A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Clinical utility and effectiveness of a training programme in the application of a new classification of narrow-band imaging for vocal cord leukoplakia: A multicentre study.

OBJECTIVE: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. DESIGN: Prospective multicentre study. SETTING: Tertiary hospitals. PARTICIPANTS: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. MAIN OUTCOME MEASURES: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. RESULTS: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. CONCLUSION: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

[Inhibitory effects of celecoxib combined with capecitabine on H22 hepatoma mice and its mechanism].

OBJECTIVE: To evaluate the inhibitory effect and its mechanism of celecoxib combined with capecitabine on the growth of implanted H22 hepatoma in mice. METHODS: Tumor model was established by hypodermical injection of H22 cells in BALB/c nude mice. Forty mice were equally randomly divided into 4 groups: control group, celecoxib group (receiving 100 mg/kg celecoxib), capecitabine group (receiving 755 mg/kg capecitabine), and combined treatment group (receiving 100 mg/kg of celecoxib and 755 mg/kg of capecitabine). From the third post-implantation day, each mouse was given relevant drug (or normal saline) by oral gavage. Fifteen days later, all mice were sacrificed and the tumor tissues were measured. The mRNA and protein levels of nuclear factor kappa-B (NF-ΚB) p65 and cyclooxygenase (COX)-2 in tumor tissues were detected by the quantitative polymerase chain reaction (qPCR)and Western blotting, respectively. RESULTS: The tumor inhibition rate was 30.2% in celecoxib group and 49.9% in capecitabine group, which was significantly lower than that (75.4%) in the combined treatment group (P<0.01,P<0.05, respectively). qPCR showed a significant decrease of the mRNA expression of COX-2 in celecoxib group and combined treatment group when compared with control group (P<0.001), but no significant change in NF-ΚB p65.Capecitabine had no significant effects on the mRNA expression of COX-2 and NF-ΚB p65. Western blotting showed that celecoxib and combined treatment significantly inhibited the protein expression of COX-2 and NF-ΚB p65(P<0.05), but not capecitabine. CONCLUSION: Celecoxib can enhance the antitumor effect of capecitabine by inhibiting the expressions of COX-2 and NF-ΚB p65 in mice bearing H22 implanted tumor.

Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression.

BACKGROUND AND AIM: Circulating miRNAs exist in serum and plasma and they can be used as a potential noninvasive molecular marker for colorectal cancer (CRC) diagnosis. The present study was to test the availability of direct amplification of miRNAs from plasma without RNA extraction, and to evaluate its clinical application value in CRC. METHODS: Plasma miR-21, miR-221 and miR-222 levels were determined in 103 CRC patients and 37 healthy normal controls by quantitative reverse transcription-polymerase chain reaction. Immunohistochemical staining for p53, carcinoembryonic antigen (CEA), estrogen receptor (ER) and progesterone receptor (PR) was carried out in the same CRC patient cohort. The correlation between miR-221 levels and protein levels of p53, CEA, ER and PR, clinicopathological features or overall survival was analyzed. RESULTS: A standard curve shows a good linearity between the log of sample input and C(T) values over three orders of magnitude of plasma miR-21, miR-221 and miR-222. ROC curve analysis reveals that the plasma levels of miR-221 is a potential biomarker for differentiating CRC patients from controls. Kaplan-Meier curve assessment shows that the elevated plasma miR-221 level is a significant prognostic factor for poor overall survival in CRC patients. The immunohistochemistry analysis demonstrates a significant correlation between plasma miR-221 level and p53 expression. CONCLUSIONS: The direct amplification of plasma miR-221 can be used as a potential noninvasive molecular marker for diagnosis and prognosis of CRC and is correlated with p53 expression.

The role of Skp2 in extranodal NK/T-cell lymphoma.

BACKGROUND AND OBJECTIVE: Expression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T cell lymphoma. METHODS: The clinicopathological data of 39 patients with extranodal NK/T cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin fixed, paraffin embedded tissue sections. RESULTS: Among the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83 135.34 months), the 1 and 2 year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1 and 2 year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P <0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T cell lymphoma. CONCLUSION: High expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T cell lymphoma.

