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e15606Background: Cancer-associated fibroblasts (CAFs) reportedly regulate tumor progression by inducing tumor-stromal interaction; however, the roles of CAFs in hepatocellular carcinoma (HCC) deve...

347 Background: HBV infection is one of the main reasons for hepatocellular carcinoma(HCC). Patients with advanced HBV-associated HCC have poor prognosis. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. Prediction of 3-month OS and OS survival rate of advanced HCC patients is very important. A new prognostic system called PS-JIS system (proposed Performance Status combined Japan Integrated Staging system, variables and risk classification criteria are listed below) was established in 2015 and now we want to compare this new prognostic system and other three current staging systems in predicting the survival rate of patients with advanced HBV-associated HCC. Methods: From September 2008 to June 2010, 220 patients with advanced HCC who didn’t receive anti-cancer therapy recommended by NCCN guidelines were analyzed. Data were collected to classify patients according to CLIP (Cancer of the Liver Italian Program), PS-JIS, GETCH(Groupe d’étude et de Traitement du Carcinome Hepatocellulaire) and TNM staging system at diagnosis. OS and 3-month OS were the end points used in the analysis. Results: When predicting 3-month survival, ROC analysis show AUC of CLIP, PS-JIS, GETCH and TNM is 0.806, 0.761, 0.654 and 0.643. AUC of CLIP and PS-JIS is similar (P=0.1174), both significantly higher than the other two staging system (P

292 Background: The prognosis of hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE) is far from being identified. The present study aimed to assess role of blood cell counts, routine liver function tests and neutrophil to hemoglobin ratio (NHR) in predicting the progression-free survival (PFS) of these patients. Methods: A total of 243 HCC patients receiving TACE were analyzed retrospectively. Results: Cancer of the Liver Italian Program (CLIP) score system was identified to be the best score system among current 12 staging systems for this patient subgroup according akaike information criterion (AIC) index and linear trend χ2. Then, the novel prognostic value of parameters was determined by integration into CLIP score system. As a result, NHR were confirmed to an independent predictor for PFS of HCC patients receiving TACE (p = 0.001) with the other parameters, including neutrophil and neutrophil-lymphocyte ratio (NLR), failed to reach statistical significance. Moreover, NHR improved the performance of CLIP by adjusted into it, thus improved the discriminatory ability. Furthermore, NHR were defined value ≤ 0.02 as low level and > 0.02 as high level, according to which patients were dichotomized into two groups. HCC patients receiving TACE with low NHR presented higher 1 year disease control rate (DCR) (50.0% vs 39.35%) and 2 year DCR (45.4% vs 27.0%) compared with patients with high NHR level. Besides, NHR level was associated with prognostic factors such as portal vein thrombosis and distant metastasis. Furthermore, in order to determine the mechanism of predictive value of AHR, we tested the proportion of myeloid deprived suppressive cell (MDSC) in peripheral blood mononuclear cells (PBMC) of 43 HCC patients. It was revealed that MDSC was positively correlated with neutrophil (P< 0.05). Since MDSC was cancer promoter, it might be the mechanism of the prognostic value of NHR. Conclusions: The present study firstly identified NHR as an independent prognostic factor in HCC patients receiving TACE. The positive correlation of MDSC and neutrophil might be the latent mechanism.

206 Background: Inflammatory microenvironment plays an important role in the progression of HCC. Peripheral blood LMR, as a novel inflammatory biomarker combining an estimate of host immune homeostasis and tumor microenvironment, has been found to be a predictor for clinical outcomes in various malignancies. There have been no reports regarding the prognostic value of LMR in advanced HCC until now. We want to investigate the prognostic value of LMR in patients with advanced HBV-associated hepatocellular carcinoma. Methods: From September 2008 to June 2010, a total of 174 patients with HBV-associated advanced HCC without fever or signs of infections were analyzed. Clinicopathological parameters, including LMR, were evaluated to identify predictors of overall survival. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. Results: Univariate and multivariate analyses showed that LMR was an independent prognostic factor in overall survival in patients with advanced HCC(P < 0.01 ). The best cutoff point of LMR was 4.52. All patients were dichotomized into either a low LMR group( ≤ 4.52) or a high LMR group( > 4.52). Overall survival(OS) of high LMR group was significantly longer than that of low LMR group(P < 0.01 ). High LMR group patients had significantly higher 6-month OS rate(50% vs 23%, P < 0.01) than that of low LMR group patients. Higher LMR level was significantly correlated with the presence of metastasis and larger tumor size(P < 0.05). Conclusions: LMR is an independent prognostic factor of advanced HCC patients. Higher Baseline LMR levels indicates better prognosis.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor and testing drug efficacy in clinical trials is hazardous. This study was aimed to evaluate different prognostic scoring systems for HCC in estimating prognosis (3-month survival and overall survival (OS)).From November 2008 to April 2010, 208 patients with advanced HCC who were not amendable to locoregional therapy were included in this study. Data were collected to classify patients according to the following: the Japanese integrated staging scoring system, TNM stage by the Liver Cancer Study Group of Japan criteria, TNM 6th edn, the cancer of the liver Italian program scoring system (CLIP), the advanced liver cancer prognostic system (ALCPS), the model of end-stage liver disease, the Groupe d'étude et de Traitement du Carcinome Hepatocellulaire (GETCH) scoring system, the Chinese University prognostic index staging system (CUPI), the Okuda scoring system, the Child-Pugh score, the Tokyo scoring system and the Barcelona Clinic liver cancer staging. Survival analysis and relative operating characteristic (ROC) were utilized to access the prognostic value of each scoring system.ALCPS performed best, with the largest area under the ROC curve in predicting 3-month OS (sensitivity 76.32%, specificity 78.72%). CLIP and CUPI were similar to ALCPS in prognostic discrimination but with relatively lower power.ALCPS, CLIP and CUPI are the preferred scoring systems in the prediction of OS and 3-month survival among the 12 systems analyzed, and should be used as inclusion criteria in clinical trials for advanced HCC patients.

