Background: Histone deacetylase (HDAC) plays a crucial role in regulating the expression and activity of a variety of genes associated with tumor progression and immunotherapeutic processes. The aim of this study was to characterize HDAC pathway copy number variation (CNV) in pan-cancer.Methods: A total of 10,678 tumor samples involving 33 types of tumors from The Cancer Genome Atlas (TCGA) were included in the study.Results: HDAC pathway CNV and CNV gain were identified as prognostic risk factors for pan-cancer species. The differences of tumor characteristics including tumor mutational burden, tumor neoantigen burden, high-microsatellite instability, and microsatellite stable between HDAC pathway CNV altered-type group and wild-type group varied among the various cancer species. In some cancer types, HDAC pathway CNV alteration was positively correlated with loss of heterozygosity, CNV burden, ploidy, and homologous recombination defect score markers, while it was significantly negatively correlated with immune score and stroma score. There were significant differences in immune characteristics such as major histocompatibility complex class I (MHC-I), MHC-II, chemokines, cytolytic-activity, and IFN-γ between the two groups. Immune cycle characteristics varied from one cancer type to another.Conclusion: This study reveals a tumor and immune profile of HDAC pathway CNV as well as its unlimited potential in immune prognosis.

Objectives: We aim to evaluate the epidemiological features, timing, predictors and clinical impacts of chemotherapy-associated myelotoxicity in Chinese gastric cancer population receiving six established cytotoxic conventional regimens (CF/XP, EC(O)F/EC(O)X, DC(O)F/DC(O)X, PC(O)F/PC(O)X, FOLFOX4, or mFOLFOX7/XELOX). Patients and methods: A 4-year multicenter, prospective, observational study was conducted in multiple hospitals/institutes spanning three major regions in China. A total of 1,285 patients with gastric cancer, treated with six selected regimens between 2010 and 2014 were included. Kaplan-meier analysis was applied to estimate the time to develop myelotoxicity events for each regimen. Multivariable logistic regression model was built to identify predictors associated with chemotherapy-induced myelotoxicity, evaluating detailed specific factors of patients, disease and treatment patterns. Results: Triplet regimens were associated with more moderate-to-severe myelotoxicity events than doublet regimens. DC(O)F/DC(O)X group presented with moderate-to-severe anaemia, thrombocytopenia, and leukopenia earlier than other regimen groups, with median time of 3.5, 4.8 and 3.3 cycles, respectively. PC(O)F/PC(O)X group had a shortest time to develop Moderate-to-Severe neutropenia (median time, 3.3 cycles). Multivariate analysis identified several independent predictors for moderate-to-severe myelotoxicity, including: baseline Hb<12.0 g/dL, male gender, KPS<80, previously treated with surgery, tumor located at gastroesophageal junction(GEJ), DC(O)F/DC(O)X regimen, palliative intent, triplet combination therapy and No. of cycles received≥4. Dose reductions≥20% occurred in 16.7% of patients and treatment delays≥7 days presented in 21.1% of patients, resulting in patients receiving an actual average Relative Dose Intensity (RDI) of 0.733. Conclusions: Myelotoxicity events were frequently observed within the gastric cancer population undertaking multicycle polychemotherapy. Predictive models based on risk factors identified for moderate-to-severe myelotoxicity should enable the targeted use of appropriate supportive care in an effort to facilitate the delivery of full chemotherapy doses on schedule.

OBJECTIVE:Many previous studies that examined the association between CTLA-4 rs231775 polymorphism and CRC risk have produced inconsistent results. In this study, a meta-analysis was performed to systematically summarize the possible association.METHODS:We identified relevant studies using PubMed, Embase, and China National Knowledge Infrastructure literature databases. Eligible studies were selected using specific criteria. Data were extracted independently by two authors. The pooled OR with 95% CI was estimated by applying the fixed-effects model to examine the association of interest.RESULTS:Eight studies were identified for the meta-analysis. In overall analysis, we observed an significantly increased CRC risk attributed to the AG genotype as compared to the AA genotype (OR: 1.17, 95% CI: 1.02-1.35 for AG vs AA). Stratified analysis according to ethnicity also showed a significant association in Caucasians under the AG vs AA model (OR: 1.22, 95% CI: 1.03-1.46). No significant heterogeneity or publication bias was tested in our meta-analysis.CONCLUSION:In conclusion, the meta-analysis suggests that rs231775 in the CTLA-4 gene may be a risk factor for CRC, especially in Caucasians.

