• Title/Summary/Keyword: Tumor environment

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High Pressure Extraction Process of Low Quality Fresh Ginseng for Enhancing Anticancer Activities (파삼의 항암활성 증진이 가능한 고압 추출 공정)

  • Ha, Ji-Hye;Kim, Young;Jeong, Seung-Seop;Jeong, Myoung-Hoon;Jeong, Heon-Sang;Jeong, Jae-Hyun;Yu, Kwang-Wan;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.6
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    • pp.397-406
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    • 2009
  • The low quality fresh ginseng was extracted by water at $80^{\circ}C$ and 240 bar for 20 min (HPE, High pressure extraction process). The cytotoxicity on human normal kidney cell (HEK293) and human normal lung cell (HEL299) of the extracts from HPE showed 28.43% and 21.78% lower than that from conventional water extraction at $100^{\circ}C$ in adding the maximum concentration of $1.0\;mg/m{\ell}$. The human breast carcinoma cell and lung adenocarcinoma cell growth were inhibited up to about 86%, in adding $1.0\;mg/m{\ell}$ of extracts from HPE. This values were 9-12% higher than those from conventional water extraction. On in vivo experiment using ICR mice, the variation of body weight of mice group treated fresh ginseng extracts from HPE of 100 mg/kg/day concentration was very lower than control and other group. The extracts from HPE was showed longer survival times as 35.65% than that of the control group, and showed the highest tumor inhibition activities compared with other group, which were 70.64% on Sarcoma-180 solid tumor cells. On the high performance liquid chromatogram (HPLC), amount of ginsenoside-$Rg_2$, $Rg_3$, $Rh_1$ and $Rh_2$ on fresh ginseng were increased up to 43-183% by HPE, compared with conventional water extracts. These data indicate that HPE definitely plays an important role in effectively extracting ginsenoside, which could result in improving anticancer activities. It can be concluded that low quality fresh ginseng associated with this process has more biologically compound and better anticancer activities than that from normal extraction process.

Induction of Apoptosis by Pectenotoxin-2 Isolated from Marine Sponges in U937 Human Leukemic Cells (인체 혈구암세포 U937에서 해양해면동물에서 추출된 Pectenotoxin-2에 의한 Apoptosis의 유발에 관한 연구)

  • Shin, Dong Yeok;Kang, Ho Sung;Bae, Song-Ja;Jung, Jee H.;Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.2
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    • pp.63-70
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    • 2006
  • Natural product compounds are the source of numerous therapeutic agents. The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets including anticancer agents. Among these, pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, which depolymerizes actin filaments, was found to be highly effective and more potent to activate an intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those with functional p53 both in vitro and in vivo. However, the anti-proliferative mechanism of the compound at non-cytotoxic concentrations has not yet been explored. In the current study, we sought to investigate anti-proliferation and apoptosis of PTX-2 against U937 human leukemic cells and its underlying molecular mechanism. Exposure of U937 cells to PTX-2 resulted in growth inhibition and induction of apoptosis in dose- and time-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. The anti-proliferative effect of PTX-2 was associated with a marked increase in the expression of cyclin-dependent kinase p21 (WAF1/CIP1) mRNA which was tumor suppressor p53-independent. The increase in apoptosis was connected with a time-dependent down-regulation of anti-apoptotic Bcl-XL and inhibitor of apoptosis proteins (IAPs) family such as XIAP and cIAP-2. Though additional studies are needed, these findings suggested that PTX-2-induced inhibition of U937 cells was associated with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of PTX-2.

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Wording on Acupuncture "鍼" & "針" Used by Historic Doctors (역대의학성씨(歷代醫學姓氏)의 침(針)과 침(鍼)에 대하여)