We and others had proven that hypoxia-induced autophagy was essential to regulate cancer cell destiny under anticancer therapeutic stress. Here, we addressed the clinicopathologic effect of HIF-1α and autophagic Beclin 1 in primary duodenal adenocarcinoma (PDA). HIF-1α and Beclin 1 expression level were semi-quantitatively evaluated using tissue microarrays and immunohistochemistry (IHC) staining in 141 PDA patients. Among these patients, 77 acted as training set to select HIF-1α and Beclin 1 IHC cutoff score for patient outcome, and 64 cases were used as testing set to evaluate their prognostic effect. We found that Beclin 1 was cytoplasmic overexpressed, defined by training set fixed cutoff point, in 49.6 % PDA tissue, compared to 46.8 % patients had HIF-1α high expression. In testing set, Beclin 1 overexpression predicted a superior 5-year overall survival (OS) in both univariate (P = 0.010) and multivariate (P = 0.017) analyses. However, we did not detect any correlation between HIF-1α level and patient prognosis (P = 0.989). Significantly, among Beclin 1 overexpressed patients, radical surgery plus adjuvant chemotherapy had a 23.1-month OS improvement than given radical surgery alone (59.2 vs 36.1 months; P = 0.01). For Beclin 1 lowly expressed patients, radical surgery plus adjuvant chemotherapy and given radical surgery alone had the similar OS (P = 0.283). Contrary to previous studies, we failed to detect any correlation between Beclin 1 and HIF-1α levels in PDA (correlation coefficient 0.217, P = 0.099). In conclusions, our results confirmed that Beclin 1 was a favorable prognostic biomarker for PDA, and might be used to identify particular patients for more selective therapy.

Even though ER-positive, HER2-negative breast tumors represent a subset of breast cancers with a better clinical outcome, approximately 12.7 % of patients in this subgroup ultimately develop cancer-related mortality. Recent studies had confirmed that hypoxia-induced autophagy-related gene Beclin 1 expression might be important for disease progression and be correlated with patient outcome in several tumors. Here, we examined the autophagic Beclin 1 and hypoxic HIF-1α levels in 378 ER-positive, HER2-negative breast cancer patients by immunohistochemistry using tissue microarray. We found that Beclin 1 was highly expressed in normal mammary gland epithelia. In contrast, it was either not expressed or only moderately expressed in 78.0 % of breast adenocarcinoma tissue. Compared to the subset overexpressing Beclin 1, the subset in which Beclin 1 levels were reduced had a poor 5-year overall survival rate (OS, 85.1 % vs. 94.1 %, P = 0.005) and a poor distant metastasis-free survival (DMFS, 79.1 % vs. 89.3 %, P = 0.037). Cox multivariate analysis confirmed that Beclin 1 was indeed an independent prognostic factor for OS and DMFS. Additionally, Beclin 1 positively correlated with HIF-1α expression (r = 0.206, P < 0.001). Importantly, among patients with HIF-1α overexpression, low levels of Beclin 1 predicted a worse OS. Our study confirmed that deficiency of Beclin 1 was a negative prognostic factor for OS and DMFS in ER-positive, HER2-negative breast cancer. The combination of Beclin 1 and HIF-1α refined the risk definition of the patient subset and provided a novel way to identify those with a high risk of relapse.

Various studies on lymphoma microenvironment have demonstrated the prognostic impact of tumor-associated macrophages (TAMs) in patients with B-cell lymphoma. Little is known about the correlation between TAMs and treatment outcome in mature T- and natural killer (NK) cell lymphomas. We analyzed the prognostic relevance of CD68+ TAMs by immunohistochemical analysis in 64 Chinese patients with mature T- and NK-cell lymphomas. Higher number of infiltrated TAMs was significantly related to B symptoms and extranodal involvement (p < 0.05). The TAMs content did not differ significantly between pathological subtypes. Using the mean value of TAMs per high-power field (hpf) as the cutoff point (87/hpf), 36 cases (56.2 %) were categorized as low level of TAMs content and 28 cases (43.8%) as high level. Patients with high level of TAMs content had a worse 5-year overall survival compared to those with low level (28.1 vs. 44.3 %, p = 0.039). In multivariate analysis, TAMs content remained an independent biological variable for survival distinct from the International Prognostic Index (Cox multivariate model, p = 0.009). High TAMs content indicated an adverse overall outcome in mature T- and NK-cell lymphomas. Our results show that expression of stromal TAMs may become a useful marker for prognosis of mature T- and NK-cell lymphomas.

