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MicroRNAs (miRNAs) are a class of non-coding RNAs approximately 21 nt in length which play important roles in regulating gene expression in plants. Although many miRNA studies have focused on a few model plants, miRNAs and their target genes remain largely unknown in hot pepper (Capsicum annuum), one of the most important crops cultivated worldwide. Here, we employed high-throughput sequencing technology to identify miRNAs in pepper extensively from 10 different libraries, including leaf, stem, root, flower, and six developmental stage fruits. Based on a bioinformatics pipeline, we successfully identified 29 and 35 families of conserved and novel miRNAs, respectively. Northern blot analysis was used to validate further the expression of representative miRNAs and to analyze their tissue-specific or developmental stage-specific expression patterns. Moreover, we computationally predicted miRNA targets, many of which were experimentally confirmed using 5' rapid amplification of cDNA ends analysis. One of the validated novel targets of miR-396 was a domain rearranged methyltransferase, the major de novo methylation enzyme, involved in RNA-directed DNA methylation in plants. This work provides the first reliable draft of the pepper miRNA transcriptome. It offers an expanded picture of pepper miRNAs in relation to other plants, providing a basis for understanding the functional roles of miRNAs in pepper.

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.

Acyl-homoserine lactone–mediated quorum sensing (QS) regulates diverse activities in many species of Proteobacteria . QS-controlled genes commonly code for production of secreted or excreted public goods. The acyl-homoserine lactones are synthesized by members of the LuxI signal synthase family and are detected by cognate members of the LuxR family of transcriptional regulators. QS affords a means of population density-dependent gene regulation. Control of public goods via QS provides a fitness benefit. Another potential role for QS is to anticipate overcrowding. As population density increases and stationary phase approaches, QS might induce functions important for existence in stationary phase. Here we provide evidence that in three related species of the genus Burkholderia QS allows individuals to anticipate and survive stationary-phase stress. Survival requires QS-dependent activation of cellular enzymes required for production of excreted oxalate, which serves to counteract ammonia-mediated alkaline toxicity during stationary phase. Our findings provide an example of QS serving as a means to anticipate stationary phase or life at the carrying capacity of a population by activating the expression of cytoplasmic enzymes, altering cellular metabolism, and producing a shared resource or public good, oxalate.

AIM: To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target. METHODS: All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment. Clinical and pathological information were obtained from the medical records. Gene expression microarray data from 60 cancer and 19 non-cancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA. Tissue microarrays were constructed from 368 gastric cancer patients. Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity. Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated. RESULTS: PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients (log transformed expression level: 7.6 ± 0.65 vs 6.3 ± 0.51, P < 0.001). Moreover, differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers (log transformed expression level: 7.8 ± 0.70 vs 6.7 ± 0.71, P < 0.001). PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368 (39.1%) human gastric cancer cases. PKM2 expression was not related with stage (P = 0.811), but strongly correlated with gastric cancer differentiation (P < 0.001). Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones. Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells; in contrast, signet-ring cell cancers showed only 17.7% PKM2-positive cells. Importantly, PKM2 expression was correlated with shorter overall survival (P < 0.05) independent of stage only in signet-ring cell cancers. CONCLUSION: PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas. Its function and potential as a prognostic marker should be further verified in gastric cancer.

Pantoea ananatis is the causative agent of sheath and grain rot in rice. Here, we present the complete genome sequence of P. ananatis strain PA13, originally isolated from a diseased rice grain.

