Conductive Glassy Nonconjugated Open-Shell Radical Polymer with Organosulfur Backbone for Macroscopic Conductivity.

Nonconjugated organic radicals with an open-shell radical active group exhibit unique functionality due to their radical pendant site. Compared with the previously studied doped conjugated polymers, radical polymers reveal superior processability, stability, and optical properties. Despite the success of organic radical polymer conductors based on the TEMPO radicals, it still requires potential design substitutions to meet the fundamental limits of charge transport in the radical polymer. To do so, we demonstrate that the amorphous, nonconjugated radical polymer with backbone-pendant group interaction and low glass transition temperature enables the macromolecules to have rapid charge transport in the solid state, resulting in conductivity higher than 32 S m-1. This charge transport is due to the formation of the local ordered regime with an energetically favored orientation caused by the strong coupling between the backbone and pendant group, which can significantly modulate the polymer packing with active electronic communications. The nonconjugate nature of the radical polymer maintains an optical transparency up to 98% at a 1.5 µm thick film. Thus, this effort will be a dramatically advanced model in the organic radical community for the creation of next-generation polymer conductors.

SP-8356 inhibits acute lung injury by suppressing inflammatory cytokine production and immune cell infiltration.

This study investigated the anti-inflammatory and protective properties of SP-8356, a synthetic derivative of (1S)-(-)-verbenone, in a mouse model of LPS-induced acute lung injury (ALI). By targeting intracellular signaling pathways and inflammatory responses, SP-8356 demonstrated a potent ability to attenuate deleterious effects of proinflammatory stimuli. Specifically, SP-8356 effectively inhibited the activation of crucial signaling molecules such as NF-κB and Akt, and subsequently dampened the expression of inflammatory cytokines in various lung cellular components. Intervention with SP-8356 treatment also preserved the structural integrity of the epithelial and endothelial barriers. By reducing immune cell infiltration into inflamed lung tissue, SP-8356 exerted a broad protective effect against ALI. These findings position SP-8356 as a promising therapeutic candidate for pulmonary inflammatory diseases that cause ALI.

Preliminary evaluation of the effect of revised reimbursement scheme in outpatient hemodialysis for medical aid recipients in Korea.

Background: South Korea has universal health coverage guaranteeing equitable healthcare for all. However, equity issues have been raised regarding hemodialysis reimbursement for medical aid recipients with chronic kidney disease. Physicians and civic groups demanded a revision of the discriminatory policy, and in response, the Ministry of Health and Welfare amended the hemodialysis case payment scheme. This study aims to evaluate the effectiveness of the reform and detect any unintended policy outcomes. Methods: Data from the Health Insurance Review and Assessment Service of Korea was used. All subjects were patients with chronic kidney disease who received outpatient hemodialysis and medical aid from April 2017 to March 2022. The data was analyzed with descriptive statistics, and the generalized estimation equation was used to control for covariates and identify policy effects. Results: The reform of the case payment scheme in 2021 raised the compensation level per hemodialysis case, which was fixed for 7 years from 2014, by approximately 2,000 Korean won. There was no negative effect such as additional expenditure resulting from an unintentional increase in medical use. Conclusion: A year has passed since the implementation of the outpatient hemodialysis rate system reform for medical aid recipients. Our results indicate that the reform has gone smoothly, and we anticipate continuous efforts by the government to guarantee universal health coverage to medical aid recipients. Through such consistent endeavors to correct the discriminatory aspects of policies, South Korea will achieve true universal health coverage.

Natural products as IL-6 inhibitors for inflammatory diseases: Synthetic and SAR perspective.

Interleukin-6 (IL-6), a pleiotropic cytokine, plays a pivotal role in the pathophysiology of various diseases including diabetes, atherosclerosis, Alzheimer's disease, multiple myeloma, rheumatoid arthritis, and prostate cancer. The signaling pathways associated with IL-6 offer promising targets for therapeutic interventions in inflammatory diseases and IL-6-dependent tumors. Although certain anti-IL-6 monoclonal antibodies are currently employed clinically, their usage is hampered by drawbacks such as high cost and potential immunogenicity, limiting their application. Thus, the imperative arises to develop novel small non-peptide molecules acting as IL-6 inhibitors. Various natural products derived from diverse sources have been investigated for their potential to inhibit IL-6 activity. Nevertheless, these natural products remain inadequately explored in terms of their structure-activity relationships. In response, our review aims to provide syntheses and structure activity perspective of natural IL-6 inhibitors. The comprehensive amalgamation of information presented in this review holds the potential to serve as a foundation for forthcoming research endeavors by medicinal chemists, facilitating the design of innovative IL-6 inhibitors to address the complexities of inflammatory diseases.

