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Sesame (Sesamum indicum) is one of the most widely cultivated crops in Asia and Africa. The identification of the geographical origins of sesame seeds is important for the detection of fraudulent samples. This study was conducted to build a prediction model and suggest potential biomarkers for distinguishing the geographical origins of sesame seeds using mycobiome (fungal microbiome) analysis coupled with multivariate statistical analysis. Sesame seeds were collected from 25 cities in Korea, six cities in China, and five sites in other countries (Ethiopia, India, Nigeria, and Pakistan). According to the expression of fungal internal transcribed spacer (ITS) sequences in sesame seeds, 21 fungal genera were identified in sesame seeds from various countries. The optimal partial least squares-discriminant analysis model was established by applying two components with unit variance scaling. Based on seven-fold cross validation, the predictive model had 94.4% (Korea vs. China/other countries), 91.7% (China vs. Korea/other countries), and 88.9% (other countries vs. Korea/China) accuracy in determining the geographical origins of sesame seeds. Alternaria, Aspergillus, and Macrophomina were suggested as the potential fungal genera to differentiate the geographical origins of sesame seeds. This study demonstrated that mycobiome analysis could be used as a complementary method for distinguishing the geographical origins of raw sesame seeds.

Purpose The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC. Materials and methods Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR). Results A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay. Conclusion In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.

High-intensity focused ultrasound (HIFU) is regarded as an effective skin-lifting device; however, literature regarding treatment of the aging neck and décolletage with HIFU is scarce. Our study aimed to evaluate the efficacy of combination with HIFU and low-fluence Q-switched Nd:YAG (LQSNY) laser on the aging neck and décolletage. Nineteen women were assessed. HIFU at two visits and LQSNY laser at six visits were used to irradiate the neck and chest. At week 16, improvements were rated using the Dedo classification, Fabi/Bolton Chest Wrinkle Scale (FBCWS), and Global Aesthetic Improvement Scales (GAIS). Erythema and melanin indices (EMIs) and cervicomental angle were measured. Subject GAIS and satisfaction were evaluated at follow-up visits. At week 16, neck sagging and chest rhytides were improved on Dedo classification and FBCWS, respectively. Pigmentation and rhytides of the neck and chest were rated as improved in 30 % or more of the subjects by physician GAIS and in approximately 80 % of the subjects by subject GAIS. The above differences seemed to be attributable to the initial expectation level and mild severity pertaining to dress custom in Korea. Eighty-four percent of subjects were satisfied with treatment outcomes. EMIs were decreased on the chest. The combination of HIFU and LQSNY is an effective treatment option to mitigate rhytides and pigmentation of the neck and décolletage.

Background The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. Patients and methods Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period. Results Of 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59–1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ. Conclusions Final safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ. Trial registration ClinicalTrials.gov ( NCT02149524 ); EudraCT ( 2013-004172-35 ).

This study was conducted to validate the survival benefit of metastasectomy plus chemotherapy over chemotherapy alone for treatment of Krukenberg tumors from gastric cancer and to identify prognostic factors for survival.Clinical data from 216 patients with Krukenberg tumors from gastric cancer were collected. Patients were divided into two arms according to treatment modality: arm A, metastasectomy plus chemotherapy and arm B, chemotherapy alone.Overall survival (OS) was significantly increased in arm A relative to arm B for patients initially diagnosed with stage IV gastric cancer (18.0 months vs. 8.0 months; p0.001) and those with recurrent Krukenberg tumors (19.0 months vs. 9.0 months; p=0.002), respectively. Metastasectomy (hazard ratio [HR], 0.458; 95% confidence interval [CI], 0.287 to 0.732; p=0.001), signet-ring cell pathology (HR, 1.583; 95% CI, 1.057 to 2.371; p=0.026), and peritoneal carcinomatosis (HR, 3.081; 95% CI, 1.610 to 5.895; p=0.001) were significant prognostic factors for survival.Metastasectomy plus chemotherapy offers superior OS when compared to palliative chemotherapy alone in gastric cancer with Krukenberg tumor. Prolonged survival applies to all patients, regardless of gastric cancer stage. Metastasectomy, signet-ring cell pathology, and peritoneal carcinomatosis were prognostic factors for survival. Future prospective randomized trials are needed to confirm the optimal treatment strategy for Krukenberg tumors from gastric cancer.

PURPOSE The purpose of this study is to retrospectively compare the efficacy and tolerability between three regimens for first-line chemotherapy-gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM)-in patients with advanced pancreatic cancer. MATERIALS AND METHODS There was a total of 127 patients who underwent chemotherapy for pancreatic cancer between January 2007 and November 2011 at our institution. Patients were treated with either GEM (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks), GEM-T (gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks and erlotinib 100 mg daily), or GEM-X (gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks and capecitabine 850 mg/m(2) twice daily for 2 weeks followed by 1 week's rest) as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity were evaluated. RESULTS The patient population was divided into groups depending on their first-line treatment: GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved ORR (21.2% vs. 12.7% and 15.9%), PFS (8.9 vs. 5.2 and 3.9 months; p < 0.001), and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. There were higher incidences of some non-hematologic adverse events with GEM-X and GEM-T compared to GEM, but most were grade 1 or 2. CONCLUSION GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in advanced pancreatic cancers. It is worthy to further investigate which agent has a clinical advantage as a combination drug with gemcitabine in pancreatic cancer and to explore the predictive markers leading to personalize anti-cancer treatment.