In the present study we investigated the in vitro apoptosis inducing effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand ciglitazone (CGZ) on acute promyelocytic leukemia (APL) NB4 cells and its mechanisms of action. The results revealed that CGZ (10-50 micromol/l) inhibited the growth of leukemia NB4 cells and caused apoptosis in a time- and dose-dependent manner. Apoptosis was observed clearly by flow cytometry (FCM) and DNA fragmentation analysis. After treatment by CGZ for 48 h, the percentage of disruption of mitochondrial membrane potential (Deltapsim) was increased in a dose-dependent manner. Western blotting demonstrated the cleavage of caspase-3 zymogen protein and a time-dependent cleavage of poly (ADP-ribose) polymerase (PARP). The results also demonstrated that PPAR-gamma expression was increased concomitantly when apoptosis occurred, and that CGZ-induced apoptosis was inhibited by the PPAR-gamma antagonist GW9662, suggesting a PPAR-gamma dependent signaling pathway in CZG-induced cell death. Moreover, CGZ treatment remarkably downregulated the expression of the X-linked inhibitor of apoptosis protein (XIAP), which was inhibited by GW9662. Of note, a small-molecule XIAP antagonist (1396-12) mimicked the effect of CGZ-induced apoptosis via activation of caspase-3, 7 and 9. The apoptosis-inducing effects by CGZ on fresh APL cells were also found to be remarkable by using FCM and Wright's staining observation. Taken together, our results suggest that downregulation of XIAP and activation of capase-3 play an important role in mediating the PPAR-gamma-dependent cell death induced by CGZ in APL cells. These data provide a novel insight into potential therapeutic strategies for treatment of leukemia.

To study the gene polymorphism of HLA-A, B, DRB1 alleles in patients with chronic myelogenous leukemia and to explore the correlation of HLA with chronic myelogenous leukemia, the polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO) was used to analyze the polymorphism of HLA-A, B, DRB1 alleles of 293 CML Patients and 406 randomized and synchronous blood donors (healthy and unrelated with patients) from Guangdong Han population. The results indicate that the gene frequency of HLA-A*24 in CML group was 15.53% lower than that of control group (22.09%, RR = 0.63, p = 0.005); the gene frequency of HLA-B*13 in CML group was 10.41% higher than that of control group (6.74%, RR = 1.68, p = 0.016). The gene frequency of HLA- DRB1*14 in CML group was 7.51% lower than that of control group (11.89%, RR = 0.58, p = 0.008). The differences were all statistically significant. It is concluded that the gene frequency of HLA-A*24, HLA- DRB1*14 in CML patients is significantly lower than normal people in Guangdong. The gene frequency of HLA-B*13 in CML patients is significantly higher than normal people in Guangdong. Further study is needed to make sure whether HLA-A*24 and HLA- DRB1*14 are protective gene markers for CML acquisition on Guangdong Chinese Han population and whether HLA-B*13 is a gene marker for CML susceptibility on this population.

Veno-occlusive disease of the liver (VOD) is one of the most common complications in patients after hematopoietic stem cell transplantation (HSCT). So far, the mortality of severe VOD is almost 100%. How to deal with the disease remains to be an unresolved problem. This study was to explore more efficient methods of prevention and treatment of VOD.Clinical data of 18 patients undergoing allogeneic HSCT were analyzed. All the patients were pretreated with busulfan and cyclophosphamide, and treated with prostaglandin E1, glutathione and ornithine aspartate before HSCT to prevent VOD. Prostagland E1, low molecular weight heparin and tissue plasminogen activator (tPA) were used to treat the patient with VOD.The serum level of glutamate-pyruvate transaminase was elevated in 11 patients after HSCT, and all the patients were cured. Only 1 patient suffered VOD which was severe. Prostaglandin E1 and low molecular weight heparin were not effective in this case, while tPA was. The side effect of tPA was bleeding of the skin and mucosa.The combination of prostaglandin E1, glutathione and ornithine aspartate is probably effective and safe in preventing VOD for it aims at many aspects of pathogenesis of VOD. tPA can be used carefully as a choice of treating severe VOD.

18 Background: Advance directives (ADs) are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, which might violate patients’ personal will. This study was aimed to examine the acceptance of ADs among Chinese cancer patients and their families and patient participation in this procedure. Finally, to analyze the moral risk involved. Methods: Participants included 412 adult cancer patients from 9 leading hospitals across China. An AD was introduced to the main decision makers for each patient; if they wished to sign it, the AD would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients’ awareness of their disease, and participation in an AD. Results: A total of 246 patients and their family members rejected systematic discussion of AD, the majority (95.5%) of whom were under anti-cancer treatment. An additional 166 patients or their families accepted the concept of an AD and signed an AD to give up invasive treatment. This decision was make shortly after termination of anti-cancer therapy. Correlational analysis revealed that patients living in villages and who were subordinate members in their families tended to accept an AD. Of these, only 24 patients participated in the decision making. Correlational analysis revealed that patients with a better financial situation, living in cities, and superordinate status in their families tended to participate in the AD discussion, as well as those who usually made medical decisions themselves. Nearly all the patients deciding their own AD knew their entire situation, including diagnosis and prognosis. For 101 patients, anti-cancer therapy was ended prematurely, with as many as 37 patients not told about their potential loss of health interests. Conclusions: ADs were widely accepted among Chinese cancer patients when anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an AD. Thus, AD could be formally introduced to the family of Chinese cancer patients after termination of anti-cancer therapy.

e21509 Background: Extragastrointestinal stromal tumor (EGIST) shows features of GIST outside the gastrointestinal tract, occurring mainly in the omentum, mesentery and retroperitonium. EGIST is ra...

