Efficacy and safety of intermittent versus continuous dose apatinib plus docetaxel as second-line therapy in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma: a randomized controlled study.

Background: Previous studies of the second-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJAC) had reported that apatinib combined with chemotherapy improved the treatment outcomes. However, the benefits were sometimes limited due to the tolerance of continuous dose regimen. This randomized controlled study aimed to investigate the efficacy and safety of intermittent or continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC. Methods: Advanced GC/GEJAC patients who failed first-line chemotherapy were recruited (enrollment time: from September 15, 2017 to July 21, 2019), and randomly assigned to either the intermittent dose group (IG group) or the continuous dose group (CG group) (1:1 ratio) using the block randomization method. In the IG group, patients received apatinib 500 mg/d for 5 consecutive days then held for 2 days plus docetaxel 60 mg/m2 q3w, in a 3-week cycle. In the CG group, patients received apatinib 500 mg daily plus docetaxel 60 mg/m2 q3w, in a 3-week cycle. The progression free survival (PFS) was evaluated every two cycles and follow-ups were performed monthly. The primary endpoint was PFS, and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: In total, 76 eligible patients were enrolled and randomly assigned (1:1 ratio). The IG group exhibited similar PFS compared to the CG group [median PFS: 3.88 (95% CI: 1.72-6.03) months vs. 3.98 (95% CI: 1.06-6.90) months, P=0.546] and OS [median OS: 9.00 (95% CI: 5.31-12.70) months vs. 9.40 (95% CI: 5.20-13.59) months, P=0.310]. ORR (21.1% vs. 18.4%, P=0.773) and DCR (60.5% vs. 60.5%, P=1.000) were of not statistically different between the IG and CG groups. As for safety, the IG group exhibited less frequent hypoproteinemia (31.6% vs. 55.3%, P=0.037) and lactate dehydrogenase increased (18.4% vs. 44.7%, P=0.014), while no differences in other adverse events were observed between the two groups. Conclusions: Intermittent dose apatinib plus docetaxel was equally effective and more tolerable than continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC. Trial Registration: ClinicalTrials.gov NCT03334591.

Transarterial Chemoembolization Combined with Sorafenib in Patients with BCLC Stage C Hepatocellular Carcinoma.

PURPOSE: Transcatheter arterial chemoembolization (TACE) and targeted therapy have become common methods in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of TACE combined with sorafenib (TACE-sorafenib) and TACE alone for the treatment of Barcelona clinical stage C HCC. METHODS: The clinical data of 75 patients with BCLC stage C HCC who received TACE-sorafenib or TACE as the initial treatment were retrospectively analyzed. Tumor response, time to progression (TTP), overall survival (OS), and adverse events were compared at 1 month after surgery in the two groups. RESULTS: One month after treatment, the disease control rate in the TACE-sorafenib group was higher than that in the TACE group alone (82.76% and 57.50%, respectively, P = 0.018). The median values of TTP and OS in the TACE-sorafenib group were longer than those in the TACE group (TTP was 7.6 and 3.4 months, respectively, P = 0.002; OS was 13.6 and 6.3 months, respectively, P = 0.041). The cumulative survival time at 3 months, 6 months, and 1 year was higher in the TACE-sorafenib group than in the TACE group (83.5%, 71.2%, 45.7% vs 57.4%, 40.6%, 21.2%). Sorafenib-related side effects such as hypertension, hand-foot syndrome, and oral ulcers were more common than those in the TACE group alone (P<0.05). CONCLUSION: Compared with TACE treatment alone, TACE combined with sorafenib in BCLC-C stage HCC significantly improved disease control rate, TTP, and OS, and no significant increase in adverse reactions was observed.

Effectiveness and safety of low-dose apatinib in advanced gastric cancer: A real-world study.

