of calculated object points and the average calculation time of the proposed method have been reduced compared to those of the conventional NLUT, TR-NLUT and MPEG-NLUT by 38.14%, 69.48%, and 67.41% and 35.30%, 66.39%, and 64.46%, respectively.

Numerous derivatives of kojic acid have been synthesised to expand its immunopharmacological uses. Kojic acid is known to have anti-cancer, anti-inflammatory, and anti-melanogenesis effects. We found that (5-hydroxy-4-oxo-4H-pyran-2-yl)methyl 6-hydroxynaphthalene-2-carboxylate (MHNC) strongly suppressed the production of nitric oxide (NO) in an initial screening experiment. In this study, we explored the in vitro and in vivo anti-inflammatory activity of MHNC and its inhibitory mechanisms using lipopolysaccharide (LPS)-treated RAW264.7 cells and HCl/EtOH-treated ICR mice. MHNC dose-dependently diminished the secretion of nitric oxide (NO) and prostaglandin (PG)E2 in LPS-treated RAW264.7 cells. This compound also suppressed the upregulation of mRNA levels for the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 genes. Additionally, the transcriptional activation of these genes was inhibited by MHNC through the suppression of the nuclear translocation of nuclear factor (NF)-κB subunits (p65 and p50), as determined by a luciferase reporter assay. Interestingly, MHNC treatment was found to suppress a series of upstream signalling cascades consisting of IκBα, AKT, PDK1, Src, and Syk for NF-κB activation. Furthermore, a direct enzyme assay with purified Src and Syk and luciferase assays using Src and Syk overexpression indicated that these enzymes were directly inhibited by MHNC. Finally, MHNC (20mg/kg) prevented inflammatory symptoms of the stomach in mice treated with HCl/EtOH by reducing phospho-IκBα levels. Taken together, our data suggest that MHNC may negatively modulate in vitro and in vivo inflammatory responses via the direct suppression of Syk/Src and NF-κB., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: Our study examines thyroid transcription factor 1 (TTF-1) expression in 40 primary adenoid cystic carcinomas (ACCs) arising in various sites and compares TTF-1 expression between primary and metastatic ACCs in 12 cases with distant metastases., Methods: Forty patients with ACCs, including 12 pairs of primary and metastatic ACCs, were evaluated for the immunohistochemical expression of TTF-1 (clone SPT24). In addition, 10 metastatic ACCs to the lung were tested on napsin A and a different TTF-1 antibody (clone 8G7G3) for further evaluation., Results: No primary ACCs showed TTF-1 immunoreactivity (clone SPT24). TTF-1 was positive in five (41.7%) of 12 metastatic ACCs; all five cases were found only in the lung and comprised five (50.0%) of 10 cases. In all positive cases, staining was focal and detected only in the cribriform histologic subtype. Staining patterns using both antibodies (both SPT24 and 8G7G3) were very similar, and TTF-1-positive tumor cells were also positive for napsin A. Extrapulmonary ACCs were all negative for TTF-1 regardless of origination and metastasis., Conclusions: TTF-1- and napsin A-positive ACCs in the lung should not be considered primary ACCs because TTF-1 and napsin A can be expressed in metastatic ACCs of the lung.

A novel directional backlight system based on volume-holographic optical elements (VHOEs) is demonstrated for time-sequential autostereoscopic three-dimensional (3-D) flat-panel displays. Here, VHOEs are employed to control the direction of light for a time-multiplexed display for each of the left and the right view. Those VHOEs are fabricated by recording interference patterns between collimated reference beams and diverging object beams for each of the left and right eyes on the volume holographic recording material. For this, self-developing photopolymer films (Bayfol® HX) were used, since those simplify the manufacturing process of VHOEs substantially. Here, the directional lights are similar to the collimated reference beams that were used to record the VHOEs and create two diffracted beams similar to the object beams used for recording the VHOEs. Then, those diffracted beams read the left and right images alternately shown on the LCD panel and form two converging viewing zones in front of the user's eyes. By this he can perceive the 3-D image. Theoretical predictions and experimental results are presented and the performance of the developed prototype is shown.