Expression of activating transcription factor 7 is correlated with prognosis of colorectal cancer.

BACKGROUND: It is important to identify some tumor-related factors for early detection, treatment, and evaluation of prognosis in colorectal cancer (CRC). In our study, we investigated the clinical and prognostic role of activating transcription factor 7 (ATF7) in CRC. MATERIALS AND METHODS: Expression of ATF7 was detected with immunohistochemistry in 72 cases with complete follow-up data and post-operation tissue specimens. Correlation between ATF7 and other clinicopathological factors was calculated with Chi-square test and the impact of ATF7 on survival were analyzed with Log-rank test and Cox regression models. RESULTS: Among 72 cases, ATF7 expression was detected in 43 cases (59.7%) and 29 cases (40.3%) without ATF7 expression. The correlation between ATF7 expression and pathological stage was investigated (P = 0.041). The 5-year overall survival (OS) of with or without ATF7 expression was 79% versus 51% respectively (P < 0.001) and the 5-year progression free survival (PFS) was 74% versus 41% (P < 0.001). The media OS was 69 months versus 52 months (P = 0.002) and the media PFS was 65 months versus 42 months (P = 0.002). ATF7 expression and numbers of lymph nodes involvement were prognostic factors for OS according to univariated and multivariated analysis and for PFS it was ATF7 expression and lymph nodes involvement. CONCLUSION: It is negatively related between ATF7 expression and pathological stage and positive correlation with OS and PFS in CRC. ATF7 expression is a favorable factor for survival of patients with CRC.

Lectin from Agrocybe aegerita as a glycophenotype probe for evaluation of progression and survival in colorectal cancer.

BACKGROUND: Agrocybe aegerita Lectin (AAL) has been identified to have high affinity for sulfated and α2-3- linked sialic acid glycoconjugates, especially the sulfated and sialyl TF (Thomsen-Friedenreich) disaccharide. This study was conducted to investigate the clinicopathological and prognostic value of AAL in identifying aberrant glycosylation in colorectal cancer (CRC). MATERIALS AND METHODS: Glycoconjugate expression in 59 CRC tissues were detected using AAL-histochemistry. Clinicopathological associates of expression were analyzed with chi- square test or Fisher's exact test. Relationships between expression and the various clinicopathological parameters was estimated using Kaplan-Meier analysis and Cox regression models. RESULTS: AAL specific glycoconjugate expression was significantly higher in tumor than corresponding normal tissues (66.1% and 46.1%, respectively, p=0.037), correlating with depth of invasion (p=0.015) and TNM stage (p=0.024). Patients with lower expression levels had a significantly higher survival rate than those with higher expression (p=0.046 by log rank test and p=0.047 by Breslow test for overall survival; p=0.054 by log rank test and P=0.038 by Breslow test for progress free survival). A marginally significant association was found between AAL specific glycoconjugate expression and overall survival by univariate Cox regression analysis (p=0.059). CONCLUSIONS: Lower AAL specific glycoconjugate expression is a significant favorable prognostic factor for overall and progress free survival in CRC. This is the first report about the employment of AAL for histochemical analysis of cancer tissues. The binding characteristics of AAL means it has potential to become a powerful tool for the glycan investigation and clinical application.

Efficacy of gemcitabine combined with oxaliplatin, L-asparaginase and dexamethasone in patients with newly-diagnosed extranodal NK/T-cell lymphoma.