Apatinib has been demonstrated to be effective and safe among patients with gastric cancer failing after at least two lines chemotherapy. This study aimed to evaluate its effectiveness and safety of low-dose apatinib for the treatment of gastric cancer in real-world practice. We performed a prospective, multicenter observation study in a real-world setting. Patients with advanced gastric cancer more than 18 years old were eligible and received low-dose apatinib (500 mg or 250mg per day) therapy. The median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Between September 2017 and April 2019, a total of 747 patients were enrolled. The mPFS was 5.56 months (95% CI 4.47-6.28), and mOS was 7.5 months (95% CI 6.74-8.88). Four patients achieved complete response, 47 achieved partial response, and 374 patients achieved stable disease. The ORR was 6.83% and DCR was 56.89%. In addition, multivariate Cox regression analysis indicated that hand-foot syndrome was one independent predictor for PFS and OS. The most common adverse events (AEs) at any grade were hypertension (36.55%), proteinuria (10.26%), hand-foot syndrome (33.53%), fatigue (24.9%), anemia (57.35%), leukopenia (44.49%), thrombocytopenia (34.21%), and neutropenia (53.33%). Grade 3-4 AEs with incidences of 5% or greater were anemia (13.97%), thrombocytopenia (7.14%), and neutropenia (6.67%). No treatment-related death was observed during the treatment of apatinib. The prospective study suggested that low-dose apatinib was an effective regimen for the treatment of advanced gastric cancer with tolerable or controlled toxicity in real world. Trial registration: NCT03333967.

High Expression of Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) in Esophageal Squamous Cell Carcinoma and its Clinical Prognostic Significance.

BACKGROUND Recently, targeted therapy for malignant tumors has developed rapidly, but there is still no effective targeted therapy for advanced esophageal squamous cell carcinoma (ESCC). Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a key enzyme involved in folate metabolism and is closely related to the proliferation in many cancers. However, few studies have explored the expression of MTHFD2 in ESCC and its prognostic significance. MATERIAL AND METHODS The expressions of MTHFD2, ki67, and p53 in ESCC tissues were detected by immunohistochemistry. Further, MTHFD2 expression level in ESCC and its correlations with patients' clinicopathological characteristics and survival prognosis were investigated. RESULTS The enhanced expression of MTHFD2 was observed in ESCC specimens compared with adjacent normal tissue. The increased expression of MTHFD2 was closely related to pathological grading (P=0.020) and tumor TNM stage (P=0.019). In addition, patients with high expression of MTHFD2 had worse survival than those with low MTHFD2 expression (P<0.05). High expression of MTHFD2 in ESCC tissues was often associated with high expression of ki67 and p53 (P<0.05). CONCLUSIONS MTHFD2 had significantly enhanced expression in ESCC tissues and was associated with pathological grading and TNM stage. Taken together, high expression of MTHFD2 was an independent unfavorable prognostic parameter for overall survival (OS) of ESCC patients, suggesting that MTHFD2 might be a potential therapeutic target for ESCC in the future.

Clinical research of individualized therapy in advanced esophageal cancer based on the ERCC1 C8092A genotype.

The present study aimed to explore the role and clinical value of the detection of Excision repair cross-complementing 1(ERCC1) C8092A polymorphisms in individualized therapy of patients with advanced esophageal cancer. A total of 127 patients with advanced esophageal cancer were enrolled between January 2010 and January 2014 in Anhui Provincial Hospital. Patients were randomly assigned in a 1:2 ratio to a standard treatment group or an individualized treatment group, respectively, prior to ERCC1 C8092A assessment. Patients in the standard treatment group were treated with paclitaxel and cisplatin. The DNA was obtained from the peripheral blood of individualized treatment patients, amplified by PCR and sequenced to determine the ERCC1 C8092A polymorphism prior to the administration of chemotherapies. Patients with the ERCC1 C8092A genotype of A/A or A/C received paclitaxel and cisplatin, and those with the genotype of C/C received paclitaxel and fluorouracil. The primary endpoint was response rate (RR). The secondary endpoints included toxicity of chemotherapy, progression-free survival (PFS) and overall survival (OS) times. Differences between the groups were evaluated by χ2 test. Differences in survival were analyzed by Kaplan-Meier survival curves. The survival rate was analyzed by log-rank test. Follow-up data was obtained until December 2015. The RR was obtained for 15 patients (34.8%) in the standard treatment group and 45 patients (53.6%) in the individualized treatment group (χ2=3.095; P=0.046). For adverse events, nausea and vomiting and anemia were significantly decreased in the individualized treatment group compared with the standard treatment group (P=0.001 and P=0.004, respectively). The median progression free survival time was 4.4 months [95% confidence interval (CI)3.8-5.0 months] in the standard treatment group and 6.6 months (95% CI, 5.8-7.4 months) in the individualized treatment group (P=0.018). The median overall survival time was 11.4 months (95% CI, 10.1-12.7 months) in the standard treatment group and 14.2 months (95% CI, 13.2-15.2 months) in the individualized treatment group (P=0.008). The RR, toxicity of chemotherapy, PFS and OS were significantly improved in the individualized treatment group compared with the standard treatment group. Detection of ERCC1 gene polymorphisms maybe performed for patients with advanced esophageal cancer to improve individualized therapy, which requires additional study.

