In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.
Although being one of the major causes of malignancy related death globally, hepatocellular carcinoma (HCC) has not received much attention in respect of novel drug development. Fortunately, several new drugs were found to be effective and tolerable in patients with advanced HCC from a number of phase 3 studies during the recent several years. Novel multi-targeted kinase inhibitors and immune checkpoint inhibitors were approved for clinical use, and combination strategies to maximize the potent of drugs demonstrated promising antitumor activity and safety with high response rate and improved safety profile. The increased number of available agents for HCC will contribute to change of treatment strategies and prognosis of patients with advanced HCC. Still, there is a many critical questions remain unanswered. Currently ongoing trials and future studies will provide better understanding of tumor biology and optimized criteria for patient selection and combination therapies.
Journal of The Korean Society of Inherited Metabolic disease
/
v.24
no.1
/
pp.10-16
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2024
Congenital Disorders of Glycosylation (CDG) represent a complex group of inherited metabolic disorders resulting from defects in multiple pathways of glycosylation, a critical biochemical process for protein functionality and cellular communication. This review provides a comprehensive overview of CDG, including its history, epidemiology, classification, diagnostic complexities, and therapeutic developments. Despite advancements in understanding CDG and identifying over 160 subtypes, challenges remain due to the diverse clinical manifestations and multi-systemic involvement. Targeted therapy is available for only a few CDGs, but promising treatments are being investigated. Ongoing research is vital to developing targeted treatments and improving patient outcomes.
Acute lymphoblastic leukemia (ALL) is one of the most rapidly changing hematological malignancies with advanced understanding of the genetic landscape, detection methods of minimal residual disease (MRD), and the development of immunotherapeutic agents with good clinical outcomes. The annual incidence of adult ALL in Korea is 300-350 patients per year. The WHO classification of ALL was revised in 2022 to reflect the molecular cytogenetic features and suggest new adverse-risk subgroups, such as Ph-like ALL and ETP-ALL. We continue to use traditional adverse-risk features and cytogenetics, with MRD-directed post-remission therapy including allogeneic hematopoietic cell transplantation. However, with the introduction of novel agents, such as ponatinib, blinatumomab, and inotuzumab ozogamicin incorporated into frontline therapy, good MRD responses have been achieved, and overall survival outcomes are improving. Accordingly, some clinical trials have suggested a possible era of chemotherapy-free or transplantation-free approaches in the near future. Nevertheless, relapse of refractory ALL still occurs, and some poor ALL subtypes, such as Ph-like ALL and ETP-ALL, are unsolved problems for which novel agents and treatment strategies are needed. In this review, we summarize the currently applied diagnostic and therapeutic practices in the era of advanced genetic analysis and targeted immunotherapies in United States and Europe and introduce real-world Korean data.
Metabolizable energy (ME) required for basal metabolism, activity and growth was considered as the criterion for targeting specific increases in body weight (100 g/week) of broiler chicks during the grower phase (5-20 weeks) and its impact was evaluated on breeder performance. Broiler female chicks (460) from a synthetic dam line were randomly distributed to 4 test groups with 23 replicates of 5 birds each and housed in cages. The first group (ME-100) was offered a calculated amount of ME by providing a measured quantity of grower diet (160 g protein and 2,600 kcal ME/kg) which increased with age and weight gain (133-294 kcal/bird/day). The other three groups were offered 10 or 20% less ME (ME-90 and ME-80, respectively) and 10% excess ME (ME-110) over the control group (ME-100). From 21 weeks of age, a single breeder diet (170 g protein and 2,600 kcal ME/kg) was uniformly fed to all groups and the impact of grower ME restriction on breeder performance evaluated up to 58 weeks. The targeted body weight gain of 1,600 g in a 16-week period was achieved by pullets of the ME-100 group almost one week earlier by gaining 8.7 g more weight per week. However, pullets in the ME-90 group gained 1,571 g during the same period, which was closer to the targeted weight. At 20 weeks of age, the conversion efficiency of feed (5.21-5.37), ME (13.9-14.1 kcal/g weight gain) and protein (0.847-0.871 g/g weight gain), eviscerated meat yield, giblet and tibia weights were not influenced by ME restriction, but the weights of abdominal fat and liver were higher with increased ME intake. Reduction of ME by 10% in the grower period significantly delayed sexual maturity (169.3 d), but increased egg production (152.5 /bird) with better persistency. Improved conversion efficiency of feed, ME and protein per g egg content were also observed in this group up to 56 weeks. The fertility and hatchability at 58 weeks of age were higher in the ME-90 group compared to the control and 10% excess ME feeding. In conclusion, the present study revealed the possibility of achieving targeted weight gain in broiler growers by feeding measured quantities of ME during the rearing period with consequential benefits in breeder performance.
The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles.
Kim, Chiwoo;Hwang, Jeongyun;Yang, Aram;Kim, Jinsup;Lee, Taeheon;Jang, Ja-Hyun;Cho, Sung Yoon;Jin, Dong-Kyu
Journal of The Korean Society of Inherited Metabolic disease
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v.17
no.2
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pp.69-76
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2017
Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene on chromosome 7q21.3, and a type of urea cycle disorder that causes hyperammonemia. Although neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, a type of citrin deficiency, have been described well in many articles for several decades, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), the other type of citrin deficiency, has been only identified recently. There was previously no case report about FTTDCD in Korea. Patients with FTTDCD could present with loss of appetite, fatigue, failure to thrive, hypoglycemia, hypercitrullinemia, dyslipidemia, and an increased lactate/pyruvate ratio. Routine evaluation may not reveal the cause of hypoglycemia caused by citrin deficiency. We recently had a case that presented with recurrent hypoglycemia in a 30-month-old boy. Chemistry profiling, urine organic acid analysis, plasma acylcarnitine analysis, and hormone studies indicated values within the normal range or non-specific findings. Mutation analysis to identify the cause of hypoglycemia identified the subject as a compound heterozygote carrying each of the c.852_855del ($p.Met285Profs^*2$), and c.1177+1G>A mutant alleles. We report here on this unusual case of citrin deficiency presenting with FTTDCD for the first time in Korea.