Stratifying patients with brain metastasis (BM) from hepatocellular carcinoma (HCC) by prognostic factors can be useful when making treatment decisions. Nevertheless, a diagnosis-specific graded prognostic assessment (GPA) for HCC has not been well established. We retrospectively reviewed the data from 118 HCC patients newly diagnosed with BM at the Yonsei University Health System between 1985 and 2011. After univariate and multivariate analyses of prognostic factors, those shown to significantly affect survival were used to develop a HCC-specific GPA (HCC-GPA) index. The median overall survival after BM in all patients was 6.1 weeks (95% confidence interval 4.8-7.4 weeks). Using the prognostic factors identified via multivariate analysis, we developed a HCC-GPA index, including number of brain metastases (single: 0.5, multiple: 0 points), alpha-feto protein (

580 Background: SB3 is an approved biosimilar of reference trastuzumab (TRZ). At additional 2-year follow-up after completing neoadjuvant and adjuvant treatment, there was a difference in event-free survival (EFS), but no difference in overall survival (OS) between SB3 and TRZ. Upon monitoring quality attributes of TRZ, a marked downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) was observed in TRZ lots with expiry dates from Aug 2018 to Dec 2019. Some of the lots were used in the Phase III study. This is a post-hoc analysis of EFS and OS by ADCC status from a 3-year follow-up to investigate the difference in EFS between SB3 and TRZ. Methods: After completion of neoadjuvant and adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study (NCT02771795). Within the TRZ group, patients exposed to at least one shifted ADCC lot and those never exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS and OS after 3-year follow-up was analyzed by ADCC status in the long-term follow-up set. Results: 367 patients (SB3, N = 186; TRZ, N = 181) were enrolled in the follow-up study. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 40.8 months in SB3 and 40.5 months in TRZ, 3-year EFS rates were 92.5% in SB3, 94.5% in Unexposed, and 82.5% in Exposed and OS rates were 97.0%, 100%, and 90.6%, respectively. Exposed was associated with decreased EFS compared to Unexposed (HR 0.14, 95% CI 0.04-0.51, p= 0.003). There was a trend of decreased OS in Exposed compared to Unexposed, however, there was no significant difference (HR 0.14, 95% CI 0.02-1.15, p= 0.068). Between SB3 and Unexposed, no difference was observed in EFS (HR 1.06, 95% CI 0.33-3.44, p= 0.923), or OS (HR 0.54, 95% CI 0.05-5.44, p= 0.600). Conclusions: Within the TRZ group, Exposed showed significantly lower EFS compared to Unexposed, and a similar trend was observed in OS with no statistical significance. Between SB3 and Unexposed, no significant difference in EFS or OS was observed. Clinical trial information: NCT02771795.

The BRAF mutation has been shown to be associated with aggressive clinicopathologic characteristics of papillary thyroid cancer (PTC). However, several studies that analyzed hundreds of patients have not demonstrated any correlation. The objective of this study was to investigate the relationship of the BRAF mutation with clinicopathologic factors in a large group of homogenous PTC patients.We collected data of PTC patients who received curative resection of the thyroid gland and who had undergone BRAF mutation tests of their thyroid cancer tissue. Minor variant PTCs and mixed-type thyroid cancers were excluded in this analysis. Clinicopathologic characteristics, including age, sex, BRAF mutation, tumor histology, size, extrathyroidal extension, tumor margin, lymph node metastasis, multifocality, stage, and associated thyroid disease, were collected. The relationship of the BRAF mutation with clinicopathologic factors was analyzed in each homogenous histologic PTC.There were 3130 PTC patients who met the criteria, and these patients were divided into three major histologic groups: conventional PTC (n = 2947), diffuse sclerosing variant PTC (n = 98), and follicular variant PTC (n = 85). The BRAF mutation was variably detected in 75.3%, 61%, and 40% of patients, respectively. In conventional PTC cases, the BRAF mutation was significantly associated with large tumor size, extrathyroidal extension, and lymph node metastasis. Coexistent chronic lymphocytic thyroiditis was significantly less prevalent in the BRAF mutant group. Age, sex, and tumor margin status were not significantly correlated with the BRAF status. There was no evidence that any clinicopathologic factors were linked with the BRAF mutation status in diffuse sclerosing and follicular variant PTCs.The BRAF mutation was differentially detected in each histologic subtype of PTC and was strongly correlated with pathologic factors, most strongly with no coexistent chronic lymphocytic thyroiditis, in conventional PTC. The BRAF mutation is suggested to be a poor prognostic marker in conventional PTC, and the BRAF mutational analysis may lead to better management for individual PTC patients.

Small-cell lung cancer (SCLC) is one of the most aggressive and lethal forms of lung cancers. Chemotherapy and radiotherapy would be standard modality for SCLC with median survival being less than 4 months only. Complementary treatment to chemotherapy is desired. Oncothermia will be one of the candidates to this addition. We have made a study of 31 SCLC patients from April 2006 to March 2012. 23 cases were treated with combined chemotherapy and oncothermia, and 8 cases were treated with chemotherapy alone. Three patients from 14 patients (14/31) died in the study period; there were equal numbers in the two arms, including one long survival case of 28 months and one of 26 months, in the combination and chemo-group, respectively .16 patients (16/31) are alive: 4 patients with chemotherapy only, including one long survival case of 28.7 months, and 11 cases with combined therapy including three long survival cases of more than 3 years. We conclude that the combined use of chemotherapy and oncothermia has significantly enhanced the survival rate in comparison with the use of chemotherapy alone (log-rank test: P value < 0.02).

Clinical application of the prognostic gene expression signature has been delayed due to the large number of genes and complexity of prediction algorithms. In the current study we aimed to develop an easy-to-use risk score with a limited number of genes that can robustly predict prognosis of patients with hepatocellular carcinoma (HCC). The risk score was developed using Cox coefficient values of 65 genes in the training set (n = 139) and its robustness was validated in test sets (n = 292). The risk score was a highly significant predictor of overall survival (OS) in the first test cohort (P = 5.6 × 10−5, n = 100) and the second test cohort (P = 5.0 × 10−5, n = 192). In multivariate analysis, the risk score was a significant risk factor among clinical variables examined together (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = 0.001 for OS). Conclusion: The risk score classifier we have developed can identify two clinically distinct HCC subtypes at early and late stages of the disease in a simple and highly reproducible manner across multiple datasets. (HEPATOLOGY 2011)

