• Journal of Microbiology and Biotechnology
• /
• 제28권12호
• /
• pp.2079-2094
• /
• 2018

Sunflower trypsin inhibitor (SFTI) is a 14-amino-acid bicyclic peptide that contains a single internal disulfide bond. We initially constructed chimeras of SFTI with N-terminal secretion signals from the Escherichia coli OmpA and Pseudomonas aeruginosa ToxA, but only detected small amounts of protease inhibition resulting from these constructs. A substantially higher degree of protease inhibition was detected from a C-terminal SFTI fusion with E. coli YebF, which radiated more than a centimeter from an individual colony of E. coli using a culture-based inhibitor assay. Inhibitory activity was further improved in YebF-SFTI fusions by the addition of a trypsin cleavage signal immediately upstream of SFTI, and resulted in production of a 14-amino-acid, disulfide-bonded SFTI free in the culture supernatant. To assess the potential of the secreted SFTI to protect the ability of a cytotoxic protein to kill tumor cells, we utilized a tumor-selective form of the Pseudomonas ToxA (OTG-PE38K) alone and expressed as a polycistronic construct with YebF-SFTI in the tumor-targeted Salmonella VNP20009. When we assessed the ability of toxin-containing culture supernatants to kill MDA-MB-468 breast cancer cells, the untreated OTG-PE38K was able to eliminate all detectable tumor cells, while pretreatment with trypsin resulted in the complete loss of anticancer cytotoxicity. However, when OTG-PE38K was co-expressed with YebF-SFTI, cytotoxicity was completely retained in the presence of trypsin. These data demonstrate SFTI chimeras are secreted in a functional form and that co-expression of protease inhibitors with therapeutic proteins by tumor-targeted bacteria has the potential to enhance the activity of therapeutic proteins by suppressing their degradation within a proteolytic environment.

• 혜화의학회지
• /
• 제3권2호
• /
• pp.315-321
• /
• 1995

An extensive anticancer drug screening from natural resources has been carried out primarily using murine tumor model for past fourty years. Recently a new screening program from NCI, so called disease-oriented screening system. has been estabished to detect anticancer drugs that show selective growth inhibition toward variety of tissue specific human solid tumors originated from leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate amd breast. To develope the anticancer drugs from oriental medicinal herbs, we investigated the cytotoxic effects against human tumor cell panels with 23 kinds of MeOH extract of medicinal herbs. Evodiae Fructus, Meliae Toosendan Fructus, Saussureae Radix and Pharbitidis Semen showed strong activities against several tumor cell lines.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
• /
• pp.139-140
• /
• 2001

Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901, an intestinal bacterial metabolite derived from the protopanaxadiol saponin of Panax ginseng C.A. Meyer, has been reported to have anti-tumor effects including inhibition of angiogenesis, invasion and metastasis, as well as induction of tumor cell apoptosis. (omitted)

• Journal of Ginseng Research
• /
• 제29권4호
• /
• pp.176-181
• /
• 2005

Our previous reports demonstrated that ip. administration of Korean red ginseng acidic polysaccharide (RGAP) exerts antitumor activity In mice. The present study was carried out to compare the effects of ip. and p.o. routes of administration of RGAP on either normal or tumor-bearing BALB/c mice. RGAP was administered either ip. or p.o. at doses of 100, 300, 500, 1000 mg/kg for 1 or 5 weeks. Peritoneal macrophages from mice treated with RGAP p.o. at a dose of 300 mg/kg either for 1 or 5 weeks did not exhibit growth inhibition activity toward WEHI-I64 tumor cells. However, administration of RGAP at a dose of 600 mg/kg for both 1 and 5 weeks increased the antitumor activity of macrophages. Oral administration of RGAP (600 mg/kg) for 5 weeks and ip. administration of RGAP (300 mg/kg) for 1 week resulted in antitumor activities of $40\%$ and $45\%$, respectively, indicating that the effect of i.p. injection is more potent 2 and 5 times than that of p.o. one in terms of dose and duration, respectively. Tumor inhibition rates of RGAP at doses of 300, 500, 1000 mg/kg in mice transplanted with B16-F10 melanoma were 4.4, 12.0, and $45.4\%$, respectively, meaning that p.o. dose higher than 500 mg/kg possess marked antitumor activity. The results above suggests that p.o. administration of RGAP also show antitumor activity in vivo depending on the dose.

