• Title/Summary/Keyword: therapeutic agents

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Immune Function-enhancing Effects of Bojungikkitanggami-bang (보중익기탕가미방의 면역기능 증진 효과)

  • Lee Sang Hun;Lee Seung Eon;Lee Si Hyeong;Shin Jo Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.2
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    • pp.528-533
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    • 2004
  • The immune system acts to protect the host from infectious agents that exist in the environment and from other noxious insults. The immune system has two functional divisions: the innate and the acquired. Both components involve various factors such as cytokines. A number of methodologies exist to assess aspects of immune function. There are large inter-individual variations in many immune functions even among the healthy. Genetics, age, gender, smoking habits, habitual levels of exercise, alcohol consumption, diet, stage in the female menstrual cycle, stress, history of infections and vaccinations, and early life experiences are likely to be important contributors to the observed variation. While it is clear that individuals with immune responses significantly below 'normal' are more susceptible to infectious agents and exhibit increased infectious morbidity and mortality, it is not clear how the variation in immune function among healthy individuals relates to variation in susceptibility to infection. Oriental medicine is an important factor contributing to immune competence. The author investigated the immune enhancement effects of Bojungikkitanggami-bang (BITB). The forced swimming test (FST) has been used as a screening model for new immune enhancement agents. In the present study, the author investigated the effects of BITB on FST and blood biochemical parameters related to fatigue, glucose (Glc); blood urea nitrogen (BUN); lactate dehydrogenase (LDH); creatinine; and total protein (TP). The author found that BITB (1 g/kg) significantly reduced the immobility time in the FST compared to the control. In addition, the contents of Glc, LDH, BUN, TP in the blood serum were increased in BITB (1g/kg)-fed group. Also, the author investigated the effects of BITB on the production of cytokines in human T-cell line, MOLT-4 cells. BITB (1 mg/ml) significantly increased the interferon (IFN)-vproduction compared with media control (about 2.2-fold for IFN-γ) at 24 h. However, BITB has not affect the production of IL-2 and IL-4. In addition, BITB increased the protein expression level of IFN-γ in MOLT-4 cells. Thus, BITB may have therapeutic value in generating or enhancing immune function in a clinical setting.

A Monte Carlo Study of Dose Enhancement with kilovoltage and megavoltage photons (몬테칼로 기법을 이용한 kV, MV X선에서의 선량증가 효과 비교 평가)

  • Hwang, ChulHwan;Im, In-Chul;Kim, Jung-Hoon
    • Journal of the Korean Society of Radiology
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    • v.11 no.2
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    • pp.87-94
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    • 2017
  • Monte Carlo simulations were used to assess dose enhancement effects for 60-, 90-, 120-, and 150-kV X-rays, and for 6- and 15-MV X-rays. The MCNPX code was used for a computer simulation of the ICRU slab phantom, and gold, gadolinium, and iron oxide (Fe2O3) were employed as dose enhancement agents. In consideration of the buildup region of the incident energy, agent concentrations of 5, 10, 15, and 20 mg/g were inserted on the surface of the phantom at a depth of 5 cm. Based on baseline values obtained in the absence of dose enhancement agents, a quantitative analysis was performed by evaluating depth-dependent changes in the absorbed energy and the dose enhancement factor (DEF). A higher concentration of dose enhancement agents led to a greater dose enhancement effect with iron oxide, gadolinium, and gold in descending order. For kilovoltage (kV) X-rays, as the incident energy was decreased and as the energy became closer to the ionization potential of the atoms in the enhancement agent, the dose enhancement effect increased. In the megavoltage (MV) X-ray range, dose enhancement was higher at 6 MV compared with 15 MV. However, the overall dose enhancements were significantly lower compared to the results obtained with kV X-rays.

Luteolin-loaded Phytosomes Sensitize Human Breast Carcinoma MDA-MB 231 Cells to Doxorubicin by Suppressing Nrf2 Mediated Signalling

  • Sabzichi, Mehdi;Hamishehkar, Hamed;Ramezani, Fatemeh;Sharifi, Simin;Tabasinezhad, Maryam;Pirouzpanah, Mohammadbagher;Ghanbari, Parisa;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5311-5316
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    • 2014
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.

Effect of DA-6034, a Derivative of Flavonoid, on Experimental Animal Models of Inflammatory Bowel Disease

  • Kim, You-Sun;Son, Mi-Won;Ko, Jun-Il;Cho, Hyeon;Yoo, Moo-Hi;Kim, Won-Bae;Song, In-Sung;Kim, Chung-Yong
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.354-360
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    • 1999
  • Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034,$ 7-carboxymethyloxy-3^{l}, 4^{l},$ 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD : two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3~3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 gm/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

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Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways

  • Pandurangan, Ashok Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2201-2205
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    • 2013
  • Colorectal cancer (CRC) is one of the most common cancers in many parts of the world. Its development is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested an association of the phosphoinositide-3-kinase (PI3K)/Akt pathway with colon tumorigenesis. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human colon cancers and inhibitors of PI3K/Akt signaling have been suggested as potential therapeutic agents. Around 80% of human colon tumors possess mutations in the APC gene and half of the remainder feature ${\beta}$-catenin gene mutations which affect downstream signaling of the PI3K/Akt pathway. In recent years, there has been a great focus in targeting these signaling pathways, with natural and synthetic drugs reducing the tumor burden in different experiment models. In this review we survey the role of PI3K/Akt/mTOR and Wnt signaling in CRC.