Background: Cholangiocarcinoma is one of the most common malignancies in China. Surgical resection is the only treatment option; however, diagnosis at advanced stage precludes surgery. Comprehensive knowledge of prognostic markers is missing. Hence, the aim of this study was to determine clinicopathological indexes that would be indicative of prognosis in post-operative cases of cholangiocarcinoma.Material/Methods: A retrospective analysis of 293 cases of cholangiocarcinoma patients attending the 301 Military Hospital in Beijing, China between January 2004 and December 2010 were included in the study. The patients had follow-up history until August 2012. Cox proportional hazards model analysis was performed to identify indexes of prognosis. All indicators were analyzed by univariate and multivariate analysis.Results: The median follow-up time was 55.90 months, with recurrence and metastasis in 162 cases (55.3%) and death in 223 cases (76.1%). The 1-year, 3-year, and 5-year survival rates were 71.7%, 38.2%, and 10.6%, respectively. The independent risk factors of overall survival were degree of tumor differentiation, TNM stage, surgical margin, intraoperative blood transfusion, tumor location, alkaline phosphatase levels in blood, and relapse.Conclusions: Good prognosis in cholangiocarcinoma patients is indicated by highly differentiated tumor, early stages of TNM staging, no resection margin invaded, no intraoperative blood transfusion, intrahepatic tumor, normal alkaline phosphatase levels, and no relapse.

Aim: To explore the relationship of clinicopathological features and the proteins of C-met expression in the prognosis of cholangiocarcinoma. Methods: Clinical data and the completed follow-up information of patients with cholangiocarcinoma who underwent cholangiocarcinoma operation from January 2004 to December 2010 were analyzed retrospectively. The relationship of clinicopathological features and C-met in the prognosis of the patients was analyzed. Results: Patients with high expression of C-met had significantly shorter overall survival than those with low expression of C-met, the difference being statistically significant (P = .003). Patients with high C-met expression had significantly shorter disease-free survival time than those with low expression of C-met, the difference being statistically significant (P = .009). By COX multivariate analysis, high C-met expression in tumor tissues was an independent risk factor in predicting overall survival and disease-free survival for patients with cholangiocarcinoma (P = .038, .048, relative risk = 1.390, 1.427). Conclusion: Patients with high C-met expression in cancer tissues had shorter disease-free survival and overall survival. High expression of C-met is an independent risk factor for overall survival and disease-free survival.

OBJECTIVE:To observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma.METHODS:Clinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology, Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods.RESULTS:The disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9% (61/71) vs. 59.3% (16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1% (41/45) vs. 68.1% (32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However, the differences were not statistically significant (P>0.05).CONCLUSIONS:Cetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.

The objective of the current study was to investigate the significance and biologic characteristic of neuroendocrine cell differentiation (NED) in gastric carcinoma by comparing the prognosis and clinicopathologic characteristics between patients with or without NED. Retrospective analyses of neuroendocrine markers, neuron specific enolase (NSE), chromogranin A (CgA), and synaptophysin (Syn) were performed in 174 human gastric carcinoma patients. NED association was found in 21.3% gastric carcinoma patients, with or without NED, and was correlated with tumor location, cancer emboli, infiltrative depth, TNM stage and distant metastasis (P < 0.05 in each case). The 1-year and 3-year survival rate of the patients who suffered from gastric carcinoma with NED were significantly lower than those without NED. The overall survival time of patients with NED was shorter than those with gastric carcinoma without NED, with a significant difference between the two types (P = 0.037). Cumulatively, gastric carcinoma patients with NED had shorter postoperative survival time and poorer prognosis.