A new robust MPEG-based novel look-up table (MPEG-NLUT) is proposed for accelerated computation of video holograms of fast-moving three-dimensional (3-D) objects in space. Here, the input 3-D video frames are sequentially grouped into sets of four, in which the first and remaining three frames in each set become the reference (RF) and general frames (GFs). Then, the frame images are divided into blocks, from which motion vectors are estimated between the RF and each of the GFs, and with these estimated motion vectors, object motions in all blocks are compensated. Subsequently, only the difference images between the motion-compensated RF and each of the GFs are applied to the NLUT for CGH calculation based on its unique property of shift-invariance. Experiments with three types of test 3-D video scenarios confirm that the average number of calculated object points and the average calculation time of the proposed method, have found to be reduced down to 27.34%, 55.46%, 45.70% and 19.88%, 44.98%, 30.72%, respectively compared to those of the conventional NLUT, temporal redundancy-based NLUT (TR-NLUT) and motion compensation-based NLUT (MC-NLUT) methods.

Numerous studies have suggested that increased sialylation and fucosylation levels are signs of cancer progression. The majority of studies have focused on cell surface and bloodstream glycosylation changes associated with cancer progression, while little attention has been paid to changes in the glycosylation of cytosolic proteins. We compared the mannosylation, sialylation and fucosylation levels of cytosolic proteins obtained from human cervical tissues without neoplastic lesions vs. with cancer, using lectin blot and enzyme-linked lectin assay (ELLA) systems. There were no quantitative differences in mannosylation levels between the cytosolic proteins of normal and cancer tissues. However, we found markedly reduced sialylation (P<0.001) and fucosylation (P<0.01) in the proteins of cancer tissues. The ELLA system for detecting sialylation had extremely high sensitivity (91-100%) and specificity (82-100%) in distinguishing normal and cancer tissues. Thus, the changes in the glycosylation of cytosolic proteins during carcinogenesis of the cervix are quite different from previous observations concerning glycoconjugates in the bloodstream or on the cell surface. We suggest that changes in the glycosylation of intracellular proteins may be useful markers of the development of cervical cancer.

Background/aims: The aim of this study was to investigate whether profiling metabolic compounds in human colon cancer cells with induced 5-florouracil resistance enables identification of predictive biomarkers for 5-florouracil resistance., Methodology: 5-florouracil resistant and parental cells were extracted using methanol/chloroform solution, and analyzed by MALDI-TOF. Principal components analysis and discriminant analysis was performed to select low-mass ions with strong discriminating power between 5-florouracil resistant and parental cells. The correlation between the intensities of low-mass ions and intrinsic 5-florouracil resistance in 11 colon cancer cells was analyzed using the Spearman rank coefficient., Results: Eleven low-mass ions had strong discrimi-nating power between 5-florouracil-resistant and parental cells. Of these, the intensity of a low-mass ion with 256.29 m/z was negatively correlated with intrinsic 5-florouracil resistance in 11 colon cancer cells (r = -0.6545, P = 0.0338). By searching the H+ adduct with 0.05 m/z tolerance in the Human Metabolome Database, a low-mass ion of 256.29 m/z was identified as palmitic amide. Interestingly, extracellular treatment with palmitic amide reduced 5-florouracil resistance and invasiveness in 5-florouracil-resistant cells., Conclusions: Palmitic amide showed potential not only as a predictor of 5-florouracil resistance, but also for reduction of 5-florouracil resistance in colon cancer cells.

Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases.

