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Abstract Background Tumor length is an important prognostic factor for many carcinomas, but its role in esophageal cancer remained undetermined. The aim of this study was to investigate the effect of tumor length on survival for patients with confined tumors (grade pT1-2) without lymph-node metastases in esophageal squamous cell carcinoma. Methods We enrolled 201 patients with esophageal squamous cell carcinoma (SCC) who had undergone surgical resection and been confirmed as pT1-2N0M0. The relationship of tumor length with overall survival was assessed and compared with other factors detailed in the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system published in 2009. Results The overall survival (OS) rates at 1, 3, and 5 years were 93.0%, 83.7%, and 69.2%, respectively. The tumor length adversely affected OS, with the 5-year rate being 93.5%, 82.0%, 68.6%, 67.9%, 55.3% and 41.1%, respectively for tumor lengths of less than 10 mm, 10 to 20 mm, 20 to 30 mm, 30 to 40 mm, 40 to 50 mm, and greater than 50 mm (P< 0.001). Multivariate analyses showed that the pathologic T classification and grade of tumor was significantly associated with OS. Tumor length of 30 mm or more remained an independent prognostic factor (P = 0.04), as did the other current TNM factors. Conclusion Tumor length appears to affect the OS of patients with early-stage esophageal squamous cell carcinoma. It may provide additional prognostic information for the current TNM staging system.

Breast cancer is one of the most common types of carcinoma in humans. The aim of the present study was to identify the role of Notch 1 in the proliferation and invasion of human breast cancer cells. Firstly, the levels of Notch 1 were determined by western blot analysis in breast cancer cell lines, and the results revealed that the expression levels of Notch 1 were markedly higher in MDA-MB-231 and MCF-7 cells, and lower in MCF-10A cells, compared with human mammary epithelial cells. An MTT assay was used to determine the viability of breast cancer cells. The optical density (OD)490 values were significantly decreased in Notch 1 short hairpin (sh)RNA-transfected MCF-7 and MDA-MB-231 cells, compared with the OD490 values in the negative control shRNA-transfected cells. The MCF-7 cells and MDA-MB-231 cells were also treated with increasing concentrations of MRK003, a Notch 1 inhibitor, for 24, 48 and 72 h, respectively. The inhibition rate was gradually increased in the MRK003-treated cells in a time- and dose-dependent manner. The invasive ability of the cells was determined using a Transwell migration assay. The migration ability was significantly decreased in the Notch 1-transfected MCF-7 cells and MDA-MB-231 cells. The molecular mechanism was examined, and the knockdown of Notch 1 significantly decreased the expression levels of ß-catenin, matrix metalloproteinase (MMP)-2 and MMP-9, and was also correlated with the downregulation of ß-catenin in the nucleus. In conclusion, Notch 1 was key in the progression of breast cancer, and knocking down the expression of Notch 1 significantly suppressed the proliferation and invasion of breast cancer cells. This provides novel clues for cancer therapy in human breast cancer. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). The efficacy and roles of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in protection neurocognitive function (NCF) and improvement quality of life (QOL) were investigated and compared with WBRT alone in the treatment of NSCLC patients with BM.Methods: A total of 238 NSCLC patients with BM were reviewed and categorized into WBRT plus TMZ (RCT) arm and WBRT alone (RT), respectively. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. NCF was assessed by using revised Hopkins Verbal Learning Test (HVLT-R), Controlled Oral Word Association (COWA) test and Trail-making Test (TMT). QOL was assessed by the Functional Assessment of Cancer Treatment-Lung (FACT-L) Chinese version 4.0 questionnaire.Results: The average intracranial objective response (ORR) and disease control rate (DCR) for all the patients were 26.9 and 95.8%, respectively. The intracranial ORR and DCR for RCT and RT arm were 34.9% vs. 20.2% (p = 0.01) and 98.4% vs. 92.7% (p = 0.03), respectively. The median intracranial progression-free survival (PFS) and overall survival (OS) of NSCLC patients with BM were 5.2 and 7.3 months, respectively. The median PFS of RCT arm was significantly longer than that of RT arm (5.9 vs. 4.9 months, p = 0.002). The median OS of the RCT arm was also slightly longer than that of the RT arm (8.5 vs. 5.9 months), but without statistical significance (p = 0.11). Multivariate analysis indicated that TMZ was a significant factor for PFS. Statistically significant differences on NCF and QOL were observed between CRT and RT arms at 5 months. RCT showed a trend of toxicities increase compared with RT, however, the toxicities were tolerable and manageable.Conclusions: Adding TMZ to WBRT in the treatment of NSCLC patients with BM could improve the intracranial ORR, DCR, and median PFS compared with WBRT alone. Although no remarkable difference on median OS was found, adding TMZ could prevent NCF and QOL from worsening. The side effects increased by adding TMZ, but the difference was not statistical significance and toxicities were well tolerated. [ABSTRACT FROM AUTHOR]

Background and objective As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Methods Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. Results The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001). Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity. Conclusion Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable. [ABSTRACT FROM AUTHOR]

