• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2575-2580
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• 2015

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.

• The Korean Journal of Pain
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• 제28권4호
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• pp.236-243
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• 2015

Background: Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. Methods: Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. Results: Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. Conclusions: Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.

• Molecules and Cells
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• 제24권1호
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1571-1576
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• 2016

Alteration of the acetylation status of chromatin and other non-histone proteins by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment of cancers. The present study was sought to identify compounds with positive pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by Cai et al, 2015 formed the test compounds for the present pharmacological evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in comparison to all the compounds in the analogue dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify compounds with even better high affinity and pharmacological profile than 6H and Vorinostat, virtual screening was performed. A total of 83 compounds similar to Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695 (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and 6H, were the best docked compounds among the virtually screened compounds. However, in spite of having good affinity, none of the virtually screened compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report Vorinostat hydroxamate analogue 6H to be a potential candidate for HDAC inhibition in treatment of cancers through an epigenetic strategy.

• 한국발생생물학회지:발생과생식
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• 제18권4호
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• pp.225-231
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• 2014

Autophagy is a homeostatic degradation process that is involved in tumor development and normal development. Autophagy is induced in cancer cells in response to chemotherapeutic agents, and inhibition of autophagy results in enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial drug, is a lysosomotropic agent and is currently used as a potential anticancer agent as well as an autophagy inhibitor. Here, we evaluate the characteristics of these dual activities of CQ using human colorectal cancer cell line HCT15. The results show that CQ inhibited cell viability in dose- and time-dependent manner in the range between 20 to 80 uM, while CQ did not show any antiproliferative activity at 5 and 10 uM. Cotreatment of CQ with antitumor agent NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability at low concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced the lethal effect at high concentrations. Acridine orange staining revealed that CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses of CQ produced cellular reactive oxygen species (ROS) and cotreatment of antioxidants, such as NAC and trolox, with high doses of CQ rescued the cell viability. These results suggest that CQ may exert its dual activities, as autophagy inhibitor or LMP inducer, in concentration-dependent manner.

• 동의생리병리학회지
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• 제20권4호
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• pp.1027-1031
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• 2006

In oriental medicine, Geijibokryunghwan(GBH) was used to improvement various symptoms created by the thrombosis. We investigated the effects of an oriental medicinal prescriptions, Geijibokryunghwan (GBH) consisting of herbs of Cinnamomi Ramufus (Geiji; 桂枝), Poria cocos (Bokrung; 茯?), Moutan Cortex Radicis(Modanpi; 牧丹皮), Paeoniae Radix (Jakyak; 芍藥) and Persicae Semen (Doin; 桃仁) on tumor growth-inhibitory activity and cancer chempreventive activity in assays representing three maior stages of carcinogenesis. Cancer chempreventive agents include nonsteroidal anti-inflammatory drugs (NSAIDS) such as indomethacin, aspirin, piroxicam, and sulindac, all of which inhibit cyclooxygenase (COX). Effects of the GBH extracts on carrageenan-induced edema Inflammation using female (C57BL/6XC3H) Fl (B6C3Fl ) mice and tumorigenesis were examined. Finally, cyclooxygenase metabolites were determined after extracts treatment. These data suggest that GBH extracts merits investigation as a potential cancer chempreventive agent in humans.

• Journal of Yeungnam Medical Science
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• 제38권3호
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• pp.251-257
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• 2021

Vedolizumab (VDZ) has been approved for the treatment of inflammatory bowel diseases (IBDs) in patients aged ≥18 years. We report a case of a pediatric patient with Crohn disease (CD) who was successfully treated with VDZ. A 16-year-old female developed severe active pulmonary tuberculosis (TB) during treatment with infliximab (IFX). IFX was stopped, and TB treatment was started. After a 6-month regimen of standard TB medication, her pulmonary TB was cured; however, gastrointestinal symptoms developed. Due to the concern of the patient and parents regarding TB reactivation on restarting treatment with IFX, VDZ was started off-label. After the second dose of VDZ, the patient was in clinical remission and her remission was continuously sustained. Ileocolonoscopy at 1-year after VDZ initiation revealed endoscopic healing. Therapeutic drug monitoring conducted during VDZ treatment showed negative antibodies to VDZ. No serious adverse events occurred during the VDZ treatment. This is the first case report in Korea demonstrating the safe and effective use of VDZ treatment in a pediatric CD patient. In cases that require recommencement of treatment with biologics after recovery of active pulmonary TB caused by anti-tumor necrosis factor agents, VDZ may be a good option even in pediatric IBD.

• 동의신경정신과학회지
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• 제12권2호
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• pp.173-183
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• 2001

Substance P can stimulate secretion of tumor necrosis $factor-\;{\alpha}\;(TNF-\;{\alpha}\;)$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Chilbogeum can modulate cytokines secretion from primary cultures of rat astrocytes. Chilbogeum $(10\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and Substance P. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Chilbogeum $(10,\;100\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and Substance P decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and Substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in Alzheimer's disease (AD) pathology, during which they themselves may produce still more inflammatory cytokines. Chilbogeum $(10,\;100\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by CCF-STTG1 astrocytoma cells stimulated with $A\;{\beta}$ and IL-1. These results suggest that Chilbogeum may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Chilbogeum has an antiinflammatory activity in AD brain.

• 대한의생명과학회지
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• 제3권2호
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• pp.71-76
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• 1997

실험적 자궁암 치료제로서 본 연구소에서 합성한 마이토센유사체를 인체 자궁암세포주인 SiHa, C33A, HeLa, CaSki에 처리하여, 체외 항암활성 측정시 합성 마이토센유사체들은 이 들 세포주에 대하여 대조 항암제들에 비하여 의의있는 세포독성을 보였으며, SiHa 세포주를 이용한 종양클론형성 억제검사에서는 22번 화합물만이 종양성장 억제활성이 가장 우수하였고 다른 화합물들은 대조항암제들에 비하여 활성이 낮았다. 이 마이토센유사체들에 대한 체외 항암감수성결과는 향후 전임상적인 자궁경부암 화합요법제의 기초자료로 유용할것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.915-921
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• 2015

Context: In the last half century, discovering, developing and introducing of clinical agents from marine sources have seen great successes, with examples including the anti-cancer compound trabectedin. However, with increasing need for new anticancer drugs, further exploration for novel compounds from marine organism sources is strongly justified. Objective: The major aim of this study was to evaluate the antitumor and antioxidant potential of Sargassum tenerrimum J.Agardh (Sargassaceae) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Materials and Methods: An ethanol extract of S. tenerrimum (EEST) from whole algae was used to evaluate cytotoxicity followed by in vivo assessment of toxicity, using biochemical parameters including hepatic and non-hepatic enzymes. Antioxidant properties were examined in animals bearing EAC treated with daily oral administration of 100-300 mg/kg extract suspension. Results: Antitumor effects of EEST in EAC bearing mice was observed with LD50 1815 mg/kg. Parameters like body weight, tumor volume, packed cell volume, tumor cell count, mean survival time and increase in life span in animals in the EAC bearing animals treated with EEST 300 mg/kg was comparable with control group. Significant differences were also seen with changes in total protein content, hepatic enzymes contents, MDA level, and free radical scavenging enzymes in untreated vs. EEST treated group animals. Conclusions: Evaluation of antioxidant enzymes and hepatic enzymes in the EAC animal model treated with EEST exhibited similar effects as the positive control drug 5-flurouracil. S. tenerrimum extracts contain effective antioxidants with significant antitumor activity.