Association between periostin and epithelial-mesenchymal transition in esophageal squamous cell carcinoma and its clinical significance.

The present study aimed to investigate the association between periostin (POSTN), epithelial cadherin (E-cad) and vimentin (Vim) expression levels in esophageal squamous cell carcinoma (ESCC) tissues, and its clinicopathological significance. A total of 58 patients with esophageal cancer were enrolled. Immunohistochemistry was performed to quantify the expression levels of POSTN, E-cad and Vim. E-cad expression was reduced in ESCC tissue, which was associated with severe tumor node metastasis (TNM) stage (P<0.001), lymphatic metastasis (P<0.001) and vascular invasion (P=0.026). Conversely, Vim expression was found to be increased in ESCC tissues, and had associations with TNM stage (P=0.039) and lymphatic metastasis (P=0.039). POSTN overexpression observed in ESCC cells was associated with attenuation of E-cad expression (P<0.001) and elevated expression levels of Vim (P<0.001). Additionally, significant correlations between the overexpression of POSTN in ESCC cells and clinicopathological variables including TNM staging (P=0.009), degree of differentiation (P<0.001), lymphatic metastasis (P=0.009) and vascular invasion (P=0.002) were verified. Multivariate analysis revealed that overexpression of POSTN in ESCC cancer cells is able to predict the poor prognosis of patients independently of overall survival (P=0.022) and disease free survival (P=0.019). The preliminary findings of the present study demonstrate that POSTN is involved in the epithelial-mesenchymal transition of ESCC cells, and may therefore be a predictive factor for tumor invasion and metastasis, as well as an indicator of poor prognosis for patients with ESCC.

Expression and significance of GRHL2 in esophageal cancer.

Esophageal cancer (EC) is one of the most common causes of cancer-related mortality in the world. Although much effort has been made to improve the 5-year survival rate of patients with EC, it still remains low due to diagnosis at an advanced stage, aggressive local invasion, early metastasis, and resistance to chemotherapy. Although grainyhead-like 2 (GRHL2) has attracted interest since it has been recently identified as a novel suppressor of the epithelial-mesenchymal transition, clinical values of GRHL2 and its relationship with the metastasis-related factors, such as hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), remain unclear. In order to investigate the expression of GRHL2, HIF-1α, and VEGF, and their correlation with angiogenesis in EC, 63 patients with EC were examined. The expression of GRHL2, HIF-1α, and VEGF in tumor tissues was higher than that in adjacent tissues and was associated with tumor differentiation. GRHL2 expression was significantly correlated with lymph node metastasis and invasion depth, whereas VEGF expression was associated with tumor (TNM) stage. A significant correlation was found between the expression of GRHL2 and HIF-1α. The patients expressing low GRHL2 and high HIF-1α showed significant reduction in both overall survival rate and disease-free survival rate. The results demonstrated that abnormal expression of GRHL2 is common in EC, and low expression of GRHL2 accompanied by a high expression of HIF-1α indicates poor prognosis.

Relationship between Helicobacter pylori infection and vomiting induced by gastrointestinal cancer chemotherapy.

