• Molecules and Cells
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• v.42 no.11
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• pp.773-782
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• 2019

Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, $p21^{Cip1/WAF1}$ is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of $p21^{Cip1/WAF}$. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of $p21^{Cip1/WAF1}$, leading to H3K9me3 and SAHFs formation.

• Archives of Plastic Surgery
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• v.48 no.4
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• pp.417-426
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• 2021

Background Soft tissue coverage plays a vital role in replacing the vascularity of the underlying bone in Gustilo type IIIB fractures. The aim of this article was to evaluate the feasibility of local pedicled flaps in type IIIB fractures at a tertiary care center. Methods We included all cases of open Gustilo-Anderson type IIIB fractures of the tibia treated with local flap coverage from January 2017 to February 2019. We carried out a retrospective analysis to investigate the relationships of complications, hospital stay, and cost-effectiveness with the choice of flap, infective foci, site and size of the defect, and type of fixation. Results Out of 138 Gustilo type IIIB fractures analyzed in our study, 27 cases had complications, of which 19 (13.76%) involved flap necrosis, four (2.89%) were infections, three (2.17%) involved partial necrosis, and one (0.72%) was related to bone spur development. Flap complications showed a statistically significant association with the perforator flap category (propeller flaps in particular) (P=0.001). Flap necrosis showed a significant positive correlation with cases treated within 3 weeks after trauma (P=0.046). A significant positive correlation was also found between defect size and the duration of hospital stay (P=0.03). Conclusions Although local flaps are harvested from the same leg that underwent trauma, their success rate is at least as high as microvascular flaps as reported from other centers. Amidst the local flaps, complications were predominantly associated with perforator flaps.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.369-374
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• 2008

Purpose: F-18 FDG PET/CT has excellent sensitivity and specificity for staging non-Hodgkin lymphomas, but to the author's knowledge few studies to date have evaluated FDG PET/CT in peripheral T cell lymphoma. We evaluated the usefulness of F-18 FDG PET/CT in staging of patients with peripheral T cell lymphoma, especially indolent cutaneous T cell lymphomas. Materials and Methods: Twenty five patients (M:F=17:8, age $53.7{\pm}14.8$ yrs) with biopsy-proven indolent cutaneous T cell (CL) or noncutaneous T cell lymphomas (NCL) underwent PET/CT scans for staging at baseline. Peak standardized uptake values (p-SUV) of all abnormal foci were measured and compared between cutaneous and noncutaneous lesions. F-18 FDG PET/CT was performed on 6 patients with indolent CL and on 19 patients with NCL. Results: All 6 patients with indolent CL had no significant FDG avidity in the skin despite histologically positive cutaneous lesions. However, FDG avidity appeared in extracutaneous lesions (lymph nodes) in two patients with CL where CT imaging suggested lymphoma involvement (mean p-SUV $4.26{\pm}0.37$ in noncutaneous lesions in CL). In NCL, FDG avidity was demonstrated in all lesions where CT imaging suggested lymphoma involvement (mean p-SUV, $8.52{\pm}5.00$ in noncutaneous lesions in NCL). Conclusion: F-18 FDG PET/CT has the limitation of usefulness for the evaluation of the skin in indolent CL. In contrast, F-18 FDG PET/CT is sensitive in staging evaluation of extracutaneous lesions regardless of CL or NCL.

• Journal of Gastric Cancer
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• v.1 no.3
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• pp.174-179
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• 2001

Purpose: For curative resection of recurrent gastric cancer, it is imperative that there be no unrecognized foci of tumoral disease outside the operation field. PET (positron emission tomography) with FDG (18 fluoro-2 deoxy-D-glucose) is a whole-body imaging technique that exploits the increased rate of glycolysis in tumor cells to detect disease. The authors evaluated the usefulness of FDG-PET in assessing resectability of recurrent gastric cancer. Materials and Methods: Seven patients with recurrent gastric cancer were studied with FDG-PET from December 1998 to October 2000. All FDG-PET images were interpreted in conjunction with conventional diagnostic methods. All imaging results were correlated with the pathological diagnosis and clinical outcome. Results: A final diagnosis of recurrence was obtained at 14 sites in all 7 patients by histology or clinical follow up. Locoregional recurrence, including distant metastasis, developed in 6 of 7 patients and distant recurrence in only one. FDG-PET detected all recurrent sites (5 locoregional and 5 distant) in 5 patients without peritoneal recurrence, but did not detect peritoneal seeding in 2 patients with peritoneal recurrence. The accuracy of FDG-PET in estimating resectability was $71.4\%$ (5/7), and that of CT and PET together was $85.7\%$ (6/7). A curative resection could be performed in three of the recurrent patients (2 locoregional and 1 distant recurrence). Conclusion: Our results suggest that FDG-PET may be useful for detecting locoregional and distant recurrence of gastric cancer and for selecting appropriate treatment. However, considering that FDG-PET was limited in detecting peritoneal seeding and determining the exact anatomical extension of tumor, it should be used in conjunction with other anatomical images.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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• pp.239-245
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• 2005

