Yoon Ho Ko

Nasal-type NK/T cell lymphoma: clinical features and treatment outcome.

Nasal-type NK/T cell lymphoma is an increasingly recognised disease entity of aggressive clinical behaviour. The objective of this study was to investigate clinical features and treatment outcomes in patients with nasal-type NK/T cell lymphoma. From January 1991 to December 2003, 26 patients diagnosed as nasal-type NK/T cell lymphoma were included in the analysis. One half of patients presented with poor performance status (ECOG ⩾2); 46% of patients were categorised as high intermediate or high-risk group according to IPI; and 46% of patients were diagnosed at advanced stage. The median survival for 26 patients with nasal-type NK/T cell lymphoma was 7.4 months (95% CI, 0.1, 16.9). The treatment outcome of primary anthracycline-based chemotherapy was poor: 60% CR rate in localised disease and 0% CR rate in advanced disease. After a median follow-up of 24.4 months (range 3.1–99.0) in patients with localised disease who had achieved a CR (range 29.6–165.7), three patients (50.0%) developed disease recurrence at 6.1, 21.8, and 52.1 months, respectively, and all patients presented with locoregional failure. The predictive factors for poor survival were of age greater than 60, advanced stage and poor performance in multivariate analysis. In conclusion, Nasal-type NK/T cell lymphomas showed a poor response to the conventional anthracycline-based chemotherapy, and thus an investigation for an innovative therapy is urgently needed to improve survival in these patients.

BRAF mutations in non-Hodgkin's lymphoma

Ras proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. BRAF, which encodes an RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers. The activating mutation of BRAF is known to play a role in tumour development. As there have been no data on the BRAF mutation in non-Hodgkins lymphoma (NHL), we analysed the genomic DNAs from 164 NHLs by polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) for the detection of somatic mutations of BRAF (exons 11 and 15). Overall, we detected BRAF mutations in four NHLs (2.4%). Whereas most BRAF mutations in human cancers involved V599 of BRAF, all of the four BRAF mutations in the NHLs involved other amino acids (one G468A, two G468R and one D593G). To our knowledge, this is the first report on BRAF mutation in NHL, and the data indicate that BRAF is occasionally mutated in NHL, and suggest that BRAF mutation may contribute to the tumour development in some NHLs.

Prognostic significance of autophagy-related protein expression in resected pancreatic ductal adenocarcinoma.

Objectives Autophagy is a critical intracellular pathway for the removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins to clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods The expression of 5 autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. Results Of the 73 patients, autophagy-related protein expression frequencies were 49.3% (36/73) for Atg5, 63.9% (46/72) for Ambra1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P = 0.059). Multivariate analysis revealed that beclin-1 overexpression and increases in the alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio of 5.365, P = 0.001 and hazard ratio of 5.270, P = 0.022, respectively). Conclusions The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.

Prognostic significance of CD44s expression in resected non-small cell lung cancer.

BackgroundCD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC).MethodsUsing immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82) and squamous cell carcinoma (SCC; n = 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically.ResultsHigh CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P < 0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P < 0.001), high-grade tumor differentiation (P = 0.046), and high CD44s expression (P = 0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015). No significant association was found between CD44s and clinical outcome (P = 0.311).ConclusionsHigh CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

IL‐6 is an independent risk factor for resistance to erythropoiesis‐stimulating agents in hemodialysis patients without iron deficiency

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis‐stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty‐eight patients receiving hemodialysis at a single institution were evaluated in a cross‐sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin‐6 (IL‐6) levels. Serum C‐reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL‐6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.

Effect of green tea extracts on oxaliplatin-induced peripheral neuropathy in rats

BackgroundA common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin.MethodsWe conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models.ResultsA total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4 mg/kg) with or without green tea (300 mg/kg orally once daily) was administered intraperitoneally twice per week for 6 weeks. At 4 and 6 weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6 weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group.ConclusionsGreen tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.

Absence of Autophagy-Related Proteins Expression Is Associated with Poor Prognosis in Patients with Colorectal Adenocarcinoma

Background/Aim. Autophagy, a cellular degradation process, has paradoxical roles in tumorigenesis and the progression of human cancers. The aim of this study was to investigate the expression levels of autophagy-related proteins in colorectal cancer (CRC) and to evaluate their prognostic significance. Methods. This study is a retrospective review of immunohistochemical and clinicopathological data. All specimens evaluated were obtained from 263 patients with colorectal cancer who had undergone surgery between November 1996 and August 2007. The primary outcomes measured were the expression levels of three autophagy-related proteins (ATG5, BECN1/Beclin 1, and Microtubule-associated protein 1 light chain 3B (LC3B)) by immunohistochemistry and its association in clinicopathological parameters and patient survival. Results. The autophagy-related protein expression frequencies were 65.1% (151/232) for ATG5, 71.3% (174/244) for BECN1, and 74.7% (186/249) for LC3B for the 263 patients. Correlation between the expression of autophagy-related proteins was significant for all protein pairs. Multivariate analysis showed that negative LC3B expression and absence of autophagy-related proteins expression were independently associated with poor prognosis. Conclusion. Absence of autophagy-related proteins expression is associated with poor clinical outcome in CRC, suggesting that these proteins have potential uses as novel prognostic markers.

Soluble Interleukin-6 Receptor is a Prognostic Marker for Relapse-Free Survival in Estrogen Receptor-Positive Breast Cancer

Considering the protumorigenic roles of interleukin-6 (IL-6) transsignaling, we assessed the serum levels of IL-6, soluble interleukin-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in 143 patients with breast cancer. Serum levels of IL-6 were elevated with advanced T and N stage. Serum levels of sIL-6R were lower in patients with estrogen receptor-positive cancer. The median values of IL-6 and sgp130 did not differ between patients with recurrence and those without recurrence. However, higher serum levels of sIL-6R at diagnosis were associated with significantly shorter relapse-free survival in patients with estrogen receptor-positive breast cancer.

Clinical characteristics and prognostic factors for primary appendiceal carcinoma.

Aim:  Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms.

Viral microRNA profile in Epstein-Barr virus-associated peripheral T cell lymphoma

Effie Liakopoulou Hayley M. Greenfield Bronwen E. Shaw Sudhir Tauro Jennifer L. Byrne Mike Dennis John Burthem Guy S. Lucas Charles Craddock Nigel H. Russell John A. Liu Yin University Department of Haematology, Manchester Royal Infirmary, Manchester, Department of Haematology, Christie Hospital, Manchester, Department of Haematology, City Hospital, Nottingham, and Department of Haematology, University Hospital Birmingham, Birmingham, UK. E-mail: john.yin@cmmc.nhs.uk