• BLOOD RESEARCH
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• v.53 no.4
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• pp.276-280
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• 2018

Background Chronic lymphocytic leukemia (CLL) exhibits profound heterogeneity in its clinical course. Its clinicohematological and cytogenetic features play a significant role in determining the clinical course and in predicting the treatment response and prognosis. In this context, 17p deletion is known to predict a poor prognosis, as these cases are refractory to conventional therapy. This study aimed to evaluate the clinicohematological characteristics, outcomes, and prognostic factors among CLL patients with and without del 17p in Pakistan. Methods This prospective observational study was conducted at the Department of Haematology, Armed Forces Institute of Pathology (Rawalpindi, Pakistan) between January 2013 and December 2017. Patients were diagnosed based on the International Workshop on Chronic Lymphocytic Leukaemia IWCLL criteria, their clinicohematological parameters were recorded, and cytogenetic analyses were performed. The time from diagnosis to treatment and the 2-year overall survival rate were also evaluated. Results We evaluated 130 CLL cases, including 24 patients (18.5%) with del 17p, who included 18 men (75%) and 6 women (25%). The median age was 68 years. Binet stage C was detected at the presentation in 16 patients (67%). Treatment was administered to 14 patients (70%) at a median interval of 11 months (range, 0-28 mo) after diagnosis. The overall response rate was 64.3%, the median event-free survival was 9 months (range, 1-23 mo), and the 2-year overall survival rate was 65%. Conclusion Del 17p is relatively common in Pakistan, and patients harboring this deletion had poor treatment response and survival outcomes.

• BMB Reports
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• v.53 no.12
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• pp.622-627
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• 2020

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anticancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.

• Molecules and Cells
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• v.44 no.1
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• pp.50-62
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• 2021

Among all cancer types, lung cancer ranks highest worldwide in terms of both incidence and mortality. The crosstalk between lung cancer cells and their tumor microenvironment (TME) has begun to emerge as the "Achilles heel" of the disease and thus constitutes an attractive target for anticancer therapy. We previously revealed that crosstalk between lung cancer cells and endothelial cells (ECs) induces chemoresistance in multicellular tumor spheroids (MCTSs). In this study, we demonstrated that factors secreted in response to crosstalk between ECs and lung cancer cells play pivotal roles in the development of chemoresistance in lung cancer spheroids. We subsequently determined that the expression of hypoxia up-regulated protein 1 (HYOU1) in lung cancer spheroids was increased by factors secreted in response to crosstalk between ECs and lung cancer cells. Direct interaction between lung cancer cells and ECs also caused an elevation in the expression of HYOU1 in MCTSs. Inhibition of HYOU1 expression not only suppressed stemness and malignancy, but also facilitated apoptosis and chemosensitivity in lung cancer MCTSs. Inhibition of HYOU1 expression also significantly increased the expression of interferon signaling components in lung cancer cells. Moreover, the activation of the PI3K/AKT/mTOR pathway was involved in the HYOU1-induced aggression of lung cancer cells. Taken together, our results identify HYOU1, which is induced in response to crosstalk between ECs and lung cancer cells within the TME, as a potential therapeutic target for combating the aggressive behavior of cancer cells.

• Journal of The Korean Association For Science Education
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• v.29 no.2
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• pp.253-266
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• 2009

This study was focused on analyzing students' informal reasoning patterns and their considerations in decision-making on socioscientific issues. This study involved 20 undergraduate students (10 biology majors and 10 non-biology majors) and showed how the two groups responded on socioscientific issues. Semi-structured interviews were conducted twice respectively based on six scenarios of gene therapy and human cloning. The result showed 93% of the total number of participants' decisions were made by rationalistic reasoning, whereas emotional reasoning was 49%, and intuitive reasoning was 27%. Students usually used two or three informal reasoning patterns together. Most of the students took more consideration on social factors. Some perceived ethical and moral implications of the issues, but they did not consider them seriously. They made their decisions depending on their own values, etc. 65% of the participants got their information on socioscientific issues from the mass media. Biology majors hardly used intuitive reasoning compared to non-biology majors. The Biology major group took into deep considerations on socioscientific issues while the non-biology major group seemed to interpret the given scenarios simply. This implied that the content knowledge was a significant factor of their decision-making. Therefore, it is necessary to develop proper science courses for non-major students to improve their decision-making on socioscientific issues. So, when we develop educational materials or programs, we should consider students' reasoning patterns, their considerations in decision-making, and their content knowledge. And because the mass media has the potential to play a key role for an effective education, we need to make a plan to make a practical application.

