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( C Breitbach ),( M Cho ),( T H Hwang ),( C W Kim ),( U B Jeon,),( H Y Woo ),( K T Yoon ),( J W Lee ),( J Burke ),( T Hickman ),( K Duboi ),( L Longpre ),( R Patt ),( D H Kirn ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: JX-594 is a targeted oncolytic vaccinia virus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus granulocyte macrophage?colony stimulating factor (GM-CSF) expression is accompanied by tumor vascular disruption and anti-tumoral immunity (Reviewed in Nat Rev Cancer 2009). JX-594 was well-tolerated intravenously (IV) (Nature 2011) and intratumorally (IT) (Lancet Oncol 2008). Complementary anti-tumor effects are predicted with JX-594 followed by sorafenib due to acute vascular disruption effects with JX-594 and anti-angiogenic effects with sorafenib. Objectives: The primary objective of the study was to determine the safety of JX-594 followed by sorafenib in patients with advanced HCC. Secondary objectives include disease control rate (DCR) based on mRECIST and/or Choi response criteria at Day 6 (optional), Day 25 (after JX-594 only), 6 and 12 weeks. Methods: Treatment-refractory HCC patients received JX-594 for three weeks (Day 1 IV, Day 8 IT and Day 22 IT) followed by sorafenib. An IT boost dose of JX-594 at Week 12 was optional. Results: Twenty-five (25) patients were treated in this study; twenty (20) were refractory to sorafenib. Enrollment has been completed. The sequential treatment regimen was well-tolerated. Transient flu-like symptoms (Grade 1-2) and transient leukopenia (lymphopenia, neutropenia) were the most common adverse events following JX-594 therapy. Sorafenib toxicities were consistent with the expected toxicity profile. After JX-594 alone at Day 25, 56% of patients exhibited Choi tumor responses (range 19-48% reduced enhancement). Following subsequent sorafenib therapy, 76% had Choi responses at Week 6-12, including 83% sorafenib-failure patients. The disease control rate was 80% with JX-594 alone and 38% following initiation of sorafenib. Conclusions: JX-594 was well-tolerated and associated with Choi tumor responses following IV and IT injections in patients with advanced HCC. Subsequent sorafenib was associated with the expected toxicity profile. Further trials of JX-594 in HCC patients are warranted.
Effects of Age and High Frequency Hearing Loss on Binaural Speech Understanding Using HINT Study
Kim, Sung-Hee,Frisina Robert D.,Frisina Susan T.,Mapes Frances M.,Hickman Elizabeth D.,Frisina D. Robert The Acoustical Society of Korea 2007 韓國音響學會誌 Vol.26 No.e1
It has long been known that high-frequency sensorineural hearing loss (HFHL) can contribute to difficulty in speech understanding by elderly listeners. This study evaluated the relative contribution of HFHL and age to speech understanding. Subjects included adult middle-aged and old groups with normal hearing or with limited HFHL. The Hearing-in-Noise-Test (HINT) was used to measure speech perception performance in quiet and in noise. The middle-aged groups showed significant effects of HFHL for speech intelligibility in quiet and in noise, but the old groups showed the difference in quiet only due to high frequency hearing. The results suggest that HFHL may affect speech intelligibility differently with age and therefore hearing aid selection needs to take into account the influence of age.