There is currently no standard first-line regimen for patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). In this study, we investigated the efficacy and toxicity of gemcitabine (GEM) combined with oxaliplatin (L-OHP), L-asparaginase (L-ASP) and dexamethasone (DXM) (GOLD regimen) as a systemic treatment scheme for newly-diagnosed ENKTCL cases. A total of 55 patients were recruited at the Henan Province Cancer Hospital and the Cancer Center of Sun Yat-sen University between May, 2008 and August, 2012. The GOLD regimen included a 14-day treatment cycle with GEM (1,000 mg/m2) on day 1, L-OHP (100 mg/m2) on day 1, L-ASP (10,000 U/m2) on days 1-5 and DXM (20 mg b.i.d.) on days 1-4. The response rate, survival rate and treatment toxicity were analyzed. The overall response rate was 91% (48/55) with a complete response in 62% (34/55) and a partial response in 29% (15/55) of the patients. For all patients, the 1-, 2- and 3-year progression-free survival (PFS) rate was 86, 64 and 57% and the overall survival (OS) 91, 80 and 74%, respectively. The 1-year PFS in patients with stage I/II vs. those with III/IV disease was 87 vs. 66% (P<0.001) and the 1-year OS was 98 vs. 75%, respectively (P<0.001). No chemotherapy-related mortality or severe complications were recorded. In conclusion, the GOLD regimen was found to be highly effective and safe for the treatment of patients with newly-diagnosed ENKTCL.

Activating transcription factor 1 is a prognostic marker of colorectal cancer.

OBJECTIVE: Identifying cancer-related genes or proteins is critical in preventing and controlling colorectal cancer (CRC). This study was to investigate the clinicopathological and prognostic value of activating transcription factor 1 (ATF1) in CRC. METHODS: Protein expression of ATF1 was detected using immunohistochemistry in 66 CRC tissues. Clinicopathological association of ATF1 in CRC was analyzed with chi-square test or Fisher's exact test. The prognostic value of ATF1 in CRC is estimated using the Kaplan-Meier analysis and Cox regression models. RESULTS: The ATF1 protein expression was significantly lower in tumor tissues than corresponding normal tissues (51.5% and 71.1%, respectively, P = 0.038). No correlation was found between ATF1 expression and the investigated clinicopathological parameters, including gender, age, depth of invasion, lymph node status, metastasis, pathological stage, vascular tumoral emboli, peritumoral deposits, chemotherapy and original tumor site (all with P > 0.05). Patients with higher ATF1 expression levels have a significantly higher survival rate than that with lower expression (P = 0.026 for overall survival, P = 0.008 for progress free survival). Multivariate Cox regression model revealed that ATF1 expression and depth of invasion were the predictors of the overall survival (P = 0.008 and P = 0.028) and progress free survival (P = 0.002 and P = 0.005) in CRC. CONCLUSIONS: Higher ATF1 expression is a predictor of a favorable outcome for the overall survival and progress free survival in CRC.

p63 Expression is a prognostic factor in colorectal cancer.

p63 is highly expressed in some malignant tumors and is associated with tumorigenesis, invasion and metastasis. The aim of our study was to evaluate the clinical significance of p63 in colorectal cancer (CRC). p63 expression was detected by immunohistochemistry in 66 CRC patients. Correlations between p63 expression and clinicopathological factors, progression-free survival (PFS) and overall survival (OS) were analyzed. Among the 66 CRC cases, 31 cases (47%) exhibited a high score of p63 expression, while 35 cases (53%) were marked with a low score. The p63 level correlated with peritumoral deposits (p=0.021). The 5-year OS rates in the low p63 score and high p63 score groups were, respectively, 49% and 74% (p<0.001). The 5-year PFS rates in the low p63 score and high p63 score groups were, respectively, 44% and 71% (p<0.001). Univariate analysis revealed that p63 expression was correlated with OS and PFS. Multivariate analysis suggested that p63 expression was an independent prognostic factor for OS (p=0.035). In conclusion, p63 was negatively correlated with peritumoral deposits and positively associated with OS and PFS in CRC. The data suggest that p63 is a potential prognostic factor for CRC.

XRCC1 polymorphisms and risk of nasopharyngeal carcinoma: a meta-analysis.

