• Journal of Pharmaceutical Investigation
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• 제30권2호
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• pp.127-131
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• 2000

Previously, we have reported an antitumor efficacy of liposomal N-(phosphon-acetyl)-L-aspartic acid (or PALA) in C-26 tumor bearing Balb/c mice, where PALA in liposome was administered one day after tumor inoculation. In this report, we have investigated the therapeutic potency of liposomal formulation of PALA, which was administered eight days after tumor inoculation in the same C-26 tumor bearing mice. The C-26 murine colon tumor inoculated mice were randomized for the in vivo therapy and the survival was measured after a single intraperitoneal injection of the drug. When the therapy was initiated eight days after tumor inoculation, DSPC-PALA at 150 mg/kg resulted in a significant increase in median survival time (MST) of 56% over the control group which received MES/HEPES buffer alone. However, none of the free PALA and DSPG-PALA liposome doses caused a statistically significant increase in MST over control group at the 95% confidence level. At 750 mg/kg dose, free PALA caused a marginally significant improvement in MST by 34%, but both 375 mg/kg and 150 mg/kg doses of free PALA caused only a 2% and a 4% increase in MST, respectively. These results show that PALA in neutrally charged liposome can exhibit considerably greater potency than free PALA in established C-26 tumor bearing mice.

• Biomolecules & Therapeutics
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• 제8권3호
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• pp.228-234
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• 2000

We have synthesized a novel platinum(II) coordination complex containing trans-ι-1,2-diaminocy-clohexane (DACH) as a carrier ligand and 1,2-dichloroethane (DCE) as a leaving group. A new series of [Pt(trans-ι-DACH)(DCE)](PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocar-cinoma cells and normal primary cultured kidney cells. The new platinum complex has demonstrated high efficacy in the cytotoxicity against MKN-45/P, MKN-45/ADM and MKN-45/CDDP cell-lines. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined by MTT assay, the [$^3H$]-thymidine uptake arid glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new, clinically available anticancer chemotherapeutic agents.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.550-555
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• 2002

The discovery and development of the taxane class of antitumor compounds represent significant advances in the treatment of patients with a variety of malignancies. These drugs are effectively used in the treatment of breast cancer. In this study we evaluated the efficacy of fractionated usage of both paclitaxel and docetaxel as a single agent in the breast cancer cell line MCF-7. It has been shown that the cytotoxic effect of paclitaxel was increased when the divided $IC_{50}$ concentrations were used sequentially and in contrast to paclitaxel, cytotoxic effect of docetaxel was decreased with the same schema and the single dose of $IC_{50}$ concentration was optimal. The cause of the difference between the cytotoxic effects of two agents with this schedule is obscure. Demonstrating mechanisms, which are responsible for these differences, will be important for more rational use of taxoids and to provide basis for the following clinical trials.

• 대한의생명과학회지
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• 제25권2호
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• pp.159-169
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• 2019

Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

• 대한의생명과학회지
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• 제27권1호
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• pp.1-11
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• 2021

Cancer stem cells, which are known to drive tumor formation and maintenance, are a major obstacle in the effective treatment of various types of cancer. Trans-membrane glycoprotein mucin 1 antigen and cell surface glycogen CD44 antigen are well-known surface markers of breast cancer cells and breast cancer stem cells, respectively. To effectively treat cancer cells and cancer stem cells, we developed a new drug-encapsulating liposome conjugated with dual-DNA aptamers specific to the surface markers of breast cancer cells and their cancer stem cells. These two aptamer (Apt)-targeted liposomes, which were prepared to encapsulate doxorubicin (Dox), were named "Dual-Apt-Dox". Dual-Apt-Dox is significantly more cytotoxic to both cancer stem cells and cancer cells compared to liposomes lacking the aptamers. Furthermore, we demonstrated the inhibitory efficacy of Dual-Apt-Dox against the experimental lung metastasis of breast cancer stem cells and cancer cells in athymic nude mice. We also showed the potent antitumor effects of dual-aptamer-conjugated liposome systems by targeting cancer cells as well as cancer stem cells. Thus, our data indicate that dual-aptamer-conjugated liposome systems can prove to be effective drug delivery vehicles for breast cancer therapy.

