• Biomolecules & Therapeutics
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• 제7권4호
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• pp.329-334
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• 1999

Recently, cellular signal transduction mechanisms are greatly understood. However, bone cell signaling is not completely characterized. Interestingly, bone cells synthesize a number of growth factors such as IGF-I PDGF, IGF-II etc., suggesting these growth factors play important roles in bone cell signaling. In the present study, potential roles of nitric oxide (NO) and protein kinases in osteoblast signal transduction are proposed.

• Biomolecules & Therapeutics
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• 제14권1호
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• pp.25-29
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• 2006

We tested effects of bioactive lysophospholipids including lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), sphingosylphosphorylcholine (SPC), and sphingosine I-phosphate (S1P) on membrane potential in C6 glioma cells to understand action mechanism of the lysophospholipids. Membrane potential was estimated by measuring fluorescence change of DiBAC-loaded glioma cells. LPA largely increased membrane potential and the increase was gradually diminished. LPC also increased the membrane potential, however, the increase sustained. SPC induced smaller increase of membrane potential than LPC. SIP was not able to change the membrane potential. We tested effects of suramin and pertussis toxin on lysophospholipid-induced membrane potential increase. However, there wasn't any effect. The membrane potential increase was partially diminished in $Na^+$-free media, suggesting $Na^+$ influx as a component of membrane potential changes. Thus, involvement of $Na^+$ influx in the increase of membrane potential by lysophospholipids and independence of suramin-sensitive GPCRs and pertussis toxin-sensitive G proteins are found in this study.

• Genomics & Informatics
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• 제19권4호
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• pp.47.1-47.12
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• 2021

Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the few human oncogenic viruses, which causes a variety of malignancies, including Kaposi's sarcoma, multicentric Castleman disease, and primary effusion lymphoma, particularly in human immunodeficiency virus patients. The currently available treatment options cannot always prevent the invasion and dissemination of this virus. In recent times, siRNA-based therapeutics are gaining prominence over conventional medications as siRNA can be designed to target almost any gene of interest. The ORF57 is a crucial regulatory protein for lytic gene expression of KSHV. Disruption of this gene translation will inevitably inhibit the replication of the virus in the host cell. Therefore, the ORF57 of KSHV could be a potential target for designing siRNA-based therapeutics. Considering both sequence preferences and target site accessibility, several online tools (i-SCORE Designer, Sfold web server) had been utilized to predict the siRNA guide strand against the ORF57. Subsequently, off-target filtration (BLAST), conservancy test (fuzznuc), and thermodynamics analysis (RNAcofold, RNAalifold, and RNA Structure web server) were also performed to select the most suitable siRNA sequences. Finally, two siRNAs were identified that passed all of the filtration phases and fulfilled the thermodynamic criteria. We hope that the siRNAs predicted in this study would be helpful for the development of new effective therapeutics against KSHV.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.493-509
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• 2015

Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris$^{(R)}$(anti-CD30-drug conjugate) and Kadcyla$^{(R)}$(anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2263-2267
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• 2012

Objective: MicroRNAs (miRNAs) play important roles in carcinogenesis. The aim of the present study was to explore the effects of miR-181b on gastric cancer. Methods: The expression level of miR-181b was quantified by qRT-PCR. MTT, flow cytometry and matrigel invasion assays were used to test proliferation, apoptosis and invasion of miR-181b stable transfected gastric cancer cells. Results: miR-181b was aberrantly overexpressed in gastric cancer cells and primary gastric cancer tissues. Further experiments demonstrated inducible expression of miR-181b by Helicobacter pylori treatment. Cell proliferation, migration and invasion in the gastric cancer cells were significantly increased after miR-181b transfection and apoptotic cells were also increased. Furthermore, overexpression of miR-181b downregulated the protein level of tissue inhibitor of metalloproteinase 3 (TIMP3). Conclusion: The upregulation of miR-181b may play an important role in the progress of gastric cancer and miR-181b maybe a potential molecular target for anticancer therapeutics of gastric cancer.

• Bulletin of the Korean Chemical Society
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• 제35권10호
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• pp.2985-2989
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• 2014

Autophagy is a self-digestion process in which intracellular structures are degraded in response to stress. Notably, prolonged autophagy leads to cell death. In this study, we investigated whether CX-4945, an orally available protein kinase 2 (CK2) inhibitor, induces autophagic cell death in human cervical cancer-derived HeLa cells and in human prostate cancer-derived LNCaP cells. CX-4945 treatment of both cell lines resulted in the formation of autophagosomes, in the conversion of microtubule-associated protein 1 light chain 3 (LC3), and in down-regulation of the Akt-mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (S6K) signaling cascade. Thus, pharmacologic inhibition of CK2 by CX-4945 induced autophagic cell death in human cancer cells by down-regulating Akt-mTOR-S6K. These results suggest that autophagy-inducing agents have potential as anti-cancer drugs.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1999년도 춘계학술대회
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• pp.1-4
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• 1999

The potential therapeutic benefit of nicotinic ligands in a variety of neurodegenerative pathologies involving the CNS has energized research efforts to develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands. In particular, there has been a concerted effort to develop nicotinic compounds with selectivity for CNS nAChRs as potential pharmacological tools in the management of these disorders. The characterization of other novel nicotinic ligands such as epibatidine. showing a marked increase in potency at nAChRs, has provided additional support for the development of potent, selective ligands at individual nAChR subtypes. We have developed and studied a number of nicotinic compounds to identify potential candidates exhibiting such selectivity. In the present study, we report the synthesis and biological evaluations of some azabicyclic and azatricyclic nicotine analogs to decipher the relationship among steric requirements of the nicotine's pyrrolidine ring system, binding affinity and subtype-selectivity.

• Biomolecules & Therapeutics
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• 제21권5호
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• pp.323-331
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• 2013

TGF-${\beta}$ pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-${\beta}$ related functional contexts. This review discusses the molecular mechanism of the TGF-${\beta}$ pathway and describes the different ways of tumor suppression and promotion by TGF-${\beta}$. In the last part of the review, the data on targeting TGF-${\beta}$ pathway for cancer treatment is assessed. The TGF-${\beta}$ inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.

• Journal of Microbiology and Biotechnology
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• 제17권6호
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• pp.879-890
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• 2007

The identification of tumor antigens is essential for the development of anticancer therapeutic vaccines and clinical diagnosis of cancer. SEREX (serological analysis of recombinant cDNA expression libraries) has been used to identify such tumor antigens by screening sera of patients with cDNA expression libraries. SEREX-defined antigens provide markers for the diagnosis of cancers. Potential diagnostic values of these SEREX-defined antigens have been evaluated. SEREX is also a powerful method for the development of anticancer therapeutics. The development of anticancer vaccines requires that tumor antigens can elicit antigen-specific antibodies or T lymphocytes. More than 2,000 antigens have been discovered by SEFEX. Peptides derived from some of these antigens have been evaluated in clinical trials. This review provides information on the application of SEREX for identification of tumor-associated antigens (TAA) for the development of cancer diagnostics and anticancer therapeutics.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3629-3633
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• 2015

Cancer stem cells (CSCs) are rare subpopulations within tumors which are recognized as culprits in cancer recurrence, drug resistance and metastasis. However, the molecular mechanisms of how CSCs are regulated remain elusive. Kr$\ddot{u}$ppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse functions in cell differentiation, proliferation, embryogenesis and pluripotency. Recent progress has highlighted the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for better therapeutics of cancer disease, it is crucial to develop a deeper understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we summarized the current understanding of the transcriptional regulation of K LF4 in CSCs, and discussed the functional implications of targeting CSCs for potential cancer therapeutics.