Objective: To compare accuracy of serum human epididymis protein 4 (HE4) levels with cancer antigen 125 (CA-125) levels as biomarkers for ovarian cancer., Methods: The study population included 94 Korean women, including 32 patients with a diagnosis of ovarian cancer and 62 patients with a diagnosis of benign ovarian tumor. All diagnoses were confirmed by histopathological analysis. Serum HE4 levels were assessed using an HE4 enzyme immunoassay, which were performed according to the manufacturer's instructions. Serum CA-125 levels were determined using a Modular analytics E170 module., Results: The median serum CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than those with other benign tumors (CA-125, 394.1 U/mL vs. 22.7 U/mL; HE4, 56.7 pM vs. 18.5 pM; P < 0.05 in both). An additional comparison revealed that the patients with endometriosis had greater median serum CA-125 levels than those with other benign ovarian tumors (32.0 U/mL vs. 17.9 U/mL, P = 0.03). Conversely, the median serum HE4 levels were similar among the two benign ovarian tumor groups, with no statistically significant difference observed (19.0 pM vs. 18.2 pM, P = 0.49). The receiver operating characteristics curve analysis for the benign ovarian tumor and ovarian cancer patients showed that HE4 showed a greater area under the curve with borderline significance when compared with CA-125 in both groups (0.93 vs. 0.85)., Conclusion: Serum HE4 levels may not only allow for the detection of ovarian cancer, but also allow for better differentiation of cases of ovarian cancer versus other benign ovarian tumors compared with serum CA-125.

A novel approach for fast generation of video holograms of three-dimensional (3-D) moving objects using a motion compensation-based novel-look-up-table (MC-N-LUT) method is proposed. Motion compensation has been widely employed in compression of conventional 2-D video data because of its ability to exploit high temporal correlation between successive video frames. Here, this concept of motion-compensation is firstly applied to the N-LUT based on its inherent property of shift-invariance. That is, motion vectors of 3-D moving objects are extracted between the two consecutive video frames, and with them motions of the 3-D objects at each frame are compensated. Then, through this process, 3-D object data to be calculated for its video holograms are massively reduced, which results in a dramatic increase of the computational speed of the proposed method. Experimental results with three kinds of 3-D video scenarios reveal that the average number of calculated object points and the average calculation time for one object point of the proposed method, have found to be reduced down to 86.95%, 86.53% and 34.99%, 32.30%, respectively compared to those of the conventional N-LUT and temporal redundancy-based N-LUT (TR-N-LUT) methods.

The Beijing Mycobacterium tuberculosis family is widely distributed and is the most common M. tuberculosis strain in East Asia. The highly transmissible and predominant Beijing M. tuberculosis strain in Korea, M. tuberculosis K1, was characterized using an aerobic challenge mouse model and a latent tuberculosis model with M. tuberculosis H37Rv as a reference. M. tuberculosis K1 multiplied over ten times more rapidly than M. tuberculosis H37Rv during the early stage of infection and induced high levels of histopathology in the lung. Low levels of T helper cell (Th) Th1 [interferon (IFN)-γ, interleukin (IL)-12p40] and Th2 cytokines (IL-4, IL-10) were induced in the lungs of M. tuberculosis K1-infected mice. In the latent model, mice infected with M. tuberculosis K1 exhibited more frequent relapse from the latent state than did mice infected with M. tuberculosis H37Rv. In conclusion, M. tuberculosis K1, a prevalent Beijing strain in Korea, is expected to spread due to its rapid growth during the early stages of infection, low-level induction of the immune response and high relapse rates from a latent state.

The role of autophagy in tumor development is paradoxical. Although some genetic evidence has indicated that autophagy has as a tumor suppressor function, it also provides some advantages to tumors under metabolic stress conditions. Autophagy is regulated by several autophagy-related gene (ATG) proteins. In mammals, 16 different ATG genes have been identified. To investigate the clinicopathological role of ATG5 in colorectal cancer, we firstly investigated its expression in patients with sporadic colorectal cancer. Expression analysis revealed ATG5 to be strongly down-regulated in colorectal cancer (38/40 patients). Interestingly, immunohistochemical analysis of colorectal cancer tissues indicated that increased ATG5 expression is associated with lymphovascular invasion (p=0.035). The findings in our limited clinical cohort indicate that ATG5 could be a potential prognostic or diagnostic biomarker.

