In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.
Recently, there have been impressive advancements in understanding of the immune mechanisms underlying cutaneous inflammatory diseases. To understand these diseases on a deeper level and clarify the therapeutic targets more precisely, numerous studies including in vitro experiments, animal models, and clinical trials have been conducted. This has resulted in a paradigm shift from non-specific suppression of the immune system to selective, targeted immunotherapies. These approaches target the molecular pathways and cytokines responsible for generating inflammatory conditions and reinforcing feedback mechanisms to aggravate inflammation. Among the numerous types of skin inflammation, psoriasis and atopic dermatitis (AD) are common chronic cutaneous inflammatory diseases. Psoriasis is a IL-17-mediated disease driven by IL-23, while AD is predominantly mediated by Th2 immunity. Autoimmune bullous diseases are autoantibody-mediated blistering disorders, including pemphigus and bullous pemphigoid. Alopecia areata is an organ-specific autoimmune disease mediated by CD8+ T-cells that targets hair follicles. This review will give an updated, comprehensive summary of the pathophysiology and immune mechanisms of inflammatory skin diseases. Moreover, the therapeutic potential of current and upcoming immunotherapies will be discussed.
Jongho Ham;Jae Woo Shin;Byeong Cheol Ko;Hye Young Kim
IMMUNE NETWORK
/
v.22
no.1
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pp.11.1-11.26
/
2022
When epithelial cells are exposed to potentially threatening external stimuli such as allergens, bacteria, viruses, and helminths, they instantly produce "alarmin" cytokines, namely, IL-33, IL-25, and TSLP. These alarmins alert the immune system about these threats, thereby mobilizing host immune defense mechanisms. Specifically, the alarmins strongly stimulate type-2 immune cells, including eosinophils, mast cells, dendritic cells, type-2 helper T cells, and type-2 innate lymphoid cells. Given that the alarm-raising role of IL-33, IL-25, and TSLP was first detected in allergic and infectious diseases, most studies on alarmins focus on their role in these diseases. However, recent studies suggest that alarmins also have a broad range of effector functions in other pathological conditions, including psoriasis, multiple sclerosis, and cancer. Therefore, this review provides an update on the epithelium-derived cytokines in both allergic and non-allergic diseases. We also review the progress of clinical trials on biological agents that target the alarmins and discuss the therapeutic potential of these agents in non-allergic diseases.
Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.
Kim, Sang Min;Lee, Jin Yong;Lee, Sun Haeng;Doh, Tae Yun
The Journal of Pediatrics of Korean Medicine
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v.32
no.3
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pp.100-118
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2018
Objectives The purpose of this study is to analyze some of the TCM (traditional Chinese medicine) clinical research literatures about pediatric night crying in order to learn clinical application of Korean medicine treatment for pediatric night crying. Methods We searched clinical trial literatures about TCM treatment of pediatric night crying from the CNKI (China National Knowledge Infrastructure) (January 2000 to June 2018). We analyzed the literature in regards to the treatment methods and the results. Results Among the 459 searched studies, 13 randomized controlled trials and 41 case studies were selected and analyzed. In most of the studies, the effectiveness of TCM in treating patients was significantly high, so we confirmed the effectiveness of TCM on pediatric night crying. The most commonly used pattern differentiations (辨證) were Spirit damage due to fright and fear (驚恐傷神), Spleen deficiency and cold (脾虛寒) and Heart fire heat (心火熱). Methods of treatment include herbal medicines (internal medicine and external application), massage therapy (Tuina methods), acupuncture and other treatments (bloodletting). The most commonly used herb medicines were Cicadidae Periostracum (蟬?), Poria Cocos (茯?), Glycyrrhizae Radix (甘草), Uncariae Ramulus et Uncus (釣鉤藤), Junci Medulla (燈心草), Fossilia Ossis Mastodi (龍骨), Atractylodis Rhizoma Alba (白朮), Cinnabaris (朱砂), and Coptidis Rhizoma (黃連). The most commonly used massage methods were Clearing Liver Channel (淸肝經), Clearing Heart Channel (淸心經), Kneading $Xi{\check{a}}oti{\bar{a}}nx{\bar{i}}n$ (?小天心), Supplementing Spleen Channel (補脾經), Clearing $Ti{\bar{a}}nh{\acute{e}}shu{\check{i}}$ (淸天河水), and Rubbing Abdomen (摩腹). Conclusions Based on the results of clinical studies from China, the use of Korean medicine for the treatment of pediatric night crying has been shown to be effective in relieving symptoms. Based on the results of this study, it is possible to widen the scope of Korean medicine by additionally reviewing clinical and experimental studies on pediatric night crying.