Background Roses (Rosa sp.), which belong to the family Rosaceae, are the most economically important ornamental plants—making up 30% of the floriculture market. However, given high demand for roses, rose breeding programs are limited in molecular resources which can greatly enhance and speed breeding efforts. A better understanding of important genes that contribute to important floral development and desired phenotypes will lead to improved rose cultivars. For this study, we analyzed rose miRNAs and the rose flower transcriptome in order to generate a database to expound upon current knowledge regarding regulation of important floral characteristics. A rose genetic database will enable comprehensive analysis of gene expression and regulation via miRNA among different Rosa cultivars. Results We produced more than 0.5 million reads from expressed sequences, totalling more than 110 million bp. From these, we generated 35,657, 31,434, 34,725, and 39,722 flower unigenes from Rosa hybrid: ‘Vital’, ‘Maroussia’, and ‘Sympathy’ and Rosa rugosa Thunb. , respectively. The unigenes were assigned functional annotations, domains, metabolic pathways, Gene Ontology (GO) terms, Plant Ontology (PO) terms, and MIPS Functional Catalogue (FunCat) terms. Rose flower transcripts were compared with genes from whole genome sequences of Rosaceae members (apple, strawberry, and peach) and grape. We also produced approximately 40 million small RNA reads from flower tissue for Rosa, representing 267 unique miRNA tags. Among identified miRNAs, 25 of them were novel and 242 of them were conserved miRNAs. Statistical analyses of miRNA profiles revealed both shared and species-specific miRNAs, which presumably effect flower development and phenotypes. Conclusions In this study, we constructed a Rose miRNA and transcriptome database, and we analyzed the miRNAs and transcriptome generated from the flower tissues of four Rosa cultivars. The database provides a comprehensive genetic resource which can be used to better understand rose flower development and to identify candidate genes for important phenotypes.

We report the complete genome sequence of Burkholderia gladioli BSR3, isolated from a diseased rice sheath in South Korea.

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.

Nanocomposites with multi-walled carbon nanotubes (MWNT) and polystyrene (PS) were synthesized via an in-situ bulk sonochemical polymerization under the application of ultrasonication to open pi-bonds in the MWNT, thus enhancing the PS polymerization. Sonication of vinyl monomers such as styrene leads to radical initiation of polymerization. Various characteristics such as morphology, thermal property of the synthesized PS in the presence of the MWNT in the PS/MWNT composites were examined by SEM, TEM, thermogravimetric analysis, respectively. Their rheological properties were also investigated using a stress-controlled rotational rheometer under small amplitude oscillation and steady transient shear in their melt state.

The bacterium Burkholderia glumae causes rice grain rot by producing toxoflavin, whose expression is regulated by quorum sensing (QS). We report a major deviation from the current paradigm for the regulation of bacterial polar flagellum genes. The N-octanoyl homoserine lactone (C8-HSL)-deficient mutant of B. glumae is aflagellate and has lost the ability to swim and swarm at 37 degrees C. Mutagenesis of the bacterium with the mini-Tn5rescue identified an IclR-type transcriptional regulator, called QsmR, which is important for flagellum formation. TofR, which is a cognate C8-HSL receptor, activated qsmR expression by binding directly to the qsmR promoter region. From the flagellum gene cluster, we identified flhDC homologues that are directly activated by QsmR. FlhDC in turn activates the expression of genes involved in flagellum biosynthesis, motor functions and chemotaxis in B. glumae. Non-motile qsmR, fliA and flhDC mutants produced toxoflavin, but lost pathogenicity for rice. The unexpected discovery of FlhDC in a polarly flagellate bacterium suggests that exceptions to the typical regulatory mechanisms of flagellum genes exist in Gram-negative bacteria. The finding that functional flagella play critical roles in the pathogenicity of B. glumae suggests that either QS or flagellum formation constitutes a good target for the control of rice grain rot.

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)

