PURPOSE: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. MATERIALS AND METHODS: We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. RESULTS: The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. < or =90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. CONCLUSION: Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.
Cisplatin ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Lung ; Lung Neoplasms ; Multivariate Analysis ; Paclitaxel ; Radiotherapy, Conformal ; Retrospective Studies

Purpose: The purpose of this study was to evaluate the treatment outcomes and toxicity profile of patients with early glottic cancer who underwent hypofractionated radiation therapy (RT) with 3.5 Gy per fraction. Materials and Methods: A retrospective review was performed of the medical records of 35 patients with early stage (T1-2N0M0) glottic cancer who underwent definitive RT. The dose fractionation scheme was 59.5 Gy in 17 fractions. Posterior commissure was excluded from the clinical target volume (CTV) for 26 patients (74.3%) without glottic lesions close to this region. Results: With a median follow-up of 16.23 months (range, 6.82 to 67.15 months), no local, regional, or distant recurrence was reported. Acute hoarseness (65.7%), mucositis (68.6%), radiation dermatitis (60.0%) was frequent. One patient (2.9%) reported grade 3 acute toxicity (mucositis) and there was no grade 4–5 acute toxicity. There was no grade ≥3 late toxicities; however, grade 1 late intermittent hoarseness was frequent (45.7%). The receiver operative characteristic analysis revealed that mean hypopharyngeal dose was predictive for acute grade ≥2 mucositis (area under the curve=0.9314; 95% confidence interval, 0.8524–1). The optimal threshold of mean hypopharyngeal dose for occurrence of acute grade ≥2 mucositis was 26.31 Gy, with a specificity and sensitivity of 83.3% and 88.2%, respectively. Conclusion Hypofractionated RT with fraction size of 3.5 Gy for early glottic cancer is effective. The hypopharyngeal mean dose could predict the occurrence of grade ≥2 acute mucositis. The posterior commissure can be safely excluded from the CTV.

Identifying the roles of genes in cancer is critical in discovering potential genetic therapies for cancer care. Translocon-associated protein delta (TRAPδ), also known as signal sequence receptor 4 (SSR4), is a constituent unit in the TRAP/SSR complex that resides in the endoplasmic reticulum and plays a key role in transporting newly synthesized proteins into the endoplasmic reticulumn.However, its biological role in disease development remains unknown to date. This is the first study to identify the role of TRAPδ/ SSR4 in colorectal cancer cells in vitro. Upon successful transient knockdown of TRAPδ/ SSR4, we observed significant reduction of cell viability in all colorectal cancer cell lines tested. Both HCT 116 and SW480 cell lines were significantly arrested at S and G1 phases, while DLD-1 cells were significantly apoptotic. Moreover, TRAPδ/ SSR4 stable knockdown HCT 116 and SW480 cells showed significantly lower viability, anchorage-independent growth, and increased S and G1 phase arrests. Overall, we conclude TRAPδ/ SSR4 is a potential oncogene in human colorectal cancer cells.

Identifying the roles of genes in cancer is critical in discovering potential genetic therapies for cancer care. Translocon-associated protein delta (TRAPδ), also known as signal sequence receptor 4 (SSR4), is a constituent unit in the TRAP/SSR complex that resides in the endoplasmic reticulum and plays a key role in transporting newly synthesized proteins into the endoplasmic reticulumn.However, its biological role in disease development remains unknown to date. This is the first study to identify the role of TRAPδ/ SSR4 in colorectal cancer cells in vitro. Upon successful transient knockdown of TRAPδ/ SSR4, we observed significant reduction of cell viability in all colorectal cancer cell lines tested. Both HCT 116 and SW480 cell lines were significantly arrested at S and G1 phases, while DLD-1 cells were significantly apoptotic. Moreover, TRAPδ/ SSR4 stable knockdown HCT 116 and SW480 cells showed significantly lower viability, anchorage-independent growth, and increased S and G1 phase arrests. Overall, we conclude TRAPδ/ SSR4 is a potential oncogene in human colorectal cancer cells.

Identifying the roles of genes in cancer is critical in discovering potential genetic therapies for cancer care. Translocon-associated protein delta (TRAPδ), also known as signal sequence receptor 4 (SSR4), is a constituent unit in the TRAP/SSR complex that resides in the endoplasmic reticulum and plays a key role in transporting newly synthesized proteins into the endoplasmic reticulumn.However, its biological role in disease development remains unknown to date. This is the first study to identify the role of TRAPδ/ SSR4 in colorectal cancer cells in vitro. Upon successful transient knockdown of TRAPδ/ SSR4, we observed significant reduction of cell viability in all colorectal cancer cell lines tested. Both HCT 116 and SW480 cell lines were significantly arrested at S and G1 phases, while DLD-1 cells were significantly apoptotic. Moreover, TRAPδ/ SSR4 stable knockdown HCT 116 and SW480 cells showed significantly lower viability, anchorage-independent growth, and increased S and G1 phase arrests. Overall, we conclude TRAPδ/ SSR4 is a potential oncogene in human colorectal cancer cells.

Purpose: We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for “early brain metastasis”, which occurs before extracranial recurrence (ECR), and “late brain metastasis”, which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors. Results: The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026). Conclusion PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.

PURPOSE: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirty-two patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. RESULTS: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (> or =50%) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. CONCLUSION: High Met extent (> or =50%) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.
Biopsy ; Carcinoma ; Carcinoma, Squamous Cell ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; Paraffin ; Receptor, Epidermal Growth Factor

The Peutz-Jeghers syndrome has three cardinal features: gastrointestinal polypasis, mucocutaneous piginentation and autosomal dominant heredity. This syndrome is ciinically important because of the complication caused by the gastrointestinal ployp, leading to abdominal pain, gastrointestinal bleeding and intussusception. We experienced a case of Peutz-Jeghers syndrome who complained of dizziness, vague abdominal pain, melanin pigmentations of the lips, oral mucosa and digits and reported with the review of the literature.
Abdominal Pain ; Anemia* ; Dizziness ; Hemorrhage ; Heredity ; Intussusception* ; Lip ; Melanins ; Mouth Mucosa ; Peutz-Jeghers Syndrome ; Pigmentation

Purpose: Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen. Materials and Methods: Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction. Results: We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment. Conclusion The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Purpose: Bone age (BA) is needed to assess developmental status and growth disorders. We evaluated the clinical performance of a deep-learning-based BA software to estimate the chronological age (CA) of healthy Korean children. Methods: This retrospective study included 371 healthy children (217 boys, 154 girls), aged between 4 and 17 years, who visited the Department of Pediatrics for health check-ups between January 2017 and December 2018. A total of 553 left-hand radiographs from 371 healthy Korean children were evaluated using a commercial deep-learning-based BA software (BoneAge, Vuno, Seoul, Korea). The clinical performance of the deep learning (DL) software was determined using the concordance rate and Bland-Altman analysis via comparison with the CA. Results: A 2-sample t-test (P<0.001) and Fisher exact test (P=0.011) showed a significant difference between the normal CA and the BA estimated by the DL software. There was good correlation between the 2 variables (r=0.96, P<0.001); however, the root mean square error was 15.4 months. With a 12-month cutoff, the concordance rate was 58.8%. The Bland-Altman plot showed that the DL software tended to underestimate the BA compared with the CA, especially in children under the age of 8.3 years. Conclusion The DL-based BA software showed a low concordance rate and a tendency to underestimate the BA in healthy Korean children.