BACKGROUND: Nausea and vomiting are the most common adverse reactions to chemotherapy. AIM: To discuss the relationship between Helicobacter pylori and chemotherapy-induced nausea and vomiting (CINV). METHODS: A total of 112 patients with malignant tumours of the gastrointestinal tract was selected. Based on the 14C-urea breath test results, the patients were divided into H. pylori-positive (n = 59) and H. pylori-negative (n = 53) groups. Both groups received prophylactic antiemetic treatment during chemotherapy. The incidence of nausea and vomiting and their effects on the patients' life functions was recorded using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemetic Tool (MAT) and the Functional Living Index Emesis (FLIE) from 0-120 h after chemotherapy. Records of the H. pylori-positive and H. pylori-negative groups were compared. RESULTS: The rates of nausea and vomiting remission were higher in the H. pylori -negative group than in the H. pylori -positive group. The proportions of no effect in daily life (NIDL) patients in the nausea and vomiting section were 73.4 and 75.5% in the H. pylori -negative group respectively. There was a higher proportion of NIDL patients in the H. pylori -negative group than in the H. pylori -positive group (P < 0.001, P = 0.046). A multivariate unconditional logistic regression analysis was performed, and the results showed that H. pylori infection was a factor affecting the nausea scores on the FLIE (odds ratio = 0.757, 95% confidence interval 0.597-0.960, P = 0.021). CONCLUSION: H. pylori infection in patients with cancer may be a factor that increases CINV.

Coexpression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance.

BACKGROUND: Both periostin (PN) and epidermal growth factor receptor (EGFR) can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC) still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. PATIENTS AND METHODS: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ (2) or Kruskal-Wallis method. Spearman's rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan-Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS) and overall survival (OS). RESULTS: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044), differentiation grade (P=0.003), venous invasion (P=0.010), invasion depth (P=0.007), lymphatic metastasis (P=0.000), and tumor stage (P=0.000). The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000), invasion depth (P=0.022), and tumor stage (P=0.000). Kaplan-Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000) and DFS (P=0.000), which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS in the ESCC patients (P<0.05). Moreover, the risk of death for the ESCC patients with low expression of two biomarkers and high expression of single biomarker was 0.243 times (P=0.000) and 0.503 times (P=0.030), respectively, than that for patients with high expression of two biomarkers. CONCLUSION: PN and EGFR are related to miscellaneous clinicopathologic characteristics. Coexpression of PN and EGFR is more closely to be of predictive value on ESCC development and progression, which may offer a novel and potential target strategy for ESCC treatment in the future.

Antitumor and antimetastatic effects of pemetrexed-loaded targeted nanoparticles in B16 bearing mice.

Using nanoparticle delivery for anticancer therapy is a potential new drug modality. We developed a novel gelatinase-stimuli nanoparticle. In this study, we studied the antitumor and antimetastasis effect of pemetrexed-loaded targeted nanoparticles and evaluated the correlation between E-cadherin expression and lung metastasis in subcutaneous xenograft model. Compared with free pemetrexed, pemetrexed-loaded targeted nanoparticles exhibited the best antitumor and antimetastasis efficacy among the four therapeutic groups. The study also indicated that there was an inverse correlation between lung metastasis and E-cadherin expression. These results showed pemetrexed-loaded targeted nanoparticles may be a potent drug for tumor therapy and our preclinical data could provide new direction for clinical therapy of malignant melanoma.

Clinical features and prognosis-associated factors of non-small cell lung cancer exhibiting symptoms of bone metastasis at the time of diagnosis.

The present study aimed to analyze the clinical characteristics and prognosis-related factors of non-small cell lung cancer (NSCLC) patients with bone metastases at the time of diagnosis. A total of 46 NSCLC patients with skeletal metastases at the time of diagnosis from Anhui Provincial Hospital and Anhui Provincial Cancer Hospital Affiliated to Anhui Medical University (Hefei, China) between February 2010 and February 2012 were investigated retrospectively. The median age was 58 years, with a range of 40-80 years, the ratio of males and females was 2:1, and adenocarcinoma and squamous cell carcinoma accounted for 71.7 and 28.3% of cases, respectively. Furthermore, 84.8% of patients exhibited multiple skeletal metastases at more than two sites and 54.3% of patients experienced skeletal-related events at the time of diagnosis. The median overall survival (OS) time of the patients was 237 days, and Kaplan-Meier analysis demonstrated that patients with adenocarcinoma (P=0.002), single bone metastases (P=0.023), an Eastern Cooperative Oncology Group performance status of 0-1 (P<0.001) or positive expression of estrogen receptor (ER)-ß (P=0.039) exhibited significantly longer survival times. Furthermore, multivariate analysis identified the following independent predictors of OS: Tumor subtype (P=0.022), the number of bone metastases (P=0.016) and an ER-ß-positive tumor (P=0.035). In the cohort of NSCLC patients with bone metastases at the time of diagnosis, adenocarcinoma and multiple skeletal metastases were most common.

MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box P4 (FOXP4).

MicroRNAs (miRNAs) are a class of small, non-coding RNAs, which have demonstrated to important gene regulators, and have critical roles in diverse biological processes including cancer cell proliferation. Previous studies suggested microRNA-338-3p (miR-338-3p) was down-regulated and play tumor suppressor roles in gastric cancer, colorectal carcinoma and lung cancer. However, the role of miR-338-3p in hepatocellular carcinoma (HCC) is still unclear. In this study, we analyzed the expression of miR-338-3p in HCC tissues and HCC cell lines. We find that miR-338-3p was downregulated in HCC tissues and cell lines. Then functional studies demonstrate ectopic miR-338-3p expression significantly suppressed the in vitro proliferation and colony formation of HCC cells and cause to cell cycle arrest. Using bio-informatic method and report assay we identified a novel miR-338-3p target, FOXP4 in HCC cells. Furthermore, knockdown of FOXP4 have the similar effects in HCC corrected with miR-338-3p. These findings suggest that miR-338-3p regulates survival of HCC cells partially through the downregulation of FOXP4. Therefore, targeting with the miR-338-3p/FOXP4 axis might serve as a novel therapeutic application to treat HCC patients.

Overexpression of AGGF1 is correlated with angiogenesis and poor prognosis of hepatocellular carcinoma.

Angiogenic factor with G-patch and FHA domains 1 (AGGF1) is a factor implicating in vascular differentiation and angiogenesis. Several lines of evidence indicate that aberrant expression of AGGF1 is associated with tumor initiation and progression. The aim of this study was to investigate the expression and prognostic value of AGGF1 in hepatocellular carcinoma (HCC), as well as its relationship with clinicopathological factors and tumor angiogenesis. Immunohistochemistry was performed to evaluate the expression of AGGF1 in HCC and paracarcinomatous tissues collected from 70 patients. Vascular endothelial growth factor (VEGF) and CD34 expression levels were examined in the 70 HCC tissues. Prognostic significance of tumoral AGGF1 expression was determined. Notably, AGGF1 expression was significantly higher in HCC than in surrounding non-tumor tissues (65.7 vs. 25.7 %; P < 0.001). AGGF1 expression was significantly correlated with tumoral VEGF expression and CD34-positive microvessel density. Moreover, AGGF1 expression was significantly associated with tumor size, tumor capsule, vascular invasion, Edmondson grade, alpha-fetoprotein level, and TNM stage. Kaplan-Meier survival analysis showed that high AGGF1 was correlated with reduced overall survival (OS) rate (P = 0.001) and disease-free survival (DFS) rate (P < 0.001). Multivariate analysis identified AGGF1 as an independent poor prognostic factor of OS and DFS in HCC patients (P = 0.043 and P = 0.010, respectively). Taken together, increased AGGF1 expression is associated with tumor angiogenesis and serves as an independent unfavorable prognostic factor for OS and DFS in HCC. AGGF1 may represent a potential therapeutic target for HCC.

miR-26a promoted by interferon-alpha inhibits hepatocellular carcinoma proliferation and migration by blocking EZH2.

BACKGROUNDS: Interferon (IFN)-α has been used to treat hepatocellular carcinoma (HCC). Here, we report that the IFN-α-induced microRNA-26a (miR-26a) can inhibit HCC proliferation and invasion by suppressing enhancer of zeste homologue 2 (EZH2) expression in tumor cells. MATERIALS AND METHODS: First, the miR-26a transcription level was quantified by real-time quantitative PCR in the HCC specimens from IFN-α-treated HCC patients. Next, we transfected HepG2 cells with miR-26a mimics and miR control, and then we investigated the influence of miR-26a mimic transfection on HepG2 cell proliferation and invasion. RESULTS: It was shown that there was increased miR-26a accompanied with downregulated EZH2 expression in the HCC specimens, and EZH2 mRNA levels were inversely correlated with miR-26a expression. There was a dose-response correlation between the IFN-α dosage and EZH2 expression. In addition, the miR-26a mimic transfection decreased the EZH2 expression level significantly in the transfected HepG2 cells and inhibited HepG2 cell proliferation and invasion effectively. CONCLUSION: Our results indicate that miR-26a exerts growth inhibition in HCC and that its inhibitory effect is mediated briefly by blocking EZH2 expression.

