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Recurrence risk score and its clinical significance.

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.

Distribution of candidate genes in biological process categories of the Gene Ontology database.

Methods

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.

Supplementary Figures S1-S6; Supplementary Tables S1-S2.

The yeast species Hyphopichia is common in nature and strongly competitive under harsh environmental conditions. Here, we characterized Hyphopichia burtonii KJJ43 and H. pseudoburtonii KJS14, which exhibit strong halotolerance, using genomic and transcriptomic analyses. The genomes of H. burtonii and H. pseudoburtonii comprised eight chromosomes with 85.17% nucleotide identity and significant divergence in synteny. Notably, both Hyphopichia genomes possessed extended gene families of amino acid permeases and ATP-binding cassette (ABC) transporters, whose dynamic expression patterns during osmotic stress were revealed using transcriptome profiling. Intriguingly, we found unique features of the HOG pathway activated by Hog1p even under non-osmotic stress conditions and the upregulation of cytosolic Gpd1p protein during osmotic stress. Associated with hyperfilamentation growth under high osmotic conditions, a set of genes in the FLO family with induced expression in response to NaCl, KCl, and sorbitol supplementation were identified. Moreover, comparative transcriptome analysis reveals the NaCl-specific induction of genes involved in amino acid biosynthesis and metabolism, particularly BAT2. This suggests the potential association between oxoacid reaction involving branched-chain amino acids and osmotolerance. The combined omics analysis of two Hyphopichia species provides insights into the novel mechanisms involved in salt and osmo-stress tolerance exploited by diverse eukaryotic organisms. This article is protected by copyright. All rights reserved.

Fungal sexual reproduction requires complex cellular differentiation processes of hyphal cells. The plant pathogenic fungus Fusarium graminearum produces fruiting bodies called perithecia via sexual reproduction, and perithecia forcibly discharge ascospores into the air for disease initiation and propagation. Lipid metabolism and accumulation are closely related to perithecium formation, yet the molecular mechanisms that regulate these processes are largely unknown. Here, we report that a novel fungal specific bZIP transcription factor, F. graminearum perithecium overproducing 1 (Fpo1), plays a role as a global transcriptional repressor during perithecium production and maturation in F. graminearum. Deletion of FPO1 resulted in reduced vegetative growth, asexual sporulation and virulence and overproduced perithecium, which reached maturity earlier, compared with the wild type. Intriguingly, the hyphae of the fpo1 mutant accumulated excess lipids during perithecium production. Using a combination of molecular biological, transcriptomic and biochemical approaches, we demonstrate that repression of FPO1 after sexual induction leads to reprogramming of carbon metabolism, particularly fatty acid production, which affects sexual reproduction of this fungus. This is the first report of a perithecium-overproducing F. graminearum mutant, and the findings provide comprehensive insight into the role of modulation of carbon metabolism in the sexual reproduction of fungi.

Honeybees are one of the most environmentally important insects, as their pollination of various plant species contributes to the balance among different ecosystems. It has been studied extensively for their unique attribute of forming a caste society. Unlike other insects, honeybees communicate socially by secreting pheromones or by exhibiting specific patterns of motion. In the honeybee industry, the Asian honeybees (Apis cerana) and the Western honeybees (Apis mellifera) are dominant species. However, molecular research on the transcriptomes of A. cerana has not been studied as extensively as those of A. mellifera. Therefore, in this study, caste-specific transcriptional differences were analyzed, which provides a comprehensive analysis of A. cerana. In our dataset, we analyzed gene expression profiles using organs from worker, drone, and queen bees. This gene-expression profile helped us obtain more detailed information related to organ-specific genes, immune response, detoxification mechanisms, venom-specific genes, and ovary development. From our result, we found 4096 transcripts representing different gene-expression pattern in each organ. Our results suggest that caste-specific transcripts of each organ were expressed differently even under natural conditions. These transcriptome-wide analyses provide new insights into A. cerana and that promote honeybee research and conservation.