To retrospectively analyze the curative effects and prognostic factors of HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia patients (CML).Of the 35 CML patients, 26 were males and 9 were females, with a median age of 32 (12 - 50) years. 30 patients were in chronic phase of CML, 5 patients were in accelerated phase. Allo-HSCT from HLA identical siblings was performed for 35 patients, of whom 11 received bone marrow transplantation (BMT) and 24 peripheral blood stem cell transplantation (PBSCT). Conditioning regimens was TBI (total-body irradiation) + CY (CTX) protocol in 8 patients and BU/CY protocol in 27 patients. The average follow-up was 48 months (range 7 - 108 months).34 (97.1%) patients were successfully engrafted. Among them, 21 patients (60.0%) had three years disease-free (DFS) survival. The overall 5-year survival (OS) was 57.1%. Two patients (5.7%) relapsed. Transplant-related mortality occurred in 12 patients. Hemorrhagic cystitis (HC) occurred in 5 patients and HVOD was observed in 1 patient. Acute graft-versus-host disease (aGVHD) occurred in 18 patients (51.4%), among them 7 patients (20.0%) were of grade III-IV. Chronic GVHD was in 17 patients (48.5%). There was no significant difference in 3-years DFS between BMT group and PBSCT group (54.5% vs. 62.5%, P0.05). The 3-year disease-free survival (DFS) was 42.9% in TBI/CY group and 55.6% in BU/CY group (P0.05). In univariate prognostic analysis model, the DFS at 3 years is 75% and 47.4% foror =30 years patients and30 years patients, respectively, P0.05. The 3-year DFS of patients with first chronic phase is higher than patients with advanced diseases (61.3% vs. 40%, P0. 05). The 3-year DFS in patients of grade I - II GVHD was higher than that in patients of grade III-IV GVHD (81.8% vs. 14.3%, P0.05).The patients who had transplantation done within 1 year after diagnosis during their first chronic phase of disease and who had low-grade GVHD have better prognosis. Those patients who had III-IV acute GVHD are prone to incorporate severe infection, which was a worse prognostic factor of allo-HSCT for chronic myelogenous leukemia.

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and also is an important factor affecting the outcome of transplantation. Some researches showed that either acute or chronic GVHD is often accompanied by graft-versus-leukemia (GVL) effect, and this positive effect is associated with the decrease of leukemia relapse and the prolongation of disease-free survival of recipients. This study was to assess the influence of GVHD on the outcome of allo-HSCT.Twenty-six patients with hematologic malignancies received allo-HSCT from Mar. 1995 to Oct. 2005. The occurrence of GVHD, relapse of leukemia, and survival of recipients were analyzed retrospectively, and the correlations of GVHD to leukemia relapse and patients' survival were evaluated.With a median follow-up of 20 months (range 2-127 months) after transplantation, 20 (76.9%) patients developed GVHD, 1 of which had tumor relapsed; 3 of the 6 patients without GVHD had tumor relapsed. The relapse rate was significantly lower in the recipients with GVHD than in the recipients without GVHD (P0.05). After transplantation, 16 patients survived disease-freely, and 10 died. Kaplan-Meier survival curves showed that the 3-year disease-freely survival rate was 60%. The disease-freely survival rate was significantly higher in the recipients with GVHD than in the recipients without GVHD (15/20 vs. 1/6, log-rank=7.30, P0.05). Cox regression models showed a significantly decreased risk of death in the recipients with GVHD (risk ratio=0.2, P0.05). Of the 20 recipients with GVHD, 17 achieved complete response (CR), 15 of whom survived disease-freely; no survived in the 3 patients who did not achieve CR. The disease-freely survival rate was significantly higher in the recipients achieved CR than in the recipients did not (P0.05).GVHD is an important factor that may influence the outcome of allo-HSCT. Treatment efficacy of GVHD is significantly associated with the disease-free survival of recipients. Early recognition and treatment of acute GVHD is the key factor of successful treatment.

Ponicidin, an ent-kaurane diterpenoid derived from a constituent of the herbal supplement PC-SPES, Rabdosia rubescens, is recently reported to have anti-tumor effects on a large variety of cancers. In this study, we demonstrate that ponicidin exhibits cytotoxicity, induces apoptosis, disrupts the mitochondrial membrane potential, and triggers the activation of caspase-3, -8 and -9 in lung cancer A549 and GLC-82 cells. Ponicidin treatment of lung cancer cells caused downregulation of anti-apoptotic protein Bcl-2 and survivin as well as upregulaton of pro-apoptotic protein Bax in a time dependent manner when apoptosis ocurred. Ponicidin induced activation of caspase-3 can be blocked by a caspase-3-specific inhibitor z-DEVD-FMK Furthermore, the caspase-8-specific inhibitor z-IETD-FMK could block the ponicidin-induced activation of caspase-3, PARP cleavage, and prevented the release of cytochrome c from mitochondria into the cytoplasm. This indicate that activated caspase-8 initiates the release of cytochrome c during ponicidin-induced apoptosis. We therefore conclude that ponicidin has significant apoptosis-inducing effects by activation of caspase-3 -8, and -9 as well as downregulation of anti-apoptotic protein Bcl-2, survivin and upregulation of pro-apoptotic protein Bax, with caspase-8 acting as an upstream activator. The data offer a potential mechanism for ponicidin-induced apoptosis in lung cancer cells, suggesting that ponicidin may severve as an effective reagent for the treatment of lung cancer, and that in vivo anti-cancer effects as well as its potential clinical effectiveness need further investigation.