Park, Yong-Su;Han, Donguk;Kim, Nam-Shin;Cho, Dong-Gil;Shim, Yun-Jin;Cha, Jin-Yeol
Journal of the Korean Society of Environmental Restoration Technology
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v.18
no.6
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pp.151-165
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2015
This study surveys and analyzes the ecology of Gangseo area to be developed near Nakdonggang River and West Nakdonggang River in Busan - before its development. With the result of the surveys as its basis, the study also finds ways to conserve the area's bird habitats in response to the planned development. According to the site surveys over four seasons, West Nakdonggang River which is near the targeted development area is a wintering ground for migratory birds. Some representative bird types in this area are ducks, geese, and other water birds. There are even six legally protected species. The average altitude of their flight is calculated to be $92.4{\pm}18.8m$ and the main purpose for the migration is determined to be for food. According to evalution of the conservation value of the area, Nakdonggang River and West Nakdonggang River turns out to have the highest conservation value. Other areas are developable as long as it was environmentally friendly. Therefore, this study suggests incorporation of ecological parks and biotopes within the targeted development area along with the proposal for spaces in the surroundings where the wintering birds can rest and feed. Especially for the wintering birds that rest at Nakdonggang River and West Nakdonggang River, their flight direction and pattern was examined to determine that their resting ground should be located 50~100m off of the river bank. Furthermore, this study proposes ways to maximize bird habitat by building ecological corridors between the agricultural channel and other small streams in the targeted development area and the habitats in the surroundings. Lastly, the study suggests the construction of low buildings, at most 20m in height, near Nakdonggang River and West Nakdonggang River considering the birds' flight altitude and direction.
Mira Chang;Oh, Keon-Bong;Lee, Kyung-Kwang;Han, Yong-Mahn
Proceedings of the Korean Society of Developmental Biology Conference
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2003.10a
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pp.86-86
/
2003
Research has been in progress for more than a decade to production of useful proteins by genetic modification in cattle. However, the levels of protein production in transgenic cattle have been reported very low. To enhance protein production in transgenic animal, we tried homologous recombination to donor cells for production of transgenic clone cattle through nuclear transfer procedure. Thus, we constructed the two targeting vectors of human thrombopoietin (TPO) at bovine $\beta$-casein locus using homologous recombination with 13.6 kb and 9.6 kb homology. In two targeting vectors, positive selection was through the neomycin resistance gene and negative selection was by the diphtheria toxin (DT). Gene targeting was attempted in bovine embryonic fibroblasts (bEF) and bovine ear skin fibroblasts (bESF). To determine the most appropriate concentration of neomycin for bEF and bESF, G4l8 resistance was confirmed by culturing the cells in various concentrations of the drug and both of the cells were optimally selected at $900 \mu g/ml$ of neomycin. The transfected bEF and bESF by the targeting vectors were colonized efficiently at the ratio of DNA to transfection reagent such as $4 \mu g$:2 ${mu}ell$ and $1 \mu g$:$2 \mu l$. Comparing number of healthy clones from passage 4 to passage 8, bESF (17%) persist in culture for much longer than bEF (6%). The two gene-targeted bESF clones of 30 random-integrated clones with 9.6 kb homology length were confirmed, however, nothing was out of 72 random integration clones with 13.6 kb homology length, The DT also worked more efficiently in clones transfected with the vector of 9.6 kb homology length. Our data suggests that the choice of donor cell for long culture period should be considered to obtain targeted cell clone, and the gene-targeting frequency and the DT working efficiency are dependent on the length of target homology.
To help reduce the 'breakfast-skip' rate of the high school students and improve such 'breakfast-skipping' practice this study devised a new covenience menu for school breakfast Program. Dictated by a dietitian the form of cooking was rendered within directly-cookable convenient food; The price of menu ranged from 1,500-2,000won taking into account the parents' survey ; the menu formation drew largely from the student food preference survey and their favorites. The composition of menu - the Korean dish and the western dish put together-were of two folds and was based on the two: main menu, subsidiary menu. While main menu used rice, the subsidiary one used fruits, salads, milk, and juices. Energy intake sufficiency standard was set at a level of between 1/4 and 1/3 of the relevent group(mid&high students, 15-18 yrs old)'s approximated energy need, drawn from the Dietary Reference Intakes For Koreans(2010). 10 disparate, divised menus were tested deliberately- cooked at a site, thereafter qualifed and supplemented to meet the targeted energy amount. The nuturitional facts of each menu set were measured through the usage of CAN-PRO 3.0, Computer Aided Nutritional Analysis Program, for professionals. Completed menu set were then given in photograph. The results of this study were as follows : The results of this study were as follows : the newly developed menu's calories and nuturitional content were as follows in the ratio of Dietary Reference Intakes For Koreans(2010) : Calories 95.7%(4.3% below the targeted intake standard), Protein(131.1%), Calcium(130.2%) the both of which marked higher than the recommended daily intake, iron(71.0%), Potassium(93.1%) both of which figure lower than the recommended daily intake. The cost of ingredients per each person was 1,335won, which was lower than the targeted cost(1500won). When calculated, hypothetically provided breakfast's labor hour needed per 1 meal is shown to be average 1.2 minute. In conslusion : Convenience style school breakfast program would bring an increse in the intake of high school students' breakfast, which may contribute not only to the sound physical growth but to academic performance. Various developments of the school breakfast program is much needed continually.
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