• Food Science and Biotechnology
• /
• 제16권1호
• /
• pp.133-137
• /
• 2007

The Strain TFM-7, Which has an antitumor effect, was isolated from Kefir and identified based on analysis using the API 50 CHL kit and 265 rDNA sequencing. Strain TFM-7 was confirmed to belong to the genus Kluyveromyces. Analysis of the 265 rDNA nucleotide sequences found strain TFM-7 to be related to Kluyveromyces marxianus. NRRL Y-828IT. K. marxianus. TFM-7 was cultured with potato dektrose broth medium at $27^{\circ}C$ for 72 hr, and its inhibition effects on the proliferation of seven tumor cell lines and a normal cell line were assessed using the MTT assay. The antitumor effects and growth characteristics of K. marxianus TFM-7 were investigated during a culture period of 7 days. By the $3^{rd}\;day$, K. marxianus TFM-7 showed a dry cell weight 2.39 g/L, a pH of 4.39, an ethanol content of 0.89%, and an inhibition effect on the proliferation of seven tumor cell lines above 50%, except for A-549 tumor cell line. K. marxianus TFM-7 was the most effective at inhibiting the growth of Hep-2 cell line among all tumor cell lines tested. Growth inhibition of a normal cell line, NIH/3T3, was less than 35%, suggesting a decreased level of cytotoxicity toward normal cells. These results indicate that K. marxianus TFM-7 may have used as a yeast strain with antitumor activity.

• Radiation Oncology Journal
• /
• 제30권4호
• /
• pp.226-227
• /
• 2012

• IMMUNE NETWORK
• /
• 제22권5호
• /
• pp.38.1-38.24
• /
• 2022

Exosomes, which are well-known nanoscale extracellular vesicles, are multifunctional biomaterials derived from endosomes and perform various functions. The exosome is a critical material in cell-cell communication. In addition, it regulates the pathophysiological conditions of the tumor microenvironment in particular. In the tumor microenvironment, exosomes play a controversial role in supporting or killing cancer by conveying biomaterials derived from parent cells. Innate immunity is a crucial component of the host defense mechanism, as it prevents foreign substances, such as viruses and other microbes and tumorigenesis from invading the body. Early in the tumorigenesis process, the innate immunity explicitly recognizes the tumor via Ags and educates the adaptive immunity to eliminate it. Recent studies have revealed that exosomes regulate immunity in the tumor microenvironment. Tumor-derived exosomes regulate immunity against tumor progression and metastasis. Furthermore, tumor-derived exosomes regulate polarization, differentiation, proliferation, and activation of innate immune cells. Exosomes produced from innate immune cells can inhibit or support tumor progression and metastasis via immune cell activation and direct cancer inhibition. In this study, we investigated current knowledge regarding the communication between tumor-derived exosomes and innate immune cell-derived exosomes (from macrophages, dendritic cells, NK cells, and neutrophils) in the tumor microenvironment. In addition, we discussed the potential development of exosomal immunotherapy using native or engineered exosomes against cancer.

• Advances in Traditional Medicine
• /
• 제7권5호
• /
• pp.459-465
• /
• 2008

The present study was undertaken to investigate the effect of in vivo administration of neem oil intra-peritoneally (i.p.) to mice bearing a progressively growing transplantable T cell lymphoma of spontaneous origin, designated as Daltons lymphoma (DL), on the tumor growth. Mice were administered various doses of neem oil mixed in groundnut oil, which was used as a diluting vehicle or for administration to control DL-bearing mice. Administration of neem oil resulted in an acceleration of tumor growth along with a reduction in the survival time of the tumor-bearing host. Neem oil administered DL-bearing mice showed an augmented apoptosis in splenocytes, bone marrow cells and thymocytes along with an inhibition in the anti-tumor functions of tumor-associated macrophages. Thus this study gives an altogether a novel information that neem oil instead of the popular belief of being anti-tumor and immunoaugmentary may in some tumor-bearing conditions, behave in an opposite way leading to an accelarated tumor progression along with a collapse of the host's anti-tumor machinery. These observations will thus have long lasting clinical significance, suggesting caution in use of neem oil for treatment of cancer.

