• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.19-27
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• 2022

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

• Phonetics and Speech Sciences
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• v.12 no.2
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• pp.73-80
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• 2020

Breathing is the voice's driving force and also acts as a regulator of larynx function and efficiency. Respiratory distress is a side effect of general anesthesia in thyroid surgery. Therefore, this study's objective was to provide practical and complementary information for voice recovery after thyroid surgery, based on aerodynamic evaluation pre- and post-thyroidectomy. From May 2014 to July 2015, aerodynamic evaluations were performed on 34 female patients diagnosed with thyroid papillary cancer one week before surgery (PRE), one month after surgery (P1), and three months after surgery (P3). The Phonatory Aerodynamic System (model 6600, KayPENTAX, USA) was employed for this purpose, and a total of 29 analysis parameters were selected. The results showed statistically significant differences in peak expiratory airflow (p=0.004), mean pitch (p<0.01), expiration airflow duration (p=0.001), and expiratory volume (p=0.018), based on time factors. In the comparison of time factors, peak expiratory airflow and mean pitch parameters were different in PRE-P1 and PRE-P3. Expiration airflow duration and expiratory volume parameters were different in PRE-P3 and P1-P3. The interaction effect of time and surgical range was significant only for expiratory volume (p=0.024). Female patients who undergo thyroidectomy require post-operative breathing training, and exhalation improvement is considered to reflect a positive lifestyle after surgery.

• Archives of Plastic Surgery
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• v.42 no.4
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• pp.461-468
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• 2015

Background Functional restoration of the facial expression is necessary after facial nerve resection to treat head and neck tumors. This study was conducted to evaluate the functional outcomes of patients who underwent facial nerve cable grafting immediately after tumor resection. Methods Patients who underwent cable grafting from April 2007 to August 2011 were reviewed, in which a harvested branch of the sural nerve was grafted onto each facial nerve division. Twelve patients underwent facial nerve cable grafting after radical parotidectomy, total parotidectomy, or schwannoma resection, and the functional facial expression of each patient was evaluated using the Facial Nerve Grading Scale 2.0. The results were analyzed according to patient age, follow-up duration, and the use of postoperative radiation therapy. Results Among the 12 patients who were evaluated, the mean follow-up duration was 21.8 months, the mean age at the time of surgery was 42.8 years, and the mean facial expression score was 14.6 points, indicating moderate dysfunction. Facial expression scores were not influenced by age at the time of surgery, follow-up duration, or the use of postoperative radiation therapy. Conclusions The results of this study indicate that facial nerve cable grafting using the sural nerve can restore facial expression. Although patients were provided with appropriate treatment, the survival rate for salivary gland cancer was poor. We conclude that immediate facial nerve reconstruction is a worthwhile procedure that improves quality of life by allowing the recovery of facial expression, even in patients who are older or may require radiation therapy.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.127-132
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• 2000

Purpose : To determine if the tumor intersitial fluid pressure (TIFP) and/or its change in patients with metastatic Iymph node in head and neck area can predict radiotherapy outcome. Materials and Methods : In 26 biopsy Proven metastatic Iymph node Patients in head and neck area with accessible by direct inspection and palpation, and of sufficient thickness (>1 cm) to permit accurate needle placement, we measured TIFP at cervical Iymph node before and during radiotherapy. Tumor size was measured clinically and radiologically. Results : The mean preradiotherapy TIFP was 24.7 mmHg. Preradiotherapy TIFP had marginally significant relationship with tumor size (p=0.06). Preradiotherapy TIFP significantly decreased when tumor size decreased (p=0.009). Preradiotherapy TIFP was not different between complete response group and group with partial or less response (p=0.75). Radiotherapy outcome was not different between group with above and group with below than average TIFP (p=0.229). TIFP decreased 36mmHg in complete response group and 29.7 mmHg in group with partial or less response. Conclusion :The mean TIFP was elevated with 24.7 mmHg. Preradiotherapy TIFP had marginally significant relationship with tumor size (p=0.06). TIFP decreased 36 mmHg in complete response group and 29.7 mmHg in group with partial or less respone but there was no statistically significant relationship in two groups.

• Journal of Dental Rehabilitation and Applied Science
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• v.18 no.2
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• pp.113-118
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• 2002

Conventional radiograph, computed tomograph (CT), magnetic resonance image (MRI) are commonly used methods for diagnosis of oro-maxillofacial cancer. MRI is an effective tool to verify soft tissue lesion however, metal produces black artifacts in the image. Therefore, metal structure should be removed before taking MRI to diagnose head and neck cancer patients. A 52-year-old female patient with adenocarcinoma in the posterior right soft palate was referred to take a MRI before surgery. She has 7-unit porcelain fused to metal bridge in the maxilla. Eight-unit Tagis-Vectris fixed partial denture was fabricated to replace her existing PFM bridge to take a MRI without any artifact before and after surgery. The patient satisfied with her restorations in terms of esthetics, function after 11 months. Even though minor staining was detected, Tagis-Vectris restoration fixed partial denture was intact during observation period.

