1.Whole-Genome and Transcriptome Sequencing Identified NOTCH2 and HES1 as Potential Markers of Response to Imatinib in Desmoid Tumor (Aggressive Fibromatosis): A Phase II Trial Study
Joonha KWON ; Jun Hyeong LEE ; Young Han LEE ; Jeeyun LEE ; Jin-Hee AHN ; Se Hyun KIM ; Seung Hyun KIM ; Tae Il KIM ; Kum-Hee YUN ; Young Suk PARK ; Jeong Eun KIM ; Kyu Sang LEE ; Jung Kyoon CHOI ; Hyo Song KIM
Cancer Research and Treatment 2022;54(4):1240-1255
Purpose:
Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to treat desmoid tumor. However, the molecular mechanism of why imatinib works remains unclear. Here, we describe potential roles of NOTCH2 and HES1 in clinical response to imatinib at genome and transcriptome levels.
Materials and Methods:
We identified somatic mutations in coding and noncoding regions via whole-genome sequencing. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale whole-genome sequencing and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response.
Results:
Among 20 patients, four (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥ 1 year. With gene-wise functional analyses, we detected a significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on Pan-Cancer Analysis of Whole Genomes data analyses, NOTCH2 mutations affect expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate between responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders.
Conclusion
Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.
2.Evaluation of the validity of Qraycam for tooth examination during epidemiological surveys.
Kum Ho LEE ; Se Hee KIM ; Dong Kie KIM ; Byoung Jin LEE
Journal of Korean Academy of Oral Health 2015;39(4):259-266
OBJECTIVES: The aim of this study was to evaluate applicability of the Qraycam device for detecting caries and filling body during tooth examinations. METHODS: Fifty-two subjects aged 25 to 34 years were recruited for tooth examination. Two examiners (an epidemiologic expert and a non-expert) performed visual tooth examination using only dental operating light, dental mirror, and air-drying without a dental explorer. Pictures or videos of every tooth surface were obtained under visual ray and 405 nm blue ray, respectively, by using Qraycam. The two examiners then evaluated these videos or images more than 7 days after visual examination. RESULTS: The results of the visual, visible ray image, and 405 nm blue ray image examinations showed very good kappa agreement with the gold standard for both examiners. The 405 nm blue ray image examination showed higher kappa agreement than visible ray image examination, and was similar to visual examination. Accuracy of detecting caries was enhanced by using 405 nm blue ray images from Qraycam. Accuracy of detecting filling body on 405 nm blue ray image examination was almost same as that by visual examination. CONCLUSIONS: Tooth examination with Qraycam images revealed high agreement with the gold standard and showed accuracy for detecting caries and filling body. Therefore, Qraycam would enhance the quality of oral epidemiologic survey including tooth examination and save cost and time of survey.
ROC Curve
;
Tooth*
3.Adhesion Activity of Lactobacillus plantarum PM 008 Isolated from Kimchi on the Intestine of Mice.
Se Eun JANG ; Yang Jin HYUN ; Young Joo OH ; Kum Boo CHOI ; Taesok KIM ; Ik Hyun YEO ; Myung Joo HAN ; Dong Hyun KIM
Journal of Bacteriology and Virology 2011;41(2):83-90
Lactic acid bacteria (LAB), including L. plantarum isolated from Kimchi, are beneficial and safe microorganisms that improve disturbances of the indigenous microflora and the host's immune system. The adhesion abilities of Kimchi-derived L. plantarum PM008 and yogurt-derived L. casei were measured in vitro and in vivo. When L. plantarum or L. casei was incubated with Caco-2 cells, these Lactobacillus strains were potently attached. When these strains were orally administered to mice, the LABs were attached on the large intestine of mice. The attachment of L. plantarum on murine intestine or Caco-2 intestinal epithelial cell lines was more potent than that of L. casei, although numbers of LAB between their feces were not different. Treatment with either L. plantarum or L. casei for 14 days suppressed fecal beta-glucuronidase activity, although treatment for one day did not affect it. L. plantarum showed more potent inhibition than L. casei. In addition, L. plantarum and L. casei were stable to artificial gastric and intestinal juice. L. plantarum was more stable than L. casei. Based on these findings, the survival and adhesion effects of orally administered LAB strains in the intestine may increase numbers of LAB in intestine and express their biological activities.
