• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7363-7369
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• 2014

The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups for antitumor efficacy. The isomeric block copolymers, ${\alpha}$- and ${\gamma}$-folate-polyethyleneglycol-distearoyl phosphatidylethanolamine (${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPEDOX micelles) were prepared via the film formation method. Compared with MPEG-DSPE-DOX micelles, the ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPE-DOX micelles presented a higher cellular uptake behavior in the live cell study. Cell viability percentages were 81.8%, 57.3%, 56.6% at 2 hours for MPEG-DSPE-DOX, ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles, respectively (p<0.05). Using the KB xenograft tumor model, both ${\alpha}$- and ${\gamma}$-folate-conjugated micelles were found to have better antitumor effects with lower toxicity in comparison with MPEG-DSPE-DOX micelles. No difference in in vivo antitumor efficacy was found between ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles. The folate-conjugated micelles might be a potentially useful strategy for tumor targeting of therapeutic agents, whether grafting with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups.

• IMMUNE NETWORK
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• 제11권1호
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• pp.79-94
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• 2011

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

• 동의생리병리학회지
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• 제20권6호
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• pp.1678-1727
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• 2006

This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.98-98
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• 2003

${\beta}$-(1,3)-D-Glucans have been known to exhibit antitumor and antimicrobial activities. The presence of dectin-1,${\alpha}$, ${\beta}$-glucan receptor of dendritic cell, on macrophage has been controvertial. RT-PCR analysis led to the detection of dectin-1${\alpha}$ and ${\beta}$ in murine macrophage Raw264.7 cell line. Among the various organs of mouse, dectin-1${\alpha}$ and ${\beta}$ were detected in the thymus, lung, spleen, stomach and intestine. To analyze gene expression modulated by ${\beta}$-glucan treated murine Raw264.7 macrophage, total mRNA was applied to cDNA microarray to interrogate the expression of 7,000 known genes. cDNA chip analysis showed that ${\beta}$-glucan of P. osteatus increased gene expressions of immunomodulating genes, membrane antigenic proteins, chemokine ligands, complements, cytokines, various kinases, lectin associated genes and oncogenes in Raw 264.7 cell line. When treated with ${\beta}$-glucan of P. osteatus and LPS, induction of gene expression of TNF-${\alpha}$ and IFN-R1 was confirmed by RT-PCR analysis. Induction of TNF-R type II expression was confirmed by FACS analysis. IL-6 expression was abolished by EDTA in ${\beta}$-glucan and LPS treated Raw264.7 cell line, indicating that ${\beta}$-glucan binds to dectin-l in a Ca$\^$＋＋/ -dependent manner. To increase antitumor efficacy of ${\beta}$-glucan, ginsenoside Rh2 (GRh2) was co-treated with ${\beta}$-glucan in vivo and in vitro tests. IC$\sub$50/ values of GRh2 were 20 and 25 $\mu\textrm{g}$/$m\ell$ in SNU-1 and B16 melanoma F10 cell line, respectively. Co-treatment with ${\beta}$-glucan and GRh2 showed synergistic antitumor activity with cisplatin and mitomycin C both in vitro and in vivo. Single or co-treatment with ${\beta}$-glucan and GRh2 increased tumor bearing mouse life span. Co-treatment with ${\beta}$-glucan and GRh2 showed more increased life span with mitomycin C than that with cisplatin. Antitumor activities were 67% and 72 % by co-injection with ${\beta}$-glucan and GRh2 in the absence or presence of mitomycin C, respectively.

• 대한한의학회지
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• 제23권2호
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• pp.211-224
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• 2002

Background and Objective : In order to investigate the effects of Gilgyunglwedok-tang (GRT) on antitumor activity and antimetastatic activity, studies were done experimentally. Materials and Methods : Experimental studies were perfonned for the cytotoxic effect on BALB/c mouse lung fibroblast cells, the proliferating effect of splenic lymphocyte, the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclear cells (PBMCs), the cytotoxic effect on A549, SK-OV-3, SK-MEL-2, MCF-7 cells, the inhibitory effect on the activity of DNA topoisomerase I, the T/C% in ICR mice bearing S-180, the inhibitory effect of Cell adhesive of A549 Cells and SK-OY-3 Cells to complex extracellular matrix, the inhibitory effect on lung colonies, the change of lung tissue, the antiangiogenic activity, and the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line. Results and Conclusion : The results were obtained as follows : 1. In the cytotoxic effect on BALB/C mouse lung fibroblast Cell, GHT didn't show the significant cytotoxic effect on BALB/C mouse lung fibroblast cell compared to the control group. 2. In thymidine uptake assay, GHT showed the significant proliferating effect of splenic lymphocyte in proportion to the concentration. 3. In the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclea cells (PBMCs) of mice, GRT had no significant change to the normal group in CD4. However, GRT showed an increase to the normal group in CD8 and GHT in the only $1\mu\textrm{g}/ml$ category showed an increase to the normal group in B220. 4. In the cytotoxic effect of GRT on A549, SK-OY-3, SK-MEL-2 and MCF-7 cells, there was no significant cytotoxic effect compared to the control group. 5. In the inhibitory effect on the activity of DNA topoisomerase I, GHT in the $10\mu\textrm{g}/ml$ category showed the inhibitory effect on the activity of DNA topoisomerase I in proportion to the concentration. 6. In the T/C% in ICRmice bearing S-180, GHTtreated group showed 123.7% of T/C% compared to the control group. 7. In the inhibitory effect of cell adhesive of A549 Cells and SK-OV-3 Cells to complex extracellular matrix, GRT in the only $100\mu\textrm{g}/ml$ category showed the significant inhibitory effect compared to the control group. 8. In the inhibitory effect on lung colonies, GHT showed the significant inhibitory effect on lung colonies compared to the control group. 9. In the change of lung tissue, GHT showed a significant decrease of lung cancer growth, interalveolar fibrosis and hyaline material compared to the control group. In the development of lymphocyte around lung cancer cells and lung parenchymal, GHT showed the significant inducement efficacy compared to the control group. 10. In CAM assay, the antiangiogenic activity of GHT showed 30%. 11. In the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line, GHT had no significant inhibitory effect on MMP-2 and MMP-9 gene expression compared to the control group. According to the above results, it could be suggested that GHT has an antitumor activity and antimetastatic activity.