Hypoxia-inducible factor 1α in breast cancer prognosis.

BACKGROUND: Recent studies have assessed the relationship between hypoxia-inducible factor 1α (HIF-1α) expression and prognosis in breast cancer patients with inconsistent conclusions. To comprehensively and quantitatively summarize the evidence on the survival of patients with breast cancer, a meta-analysis was performed. METHODS: Systematic literature searching was applied to the databases of PubMed, Embase and Web of science until April 1, 2013. Pooled HR with 95% CI was used to evaluate the association between HIF-1α expression and survival in breast cancer patients. RESULTS: Fourteen papers including 2933 patients were subjected to the final analysis. Of these, 7 provided data on overall survival (OS), 8 on disease-free survival (DFS), 3 on distant metastasis-free survival (DMFS) and 3 on relapse-free survival (RFS). We observed that high expression of HIF-1α in breast cancer patients was an indicator of poor prognosis on OS (HR = 1.46, 95% CI: 1.12-1.92, P = 0.006), DFS (HR = 1.91, 95% CI: 1.43-2.57, P<0.001), DMFS (HR=2.17 95% CI: 1.16-4.05, P=0.015) and RFS (HR=1.33 95% CI: 1.09-1.61, P=0.005). Significant heterogeneity was observed in the analyses of OS and DFS. Subgroup analyses by the cut-off value and antibody for IHC were conducted. CONCLUSION: High expression of HIF-1α indicated a poor prognosis for patients with breast cancer.

Overexpression of periostin is significantly correlated to the tumor angiogenesis and poor prognosis in patients with esophageal squamous cell carcinoma.

Recent studies have found that periostin (PN), as a kind of secreted glycoprotein, is closely related to the metastatic potential and prognosis of many kinds of tumors. This study aimed to examine the expression of PN in patients with esophageal squamous cell carcinoma (ESCC) and explore the relationship of PN expression with clinicopathologic factors, tumor angiogenesis and prognosis. The results showed that increased PN protein expression was prevalent in ESCC and was significantly associated with lymphatic metastasis (P=0.008), tumor differentiation (P=0.04), venous invasion (P=0.014) and TNM stage (P=0.001). Additionally, expression of PN was found to be an independent prognostic factor in ESCC patients. High expression of PN protein is closely correlated to the tumor progression and angiogenesis and poor survival of ESCC. Taken together, PN is a promising biomarker to identify individuals with poor prognostic potential and concludes the possibility of its use as a prognostic marker in patients with ESCC.

A phase II study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma.

AIM: To evaluate the efficacy and safety of paclitaxel-nedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma (ESCC). METHODS: A two-center, open-label, single-arm phase II study was designed. Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Patients received 175 mg/m² of paclitaxel over a 3 h infusion on 1 d, followed by nedaplatin 80 mg/m² in a 1 h infusion on 2 d every 3 wk until the documented disease progression, unacceptable toxicity or patient's refusal. RESULTS: Of the 36 patients assessable for efficacy, there were 2 patients (5.1%) with complete response and 16 patients (41.0%) with partial response, giving an overall response rate of 46.1%. The median progression-free survival and median overall survival for all patients were 7.1 mo (95%CI: 4.6-9.7) and 12.4 mo (95%CI: 9.5-15.3), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (15.4%), nausea (10.3%), anemia (7.7%), thrombocytopenia (5.1%), vomiting (5.1%) and neutropenia fever (2.6%). CONCLUSION: The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.

Correlation between the CD4+CD25high regulatory T cells and the outcome of chemotherapy in advanced esophageal carcinoma.