Animals
;
Bacteria
;
Caco-2 Cells
;
Epithelial Cells
;
Feces
;
Glucuronidase
;
Humans
;
Immune System
;
Intestine, Large
;
Intestines
;
Lactic Acid
;
Lactobacillus
;
Lactobacillus casei
;
Lactobacillus plantarum
;
Mice
;
Pyridines
;
Thiazoles
4.A Case of the Main Pancreatic Duct Injury Due to Blunt Abdominal Trauma Cured by Conservative Management Including Octreotide Administration.
Yun Hyeong CHO ; Jun Pyo CHUNG ; Soo Young KIM ; Seung Hyun CHO ; Juck Kum CHU ; Seung Woo PARK ; Se Joon LEE ; Si Young SONG ; Kwan Sik LEE ; Jae Bock CHUNG ; Sang In LEE ; Jin Gyung KANG
Korean Journal of Gastrointestinal Endoscopy 2002;25(2):121-124
Pancreatic trauma is uncommon, but carries high morbidity and mortality rates, especially when diagnosis is delayed or inappropriate surgery is attempted. The principal cause of pancreas specific complication and pancreas specific mortality is the presence of an injury to the pancreatic ductal system. It has been suggested that the main pancreatic duct injury is an indication of surgery or endoscopic therapy depending on the extent of leakage. Recently, we experienced a 53-year-old man who had an injury to the main pancreatic duct due to blunt abdominal trauma by a handlebar. Endoscopic retrograde pancreatography correctly diagnosed a leak at the main pancreatic duct, but his stable clinical condition and narrow main pancreatic duct precluded surgery or endoscopic therapy. Interestingly, this case was successfully treated by conservative management including octreotide administration.
Diagnosis
;
Humans
;
Middle Aged
;
Mortality
;
Octreotide*
;
Pancreas
;
Pancreatic Ducts*
5.Clinical Prognostic Values of Vascular Endothelial Growth Factor, Microvessel Density,and p53 Expression in Esophageal Carcinomas.
Myung Ju AHN ; Se Jin JANG ; Yong Wook PARK ; Jung Hye CHOI ; Ho Suk OH ; Chul Burm LEE ; Hong Kyu PAIK ; Chan Kum PARK
Journal of Korean Medical Science 2002;17(2):201-207
Vascular endothelial growth factor (VEGF) is known to play a key role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on esophageal carcinoma and the correlation between VEGF and p53. Tissue samples were taken from 81 patients with esophageal carcinoma after surgery. VEGF and p53 expressions were examined by immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and 51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE) in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no correlation was noted between VEGF and p53 expression. Whereas the tumor size, nodal status, depth of invasions, and tumor stage were associated with poor overall survival, VEGF expression or p53 expression was not. These results indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since the VEGF expression is not correlated with the p53 expression, microvessel density or clinicopathological findings, further studies with other angiogenic molecules are needed to determine the role in esophageal carcinomas.
Adult
;
Aged
;
Capillaries
;
Carcinoma, Squamous Cell/classification/*metabolism/pathology
;
Endothelial Growth Factors/*biosynthesis
;
Esophageal Neoplasms/classification/*metabolism/pathology
;
Female
;
Humans
;
Lymphatic Metastasis
;
Lymphokines/*biosynthesis
;
Male
;
Middle Aged
;
Neoplasm Staging
;
*Neovascularization, Pathologic
;
Prognosis
;
Retrospective Studies
;
Tumor Suppressor Protein p53/*biosynthesis
;
Vascular Endothelial Growth Factor A
;
Vascular Endothelial Growth Factors
6.Expression of Cyclooxygenase-2 in Human Breast Carcinoma: Relevance to Tumor Angiogenesis and Expression of Estrogen Receptor.