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.

We isolated Gordonia sp. strain JH63, which has steroid-degrading abilities, from human skin. The complete genome sequence showed that this strain possesses a 5,175,911-bp chromosome and a 162,832-bp plasmid with 4,525 and 159 coding sequences, respectively.

We isolated Gordonia sp. strain JH63, which has steroid-degrading abilities, from human skin. The complete genome sequence showed that this strain possesses a 5,175,911-bp chromosome and a 162,832-bp plasmid with 4,525 and 159 coding sequences, respectively.

Background Nitrogen (N) is a key macronutrient essential for plant growth, and its availability has a strong influence on crop development. The application of synthetic N fertilizers on crops has increased substantially in recent decades; however, the applied N is not fully utilized due to the low N use efficiency of crops. To overcome this limitation, it is important to understand the genome-wide responses and functions of key genes and potential regulatory factors in N metabolism. Results Here, we characterized changes in the rice (Oryza sativa) transcriptome, including genes, newly identified putative long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) and their target mRNAs in response to N starvation using four different transcriptome approaches. Analysis of rice genes involved in N metabolism and/or transport using strand-specific RNA-Seq identified 2588 novel putative lncRNA encoding loci. Analysis of previously published RNA-Seq datasets revealed a group of N starvation-responsive lncRNAs showing differential expression under other abiotic stress conditions. Poly A-primed sequencing (2P-Seq) revealed alternatively polyadenylated isoforms of N starvation-responsive lncRNAs and provided precise 3′ end information on the transcript models of these lncRNAs. Analysis of small RNA-Seq data identified N starvation-responsive miRNAs and down-regulation of miR169 family members, causing de-repression of NF-YA, as confirmed by strand-specific RNA-Seq and qRT-PCR. Moreover, we profiled the N starvation-responsive down-regulation of root-specific miRNA, osa-miR444a.4-3p, and Degradome sequencing confirmed MADS25 as a novel target gene. Conclusions In this study, we used a combination of multiple RNA-Seq analyses to extensively profile the expression of genes, newly identified lncRNAs, and microRNAs in N-starved rice roots and shoots. Data generated in this study provide an in-depth understanding of the regulatory pathways modulated by N starvation-responsive miRNAs. The results of comprehensive, large-scale data analysis provide valuable information on multiple aspects of the rice transcriptome, which may be useful in understanding the responses of rice plants to changes in the N supply status of soil. Electronic supplementary material The online version of this article (10.1186/s12864-018-4897-1) contains supplementary material, which is available to authorized users.

Arsenite-resistance protein 2 (Ars2) is an important nuclear protein involved in various RNA metabolisms in animals and plants, but no Ars2 ortholog has been studied in filamentous fungi. Although it is an essential gene in most model eukaryotes, FgARS2 null mutants were viable in the plant pathogenic fungus Fusarium graminearum. The deletion of FgARS2 resulted in pleiotropic defects in various fungal developmental processes. Fgars2 mutants were irregular in nuclear division, and conidial germination was significantly retarded, causing the fungus to manifest its hypersensitive phenotypes under DNA damage stress. While FgARS2 deletion caused abnormal morphologies of ascospores and defective ascospore discharge, our data revealed that FgARS2 was not closely involved in small-non-coding RNA production in F. graminearum. The dominant nuclear localization of FgArs2-green fluorescent proteins (GFP) and abnormal nuclear division in FgARS2 deletion mutant implicated that FgArs2 functions in the nucleus. Intriguingly, we found that FgArs2 established a robust physical interaction with the cap binding complex (CBC) to form a tertiary complex CBC-Ars2 (CBCA), and disruption of any CBCA complex subunit drastically attenuated the virulence of F. graminearum. The results of the study indicate that Ars2 regulates fungal development, stress response, and pathogenesis via interaction with CBC in F. graminearum and provide a novel insight into understanding of the biological functions of Ars2 in filamentous fungi.

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.