Design of High-Payload Ascorbyl Palmitate Nanosuspensions for Enhanced Skin Delivery.

A high-payload ascorbyl palmitate (AP) nanosuspension (NS) was designed to improve skin delivery following topical application. The AP-loaded NS systems were prepared using the bead-milling technique, and softly thickened into NS-loaded gel (NS-G) using hydrophilic polymers. The optimized NS-G system consisted of up to 75 mg/mL of AP, 0.5% w/v of polyoxyl-40 hydrogenated castor oil (Kolliphor® RH40) as the suspending agent, and 1.0% w/v of sodium carboxymethyl cellulose (Na.CMC 700 K) as the thickening agent, in citrate buffer (pH 4.5). The NS-G system was embodied as follows: long and flaky nanocrystals, 493.2 nm in size, -48.7 mV in zeta potential, and 2.3 cP of viscosity with a shear rate of 100 s-1. Both NS and NS-G provided rapid dissolution of the poorly water-soluble antioxidant, which was comparable to that of the microemulsion gel (ME-G) containing AP in solubilized form. In an ex vivo skin absorption study using the Franz diffusion cell mounted on porcine skin, NS-G exhibited faster absorption in skin, providing approximately 4, 3, and 1.4 times larger accumulation than that of ME-G at 3, 6, and 12 h, respectively. Therefore, the high-payload NS makes it a promising platform for skin delivery of the lipid derivative of ascorbic acid.

HIF-1α inhibition by MO-2097, a novel chiral-free benzofuran targeting hnRNPA2B1.

INTRODUCTION: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator mediating adaptive responses to hypoxia. It is up-regulated in the tumor microenvironment and recognized as an effective anticancer drug target. Previously, we discovered that the natural compound moracin-O and its synthetic derivative MO-460 inhibited HIF-1α via hnRNPA2B1. OBJECTIVES: This study aimed to develop novel HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural products moracins-O and P. METHODS: In an ongoing search for novel HIF-1 inhibitors, a series of nature-inspired benzofurans with modifications on the chiral rings of moracins-O and P were synthesized. They showed improved chemical tractability and were evaluated for their inhibitory activity on HIF-1α accumulation under hypoxic conditions in HeLa CCL2 cells. The most potent derivative's chemical-based toxicities, binding affinities, and in vivo anti-tumorigenic effects were evaluated. Further, we examined whether our compound, MO-2097, exhibited anticancer effects in three-dimensional cultured organoids. RESULTS: Herein, we identified a novel synthetic chiral-free compound, MO-2097, with reduced structural complexity and increased efficiency. MO-2097 exhibited inhibitory effects on hypoxia-induced HIF-1α accumulation in HeLa CCL2 cells via inhibition of hnRNPA2B1 protein, whose binding affinities were confirmed by isothermal titration calorimetry analysis. In addition, MO-2097 demonstrated in vivo efficacy and biocompatibility in a BALB/c mice xenograft model. The immunohistochemistry staining of MO-2097-treated tissues showed decreased expression of HIF-1α and increased levels of apoptosis marker cleaved caspase 3, confirming in vivo efficacy. Furthermore, we confirmed that MO-2097 works effectively in cancer patient-based organoid models. CONCLUSION: MO-2097 represents a promising new generation of chemotherapeutic agents targeting HIF-1α inhibition via hnRNPA2B1, requiring further investigation.

Copper-Catalyzed C-C Cross-Couplings of Tertiary Alkyl Halides with Anilines Enabled by Cyclopropenimine-Based Ligands.

Catalytic cross-couplings of tertiary alkyl electrophiles with carbon nucleophiles offer a powerful platform for constructing quaternary carbon centers, which are prevalent in bioactive molecules. However, these reactions remain underdeveloped primarily because of steric challenges that impede efficient bond formation. Herein, we describe the copper-catalyzed synthesis of such centers through the C(sp3)-C(sp2) bond-forming reaction between tertiary alkyl halides and arene rings of aniline derivatives, enabled by the strategic implementation of bidentate bis(cyclopropenimine) ligands. The copper catalyst bound by two imino-nitrogen atoms of these ligands, which have never been employed in metal catalysis previously, is highly effective in rapidly activating tertiary halides to generate alkyl radicals, allowing them to react with aryl nucleophiles under mild conditions with remarkably short reaction times (1-2 h). Various tertiary halides bearing carbonyl functional groups can be coupled with secondary or primary anilines, furnishing a range of quaternary carbon centers in good yields. Several mechanistic observations support the generation of copper(II) species and alkyl radicals which as a result elucidate the steps in the proposed catalytic cycle.