• 대한임상검사과학회지
• /
• 제54권1호
• /
• pp.38-48
• /
• 2022

Carcinoembryonic antigen (CEA)는 다양한 종양에서 발현되는 자가 항원으로 면역치료에서 강력한 표지 인자이며 면역치료를 위한 표적 종양항원으로 널리 알려져 있다. 그러나 수지상세포 단독 치료는 동물모델에서 종양의 발생을 억제하는 데 효과가 있지만 이미 확립된 종양을 제거하는 데는 한계가 있다. 본 연구에서는 항종양 면역 효과를 증가시키기 위하여 화학치료제인 cyclophosphamide (CYP)와 종양 특이 면역치료법인 수지상세포 백신의 병합치료 효과를 CEA를 발현하는 마우스 종양 모델에서 검증하였다. 종양세포 주입 후 2일 소종양군과 10일 대종양군에서 CYP의 항종양 효과를 비교한 결과, 소종양군에서는 100 mg/kg에서 뚜렷한 종양 성장의 억제 효과가 관찰되었지만 대종양군에서는 약한 억제 효과가 관찰되어 본 연구에서는 대종양군을 병합치료의 적합한 모델로 설정하였다. CYP 와 수지상세포 백신의 병합치료(화학면역치료) 시 종양항원 특이 면역반응이 증가되었을 뿐만 아니라 상승적인 항종양 효과가 나타났다. 또한 CYP 치료에서 나타나는 체중 감소 및 조절 T세포와 골수유래 억제세포의 증가에 의한 면역억제는 화학면역치료에 의해 개선되었다. 항원 특이 면역치료를 병합한 화학면역치료가 화학치료의 부작용을 감소시키고 항종양 효과를 증가시킬 수 있는 치료 전략이 될 수 있을 것이다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권2호
• /
• pp.535-538
• /
• 2016

Background: Cyclooxygenase 2 (COX-2) is important as an enzyme in the pathway leading to the production of prostaglandin E2 (PGE2) and arachidonic acid. This pathway is known to play a role in inflammation, tumor growth, invasiveness and metastasis, inhibition of apoptosis and angiogenesis. Inhibition of COX-2 has been shown to be a promising antitumor and antiangiogenic strategy in several tumor types, including renal cell carcinoma (RCC). Therefore, we decided to evaluate the immunohistochemical expression of this marker and its association with several clinicopathological characteristics in a series of cases. Materials and Methods: COX-2 expression was examined immunohistochemically in tumor tissues obtained from 96 patients who underwent radical (94 cases) or partial (2 cases) nephrectomy. Correlations between COX-2 expression and clinicopathologic findings including pathologic stage, nuclear grade and other indicator of prognosis were examined. Results: Of 96 tumors, 20.9% were positive for COX-2 expression. A correlation was found between COX-2 expression and tumor histological subtype (P=0.03).The papillary subtype showed maximum expression of this marker (43.8%) and the clear subtype minimum (14.7%). There were also possible links between COX-2 expression and pathologic stage, nuclear grade and nodal involvement but the results were not statistically significant (P=0.8, P= 0.14 and P=0.06, respectively). No correlation was found between COX2 expression and patient age, gender, tumor size, metastasis or survival. Conclusions: In our study, COX-2 expression was correlated with the histological subtype of RCC. Additional research is required to determine the link between COX-2 expression and prognosis and also evaluation of probable effectiveness of COX-2 inhibitor drugs in treatment of RCC patients.