AIM To investigate human epidermal growth factor 2 (HER2) overexpression and validate its prognostic effect in stage II-III gastric cancer. METHODS We reviewed the data of patients who were diagnosed with gastric cancer between March 2008 and October 2013 at the Yonsei University Medical Center. Among these patients, 384 patients who met the inclusion criteria were analyzed retrospectively. RESULTS Thirty-two (8.3%) of the 384 stage II-III gastric cancer patients exhibited HER2 overexpression. The median follow-up duration was 26.0 mo. HER2-negative patients had superior recurrence-free survival (RFS) compared to HER2-positive patients (HR = 0.52, 95%CI: 0.30-0.89; P = 0.015). The median overall survival (OS) was significantly prolonged in the HER2-negative group compared with the HER2-positive group (55.0 mo vs 38.0 mo, HR = 0.43, 95%CI: 0.21-0.88, P = 0.021). OS was also prolonged in HER2-negative patients who received adjuvant chemotherapy compared to HER2-positive patients (55.0 vs 38.0 mo, HR = 0.42, 95%CI: 0.18-1.00, P = 0.051). In patients who did not receive adjuvant chemotherapy, the median RFS was prolonged in the HER2-negative group compared to the HER2-positive group (not reached vs 12.0 mo, HR = 0.17, 95%CI: 0.06-0.49, P = 0.001). In a multivariate analysis, HER2 status (HR = 0.421, 95%CI: 0.206-0.861, P = 0.018) and Eastern Cooperative Oncology Group performance status (HR = 2.002, 95%CI: 1.530-2.618, P < 0.001) were independent predictors of OS. CONCLUSION Our findings showed that HER2-positive patients had inferior OS and RFS. Stage II-III HER2-positive patients might be potential candidates for targeted therapies involving trastuzumab.

The amylolytic yeast Saccharomycopsis fibuligera is the predominant yeast in the starter product, nuruk, which is utilized for rice wine production in South Korea. Latest molecular studies explore a recently developed interspecific hybridization among stains of S. fibuligera with a unique genetic feature. However, the origin of the natural hybridization occurrence is still unclear. Thus, to respectively distinguish parental and hybrid strains, specific primer sets were applied on 141 yeast strains isolated from different nuruk samples fermented in different provinces. Sixty-seven strains were defined accordingly as parental species with genome A while 8 strains were defined as hybrid strains. Unexpectedly, another parental species with genome B could not be found among the strain pools yet. Furthermore, it was observed that hybrid strains are phenotypically different from A genome strains; asci containing tetrad ascospores were observed in A genome strains more frequent than in hybrid strains. Nevertheless, hybrid strains were slightly more thermotolerant than A genome strains. Interestingly, all hybrid strains were located only in Jeju province. Based on these sets of data, we speculated that the unique climate of Jeju province might play an evolutionary role in the interspecific hybridization between A genome strains, as well as the unculturable allopatric B genome strains.

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.

Here, we report the complete genome sequence of Kocuria indica CE7, isolated from human skin. This strain possesses a 2,809-kbp chromosome and a 32-kbp plasmid with 2,507 coding sequences. In particular, the genome contains multiple genes potentially involved in adaptations in pH homeostasis and salt tolerance.

The plant pathogen Burkholderia glumae uses quorum sensing (QS) that allows bacteria to share information and alter gene expression on the basis of cell density. The wild-type strain of B. glumae produces quorum-sensing signals (autoinducers) to detect their community and upregulate QS-dependent genes across the population for performing social and group behaviors. The model organism B. glumae was selected to investigate adaptation, estimate evolutionary parameters, and test diverse evolutionary hypotheses by using experimental evolution. The wild-type B. glumae virulent strain showed genotypic changes during regular subculture due to oxygen limitation. The laboratory-evolved clones failed to produce the signaling molecule of C8-HSL/C6-HSL for activation of the quorum-sensing system. Further, the laboratory-evolved clones failed to produce catalase and oxalate for protecting themselves from the toxic environment at stationary phase and phytotoxins (toxoflavin) for infecting rice grain, respectively. The laboratory-evolved clones were completely sequenced and compared with the wild-type. Sequencing analysis of the evolved clones revealed that mutations in QS-responsible genes (iclR), sensor genes (shk, mcp), and signaling genes (luxR) were responsible for quorum-sensing activity failure. The experimental results and sequencing analysis revealed quorum-sensing process failure in the laboratory-evolved clones. In conclusion, the wild-type B. glumae strain was often exposed to oxidative stress during regular subculture and evolved as an avirulent strain (quorum-sensing mutant) by losing the phenotypic and genotypic characteristics.