Objective: The purpose of this study was to investigate the difference in muscle strength, kinematics, and kinetics between injured and non-injured sides of the leg after Achilles Tendon Rupture surgery during walking and running. Method: The subjects (n=11; age = 30.63 ± 5.69 yrs; height = 172.00 ± 4.47 cm; mass = 77.00 ± 11.34 kg; time lapse from surgery = 29.81 ± 10.27 months) who experienced Achilles Tendon Rupture (ATR) surgery participated in this study. The walking and running trials were collected using infrared cameras (Oqus 300, Qualisys, Sweden, 100 Hz) on instrumented treadmill (Bertec, U.S.A., 1,000 Hz) and analyzed by using QTM (Qualisys Track Manager Ver. 2.15; Qualisys, U.S.A). The measured data were processed using Visual 3D (C-motion Inc., U.S.A.). The cutoff frequencies were set as 6 Hz and 12 Hz for walking and running kinematics respectively, while 100 Hz was used for force plate data. Results: In ATR group, muscle strength there were no difference between affected and unaffected sides (p> .05). In kinematic analysis, subjects showed greater ROM of knee joint flexion-extension in affected side compared to that of unaffected side during walking while smaller ROM of ankle dorsi-plantar and peak knee flexion were observed during running (p< .05). In kinetic analysis, subjects showed lower knee extension moment (running at 2.2 m/s) and positive ankle plantar-flexion power (running at 2.2 m/s, 3.3 m/s) in affected side compared to that of unaffected side (p< .05). This lower positive ankle joint power during a propulsive phase of running is related to slower ankle joint velocity in affected side of the subjects (p< .05). Conclusion: This study aimed to investigate the functional evaluation of the individuals after Achilles tendon rupture surgery through biomechanical analysis during walking and running trials. Based on the findings, greater reduction in dynamic joint function (i.e. lower positive ankle joint power) was found in the affected side of the leg compared to the unaffected side during running while there were no meaningful differences in ankle muscle strength and walking biomechanics. Therefore, before returning to daily life and sports activities, biomechanical analysis using more dynamic movements such as running and jumping trials followed by current clinical evaluations would be helpful in preventing Achilles tendon re-rupture or secondary injury.
Schnutenhaus, Sigmar;Doering, Isabel;Dreyhaupt, Jens;Rudolph, Heike;Luthardt, Ralph G.
Journal of Periodontal and Implant Science
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v.48
no.4
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pp.236-250
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2018
Purpose: Resorption of the alveolar bone is an unavoidable consequence of tooth extraction when appropriate alveolar ridge preservation (ARP) measures are not taken. The objective of this trial was to test the hypothesis that dimensional changes in the alveolar bone after tooth extraction would be reduced by inserting an equine collagen membrane and a collagen cone to fill and seal the alveolus (as ARP), in comparison to extraction with untreated alveoli. Methods: In this randomized clinical trial, 31 patients were directly treated with the collagen material after extraction of a tooth from the maxilla (the ARP group). Twenty-nine patients served as the control group. After extraction, no further treatment (i.e., no socket preservation measures) was performed in the control group. Changes in the alveolar process immediately after extraction and after an 8 (${\pm}1$)-week healing period were evaluated 3-dimensionally. Blinded analyses were performed after superimposing the data from the digitalized impressions and surfaces generated by cone-beam computed tomography. Results: Both the ARP and control groups showed a reduction of bone in the alveolar area after tooth extraction. However, significantly less bone resorption was detected in the clinically relevant buccal region in the ARP group. The median bone reduction was 1.18 mm in the ARP group and 5.06 mm in the control group (P=0.03). Conclusions: The proposed hypothesis that inserting a combination material comprising a collagen cone and membrane would lead to a difference in alveolar bone preservation can be accepted for the clinically relevant buccal distance. In this area, implantation of the collagen material led to significantly less alveolar bone resorption. German Clinical Trials Register at www.drks.de, DRKS00004769.