Background and Objective: Epidermal growth factor receptor (EGFR)-activating mutation predicts excellent response to EGFR tyrosine kinase inhibitors (TKIs). However, lung cancer patients are often with unknown EGFR mutation status because there are little tumor specimen to determine. TKIs induce tumor cell apoptosis which associates with several apoptosis-related genes. To explore the association between GNAS1 T393C polymorphism and therapeutic efficacy of TKI in pretreated advanced non-small cell lung cancer (NCSLC) with unknown EGFR mutation status., Methods: A total of 116 patients were recruited for the study from Zhejiang Cancer Hospital, all of whom were treated with gefitinib or erlotinib after failure to prior chemotherapy. We detected the genotype of peripheral blood lymphocytes of patients with GNAS1 T393C polymorphism through polymerase chain reaction (PCR). Statistical analysis was performed by SPSS version 18.0., Results: The overall response rate was 29.3%. No significant associations were found among GNAS1 T393C polymorphism and the objective response rate. The disease control rate of patients with GNAS1 T393C CC genotype was lower than that of patients with variant genotype (TT or CT) (46.2% vs 73.8%, P=0.039). Univariate analysis identified gender, smoking history, histology and GNAS1 T393C polymorphism as predictive marker of PFS (P=0.04, P<0.001, P<0.001 and P=0.005). Multivariate analysis of factors, including smoking history, performance status score, histology, GNAS1 T393C polymorphism demonstrated that GNAS1 T393C polymorphism was correlated independently with PFS (P=0.007)., Conclusions: Our data suggest the role of GNAS1 T393C CC genotype as a poor predictive marker both of DCR and PFS in advanced NSCLC patients treated with tyrosine kinase inhibitor.

Background: The preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients., Methods: The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model., Results: The objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity., Conclusions: Icotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Background and Objective: BIM gene is a member of the BCL-2 family, is involved in cell death. The aim of this study is to explore the relationship between BIM gene polymorphism and therapeutic efficacy in the retreatment advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitor (EGFR-TKI)., Methods: In the study, there were 123 patients who were diagnosed with advanced NSCLC in Zhejiang Province Cancer Hospital between January 2009 to October 2012, all of who were received gefitinib and erlotinib therapy after failure to chemotherapy. We detected the genotype of peripheral blood leukocytes of patients with BIM gene polymorphism though polymerase chain reaction (PCR). Statistical analysis was performed by SPSS version 13.0., Results: On the disease control rates, BIM gene with no polymorphism type was slightly better trend than polymorphism types in disease control rate DCR (75.5% vs 57.1%, χ²=2.931, P=0.087). Univariate analysis the median PFS, women were longer than men (6.9 months vs 4.5 months, χ² =7.077, P=0.008). Non-smokers were longer than smokers (8.0 months vs 2.5 months, χ² =15.277, P<0.001). Adenocarcinoma were longer than others pathological type (7.0 months vs 2.0 months, χ² =14.978, P<0.001). The median PFS in BIM gene with no polymorphism type were longer than with polymorphism type (6.0 months vs 3.5 months, χ²=7.035, P=0.008). Multi-factor analysis showed that smoking, pathological type, the BIM gene polymorphism were the independent prognostic factors for PFS., Conclusions: The patients with the BIM gene no polymorphism have longer the median progression-free time than the polymorphism types in retreatment advanced non-small cell lung cancer patients with tyrosine kinase inhibitor.

Background and Objective: As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital., Methods: Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests., Results: The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001). Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity., Conclusions: Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

Background and Objective: The appearance of highly effective and low toxic drugs enables an increasing number of advanced non-small cell lung cancer (NSCLC) patients to receive third-line therapy. No other standard choice for third-line therapy aside from erlotinib is possible. This study respectively explores the efficacy and safety of single chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and doublet chemotherapy in advanced NSCLC third-line treatment., Methods: This study included 115 NSCLC patients in the stage IIIb or IV who were retrospectively reviewed to investigate the differences of survival time between different treatments. Univariate and multivariate analyses were conducted based on the Kaplan-Meier method and Cox proportional-hazards model., Results: The median progression free survival (PFS) values in the single agent, EGFR-TKIs and doublet groups were 2.30, 3.17 and 2.37 months, respectively (P=0.045). The median overall survival from the initiation of the third-line treatment were 8.00, 10.40 and 7.87 months in the three groups (P=0.110). The rates of stage III-IV toxicities were 33.3%, 18.2% and 68.8% (P<0.001), respectively. After the third-line treatment, the PFS was significantly increased in patients with a performance status (PS) of 0 to 1 (P<0.001), and the survival time was prolonged in patients who never smoke (P=0.011), have good PS (P<0.001), and have disease control after both first- and second-line treatments (P=0.044) using multivariate analysis., Conclusion: Advanced NSCLC patients who never smoke, have good PS scores, and have good disease control from the first- and second-line therapies could benefit more in third-line treatment. EGFR-TKIs therapy showed increased PFS compared with single and doublet agents.