Purpose The aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third-line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response. Materials and Methods Fifty gastric carcinoma patients who were treated by third-line sequential chemotherapy between November 2004 and July 2010 were enrolled in this study. Their overall survival (OS) and time to progression (TTP) were set up as primary and secondary end points. For the sequence of chemotherapy regimen, two arms were used. Arm A was defined as 5-fluorouracil (5-FU)+cisplatin (FP) or folinic acid, 5-FU and oxaliplati (FOLFOX), followed by folinic acid, 5-FU and irinotecan (FOLFIRI), and paclitaxel or docetaxel plus 5-FU, with or without epirubicin. Arm B was defined as FP or FOLFOX, followed by paclitaxel or docetaxel plus 5-FU, and FOLFIRI. Results The median OS of all patients was 16.0 months (95% confidence interval, 13.6 to 18.3 months), which is longer than historical control of patients who did not receive third-line chemotherapy. The sequence of second and third-line regimen, including irinotecan and taxane, did not present significant difference in OS or TTP after failure of 5-FU with platinum chemotherapy. In survival analysis of patients' clinicopathologic characteristics, poor prognosis was shown in patients with poorly differentiated histologic features, elevated serum carcinoembryonic level, and shorter TTP of first line chemotherapy. Conclusion It is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles. Development of individualized chemotherapy regimens based on gene expression profiles is warranted.

Aims Despite continual efforts to develop prognostic and predictive models of colorectal cancer by using clinicopathological and genetic parameters, a clinical test that can discriminate between patients with good or poor outcome after treatment has not been established. Thus, the authors aim to uncover subtypes of colorectal cancer that have distinct biological characteristics associated with prognosis and identify potential biomarkers that best reflect the biological and clinical characteristics of subtypes. Methods Unsupervised hierarchical clustering analysis was applied to gene expression data from 177 patients with colorectal cancer to determine a prognostic gene expression signature. Validation of the signature was sought in two independent patient groups. The association between the signature and prognosis of patients was assessed by Kaplan–Meier plots, log-rank tests and the Cox model. Results The authors identified a gene signature that was associated with overall survival and disease-free survival in 177 patients and validated in two independent cohorts of 213 patients. In multivariate analysis, the signature was an independent risk factor (HR 3.08; 95% CI 1.33 to 7.14; p=0.008 for overall survival). Subset analysis of patients with AJCC (American Joint Committee on Cancer) stage III cancer revealed that the signature can also identify the patients who have better outcome with adjuvant chemotherapy (CTX). Adjuvant chemotherapy significantly affected disease-free survival in patients in subtype B (3-year rate, 71.2% (CTX) vs 41.9% (no CTX); p=0.004). However, such benefit of adjuvant chemotherapy was not significant for patients in subtype A. Conclusion The gene signature is an independent predictor of response to chemotherapy and clinical outcome in patients with colorectal cancer.

e12631Background: SB3 was approved by the European Commission as a trastuzumab (TRZ) biosimilar. Here, we report safety and survival data with a follow-up of at least 12 treatment-free months after...

Biliary tract carcinoma is often diagnosed at an advanced stage, and there is currently no established palliative standard of care. This phase II study investigated the efficacy and safety of combination chemotherapy of oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) in biliary tract carcinoma. Patients with unresectable or recurrent biliary tract carcinoma were enrolled, including pretreated and chemotherapy-naive patients. Treatment consisted of intravenous oxaliplatin (100 mg/m 2 , day 1) followed by leucovorin (100 mg/m 2 , day 1) and 5-FU (1000 mg/m 2 , days 1 and 2). Treatment was repeated every 3 weeks. The efficacy and safety of the treatment were determined. Twenty-eight patients were evaluable, and a total of 166 cycles were administered (median five cycles). One complete response (3.6%) and five partial responses (17.9%) were noted, with a response rate of 21.5% [95% confidence interval (Cl): 6.2-36.7], according to Response Evaluation Criteria in Solid Tumors criteria. The median time to progression and overall survival was 3.5 months (95% Cl: 2.7-4.3) and 10.0 months (95% Cl: 7.2-12.8), respectively. The 1 -year survival rate was 17.8%. Grade 3/4 neutropenia and thrombocytopenia were recorded in 18 and 4% of the patients, respectively. No treatment-related death was observed. Oxaliplatin in combination with leucovorin and 5-FU should be considered a feasible chemotherapy regimen for patients with recurrent/ metastatic biliary tract carcinoma.

Background: We conducted a phase II study to assess the efficacy and tolerability of docetaxel and epirubicin as salvage chemotherapy in advanced/metastatic gastric cancer patients with documented progression after 5-fluorouracil/platinum-based combination chemotherapy. Methods: Docetaxel 75 mg/m2 and epirubicin 50 mg/m2 were administered on days 1 and 2, respectively, every 3 weeks. Treatment continued until progression of disease or until a life-threatening adverse event occurred. The primary objectives of this study were to evaluate the safety profile and response rate to this treatment regimen. Results: Thirty-four patients were enrolled in the study. Twenty-six patients had locally advanced or metastatic disease at the time of diagnosis, and 8 patients had recurrent disease after surgical resection of the primary tumor. A total of 157 chemotherapy cycles were administered. Seven (21.8%) patients had a partial response and 12 (37.5%) patients had stable disease. The median time to progression and overall survival were 4.1 and 13.4 months, respectively. Grade III/IV hematologic toxicities included neutropenia in 16 patients (47%) and febrile neutropenia in 8 patients (24%). Nonhematologic toxicities were rare. Conclusion: A combination of chemotherapy with docetaxel and epirubicin showed moderate activity as salvage treatment in advanced/metastatic gastric cancer, especially in patients who had responded to prior chemotherapy.

Purpose: This study was aimed at developing and validating a quantitative multigene assay for predicting tumor recurrence after gastric cancer surgery. Experimental Design: Gene expression data were generated from tumor tissues of patients who underwent surgery for gastric cancer (n = 267, training cohort). Genes whose expression was significantly associated with activation of YAP1 (a frequently activated oncogene in gastrointestinal cancer), 5-year recurrence-free survival, and 5-year overall survival were first identified as candidates for prognostic genes (156 genes, P < 0.001). We developed the recurrence risk score (RRS) by using quantitative RT-PCR to identify genes whose expression levels were significantly associated with YAP1 activation and patient survival in the training cohort. Results: We based the RRS assay on 6 genes, IGFBP4, SFRP4, SPOCK1, SULF1, THBS, and GADD45B, whose expression levels were significantly associated with YAP1 activation and prognosis in the training cohort. The RRS assay was further validated in an independent cohort of 317 patients. In multivariate analysis, the RRS was an independent predictor of recurrence [HR, 1.6; 95% confidence interval (CI), 1.02–2.4; P = 0.03]. In patients with stage II disease, the RRS had an HR of 2.9 (95% CI, 1.1–7.9; P = 0.03) and was the only significant independent predictor of recurrence. Conclusions: The RRS assay was a valid predictor of recurrence in the two cohorts of patients with gastric cancer. Independent prospective studies to assess the clinical utility of this assay are warranted. Clin Cancer Res; 22(24); 6228–35. ©2016 AACR.