Discovery of a novel BLT2 antagonist for the treatment of inflammatory airway diseases.

Leukotriene B4 (LTB4) is a potent chemoattractant that can recruit and activate immune cells such as neutrophils, eosinophils, and monocytes to sites of inflammation. Excessive production of LTB4 has been linked to acute and chronic inflammatory diseases, including asthma, rheumatoid arthritis, and psoriasis. Inhibiting the binding of LTB4 to its receptors, BLT1 and BLT2, is a potential strategy for treating these conditions. While several BLT1 antagonists have been developed for clinical trials, most have failed due to efficacy and safety issues. Therefore, discovering selective BLT2 antagonists could improve our understanding of the distinct functions of BLT1 and BLT2 receptors and their pharmacological implications. In this study, we aimed to discover novel BLT2 antagonists by synthesizing a series of biphenyl analogues based on a BLT2 selective agonist, CAY10583. Among the synthesized compounds, 15b was found to selectively inhibit the chemotaxis of CHO-BLT2 cells with an IC50 value of 224 nM without inhibiting the chemotaxis of CHO-BLT1 cells. 15b also inhibited the binding of LTB4 and BLT2 with a Ki value of 132 nM. Furthermore, 15b had good metabolic stability in liver microsomes and moderate bioavailability (F = 34%) in in vivo PK studies. 15b also showed in vivo efficacy in a mouse model of asthma, reducing airway hyperresponsiveness by 59% and decreasing Th2 cytokines by up to 46%. Our study provides a promising lead for the development of selective BLT2 antagonists as potential therapeutics for inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease.

Machine Learning-Based Approach to Developing Potent EGFR Inhibitors for Breast Cancer-Design, Synthesis, and In Vitro Evaluation.

The epidermal growth factor receptor (EGFR) is vital for regulating cellular functions, including cell division, migration, survival, apoptosis, angiogenesis, and cancer. EGFR overexpression is an ideal target for anticancer drug development as it is absent from normal tissues, marking it as tumor-specific. Unfortunately, the development of medication resistance limits the therapeutic efficacy of the currently approved EGFR inhibitors, indicating the need for further development. Herein, a machine learning-based application that predicts the bioactivity of novel EGFR inhibitors is presented. Clustering of the EGFR small-molecule inhibitor (∼9000 compounds) library showed that N-substituted quinazolin-4-amine-based compounds made up the largest cluster of EGFR inhibitors (∼2500 compounds). Taking advantage of this finding, rational drug design was used to design a novel series of 4-anilinoquinazoline-based EGFR inhibitors, which were first tested by the developed artificial intelligence application, and only the compounds which were predicted to be active were then chosen to be synthesized. This led to the synthesis of 18 novel compounds, which were subsequently evaluated for cytotoxicity and EGFR inhibitory activity. Among the tested compounds, compound 9 demonstrated the most potent antiproliferative activity, with 2.50 and 1.96 µM activity over MCF-7 and MDA-MB-231 cancer cell lines, respectively. Moreover, compound 9 displayed an EGFR inhibitory activity of 2.53 nM and promising apoptotic results, marking it a potential candidate for breast cancer therapy.

Cantharidin-Based Verbenone Derivatives as a Novel Insecticide against Plutella xylostella: Design, Synthesis, Insecticidal Activity Evaluation, and 3D QSAR Study.

The diamondback moth is a detrimental insect pest of brassicaceous crops which was among the first crop insects to be reported as DDT resistant. It has since proven to be significantly resistant to nearly every synthetic insecticide used in the field in many crucifer-producing regions. Due to insecticide control failures in some parts of the world, economically viable crucifer production is now all but impossible. As a result, there has been an increasing effort to identify new compounds with strong pesticidal activity. Cantharidin is one such compound that has been shown to be highly effective against a variety of insect pests. However, its chemical synthesis and potential toxicity to non-target organisms have been a major source of concern. Herein, using rational design approaches, a new series of cantharidin-based verbenone derivatives were synthesized and evaluated for their insecticidal activities against the diamondback moth. Among different compounds screened, compounds 6a, 6h, 6i, and 6q emerged as the most potent compounds exhibiting 100% mortality at a concentration of 100 mg/L after four days. These compounds demonstrated a good anti-feeding effect against the diamondback moth on cabbage leaves. Subsequently, a 3D QSAR study was carried out to identify the key structural features of the synthesized compounds and their correlation with insecticidal activity.