OBJECTIVE: Previous studies on the association between X-ray repair cross-complementing protein 1 (XRCC1) polymorphisms and nasopharyngeal carcinoma (NPC) risk showed inconsistent results. The aim of this study was to evaluate the effects of XRCC1 variants on NPC risk. METHODS: A meta-analysis was performed with all eligible studies covering a total of 1,341 cases and 1,425 controls for the Arg194Trp polymorphism, 1,260 cases and 1,207 controls for the Arg280His polymorphism, and 1,644 cases and 1,678 controls for the Arg399Gln polymorphism. RESULTS: No associations was found between Arg194Trp and Arg280His polymorphisms with NPC risk under all contrast models (co-dominant, dominant, and recessive models). However a deleterious effect of the 399Gln genotype was observed under the co-dominant model (Gln/Gln versus Arg/Arg, OR = 1.30, 95% CI : 1.01-1.69, P = 0.04). Under the recessive model (Gln/Gln versus Arg/Arg+Arg/Gln), the P value was marginally significant (OR = 1.28, 95% CI : 1.00-1.65, P = 0.05). However, the effect of the 399Gln genotype on NPC became non-significant after excluding one study from the meta-analysis because of departure from Hardy-Weinberg equilibrium. CONCLUSIONS: No associations were found between Arg194Trp and Arg280His polymorphisms with NPC risk, whereas the Arg399Gln genotype was associated with increased risk.

Diagnostic and prognostic value of circulating miR-221 for extranodal natural killer/T-cell lymphoma.

Extra-nodal natural killer T-Cell (NK/T-cell) lymphoma is a progressive cancer with poor prognosis due to the lack of disease specific treatment. To develop specific therapeutic strategies, it is essential to identify tumor markers. Recent studies show that circulating microRNA (miRNA) may serve as diagnostic and/or prognostic markers for some diseases. To explore miRNAs as potential diagnostic and/or prognostic markers of NK/T-cell lymphoma, in our study, we compared circulating miR-221 levels in 79 patients and 37 normal subjects by real-time PCR amplification directly from plasma samples, and correlated patient's miR-221 levels with their clinic features and treatment outcomes. We observed a significant difference between the patient and control groups (p=0.038), and a correlation of plasma miR-221 level in patient with sex, as well as a reverse correlation with performance status and the overall survival after treatment. Univariate and multivariate analyses further revealed that plasma miR-221 level, age, B symptoms, LDH level and complete response after primary treatment all present prognostic values when judged by overall survival (OS). Together, our results show that it is feasible to perform direct amplification of plasma miRNAs without total RNA extraction, and plasma miR-221 may be a diagnostic and prognostic marker for NK/T-cell lymphoma.

[Effect of KRAS mutation on efficacy of Cetuximab combined with chemotherapy in advanced colorectal cancer patients].

OBJECTIVE: To explore the relationship between KRAS gene status and efficacy of Cetuximab (C225) combined with chemotherapy on advanced colorectal cancer in Chinese patients, and to evaluate the safety of C225. METHODS: From May 2006 to March 2009, 81 patients with advanced colorectal cancer received Cetuximab combined with chemotherapy were enrolled in this study. The rate of KRAS mutation and the relationship of KRAS with response rate (RR), progression-free survivor (PFS), overall survival (OS) and adverse reaction of C225 were analyzed retrospectively. RESULTS: All the 81 patients received C225 therapy, and the overall RR was 33.3%. The RR of initiate therapy was 57.1%; of the second line and over the third line therapy was 38.5% and 22.0% respectively. KRAS gene phenotype examination was performed in 44 patients whose tumor samples were available. KRAS mutation was found in 20 cases (45%). Out of 44 patients, 43 were evaluable for response. RR was 5% and 43.48% in KRAS mutation and wild KRAS patients respectively (P =0.002). The median PFS was 7.0 weeks and 18.6 weeks in mutational KRAS patients and wild KRAS patients, reaching statistical significance (P =0.003). The median OS was 15.2 months and 17.3 months in mutational KRAS patients and wild KRAS patients respectively without statistical significance (P =0.463). The common adverse reactions were leucopenia, nausea, vomiting and rash. All the adverse reactions were tolerated. The incidence of skin rash in patients with mutational KRAS and patients without KRAS mutation was 40% and 42% respectively, without statistical significance (P =0.91). CONCLUSION: C225 combined with chemotherapy is well-tolerated in Chinese patients with advanced colorectal cancer, and it can significantly prolong PFS of patients with wild KRAS as compared to patients with KRAS mutation.