Haematobacter massiliensis OT1 was isolated from human skin. This strain can catabolize 4-hydroxybenzoate., Haematobacter massiliensis OT1 was isolated from human skin. This strain can catabolize 4-hydroxybenzoate. Here, we present the first complete whole-genome sequence of this species, which has one chromosome (2,467 kbp) and nine plasmids (total of 1,765 kbp). The analysis of the H. massiliensis OT1 genome indicated a potential for autotrophic growth.

Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response., The prognosis and treatment of gastric cancer is complicated by heterogeneity. Here, the authors reveal two molecular subtypes, the mesenchymal subtype associated with poor survival and chemoresistance, and the epithelial phenotype associated with better survival and sensitivity to chemotherapy.

Epigenetic gene regulation is essential for developmental processes. Eggless (Egg), the Drosophila orthologue of the mammalian histone methyltransferase, SETDB1, is known to be involved in the survival and differentiation of germline stem cells and piRNA cluster transcription during Drosophila oogenesis; however the detailed mechanisms remain to be determined. Here, using high-throughput RNA sequencing, we investigated target genes regulated by Egg in an unbiased manner. We show that Egg plays diverse roles in particular piRNA pathway gene expression, some long non-coding RNA expression, apoptosis-related gene regulation, and Decapentaplegic (Dpp) signaling during Drosophila oogenesis. Furthermore, using genetic and cell biological approaches, we demonstrate that ectopic upregulation of dpp caused by loss of Egg in the germarium can trigger apoptotic cell death through activation of two pro-apoptotic genes, reaper and head involution defective. We propose a model in which Egg regulates germ cell differentiation and apoptosis through canonical and noncanonical Dpp pathways in Drosophila oogenesis.

Paracoccus yeei TT13 was isolated from human skin because of its ability to degrade propylene glycol. Here, we present the whole-genome sequence of this strain; it possesses one 3.58-Mb chromosome and six plasmids. TT13 genome analysis indicated that this bacterium has denitrification potential.

Here, we present the complete whole-genome sequences of three Moraxella osloensis strains with octylphenol polyethoxylate-degrading abilities. These strains were isolated from human skin.

Paracoccus yeei TT13 was isolated from human skin because of its ability to degrade propylene glycol. Here, we present the whole-genome sequence of this strain; it possesses one 3.58-Mb chromosome and six plasmids. TT13 genome analysis indicated that this bacterium has denitrification potential.

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 ).

Sodium is an abundant cation required for protein function and maintenance of cellular osmotic homeostasis. High concentrations of sodium are toxic, and fungi have evolved efficient sodium efflux systems. In this study, we characterized a novel sodium tolerance mechanism in the plant pathogen Fusarium graminearum. Fusarium graminearum sodium sensitive 1 (Fss1) is a nuclear transcription factor with a Zn(II)2 Cys6 fungal-type DNA-binding domain required for sodium tolerance. RNA-seq and genetic studies revealed that a P-type ATPase pump, exitus natru (Latin: exit sodium) 1 (FgEna5), mediates the phenotypic defects of FSS1 mutants. A homologue of PACC (PAC1) was required for FgEna5-dependent sodium and lithium tolerance independent of Fss1. The results of this study revealed that F. graminearum has a distinct and novel pathway for sodium tolerance not present in other model fungi.

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.