• BMB Reports
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• v.51 no.11
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• pp.584-589
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• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1449-1452
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• 2016

Background: Adult rhabdomyosarcoma (RMS) is a rare and aggressive disease with limited data compared with pediatric RMS. The goal of this study was to determine the treatment outcome and identify factors related to survival outcome in Thailand. Materials and Methods: Adult patients (${\geq}15$ years old) with the pathological diagnosis of RMS between 1985 and 2010 were reviewed. The data were retrospectively reviewed from the pathological results and medical records from Srinagarind Hospital, Khon Kaen University. Results: A total of 34 patients were identified in the study. The median age at diagnosis was 35.5 years and the most common primary sites were extremity and the head and neck region. The incidence of pleomorphic RMS increased with age and none was found in those aged younger than 20 years old. The median survival time was 9.33 months (95%CI: 5.6-13.1). The 1- and 5- year survival rates were 38.2% (22.3-54.0) and 20.6% (9.1-35.3). On multivariate analysis, age and size of tumor did not predict better outcome while chemotherapy and surgery were significantly associated with longer survival. Conclusions: Outcome of adult RMS was poor. Surgery and chemotherapy are strongly associated with better prognosis and multimodality treatment should be incorporated in the clinic.

• Restorative Dentistry and Endodontics
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• v.9 no.1
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• pp.15-24
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• 1983

Irradiation is frequently employed as the sole therapy for oral cancer. These irradiated patients presents peculiar and progressive dental problems. But there is only scanty informations concerning specific approaches to endodontic treatment for head and neck cancer patients who have been subjected to tumorcidal doses of radiation therapy. The purpose of the present study was to determine the effects of cobalt-60 radiation on the pulpal healing of dogs after the direct pulp capping. As the experimental animals, 10 dogs (above 7-8 months after birth) were divided into 3 groups (Control, Group I, Group II). The cobalt-60 was irradiated to the Group I and Group II each 1,009 and 1,562.5 rads as single dose. As the capping material Dycal$^{(R)}$(L.D. Caulk company) was selected. After the direct pulp capping the dogs were sacrified 1, 2, 3, 4, week interval and made the original slides cut with a thickness of 8 microns and stained with hematoxylin and eosin. After examination and comparision of all specimen, the results of this study were drawn as follows; 1. The formation of reparative dentin was observed from the 1st week in the Control group, the 2nd week in the Group I & II. The few and irregular tuble structure was appeared in the 4th week in the Control group only, but failed in the Group I & II. 2. The continuity of dentin bridge was appeared in the 3rd week in all group and the degeneration of odontoblast in the 1st week of the Group II. 3. The congestion and hemorrhage in the pulp tissue were observed in all groups until 3rd week. The inflammation was appeared within the 2nd week in the Group I and especially marked in the Group II, but absent in the Control group. 4. In cases Dycal into the pulp tissue deeply, the local necrosis of pulp and decrease of dentin formation was observed.

• Archives of Craniofacial Surgery
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• v.20 no.1
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• pp.17-23
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• 2019

Background: The resection of head and neck cancer can result in postoperative defect. Many patients have difficulty swallowing and masticating, and some have difficulty speaking. Various types of flaps are used for palatal reconstruction, but flap selection remains controversial. Therefore, our study will suggest which flap to choose during palatal reconstruction. Methods: Thirteen patients who underwent palatal reconstruction from 30 January, 1989 to 4 October, 2016 at our institution. Size was classified as small when the width was < $4cm^2$, medium when it was $4-6cm^2$, and large when it was ${\geq}6cm^2$. Based on speech evaluation, the subjects were divided into a normal group and an easily understood group. After surgery, we assessed whether flap selection was appropriate through the evaluation of flap success, complications, and speech evaluation. Results: Defect size ranged from $1.5{\times}2.0cm$ to $5.0{\times}6.0cm$. In four cases, the defect was in the anterior third of the palate, in eight cases it was in the middle, and there was one case of whole palatal defect. There were three small defects, two medium-sized defects, and eight large defects. Latissimus dorsi free flaps were used in six of the eight large defects in the study. Conclusion: The key to successful reconstructive surgery is appropriate selection of the flap with reference to the characteristics of the defect. Depending on the size and location of the defect, the profiles of different flaps should be matched with the recipient from the outset.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.235-245
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• 1989

Rhabdomyosarcoma is a highly malignant soft tissue sarcoma that can arise in any site of the body containing striated muscle or its mesenchymal analgae. It is the most common childhood sarcoma with two peak age frequencies, one at ages 2 to 6, and one in the adolescence. The site, stage and extent of disease, and pathologic characteristics of the tumor contribute to prognostic factors that influence therapeutic decisions. The results of treatment of 52 patients with rhabdomyosarcoma, who were treated at Department of Radiation Oncology, Yonsei University College of Medicine, Yosei Cancer Center from 1976 to 1987 were retrospectively analyzed. The most frequent clinical group and primary sites were IRS group III (57.7%) and head and neck (42.3%) including orbit (11.5%) and parameningeal region(13.5%). The overall and disease free 5 year survival rate of eligible 41 patients were 31.7%, 29.3%, respectively. The complete remission (CR) rate was 50% in clinical group III and 0% in IV. Primary tumors of the orbit, clinical group 1 and embryonal subtype had the best prognosis. The Survival rate was improved by additiion of chemotherapy to operation and radiation therapy.