• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1425-1430
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• 2012

Cyclin L2 is a novel member of the cyclin family, recently implicated in the regulation of cell cycle progression and/or transcriptional regulation. The present study was undertaken to investigate the effects of overexpression on tumor cell growth and chemosensitivity in human gastric cells in vitro. Cyclin L2 was transfected into human gastric cancer cell line BCG823 and expressed with a mammalian expression vector pcDNA3.1. The effects and mechanisms of cyclin L2 on cell growth, cell cycling and apoptosis were studied. Compared to control vectors, overexpression of cyclin L2 inhibited the growth of BCG823 cells and enhance their chemosensitivity to fluorouracil, docetaxel and cisplatin. The anti-proliferative effects of cyclin L2 could be due to G0/G1 arrest and apoptosis. Cyclin L2 induced G0/G1 arrest and apoptosis involved upregulation of caspase-3 and down regulation Bcl-2 and survivin. The results indicated that overexpression of cyclin L2 protein may promote efficient growth inhibition and enhance chemosensitivity to chemotherapeutic agents in human gastric cancer cells by inducing G0/G1 cell cycle arrest and apoptosis.

• The Korean Journal of Pain
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• 제26권1호
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• pp.65-71
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• 2013

More than 80% of cancer patients experience cancer pain. Among them, more than 50% experience moderate to severe pain. To control cancer pain, a variety of methods have been used, including medications and nerve blocks. In some patients, however, it is impossible to perform nerve blocks due to caner metastasis into the epidural space, while in other patients, opioid dose escalation is impossible due to opioid side effects; thus, cancer pain management is difficult. Scrambler therapy is a novel approach for pain control that uses EKG-like pads, which are applied above and below the site of pain. Scrambler therapy synthesizes 16 different types of nerve action potentials that provide "non-pain" information via cutaneous nerves. The advantages of this treatment are that it is non-invasive and safe and has no significant side effects. In this case series, we report the treatment results of using scrambler therapy in three cancer patients with intractable pain.

• 한국임상약학회지
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• 제26권4호
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• pp.269-282
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• 2016

Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, has increased in cancer patients and adversely affects their prognosis. Low-molecular-weight heparins are recommended as efficacious and safe anticoagulation treatment in cancer patients. However, in practice, oral anticoagulation is preferred, especially if longterm or extended treatment is necessary. Novel oral anticoagulants have recently emerged as an alternative to the standard therapy owing to the ease of administration, predictable anticoagulation effect without the need of laboratory monitoring, and fewer drug interactions. These new agents have been shown as effective and safe for the management of cancer-associated thrombosis in ongoing head-to-head comparative trials. Here we review the advances and limitation of current anticoagulant therapies.

• BMB Reports
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• 제47권3호
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• pp.158-166
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• 2014

Cell proliferation is a delicately regulated process that couples growth signals and metabolic demands to produce daughter cells. Interestingly, the proliferation of tumor cells immensely depends on glycolysis, the Warburg effect, to ensure a sufficient amount of metabolic flux and bioenergetics for macromolecule synthesis and cell division. This unique metabolic derangement would provide an opportunity for developing cancer therapeutic strategy, particularly when other diverse anti-cancer treatments have been proved ineffective in achieving durable response, largely due to the emergence of resistance. Recent advances in deeper understanding of cancer metabolism usher in new horizons of the next generation strategy for cancer therapy. Here, we discuss the focused review of cancer energy metabolism, and the therapeutic exploitation of glycolysis and OXPHOS as a novel anti-cancer strategy, with particular emphasis on the promise of this approach, among other cancer metabolism targeted therapies that reveal unexpected complexity and context-dependent metabolic adaptability, complicating the development of effective strategies.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• Nuclear Medicine and Molecular Imaging
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• 제40권5호
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• pp.237-242
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• 2006

Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment has led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest In suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner.

• BMB Reports
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• 제55권1호
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• pp.48-56
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• 2022

Small extracellular vesicles (sEVs) secreted by most cells carry bioactive macromolecules including proteins, lipids, and nucleic acids for intercellular communication. Given that some immune cell-derived sEVs exhibit anti-cancer properties, these sEVs have received scientific attention for the development of novel anti-cancer immunotherapeutic agents. In this paper, we reviewed the latest advances concerning the biological roles of immune cell-derived sEVs for cancer therapy. sEVs derived from immune cells including dendritic cells (DCs), T cells, natural-killer (NK) cells, and macrophages are good candidates for sEV-based cancer therapy. Besides their role of cancer vaccines, DC-shed sEVs activated cytotoxic lymphocytes and killed tumor cells. sEVs isolated from NK cells and chimeric antigen receptor (CAR) T cells exhibited cytotoxicity against cancer cells. sEVs derived from CD8⁺ T and CD4⁺ T cells inhibited cancer-associated cells in tumor microenvironment (TME) and activated B cells, respectively. M1-macrophage-derived sEVs induced M2 to M1 repolarization and also created a pro-inflammatory environment. Hence, these sEVs, via mono or combination therapy, could be considered in the treatment of cancer patients in the future. In addition, sEVs derived from cytokine-stimulated immune cells or sEV engineering could improve their anti-tumor potency.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1719-1722
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• 2012

The Wiskott-Aldrich Syndrome Protein family Verprolin - homologous proteins (WAVEs), encoded by a metastasis promoter gene, play considerable roles in adhesion of immune cells, cell proliferation, migration and destruction of foreign agents by reactive oxygen species. These diverse functions have lead to the hypothesis that WAVE proteins have multi-functional roles in regulating cancer invasiveness, metastasis, development of tumor vasculature and angiogenesis. Differentials in expression of WAVE proteins are associated with a number of neoplasms include colorectal cancer, hepatocellular cancer, lung squamous cell carcinoma, human breast adenocarcinoma and prostate cancer. In this review we attempt to unify our knowledge regarding WAVE proteins, focusing on their potentials as diagnostic markers and molecular targets for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.23-29
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• 2015

Background: Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge-scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.418-426
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• 2022

Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1⁺ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8⁺ T cells having CD8⁺CD44⁺CD62L^low phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.