Summary Burkholderia glumae BGR1 produces a broad-host range phytotoxin, called toxoflavin, which is a key pathogenicity factor in rice grain rot and wilt in many field crops. Our molecular and genetic analyses of toxoflavin-deficient mutants demonstrated that gene clusters for toxoflavin production consist of four transcriptional units. The toxoflavin biosynthesis genes were composed of five genes, toxA to toxE, as Suzuki et al. (2004) reported previously. Genes toxF to toxI, which are responsible for toxoflavin transport, were polycistronic and similar to the genes for resistance-nodulation-division (RND) efflux systems. Using Tn3-gusA reporter fusions, we found that ToxR, a LysR-type regulator, regulates both the toxABCDE and toxFGHI operons in the presence of toxoflavin as a coinducer. In addition, the expression of both operons required a transcriptional activator, ToxJ, whose expression is regulated by quorum sensing. TofI, a LuxI homologue, was responsible for the biosynthesis of both N-hexanoyl homoserine lactone and N-octanoyl homoserine lactone (C8-HSL). C8-HSL and its cognate receptor TofR, a LuxR homologue, activated toxJ expression. This is the first report that quorum sensing is involved in pathogenicity by the regulation of phytotoxin biosynthesis and its transport in plant pathogenic bacteria.

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.

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

Background: Gastric cancer is composed of disease subgroups with heterogeneous clinical and biological behaviors. A previous study identified two subgroups with distinct gene-expression profiles strongly associated with prognosis. To identify molecular biologic differences between these two subgroups, we performed an integrative analysis of mRNA, microRNA, and protein expression. Methods: Array technologies were used to generate microRNA and protein expression profiles of frozen tissue samples from 60 patients with gastric cancer. All patients underwent curative gastric resection in 2005 and distributed from stage I to IV and their clinical characteristics were collected. BRB-ArrayTools were used for microarray data analysis. Data was compared between gastric cancer tissue and normal gastric tissue and also between two different prognostic groups. Aberrantly expressed microRNA and associated mRNA in patients with poor-prognosis gastric cancer were validated by quantitative RT-PCR and tissue microarray, respectively. Results: Four microRNAs were aberrantly expressed in gastric cancer tissue, especially poor prognostic group (P < 0.05). In the poor-prognosis subgroup, miR-196b showed the most significantly high expression patterns and also miR-135b, miR-93. On the contrary, miR-29c* was down-regulated. MiR-196b expression was positively correlated with HOXA10 expression (r = 0.726; P < 0.001), which was significantly increased in poor-prognosis patients (P < 0.001). HOXA10 protein-positive expression was identified in 56 of 368 gastric cancer tissue microarray samples. In reverse-phase protein array, 46/124 proteins were expressed differently (P < 0.05); COX2 (P < 0.001) and cyclin B1 (P = 0.017) were clearly over-expressed in the poor-prognosis group. Conclusion: Integrative analysis of RNA and protein expression profile facilitates interpretation of the molecular biologic heterogeneity of cancer. Co-activation of miR-196b and HOXA10 characterized a poor-prognosis subgroup of patients with gastric cancer. As HOXA10 is involved in the proliferation of hematopoietic stem cells and progenitor cells, the relevance of hematopoietic progenitor cell and gastric cancer development/progression should be further investigated. Citation Format: Jae Yun Lim, Sun Och Yoon, So-Young Seol, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Ju-Seog Lee, Jae Yong Cho. Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype. [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 1961. doi:10.1158/1538-7445.AM2013-1961

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.

Background: PKM2 (M2 isoform of pyruvate kinase) was identified as a driver of aerobic glycolysis, leading to cell growth and tumor development. PKM2 is usually known to overexpress in cancer, however, there are still remaining questions about the function and the potential as anti-cancer treatment target. We investigated the expression status of PKM2 in gastric cancer tissues and evaluated the possibility of biomarker and anticancer target. Methods: Paraffin-embedded tissue microarray blocks of gastric adenocarcinoma tissue specimens were obtained from 363 gastric cancer patients. All patients underwent curative gastric resection from 1999 to 2007 and distributed from stage I to IV and their clinical characteristics were collected. IHC (Immunohistochemical) assay was performed to evaluate PKM2 expression levels. The correlation of PKM2 expression level with gastric cancer prognosis / stage / histology was evaluated. Results: In our previous microarray study using 60 gastric cancer tissues, we identified PKM2 mRNA overexpressed in cancer tissue than non-cancer tissue (P 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 4540. doi:1538-7445.AM2012-4540