  • Kim, Hong-Kyoon;An, Sang-Woo
    • The Journal of Korean Medical History
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    • v.25 no.2
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    • pp.155-193
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    • 2012
  • From the part "歷代醫學姓氏(Historic Doctors)" in "醫林撮要(Uirimchualyo)", the following has been noticed and concluded. 1. Because acupuncture was originated from stony needle, the word "石(sok)" contains the meaning of needle, and from this point on, words like 石(sok), 砭石(pyumsok), 箴石(Jamsok), 鑱石(Chamsok) had been derived. 2. The word 砭石(pyumsok) used in "Hwangjenaekyong(Yellow Emperor's Canon of Medicine or Hwangdineijing)" should be interpreted as acupuncture in a verb form, not a noun form. 3. 鑱石(Chamsok) or 鑱鍼(Chamchim) was used for surgical treatment for tumor, by cutting open tumors and pressing the pus out. Therefore, 砭石(pyumsok), 鑱石(Chamsok) are the same kind of needles, and 鑱鍼(Chamchim) is the tool improved from 鑱石(Chamsok) used in the Bronze Age. 4. Kwakpak put a note on 鑱石(Chamsok) in "山海經(Sanhaekyong)" that reads "it is defined as 砥鍼(Jichim) and treats tumor." This let us know the shape of 石(sok), 砭石(pyumsok), 鑱(Chamsok), 鑱鍼(Chamchim), and the stone that can be used as a surgical tool with slim & sharp shape is obsidian. 5. Because obsidian is only found around Mt. Baekdu and limited area in South Korea & Japan in Asia, it is closely related with the life & medical environment of the tribe "Mt. Baekdu". 6. The development of 鑱鍼(Chamchim) was influenced by surgical treatment used in early stage of civilization, and its origin is traced upto Gochosun dynasty. Korea's own traditional medical knowledge is derived from this surgical treatment skill. 7. Because the acupuncture is originated from Gochosun dynasty, 鍼(chim) was derived from 箴(Jam) of 箴石(Jamsok), 䥠(Chim) & 䥠(Chim) both were used for a time being, and finally settled into 鍼(Chim). 8. The word 針(Chim) showed up at Myung dynasty, and started to be used in Korea from early Chosun dynasty. 9. In the early Chosun dynasty, 鍼(Chim) was used for medical term, and 針(Chim) for non-medical term. In the mid Chosun dynasty, 針(Chim) was used as a term for tool, and 鍼(Chim) as a term for acupunctural medical treatment. 10. Under the order of King Sunjo, Dr. Yesoo Yang published "醫林撮要(Uirimchualyo)", added "醫林撮要續集(Sequel to Uirimchualyo)", and added "歷代醫學姓氏(Historic Doctors)" again which eventually made totally 13 books of "醫林撮要(Uirimchualyo)". In addition, many parts of "醫林撮要續集(Sequel to Uirimchualyo)" were quoted in "東醫寶鑑(Donguibogam)", and influenced much in publishing "Donguibogam". 11. In "歷代醫學姓氏(Historic Doctors)" of "醫林撮要(Uirimchualyo)", the same way in "Donguibogam", referred to 針(Chim) as a term for a needle, and 鍼(Chim) as a term for Acupuncture. 12. From the usage of 針(Chim) & 鍼(Chim), shown in "鄕藥集成方(Hyangyakjipsungbang)", "醫林撮要(Uirimchualyo)" and "東醫寶鑑(Donguibogam)", we can notice the spirit of doctors who tried to take over the legitimacy of Korean tradition, and their elaboration & historical view that expresses confidence on our own medical technology, through the wording 鍼(Chim).

Metastasis prognostic factors and cancer stem cell-related transcription factors associated with metastasis induction in canine metastatic mammary gland tumors

  • Kim, Saetbyul;Bok, Eunyeong;Lee, Sangyeob;Lee, Hyeon-Jeong;Choe, Yongho;Kim, Na-Hyun;Lee, Won-Jae;Rho, Gyu-Jin;Lee, Sung-Lim
    • Journal of Veterinary Science
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    • v.22 no.5
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    • pp.62.1-62.13
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    • 2021
  • Background: Canine mammary gland tumor (MGT) is the most common cancer in aged female dogs. Although it's important to identify reliable metastasis or prognostic factors by evaluating related to cell division, adhesion, and cancer stem cell-related transcription factor (TF) in metastasis-induced canine MGT, but there are limited studies. Objectives: We aimed to identify metastasis prognostic factors and cancer stem cell-TFs in canine MGTs. Methods: Age-matched female dogs diagnosed with MGT only were classified into metastatic and non-metastatic groups by histopathological staining of MGT tissues. The mRNA levels of cancer prognostic metastasis molecular factors (E-cadherin, ICAM-1, PRR14, VEGF, HPRT1, RPL4 and hnRNP H) and cancer stem cell-related TFs (Oct4, Sox2, and Nanog) were compared between metastatic and non-metastatic canine MGT tissues using qRT-PCR analysis. Results: The mRNA levels of ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog in metastatic MGT group were significantly higher than those in non-metastatic MGT group. However, mRNA level of RPL4 was significantly lower in metastatic MGT group. Loss of E-cadherin and HPRT1 was observed in the metastatic MGT group but it was not significant. Conclusions: Consistent expression patterns of all metastasis-related factors showing elevation in ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog, but decreases in RPL4 levels occurred in canine MGT tissues, which was associated with metastasis. Thus, these cancer prognostic metastasis factors and TFs of cancer stem cells, except for E-cadherin and HPRT1, can be used as reliable metastasis factors for canine MGT and therapeutic strategy.