• Korean Journal of Radiology
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• v.23 no.1
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• pp.60-67
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• 2022

Objective: To categorize multiparametric MRI features of Bacillus Calmette-Guérin (BCG)-related granulomatous prostatitis (GP) and discover potential manifestations for its differential diagnosis from prostate cancer. Materials and Methods: The cases of BCG-related GP in 24 male (mean age ± standard deviation, 66.0 ± 9.4 years; range, 50-88 years) pathologically confirmed between January 2011 and April 2019 were retrospectively reviewed. All patients underwent intravesical BCG therapy followed by a MRI scan. Additional follow-up MRI scans, including diffusion-weighted imaging (DWI), were performed in 19 patients. The BCG-related GP cases were categorized into three: A, B, or C. The lesions with diffusion restriction and homogeneous enhancement were classified as type A. The lesions with diffusion restriction and a poorly enhancing component were classified as type B. A low signal intensity on high b-value DWI (b = 1000 s/mm²) was considered characteristic of type C. Two radiologists independently interpreted the MRI scans before making a consensus about the types. Results: The median lesion size was 22 mm with the interquartile range (IQR) of 18-26 mm as measured using the initial MRI scans. The lesion types were A, B, and C in 7, 15, and 2 patients, respectively. Cohen's kappa value for the inter-reader agreement for the interpretation of the lesion types was 0.837. On the last follow-up MRI scans of 19 patients, the size decreased (median, 5.8 mm; IQR, 3.4-8.5 mm), and the type changed from A or B to C in 11 patients. The lesions resolved in four patients. In five patients who underwent prostatectomy, caseous necrosis on histopathology matched with the non-enhancing components of type B lesions and the entire type C lesions. Conclusion: BCG-related GP demonstrated three imaging patterns on multiparametric MRI. Contrast-enhanced T1-weighted imaging and DWI may play a role in its differential diagnosis from prostate cancer.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.315-325
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• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

• Journal of The Korea Institute of Healthcare Architecture
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• v.30 no.1
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• pp.37-44
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• 2024

Purpose: The planning of medical facilities involves formulating a comprehensive medical basic plan, translating it into spatial dimensions through a space program. Feasibility assessment often relies on empirical methods like floor area per bed. However, with the shift towards specialized medical concepts, proportional scaling to bed numbers is challenging. This study proposes scale planning improvements during the feasibility assessment stage for comprehensive hospitals, analyzing cases using area determination factors and standard areas based on medical resources. Methods: The Korean Development Institute's Public Investment Management Center (KDI) identified issues in the scale determination of medical facilities in the Preliminary Feasibility Study Guidelines and investigated alternative approaches for determining the scale of a case that passed the preliminary feasibility study in 2019. The study assessed the feasibility of applying individual factors to determine not only the number of beds but also the scale at the sector and department levels. Additionally, a statistical analysis was conducted to examine the correlation between the total number of beds and various area determination factors. Results: Results suggest a strong correlation between total beds and major equipment needs, but in hospitals with <500 beds, this correlation weakens. Ward section scale is better calculated per ward type, not just total beds. Outpatient department scale depends on specialists, influencing treatment room numbers. Medical personnel play a crucial role in determining the scale of sections like rehabilitation therapy rooms, operating rooms, dialysis rooms, and overall facility scale.