Adoptive Cell Therapy of Melanoma with Cytokine-induced Killer Cells

  • Kim, Ji Sung;Kim, Yong Guk;Pyo, Minji;Lee, Hong Kyung;Hong, Jin Tae;Kim, Youngsoo;Han, Sang-Bae
    • IMMUNE NETWORK
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    • v.15 no.2
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    • pp.58-65
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    • 2015
  • Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.

Microarray and Next-Generation Sequencing to Analyse Gastric Cancer

  • Dang, Yuan;Wang, Ying-Chao;Huang, Qiao-Jia
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8035-8040
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    • 2014
  • Gastric cancer is the second after lung cause of cancer-related mortality in the world. Early detection and treatment can lead to a long survival time. Recently microarrays and next generation sequencing (NGS) have become very useful tools of comprehensive research into gastric cancer, facilitating the identification of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discovery to practical clinical benefits. Although there are many biomarkers and target agents, only a minority of patients are tested and treated accordingly. Microarray technology with maturity was established more than 10 years ago, and has been widely used in the study of functional genomics, systems biology, and genomes in medicine. Second generation sequencing technology is more recent, but development is very fast, and it has been applied to the genome, including sequencing and epigenetics and many aspects of functional genomics. Here we review insights gained from these studies regarding the technology of microarray and NGS, how to elucidate the molecular basis of gastric cancer and identify potential therapeutic targets, and how to analyse candidate genes. We also discuss the challenges and future directions of such efforts.

Roles of growth factors, calcitonic polypeptides and neuropeptides in bone metabolism, osteoporosis and rheumatis arthritis

  • Lee, Tae-Kyun;Kim, June-ki;Kim, Kap-Sung;Chang, Jun-Hyuk;Jeong, Ji-cheon;Nam, Kyung-Soo;Kim, Cheorl-Ho
    • The Journal of Dong Guk Oriental Medicine
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    • v.9
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    • pp.1-23
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    • 2000
  • Osteoporosis is a common disorder characterized by reduced bone mineral density, deterioration of the microarchitecture of bone tissue and increased risk of fracture. The aim of treatment of osteoporosis is to maintain and, ideally, to restore bone strength safely. In recent years the role of polypeptide growth factors in bone metabolism has begun to appear. It has been proposed that alterations in the expression or production of growth factor can modulate the proliferation and activity of bone forming cells. Thus, the role of structurally diverse peptides for the management and diagnosis of osteoporosis has attracted the attention of many investigators. This paper reviews numerous findings concerning the use of polypeptides, hormones, and growth factors, for the management of osteoporosis. Many of the compounds mentioned here are experimental prototypes of new therapeutic classes. Though it is unlikely that some of the compounds may ever be used clinically, development of safe and efficacious agents in each class will define the future course of therapy for osteoporosis.

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Inhibition Effect of Gleditsia Sinensis Lam on T tyrosinase Activity and Reactive Oxygen Species related to Melanin Biosynthesis

  • Kim, Yeon-Zu;Kim, Jin;Park, Hee-Jung;Lee, Chang-Moon;Lee, Ki-Young
    • 한국생물공학회:학술대회논문집
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    • 2005.04a
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    • pp.541-543
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    • 2005
  • Recently many efforts have been made to develop new therapeutic agents against skin pigmentation abnormalities. The aim of this study is to investigate the skin-whitening effect of Gleditsia Sinensis Lam and to develop new drug delivery carrier. Inhibitory effaces of Gleditsia Sinensis Lam extracts on melanin synthesis were studied. Namely, UV-absorbing ability, free radical scavenging activity and tyrosinase inhibitory of Gleditsia Sinensis Lam extracts were investigated As a result, the extracts of Gleditsia Sinensis Lam were found to inhibit the activity of tyrosinase. Moreover they absorbed wavelength in the UV-B and UV-C region, and extracts of Gleditsia Sinensis Lam had free radical scavenging activity. In this study, in order to administer these ingredient effectively, the shape of liposome observed by TEM was spherical and uniform.

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Natural Product Research in Dental Caries Prevention (임상가를 위한 특집 1 - 충치예방과 관련된 천연물(natural products) 연구의 현황)

  • Jeon, Jae-Gyu
    • The Journal of the Korean dental association
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    • v.50 no.9
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    • pp.544-551
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    • 2012
  • Dental caries is a biofilm-related oral disease, and continues to afflict the majority of the world's population. Although fluoride, delivered in various modalities, remains the mainstay for the prevention of caries, additional approaches are required to enhance its effectiveness. Natural products have been used as a major source of innovative and effective therapeutic agents throughout human history, and have shown promise as a source of components for the development of new drugs. In addition. studies using natural products to prevent or treat oral diseases such as dental caries have received a great deal of attention. A number of compounds, such as epicatechin, allicin and sanguinarine, isolated from natural products, have also been investigated for their efficacy against oral microbial pathogens. However, the use of natural products as an anti-caries agent in clinical practice was controversial because of inadequate knowledge concerning their mechanisms of action and chemical characterization. This study focuses on the current knowledge of natural products in dental caries prevention and suggests natural products are importance sources for the prevention of dental caries.