Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Background: Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. Objective: The purpose of this study is to uncover possible roles of MDA5 in psoriasis. Methods: Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. Results: As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. Conclusion These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.

Background: Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. Objective: The purpose of this study is to uncover possible roles of MDA5 in psoriasis. Methods: Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. Results: As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. Conclusion These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.

This study was performed to select the proper assessing methods for learning outcomes in undergraduate education of medical humanities (MH), and to evaluate whether student assessments in MH curricula are related to the graduate outcomes (GO)and/or periodic phase outcomes (PO). We searched the reasonable assessing methods for GO and PO of MH curricula of Keimyung University School of Medicine (KUSM). The outcomes are composed of six competencies including patient care, communication, patient support, professionalism, problem solving and research, and self-development. Then, we analyzed whether student assessments carried out during formal MH curricula properly achieved their PO, furthermore their GO. Four competencies including communication, patient support, professionalism, self-development were lightened to be closely related to outcomes for MH. Only the component of problem solving was settled to be related to MH in the competency of problem solving and research. The competency of patient care was excluded from the relationship with MH. The assessing methods for the GO and three PO recommended from educational experts, and there were various available assessing methods based on medical situations and clinical contexts including direct observation of clinical skills, 360 degree feedback, peer review, self-assessment, project-based assessment, portfolio-based assessment, discussion & presentation-based assessment, log-based assessment. For the outcome-achieving from formal MH curricula, the MH programs of phase-1 (1st and 2nd grades) almost accomplished the PO of communication, patient supporting and professionalism, and considerably accomplished the PO of problem solving and self-development. The MH programs of phase-2 (3rd and 4th grades) accomplished considerably their PO as the competencies of professionalism and problem solving, and partially as communication, patient supporting and self-development. However, as only one program, public health law, was provided for MH program in phase-3 (5th and 6th grades), the extra methods to evaluate their MH outcomes are needed. Many assessing methods can be available for the most MH competencies consisting of the GO of KUSM, and the proper assessing methods for each MH competency should be selected based on programs and learning contexts in MH education. While formal MH curricula of the school variously accomplished the MH competencies of GO according to periodic phases of curricula, it is recommended to enhance the feasibility and effectiveness of evaluation for GO in MH curricula of the school.

Background: Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed. Objective: The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis. Methods: We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model. Results: Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis. Conclusion Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.

Exenatide extended-release was recently developed as an antidiabetic drug; it acts as a glucagon-like peptide-1 receptor agonist. A 54-year-old male visited our clinic complaining of a subcutaneous tender nodule on his left thigh that had developed over the course of 1 week. The patient had received exenatide extended-release injections for 5 months to treat diabetes. A histopathologic examination showed septal and lobular panniculitis with lymphohistiocyte and eosinophil infiltration. The patient was diagnosed with eosinophilic panniculitis (EP) due to exenatide extended- release injection. EP is a rare type of panniculitis characterized by a prominent infiltrate of eosinophils in the subcutaneous fat layer. It is a histologic reaction pattern that is associated with various clinical conditions. Among the injection- site reactions reported in exenatide extended-release users, injection-site nodules occur infrequently. Clinicians who treat diabetics who use exenatide extended-release should be aware of the possible occurrence of injection-site nodules.