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

AIM: To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence. METHODS: TXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real-time reverse transcription polymerase chain reaction in 68 independent stage III gastric cancer patients. The correlation between gene expression and cancer prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression patterns of each protein. RESULTS: TXN was a prognosis-related gene (P = 0.009), whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expression microarray data. In the 68 stage III patients, the expression levels of both TXN and TXNIP had a statistically significant effect on recurrence-free survival (RFS, P = 0.008 and P = 0.036, respectively). The low TXN and high TXNIP expression group exhibited a better prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis (P < 0.001 for RFS and P = 0.001 for overall survival). More than half of the patients in the simultaneously high TXN and low TXNIP expression group experienced a recurrence within 1 year after curative surgery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors as well as with genes related to energy, protein synthesis and autophagy. CONCLUSION: TXN and TXNIP are promising prognostic markers for gastric cancer, and performing personalized adjuvant treatment based on TXN and TXNIP expression levels would be an effective practice in the treatment of gastric cancer.

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)

Background Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. Methodology/Principal Findings Using microarray technology, we generated a gene expression profile of human gastric cancer–specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. Conclusions/Significance We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.

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

Background: Gastric cancer is the second cause of cancer-related deaths worldwide. After curative surgery, relapse occurs in a large number of patients except for early gastric cancer patients. Even though within the same stage, gastric cancer patients present diverse clinical manifestations and prognosis. The clinical diversity of gastric cancer arises from the molecular biological diversity, which is caused by changes in different genes. This study aimed to identify potential biomarkers which could be used to classify patients according to prognosis and also become new therapeutic targets. Procedures: We obtained whole genome expression microarray data of 65 primary gastric adenocarcinoma patients and the results were validated by quantitative reverse transcription polymerase chain reaction experiment of 68 gastric cancer tissues. We uncovered prognostic subgroups of gastric cancer and identified expressions of a limited number of genes are significantly associated with prognosis. Immunohistochemical assay using 328 gastric cancer tissues was performed to validate protein levels of biomarker gene. Results: A gene encoding thioredoxin (TXN) was found to be markedly elevated in many gastric cancer tissues and strongly related to poor prognosis (p=0.009) in univariate analysis. Conversely, thioredoxin interacting protein (TXNIP), TXN inhibitor, was significantly decreased in patients with poor prognosis. Systems analysis revealed TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors and also with energy and protein synthesis. It was validated that TXN and TXNIP expression were significant prognostic biomarker even in the same stage patients. When patients were classified into the three groups by expression level of TXN and TXNIP, TXN low and TXNIP high expression group showed better prognosis than others; recurrence free survival (p Conclusion: TXN and TXNIP are promising prognostic markers for gastric cancer and agents that target TXN or up modulate TXNIP could be used in target therapy for gastric cancer patients who are selected based on TXN and TXNIP gene signatures. 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 2268. doi:10.1158/1538-7445.AM2011-2268

Gene-expression profiling has been applied in specific settings such as to elucidate the mechanisms of biological pathways, to classify subtypes of a disease, and to predict cancer prognosis. Furthermore, the Connectivity Map using gene-expression signature can categorize the biological responses to a large number of diverse small molecule therapeutics. To find new agents targeting gastric cancer, we analyzed global human gastric cancer gene expression profile using the Connectivity Map. From 3360 gastric cancer specific genes, it was revealed that the candidate compounds for targeting gastric cancer were histone deacetylase inhibitors (HDACi) such as vorinostat. We validated the therapeutic efficacy of vorinostat in gastric cancer cell lines. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines, but showed a different pattern in each cell line. Pharmacological or genetic inhibition of autophagy respectively by chloroquine and a siRNA against Beclin 1 increased the therapeutic efficacy of vorinostat, indicating a mechanism of drug resistance. Further transcriptome analysis will make it possible to find a predictive biomarker gene signature for vorinostat and as such can help in the future to better understand the action mechanisms of vorinostat. In conclusion, we showed that systems analysis using Connectivity Map with a human gastric cancer gene signature can be novel approach to find targeting agents for gastric cancer. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C163.