BACKGROUND/AIMS: In patients with esophageal carcinoma, local immune suppression and the expression of soluble immunosuppressive factors have been observed. We aimed to investigate the correlation between the level of CD4+CD25high regulatory T (Treg) cell and the outcome of chemotherapy in advanced esophageal carcinoma. METHODOLOGY: Forty-eight cases of advanced esophageal carcinoma patients were enrolled from June 2006 to December 2008. CD3+CD8+ T cell, CD3+CD4 T cell, CD4+CD25+ Treg cell and NK cell were determined before and after chemotherapy. After two cycles of chemotherapy, its effect was evaluated and the survival time was followed-up. RESULTS: Significant downregulation of CD4+CD25high Treg cell was noted in the advanced esophageal carcinoma patients after chemotherapy (p<0.05). However, there were no obvious differences in the CD3+CD8+ T cell, CD3+CD4+ T cell and NK cell before and after chemotherapy (p>0.05). Log-rank test showed age and the decrease of CD4+CD25high Treg cell after chemotherapy correlated with the median survival time (p<0.05). The COX multivariate analysis also suggested that the decrease of CD4+CD25high Treg cell after chemotherapy was an independent prognostic factor (p<0.05). CONCLUSIONS: Our results suggest that the downregulation of CD4+CD25high Treg cell after chemotherapy may be a predictor for the outcome of chemotherapy in advanced esophageal carcinoma patients.

Association of TNF-α-308 and -238 polymorphisms with risk of cervical cancer: a meta-analysis.

Published data on the associations between tumor necrosis factor-alpha (TNF-α) promoter -308G>A and -238G>A polymorphisms and cervical cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Data were collected from MEDLINE and PubMed databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a fixed/random effect model. 13 separate studies including 3294 cases and 3468 controls were involved in the meta-analysis. We found no association between TNF-α-308G>A polymorphism and cervical cancer in overall population. In subgroup analysis, significantly elevated risks were found in Caucasian population (A vs. G: OR=1.43, 95% CI=1.00- 2.03; AA vs. GG: OR=2.09, 95% CI=1.34-3.25; Recessive model: OR=2.09, 95% CI=1.35-3.25) and African population (GA vs. GG: OR=1.53, 95% CI=1.02-2.30). An association of TNF-α-238G>A polymorphism with cervical cancer was found (A vs. G: OR=0.61, 95% CI=0.47-0.78; GA vs. GG: OR=0.59, 95% CI=0.45-0.77; Dominant model: OR=0.59, 95% CI=0.46-0.77). When stratified by ethnicity, similar association was observed in Caucasian population (A vs. G: OR=0.62, 95% CI=0.46-0.84; GA vs. GG: OR=0.59, 95% CI=0.43-0.82; Dominant model: OR=0.60, 95% CI=0.44-0.83). In summary, this meta-analysis suggests that TNF-α-238A allele significantly decreased the cervical cancer risk, and the TNF-α-308G>A polymorphism is associated with the susceptibility to cervical cancer in Caucasian and African population.

Genetic polymorphisms of ERCC1 and their effects on the efficacy of cisplatin-based chemotherapy in advanced esophageal carcinoma.

The aim of this study was to investigate the relationship between the ERCC1-C8092A, ERCC1-C19007T and GSTP1-A105G genetic polymorphisms and the curative effect of cisplatin-based chemotherapy in advanced esophageal carcinoma. A total of 256 pathologically confirmed advanced esophageal carcinoma patients were given regimens of cisplatin and 5-fluorouracil. Clinical evaluations were obtained from 241 patients who completed the therapy. The remission rate of patients with ERCC1-C8092A, A/C or A/A was higher compared to that of patients with C/C (51.75 vs. 29.59%, P<0.01). Progression-free survival of patients with ERCC1-C8092A, A/C or A/A was longer compared to that of patients with C/C (7.5 months vs. 4.5 months, P<0.0001). The C19007T and GSTP1-A105G genetic polymorphisms were not positively correlated with remission rates and progression-free survival of patients. In conclusion, the ERCC1-C8092A genetic polymorphism may be correlated with the efficacy of cisplatin-based chemotherapy in cases of advanced esophageal carcinoma. Further studies with a larger sample size are needed for tailored chemotherapy treatment of advanced esophageal carcinoma.