PURPOSE Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatment for gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreductin 1-α (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer. MATERIALS AND METHODS For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction in 56 independent stage III gastric cancer patients. Immunohistochemical staining was performed to examine the protein expression level of ERO1L in 231 gastric cancer patients. Correlation between gene expression and cancer prognosis was evaluated. RESULTS Patients with high ERO1L expression had poorer survival than those with low expression (p < 0.01). Functional assays demonstrated that ERO1L knockdown inhibited cell proliferation, migration, invasion, and chemoresistance. In addition, involvement of inactivation of Akt and JNK signaling in molecular mechanisms of ERO1L inhibition was demonstrated. CONCLUSION High expression of ERO1L is associated with poor prognosis of patients with gastric cancer. These results indicate that ERO1L expression may be a clinically promising therapeutic target for prevention of gastric cancer.

This paper presents genetic algorithm-based post-outage voltage and reactive power calculations for transmission line and transformer outages. Deficiencies of the traditional sensitivity-based (linear) methods are overcome by formulation of a line outage as nonlinear constrained optimization problem for a bounded network. The proposed optimization problem is later solved for bounded network variables by genetic algorithms. The accuracy of the method is tested on IEEE 14-bus and IEEE 57-bus test systems. Simulation results are compared both with the results of a full power flow study and with the results of the papers presented in the literature. The results have shown that the proposed method improves the accuracy of post-outage voltage and reactive power values with less computational effort.

Aim To compare capecitabine and oxaliplatin (XELOX) with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy. Methods Clinical data from 206 patients who received XELOX or S-1 regimens as adjuvant chemotherapy in stage III gastric cancer were collected. Patients were divided into 2 groups according to regimen; the groups were XELOX (n = 114) and S-1 monotherapy (n = 92). Results 3-year disease-free survival (DFS) was higher in the S-1 group than in the XELOX group (66.6% vs 59.1%; p = 0.636). 3-year overall survival (OS) was 75.6% in the S-1 group and 69.6% in the XELOX group (p = 0.495). But, the difference was not statistically significant. Especially, for patients with stage IIIC disease, 3-year overall survival was 55.2% in the XELOX group and 39.0% in the S-1 group (hazard ratio, HR 0.50, 95% confidence interval, CI 0.23–1.10; p = 0.075). In multivariate analysis, N stage (HR, 5.639; 95% CI, 1.297–24.522; p = 0.021) and cycle completion as planned (HR, 5.734; 95% CI, 3.007–10.936; p

509 Background: SB3, a proposed biosimilar to the originator trastuzumab (TRZ), demonstrated similarity to its originator in terms of biological activities and pharmacokinetic (PK) equivalence. This study compared SB3 to TRZ in terms of efficacy, safety, PK, and immunogenicity in patients treated by neoadjuvant therapy for HER2 positive early breast cancer (NCT02149524). Methods: Phase III, randomized, double blind, multicenter study compared neoadjuvant SB3 or TRZ for 8 cycles concurrently given with chemotherapy (docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide). Then patients underwent surgery followed by 10 cycles of SB3 or TRZ. The primary endpoint was breast pathologic complete response (bpCR) rate. Equivalence was declared if the 90% confidence interval (CI) of the ratio or the 95% CI of the difference of the bpCR rates in the per-protocol set (PPS) were contained within the pre-defined equivalence margins (0.785, 1.546) and (-13%, 13%), respectively. Secondary endpoints were total pathologic complete response (tpCR), overall response rate (ORR), event-free survival, PK, immunogenicity, and safety. Results: 800 patients were included in PPS. The bpCR rates were 51.7% for SB3 and 42.0% for TRZ. The ratio of bpCR rate was 1.259 and its 90% CI was 1.112-1.426, within the pre-defined equivalence margin. The difference of bpCR rate was 10.70% and its 95% CI was 4.13-17.26; the lower margin was contained within, the upper margin was outside the pre-defined equivalence margin. Secondary endpoints were comparable between SB3 vs TRZ: tpCR rate (45.8% vs 35.8%); ORR (96.3% vs 91.2%). Safety was comparable between SB3 vs TRZ during neoadjuvant period: incidence of treatment-emergent adverse events (96.6% vs 95.2%), most commonly neutropenia, alopecia, and nausea; incidence of serious adverse events (10.5% vs 10.7%). PK equivalence was demonstrated and immunogenicity between SB3 vs TRZ was comparable (0.7% vs 0.0%). Conclusions: Equivalence was demonstrated between SB3 and TRZ based on the ratio of bpCR rates. Safety, PK, and immunogenicity were similar. Complete safety and survival data will follow. Clinical trial information: NCT02149524.

Affiliation number 9 for the 11th and last authors is incorrect. The correct affiliation is: Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyunghee University, Seoul, Korea.

Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops. The fungus produces mycotoxins that are harmful to animal and human. In this study, a systematic analysis of 17 phenotypes of the mutants in 657 Fusarium graminearum genes encoding putative transcription factors (TFs) resulted in a database of over 11,000 phenotypes (phenome). This database provides comprehensive insights into how this cereal pathogen of global significance regulates traits important for growth, development, stress response, pathogenesis, and toxin production and how transcriptional regulations of these traits are interconnected. In-depth analysis of TFs involved in sexual development revealed that mutations causing defects in perithecia development frequently affect multiple other phenotypes, and the TFs associated with sexual development tend to be highly conserved in the fungal kingdom. Besides providing many new insights into understanding the function of F. graminearum TFs, this mutant library and phenome will be a valuable resource for characterizing the gene expression network in this fungus and serve as a reference for studying how different fungi have evolved to control various cellular processes at the transcriptional level., Author Summary Large collections of mutant lines allow for identification of gene functions. Here we constructed a mutant library of 657 putative transcription factors (TFs) through homologous recombination in the head blight fungus, Fusarium graminearum, providing a resource for understanding gene regulation in fungus. By screening these mutants in 17 phenotypic categories, we constructed a dataset of over 11,000 phenotypes. This study provides new insight into understanding multiple phenotypes caused by single TF as well as regulation of gene expression at the transcription level in F. graminearum. Furthermore, our TF mutant library will be a valuable resource for fungal studies through the distribution of mutants and easy access to our phenotypic and genetic data.

Purpose: Despite continual efforts to develop a prognostic model of gastric cancer by using clinical and pathologic parameters, a clinical test that can discriminate patients with good outcomes from those with poor outcomes after gastric cancer surgery has not been established. We aim to develop practical biomarker-based risk score that can predict relapse of gastric cancer after surgical treatment. Experimental Design: Microarray technologies were used to generate and analyze gene expression profiling data from 65 gastric cancer patients to identify biomarker genes associated with relapse. The association of expression patterns of identified genes with relapse and overall survival was validated in independent gastric cancer patients. Results: We uncovered two subgroups of gastric cancer that were strongly associated with the prognosis. For the easy translation of our findings into practice, we developed a scoring system based on the expression of six genes that predicted the likelihood of relapse after curative resection. In multivariate analysis, the risk score was an independent predictor of relapse in a cohort of 96 patients. We were able to validate the robustness of the six-gene signature in an additional independent cohort. Conclusions: The risk score derived from the six-gene set successfully prognosticated the relapse of gastric cancer patients after gastrectomy. Clin Cancer Res; 17(7); 1850–7. ©2011 AACR.

Objectives: The aim of this study was to evaluate the outcome of adjuvant therapy on the overall survival (OS) and disease-free survival (DFS) after curative resection (RO) of patients with TNM stage II gallbladder (GB) cancer. Methods: A total of 160 patients who had received curative resection (RO) between January 2000 and December 2009 were retrospectively reviewed. Among 61 stage II GB cancer patients, 43 received adjuvant therapy, while 18 others received surgery alone. The median follow-up period was 27.3 months (range 2.2–98.9 months). Results: OS was not significantly different among the adjuvant therapies (p = 0.180), but DFS was (p = 0.033). The 3-year OS and DFS from surgery alone, adjuvant chemotherapy, adjuvant radiotherapy, and adjuvant concurrent chemo-radiotherapy were 64, 78, 36 and 36%, and 56, 69, 14 and 47%, respectively. Overall, the chemotherapy group had a better prognosis, although there were no significant differences. Conclusions: The data from this study do not provide evidence that adjuvant therapy is an effective treatment option for curative resected GB cancer. A large randomized controlled study is necessary to confirm the efficacy of adjuvant therapy. Newer adjuvant studies should be focused on gemcitabine-based chemotherapy or chemo-radiotherapy with molecular-based target agents.

Introduction:The purpose of this study was to evaluate the efficacy of conservative treatment with progestin and pregnancy outcomes in women with early-stage endometrial cancer.Methods:We retrospectively analyzed the medical records of 35 patients with endometrial adenocarcinoma, who were treated with progestin from January 1996 to December 2006. Women with early-stage grade 1 endometrioid endometrial adenocarcinoma, who wanted to receive conservative treatment or preserve fertility, were included. All women were treated with medroxyprogesterone acetate or megestrol acetate, with regular dilation and curettage performed. Complete remission (CR) was defined as no evidence of endometrial adenocarcinoma or hyperplasia. Partial remission was diagnosed when the patient developed endometrial hyperplasia, and persistent disease was defined as residual endometrial adenocarcinoma by pathologic confirmation.Results:The median age was 31 years (range, 21-43 years), and the median follow-up period was 39 months (range, 5-108 months). Complete remission was achieved in 22 patients (62.9%), partial remission was achieved in 1 patient (2.9%), and 12 patients (34.3%) had persistent disease. The median time to CR was 9 months (range, 2-12 months). Of the 22 patients with CR, 9 (40.9%) had recurrent disease, and the median time to recurrence was 12 months (range, 8-48 months). Ten (83.3%) of the 12 patients with CR who tried to conceive were successful, and 8 of the 10 pregnancies resulted in live births. There were no congenital anomalies in babies associated with progestin treatment.Conclusions:Conservative treatment with progestin can be considered a good therapeutic option in patients with well-differentiated early-stage endometrioid endometrial adenocarcinoma who wish to preserve their uteri or become pregnant.

Background: The aim of this clinical study was to evaluate the efficacy of combination chemotherapy of oxaliplatin, leucovorin and continuous-infusion 5-fluorouracil (5-FU) for advanced gastric cancer. Methods: Patients with previously untreated gastric cancer with measurable disease received oxaliplatin (100 mg/m2, day 1), followed by leucovorin (100 mg/m2, day 1) and 5-FU (2,400 mg/m2, days 1–2), which was repeated every 2 weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Results: Forty-eight patients were enrolled, and 45 were evaluable for response. A total of 320 cycles of chemotherapy were administered (median 6 cycles per patient). One complete response (2.1%) and 19 partial responses (39.6%) were noted, resulting in an ORR of 41.7% (95% confidence interval, CI: 27.7–55.6%) by intent-to-treat analysis. With a median follow-up duration of 22 months, the median PFS was 5.3 (95% CI: 2.8–7.8) months and the median OS was 13.6 (95% CI: 9.3–17.9) months. There was 1 treatment-related death, and the most common grade 3/4 toxicity was neutropenia (36.1%). Three patients discontinued treatment because of serum creatinine elevation. Conclusion: This study reaffirms the efficacy of oxaliplatin in advanced gastric cancer, but its dose of 100 mg/m2 remains to be reconsidered in Korean patients.