The anti-proliferation effects of oridonin on acute promyelocytic leukemia (APL) cells and its mechanisms were studied in vitro. NB4 cells as well as fresh leukemia cells obtained from APL patients in culture medium were treated with different concentrations of oridonin. Cell growth inhibition, apoptosis and related pathways were assessed by MTT assay as well as flow cytometry (FCM) and western blot analysis. The data revealed that oridonin (over 16 micromol/L) could inhibit the growth of NB4 cells by induction of apoptosis. Marked changes of cell apoptosis were observed very clearly by using electron microscopy and DNA fragmentation analysis after the cells exposed to oridonin for 48 h; Western blotting showed cleavage of the caspase-3 zymogen protein (32-kDa) with the appearance of its 20-kDa subunit as well as a cleaved 89-kDa fragment of 116-kDa PARP when apoptosis occurred. The expression of Bcl-2 was down-regulated remarkably accompanied by the disruption of the mitochondrial membrane potential (delta(psi)m). The anti-proliferative and apoptosis-inducing effects by oridonin in fresh APL cells were also found remarkably using Trypan Blue dye exclusion method and Wright's staining. We concluded that oridoning has significant anti-proliferative and apoptosis-inducing effects on NB4 cells by activation of caspase-3 and cleavage of PARP as well as by down regulation of Bcl-2 and disruption of the delta(psi)m. Furthermore, oridonin demonstrated apparent cell growth inhibition effects on fresh APL cells in vitro. The results indicated that oridonin may serve as a potential anti-leukemia reagent.

Ponicidin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Ponicidin has been reported to have anti-tumor effects on a large variety of malignant diseases. In this study, we investigated the anti-proliferation effects of ponicidin on human myeloid K562 and HL-60 cells. Cell viability was measured by MTT assay; cell apoptosis was assessed by flow cytometry, DNA fragmentation analysis and Hoechst 33258 staining. Caspase-3 and poly(ADP-ribose) polymerase (PARP) activation and Bax and Bcl-2 expression were detected by Western blot analysis. The results revealed that ponicidin could significantly inhibit the growth of K562 and HL-60 cells by induction of apoptosis. The suppression was both time- and dose-dependent. Cell apoptosis was observed clearly after the cells were treated with ponicidin for 48-72 h. Western blotting showed cleavage of the caspase-3 zymogen protein (32 kDa) with the appearance of its 17 kDa subunit, together with a cleaved 89-kDa fragment of 116 kDa PARP when apoptosis occurred. Bcl-2 expression was down-regulated while Bax expression up-regulated concurrently when the cells were treated with ponicidin for 24-48 h. Therefore, we conclude that ponicidin has significant anti-proliferation effects by induction of apoptosis on myeloid leukemia cells in vitro, down-regulation of Bcl-2, and up-regulation of Bax, and that activation of caspase-3 and PARP may be an important apoptosis-inducing mechanism. The results suggest that ponicidin may serve as a potential therapeutic agent for leukemia.

Epstein-Barr virus (EBV) is associated with genesis of many human tumors, including non-Hodgkin's lymphoma (NHL). Latent membrane protein 1 (LMP1) gene is considered as an oncogene of EBV. Recent researches have suggested that LMP1 polymorphisms, especially C-terminal 30bp-deletion (del-LMP1), might be associated with carcinogenicity of EBV, and play important roles in tumorigenesis. This study was to detect expression of del-LMP1 gene in NHL patients and healthy people, and explore relationship of del-LMP1 gene to tumorigenesis and prognosis of NHL.LMPl gene segments (including the 30 bp deletion) in 48 NHL patients and 60 healthy people were amplified by polymerase chain reaction (PCR) with sequence-specific primers. PCR products were randomly chosen,and sequenced to confirm their specificities and to detect other mutations of LMP1 gene. The distributions of del-LMPl in NHL patients and healthy people were compared. Relationship of del-LMP1 gene to prognosis of NHL was analyzed.(1) LMP1 gene was detected in 23 of 48 NHL patients, 18 of 23 (78%) harbored del-LMPl; LMP1 gene was detected in 32 of 60 healthy people, 13 of 32 (41%) harbored del-LMPl. Positive rate of del-LMPl gene in NHL patients was significantly higher than that in healthy people (P0.05). (2) Among 23 EBV-related NHL patients, 15 belonged to high risk group (IPI/=3), and del-LMPl was detected in 14 of them (93%); 8 belonged to low risk group (IPI3), and del-LMPl was detected in 4 of them (50%). Positive rate of del-LMP1 in IPI/=3 group was significantly higher than that in IPI3 group (P0.05). (3)Sequencing confirmed that the 30 bp-deletion located at 168 285-168 256 nt (355-346 aa), and most C-terminal mutations located at 168 357-168 225 nt.Del-LMPl gene exists commonly in EBV-related NHL, and might correlate with prognosis of NHL.