Integration of Hybridization Strategies in Pyridine-Urea Scaffolds for Novel Anticancer Agents: Design, Synthesis, and Mechanistic Insights.

Annually, millions of new cancer cases are reported, leading to millions of deaths worldwide. Among the newly reported cases, breast and colon cancers prevail as the most frequently detected variations. To effectively counteract this rapid increase, the development of innovative therapies is crucial. Small molecules possessing pyridine and urea moieties have been reported in many of the currently available anticancer agents, especially VEGFR2 inhibitors. With this in mind, a rational design approach was employed to create hybrid small molecules combining urea and pyridine. These synthesized compounds underwent in vitro testing against breast and colon cancer cell lines, revealing potent submicromolar anticancer activity. Compound 8a, specifically, exhibited an impressive GI50 value of 0.06 µM against the MCF7 cancer cell line, while compound 8h displayed the highest cytotoxic activity against the HCT116 cell line, with a GI50 of 0.33 ± 0.042 µM. Notably, compounds 8a, 8h, and 8i demonstrated excellent safety profiles when tested on normal cells. Molecular docking, dynamic studies, and free energy calculations were employed to validate the affinity of these compounds as VEGFR2 inhibitors.

Inhibition of Osteoclast Differentiation and Promotion of Osteogenic Formation by Wolfiporia extensa Mycelium.

Osteoporosis, Greek for "porous bone," is a bone disease characterized by a decrease in bone strength, microarchitectural changes in the bone tissues, and an increased risk of fracture. An imbalance of bone resorption and bone formation may lead to chronic metabolic diseases such as osteoporosis. Wolfiporia extensa, known as "Bokryung" in Korea, is a fungus belonging to the family Polyporaceae and has been used as a therapeutic food against various diseases. Medicinal mushrooms, mycelium and fungi, possess approximately 130 medicinal functions, including antitumor, immunomodulating, antibacterial, hepatoprotective, and antidiabetic effects, and are therefore used to improve human health. In this study, we used osteoclast and osteoblast cell cultures treated with Wolfiporia extensa mycelium water extract (WEMWE) and investigated the effect of the fungus on bone homeostasis. Subsequently, we assessed its capacity to modulate both osteoblast and osteoclast differentiation by performing osteogenic and anti-osteoclastogenic activity assays. We observed that WEMWE increased BMP-2-stimulated osteogenesis by inducing Smad-Runx2 signal pathway axis. In addition, we found that WEMWE decreased RANKL-induced osteoclastogenesis by blocking c-Fos/NFATc1 via the inhibition of ERK and JNK phosphorylation. Our results show that WEMWE can prevent and treat bone metabolic diseases, including osteoporosis, by a biphasic activity that sustains bone homeostasis. Therefore, we suggest that WEMWE can be used as a preventive and therapeutic drug.

Small Molecule c-KIT Inhibitors for the Treatment of Gastrointestinal Stromal Tumors: A Review on Synthesis, Design Strategies, and Structure-Activity Relationship (SAR).

The proto-oncogenic protein, c-KIT, plays a crucial role in regulating cellular transformation and differentiation processes, such as proliferation, survival, adhesion, and chemotaxis. The overexpression of, and mutations, in c-KIT can lead to its dysregulation and promote various human cancers, particularly gastrointestinal stromal tumors (GISTs); approximately 80-85% of cases are associated with oncogenic mutations in the KIT gene. Inhibition of c-KIT has emerged as a promising therapeutic target for GISTs. However, the currently approved drugs are associated with resistance and significant side effects, highlighting the urgent need to develop highly selective c-KIT inhibitors that are not affected by these mutations for GISTs. Herein, the recent research efforts in medicinal chemistry aimed at developing potent small-molecule c-KIT inhibitors with high kinase selectivity for GISTs are discussed from a structure-activity relationship perspective. Moreover, the synthetic pathways, pharmacokinetic properties, and binding patterns of the inhibitors are also discussed to facilitate future development of more potent and pharmacokinetically stable small-molecule c-KIT inhibitors.