Advanced pancreatic cancer patients have poor prognosis and scarcely respond to conventional therapies. Clinical trials support the use of molecular-targeted therapy against epidermal growth factor receptor (EGFR) signaling. The objective of the current study was to evaluate the contribution of a monoclonal antibody against EGFR, nimotuzumab, to standard gemcitabine therapy. Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were assigned to receive gemcitabine plus nimotuzumab. The primary end point was overall survival, whereas the secondary end points included progression-free survival, objective response, and adverse side effects. A total of 18 eligible patients were accrued between December 2007 and July 2010. The disease control rate, calculated as the sum of complete response, partial response, and stable disease, was 55.6 %. The median overall survival time was 9.29 months (95 % CI, 5.499 to 13.072). The median progression-free survival was 3.71 months (95 % CI, 2.526 to 4.902), and the 1-year survival rate was 38.9 %. Of all the patients, 88.8 % had at least one adverse side effect; however, no grade 4 adverse side effect was reported. Nimotuzumab as a high-purity humanized monoclonal antibody with favorable safety profile, its value in the treatment of pancreatic cancer along with gemcitabine, particularly in the comprehensive treatment of advanced pancreatic cancer, is appealing for further prospective randomized large-scale clinical trials.

Background: Small bowel adenocarcinoma (SBA) is a rare occurrence and few studies have addressed it adequately, especially in China. Methods: Clinicopathological features, survival and prognostic analysis were retrospectively done in SBA patients admitted between 2001 and 2011 in the People's Liberation Army General Hospital. Results: The study included 68 men and 51 women with a median age of 56.5 year. Tumors mainly occurred in duodenum (93.3%). Abdominal pain was the most frequent symptom (36.8%). Patients (30.3%) who received postoperative adjuvant chemotherapy had an increased, but not significant, median overall survival (MOS) rate compared to those who did not receive chemotherapy (37 vs 35 months, p = .324). One year disease free survival rate was higher in patients receiving postoperative chemotherapy (83.3% vs 71.1%). Patients survived longer in the curative surgery group (median survival time of 49.0 months) than those in the palliative group (7.0 months) (p < .001). Node-negative patients survived longer than node-positive patients (median OS: 49.0 vs 21.0 months, p = .004). Depth (95% CI: 1.013–1.517, p = .037), node involvement (95% CI: 1.234–3.890, p = .007), palliative surgery (95% CI, 2.998–10.555, p = .0005), and the site of tumor (95% CI: 0.052–0.970, p = .045) were independent predictors of OS in a multivariate analysis. Conclusions: SBA is rare and there is lack of obvious clinical manifestations. Depth, node involvement, palliative surgery, and the site of tumor are associated with a poor prognosis. Our analysis highlights the need for further studies to find out the exact role of postoperative adjuvant chemotherapy in these patients.

Gastric cancer remains one of the most common malignancies and leading causes of cancer death in China with a complex biological behavior. The incidence of liver metastasis from gastric cancer is particularly high. The indication of hepatectomy is controversial, however, surgery should be considered. How to choose the right regimen to obtain macroscopically complete resections represents a controversial subject. Newer generation cytotoxic agents such as docetaxel, S-1 and irinotecan as well as targeted therapy agent trastuzumab exhibit promising activity in gastric cancer. Further study and clinical trials are needed to confirm the benefits of systemic treatment in gastric cancer patients with liver metastasis.