목적：자궁내막암 환자에서 수술 전에 불량한 예후 인자를 미리 알 수 있다면 치료 계획을 세우는 데 많은 도움이 된다. 이 연구의 목적은 자궁내막암 환자에서 수술 전에 시행한 자궁경부 세포 검사 결과와 불량한 예후 인자와의 상관관계를 알아보는 것이다. 연구 방법： 2000년 1월부터 2003년 12월까지 제일병원에서 수술을 시행받은 자궁내막암 환자 중에서 수술 전에 자궁경부 세포 검사를 하였던 111예의 환자를 대상으로 하였다. 모든 환자에서 전자궁적출술 및 양측 부속기절제술과 복강 내세척 세포 검사를 시행하였고, 골반 림프절 절제술은 74예에서, 또 부대동맥 림프절 절제술은 70예에서 시행하였다. 이들 환자의 수술 전에 시행한 자궁경부 세포 검사 결과를 정상, 선세포이상으로 나누어 자궁내막암의 예후인자와의 상관관계를 검토하였다. 통계는 SPSS ver. 12를 이용하여 χ2-test를 시행하였다. 결과：111예 환자의 평균 나이는 49세(24-75세)였고, 50세 미만이 55예(49.5%)이고 50세 이상이 56예(50.5%)였다. 수술전 자궁경부 세포 검사에서 70예(57.7%)는 정상, 22예(22.5%)는 AGUS, 19예(19.8%)는 adenocarcinoma 소견을 보였다. 자궁경부 세포 검사는 조직학적 분화도(p=0.000), 심부 자궁근층 침윤(p=0.000), 림프-혈관 침윤(lymphvascular space invasion)(p=0.003), 자궁경부 침윤(p=0.004), 자궁 부속기 침범(p=0.024), 복강 내 세척 세포 검사(p=0.042)와 통계학적으로 유의한 상관관계를 보였다. 고령(p=0.057), 조직학적 형태(p=0.774), 진행된 수술 병기(p=0.143), 골반 림프절 전이(p=0.139), 대동맥 주변 림프절 침윤(p=0.126)과는 통계적으로 유의하지 않았다. 결론：자궁내막암 환자에서 수술 전 자궁경부 세포 검사상 발견된 자궁경부 선세포이상은 예후 인자 중 조직학적 분화도, 심부 자궁근층 침윤, 림프-혈관 침윤, 자궁경부 침윤, 자궁 부속기 침윤, 복막 세척 세포 검사 양성과 통계학적으로 유의한 상관관계가 있었다. 따라서 자궁경부 세포 검사는 독립적인 예후인자는 아니지만, 자궁내막암 환자의 수술 전 평가 방법으로 중요시되어야 할 것이다.

14093 Background: Biliary tract carcinoma is often diagnosed at advanced stage, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A phase II trial was conducted to study a FOLFOX regimen as first- or second- line therapy in biliary tract carcinoma. Methods: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients were between 18 and 75 years of age and had histologically confirmed, measurable adenocarcinoma. Patients were stratified according to prior chemotherapy(6) and no prior chemotherapy(15). Treatment consisted of intravenous oxaliplatin (100mg/m2) as a 2 hours infusion on day 1 followed by leucovorin 100mg/m2 on day1 and 5-FU 1000∼1200mg/m2 as a 24 hours infusion on day 1,2. Treatment was repeated every 3 weeks for up to 6 cycles. Tumor response, survival and safety were determined Results: A total of 21 patients were evaluable;12 men and 9 women with a median age of 57(range 37–71). Tumor sites were: intrahepatic (n=7) and extrahepatic biliary duct (n=9); gallbladder (n=4); and ampulla (n=1). Total 115 cycles were administered (median 5 cycles, range 2∼12). According to RECIST criteria, partial response 3(14.3%), stable disease 10(47.7%) and disease progression.8(38%). The overall response rate with and without prior chemotherapy were 0%(0/6) and 20%(3/15), respectively. In patients without prior chemotherapy (15), median progression-free-survival and overall survival were 6.6(range, 1.2∼12.8) and 8.7(range, 3.7∼19.3) months. Grade 1–2 neurotoxicity, fatigue, diarrhea, anorexia, nausea were common. Grade 3 neutropenia and thrombocytopenia occurred in 23% and 4.7% of the patients respectively. There was no treatment related death. Conclusions: FOLFOX should be considered an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma. No significant financial relationships to disclose.

