The data suggest that VFE produces significant improvement in subjective, objective, and patient self-evaluation and deserves further attention as a treatment for aged atrophy of the vocal fold. It was also suggested that VFE does not improve the vocal fold bowing but may improve muscular function during voicing.

Regenerative treatments using bFGF has shown to be effective for improvement of vocal function in scar and sulcus.

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We investigated the clinical value of methylation of long interspersed nuclear element-1 (LINE-1) for the prognosis of colorectal cancer (CRC) and for the survival benefit from adjuvant chemotherapy with oral fluoropyrimidines. LINE-1 methylation in tumor DNA was measured by quantitative methylation-specific PCR in 155 samples of stage II and stage III CRC. The presence of microsatellite instability and CpG island methylator phenotype (CIMP) were assessed and 131 microsatellite stable ⁄ CIMP) cases were selected for survival analysis, of which 77 patients had received postoperative adjuvant chemotherapy with oral fluoropyrimidines. The CRC cell lines were used to investigate possible mechanistic links between LINE-1 methylation and effects of 5-fluorouracil (5-FU). High LINE-1 methylation was a marker for better prognosis in patients treated by surgery alone. Patients with low LINE-1 methylation who were treated with adjuvant chemotherapy survived longer than those treated by surgery alone, suggestive of a survival benefit from the use of oral fluoropyrimidines. In contrast, a survival benefit from chemotherapy was not observed for patients with high LINE-1 methylation. The CRC cell lines treated with 5-FU showed increased expression of LINE-1 mRNA. This was associated with upregulation of the phospho-histone H2A.X in cells with low LINE-1 methylation, but not in cells with high LINE-1 methylation. The 5-FU-mediated induction of phospho-histone H2A.X, a marker of DNA damage, was inhibited by knockdown of LINE-1. These results suggest that LINE-1 methylation is a novel predictive marker for survival benefit from adjuvant chemotherapy with oral fluoropyrimidines in CRC patients. This finding could be important for achieving personalized chemotherapy. (Cancer Sci 2011; 102: 166-174) E pigenetic alterations including CpG island hypermethylation and global hypomethylation of DNA are commonly observed in colorectal cancer (CRC).(1) The aberrant hypermethylation of CpG islands is associated with distinctive clinical features of CRC and shows promise as a diagnostic marker. (2,3) Global hypomethylation, on the other hand, has attracted much less attention and its clinical significance in cancer has not been extensively investigated.Long interspersed nuclear element-1 (LINE-1) is a non-longterminal-repeat class of retroposon that is the most successfully integrated mobile element and accounts for approximately 18% of the human genome.(4-6) The LINE-1 sequence is 6 kb in length and contains a 5¢ untranslated region (UTR), two open reading frames and a 3¢UTR. The 5¢UTR has internal promoter activity and the open reading frame encodes for nuclease and reverse transcriptase activities that are necessary for transposition. Although the majority of retroposons no longer have the ability to transpose due to mutations and deletions in their sequence, approximately 100 full-length copies of LINE-1 in the human genome retain this ability. (7,8) Because of the abundance and functional ability of LINE-1, the level of its methyla...

Objectives/Hypothesis Vocal fold atrophy, scar, and sulcus reduce the vibratory function of the vocal fold mucosa, which causes severe refractory dysphonia. We have reported encouraging preliminary results using an intracordal injection of basic fibroblast growth factor (bFGF) and showed improvement in phonatory parameters and voice. The present study summarizes our experience with 100 cases of stiffened vocal folds that were treated with bFGF injections. Study Design Retrospective chart review with Interstitial Review Board (IRB) approval. Methods Local injection of bFGF was performed in 100 cases of vocal fold pathology, which included 43 cases of vocal fold atrophy, 41 cases with scar, and 16 cases with sulcus. Ten micrograms of bFGF were injected into the vocal folds under topical anesthesia 4 times in each patient. Therapeutic outcomes were examined with maximum phonation time (MPT), voice handicap index‐10 (VHI‐10), and GRBAS scale. Results MPT, VHI‐10, and GRBAS scores significantly improved in all pathology groups. An improvement on the VHI‐10 greater than five points was observed in 82% of atrophy cases, 78% of scar cases, and 67% of sulcus cases. Improvement on the VHI‐10 was significantly better in the atrophy group than the scar or sulcus groups. The mild/moderate cases of scar and sulcus showed better improvement than severe cases. Conclusions The current large case series indicates positive effects of intracordal injection of bFGF for improvement of voice with no severe adverse events. The effects appeared best for cases of atrophy, while the treatment of severe scar and sulcus requires further improvement. Level of Evidence 4 Laryngoscope, 131:2059–2064, 2021

Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 μg of HGF per vocal fold; Step II received 3 μg of HGF; and Step III received 10 μg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus.

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4H-SiC(0001) metal-oxide-semiconductor field-effect transistors (MOSFETs) and MOS capacitors were fabricated by the following procedures: H2 etching, SiO2 deposition, and nitridation, and their electrical characteristics were evaluated. Substantially low interface state densities (4–6 × 1010 cm−2 eV−1) and high channel mobilities (80–85 cm2 V−1 s−1) were achieved by N2 annealing or NO annealing after H2 etching and SiO2 deposition. The threshold voltage of the MOSFETs fabricated with N2 annealing was shifted negatively when the oxide was formed by deposition. On the other hand, normally-off operation and high channel mobility were compatible for the MOSFETs fabricated with NO annealing.