Primary gastric choriocarcinoma PGC is a rare tumor. This study aimed to analyze cases reported in Chinese and two cases in our hospital. This study was also conducted to investigate the clinical characteristics and treatment of PGC. Methods: The Chinese Medical Current Contents and China Biology Medicine database was retrieved with the following terms: primary gastrio choriocarcinoma, stomach choriocarcinoma, and ectopic choriocarcinoma. The clinical data in published literature were retrospectively analyzed. Two cases from our hospital were also retrospectively analyzed. Results: A total of 16 patients with PGC (14 case studies and 2 cases from our hospital) were included in this study. The average age of the patients was 57.69 years (ranging from 42 years to 79 years). Among the 16 patients, 4 were females and 12 were males. The main clinical manifestation was abdominal discomfort (12/ 16). Laboratory and imaging tests were non-specific, but HCG-? in all of the patients increased (11/11). Organ or lymph node metastasis was found in 13 patients, including 6 cases in which two or more organs showed metastasis. These organs were primarily the liver, the stomach lymph nodes, the lungs, the brain, and the abdominal cavity. Pathological examination results showed that 12 of the 16 cases displayed ulcers with necrosis and hemorrhage. The four remaining cases manifested lesions. Lesions may occur in the stomach lesser curvature (5 cases), stomach sinus (6 cases), cardiac (2 cases), and gastric body (3 cases). The histological components of PGC co-existed with other factors, such as adenocarcinoma (7 cases), adenocarcinoma and squamous (2 cases), adenocarcinoma and a signet ring cell (1 case), or pure choriocarcinoma (6 cases). Surgery combined with chemotherapy was the main treatment. A total of 14 patients underwent surgical operations. Among these patients seven underwent chemotherapy after surgery and one underwent chemotherapy. Among the 10 patients who were followed up, 8 died within six months after diagnosis. Conclusion: PGC is a rare stomach cancer with poor prognosis and primarily affects older men. No characteristic clinical manifestations were observed, but HCG-? as a specific serum tumor biomarker increased in all of the affected patients. Histological components co-existed with other stomach cancers. Surgical excision combined with chemotherapy was the preferred treatment in early stages, and systemic chemotherapy was the recommended treatment in advanced stages.

The aim of the current study was to investigate how proinflammatory conditions affect growth and progression of hepatocellular carcinoma. Human hepatoma cell lines were treated with lipopolysaccharide (LPS) or cyclooxygenase-2 inhibitor, Celecoxib, and in vitro proliferation, apoptosis, and cell cycle progression were assessed. This was followed up with in vivo xenograft assays to monitor tumor growth and metastatic progression under different treatment conditions. While LPS induced cell proliferation, Celecoxib induced apoptosis. Flow cytometry analysis demonstrated that S-phase cell count in LPS group was higher than control group (41.9 ± 3.2 vs 30.6 ± 0.1%, respectively), whereas G0/G1-phase cells were significantly higher in the Celecoxib group in comparison with the control group (69.6 ± 5.0 vs 50.4 ± 1.6%, respectively) (p < 0.05). Immunoblot analyses showed induction of epidermal growth factor receptor expression and induction and nuclear accumulation of Wnt/β-catenin and p65 in LPS group. Xenograft assays showed that LPS treatment induced comparatively large, rapidly growing tumors (2,702 ± 572 mm(3)) that metastasized to lungs, whereas Celecoxib treatment alone (1,008 ± 296 mm(3)) or in combination with LPS (1,303 ± 283 mm(3)) suppressed tumor growth in comparison to control groups (2,072 ± 456 mm(3)) (n = 5; p < 0.05). Inflammation can thus promote hepatoma cell proliferation and growth, and enhance the invasion and metastatic ability of hepatocarcinoma cells through inducing tumor angiogenesis, which in turn may be related to the activation of Wnt/β-catenin and EGFR signaling pathways.

Objective Clinicopathological features and surgical outcomes in patients with solid pseudopapillary neoplasm (SPN) of the pancreas were analysed. Methods Data regarding clinicopathological features, surgery and outcome for patients with SPN were retrospectively collected and analysed. Patients were followed-up by telephone interview. Results The study included 102 patients (89 females/13 males), 99 of whom underwent surgical resection. A total of 89 patients (87.3%) were followed-up (mean duration 26.98 months, range 2–95 months); 86 (96.6%) had no relapse or metastasis. Conclusions Surgical resection is the primary therapy for SPN, and results in a good prognosis.

We retrospectively investigated germline polymorphisms in angiogenesis pathway genes (14 SNPs) and their correlation to clinical outcome (progression free survival and overall survival) in 128 patients with unresectable-advanced gastric carcinoma (AGC) treated with first-line chemotherapy. Our analysis revealed that Endostatin +4349 G>A polymorphism exhibited a worse progression free survival (PFS) and overall survival (OS) compared with the GG genotype. Significant OS difference was also observed in the endothelial nitric oxide synthase (eNOS)-786 T>C polymorphism. Hence, common germline variants in Endostatin and eNOS genes have predictive significance for clinical outcome and survivality in AGC patients treated with first-line chemotherapy.