Haeng Ji KANG ; Gu GONG ; Se Jin JANG ; Pa Jong JUNG ; Chan Kum PARK
Cancer Research and Treatment 2001;33(4):286-295
PURPOSE: This study investigates the COX-2 expression in human primary breast carcinomas and its relationship with both angiogenesis and the expression of estrogen receptor. MATERIALS AND METHODS: COX-2 expression, angiogenesis, and estrogen receptor expression were examined by immunohistochemical methods in 167 human breast carcinomas by using monoclonal antibodies against COX-2, CD34, and estrogen receptor protein. RESULTS: Although COX-2 was expressed in 77.8% of the breast carcinomas (130/167) regardless of histological types, it was not detected at all in benign epithelial cells. Interestingly, COX-2 expression was found to be significantly correlated with tumor angiogenesis (p=0.004), but not with estrogen receptor and other histopathologic parameters. CONCLUSION: The results suggest that COX-2 expression occurs frequently in breast tissue during transformation of benign epithelial cells to malignant cells regardless of the estrogen receptor status. COX-2 expression may play a role in tumor angiogenesis that is responsible for tumor growth and metastasis.
Antibodies, Monoclonal
;
Breast Neoplasms*
;
Breast*
;
Cyclooxygenase 2*
;
Epithelial Cells
;
Estrogens*
;
Humans*
;
Neoplasm Metastasis
7.Lower gastrointestinal bleeding due to cytomegalovirus ileal ulcers in an immunocompetent man.
Sung Woo CHOI ; Jun Pyo CHUNG ; Young Koo SONG ; Young Nyun PARK ; Juck Kum CHU ; Dong Joo KIM ; Jae Han JUNG ; Chang Hoon LEE ; Se Joon LEE ; Hyo Jin PARK ; Kwan Sik LEE ; Sang In LEE ; In Suh PARK ; Seung Kook SOHN
Yonsei Medical Journal 2001;42(1):147-151
Cytomegalovirus (CMV) infections are commonly reported in severely immunocompromised hosts and ulcers of the alimentary tract are frequently observed in systemic CMV infections. However, invasive and ulcerative disease of the gastrointestinal (GI) tract caused by CMV has also been reported in healthy adults. Many reports show that a CMV infection can produce localized ulcerations in the esophagus, stomach, small intestine, and colon in nonimmunocompromised individuals. The most common site of involvement by CMV infection in the GI tract is the colon followed by the upper GI tract and the least common site is the small intestine. Although GI bleeding is one of the major presenting symptoms of patients with CMV infections of the GI tract, lower GI bleeding due to CMV ileal ulcers in immunocompetent patients, to our knowledge, has not been reported in the English literature. Recently, we experienced a case of lower GI bleeding due to CMV ileal ulcers in a 57-year-old man who had no evidence of immunocompromise. This case suggests that small intestinal ulcers due to CMV infection should be included in the differential diagnosis of lower GI bleeding even in immunocompetent hosts.
Case Report
;
Cytomegalovirus Infections/complications*
;
Gastrointestinal Hemorrhage/etiology*
;
Human
;
Ileal Diseases/complications*
;
Male
;
Middle Age
;
Ulcer/complications*
8.Result of the Proximal Tibial Osteotomy for Osteoarthritic Knee
Dae Kyung BAE ; Young Yong KIM ; Se Jin KUM ; Jae Sung AHN
The Journal of the Korean Orthopaedic Association 1989;24(2):325-333
The proximal tibial osteotomy is a procedure usually employed for osteoarthritis of the knee with a predominant single compartment involvement accompanied by pain and angular deformity. It has as its objective the shift of the gravitational line of weight from an involved to a relatively uninvolved side of knee. We studied the results of proximal tibial osteotomy in 30 patients (33knees). The mean age was 55.7 years, degenerative osteoarthritis was 31 cases (93.9%) and posttraumatic osteoarthritis was 2 cases (6.1%). The results were as follows; The average distance of osteotomy between the proximal plane and distal plane was 10.3mm. The average preoperative tibiofemoral angle was varus 3.8degrees and average postoperative tibiofemoral angle was valgus 7.6 degrees. The amount of upward displacement of fibular head after proximal tibial osteotomy was from 3mm to 16mm (mean 7.5mm). The preoperative knee rating scale was 52.9 and the postoperative knee rating scale was 78. The complications of proximal tibial osteotomy were 3 cases of transient peroneal nerve palsy and 2cases of Coventry staple loosening, but the nerve palsy was completely recovered and there were no need of staple removal.