• Journal of Korean Neurosurgical Society
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• 제66권4호
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• pp.356-381
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• 2023

Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the blood-brain-barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versus-host disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.

• Tuberculosis and Respiratory Diseases
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• 제71권1호
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• pp.15-23
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• 2011

Background: Gefitinib and erlotinib are useful, molecular targeted agents in patients with non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. We compared the efficacy and toxicity of two drugs in patients with squamous cell lung cancer, most of whom are male smokers. Methods: We retrospectively reviewed the clinical information on patients with NSCLC who were treated with gefitinib or erlotinib treatment at Chonnam National University Hwasun Hospital between July 2002 and November 2009. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were compared between the two drugs. Results: A total of 182 (100 gefitinib vs. 82 erlotinib) of 584 patients treated by targeted agents had squamous histology. Of the 182 patients, 167 (91.7%) were male and 159 (87.4%) were smokers. The ORR and disease control rate (DCR) were 4.9% and 40.6%, and there was no significant difference between gefitinib and erlotinib (ORR, 5.0% vs 4.8%; p=0.970; DCR, 40.0% vs 41.4%; p=0.439). The median OS in the gefitinib group was 12.1 months, and that in the erlotinib was 12.7 months (hazard ratio [HR], 1.282; 95% confidence interval [CI], 0.771~2.134; p=0.339). The median PFS for the gefitinib group was 1.40 months, compared with 1.37 months for the erlotinib group (HR, 1.092; 95% CI, 0.809~1.474; p=0.564). Skin rash ${\geq}$grade 3 was more common in erlotinib (12.2%) than gefitinib (1.0%, p=0.003) groups. Conclusion: This retrospective study showed that the two drugs appear to have similar antitumor efficacy and toxicity except for skin rash.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4031-4036
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• 2012

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

• 한국식품영양과학회지
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• 제34권5호
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• pp.599-604
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• 2005

본 연구는 인삼의 가공방법을 개발하고 제품을 다양화하기 위해 우리나라의 전통주인 탁주로 인삼을 증자한 후 홍삼의 항산화성 및 아질산염 소거능, 항암효과를 비교 연구하였다. $A1\~~A9$시료의 $60\%$ 에탄올 추출물에서의 DPPH 라디칼 소거효과는 1,000 ppm에서 인삼의 증자 횟수와 비례하여 증가하였고, 특히 A3에서 $79.5{\pm}3.3\%$로 라디칼 소거율이 뚜렷하게 증가함을 보였다. 아질산염 소거능은 pH 1.2에서 W.G는 $25.9{\pm}4.4\%$, R.G는 $12.9{\pm}1.1\%$, $A1\~A9$는 $26.2{\pm}0.1\~56.1{\pm}0.5\%$로 증자 횟수가 증가할수록 높은 아질산염 소거능을 나타냈다. 인체유래 간암세포(Hep3B)에서의 항암효과로 실험에서 W.G는 에탄올 추출물 5,000 ppm으로 처리했을 때, $19.6{\pm}4.5\%$로 나타나 증식 억제율이 미미하였으나, R.G는 에탄을 추출물 5,000 ppm으로 처리했을 때 $54.5{\pm}6.1\%$를 나타냈으며, A9에서는 $96.3{\pm}2.4\%$로 높은 항암효과 가 관찰되었다. 이상의 결과로 볼 때 탁주를 이용한 증자홍삼이 일반 홍삼 및 백삼보다 본 실험의 항산화 및 항암 system(in vitro)을 이용하여 실험한 결과 더 높은 항암 및 항산화 효과를 나타내었다.

• Journal of Ginseng Research
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• 제44권5호
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• pp.725-737
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• 2020

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.