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Induction of Enhancement of Anti-Tumor Immunity by Polysaccharides Fractionated from Acanthopanx Senticosus (가시오가피 다당체에 의한 항종양면역의 유도)

  • Yoon, Taek-Joon;Sung, Ji-Yeon;Yu, Kwang-Won;Lee, Ho;Lee, Kwang-Ho
    • Korean Journal of Pharmacognosy
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    • v.38 no.2 s.149
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    • pp.117-122
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    • 2007
  • The specific activation of the immune system to control cancer growth in vivo has been a long-standing goal in cancer immunology. Whole tumor Iysates have been used either alone or combined with adjuvants to induce specific immune response in vivo. Here, we examined whether freezing/thawing (F/T) colon26-M3.1 tumor cell admixed with EN-3, glycoprotein purified from Acanthopanx Senticosus, could stimulate in vivo immunity by using a murine experimental tumor metastasis model produced by colon26-M3.1 carcinoma cells. Vaccination of mice with F/T treated colon26-M3.1 carcinoma cells in combination with EN-3 as an adjuvant resulted in a significant inhibition in tumor metastasis of mice against live colon26-M3.1 carcinoma challenge. In addition, the splenocytes from vaccinated mice exhibited a higher proliferating activity and secreted interferon-${\gamma}$. These results suggest that EN-3 can be applied to immunoadjuvant to enhance the antitumor immunity in vivo.

Enhanced Antitumor Efficacy with Combined Administration of Astragalus and Pterostilbene for Melanoma

  • Huang, Xin-Yan;Zhang, Song-Zhao;Wang, Wen-Xi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1163-1169
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    • 2014
  • Astragalus, a commonly used traditional Chinese medicine, has exhibited antitumor actions in patients. In this study, in vitro and in vivo antitumor effects of astragalus and synergistic antitumor efficacy in combination with pterostilbene were investigated. Melanoma cells were treated with pterostilbene (Pt), graduated doses of astragalus injection (AI), or these in combination. Cell viability was measured using a MTT assay. Released nucleosomes and caspase activity were measured using enzyme-linked immunosorbent assay. Growth inhibition in vitro and in vivo was also assessed. Analysis of variance and t tests were used for statistical analysis. Significant reduction (p<0.05) in cellular proliferation were observed with AI and AI-Pt in a time- and concentration-dependent manner. Apoptosis and caspase-3/7 activity were significantly increased by AI and AI-Pt treatment (p<0.05). In vivo, AI inhibited melanoma tumor growth, with inhibition rates ranging from 36.5 to 62.3%, by inducing apoptosis via up-regulation Bax expression and the Bax/Bcl-2 ratio and down-regulating Bcl-2 expression. AI significantly inhibits the growth of melanoma in vitro and in vivo by inducing apoptosis. These data suggest that combined treatment of astragalus with pterostilbene enhances antitumor efficacy.

Anti-inflammatory Activity of Ketoprofen Soft Hydrogel (케토푸로펜 소프트 히드로겔의 항염증효과)

  • Lee, Eun-Kyung;Shin, Young-Hee;Lee, Chi-Ho
    • Journal of Pharmaceutical Investigation
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    • v.29 no.2
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    • pp.137-143
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    • 1999
  • Ketoprofen together with various permeation enhancers was incorporated into a novel soft hydrogel which is semi-solid in a container and to form a thin film within a few minutes after applying on the skin. The effect of various enhancers on the skin permeation of ketoprofen from a soft hydrogel was investigated using in vitro and in vivo method. In vitro rat skin permeation of ketoprofen from soft hydrogel was conducted using modified Keshary-Chien diffusion cells. In vivo ketoprofen absorption was also investigated in rats, and the results were compared with that of commercial products. Anti-inflammatory activities were determined using carrageenan-induced paw edema method and adjuvant-induced arthritis method in rats. The anti-inflammatory activity of ketoprofen soft hydrogel formulation with that of commercial products were compared. In vitro as well as in vivo studies showed that $HPE-101^{\circledR}$ was the most effective skin permeation enhancer among those used in this study. Addition of an adhesive (polyisobutylene) in the soft hydrogel decreased skin permeation of ketoprofen. Paw edema and anti-arthritis tests showed that soft hydrogel containing $HPE-101^{\circledR}$ was more effective than the commercial products, which was consistent with the in vivo absorption experiment results.