Congenital Abnormalities
;
Head
;
Humans
;
Knee
;
Osteoarthritis
;
Osteotomy
;
Paralysis
;
Peroneal Nerve
9.Clinical Analysis for Prognostic Factors of Intertrochanteric Fractures
Myung Chul YOO ; Jin Hwan AHN ; Se Jin KUM ; Cheol Jin OH
The Journal of the Korean Orthopaedic Association 1989;24(3):776-785
There are many problems in treatment of intertrochanteric fractures due to osteoporosis and unstable pattern of fractures in old ages and they are different from those in young ages, for example, type of fracture, degree of osteoporosis, and general condition, ect. Anthors studied about the prognostic factors of 42 cases among 88 patients with intertrochanteric fractures, who were treated and followed up from Jan. 1982 to Dec. 1987. 1. The patients under 50 years old were mainly males(94.4%) and its chief cause of injury was traffic accident or fall down(72.2%). The cause of injury over 50 years old was slip down on ground(62.9%). 2. The osteoporosis was increased according to increased age of patients and then the unstable type of fracture was increased. In yaung patients, the unstable intertrochanteric fracture was rare despite of high violent injury. 3. The bone union of the follow-up patients was gained at average 13.8 weeks. 4. The sliding degree of lag screw was increased with unstable fracture and the incidence of metal protrusion into joint cavity was increased in the patients of eccentric fixation of lag screw into femoral head. 5. The all cases of complication were occured in osteoporotic patients over 50 years old and their causes were inadequate fixation of unstable fracture. 6. The most important factors in prognosis of intertrochanteric fractures are initial pattern of fractures, degree of osteoporosis and adequacy of reduction state(postop.).
Accidents, Traffic
;
Follow-Up Studies
;
Head
;
Hip Fractures
;
Humans
;
Incidence
;
Joints
;
Osteoporosis
;
Prognosis
10.Reliability of Singh's index Checked by the Dual Photon X-ray Absorptiometry(LUNAR D.P.X)
Myung Chul YOO ; Jin Hwan AHN ; Yong Girl LEE ; Se Jin KUM ; Jae Sung AHN ; Kyung Tae KIM
The Journal of the Korean Orthopaedic Association 1989;24(5):1376-1383
There are several methods available to check bone masses. One of them is Singhs index which is singlest way with grading trabecular pattern of the proximal femur on anteroposterior X-ray film and the other is recently developed Dual Photon X-ray Absorptiometry which measures bone mineral contents. Some authors proclaim that Singh's index has low accuracy, objectiveness and reproducibility. So we studied for reliability of Singh's index and correlation between Singh's index and bone mineral contents measured by Dual Photon X-ray Absorptiometry in 65 patients. There are significant differences between 3 orthopedic surgeons in interpreting Singh's index (interpersonal difference). There are significant differences between first and second interpretation out of same surgeons (intrapersonal difference). There are significant differences interpretating among interpreted Singh's indices from films of different radiological exposures in the same radiograph. There are fair correlations(0.60-0.66) between Singhs index and bone mineral density. The Singh's index was overestimated in low bone mineral density with under-exposed radiograph, but Singh's index was under-estimated in high bone mineral density with over-exposed radiograph. Singh's index can be useful in clinical application by some modification.
Absorptiometry, Photon
;
Bone Density
;
Femur
;
Humans
;
Orthopedics
;
Surgeons
;
X-Ray Film

Result Analysis
Print
Save
E-mail