• Title/Summary/Keyword: Tumor environment

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The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4

  • Lee, Su Jung;Noh, Kyung Tae;Kang, Tae Heung;Han, Hee Dong;Shin, Sung Jae;Soh, Byoung Yul;Park, Jung Hee;Shin, Yong Kyoo;Kim, Han Wool;Yun, Cheol-Heui;Park, Won Sun;Jung, In Duk;Park, Yeong-Min
    • BMB Reports
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    • v.47 no.2
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    • pp.115-120
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    • 2014
  • In this study, we show that Mycobacterium avium subsp. paratuberculosis MAP1305 induces the maturation of bone marrow-derived dendritic cells (BMDCs), a representative antigen presenting cell (APC). MAP1305 protein induces DC maturation and the production of pro-inflammatory cytokines (Interleukin (IL)-6), tumor necrosis factor (TNF)-${\alpha}$, and IL-$1{\beta}$) through Toll like receptor-4 (TLR-4) signaling by directly binding with TLR4. MAP1305 activates the phosphorylation of MAPKs, such as ERK, p38MAPK, and JNK, which is essential for DC maturation. Furthermore, MAP1305-treated DCs transform naive T cells to polarized $CD4^+$ and $CD8^+$ T cells, thus indicating a key role for this protein in the Th1 polarization of the resulting immune response. Taken together, M. avium subsp. paratuberculosis MAP1305 is important for the regulation of innate immune response through DC-mediated proliferation of $CD4^+$ and $CD8^+$ T cells.

Self-Assembled Nanoparticles of Bile Acid-Modified Glycol Chitosans and Their Applications for Cancer Therapy

  • Kim Kwangmeyung;Kim Jong-Ho;Kim Sungwon;Chung Hesson;Choi Kuiwon;Kwon Ick Chan;Park Jae Hyung;Kim Yoo-Shin;Park Rang-Won;Kim In-San;Jeong Seo Young
    • Macromolecular Research
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    • v.13 no.3
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    • pp.167-175
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    • 2005
  • This review explores recent works involving the use of the self-assembled nanoparticles of bile acid-modified glycol chitosans (BGCs) as a new drug carrier for cancer therapy. BGC nanoparticles were produced by chemically grafting different bile acids through the use of l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The precise control of the size, structure, and hydrophobicity of the various BGC nanoparticles could be achieved by grafting different amounts of bile acids. The BGC nanoparticles so produced formed nanoparticles ranging in size from 210 to 850 nm in phosphate-buffered saline (PBS, pH=7.4), which exhibited substantially lower critical aggregation concentrations (0.038-0.260 mg/mL) than those of other low-molecular-weight surfactants, indicating that they possess high thermodynamic stability. The SOC nanoparticles could encapsulate small molecular peptides and hydrophobic anticancer drugs with a high loading efficiency and release them in a sustained manner. This review also highlights the biodistribution of the BGC nanoparticles, in order to demonstrate their accumulation in the tumor tissue, by utilizing the enhanced permeability and retention (EPR) effect. The different approaches used to optimize the delivery of drugs to treat cancer are also described in the last section.

Antitumor Effect and Immunology Activity of Seaweeds toward Sarcoma-180 (청각과 김에서 추출한 당단백질의 Sarcoma-180에 대한 항암효과 및 면역활성)

  • CHO Kyung-Ja;LEE Young-Suk;RYU Beung-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.23 no.5
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    • pp.345-352
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    • 1990
  • This study was investigated on the antitumor of protein-polysaccharide fraction(PPF) extracted from seaweeds such as sea-staghorn and laver toward sarcoma-180 cells. In the PPF extracted from these sewaweeds, the polysaccharide contents of sea-staghorn and laver were $62.26\%$ and $65.78\%$, respectively. The highest levels of polysaccharides found in seaweeds was fructose. The major amino acids were aspartic acid, glutamic acid, glycine and cystein. The solid tumor growth inhibition showed the highest level of $53.30\%$ when 50mg/kg sea-staghorn was administrated. The life prolongation effect was $17.35\%$ at 50 mg/kg of laver. In the effects of immunologic activity, when 100mg/kg sea-staghorn was administrated, the number of circulating leucocyte showed the highest level of $82.23\%$ but decreased leucocyte for prolonged times. The number of total peritoneal exudate cells of the sea-staghorn administerated group was increased significantly in comparison with the control group. The hematobiolgoical analysis of the experimental group was similar with that of the control group. This experiments indicated that hemeastasis still maintained nor-mal state and not showed any harmful effects in normal mice.

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The Mitochondrial Warburg Effect: A Cancer Enigma

  • Kim, Hans H.;Joo, Hyun;Kim, Tae-Ho;Kim, Eui-Yong;Park, Seok-Ju;Park, Ji-Kyoung;Kim, Han-Jip
    • Interdisciplinary Bio Central
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    • v.1 no.2
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    • pp.7.1-7.7
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    • 2009
  • "To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.