We propose a novel approach to massively reduce the memory of the novel look-up table (N-LUT) for computer-generated holograms by employing one-dimensional (1-D) sub-principle fringe patterns (sub-PFPs). Two-dimensional (2-D) PFPs used in the conventional N-LUT method are decomposed into a pair of 1-D sub-PFPs through a trigonometric relation. Then, these 1-D sub-PFPs are pre-calculated and stored in the proposed method, which results in a remarkable reduction of the memory of the N-LUT. Experimental results reveal that the memory capacity of the LUT, N-LUT and proposed methods have been calculated to be 149.01 TB, 2.29 GB and 1.51 MB, respectively for the 3-D object having image points of 500 × 500 × 256, which means the memory of the proposed method could be reduced by 103 × 10(6) fold and 1.55 × 10(3) fold compared to those of the conventional LUT and N-LUT methods, respectively.

Background: Autophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. Until now, more than 30 different ATG proteins have been identified in yeast, and their mammalian counterparts also have been reported. Although the roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown., Methodology/principal Findings: To investigate the clinicopathological role of ATG10 in colorectal cancer, we analyzed ATG10 expression in colorectal cancer tissues and cell lines. Protein expression analysis showed that ATG10 is highly increased in colorectal cancer (tissue - 18/37 cases, 48%; cell line -8/12 cell lines, 66%). Immunohistochemical analysis with clinicopathological features indicated a strong association of the up-regulation of ATG10 with tumor lymph node metastasis (p = 0.005) and invasion (p<0.001). Moreover, both 5-year disease free survival and overall survival rates of patients bearing tumors that did not express ATG10 were significantly higher than those of patients bearing ATG10-expressing tumors (p = 0.012)., Conclusion/significance: Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis indicating that ATG10 may be a potential prognostic maker in colorectal cancer.

Purpose: Bacillus Calmette-Guérin (BCG) vaccine has widely been used to immunize against tuberculosis, but its protective efficacy is variable in adult pulmonary tuberculosis, while it is not efficiently protective against progressive infection of virulent Mycobacterium tuberculosis strains. In this study, the protective effects of plasmid DNA vaccine constructs encoding IL-12 or IL-18 with the BCG vaccine were evaluated against progressive infection of M. tuberculosis, using mouse aerosol challenge model., Materials and Methods: Plasmid DNA vaccine constructs encoding IL-12 or IL-18 were constructed and mice were immunized with the BCG vaccine or with IL-12 DNA or IL-18 DNA vaccine constructs together with the BCG vaccine., Results: The BCG vaccine induced high level of interferon gamma (IFN-γ) but co-immunization of IL-12 or IL-18 DNA vaccine constructs with the BCG vaccine induced significantly higher level of IFN-γ than a single BCG vaccine. The BCG vaccine was highly protective at early stage of M. tuberculosis infection, but its protective efficacy was reduced at later stage of infection. The co-immunization of IL-12 DNA vaccine constructs with the BCG vaccine was slightly more protective at early stage of infection and was significantly more protective at later stage infection than a single BCG vaccine., Conclusion: Co-immunization of IL-12 DNA vaccine with the BCG vaccine induced more protective immunity and was more effective for protection against progressive infection of M. tuberculosis.

Objective: The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years., Methods: Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout., Results: In this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered., Conclusion: The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.).

This workshop was held on July 31-August 1, 2010 and was organized to promote the academic environment and to enhance the communication among Asian countries prior to the 2nd biennial meeting of Australian Society of Gynaecologic Oncologists (ASGO), which will be held on November 3-5, 2011. We summarized the whole contents presented at the workshop. Regarding cervical cancer screening in Asia, particularly in low resource settings, and an update on human papillomavirus (HPV) vaccination was described for prevention and radical surgery overview, fertility sparing and less radical surgery, nerve sparing radical surgery and primary chemoradiotherapy in locally advanced cervical cancer, were discussed for management. As to surgical techniques, nerve sparing radical hysterectomy, optimal staging in early ovarian cancer, laparoscopic radical hysterectomy, one-port surgery and robotic surgery were introduced. After three topics of endometrial cancer, laparoscopic surgery versus open surgery, role of lymphadenectomy and fertility sparing treatment, there was a special additional time for clinical trials in Asia. Finally, chemotherapy including neo-adjuvant chemotherapy, optimal surgical management, and the basis of targeted therapy in ovarian cancer were presented.