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In vitro cytotoxicity and in vivo acute toxicity of selected polysaccharide hydrogels as pharmaceutical excipients

  • Kulkarni GT;Gowthanarajan K;Raghu C;Ashok G;Vijayan P
    • Advances in Traditional Medicine
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    • v.5 no.1
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    • pp.29-36
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    • 2005
  • Polysaccharide hydrogels constitute a structurally diverse class of biological macromolecules with a wide range of physicochemical properties. They also constitute important members of the family of industrial water-soluble polymers. They find application in Pharmacy as binders, disintegrants, suspending, emulsifying and sustaining agents. According to the International Pharmaceutical Excipients Council (IPEC), an excipient must have an established safety profile. Hence, in the present study, in vitro cytotoxicity on Vero and HEp-2 cell lines, and in vivo acute toxicity in rats were carried out to establish the safety of polysaccharide hydrogels from the seeds of Plantago ovata and Ocimum basilicum. The in vitro cytotoxicity was determined by MTT and SRB assays. In the in vivo acute toxicity, the effects of three different doses of hydrogels (100, 200 and 400 mg/kg body weight) on food and water intake, body weight, biochemical and hematological parameters were studied. The results of in vitro did not show any cytotoxicity on both the cell lines used. In the in vivo acute toxicity, the hydrogels did not show any toxic symptoms in all three dose levels. This establishes the safety of the selected hydrogels. Hence, they can be used as excipients in pharmaceutical dosage forms.

Viable Alternatives to in vivo Tests for Evaluating the Toxicity of Engineered Carbon Nanotubes

  • Kwon, Soon-Jo;Eo, Soo-Mi
    • Journal of Environmental Health Sciences
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    • v.38 no.1
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    • pp.1-7
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    • 2012
  • Carbon nanotubes (CNTs) stand at the frontier of nanotechnology and are destined to stimulate the next industrial revolution. Rapid increase in their production and use in the technology industry have led to concerns over the effects of CNT on human health and the environment. The prominent use of CNTs in biomedical applications also increases the possibility of human exposure, while properties such as their high aspect ratio (fiber-like shape) and large surface area raise safety concerns for human health if exposure does occur. It is crucial to develop viable alternatives to in vivo tests in order to evaluate the toxicity of engineered CNTs and develop validated experimental models capable of identifying CNTs' toxic effects and predicting their level of toxicity in the human respiratory system. Human lung epithelial cells serve as a barrier at the interface between the surrounding air and lung tissues in response to exogenous particles such as air-pollutants, including CNTs. Monolayer culture of the key individual cell types has provided abundant fundamental information on the response of these cells to external perturbations. However, such systems are limited by the absence of cell-cell interactions and their dynamic nature, which are both present in vivo. In this review, we suggested two viable alternatives to in vivo tests to evaluate the health risk of human exposure to CNTs.

siRNA-mediated Inhibition of hTERC Enhances Radiosensitivity of Cervical Cancer

  • Chen, Min;Xing, Li-Na
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.5975-5979
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    • 2012
  • Background: To investigate the influence of telomerase activity, apoptosis, radiosensitivity of cervical cancer after siRNA-mediated knockdown of telomerase RNA and evaluate in vivo growth with gene interference. Methods: We studied siRNA-targeting-telomerase RNA transfection into the Hela cell line. Expression of hTERC mRNA was detected by RT-PCR and telomerase activity was measured by the TRAP assay. Growth inhibition was determined by MTT assay and radiosensitivity of the cervical cancer cells was examined by colony formation assay. In addtion, effects of hTERC inhibition in vivo were studied by injection of siRNA-transfected Hela cells into nude mice. Results: The hTERC siRNA effectively downregulated the expression of hTERC mRNA and also reduced the telomerase activity to 30% of the untreated control vlaue. The viability of hTERC siRNA transfected Hela cells was reduced by 44.7% after transfection. After radiation treatment, the radiosensitivity of Hela cells with hTERC knockdown was increased. In vivo, the tumors developing from the hTERC siRNA-transfected cells were of reduced size, indicating that the hTERT siRNA also depressed the tumorigenic potential of the Hela cells. Conclusions: Our results supported the concept of siRNA-mediated inhibition of telomerase mRNA which could inhibit the expression of hTERC and telomerase activity. Furthermore, radiosensitivity was upregulated after knockdown the hTERC in vivo and in vitro.

