Survivin expression and its clinical significance in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Survivin, an inhibitor of apoptosis is expressed in several human cancers. Its expression is known to be associated with poor clinical outcome, but not widely studied in pancreatic cancer. We performed this study to determine the survivin expression in pancreatic cancer and its clinical significance as a prognostic factor.</p> <p>Methods</p> <p>We performed immunohistochemical staining for survivin, p53, and Bax in formalin-fixed, paraffin-embedded block from forty-nine pancreatic tissues. To determine the association with clinical course, we reviewed the patients' clinical record.</p> <p>Results</p> <p>Of the 49 cases of pancreatic cancer, 46 cases (93.9%) were positive for survivin expression. There was no significant association between survivin expression and p53 or bax. For clinicopathological parameters, perineural invasion was more common in survivin positive and venous invasion was more common in survivin negative (p = 0.041 and 0.040, respectively). Responsiveness to chemotherapy appeared to be slightly better in patients with low survivin expression.</p> <p>Conclusion</p> <p>Survivin expression may be associated with venous or perineural invasion, indicating metastatic route, and seems to have a potential as a predictive marker for chemotherapy. Further study of large scale is required to determine the clinical significance of survivin expression in pancreatic cancer.</p

Identification of as a Susceptibility Locus for Kawasaki Disease in Patients Younger than 6 Months of Age

Kawasaki disease (KD) is an acute febrile vasculitis predominately affecting infants and children. The dominant incidence age of KD is from 6 months to 5 years of age, and the incidence is unusual in those younger than 6 months and older than 5 years of age. We tried to identify genetic variants specifically associated with KD in patients younger than 6 months or older than 5 years of age. We performed an age-stratified genome-wide association study using the Illumina HumanOmni1-Quad BeadChip data (296 cases vs. 1,000 controls) and a replication study (1,360 cases vs. 3,553 controls) in the Korean population. Among 26 candidate single nucleotide polymorphisms (SNPs) tested in replication study, only a rare nonsynonymous SNP (rs4365796: c.1106C＞T, p.Thr369Met) in the lymphoid enhancer binding factor 1 (LEF1) gene was very significantly associated with KD in patients younger than 6 months of age (odds ratio [OR], 3.07; pcombined = 1.10 × 10-5), whereas no association of the same SNP was observed in any other age group of KD patients. The same SNP (rs4365796) in the LEF1 gene showed the same direction of risk effect in Japanese KD patients younger than 6 months of age, although the effect was not statistically significant (OR, 1.42; p = 0.397). This result indicates that the LEF1 gene may play an important role as a susceptibility gene specifically affecting KD patients younger than 6 months of age

Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04

Purpose To determine the efficacy of consolidation chemotherapy (CC) with docetaxel and cisplatin (DP) after concurrent chemoradiotherapy (CCRT) with the same agents in locally advanced non-small-cell lung cancer (LA-NSCLC). Patient and Methods Patients were randomly assigned to either CCRT alone (observation arm) or CCRT followed by CC (consolidation arm). CCRT with docetaxel (20 mg/m(2)) and cisplatin (20 mg/m(2)) was administered every week for 6 weeks with a total dose of 66 Gy of thoracic radiotherapy in 33 fractions. In the consolidation arm, patients were further treated with three cycles of DP (35 mg/m(2) each on days 1 and 8, every 3 weeks). The primary end point was 40% improvement in progression-free survival (PFS) compared with observation. Results From October 2005 to April 2011, 437 patients were randomly assigned. Seventeen patients did not start CCRT as a result of consent withdrawal or ineligibility reasons after random assignment, leaving 420 patients for this analysis (n = 211 for observation; n = 209 for consolidation). Patient characteristics were similar in both arms. In the consolidation arm, 143 patients (68%) received CC, of whom 88 (62%) completed three planned cycles. The median PFS was 8.1 months in the observation arm and 9.1 months in the consolidation arm (hazard ratio, 0.91; 95% CI, 0.73 to 1.12; P = .36). Median overall survival times were 20.6 and 21.8 months in the observation and consolidation arms, respectively (HR, 0.91; 95% CI, 0.72 to 1.25; P = .44). Conclusion CC with DP after CCRT with weekly DP in LA-NSCLC failed to further prolong PFS. CCRT alone should remain the standard of care. (C) 2015 by American Society of Clinical Oncology

Male-specific association of the <i>FCGR2A</i> His167Arg polymorphism with Kawasaki disease

<div><p>Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we performed a sex-stratified genome-wide association study (GWAS), using the Illumina HumanOmni1-Quad BeadChip data (249 cases and 1,000 controls) and a replication study for the 34 sex-specific candidate SNPs in an independent sample set (671 cases and 3,553 controls). Male-specific associations were detected in three common variants: rs1801274 in <i>FCGR2A</i> [odds ratio (OR) = 1.40, <i>P</i> = 9.31 × 10⁻⁵], rs12516652 in <i>SEMA6A</i> (OR = 1.87, <i>P</i> = 3.12 × 10⁻⁴), and rs5771303 near <i>IL17REL</i> (OR = 1.57, <i>P</i> = 2.53 × 10⁻⁵). The male-specific association of <i>FCGR2A</i>, but not <i>SEMA6A</i> and <i>IL17REL</i>, was also replicated in a Japanese population (OR = 1.74, <i>P</i> = 1.04 × 10⁻⁴ in males vs. OR = 1.22, <i>P</i> = 0.191 in females). In a meta-analysis with 1,461 cases and 5,302 controls, a very strong association of KD with the nonsynonymous SNP rs1801274 (p.His167Arg, previously assigned as p.His131Arg) in <i>FCGR2A</i> was confirmed in males (OR = 1.48, <i>P</i> = 1.43 × 10⁻⁷), but not in the females (OR = 1.17, <i>P</i> = 0.055). The present study demonstrates that p.His167Arg, a KD-associated <i>FCGR2A</i> variant, acts as a susceptibility gene in males only. Overall, the gender differences associated with <i>FCGR2A</i> in KD provide a new insight into KD susceptibility.</p></div

Male-specific association of rs1801274 in <i>FCGR2A</i>, rs12516652 in <i>SEMA6A</i>, and rs5771303 near <i>IL17REL</i> with KD.

<p>Male-specific association of rs1801274 in <i>FCGR2A</i>, rs12516652 in <i>SEMA6A</i>, and rs5771303 near <i>IL17REL</i> with KD.</p