No abstract available.
Chordoma

BACKGROUND: Obesity is a serious problem, and there have been various studies to elucidate its causes. This study aims to evaluate the relationship between obesity and proportion of supper and late-night meals among the Korean general population. METHODS: The total analyzed population was 15,757 people (mean age 44.6 years). The criterion for abdominal obesity as defined by waist circumference was follows: men ≥90 cm, women ≥85 cm. Supper and late-night meals are defined as meals eaten between 6:00 p.m. and 2:00 a.m. Calories of supper and late-night meal were divided by the total calorie intake of the day and categorized into quintiles. Various variables that can affect obesity were corrected for in the model, and logistic regression models were used to confirm the relationship between supper and late-night meals and waist circumference. RESULTS: Comparing the first quintile to the second, the third, and the fifth showed statistically significant results (Odds ratio: 1.19, 1.25, and 1.21, respectively). We also compared the breakfast group and the no breakfast group. Only the breakfast group showed statistically significant results (Odds ratio: 1.28, 1.30, 1.22, and 1.21, respectively). CONCLUSION: Risk of abdominal obesity will be decreased if one reduces the proportion of supper and late-night meals to half of the recommended calorie intake.
Breakfast ; Female ; Humans ; Logistic Models ; Male ; Meals ; Obesity ; Obesity, Abdominal ; Waist Circumference

BACKGROUND: c-Jun along with JunB, JunD, and the Fos group proteins comprise the core members of the activator protein 1 (AP1) family of transcription factors. Recently, many studies have demonstrated the key roles of AP1 in regulating a wide spectrum of biological processes, including tumorigenesis. We therefore hypothesized that c-Jun and JunB influence the differentiation and malignant change of various skin tumors. OBJECTIVE: We measured the expression levels of c-Jun and JunB in different skin tumors. METHODS: The expressions of c-Jun and JunB were examined by performing the immunohistochemical staining of 55 specimens of skin tumors, including 13 cases of seborrheic keratosis, 4 cases of keratoacanthoma, 9 cases of actinic keratosis, 4 cases of Bowen's disease, 4 cases of basal cell carcinoma, 16 cases of squamous cell carcinoma, and 5 cases of malignant melanoma. RESULTS: Immunohistochemical analysis of the skin tumor tissue samples revealed a significantly higher expression of c-Jun in malignant skin tumors (basal cell carcinoma, squamous cell carcinoma, malignant melanoma) than in benign (seborrheic keratosis, keratoacanthoma) or premalignant skin tumors (actinic keratosis, Bowen's disease). The expression of JunB, however, was significantly lower in malignant skin tumors than in benign skin tumors. CONCLUSION: These findings showed that c-Jun has a positive association with skin malignancies, while JunB has a negative association with skin malignancies. The role of AP1 as key regulators of cell proliferation and epidermal tumor progression is suggested.
Biological Processes ; Bowen's Disease ; Carcinogenesis ; Carcinoma, Basal Cell ; Carcinoma, Squamous Cell ; Cell Proliferation ; Humans ; Keratoacanthoma ; Keratosis ; Keratosis, Actinic ; Keratosis, Seborrheic ; Melanoma ; Skin* ; Transcription Factor AP-1 ; Transcription Factors

O-linked beta-N-acetylglucosamine modification is an important post-translational modification, emerging as a novel regulatory mechanism in various cellular events. Recently, several studies have shown that O-GlcNAcylation plays an essential role in human breast, lung, and colon cancers. With regard to skin cancers, the role of O-GlcNAcylation has yet to be elucidated. To investigate whether O-GlcNAcylation is linked to human skin tumor development, immunohistochemical analysis was performed to investigate the presence of O-GlcNAcylation in various skin tumors. We evaluated the levels of O-GlcNAcylation, O-GlcNAc transferase, and O-GlcNAcase in 29 benign tumors, 12 premalignant tumors, and 26 malignant tumors in skin. Compared to the benign tumors, premalignant and malignant tumors had increased patterns of O-GlcNAcylation. In addition, the O-GlcNAc transferase and O-GlcNAcase levels were higher in premalignant and malignant tumors than in benign tumors. Interestingly, O-GlcNAcase levels were significantly increased in premalignant tumors compared to benign and malignant tumors. These results suggest that O-GlcNAcylation of proteins may play an important role in the development of human skin tumors.
Breast ; Colonic Neoplasms ; Humans ; Immunohistochemistry ; Lung ; Protein Processing, Post-Translational ; Skin Neoplasms ; Skin* ; Transferases