Immunomodulatory effect of Tinospora cordifolia in tumor-bearing host

  • Singh, Nisha;Singh, Sukh Mahendra;Shrivastava, Pratima
    • Advances in Traditional Medicine
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    • v.3 no.2
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    • pp.72-79
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    • 2003
  • The present investigation was undertaken to study whether tumor-associated macrophages of Daltons lymphoma (DL), a spontaneous transplantable T cell lymphoma can be activated to tumoricidal state by alcoholic extract of Tinospora cordifolia (ALTC). In vivo administration of ALTC (200 mg/kg body weight) in DL-bearing mice resulted in an enhanced RNI production and an augmented cytotoxic response of tumor-associated macrophages. Earlier we had reported that DL-bearing mice show a regression of thymus and an enlargement of spleen. In vivo administration of ALTC to DL-bearing hosts resulted in a decrease in the weight of spleen and counts of splenocytes along with an increase in the weight of thymus as compared to control DL-bearing mice. In vivo administration of ALTC in DL-bearing mice also resulted in an increase in the proliferation of splenocytes/thymocytes and BMC. The results of this study indicate that the ALTC upon in vivo administration in DL-bearing shows immuno-modulatory effects and thus may have clinical significance.

Imaging Cancer Metabolism

  • Momcilovic, Milica;Shackelford, David B.
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.81-92
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    • 2018
  • It is widely accepted that altered metabolism contributes to cancer growth and has been described as a hallmark of cancer. Our view and understanding of cancer metabolism has expanded at a rapid pace, however, there remains a need to study metabolic dependencies of human cancer in vivo. Recent studies have sought to utilize multi-modality imaging (MMI) techniques in order to build a more detailed and comprehensive understanding of cancer metabolism. MMI combines several in vivo techniques that can provide complementary information related to cancer metabolism. We describe several non-invasive imaging techniques that provide both anatomical and functional information related to tumor metabolism. These imaging modalities include: positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) that uses hyperpolarized probes and optical imaging utilizing bioluminescence and quantification of light emitted. We describe how these imaging modalities can be combined with mass spectrometry and quantitative immunochemistry to obtain more complete picture of cancer metabolism. In vivo studies of tumor metabolism are emerging in the field and represent an important component to our understanding of how metabolism shapes and defines cancer initiation, progression and response to treatment. In this review we describe in vivo based studies of cancer metabolism that have taken advantage of MMI in both pre-clinical and clinical studies. MMI promises to advance our understanding of cancer metabolism in both basic research and clinical settings with the ultimate goal of improving detection, diagnosis and treatment of cancer patients.

Cecropin Suppresses Human Hepatocellular Carcinoma BEL-7402 Cell Growth and Survival in vivo without Side-Toxicity

  • Jin, Xiao-Bao;Wang, Ying-Jiao;Liang, Lu-Lu;Pu, Qiao-Hong;Shen, Juan;Lu, Xue-Mei;Chu, Fu-Jiang;Zhu, Jia-Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5433-5436
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    • 2014
  • Conventional chemotherapy against hepatocellular carcinoma typically causes various side effects. Our previous study showed that cecropin of Musca domestica can induce apoptosis in human hepatocellular carcinoma BEL-7402 cells in vitro. However, whether cecropin inhibits BEL-7402 cell in vivo and the question of possible side effects remained undentified. The present study confirmed tumor-inhibitory effects of cecropin in vivo, and furthermore strongly suggested that cecropin cytotoxicity in BEL-7402 cells in vivo may be mainly derived from its pro-apoptotic action. Specifically, we found that cecropin exerted no obvious side effects in tumor-bearing mice as it had no significant hematoxicity as well as visceral toxicity. Therefore, cecropin may be a potential candidate for further investigation as an antitumor agent against hepatocellular carcinoma.

In vivo Dendritic Cell Migration Tracking Using Near-infrared (NIR) Imaging (Near-infrared (NIR) 영상기법을 이용한 생체 내 수지상세포의 이동)

  • Lee, Jun-Ho;Jung, Nam-Chul;Lee, Eun Gae;Lim, Dae-Seog
    • KSBB Journal
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    • v.27 no.5
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    • pp.295-300
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    • 2012
  • Matured dendritic cells (DCs) begin migration with their release from the bone marrow (BM) into the blood and subsequent traffic into peripheral lymphoid and non-lymphoid tissues. Throughout this long movement, migrating DCs must apply specialized skills to reach their target destination. Non-invasive in vivo cell-tracking techniques are necessary to advance immune cell-based therapies. In this study, we used a DiD cell-tracking solution for in vivo dendritic cell tracking in naive mice. We tracked DiD (non-invasive fluorescence dye)-labeled mature dendritic cells using the Near Infrared (NIR) imaging system in normal mice. We examined the immunophenotype of DiD-labeled cells compared with non-labelled mature DCs, and obtained time-serial images of NIR-DC trafficking after mouse footpad injection. In conclusion, we confirmed that DiD-labeled DCs migrated into the popliteal lymph node 24 h after the footpad injection. Here, these data suggested that the cell tracking system with the stable fluorescence dye DiD was useful as a cell tracking tool to advance dendritic cell-based immunotherapy.