Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Purpose: Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. Materials and Methods: We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. Results: In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. Conclusion Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

BACKGROUND: The purpose of this study was to evaluate whether performing an assessment of myocardial deformation using speckle tracking imaging during the recovery period after dobutamine stress echocardiography (DSE) allows detection of significant coronary artery disease (CAD) in patients with chest discomfort. METHODS: DSE and coronary angiography were performed in 44 patients with chest discomfort. The mean global longitudinal peak systolic strain (GLS) was measured at rest, at low stress (dobutamine infusion rate of 10 microg/kg/min) and at recovery (5 min after cessation of dobutamine infusion) of DSE using automated function imaging with apical views. Fractional flow reserve (FFR) was also performed in patients with intermediate coronary stenosis. CAD was defined as having a > or = 70% diameter stenosis on coronary angiography or as having a FFR < 0.8. Patients were divided two groups based on the absence or presence of CAD [CAD (-) group vs. CAD (+) group]. RESULTS: There were no significant differences in the clinical characteristics and results of conventional echocardiography between the two groups. GLS at recovery was lower in the CAD (+) group than in the CAD (-) group (-18.0 +/- 3.4% vs. -21.0 +/- 1.9%, p = 0.003). The optimal cutoff of GLS at recovery for detection of CAD was -19% (sensitivity of 70.6%, specificity of 83.3%). CONCLUSION: Assessment of GLS at recovery of DSE is a reliable and objective method for detection of CAD. This finding may suggest that systolic myocardial stunning remains even after recovery of wall motion abnormalities in patients with CAD.
Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Coronary Stenosis ; Dobutamine ; Echocardiography ; Echocardiography, Stress* ; Humans ; Myocardial Stunning ; Sensitivity and Specificity ; Thorax

Exercise-induced left bundle branch block is a rare condition that has been reported along with and without demonstrable cardiac abnormalities. We describe the case of a 73-year-old female with chest pain on execration. Coronary angiography revealed normal findings. She underwent a treadmill stress test. During the exercise left bundle branch block with concomitant chest pain was demonstrated. Chest pain was relieved with cessation of exercise.
Aged ; Bundle-Branch Block* ; Chest Pain* ; Coronary Angiography ; Exercise Test ; Female ; Humans

Bicuspid ; Child ; Dentigerous Cyst ; Female ; Humans ; Mouth ; Orthodontic Extrusion ; Tooth ; Tooth, Deciduous ; Tooth, Impacted

INTRODUCTION: This study evaluated the capability of silk fibroin (SF) and recombinant human bone morphogenetic protein-2 loaded SF (SF-BMP) as a bone defect replacement matrix when grafted in a calvarial bone defect of rats in vivo. MATERIALS AND METHODS: A total 70 calvarial critical size defects (5.0 mm in diameter) made on 35 adult female Sprague-Dawley rats were used in this study. The defects were transplanted with (1) rhBMP-2 loaded silk fibroin graft (SF-BMP: 0.8+10 microg), (2) Silk fibroin (SF: 10 microg), and (3) no graft material (Raw). The samples were evaluated with soft x-rays, alkaline phosphatase activity, calcium/phosphate quantification, histological and histomorphometric analysis at postoperative 4 and 8 weeks. RESULTS: The SF-BMP group (48.86+/-14.92%) had a significantly higher mean percentage bone area than the SF group (24.96+/-11.01%) at postoperative 4 weeks.(P<0.05) In addition, the SF-BMP group (40.01+/-12.43%) had a higher % bone area at postoperative 8 weeks than the SF group (33.26+/-5.15%). The mean ratio of gray scale levels to the host bone showed that the SF-BMP group (0.67+/-0.08) had a higher mean ratio level than the SF group (0.61+/-0.09) at postoperative 8 weeks. These differences were not statistically significant.(P=0.168 and P=0.243, respectively) CONCLUSION: The rhBMP-2 loaded silk fibroin graft revealed fewer immunoreactions and inflammation as well as more new bone formation than the pure silk fibroin graft. Therefore, silk fibroin may be a candidate scaffold for tissue engineered bone regeneration.
Adult ; Alkaline Phosphatase ; Animals ; Bone Morphogenetic Protein 2 ; Bone Regeneration ; Female ; Fibroins ; Humans ; Inflammation ; Osteogenesis ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; Silk ; Tissue Scaffolds ; Transforming Growth Factor beta ; Transplants

There are several oral lesions related with AIDS, such as candidiasis, hairy leukoplakia, Kaposi's sarcoma, aphthous stomatitis, lichen planus, and other opportunistic infectious diseases. Among the others, Kaposi's sarcoma, the most common malignant tumor associated with AIDS, is closely linked to the number of CD4+ T cell. Kaposi's sarcoma often occurs in palate, the most prone site, and has characteristic clinical features in most cases. Sometimes, the tumor induces underlying bone destruction at late stage. We report a case of a 27 year-old man with AIDS-associated Kaposi's sarcoma at left lower retromolar triangle, parapharyngeal area and discuss the management of AIDS patients in dentistry.
Candidiasis ; Communicable Diseases ; Dentistry ; Humans ; Leukoplakia, Hairy ; Lichen Planus ; Palate ; Sarcoma ; Sarcoma, Kaposi ; Stomatitis, Aphthous

Blood Platelets ; Centrifugation ; Intercellular Signaling Peptides and Proteins ; Mandible ; Osteoblasts ; Osteogenesis ; Platelet Count ; Platelet-Rich Plasma ; Transplants

We report a case of a 30 year-old woman who presented with acute scalp hair loss induced by isonicotinic acid hydrazide gap (INH). Considerable hair loss started within 4 weeks of INH administration. There was no evidence of dermatitis, allergic reaction, or any other cause for the hair loss. INH was discontinued, and the hair loss stopped within 4 weeks, with new hair growth seen. There was complete recovery of hair loss after 12 weeks of alopecia. Medication-induced hair loss is an occasional adverse effect of many drugs, however hair loss induced by INH has been reported in only 1 case. The complete recovery from anagen effluvium is difficult to explain, but it could have been due to the early discontinuance of INH.
Adult ; Alopecia ; Dermatitis ; Female ; Hair ; Humans ; Hypersensitivity ; Isoniazid ; Scalp

We report a case of alopecia mucinosa in a 9-year-old girl. She presented with several papules on an erythematous patch on the right side of the ala nasi, a hairless nodular lesion on the same side of the nasal canal. Histopathologic findings obtained from the nasal canal revealed typical features of alopecia mucinosa, such as reticular degeneration, cystic space formation and mucin deposition in the pilosebaceous follicle. The case displayed no evidence or clinical features of any malignant changes, and we suspect the case to be an acute form of alopecia mucinosa.
Alopecia* ; Child* ; Female ; Humans ; Mucinosis, Follicular* ; Mucins