Comparison of Antioxidant, Anticancer and Immunomodulating Activities of Extracts from DongChongXiaCao (동충하초의 균사 및 배양액의 항산화, 항암, 면역활성의 비교)

  • Heo, Jin-Chul;Nam, Sung-Hee;Kang, Seok-Woo;Hong, In-Pyo;Lee, Kwang-Kil;Park, Ja-Young;Kim, Kyung-Hae;Han, Song-Yi;Lee, Sang-Han
    • Food Science and Preservation
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    • v.14 no.6
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    • pp.681-687
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    • 2007
  • Biological properties of DongChongXiaCao extracts and culture supernatants were evaluated using DPPH and FRAP (antioxidants), Raw 264.7 (NO production), B16-F1 cells (cell migration activity) and HUVECs (angiogenesis activity). We found that antioxidant activity was higher in mycelium culture supernatants than in mycelial extracts. Mycelial extracts and culture supernatants inhibited or increased cyclooxygenase-2 transcription activity and NO production. Various extracts and culture supernatants inhibited B16 cell migration and motility, and inhibited HUVEC tube formation. These findings indicate that DongChongXiaCao extracts and products of mycelium could be a useful biological resource for anti-oxidant and anti-cancer purposes.

Role of FAK Phosphorylation in Cobalt Chloride-Induced Epithelial-to-Mesenchymal-Like Transition (Cobalt chloride에 의해 유도되는 상피-중간엽 이행에서의 국소부착 단백질의 인산화의 역할 규명)

  • Nam, Ju-Ock
    • Journal of Life Science
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    • v.21 no.2
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    • pp.286-291
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    • 2011
  • Hypoxia is a common condition found in a wide range of solid tumors and is often associated with metastasis and poor clinical outcomes. In the present study, we found that HIF-$1{\alpha}$ was induced by cobalt chloride (500 ${\mu}M$) treatment on human lung cancer cells, A549 and H460, for 24 hr. However, cobalt chloride (500 ${\mu}M$) did not affect cell proliferation of A549 and H460 in 48 hr. Cobalt chloride (500 ${\mu}M$) additionally induced epithelial-to-mesenchymal-like transition (EMT) such as reduced E-cadherin expression and increased ${\alpha}$-SMA expression. These results were confirmed by immunofluorecence experiment in H460 cells. E-cadherin was localized on the outer cell membrane. However, when the cells were treated with 500 ${\mu}M$ cobalt chloride for 24 hr, diffuse E-cadherin staining was observed, characteristic of a migratory mesenchymal phenotype. We also found that cobalt chloride induced integrin ${\beta}3$ expression and FAK phosphorylation in human lung cancer cells using western blotting and FACS anlaysis. Our data suggest that integrin ${\beta}3$-induced FAK phosphorylation may be developed into target molecules for blocking tumor metastasis.

Sustained release of alginate hydrogel containing antimicrobial peptide Chol-37(F34-R) in vitro and its effect on wound healing in murine model of Pseudomonas aeruginosa infection

  • Shuaibing Shi;Hefan Dong;Xiaoyou Chen;Siqi Xu;Yue Song;Meiting Li;Zhiling Yan ;Xiaoli Wang ;Mingfu Niu ;Min Zhang;Chengshui Liao
    • Journal of Veterinary Science
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    • v.24 no.3
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    • pp.44.1-44.17
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    • 2023
  • Background: Antibiotic resistance is a significant public health concern around the globe. Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. Objective: This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. Methods: Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. Results: The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Conclusions: Our results suggest that sodium alginate -based hydrogels loaded with Chol-37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds.

Examining the Role of ZO Protein in the Cancer Microenvironment (암 미세환경에서 ZO 단백질의 역할 고찰)

  • Min-Hye Kim;Hee-Jae Cha
    • Journal of Life Science
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    • v.34 no.4
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    • pp.279-285
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    • 2024
  • The zonula occludens (ZO) protein serves as a scaffolding protein, providing structural support at the junctions between cells and the cytoplasmic surface. It acts as a bridge between integral membrane proteins and the cytoskeleton. Besides its structural role, it also participates in regulating cell growth and proliferation. Recent studies have highlighted the involvement of ZO protein in various diseases, including cancer. Specifically, research has indicated that ZO protein influences the cancer microenvironment surrounding cancer cells, thereby facilitating their growth and development. ZO proteins exert diverse functions in the cancer microenvironment, impacting processes such as angiogenesis, inflammatory responses, the epithelial-mesenchymal transition, and interactions with mesenchymal stem cells. The specific mechanisms vary depending on the type of cancer and environmental conditions. Recent research unveiled several signaling pathways involving ZO protein, which could potentially impede cancer progression in the tumor microenvironment. Consequently, these insights open avenues for novel treatment strategies. While the numerous physiological, structural, and morphological roles of ZO protein have been observed at the cellular and in vivo levels, understanding the signaling mechanisms it operates in vivo and how these mechanisms influence the cancer microenvironment remains a challenge. In this review, we delineate the characteristics and regulatory mechanisms of ZO protein in the context of the cancer microenvironment. Additionally, we propose leveraging the properties of ZO protein to devise defense mechanisms within the cancer cell environment and provide an overview of its in vivo role.

