• Design & Manufacturing
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• v.17 no.1
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• pp.20-26
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• 2023

Lab-on-a-disc is a circular disc shape of cartridge that can be used for blood-based liquid biopsy to diagnose an early stage of cancer. Currently, liquid biopsies are regarded as a time-consuming process, and require sophisticated skills to precisely separate cell-free DNA (cfDNA) and circulating tumor cells (CTCs) floating in the bloodstream for accurate diagnosis. However, by applying the lab-on-a-disc to liquid biopsy, the entire process can be operated automatically. To do so, the lab-on-a-disc should be designed to prevent blood leakage during the centrifugation, transport, and dilution of blood inside the lab-on-a-disc in the process of liquid biopsy. In this study, the main components of lab-on-a-disc for liquid biopsy are fabricated by injection molding for mass production, and ultrasonic welding is employed to ensure the bonding strength between the components. To guarantee accurate ultrasonic welding, the flatness of the components is optimized numerically by using the response surface methodology with four main injection molding processing parameters, including the mold & resin temperatures, the injection speed, and the packing pressure. The 27 times finite element analyses using Moldflow® reveal that the injection time and the packing pressure are the critical factors affecting the flatness of the components with an optimal set of values for all four processing parameters. To further improve the flatness of the lab-on-a-disc components for stable mass production, a quarter-disc shape of lab-on-a-disc with a radius of 75 mm is used instead of a full circular shape of the disc, and this significantly decreases the standard deviation of flatness to 30% due to the reduced overall length of the injection molded components by one-half. Moreover, it is also beneficial to use a quarter disc shape to manage the deviation of flatness under 3 sigma limits.

• Journal of Life Science
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• v.34 no.7
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• pp.520-530
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• 2024

Tumor suppressor genes (TSGs) play a crucial role in maintaining cellular homeostasis. When the function of these genes is lost, it can lead to cellular plasticity that drives the development of various cancers, including small-cell lung cancer (SCLC), which is known for its aggressive nature. SCLC is primarily driven by numerous loss-of-function mutations in TSGs, often involving genes that encode epigenetic regulators. These mutations pose a significant therapeutic challenge as they are not directly targetable. However, understanding the molecular changes resulting from these mutations might provide insights for developing tumor intervention strategies. We propose that despite the heterogeneous genomic landscape of SCLC, the effects of mutations in patient tumors converge on a few critical pathways that drive malignancy. Specifically, alterations in epigenetic regulators lead to transcriptional dysregulation, pushing mutant cells toward a highly plastic state that makes them immune evasive and highly metastatic. This review will highlight studies showing how an imbalance of epigenetic regulators with opposing functions leads to the loss of immune recognition markers, effectively hiding tumor cells from the immune system. Additionally, we will discuss the role of epigenetic regulators in maintaining neuroendocrine features and how aberrant transcriptional control promotes epithelial-to-mesenchymal transition during tumor development. Although these pathways seem distinct, we emphasize that they often share common molecular drivers and mediators. Understanding the connection among frequently altered epigenetic regulators will provide valuable insights into the molecular mechanisms underlying SCLC development, potentially revealing preventive and therapeutic vulnerabilities for SCLC and other cancers with similar mutations.

• Korean Journal of Radiology
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• v.25 no.2
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• pp.179-188
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• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

• Radiation Oncology Journal
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• v.5 no.2
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• pp.149-155
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• 1987

The success of radioation therapy depends on exact treatment of the tumor with significant high dose for maximizing local control and excluding the normal tissues for minimizing unwanted complications. To achieve these goals, correct estimation of target volume in three dimension, exact dose distribution in tumor and normal critical structures and correction of tissue inhomogeneity are required. The effect of therapy oriented CT (plannng CT) were compared with conventional simulation method in necessity of planning change, set dose, and proper distribution of tumor dose. Of 365 new patients examined, planning CT was performed in 104 patients $(28\%)$. Treatment planning was changed in $47\%$ of head and neck tumor, $79\%$ of intrathoracic tumor and $63\%$ of abdmonial tumor. in breast cancer and musculoskeletal tumors, planning CT was recommended for selection of adequate energy and calculation of exact dose to critical structures such as kidney or spinal cord. The average difference of tumor doses between CT planning and conventional simulation was $10\%$ in intrathoracic and intra-abdominal tumors but $20\%$ in head and neck tumors which suggested that tumor dose may be overestimated in conventional simulation Although some limitations and disadvantages including the cost and irradiation during CT are still criticizing, our study showed that CT Planning is very helpful in radiotherapy Planning.

• KSBB Journal
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• v.20 no.3
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• pp.220-227
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• 2005

Doxorubicin is an anthracycline-family polyketide compound with a very potent anti-cancer activity, typically produced by Streptomyces peucetius. To understand the potential target biosynthetic genes critical for the doxorubicin everproduction, a doxorubicin-specific DNA microarray chip was fabricated and applied to reveal the growth-phase-dependent expression profiles of biosynthetic genes from two doxorubicin-overproducing strains along with the wild-type strain. Two doxorubicin-overproducing 5. peucetius strains were generated via over-expression of a dnrl (a doxorubicin-specific positive regulatory gene) and a doxA (a gene involved in the conversion from daunorubicin to doxorubicin) using a streptomycetes high expression vector containing a strong ermE promoter. Each doxorubicin-overproducing strain was quantitatively compared with the wild-type doxorubicin producer based on the growth-phase-dependent doxorubicin productivity as well as doxorubicin biosynthetic gene expression profiles. The doxorubicin-specific DNA microarray chip data revealed the early-and-steady expressions of the doxorubicin-specific regulatory gene (dnrl), the doxorubicin resistance genes (drrA, drrB, drrC), and the doxorubicin deoxysugar biosynthetic gene (dnmL) are critical for the doxorubicin overproduction in S. peucetius. These results provide that the relationship between the growth-phase-dependent doxorubicin productivity and the doxorubicin biosynthetic gene expression profiles should lead us a rational design of molecular genetic strain improvement strategy.

