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

• 생명과학회지
• /
• 제15권3호
• /
• pp.406-414
• /
• 2005

암세포의 유전적 불안정성은 부적절하게 활성화된 DNA수복경로와 관련되어 있다. 전이성 암은 높은 유전적 불안정성을 나타내는데, 이와 관련하여 본 연구에서는 전이성 암세포에서의 중요한 DNA수복 단백질의 하나인 DN의존성 단백질 키나아제(DNA-PK)의 발현 변화를 조사하였다. 여러 종류의 전이도가 다른 암세포들을 대상으로 한 실험에서 전이성 암세포들은 각각의 모세포에 비하여 DNA-PK 성분의 조절 소단위인 Ku70/80의 발현 및 Ku의 DNA 결합 활성이 증강되어 있었다. 또한 DNA-PK의 촉매 소단위인 DNA-PKcs의 발현 및 whole DNA-PK복합체의 kinase의 활성도 전이도가 큰 암세포에서 그 모세포보다 증강되어 있음을 알 수 있어, 전이성 암세포의 증강된 DNA수복능은 부적절한 DNA수복을 일으켜 암의 진행 및 전이를 촉진시키는 원인이 될 수 있음을 시사하였다. 한편 암세포의 표피성장인자수용체의 신호전달의 증강은 암의 침윤과 전이에 관련되어 있으며, DNA-PK의 기 기능에도 영향을 줄 수 있는 가능성이 보고 된 바 있는데, 본 연구에서는 표피성장인자수용체의 신호전달과 DNA-PK의 관련성을 명확히 밝히기 위하여 새로 개발된 EGFR tyrosine kinase inhibitor인 PKI166의 DNA-PK의 활성에 미치는 영향을 조사하였다. PKI166는 Ku70/80 및 DNA-PKcs의 발현을 억제하였고 이와 관련하여 전이성 및 항암제 다제내성 암세포에서 PKI166에 의하여 항암제에 대한 감수성을 증가시켜 항암제 내성을 나타내는 전이성 암세포 대한 치료법 연구에 DNA-PK가 분자적 표적이 될 수 있음을 밝혔다.

• Biomolecules & Therapeutics
• /
• 제13권3호
• /
• pp.143-149
• /
• 2005

We have demonstrated previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase (CD) gene is driven by the tumor-specific L-plastin promoter. The object of this study was to evaluate the efficacy of AdLPCD together with 5-fluorocytosine (5-FC) in suppression of the growth of established human tumor cells of ovary, Consistent with the knowledge that infection of OVCAR-3 cells with AdLPCD resulted in expression of a functional intracellular CD enzyme capable of converting 5-FC to 5-fluorouracil (5-FU) (Chung and Deisseroth, 2004), statistically significant differences in cytotoxicity were observed when AdLPCD infected cells were also exposed to 5-FC for 6 days (p=0.05), 9 days (p<0.0005) and 12 days (p<0.005), compared to 5-FC exposure alone, These results indicate that the CD gene delivered by adenoviral vector could efficiently sensitize OVCAR-3, otherwise non-toxic 5-FC. On the other hand, SKOV-3 cells, an ovarian carcinoma cell line, were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The results of present study suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1997년도 추계학술대회
• /
• pp.35-39
• /
• 1997

Recent development of human genetics and techniques of gene transfer and expression have opened the way for investigating novel approaches based on the genetic modification of cells to treat both inherited and acquired diseases. This approach is referred to as gene therapy. Over the past few years, gene therapy has moved from the laboratory to phase I clinical trials. Although the clinical performance of gene transfer experiments is still in an early phase of development, the NIH of Health Recombinant DNA Advisory Comittee (RAC) has approved more than 150 protocols that involve gene transfer or putative gene therapy procedures in clinical settings. Many sectors of society in United States have participated in the design and formulation of these clinical trials through local Institutional Review Boards, the National Institutes of Health (NIH) RAC, the Chemotherapy Evaluation Program of the National Cancer institute, and the FDA. Currently, clinical trials involving gene modification are under way at many medical centers throughout the United Slates. The goals of these trials are as follows. (1) The design should be directed to short-term achievable goals. (2) Each clinical trial is best considered as an intermediate step in a multistep process. (3) The design should identify evaluable proximate endpoints for toxicity and for efficacy, (4) The potential benefits and possible risks for patients participating in these trial should be defined.