Purpose: Hypereosinophilic syndrome (HES) is an infiltrative disease of eosinophils affecting multiple organs including the iung. F-18 2-fluoro-2-deoxyglucose (F-18 FDG) may accumulate at sites of inflammation or injection, making interpretation of whole body PET scan difficult in patients with cancer. This study was to evaluate the PET findings of HES with lung involvement and to find out differential PET features between lung malignancy and HES with lung involvement. Material and Methods: F-18 FDG PET and low dose chest CT scan was performed for screening of lung cancer. light patients who showed ground-glass attenuation (GGA) and consolidation on chest CT scan with peripheral blood eosinophilia werr included in this study. The patients with history of parasite infection, allergy and collagen vascular disease were excluded. CT features and FDG PET findings were meticulously evaluated for the distribution of GGA and consolidation and nodules on CT scan and mean and maximal SUV of abnormalities depicted on F-18 FDG PET scan. In eight patients, follow-up chest CT scan and FDG PET scan were done one or two weeks after initial study. Results: F-18 FDG PET scan identified metabolically active lesions in seven out of eight patients. Maximal SUV was ranged from 2.8 to 10.6 and mean SUV was ranged from 2.2 to 7.2. Remaining one patient had maximal SUV of 1.3. On follow-up FDG PET scan taken on from one to four weeks later showed decreased degree of initially noted FDG uptakes or migration of previously noted abnormal FDG uptakes. Conclusions: Lung involvement in the HES might be identified as abnormal uptake foci on FDG PET scan mimicking lung cancer. Follow-up FDG PET and CT scan for the identification of migration or resolution of abnormalities and decrement of SUV would be of help for the differentiation between lung cancer and HES with lung involvement.

• KSBB Journal
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• v.24 no.4
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• pp.403-409
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• 2009

H2AX, a crucial component of chromatin, is implicated in DNA repair, cell cycle check point and tumor suppression. The aim of this study was to identify direct binding partners of H2AX to regulate cellular responses to above mechanisms. Literature reviews and bioinformatical tools were attempted intensively to find binding partners of H2AX, which resulted in identifying two potential proteins, breast cancer-1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1). Although it has been reported in vivo that BRCA1 co-localizes with H2AX at the site of DNA damage, their biochemical mechanism for H2AX were however only known that the complex monoubiquitinates histone monomers, including unphosphorylated H2AX in vitro. Therefore, it is important to know whether the complex directly interacts with H2AX, and also which regions of these are specifically mediated for the interaction. Using in vitro GST pull-down assay, we present here that BRCA1 and BARD1 directly bind to H2AX. Moreover, through combinational approaches of domain analysis, fragment clonings and in vitro binding assay, we revealed molecular details of the BRCA1-H2AX and BARD1-H2AX complex. These data provide the potential evidence that each of the BRCA1 nuclear localization signal (NLS) and BARD1 BRCA1 C-terminal (BRCT) repeat domain is the novel mediator of H2AX recognition.

• Journal of Yeungnam Medical Science
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• v.15 no.2
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• pp.359-370
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• 1998

Eight cases of chonproblastoma were studied by analyzing the clinical and pathologic findings. The age of eight cases ranged from 17 to 38 years old(median age, 22.7 years old). The tumors developed in the femur(3 cases), patella(2 cases), tibia(1 case), fibula(l case), and ulna(1 case). The mean diameter of tumors was 4.0cm (range, 1.5 to 8.0cm). Grossly, tumors showed grayish brown solid area with foci of secondary aneurysmal bone cyst. Histologically, the tumor cells were round or polygonal in shape with nuclear groove. And there were chondroid differentiation(7 cases), mitosis(3 cases), calcific deposits(3 cases), secondary aneurysmal bone cyst(4 cases), hemosiderin deposits(4 cases), necrosis(3 cases), vascular invasion(1 caes), and foamy histiocytes and cholesterol cleft(l cases). All cases showed no metastasis to lymph node and distant organ. Seven cases (87.5%) were immunoreactive for S-100 protein. None was immunoreactive for cytokeratin.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.452-458
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• 1997

To evaluate the pinhole scintigraphic findings and its significance, authors retrospectively compared the pinhole bone scintigrams and corresponding radiograms of 16 lesions in 14 patients with fibrous dysplasia. They were diagnosed pathologically in 10 lesions and radiologically in 6 lesions. The mean age of patients was 41.1 years. The mean interval between two studies was 1.1 days. Locations were ribs 7, pelvic bone 4, clavicle 1, long bones 4(femur 2, tibia 1, humerus 1). The radiographic findings were as follows : the central portions were radiolucent(n=9), ground-glass opacities(n=5) or sclerotic(n=2) and the peripheral appearance were sclerotic rim(n=5), septation(n=7), cortical perforation (n=10) and invisible cortical thinning(n=9). Pinhole scintigraphic findings were as follows; Central portions showed normal 1+ uptake in 6 cases(radiolucent 5, ground-glass opacity 1), slightly increased 2+ upta- ke in 7 cases(radiolucent 4, ground-glass opacity 3), and marked 3+ uptake in 3 cases(ground-glass opacity 1, sclerotic 2). The 15 of 16 lesions showed more intense uptake in the peripheral portion: slightly increased 2+ uptake corresponding to the sclerotic rim(5/5) and unvisible cortical thinning(1/9), and irregular foci of marked 3 + uptake corresponding to septation(7/7), cortical perforation(10/10) and invisible cortical thinning (8/9). One of 16 lesions showed homogeneous 2+ uptake. In conclusion, pinhole scintigram provides information on regional activity of the fibrous dysplasia, which would be helpful in diagnosis, prediction of prognosis and determination of treatment plan.