• Journal of the Korean Magnetics Society
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• v.25 no.6
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• pp.208-218
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• 2015

Recently, radiation therapy is used in the CT existing conventional two-dimensional radiation image, and set the size and location of the tumor in a manner that the image is going to change the treatment plan. After using the simulation using CT, radiation therapy it is four-dimensional or three-dimensional treatment made possible. and radiation therapy became the more effective ever before. High technology radiation therapy such as the treatment of SRS,IMRT, IGRT, SBRT, is a need to try contemplating the possibility to apply appropriate analysis and situation, so it has its own characteristics. and then it is believed that it is necessary to analyze and try it worries the proper applicability of the situation. The configuration of the various treatment that is applicable in many hospitals is necessary to try to determine how to practically apply the patients. Critical organs surrounding tumor give a small dose to avoid side effects and then the tumor has the therapeutic effect by providing a larger dose than before the radiation treatment.

• Pediatric Infection and Vaccine
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• v.30 no.1
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• pp.47-54
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• 2023

With the widespread use of broad-spectrum antibiotics in clinical practice, the emergence of multidrug-resistant (MDR) gram-negative bacteria has become a global problem. The MDR Pseudomonas aeruginosa infection is especially difficult to treat and increases mortality in critically ill patients. Ceftolozane-tazobactam (Zerbaxa^TM) is a fifth-generation cephalosporin and beta-lactamase inhibitor that has proved to be effective for treating complicated urinary tract infections and complicated intra-abdominal infections caused by MDR P. aeruginosa. Herein, we report the first case of pediatric hematologic cancer in Korea that was successfully treated for MDR P. aeruginosa bacteremia with Ceftolozane-tazobactam.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.223-230
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• 2009

Purpose: Circular stapled gastrectomy has been the favored procedure with its feasibility and the shortened operative time, but anastomotic leakage, stenosis and bleeding have been reported as problems. The aim of this study was to identify what can be done to supplement the safety of this technique by examining the potential complications of performing circular stapled gastrojejunosomy after radical subtotal gastrectomy. Materials and Methods: As subjects, this study selected 1,391 patients who underwent gastrojejunostomy after radical subtotal gastrectomy because of gastric cancer at our Department of Surgery from Jan. 1998 to Dec. 2007. The patients were divided into Group I (n=479) who underwent hand-sewn gastrojejunostomy, Group II (n=48) who underwent linear stapled gastrojejunostomy and Group III (n=864) who underwent circular stapled gastrojejunostomy. Group III was re-divided into two subgroups on the basis of the point of time that a visual check was intraoperatively performed at the anastomotic site: Group III-A (n=198) before and Group III-B (n=666) after. The characteristics and complications of the patients were then compared. Results: For the comparison of the complications between Group I, Group II and Group III, anastomotic leakage was found in 7 cases (1.5%) in Group I, in 1 case (2.0%) in Group II and in 10 case (1.2%) in Group III, and anastomotic stenosis were found in 4 cases (0.8%) in Group I, 1 case (2.0%) in Group II and 5 case (0.6%) in Group III. Anastomotic bleeding was found in 32 cases (6.7%) in Group I, in 5 cases (10.4%) in Group II and in 67 cases (7.7%) in Group III. For the comparison of complications between Group III-A and Group III-B, anastomotic bleeding was found in 57 cases (28.8%) in Group III-A and 10 cases (1.5%) in Group III-B and the difference was statistically significant (P=0.037). Conclusion: Circular stapled gastrojejunostomy after radical subtotal gastrectomy is recommended because of the safety and feasibility of this technique, but bleeding at the anastomotic site may be the critical issue. In conclusion, direct inspection for bleeding at the anastomotic site during the operation will improve the safety of performing circular stapler anastomosis.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.103-108
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• 2006

Purpose: The circular stapled Billroth I gastrectomy has been gradually popularized because of several advantages. Thus, this study aims to identify what to be supplemented for the safety of this technique by examining the potential complication after the circular stapled Billroth I gastrectomy. Materials and Methods: This study selected 594 patients who underwent the circular stapled Billroth I gastrectomy because of the gastric cancer in our department of surgery from Jan. 1998 to Dec. 2004 as the subjects. As of Jan. 2001 when the bleeding on the anastomosis site was visually checked through the small incision at the opposite curvature to the lesion of the stomach to be resected and so the operation was completed, the patients were divided into the Group I (n=219) and Group II (n=375), which were the patients before and after Jan. 2001, respectively. Then, the clinical characteristics and postoperative anastomotic complications of both groups were compared. Results: For the comparison of complications between two groups, the anastomotic leakage was found in four cases in Group I and three cases in Group II (p=0.196). The stenosis on the anastomosis region was not observed in both groups. The bleeding on the anastomosis region illustrates the statistically significant difference between Group I and Group II, with 43 cases and 2 cases, respectively (P=0.0019). Conclusion: The circular stapled Billroth I gastrectomy is recommended because of several advantages of this technique. However, the bleeding on the anastomosis site may be indicated as the critical issue. Accordingly, the visual check on the bleeding on the anastomosis site during the operation will improve the safety of circular stapler.