Objective：The objective of this study was to compare clinical and pathologic variables and prognosis of FIGO stage IB 1 adenocarcinoma and squamous cell carcinoma of uterine cervix who were treated primarily by surgery. Methods：From May 1982 to October 2000, 2,209 patients with invasive cancer of the uterine cervix were diagnosed and treated at Cheil Hospital. A retrospective review was performed of 533 patients with stage IB1 squamous cell carcinoma (group A) and 84 with adenocarcinoma (group B) of cervix who treated primarily by type 3 hysterectomy and pelvic and paraaortic lymphadenectomy. Results：Age, endometrial extension, lymph node metastasis and postoperative adjuvant therapy were not different between two group. There were more the lymphovascular space invasion in group A (136 patients, 25.5%) than group B (9 patients, 10.7%) (p＜0.0046). 5 year survival were 95.0% vs 93.8% for group A and group B (p=0.75). Using univariate analysis, pelvic node metastasis, paraaortic metastasis, postoperative adjuvant therapy were significant for survival. Multivariate analysis of 5 year survival revealed independent prognostic factor as postoperative adjuvant therapy. Conclusion：Prognosis of FIGO stage IB1 cervical cancer patients who were treated by primarily by type 3 hysterectomy and pelvic and paraaortic lymphadenectomy between adenocarcinoma and squamous cell carcinoma was found to be same.

Small dense LDL (sd-LDL) has recently emerged as an important coronary artery disease (CAD) risk factor. This study was performed to investigate how LDL particle size is related to CAD and acute coronary syndrome (ACS). Blood samples were collected from 504 patients that underwent coronary angiography to evaluate chest pain. The LDL particle size of these samples was measured. The mean LDL particle size was smaller in patients with angiographically proven CAD than in the controls (26.41 ± 0.95 vs 26.73 ± 0.64 nm, p < 0.001), and was negatively correlated with the Framingham risk score (r = -0.121, p = 0.007). Patients with more extensive CAD had smaller LDL particles. LDL particle size was also smaller in patients with acute coronary syndrome as compared to non-ACS patients (26.09 ± 1.42 vs 26.54 ± 0.63 nm, p = 0.011). These results suggest that sd-LDL is independently associated with the incidence and extent of CAD, and can be a risk factor for the development of ACS in the Korean population.

Primary breast lymphoma (PBL) is a rare clinical presentation of localized non-Hodgkin's lymphoma (NHL), and it makes up 0.04~1.1% of all breast tumors and it is 0.38~0.7% of all NHLs. The prognosis and patterns of relapse of PBL are still not clearly defined. The clinical features of PBL are different from those of breast carcinoma and the usual form of lymphoma. These features are a rapidly enlarging breast mass, multiple lesions, the absence of nipple discharge and retraction, and softer axillary lymph nodes as compared to the metastatic lymph nodes from breast carcinoma. B symptoms are unusual in PBL. A 30-year-old pregnant woman was admitted due to dysarthria and right side weakness that she had experienced for 7 days. She had several medical problems: intrauterine pregnancy at 34 weeks, some neurologic deficits and enlargement of both breasts. A biopsy from the breast and a brain magnetic reson- ance image (MRI) revealed diffuse large B cell lymphoma and multiple brain metastases, respectively. After delivery of a healthy, premature infant by Cesarean section, whole brain radiation therapy and combination chemotherapy (rituximab, cyclophosphamide, adriamycin, vincristine and prednisone) were started. She showed good response to therapy. We report here on this unusual case and we review the