• Biomolecules & Therapeutics
• /
• 제17권2호
• /
• pp.138-143
• /
• 2009

We have reported previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase gene (CD) is driven by the tumor-specific L-plastin promoter. AdLPCD vector had been evaluated for its efficacy of chemosensitization of ovarian cancer cells to 5-FC. In spite of the fact that ovarian cancer cells, i.e., OVCAR-3 and SK-OV-3, are capable for adenoviral transduction judged by LacZ reporter gene analysis, two cell lines demonstrated quite different sensitivities toward AdLPCD/5-FC system. In OVCAR-3 cells, infection of AdLPCD followed by exposure to 5-FC resulted in the suppression of cell growth with statistical significance. On the other hand, SK-OV-3 cells were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The object of study was to investigate factors that would determine the sensitivity to AdLPCD/5-FC. We evaluated conversion rate of 5-FC to 5-FU after infection of AdLPCD by HPLC analysis, $IC_{50}$ of 5-FU, the expression level of integrin receptors i.e., ${\alpha}v{\beta}3$ and ${\alpha}v{\beta}5$, and status of p53 in OVCAR-3 and SK-OV-3 cells. The results indicated that OVCAR-3 cells have few favorable features compared with SK-OV-3 cells to be more effective to the AdLPCD/5-FC strategy; higher level of ${\alpha}v{\beta}5$ integrin, higher rate of conversion of 5-FC into 5-FC, and lower $IC_{50}$ of 5-FU. The results suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• Tuberculosis and Respiratory Diseases
• /
• 제51권2호
• /
• pp.122-134
• /
• 2001

연구배경 : 종양 세포들이 항암제에 대하여 저항을 나타내는 기전인 'apoptosis에 대한 저항'에 NF-${\kappa}B$의 활성이 중요한 역할을 하리라 생각되고 있다. 즉, NF-${\kappa}B$가 종양세포의 apoptosis를 억제하는 작용을 일으킴으로써 종양 세포의 생존에 유리하게 작용하고 있음이 제시되 고 있다. 방 법 : 본 연구에서는 비소세포폐암에 대한 항암 치료의 내성에 대하여 외부 자극으로 분해되지 않는 $I{\kappa}B{\alpha}$-SR의 삽입으로 NF-${\kappa}B$의 활성을 억제시키고 이로 인해 항암제에 대한 폐암세포주의 감수성이 증가하는지 여부를 밝혀 보고자 하였다. 결 과 : 비소세포폐암 세포주로 NCI H157, NCI H460 세포주를 이용하였고, Ad-$I{\kappa}B{\alpha}$-SR를 transduction 한 후 cisplatin을 처치한 군에서 NF-${\kappa}B$의 핵 내로의 이동이 억제되었으며 대조군과 비교시 $IC_{50}$이 2-3배 정도 유의하게 낮아짐을 관찰하였다. 또한 paclitaxel의 경우에도 Ad-$I{\kappa}B{\alpha}$-SR로 감염된 폐암세포주는 대조군과 비교시 IC50이 2배 정도 유의하게 낮아짐을 관찰하였다. 이러한 항암제에 대한 감수성의 증가의 기전으로 cisplatin의 경우는 $I{\kappa}B{\alpha}$-SR의 이입이 NF-${\kappa}B$의 활성을 억제 함으로 인한 apoptosis의 증대 때문인 것으로보인다. 결 론 : 폐암세포주에서 Ad-$I{\kappa}B{\alpha}$-SR transduction은 Clsplatin, paclitaxel에 대한 폐암세포주의 감수성을 증가시킴으로 앞으로 폐암을 치료하는데 있어 새로운 치료 방법이 될 수 있을 것으로 보인다.

• 한국균학회소식:학술대회논문집
• /
• 한국균학회 2018년도 춘계학술대회 및 임시총회
• /
• pp.44-44
• /
• 2018

Fusarium head blight (FHB) caused by infection with Fusarium graminearum leads to enormous losses to crop growers, and may contaminate grains with a number of Fusarium mycotoxins that pose serious risks to human and animal health. Antagonistic bacteria that are used to prevent FHB offer attractive alternatives or supplements to synthetic fungicides for controlling FHB without the negative effects of chemical management. Out of 500 bacterial strains isolated from soil, Bacillus amyloliquefaciens JCK-12 showed strong antifungal activity and was considered a potential source for control strategies to reduce FHB. B. amyloliquefaciens JCK-12 produces several cyclic lipopeptides (CLPs) including iturin A, fengycin, and surfactin. Iturin A inhibits spore germination of F. graminearum. Fengycin or surfactin alone did not display any inhibitory activity against spore germination at concentrations less than 30 ug/ml, but a mixture of iturin A, fengycin, and surfactin showed a remarkable synergistic inhibitory effect on F. graminearum spore germination. The fermentation broth and formulation of B. amyloliquefaciens JCK-12 strain reduced the disease incidence of FHB in wheat. Furthermore, co-application of B. amyloliquefaciens JCK-12 and chemical fungicides resulted in synergistic in vitro antifungal effects and significant disease control efficacy against FHB under greenhouse and field conditions, suggesting that B. amyloliquefaciens JCK-12 has a strong chemosensitizing effect. The synergistic antifungal effect of B. amyloliquefaciens JCK-12 and chemical fungicides in combination may result from the cell wall damage and altered cell membrane permeability in the phytopathogenic fungi caused by the CLP mixtures and subsequent increased sensitivity of F. graminearum to fungicides. In addition, B. amyloliquefaciens JCK-12 showed the potential to reduce trichothecenes mycotoxin production. The results of this study indicate that B. amyloliquefaciens JCK-12 could be used as an available biocontrol agent or as a chemosensitizer to chemical fungicides for controlling FHB disease and as a strategy for preventing the contamination of harvested crops with mycotoxins.