251 Background: Prognosis of patients with advanced HCC is very poor, median overall survival varies from 3 to 6 months. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical tirals. There exists four models for end-stage liver disease: 1.) MELD: The model for end-stage Liver disease; 2.) MELD-AS: MELD+4.53×c(Na)+4.46×Ascites [Serum Na: Na

388 Background: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusions: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

To evaluate the impact of postoperative infectious complications on hepatocellular carcinoma following curative hepatectomy.We performed a retrospective analysis of 200 hepatocellular carcinoma patients who underwent hepatectomy at our institution between September 2003 and June 2011. The patients' demographics, clinicopathological characteristics and postoperative infectious complications were analyzed. The Clavien-Dindo classification was adopted to assess the severity of complications. The dynamic change in the neutrophil-to-lymphocyte ratio, defined as the absolute neutrophil count divided by the absolute lymphocyte count, after surgery was also investigated. The observation endpoints for this study were recurrence-free survival and overall survival of the patients. Statistical analysis of the survival curves was performed using the Kaplan-Meier method and the log-rank test. The prognostic value of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis. The cutoff score for each variable was selected based on receiver operating characteristic curve analysis. All statistical tests were two-sided, and significance was set at P0.05.The median age of the patients was 49 years, and the majority of patients were male (86%) and had been infected with hepatitis B virus (86%). The 30-d postoperative infectious complication rate was 34.0% (n = 68). Kaplan-Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence (P0.001). The postoperative intra-abdominal infection group exhibited a worse prognosis than the non-intra-abdominal infection group (P0.001). A significantly increased incidence of postoperative intra-abdominal infection was observed in the patients with hepatic cirrhosis (P = 0.028), concomitant splenectomy (P = 0.007) or vascular invasion (P = 0.026). The patients who had an elevated postoperative neutrophil-to-lymphocyte ratio change (1.643) clearly exhibited poorer recurrence-free survival than those who did not (P = 0.009), although no significant correlation was observed between overall survival and the change in the postoperative neutrophil-to-lymphocyte ratio. Based on multivariate analysis, hepatitis B surface antigen positivity, Child-Turcotte-Pugh class B, an elevated postoperative neutrophil-to-lymphocyte ratio change and intra-abdominal infection were significant predictors of poor recurrence-free survival. Hepatic cirrhosis, the maximal tumor diameter and intra-abdominal infection were significant predictors of overall survival.Postoperative intra-abdominal infection adversely affected oncologic outcomes, and the change in postoperative neutrophil-to-lymphocyte ratio was a good indicator of tumor recurrence in hepatocellular carcinoma patients after curative hepatectomy.

227 Background: Medical decision making of Chinese patients was family based, which was criticized for the latent moral risk. However, few studies have systematically illustrated the risks of the mode. We aimed to illustrate the determinant of patients’ role in decision making. Methods: A total of 644 adult cancer patients were included in this study between September 1, 2013 and December 31, 2013 from 13 leading general hospitals across China. A questionnaire was give to the oncologists in charge to evaluate each patient concerning the interaction between family and cancer patients, patients’ awareness of disease and participation in medical decision making in mainland China. In this study, the family statuses of patients were ranked as superordinate (one who was the major decision maker in family), equality (one discussed important issues with family members), and subordinate (those who usually don’t be involved in significant family issues). Results: Among the 644 cancer patients, only 125 (19.4%) patients made decision themselves. 291 (45.2%) patients delegated decision making to their family. The rest of 228 (35.4%) patients were involved in decision making. Patients with nonlocal insurance, which meant they traveled to the major cities for advanced medication, were inclined to let their family members make decision for them. Patients’ family status significantly determined their participation in medical decision making. Patients, as superordinate family members, tend to play a positive role in medical decision. By contrast, patients with subordinate role in family continued to play a passive role in medical decision making. Violation of medical recommendation increased according to the severity of patients’ prognosis. The reasons of violation were mainly financial problems. Distrust to doctors presented in merely about 5% of the cases. And conflicts between family members were extremely scarce. Bad news was always hidden from patients, especially for those with incurable disease. Conclusions: Medical decision making of Chinese cancer patients was family based. Patients’ awareness of disease and participation in medical decision making relied on their family status and family financial situation.

e19508 Background: Relapsed and refractory non-Hodgkin’s lymphomas (NHL) have a poor prognosis and represent a major treatment challenge. There is no standard of care for salvage regimens. Metronom...

e15096 Background: Golgi protein 73 (GP73), a membrane protein localized in the type II Golgi complex, is a candidate biomarker for hepatocellular carcinoma (HCC). However, current evidence is conf...

e15118 Background: Previous studies have demonstrated a correlation between immune microenvironment and the biology of hepatocellular carcinoma (HCC). This study aims to evaluate the prognostic val...