Background: To verify whether serum tumor abnormal protein (TAP) would correlate with the responsiveness of palliative chemotherapy in patients with advanced gastric cancer, and the variation of conventional serum tumor markers e.g., carcinoembryonic antigen (CEA), antigen 125 (CA125),carbohydrate antigen19-9 (CA19-9) of adjuvant chemotherapy in patients with early gastric cancer. Materials and Methods: Patients with histologically confirmed gastric cancer and treated with chemotherapy were enrolled into this study. TAP values of these patients were determined by detecting abnormal sugar chain glycoprotein in serum, combined with the area of agglomerated particles. For patients with advanced gastric cancer, responsiveness of palliative chemotherapy was compared with variation of TAP and the relation between variation of TAP and tumor markers in patients with early gastric cancer was analyzed. Results: Totally 82 gastric cancer patients were enrolled into this study. The value of TAP is more closely related to responsiveness of palliative chemotherapy for patients with advanced gastric cancer. The correlation between TAP and responsiveness to palliative chemotherapy is stronger than the correlation between several conventional serum tumor markers (CEA, CA125 and CA199). The variation of TAP was also positively correlated with the trend of CA125 in adjuvant chemotherapy. Conclusions: TAP is sensitive in monitoring the responsiveness to palliative chemotherapy in patients with advanced gastric cancer. But this result should be confirmed by randomized clinical trials for patients with gastric cancer.
Objectives: The purpose of this study is to develop a standard tool for pattern identifications in Korean Medicine for depression. Methods: The advisor committee for this study was organized by 15 Korean Medicine neuropsychiatry professors from 11 Colleges of Korean Medicine. The items and structure of the tools were based on reviews of published literature. In order to develop the tool, we took the consultation from discussions with the advisor committee twice and also incorporated additional advices from e-mail correspondences. Results: 1) We divided the symptoms and signs of depression into 11 pattern identifications. 2) We obtained the mean weights which reflected the standard deviations from each symptoms of the 11 pattern identifications which were scored on a 100-point scale by 15 experts. 3) We designed the Korean medicine pattern identification tool for depression. It was composed of 66 questions in the question- and-answer format. Conclusions: There are some points which should be considered in this study. First, we couldn't reach a complete agreement on the concept of 11 patterns. Second, each pattern identification has a different number of symptoms and signs. In addition, the items of symptoms and signs of each pattern identification are unequal. Third, as we did not set any clinical trials when using this tool, it was not possible to test its validity and reliability. Although there are some limits in this study, the development of pattern identification tools for depression through discussions with the advisor committee is meaningful. If the validity and reliability of the Korean Medicine pattern identification tools for depression are confirmed through clinical trial,s this tool is expected to be applied to the subsequent researches in the future.
Objective: The objective of this two-arm parallel trial was to compare the type of tooth movement during en masse retraction of the maxillary anterior teeth using labial versus lingual biocreative therapy. Methods: Twenty-eight subjects were randomized in a 1 : 1 ratio to either the labial or lingual group. En masse anterior retraction was performed using labial biocreative therapy in group A and lingual biocreative therapy in group B. Cone beam computed tomography scans were taken before and after retraction and the primary outcome was the type of tooth movement during anterior retraction. Data were analyzed using paired t-tests for comparisons within each group and independent-sample t-test for comparison of the mean treatment changes between the two groups. Results: Significant differences were found between the two groups in relation to the type of tooth movement (labiolingual inclination of the central incisor; mean difference, $5.85{\pm}1.85^{\circ}$). The canine showed significant distal tipping in the lingual group (mean difference, $6.98{\pm}1.25^{\circ}$). The canine was significantly more intruded in the lingual group (mean difference, $1.67{\pm}0.49mm$). Good anchorage control and significant soft tissue changes occurred in both groups. No serious adverse effects were detected. Conclusions: With a 10-mm retraction hook, the labial biocreative technique with the reverse curve overlay provided anterior retraction with good torque control, while in the lingual group, anterior retraction occurred with controlled tipping movement with significant distal tipping and intrusion of the canine (trial registration: The trial was registered at ClinicalTrials.gov [NCT03239275]).
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