Manufacture of antibacterial carbon fiber-reinforced plastics (CFRP) using imine-based epoxy vitrimer for medical application.

An antibacterial carbon fiber-reinforced plastics (CFRP) was manufactured based on a vitrimer containing imine groups. A liquid curing agent was prepared to include an imine group in the matrix, and was synthesized without a simple mixing reaction and any purification process. The vitrimer used as the matrix for CFRP was prepared by reacting a commercial epoxy with a synthesized curing agent. The structural and thermal properties of the vitrimer were determined by Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In addition, the temperature-dependent behavior of the vitrimer was characterized by stress relaxation, reshaping, and shape memory experiments. The mechanical properties of composites fabricated using vitrimer were fully analyzed by tensile, flexural, short-beam strength, and Izod impact tests and had mechanical properties similar to reference material. Moreover, both the vitrimer and the vitrimer composites showed excellent antibacterial activity against Staphylococcus aureus and Escherichia coil due to the imine group inside the vitrimer. Therefore, vitrimer composites have potential for applications requiring antimicrobial properties, such as medical devices.

Design, Synthesis and Biological Evaluation of Novel MDH Inhibitors Targeting Tumor Microenvironment.

MDH1 and MDH2 enzymes play an important role in the survival of lung cancer. In this study, a novel series of dual MDH1/2 inhibitors for lung cancer was rationally designed and synthesized, and their SAR was carefully investigated. Among the tested compounds, compound 50 containing a piperidine ring displayed an improved growth inhibition of A549 and H460 lung cancer cell lines compared with LW1497. Compound 50 reduced the total ATP content in A549 cells in a dose-dependent manner; it also significantly suppressed the accumulation of hypoxia-inducible factor 1-alpha (HIF-1α) and the expression of HIF-1α target genes such as GLUT1 and pyruvate dehydrogenase kinase 1 (PDK1) in a dose-dependent manner. Furthermore, compound 50 inhibited HIF-1α-regulated CD73 expression under hypoxia in A549 lung cancer cells. Collectively, these results indicate that compound 50 may pave the way for the development of next-generation dual MDH1/2 inhibitors to target lung cancer.

Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure-Activity Relationships and Molecular Docking.

Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a key role in the pathogenesis and physiology of inflammatory and autoimmune diseases, such as coronary heart disease, cancer, Alzheimer's disease, asthma, rheumatoid arthritis, and most recently COVID-19. IL-6 and its signaling pathway are promising targets in the treatment of inflammatory and autoimmune diseases. Although, anti-IL-6 monoclonal antibodies are currently being used in clinics, huge unmet medical needs remain because of the high cost, administration-related toxicity, lack of opportunity for oral dosing, and potential immunogenicity of monoclonal antibody therapy. Furthermore, nonresponse or loss of response to monoclonal antibody therapy has been reported, which increases the importance of optimizing drug therapy with small molecule drugs. This work aims to provide a perspective for the discovery of novel small molecule IL-6 inhibitors by the analysis of the structure-activity relationships and computational studies for protein-protein inhibitors targeting the IL-6/IL-6 receptor/gp130 complex.

Intrinsic Defects and Their Role in the Phase Transition of Na-Ion Anode Na2Ti3O7.

The development of high-power anode materials for Na-ion batteries is one of the primary obstacles due to the growing demands for their use in the smart grid. Despite the appealingly low cost and non-toxicity, Na2Ti3O7 suffers from low electrical conductivity and poor structural stability, which restricts its use in high-power applications. Viable approaches for overcoming these drawbacks reported to date are aliovalent doping and hydrogenation/hydrothermal treatments, both of which are closely intertwined with native defects. There is still a lack of knowledge, however, of the intrinsic defect chemistry of Na2Ti3O7, which impairs the rational design of high-power titanate anodes. Here, we report hybrid density functional theory calculations of the native defect chemistry of Na2Ti3O7. The defect calculations show that the insulating properties of Na2Ti3O7 arise from the Na and O Schottky disorder that act as major charge compensators. Under high-temperature hydrogenation treatment, these Schottky pairs of Na and O vacancies become dominant defects in Na2Ti3O7, triggering the spontaneous partial phase transition to Na2Ti6O13 and improving the electrical conductivity of the composite anode. Our findings provide an explanation on the interplay between intrinsic defects, structural phase transitions, and electrical conductivity, which can aid understanding of the properties of composite materials obtained from phase transitions.