• Journal of the Korean Society of Radiology
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• v.84 no.5
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• pp.999-1008
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• 2023

Thyroid cancer, characterized by high incidence rates, good prognosis, and frequent recurrence, is typically treated surgically. However, since the early 2000s, radiofrequency ablation, which is commonly utilized in liver, lung, and kidney cancers, is being performed for management of primary and recurrent thyroid cancers. Many studies have focused on inoperable cases of low-risk papillary microcarcinoma (≤ 1 cm) and some have investigated its role in larger lesions (up to 4 cm). Overall, these studies have reported positive results. Radiofrequency ablation for recurrent cancer has primarily been performed for locally recurrent cervical cancer, and this therapeutic approach has been attempted for treatment of distant metastases in lungs and bones, with encouraging outcomes. A growing global trend, particularly in South Korea, the United States, and Europe supports radiofrequency ablation for thyroid cancer. However, this therapy is currently not recognized as a treatment option recommended by universally accepted clinical guidelines such as those established by the National Comprehensive Cancer Network. Based on past efforts and future research, radiofrequency ablation is expected to play a key role in thyroid cancer treatment in the near future.

• Tuberculosis and Respiratory Diseases
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• v.87 no.2
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• pp.123-133
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• 2024

Interstitial lung diseases (ILDs) are a diverse collection of lung disorders sharing similar features, such as inflammation and fibrosis. The diagnosis and management of ILD require a multidisciplinary approach using clinical, radiological, and pathological evaluation. Progressive pulmonary fibrosis (PPF) is a distinct form of progressive and fibrotic disease, occurring in ILD cases other than in idiopathic pulmonary fibrosis (IPF). It is defined based on clinical symptoms, lung function, and chest imaging, regardless of the underlying condition. The progression to PPF must be monitored through a combination of pulmonary function tests (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide), an assessment of symptoms, and computed tomography scans, with regular follow-up. Although the precise mechanisms of PPF remain unclear, there is evidence of shared pathogenetic mechanisms with IPF, contributing to similar disease behavior and worse prognosis compared to non-PPF ILD. Pharmacological treatment of PPF includes immunomodulatory agents to reduce inflammation and the use of antifibrotics to target progressive fibrosis. Nintedanib, a known antifibrotic agent, was found to be effective in slowing IPF progression and reducing the annual rate of decline in FVC among patients with PPF compared to placebos. Nonpharmacological treatment, including pulmonary rehabilitation, supplemental oxygen therapy, and vaccination, also play important roles in the management of PPF, leading to comprehensive care for patients with ILD. Although there is currently no cure for PPF, there are treatments that can help slow the progression of the disease and improve quality of life.

• Archives of Plastic Surgery
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• v.51 no.4
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• pp.378-385
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• 2024

Background The best timing of closure of the hard palate in individuals with cleft lip, alveolus, and palate (CLAP) to reach the optimal speech outcomes and maxillary growth is still a subject of debate. This study evaluates changes in compensatory articulatory patterns and resonance in patients with unilateral and bilateral CLAP who underwent simultaneous closure of the hard palate and secondary alveolar bone grafting (ABG). Methods A retrospective study of patients with nonsyndromic unilateral and bilateral CLAP who underwent delayed hard palate closure (DHPC) simultaneously with ABG at 9 to 12 years of age from 2013 to 2018. The articulatory patterns, nasality, degree of hypernasality, facial grimacing, and speech intelligibility were assessed pre- and postoperatively. Results Forty-eight patients were included. DHPC and ABG were performed at the mean age of 10.5 years. Postoperatively hypernasal speech was still present in 54% of patients; however, the degree of hypernasality decreased in 67% (p < 0.001). Grimacing decreased in 27% (p = 0.015). Articulation disorders remained present in 85% (p = 0.375). Intelligible speech (grade 1 or 2) was observed in 71 compared with 35% of patients preoperatively (p < 0.001). Conclusion This study showed an improved resonance and intelligibility following DHPC at the mean age of 10.5 years, however compensatory articulation errors persisted. Sequential treatments such as speech therapy play a key role in improvement of speech and may reduce remaining compensatory mechanisms following DHPC.