577 Background: Targeted therapy has shown remarkable treatment efficacy on the outcomes of patients with advanced renal cell carcinoma. However, this advance for treatment outcomes with targeted agents has been limited to patents with clear cell histology. The optimal treatment strategy for metastatic non-clear cell renal cell carcinoma (nccRCC) remains uncertained. Recently, several vascular endothelial growth factor inhibitors have shown efficacies for nccRCC. Thus, we designed a single-arm, open label phase II study to determine the efficacy and toxicity of pazopanib in patients with nccRCC. Methods: Patients with metastatic nccRCC except for collecting duct or sarcomatoid type received 800mg/day of pazopanib daily until progression of the disease or intolerable toxicity was observed. The primary objectives were progression free survival (PFS) and second objectives were overall survival (OS), treatment response and safety profiles. Results: A total of 29 eligible patients were enrolled from September 2012 to August 2014. The median age of the patients was 59 years (range, 30-77 years) and 21 patients were male. The median PFS was 8.3 months (95% CI, 4.0-12.6 months) and median OS was not reached (range, 1.5-34.7 months). Among all 29 patients, five patients (17.2%) are ongoing treatment without disease progression. Disease progression was observed in 16 patients (55.2%) during follow up period. Five patients (17.2%) experienced a treatment-related toxicity of grade 3 or more during the study and they stopped treatment in the end. Eight patients (27%) expired during follow up period but, there were no treatment-related deaths. Conclusions: This prospective phase II study showed that pazopanib demonstrated promising activity and tolerable safety in patients with nccRCC (ClinicalTrials.gov NCT01538238). Clinical trial information: NCT01538238.

Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal neoplasm sharing histopathological features with atypical fibroxanthoma (AFX), but has additional features of deep invasion of the superficial subcutis, tumor necrosis and vascular/perineural invasion. It is not well documented in the literature because of its rarity, and its clinical course has been debated due to the lack of homogenous criteria. We describe here the case of a 91-year-old female with a 6-month history of a solitary, asymptomatic, well-defined, 3.4-cm-sized, reddish, hard, protruding mass on the lateral aspect of the right upper eyelid. On the basis of initial punch biopsy results, storiform cellular infiltrate of pleomorphic spindle and polygonal cells with frequent atypical mitoses, the lesion was identified as AFX. Following the initial biopsy, micrographic surgery was performed and a tumor-free margin was confirmed. Considering the conservation of the periocular function and the advanced age of the patient, we planned secondary intention healing rather than primary suturing. After surgery, skeletal muscle infiltration was found and the diagnosis was revised to PDS by a pathologist based on the currently accepted criteria for PDS. There has been no evidence of recurrence or periocular functional defects during a 2-year follow-up without adjuvant therapy. Although the PDS is highly malignant, complete excision under micrographic surgery can prevent recurrence without adjuvant therapy. Also, the secondary intention healing is an effective method for closure of large defects on the face.

Post outage MW line flows and voltage magnitude calculations are one of the most important steps of power system static security analysis. Most of the methods use linear models for the sake of simplicity. However, linear models may suffer from high errors especially for reactive power flows. This paper presents a new method to minimize the errors resulting from the linear system model implementation. The proposed method uses a bounded nonlinear optimization, which can be considered as the corrector of the linearized feedforward calculations.

This paper presents improved voltage and reactive power distribution factors, calculated by genetic algorithms. Deficiencies of the traditional sensitivity based linear methods are first overcome by constructing a bounded optimization procedure between the reactive power flows and the voltage magnitudes. This optimization problem is later solved by using genetic algorithms. The accuracy of the calculated post-outage voltage magnitudes and reactive power flows was tested on the IEEE 14-bus and IEEE 57-bus test systems.

Kaposi’s sarcoma (KS) is an unusual multifocal neoplastic angioproliferative disorder. We herein report a case of classic KS that occurred in a patient receiving hemodialysis for 7 years. The patient had a history of chronic renal failure due to glomerulonephritis for 20 years. Multiple reddened violaceous patches, plaques, and nodules were found on the right knee. Biopsy revealed positivity for human herpesvirus 8 (KS-associated herpesvirus) consistent with KS. Pazopanib, a multitarget tyrosine kinase inhibitor, is an effective agent for treatment of advanced soft tissue sarcoma. The patient received pazopanib for 6 months investigate its effects on KS. The skin lesions and painful symptoms showed improvement. Further studies are required to determine the mechanism underlying the anticancer action of pazopanib and the pathogenesis of KS. (Korean J Med 2015;89:113-116)

Gastric cancer is the second cause of cancer-related deaths worldwide. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. Molecular markers will be important in predicting patients' outcomes and tailoring personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. We evaluated ERO1L significantly overexpressed in gastric cancer and ERO1L was very highly expressed in hypoxic condition. The other study has identified ERO1L as included in the small group of eight genes predicting poor survival of patients with pulmonary adenocarcinoma. We show that ERO1L is a prognostic marker for overall survival among patients with gastric cancer. To investigate the function of ERO1L gene in gastric cancer cell line (AGS and MKN1), we tested the effect of ERO1L expression on gastric cancer cells. To determine the biologic role of ERO1L in regulating cancer cell proliferation, stable transfection of shRNA and expression vector for ERO1L in gastric cancer cells. Our results showed that shERO1L decrease cell proliferation. Next, we tested whether or not the ERO1L gene is involved in progression to metastatic disease in gastric cancer, especially in tumorigenesis, including migration and invasion. In Functional studies, ERO1L silencing decrease gastric cancer cell migaration and invasion, whereas EROL expression significantly increase cell migration and invasiveness. We examined whether ERO1L plays a role in chemoresistance in gastric cancer cells. After silencing or overexpressing ERO1L, we carried out cell viability assays in gastric cancer cells with a panel of chemotherapy agents used to treat gastric cancer patients: a microtubule stabilizer (paclitaxel) and an antimetabilite (5-FU). Surprisingly, Silencing ERO1L expression led gastric cancer cells to become more sensitive to paclitaxel and 5-FU. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, unequal distribution of expression patterns reflecting activation of ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. Citation Format: So-Young Seol, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho. ERO1L, a novel prognostic marker of gastric cancer patient survival, mediates cancer cell invasion and chemoresistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2014-4718