Effect of Solvent Fractions from Doenjang on Antimutagenicity, Growth of Tumor Cells and Production of Interleukin-2 (된장 분획물의 항돌연변이 및 암세포 증식 억제효과와 interleukin-2 생성에 미치는 영향)

  • Kim, Kwang-Hyuk;Park, Kun-Young;Lee, Sook-Hee;Lim, Sun-Young
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.791-797
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    • 2007
  • We studied the inhibitory effect of solvent fractions from doenjang on mutagenicity using Salmonella typhimurium TA100 in Ames test. We also investigated the effect of solvent fractions from doenjang on the growth of tumor cells and the production of interleukin-2 (IL-2). The treatment of dichlorormethane and ethylacetate fractions (2.5 mg/assay) from doenjang to Ames test system inhibited aflatoxin B$_1$ (AFB$_1$) induced mutagenicity by 96% and 97%, respectively, and showed a higher antimutagenic effect than other solvent fractions. In case of N-methyl-N'-nitro-N-nitrosoguamidine (MNNG) induced mutagenicity, the ethylacetate fraction showed the highest inhibitory effect (by 75%) among the other sol-vent fractions, although the inhibitory effect was not stronger compared to AFB$_1$ induced mutagenicity. The treatment of dichloromethane and ethylacetate fractions markedly inhibited the growth of Yac-1 (by 80% and 94%, respectively) and sacroma-180 cancer cells (by 60% and 96%, respectively) after 4 days of incubation at 37${\circ}$C. To elucidate the immunological mechanism of antitumor activity of doenjang, spleen cells of Balb/c mouse were exposed to the dichloromethane and ethyl-acetate fractions for 24 hours at 37${\circ}$C . The culture supernatants following the treatment of djchloromethane and ethylacetate factions to spleen cells increased the production of IL-2. These results indicated that the anticarcinogenic effect of doenjang was mediated by the production of IL-2.

Health Assessment for Glass Fibre Landfill at Gozan-dong, Inchon (인천시 고잔동에서 제기된 유리섬유에 의한 건강피해 역학 조사)

  • Cho, Soo-Hun;Ju, Yeong-Su;Kim, Kyung-Ryul;Lee, Kang-Kun;Hong, Kug-Sun;Eun, Hee-Chul;Song, Dong-Bin;Hong, Jae-Woong;Kwon, Ho-Jang;Ha, Mi-Na;Han, Sang-Hwan;Seong, Joo-Heon;Kang, Jong-Won
    • Journal of Preventive Medicine and Public Health
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    • v.30 no.1 s.56
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    • pp.77-101
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    • 1997
  • In September 1994, residents of Gozan-dong, Incheon City, made a petition to the government about their health problems which might be caused by previous glass fibre landfill nearby 'H' company. In february 1995, at regular academic meeting of occupational and environmental medicine, a research team of 'D' University presented that they had found glass fibres in groundwater of the area through their survey. They were suspicious of probable association between ingestion of groundwater contaminated with glass fibres and skin tumors among residents. A joint research team was formed and carried out the survey of environment concerning groundwater and its glass fibre existence, and health assessment of residents in the area and industrial workers of 'H' company during May to November, 1995. Analysis of groundwater flow system indicates that the flow lines from the glass fibre landfill pass through or terminate at the 6 houses around the landfill. This means that the groundwater of the 6 houses around the glass fibre landfill could be affected by some possible contaminants from the landfill, but the groundwater quality of the other houses was irrelevant to the landfill. The qualitative and qualitative analyses for glass fibres in 54 groundwater samples including those from the nearby 6 houses, were carried out using SEM equipped with EDS, resulting in no evidence for the presence of glass fibres in the waters. Major precipitates, formed in waters while boiling, were identified as calcium carbonates, in particulary, aragonites in needle form. The results of health assessments of 889 residents in Gozan-dong, participated in this study, showed statistically significant differences in past medical histories of skin tumor and respiratory disease between the exposed group (31 persons who inhabited in 6 houses around the landfill) and the control group, but no significant differences in past medical histories of other diseases, such as cancer mortality, current gastroscopic findings, current skin diseases and respiratory diseases, etc. Also, we could not prove any glass fibres in excised specimens of 9 skin tumors in both groups and there were no health problems possibly associated with glass fibres in employees of the 'H' company. After all, we could not authenticate the association, raised by prior investigators, between groundwater streams, assumedly contaminated with glass fibres or not, and specific disease morbidities or common disease/symptom prevalences. That is, we could not find any glass fibres in groundwater as the only exposure factor of this study hypothesis, and there were not enough certain evidences such as increasing disease prevalences, for examples, skin, respiratory and gastrointestinal diseases etc, possibly related to glass fibre exposure, in exposed group. As a matter of course, the conditions for confirming causal association, for example, strength of the association, consistency of the association, specificity of the association, temporality of the association and dose-response relationship etc, have not been satisfied. In conclusion, we were not able to certify the hypothesis that contamination of groundwater with glass fibres might cause any hazardous health effects in residents who used it for drinking.

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