Vitamin D maintains E-cadherin intercellular junctions by downregulating MMP-9 production in human gingival keratinocytes treated by TNF-α

  • Oh, Changseok;Kim, Hyun Jung;Kim, Hyun-Man
    • Journal of Periodontal and Implant Science
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    • v.49 no.5
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    • pp.270-286
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    • 2019
  • Purpose: Despite the well-known anti-inflammatory effects of vitamin D in periodontal health, its mechanism has not been fully elucidated. In the present study, the effect of vitamin D on strengthening E-cadherin junctions (ECJs) was explored in human gingival keratinocytes (HGKs). ECJs are the major type of intercellular junction within the junctional epithelium, where loose intercellular junctions develop and microbial invasion primarily occurs. Methods: HOK-16B cells, an immortalized normal human gingival cell line, were used for the study. To mimic the inflammatory environment, cells were treated with tumor necrosis factor-alpha ($TNF-{\alpha}$). Matrix metalloproteinases (MMPs) in the culture medium were assessed by an MMP antibody microarray and gelatin zymography. The expression of various molecules was investigated using western blotting. The extent of ECJ development was evaluated by comparing the average relative extent of the ECJs around the periphery of each cell after immunocytochemical E-cadherin staining. Vitamin D receptor (VDR) expression was examined via immunohistochemical analysis. Results: $TNF-{\alpha}$ downregulated the development of the ECJs of the HGKs. Dissociation of the ECJs by $TNF-{\alpha}$ was accompanied by the upregulation of MMP-9 production and suppressed by a specific MMP-9 inhibitor, Bay 11-7082. Exogenous MMP-9 decreased the development of ECJs. Vitamin D reduced the production of MMP-9 and attenuated the breakdown of ECJs in the HGKs treated with $TNF-{\alpha}$. In addition, vitamin D downregulated $TNF-{\alpha}$-induced nuclear factor kappa B ($NF-{\kappa}B$) signaling in the HGKs. VDR was expressed in the gingival epithelium, including the junctional epithelium. Conclusions: These results suggest that vitamin D may avert $TNF-{\alpha}$-induced downregulation of the development of ECJs in HGKs by decreasing the production of MMP-9, which was upregulated by $TNF-{\alpha}$. Vitamin D may reinforce ECJs by downregulating $NF-{\kappa}B$ signaling, which is upregulated by $TNF-{\alpha}$. Strengthening the epithelial barrier may be a way for vitamin D to protect the periodontium from bacterial invasion.

Anti-inflammatory effects of Lycoris chejuensis callus using biorenovation (Biorenovation 기법 적용 제주상사화 callus의 항염증 활성)

  • Hyehyun Hong;Tae-Jin Park;Yu-Jung Lee;Jung-Hwan Kim;Seung-Young Kim
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.197-203
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    • 2023
  • Callus cultivation is a method for producing a large amount of tissue of a plant in the laboratory, regardless of the environment. Lycoris chejuensis, a plant species native to jeju island, is a member of the Lycoris family has been used as a traditional medicine for the treatment of diverse diseases. In this study, we evaluated anti-inflammatory effect of biorenovated Lycoris chejuensis callus (LCB) in lipopolysaccharide (LPS)-induced RAW264.7 cells. As a result, LCB was less toxic to the cells in the concentration range of 25, 50, and 100 ㎍/mL as shown by the improved viability of LCB treated cells than compared to Lycoris chejuensis callus (LC) treatment. In addition, LCB inhibited the generation of NO and prostaglandin E2 through the suppression of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. LCB also attenuated the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α induced by LPS. The results suggest that LCB has anti-inflammatory activity on the LPS-induced inflammatory response and may be suitable for the development of potent functional cosmetic material.

Ginsenoside Rg3 Induces Apoptosis in B16F10 Melanoma Cells (ginsenoside Rg3에 의한 B16F10 흑색종 세포의 세포사멸 유도)

  • Lee, Seul Gi;Kim, Byung Soo;Nam, Ju-Ock
    • Journal of Life Science
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    • v.24 no.9
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    • pp.1001-1005
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    • 2014
  • Ginsenoside Rg3 is one of the active ingredients extracted from red ginseng, and it is an effective chemical component of the human body and well known in herbal medicine as a restorative agent. Several studies have shown that Rg3 has a potent anti-tumor effect on various cancer cell lines. However, Rg3-induced apoptosis in B16F10 melanoma cancer cells is not well understood. In the present study, we tested whether ginsenoside Rg3 could induce apoptosis in B16F10 melanoma cells. We found that Rg3 could inhibit B16F10 melanoma cell viability in a dose-dependent manner, but not normal cells, such as EA.hy.926 and NIH3T3 cells. We also found that Rg3 could induce apoptosis in B16F10 melanoma cells using tunnel-staining assay in a dose-dependent manner. Rg3 treatment induces the phosphorylation of p38 and the expression of Bax, but it inhibits the expressions of the phosphorylation of focal adhesion kinase Bcl2 and pro-caspase3. Taken together, our data suggest that Rg3 could be useful as an anti-cancer agent in B16F10 melanoma cells.