Aim: Chemokines and their receptors are involved in various processes of tumor cell biology. CC chemokine receptor 4 (CCR4), a receptor for thymus and activation-related chemokine (TARC, CCL17), is overexpressed in solid tumors including gastric cancer (GC), and its ligand, TARC, is considered to be a potent stimulator of GC cell proliferation and migration. Here, we evaluate the clinical significance of elevated serum TARC in GC patients and validate its potential as a biomarker for GC. Methods: Serum levels of TARC, MDC (CCL22), MCP-1 (CCL2), and SCF were measured by chemiluminescent immunoassay, and compared among 4 disease groups; normal, high-risk, early GC (EGC), and advanced GC (AGC) groups (each, n = 25) along the gastric carcinogenic sequences (one-way ANOVA) in training set. Serum levels of TARC and SCF were re-evaluated in following independent validation set (90 normal, 30 high-risk, 50 EGC, 50 AGC) and compared with serum carcinoembryonic antigen (CEA) levels. To evaluate the diagnostic potential of serum TARC for GC, receiver operating characteristic (ROC) curve was generated and logistic regression analysis was performed. Correlations of serum TARC with clinicopathological parameters of GC were evaluated by Spearman's correlation. Results: In training set, serum TARC and SCF were significantly correlated with each other and different between cancer and non-cancer conditions (each, p Conclusions: Serum TARC is a potential serologic biomarker for GC superior to CEA. Disclosure: All authors have declared no conflicts of interest.

Aim: Heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family, is overexpressed in human gastric cancer (GC) and considered to play an important role in carcinogenesis of GC as soluble form. This study evaluated the clinical implication of serum HB-EGF in patients with GC and validated its potential as a biomarker for GC. Methods: Serum HB-EGF level was measured by the commercially available human HB-EGF ELISA Kit and compared among 60 normal/gastritis patients (control group), 30 patients with intestinal metaplasia (IM)/dysplasia (high-risk group), 37 early GC (EGC) patients (EGC group), and 30 advanced GC (AGC) patients (AGC group) along the gastric carcinogenesis through one-way ANOVA test. Correlations of serum HB-EGF with clinicopathological parameters of GC were evaluated by Spearman's correlation. To evaluate the diagnostic potential of serum HB-EGF for GC, receiver operating characteristic (ROC) curve was generated and logistic regression analysis was performed. Results: Serum HB-EGF levels were increased along the GC carcinogenesis (gastritis-dysplasia-EGC-AGC sequence). Serum HB-EGF levels were significantly higher in AGC groups (314.4 ± 127.5) than EGC (165.3 ± 123.2), high-risk (98.7 ± 67.3) and normal control (94.7 ± 83.6) groups (each p Conclusions: Serum HB-EGF exhibited a noticeable diagnostic accuracy to predict GC. Also, serum HB-EGF levels were closely correlated with primary tumor size, depth of invasion, lymph node metastasis, and distant metastasis. Collectively, Serum HB-EGF is a potential serologic biomarker candidate for GC superior to CEA. Disclosure: All authors have declared no conflicts of interest.

4049 Background: Although systemic chemotherapy is the optimal treatment strategy for metastatic stomach cancer, several local treatments have been investigated to improve overall survival (OS) in ...

e15132 Background: Gemcitabine is the standard treatment for advanced pancreatic cancer. Though capecitabine and erlotinib are accepted as combination agent with gemcitabine, those two combination regimens have not been compared directly in clinical trial. This study compared the efficacy and tolerability between gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM) as first-line chemotherapy in patients with advanced pancreatic cancer. Methods: We collected data ofpatients if they met the following criteria: histologically or cytologically confirmed ductal adenocarcinoma of the pancreas; unresectable/metastatic disease; treated with one of GEM, GEM-X, and GEM-T as first-line treatment; measurable or evaluable lesion; age more than 18 years; Eastern Cooperative Oncology Group performance status 0, 1, or 2; and adequate hematologic, hepatic, and renal function before first-line chemotherapy. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity were evaluated. Results: Between January 2007 and November 2011, a total of 127 patients received one of GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved the objective response rate (21.2% vs. 12.7% and 15.9%), progression-free survival (8.9 vs. 5.2 and 3.9 months; p < 0.001) and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. The incidence of adverse events was not significantly different among groups. Conclusions: GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in locally advanced and metastatic pancreatic cancers. It is worthy to further investigate which agent has clinical advantage as combination drug with gemcitabine in pancreatic cancer and to explore predictive markers for each regimen leading to personalize anti-cancer treatment.

BackgroundAlthough several prognostic genomic predictors have been identified from independent studies, it remains unclear whether these predictors are actually concordant with respect to their predictions for individual patients and which predictor performs best. We compared five prognostic genomic predictors, the V7RHS, the ColoGuideEx, the Meta163, the OncoDX, and the MDA114, in terms of predicting disease-free survival in two independent cohorts of patients with colorectal cancer.Study designUsing original classification algorithms, we tested the predictions of five genomic predictors for disease-free survival in two cohorts of patients with colorectal cancer (n = 229 and n = 168) and evaluated concordance of predictors in predicting outcomes for individual patients.ResultsWe found that only two predictors, OncoDX and MDA114, demonstrated robust performance in identifying patients with poor prognosis in 2 independent cohorts. These two predictors also had modest but significant concordance of predicted outcome (r>0.3, PConclusionsFurther validation of developed genomic predictors is necessary. Despite the limited number of genes shared by OncoDX and MDA114, individual-patient outcomes predicted by these two predictors were significantly concordant.