374 Background: Postoperative intra-abdominal infection has been reported contributed to higher tumor recurrence rate and poor survival in cancer patients. The study aims to evaluate the impact of postoperative intra-abdominal infection on recurrence free survival (RFS) and overall survival (OS) in patients undergoing curative liver resection for hepatocellular carcinoma (HCC). Methods: ALL patients underwent liver resection from 2003 to 2010 were identified. The Clavien–Dindo (CD) classification was adopted to classify the complications and patients who died of postoperative complications within 30 days of surgery (grade V) were excluded form the study. Univariate and multivariate analyses were used to assess variables. Results: 215 patients were included, the overall 30-day postoperative complication rate was 36.74% (n=79), 13.95% (n=30) were intra-abdominal infectious complication. Patients with intra-abdominal infection had worse RFS (27.6% vs 50%, p5cm) and Child-Pugh class (B) were other three independent factors associated with poor prognosis. Conclusions: According to the study, postoperative intra-abdominal infection predicts tumor recurrence and poor survival after radical liver resection in HCC patients. These findings may have implications of the potential association between inflammatory response and cancer progression.

1 in The Lancet Oncology, which set a good example for local comprehensive palliative care. The Chinese medical system in urban areas is similar to the system in Japan to some extent, with free access to all medical institutions, 60-80% of patients covered by national insurance, and an under- developed system exists for primary care and organisation of palliative care resources. 2,3

e16077 Background: Most of malignant tumor patients have hypercoagulable state with plasma fibrinogen (Fib) levels increased. In this study, we aimed to investigate correlation of plasma Fib with routine prognostic factors of prostate cancer patients, including Gleason score, prostate specific antigen (PSA), TNM 7th Stage. Methods: From January 2007 to December 2012, 107 patients with prostate cancer and 44 cases of benign prostatic hyperplasia (BPH) were included in our study. Automated coagulation analyzer was used to determine the plasma fibrinogen levels. Results: The patients presented a mean age of 70.6 years, a mean PSA level of 28.73 ng/ml, clinically localized prostate cancer in 47 cases, locally advanced condition in 27cases, and distant metastatic disease in 33 cases. The fibrinogen levels were increased in cancer patients compared to that in patients with BPH (P = 0.031). Higher fibrinogen levels related to metastasis, higher TNM stage and increased PSA (p = 0.000, 0.041 and 0.004 respectively). Fib levels were irrelevant to T state, N state, and Gleason score. Conclusions: Prostate cancer patients displayed increased Fib levels. Plasma Fib is significantly increased in patients with higher PSA level,worse TNM stage and distant metastasis. The patients with high Fib might presented relative worse prognosis and should be monitored closely. [Table: see text]

e19504 Background: Nasal-type extranodal NK/T-cell lymphoma (ENKL) is a highly invasive disease with quite poor prognosis.Pegaspargase (PEG-Asp) displays a similar anti-cancer mechanism as that of L-asparaginase (L-ASP), but exhibits lighter antigenicity. The aim of the present research was to evaluate efficacy and safty of PEG-Asp-based regimen in ENKL. Methods: Data were collected from 23 patients with histologically confirmed ENKL who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to March 2012. Each patient received PEG-Asp 2500 IU/m2/IM on day 1 of each 21-day chemo-cycle. Among them, 8 received combination chemotherapy with CHOP regimen, 11 with EPOCH, and 4 with a CHOP-like regimen (CHOP + bleomycin). The CHOP regimen consisted of cyclophosphamide 750mg/m2, IV (day 1), pirarubicin 40mg/m2, IV (day 1), vincristine 1.4 mg/m2, IV (day 1), and prednisone 100mg, oral (days 1- 5). The EPOCH regimen consisted of etoposide 50mg/m2, epidoxorubicin 12 mg/m2 and vincristine 0.4mg/m2 dissolved in 500mL saline and administered as a continuous IV drip for 24 hours on days 1- 4. Cyclophosphamide 750mg/m2, IV (day 5) and prednisone 60mg/m2, oral (days 1-5), were also administered. In the CHOP-like regimen, bleomycin 15mg was added on days 1-3. Stage I-II patients received local radiotherapy after the chemotherapy. Results: The patients received the PEG-Asp-based chemotherapy for 2-5 cycles (median, 4 cycles). Eleven (47.8%) achieved complete response (CR), and the overall response rate (ORR) was 82.6%. The median time to progression (TTP) was 5 months (range, 2-6 months) and the median OS was 16 months (range, 5-38 months). The 1-year and 2-year survival rate were 82.6% (19/23) and 56.5% (13/23) , respectively. A minor glutamic-pyruvic transaminase (GPT) elevation was observed in 3 patients (13.0%), slight decrease of albumin in 3 (13.0%), reduced fibrinogen level in 2 (8.7%), grade I-II WBC bone marrow suppression in 8 (34.8%), and grade III-IV WBC bone marrow suppression in 3 (13.0%). No allergic incidences were witnessed. Conclusions: Our results suggested PEG-Asp-based chemotherapy presented potential effects in treating nasal-type ENKL with acceptable side effects profile.