The Role of Uteroglobin in the Immunomodulation of Nonsmall Cell Lung Cancer Cells (비소세포 폐암세포에서 Uteroglobin의 면역 조절 기능에 대한 연구)

  • Yoon, Jung Min;Lim, Jae-Jun;Yoo, Chul-Gyu;Lee, Choon-Taek;Han, Sung Koo;Shim, Young-Soo;Kim, Young Whan
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.4
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    • pp.336-344
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    • 2004
  • Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

The Effect of Translationally Controlled Tumor Protein (TCTP) of the Arctic Copepod Calanus glacialis on Protecting Escherichia coli Cells against Oxidative Stress (북극 동물플랑크톤 Calanus glacialis TCTP (Translationally Controlled Tumor Protein)가 산화적 스트레스 상태에서 E. coli 세포의 저항성에 미치는 효과)

  • Park, Yu Kyung;Lee, Chang-Eun;Lee, Hyoungseok;Koh, Hye Yeon;Kim, Sojin;Lee, Sung Gu;Kim, Jung Eun;Yim, Joung Han;Hong, Ju-Mi;Kim, Ryeo-Ok;Han, Se Jong;Kim, Il-Chan
    • Journal of Life Science
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    • v.30 no.11
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    • pp.931-938
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    • 2020
  • Translationally controlled tumor protein (TCTP) is one of the most abundant proteins in various eukaryotic organisms. TCTPs play important roles in cell physiological processes in cancer, cell proliferation, gene regulation, and heat shock response. TCTP is also considered an important factor in the resistance to oxidative stress induced by dithiothreitol or hydrogen peroxide (H2O2). Arctic calanoid copepods have a variety of antioxidant defense systems to regulate the levels of potentially harmful reactive oxygen species generated by ultraviolet radiation in the Arctic marine ecosystem. However, information on the antioxidant activity of TCTP in the Arctic Calanus glacialis is still scarce. To understand the putative antioxidant function of the Arctic copepod C. glacialis TCTP (Cg-TCTP), its gene was cloned and sequenced. The Cg-TCTP comprised 522 bp and encoded a 174-amino acid putative protein with a calculated molecular weight of ~23 kDa. The recombinant Cg-TCTP (Cg-r TCTP) gene was overexpressed in Escherichia coli (BL21), and Cg-rTCTP-transformed cells were grown in the presence or absence of H2O2. Cg-rTCTP-transformed E. coli showed increased tolerance to high H2O2 concentrations. Therefore, TCTP may be an important antioxidant protein related to tolerance of the Arctic copepod C. glacialis to oxidative stress in the harsh environment of the Arctic Ocean.

A Study on Establishment of Reference Value of CA 72-4 (CA 72-4 참고치 설정에 관한 연구)

  • An, Jae-Seok;Kim, Ji-Na;Joe, Ye-Ji;Yoon, Sang-Hyuk;Kim, Yoon-Cheol
    • The Korean Journal of Nuclear Medicine Technology
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    • v.25 no.2
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    • pp.25-28
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    • 2021
  • Purpose CA 72-4 is a tumor marker that uses two monoclonal antibodies, CC49 and B72.3, to measure tumor-related glycoprotein(TAG72) in the serum. CA 72-4 is used to diagnose stomach, ovarian, and pancreatic cancers, and is known to perform high specificity for stomach cancer. The purpose of this study is to re-evaluate the reference value provided by the manufacturer through revalidation of the reference value in CA 72-4. Furthermore this study was conducted to provide useful help when making a clinical diagnosis at gastric cancer center. Materials and Methods We selected 271 patients who had been to health care center in national cancer center for the month of November 2020. The gender of the subjects was 140 males and 131 females, and the age group was from 30s to 60s. The reagent used in the study was a CA 72-4 IRMA KIT (ISOTOPES, Hungary) and the results were measured using a Dream Gamma-10 gamma counter (Shinjin medics, Korea). Results Statistical analysis of the results of this study used Hoffmann's method and Bayesian's method, which are primarily used in setting reference value. As a result of measuring CA 72-4 of 271 patients, the mean value was 4.54 U/mL and the median value was 3.30 U/mL. 24 people who deviated from 3SD were excluded from the measured value, the mean calculated after that was 3.53 U/mL, median was 3.00 U/mL and SD was 1.89. The reference value calculated based on this results was set to 7.31 U/mL. Conclusion The reference value provided by the manufacturer is less than 4 U/mL. It is slightly different from the value calculated in this study, 7.31 U/mL, so it seems necessary to reset the reference value according to the laboratory environment. Currently, we are receiving inquiries about the reference value from the center for gastric cancer at National Cancer Center. If additional research is carried out along with this study, it will be possible to set more accurate reference value.