Gastric cancer is the second cause of cancer-related deaths worldwide. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. Molecular markers will be important in predicting patients’ outcomes and tailoring personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. We evaluated ERO1L significantly overexpressed in gastric cancer and ERO1L was very highly expressed in hypoxic condition. The other study has identified ERO1L as included in the small group of eight genes predicting poor survival of patients with pulmonary adenocarcinoma. To investigate the function of ERO1L gene in gastric cancer cell line (AGS, MKN1 and NCI-N87), we tested the effect of shRNA inhibition of ERO1L on gastric cancer cells. To determine the biologic role of ERO1L in regulating cancer cell proliferation, stable transfection of shRNA for ERO1L in gastric cancer cells. Our results showed that shERO1L decrease cell proliferation. Furthermore, Knock down expression by shERO1L have effects on regulating gastric cancer cell apoptosis. Next, we tested whether or not the ERO1L gene is involved in progression to metastatic disease in gastric cancer,especially in late tumorigenesis, including migration and invasion. As a results, Knock down expression for ERO1L significantly decreased the migration and invasiveness of gastric cancer cells. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, unequal distribution of expression patterns reflecting activation of ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. While further work is needed to elucidate the biological contributions of these markers in. in vivo, the results presented here provide a basis for future investigations of the functional and clinical effect of new target genes in gastric cancer. Citation Format: So-Young Seol, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho. Expression of ERO1L gene is poor prognostic factor for gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1147. doi:10.1158/1538-7445.AM2013-1147

Aims This pilot study was designed to compare the survival benefit of gemcitabine plus capecitabine (GEM-X) or gemcitabine plus erlotinib (GEM-T) over gemcitabine alone (GEM) in patients with locally advanced or metastatic pancreatic cancer. Methods Patients with previously untreated locally advanced or metastatic carcinoma of the pancreas were recruited. Patients were assigned to GEM, GEM-T, or GEM-X. The primary end points were the overall survival (OS) and response rate. Results A total of 127 patients were assigned to receive GEM (n = 47), GEM-T (n = 44), and GEM-X (n = 36). GEM-X significantly improved the objective response rate (21.2% vs. 12.7% and 15.9%) and the overall disease control rate (partial response plus stable disease; 72.7% vs. 63.8% and 59.1%) compared to GEM and GEM-T, respectively. Progression-free survival was significantly prolonged in the GEM-X group compared to the GEM and GEM-T groups (median, 8.9 months vs. 5.2 and 3.9 months, respectively; P Conclusions GEM-X is plausible first-line treatment for locally advanced and metastatic pancreatic cancers. GEM-X was superior to GEM and GEM-T accompanying acceptable levels of toxicity, and GEM-T showed similar efficacy to GEM. It is of clinical value to perform a phase III trial to compare gemcitabine plus capecitabine and gemcitabine plus erlotinib in pancreatic cancer patients. Disclosure All authors have declared no conflicts of interest.

Gastric cancer is one of the most common and cancer-related deaths worldwide and accounts for an estimated 800,000 deaths annually. Prognosis depends on the stage of disease. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. To differentiate the malignant potential appropriately, many efforts have been made to select prognostic markers. Molecular markers will be important in predicting patients’ outcomes and personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers which could be used to classify patients according to prognosis and also become new therapeutic targets. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. qRT-PCR and tissue microarray validated TXN overexpression and ERO1L have poor prognosis in gastric cancer. Finally, systems analysis revealed TXN family genes are highly correlated with many oncogene and tumor suppressor functional genes and shown relationship on energy and protein synthesis. Survival analysis based on Hierarchical-clustering of TXN family correlated mRNA expression genes revealed that TXN and TXNIP are significantly influenced the patient survival. We evaluated ERO1L and find out also significantly overexpressed in gastric tumor and suggest TXN family members are actively involved in gastric cancer. In vitro hypoxic experiment ERO1L was very highly expressed in hypoxic condition and this also supports TXN high expressed cancer cells are in hypoxic condition. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, unequal distribution of expression patterns reflecting activation of TXN family and ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. While further work is needed to elucidate the biological contributions of these markers, the results presented here provide a basis for future investigations of the functional and clinical effect of new target genes in gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4536. doi:1538-7445.AM2012-4536

Hafnia alvei is a Gram-negative rod that is rarely isolated from human specimens and is rarely pathogenic. It has been associated with gastroenteritis, pneumonia, urinary tract infection, bacteremia, and nosocomial wound infection, but extra-intestinal H. alvei infection is very rare. We present a case of biliary sepsis caused by H. alvei. A 42-year-old woman was admitted with abdominal pain and jaundice. She was diagnosed with metastatic cholangiocarcinoma and received conservative treatment. Six days later, hyperbilirubinemia and signs of sepsis developed and H. alvei was isolated from both the bile and blood. Despite treatment with antibiotics the organism was sensitive to (it was documented as susceptible to piperacillin/tazobactam and ciprofloxacin in sensitivity tests), the patient’s condition grew worse. The antibiotics were switched to meropenem and the biliary sepsis was resolved. (Korean J Med 2012;83:534-537)

Gastric foregut duplication cyst is a rare congenital anomaly. There have been very few reports of bronchogenic cysts in the abdominal cavity attached to the stomach. We report a case of a 57-year-old Korean man with an adenocarcinoma arising within a bronchogenic cyst of the stomach. Pathologic findings revealed ciliated columnar epithelium lining the cyst and a solid papillary adenocarcinoma involving the subserosa of the stomach and the skeletal part of the diaphragm. Surgical resection is the treatment of choice for foregut cysts of the stomach, and the possibility of malignancy should be considered in patients with gastric duplication cysts. (Korean J Med 2012;82:374-377)

e14500 Background: Although a few histologic and biologic markers in advanced cancers are suggested to predict overall survival, the prognostic marker of stage IV AGC is unknown. While lymphopenia ...

ESR1 is one of the most important oncogenes and therapeutic targets in breast cancer. By applying systems-level re-analysis of publicly available gene expression data, we uncovered potential regulator of ESR1. We demonstrated that orphan nuclear receptor NR2E3 regulates ESR1 via direct binding to the ESR1 promoter with concomitant recruitment of PIAS3 to promoter in breast cancer cells, and is essential for physiological cellular activity of ESR1 in estrogen receptor (ER)-positive breast cancer cells. Moreover, expression of NR2E3 was significantly associated with recurrence-free survival and favorable response to tamoxifen treatment in women with ER-positive breast cancer. Our results provide mechanistic insight into how ESR1 is regulated by NR2E3 and clinical relevance of NR2E3 in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 356. doi:10.1158/1538-7445.AM2011-356