Objective: The goal of this study was to investigate the relationship between plasma levels of insulin-like growth factors-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) and the risk for cervical intraepithelial neoplasia (CIN) and cervical cancer., Methods: Plasma levels of IGF-1 and IGFBP-3 of 44 cervical cancer patients, 82 CIN patients and 40 neoplasm-free patients were investigated. Then the associations of the plasma levels of IGF-1 and IGFBP-3 with cervical neoplasm or its clinicopathologic parameters were analyzed., Results: The mean IGF-1 concentrations were significantly different among the control, CIN, and cervical cancer groups; the levels were higher in the CIN group compared to the controls. According to the quartile category, the plasma IGF-1 level was significantly higher (p=0.0015) in the CIN group than in the controls. The IGFBP-3 level showed no association between the controls and CIN groups (p=0.842). Although the mean IGF-1/IGFBP-3 molar ratio had borderline significance (p=0.08) among the study population, the quartile comparison showed a significantly higher IGF-1/IGFBP-3 molar ratio in the CIN group compared to the control group (p=0.041)., Conclusion: Plasma levels of IGF-1 and the IGF-1/IGFBP-3 molar ratio might be useful for the development early detection of cervical lesions and used as an adjuvant diagnostic tool for cervical neoplasia after more larger scale research.

Objective: Wine has been the focus in the prevention of epithelial ovarian cancer (EOC) development because resveratrol abundant in wine has anti-carcinogenic properties. However, epidemiologic results have been heterogenous in the chemopreventive effect of wine on the development of EOC. Thus, we performed a meta-analysis for comparing EOC risk between wine and never drinkers using previous related studies., Methods: After extensive search of the literature between January 1986 and December 2008, we analyzed 10 studies (3 cohort and 7 case control studies) with 135,871 women, who included 65,578 of wine and 70,293 of never drinkers., Results: In all studies, there was no significant difference in EOC risk between wine and never drinkers (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.92 to 1.38; random effects). When we performed re-analysis according to the study design, 3 cohort and 7 case control studies showed that there were also no significant differences in EOC risk between wine and never drinkers, respectively (OR, 1.44 and 1.04; 95% CI, 0.74 and 2.82 and 0.88 to 1.22; random effects). In sub-analyses using 2 case-control studies, EOC risk was not different between former and never drinkers (OR, 1.12; 95% CI, 0.87 to 1.44; fixed effect), and between current and former drinkers (OR, 0.74; 95% CI, 0.41 to 1.34; random effects)., Conclusion: Although resveratrol, abundantly found in wine, is a promising naturally occurring compound with chemopreventive properties on EOC in preclinical studies, this meta-analysis suggests the epidemiologic evidence shows no association between wine drinking and EOC risk.

Background: The aim of this study was to compare the efficacy, safety and achievement of the target hemoglobin level (Hb >or=10 g/dl) in patients with preoperative anemia due to menorrhagia who received intravenous iron sucrose compared with oral iron protein succinylate for anemia management., Methods: Seventy-six patients with Hb levels <9.0 g/dl who were scheduled to undergo surgical treatment were randomized to receive either intravenous iron sucrose (based on the calculated total iron deficit divided into 2 ampoule infusions intravenously 3 times a week, beginning 3 weeks before surgery) or oral iron (80 mg/day of oral iron protein succinylate daily)., Results: The intravenous iron group had higher increases in Hb (3.0 vs. 0.8 g/dl; p < 0.0001) and ferritin levels (170.1 vs. 4.1 microg/l; p < 0.0001) than the oral iron group. Achieving the target Hb was also higher in the intravenous iron group than in the oral iron group (76.7 vs. 11.5%; p < 0.0001). There were tolerable adverse events in both groups., Conclusion: Preoperative intravenous iron sucrose administration is more effective than oral iron and is as safe as oral iron therapy in the correction of preoperative anemia due to menorrhagia., ((c) 2009 S. Karger AG, Basel.)