538 Background: Overexpression of enhancer of zeste homologue 2 (EZH2), a key component of polycomb proteins, has been linked to aggressive tumor behavior for breast cancer. In vitro, hypoxia-inducible factor 1 alpha (HIF-1α) transcriptionally activates EZH2 and promotes breast tumor initiating cells progression. Here, we characterized the clinicopathological effect of HIF-1α and EZH2 in breast cancer patients. Methods: Tumor specimens from 410 luminal subtype breast cancer patients were used to construct tissue microarray. EZH2 and HIF-1α level were examined by immunohistochemistry staining and Western blot analysis. With the 5-year follow up, the prognostic effect of EZH2 was subjected to multivariate analysis. Results: EZH2 and HIF-1α were highly expressed in 99 (24.1%) and 272 (70.6%) patients, respectively. EZH2 overexpression was associated with high histological grade (P=0.030), lymphatic invasion (P=0.025), HER2 overexpression (P=0.005) and hypoxic condition (P

e15021 Background: Recurrence resulting in high morbidity of hepatocellular carcinoma (HCC) patients received radical liver resection, the majority of which occur within 1 to 3 years. The study aims to find risk factors and set up a prognostic model predicting early recurrence of HCC. Methods: From 2003 to 2010, 196 HCC patients underwent liver resection were retrospectively analyzed. Univariate and multivariate analyses were used to assess variables. A recurrence risk model was developed with independent prognostic factors. Area under the ROC curve (AUC) was carried out to evaluate its predictive value. Results: The median follow-up time was 33 months (1-103M), median RFS was 22 months. Total tumor volume (TTV), hepatitis B, Child-Pugh score, and portal vein tumor thrombus were independent factors of recurrence. Patients with TTV>115cm3 had worse RFS (28.9% vs 51.7%, p3. We established a risk model consisted of the 4 parameters, and classified patients into four stages. There were significant differences between each stage, especially for the 1st year. (1-yr RFS: 80.1% vs 47.8% vs 28.6% vs 0%, p=0.000, AUC 0.682). Compared to four currently used staging systems (BCLC, TNM, CLIP, and Okuda), the new model could well predict patient’s survival with the largest AUC in both RFS and OS (Table). Conclusions: TTV has been found a preferable description of tumor burden and a prognostic factor in HCC. This prognostic model predicts early tumor recurrence and survival of patients received radical liver resection and might contributes to the selection of patients who may benefit from surgery. [Table: see text]

4131 Background: We and others had proved that hypoxia-inducible factor-1α (HIF-1α) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Methods: We addressed the clinicopathologic value of HIF-1α and Aurora-a in primary duodenal adenocarcinoma (PDA). Aurora-a and HIF-1α expression were semi-quantitative evaluated by immunohistochemistry in 140 PDA. Among which, 76 patients from one institute acted as training set, and 64 cases from another two institutes were used as testing set to validate the prognostic effect of Aurora-a and HIF-1α. Results: We found that Aurora-a was high or sufficient expressed in tumor zone, whereas low-expressed in the normal adjacent epithelia. Moreover, Aurora-a high expression, classified by training set ROC analysis-generated cutoff score, predicted an inferior overall survival both in testing set and training set. Multivariate Cox regression confirmed that Aurora-a was indeed an independent prognostic factor (Table). Contrary to previous studies, we did not detect any correlation between Aurora-a and HIF-1α in PDA. Additionally, survival analysis showed that HIF-1α level was not correlated with patient outcome (p = 0.466). Conclusions: Activation of Aurora-A, an independent negative prognostic biomarker, might be used to identify particular patients for more selective therapy. [Table: see text]

Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. However, the roles of CAFs in the liver cancer microenvironment have not been thoroughly studied. In our previous study, we successfully isolated CAFs from hepatocellular carcinoma (HCC) (H-CAFs) and proved that H-CAFs suppressed the activation of NK cells and thereby created favorable conditions for HCC progression. In our present study, we found that the proliferation of MHCC97L and Hep3B cells was significantly promoted by treatment with conditioned medium from H-CAFs. Pathological analysis also revealed that H-CAFs increased the proportion of Ki-67 (+) malignant cells and prevented them from undergoing necrosis. Moreover, the concentration of hepatocyte growth factor (HGF) cytokine in the conditioned medium of H-CAFs was higher than conditioned medium from normal skin fibroblasts (NSFs). Anti-HGF significantly reduced the proliferation-promoting capability of H-CAFs. In addition, we found that the abundance of H-CAFs correlated positively with tumor size. These results indicate that H-CAFs are an important factor for promoting the growth of HCC in vitro and in vivo, and that HGF plays a key role in HCC proliferation induced by H-CAFs.

Background Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers. Methodology/Principal Findings Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients. Conclusions/Significance Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways.

e14512 Background: Duodenal carcinoma, that with a rare incurrence, displayed a poor prognosis in the metastatic settings. The clinical trial based therapeutic regimen for advanced duodenal carcino...

2567 Background: The life expectancy of patients with advanced hepatocellular carcinoma (HCC) enrolled in clinical trials should be at least 3 month to test drug response. However, the prognosis of...

5514 Background: Accurate means to refine the prognosis of local advanced nasopharyngeal carcinoma (NPC) will improve the selection of patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm, Support Vector Machine (SVM), by integrating pathological multibiomarkers. Methods: Ninety-seven local advanced NPC patients (stage III and IVa) in a randomized controlled trial (RCT), consisting of 48 cases serving as the training set and 49 cases as testing set of SVM models, with a 5-year follow-up were selected and studied. We designed 3 SVM models by selecting the variables from 38 tissue molecular biomarkers and 3 EBV related serological biomarkers. Results: The SVM1 displayed highly prognostic sensitivity (sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 88.0%, 81.9%, 62.9%, 95.2% and 83.5%, respectively) by integrating 7 molecular biomarkers (Aurora-A, Beclin 1, Ki-67, N-cadherin, nm23-H1, P27, and TIMP 2). Th...