Identification of 2,4-Di-tert-butylphenol as a Novel Agonist for Insect Odorant Receptors.

Odorant molecules interact with odorant receptors (ORs) lining the pores on the surface of the sensilla on an insect's antennae and maxillary palps. This interaction triggers an electrical signal that is transmitted to the insect's nervous system, thereby influencing its behavior. Orco, an OR coreceptor, is crucial for olfactory transduction, as it possesses a conserved sequence across the insect lineage. In this study, we focused on 2,4-di-tert-butylphenol (DTBP), a single substance present in acetic acid bacteria culture media. We applied DTBP to oocytes expressing various Drosophila melanogaster odor receptors and performed electrophysiology experiments. After confirming the activation of DTBP on the receptor, the binding site was confirmed through point mutations. Our findings confirmed that DTBP interacts with the insect Orco subunit. The 2-heptanone, octanol, and 2-hexanol were not activated for the Orco homomeric channel, but DTBP was activated, and the EC50 value was 13.4 ± 3.0 µM. Point mutations were performed and among them, when the W146 residue changed to alanine, the Emax value was changed from 1.0 ± 0 in the wild type to 0.0 ± 0 in the mutant type, and all activity was decreased. Specifically, DTBP interacted with the W146 residue of the Orco subunit, and the activation manner was concentration-dependent and voltage-independent. This molecular-level analysis provides the basis for novel strategies to minimize pest damage. DTBP, with its specific binding to the Orco subunit, shows promise as a potential pest controller that can exclusively target insects.

Discovery of a NADPH oxidase inhibitor, (E)-3-cyclohexyl-5-(4-((2-hydroxyethyl)(methyl)amino)benzylidene)-1-methyl-2-thioxoimidazolidin-4-oneone, as a novel therapeutic for Parkinson's disease.

Several lines of evidence indicated that generation of NADPH oxidase (Nox)-mediated reactive oxygen species are associated with neuronal inflammation, leading to Parkinson's disease (PD). Novel benzylidene-1-methyl-2-thioxoimidazolidin-one derivatives as Nox inhibitors were designed and synthesized in order to increase blood-brain barrier (BBB) permeability to target Nox in brain cells. In lucigenin chemiluminescence assay, eight compounds showed excellent inhibition activity against NADPH oxidases and parallel artificial membrane permeability assay (PAMPA) identified compound 11 with high passive permeability. To validate the effect of compound 11 on neuronal inflammation, we tested the regulatory activity of compound 11 in lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines in BV-2 microglial cells and LPS-mediated microglial migration. Treatment of BV2 cells with compound 11 resulted in suppressed production of pro-inflammatory cytokines and migration activity of BV2 cells in response to LPS. To evaluate the therapeutic efficacy of compound 11 in PD animal model, compound 11 was applied to MPTP-induced PD mouse model. Oral administration of compound 11 (30 mg/kg/daily, 4 weeks) into the mice resulted in suppression of dopaminergic neuronal death in substantia nigra (SN) and in striatum as well as inhibition of microglial migration into SN. These results implicate compound 11 as a novel therapeutic agent for the treatment of PD.

Analysis of prognostic factors through survival rate analysis of oral squamous cell carcinoma patients treated at the National Cancer Center: 20 years of experience.

Objectives: This study aimed to analyze the clinicopathological prognostic factors affecting the survival of patients with oral squamous cell carcinoma (OSCC). Materials and Methods: A retrospective study was conducted on patients with OSCC who received treatment at the Oral Oncology Clinic of the National Cancer Center (NCC) from June 2001 to December 2020. The patients' sex, age, primary site, T stage, node metastasis, TNM staging, perineural invasion (PNI), lymphovascular invasion (LVI), differentiation, surgical resection margin, smoking, and drinking habits were investigated to analyze risk factors. For the univariate analysis, a Kaplan-Meier survival analysis and log-rank test were used. Additionally, for the multivariable analysis, a Cox proportional hazard model analysis was used. For both analyses, statistical significance was considered when P<0.05. Results: During the investigation period, 407 patients were received surgical treatment at the NCC. Their overall survival rate (OS) for five years was 70.7%, and the disease-free survival rate (DFS) was 60.6%. The multivariable analysis revealed that node metastasis, PNI, and differentiation were significantly associated with poor OS. For DFS, PNI and differentiation were associated with poor survival rates. Conclusion: In patients with OSCC, cervical node metastasis, PNI, and differentiation should be considered important prognostic factors for postoperative survival.