For cervical cancer screening, HPV-DNA test is expensive and is not easily available in all clinical situations. Thus, we investigated the role of p16(ink4a) immunostaining as another adjunct test to diagnose cervical neoplasia in equivocal liquid based cytology. Eighty-seven patients were randomly selected for this study (3 patients with normal, 84 patients with abnormal including 24 ASCUS, 30 LSIL, and 30 HSIL). We performed p16(ink4a) immunostaining on ThinPrep slide and on each case from the corresponding cervical biopsy tissues. High-risk HPV-DNA testing was also performed on all the subjects. We found that the immunoreactivity of p16(ink4a) is strongly correlated with the grade of cytologic and histologic diagnoses as well as with Hybrid Capture 2. In comparing the p16(ink4a) immunostaining with the Hybrid Capture 2 for accuracy of the diagnosis of CIN II/III or a higher-grade disease in the case of ASCUS/LSIL on ThinPrep, no significant differences were observed. Our data implies that p16(ink4a) immunocytochemical staining in liquid-based cytology specimens might be used as a good adjunct test to predict cervical histology in equivocal ThinPrep tests.

Background: Cytokine production profiles may reflect the clinical pictures of patients with tuberculosis (TB)., Objective: We examined the relationship between cytokine levels and clinical parameters indicating the state of disease in active pulmonary TB patients., Methods: We measured interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 levels in whole blood after stimulation with culture filtrate protein of Mycobacterium tuberculosis in 33 multi-drug resistant (MDR)-TB and 51 non-MDR-TB patients., Results: No significant difference was found in IFN-gamma production between non-MDR-TB and MDR-TB patients, but there was a marked reduction in TNF-alpha production in MDR-TB patients accompanied by a moderate increase in IL-10 levels. In contrast, the presence of cavity was associated with a significant increase in IFN-gamma, whereas no difference in TNF-alpha between the cavity and non-cavity group was observed. Those who have TB lesions in the left lung showed lower levels of IFN-gamma and TNF-alpha and higher IL-10 levels than the patients with lesions on the right side. IFN-gamma levels were significantly increased in those with moderate or advanced lesions compared with patients with mild lesions. TNF-alpha and IL-10 levels did not change with disease severity. The number of M. tuberculosis bacilli in sputum was closely associated with TNF-alpha levels. The patient group with high value (+++) of sputum culture acid-fast bacilli produced significantly reduced levels of TNF-alpha compared with medium (++) and low (+) values., Conclusion: These findings suggest that IFN-gamma, TNF-alpha or IL-10 production patterns in whole blood are associated with disease progression in active pulmonary TB., (Copyright 2008 S. Karger AG, Basel.)

Aim: To estimate the relationship between matrix metalloproteinase (MMP)-1 promoter -1607 bp polymorphism and the risk of epithelial ovarian cancer (EOC) in Korean women and to clarify the ethnic difference in genotype distribution of this polymorphism., Methods: Single nucleotide polymorphism (SNP) of MMP-1 promoter -1607 region in 133 EOC patients and 332 cancer-free patients were investigated. Then the associations of this polymorphism with EOC or its clinicopathological parameters were analyzed. In addition, genotype distributions of this polymorphism in Korean women were compared with those of other races by extracting data from the previously published literature., Results: We found no relationship between MMP-1 promoter -1607 bp polymorphism and epithelial ovarian cancer in a Korean population. Furthermore, we found ethnicity-dependent differences in genotype distributions and allele frequencies by comparison with previous articles on this topic. We report significant ethnic differences in the genotype distributions and allele frequencies of the MMP-1 promoter -1607 bp polymorphism., Conclusion: Our results indicate that MMP-1-1607 bp polymorphism shows ethnic diversity, and that the hypothesis that this polymorphism is associated with epithelial ovarian cancer is not supported by this study in a Korean population. Moreover, this finding concurs with results obtained in white Americans and Europeans.