• Journal of Pharmaceutical Investigation
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• 제30권1호
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• pp.39-45
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• 2000

We have investigated the efficacy of liposome encapsulated N-(phosphonacetyl)-L-aspartic acid (PALA) for the treatment of the C-26 murine colon tumor in Balb/c mice, and have compared it in this regard to free PALA. Healthy female Balb/c mice and C-26 tumor inoculated mice were randomized for the maximum tolerated dose (MTD) study and the in vivo therapy study, and the survival was measured after a single intraperitoneal injection of the drug. The maximum tolerated dose for intraperitoneally administered drug was found to be 750 mg/Kg for free PALA, and was greater than the maximum dose possible (150 mg/Kg) for PALA encapsulated in both DSPC and DSPG liposomes. When drug was administered one day after tumor implantation, 150 mg/Kg of PALA in DSPG liposomes increased the percentage of tumor bearing mice surviving at day 36 from 8% (buffer control) to 88%. In contrast, 150 mg/Kg free PALA increased the day 36 surviving percentage to only 25%. A 150 mg/Kg dose of PALA in DSPC liposomes increased the surviving percentage to 50%, while a 75 mg/Kg dose of PALA in sterically stabilized liposomes increased the surviving percentage to 78%. These results show that PALA in negatively charged or sterically stabilized liposomes can exhibit considerably greater potency than free PALA in C-26 tumor bearing mice.

• IMMUNE NETWORK
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• 제20권4호
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• pp.29.1-29.20
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• 2020

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

• 대한화학회지
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• 제56권2호
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• pp.251-256
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• 2012

A novel series of benzothiazole derivatives were synthesized and assayed in vivo to investigate their hypoglycemic activity by streptozotocin-induced diebetic model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well known antidiabetic agent as a reference drug. All the compounds were effective, amongst them 3d showed more prominent activity at 100 mg/kg p.o. The experimental results are statistically significant at p<0.01 and p<0.05 level.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8007-8018
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• 2014

Cervical cancer is the most common gynecologic malignancy worldwide and development of new therapeutic strategies and anticancer agents is an urgent priority. Plants have remained an important source in the search for novel cytotoxic compounds and several polyphenolic flavonoids possess antitumor properties. In this review article, data about potential anticarcinogenic activity of common natural flavonoids on various human cervical cancer cell lines are compiled and analyzed showing perspectives for the use of these secondary metabolites in the treatment of cervical carcinoma as well as in the development of novel chemotherapeutic drugs. Such anticancer effects of flavonoids seem to differentially depend on the cellular type and origin of cervical carcinoma creating possibilities for specific targeting in the future. Besides the cytotoxic activity per se, several flavonoids can also contribute to the increase in efficacy of conventional therapies rendering tumor cells more sensitive to standard chemotherapeutics and irradiation. Although the current knowledge is still rather scarce and further studies are certainly needed, it is clear that natural flavonoids may have a great potential to benefit cervical cancer patients.

• 대한암한의학회지
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• 제18권1호
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• pp.17-22
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• 2013

Objectives : The aim of this report is to evaluate antitumor efficacy of Rhus vernifciflua STOKES decoction (Chijong-tang). Methods : One advanced gastric cancer patient with peritoneal seeding and mesenteric metastasis visited Hana integrative Clinic of Korean medicine in Aug 2012 and was treated with Chijong-tang for 14 months. Results : Chijong-tang showed no side effect during its treatment (Aug 2012 ~ Oct 2013) and the patient showed no disease progression. Conclusion : This case report suggests that Rhus vernifciflua Stokes decoction (Chijong-tang) can be a potent anticancer agent for gastric cancer, but it still required further scientific and clinical evidence.