• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7439-7444
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• 2013

Aim: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. Methods: In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Results: Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Conclusion: Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.137-150
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• 1999

Macrophage play a major role in host defence against infection and tumor development and this activity is regulated through the production of several mediators. In particular, the production of NO by macrophages mediates killing or growth inhibition of tumor cells, bacteria, fungi and parasites. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammator and auto-immune disease. Therefore, it would be valuable to develop potent and selective inhibitors of for potential therapeutic use. Thus the agent that supprees the expression of iNOS mRNA or enzyme protein will be usefull for the prevention of various diseases. We are intersted in identifying selective inhibitiors of iNOS which might be useful intreating inflammatory human diseases. In summary, we have demenstrated that scopoletin, isolated from Seman Armenicae and Radix Trichosanthis the production of NO induced by $IFN-\gammer$ plus LPS in RAW 264.7 macrophages, The mechanism for the inhibition of NO production was due to suppression of the expression of iNOS mRNA or enzyme protein.

• Journal of Life Science
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• v.5 no.2
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• pp.81-89
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• 1995

The antitumor activities of the cell bound polysaccharide(CBP), water soluble polysaccharide(WSP) and sulfated polysaccharide(SP) of Zoogloea sp. were observe. The results obtained were as follows : 1) The CBP, WSP, and SP showed cytotoxic effect on the Meth A cells in vitro, however, the effect of CBP and WSP was more ten-fold greater than that pf SP. 2) When CBP, WSP, and SP was inoculated into the peritoneal cavity of the Meth A cells transplanted mice, the average survival days tended to prolonged slightly as compared with the control. 3) When Meth A cells were transplanted subcutaneously into the back side of mice, and then CBP, WSP, and Sp was inoculated into the peritoneal cavity of mice, the tumor growth inhibition ratio was 46.9% for WSP, 40.4% for CBP, and 16.2% for SP. 4) The phagocytic activity of peritoneal macrophages elicited with CBP, WSP, and SP was significantly increased than that of control. 5) The production of nitric oxide in the peritoneal macrophages stimulated with CBP, WSP, SP, and LPS aloneo was not increased than that of control. The production of nitric oxide in the peritoneal macrophages stimulated with IFN-r and CBP, IFN-r and WSP and IFN-r and SP was significantly increased than that of control, but in the case of stimulated with IFN-r and WSP was increased 50% for CBP and SP. These results suggest that the CBP, WSP and SP of Zoogloea sp. showed direct cytotoxic effect and tumor growth inhibition on Meth A cells in vitro and in vivo, and induced nitric oxide production of activated macrophages.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.39-44
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• 2018

In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.210-216
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• 1995

Partially purified water-soluble extract mixture from Ricini and Coptidis (named as RIC) showed to be a potent inhibitor of human immunodeficiency virus-1 (HIV-1) replication. RIC was evaluated for in vitro anti-HIV activity using SupTl and H9 cells infected by a recombinant virus (pSVCAT) containing chloramphenicol acetyltransferase (CAT) gene substituted for nef gene in the HIV-1 genome. RIC inhibited syncytiaformation of SupTl cells with a half maximal effective concentration, $IC_{50}$/, of 2.5 $\mu\textrm{g}$/mι and showed marked inhibition of CAT activity in the infected H9 cells and also suppressed reverse transcriptase (RT) activity in the supernatant of the infected H9 culture. However, RIC did not inhibit the activity of reverse transcriptase directly when it was mixed with the enzyme or with viral particles. Berberine, one of components of RIC, also showed similar anti-HIV activity as RIC did. The data suggest that there are active ingredients which mediate anti-HIV activity in RIC.

• Korean Journal of Pharmacognosy
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• v.27 no.3
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• pp.224-230
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• 1996

To find pharmacologically active hybrids among the inter-order protoplast fusants of Lentinula edodes and Ginoderma lucidam the antitumor test was performed and the fusant P22 was selected among them. The hot water and alkaline extracts from the cultured mycelia of P22 were purified and separated into four fractions by DEAE-cellulose anion exchange chromatography. When a dose of 20 mg/kg/day of each fractions was injected into ICR mice by i.p., the tumor inhibition ratio of Fr. IV against solid sarcoma 180 was the higher than any other fraction. Fr. IV was a protein-bound polysaccharide which was composed of 69. 12% polysacchafide and 9.76% protein and the molecular weight of Fr. IV was $6.7{\times}10^4$ dalton.

• KSBB Journal
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• v.13 no.4
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• pp.357-363
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• 1998

The antitumor effects of mice fed with cell lysate of Lactobacillus plantarum were studied. The abdominal cancer induced by Sarcoma-180 was markedly inhibited and the expected life span was extended by 60% for the Balb/c mice fed with L. plantarum cell lysate for two weeks. A similar result was obtained for the rat inoculated with Spontaneous Osteosarcoma(SOS). The primary tumor volume of SOS was reduced by 70% for the rats fed with L. plantarum cell lysate (100mg/kg/day) for one week before the inoculation of SOS, while only 42% for the rats fed with the same amount of cell lysate for one week after the inoculation of tumor cell line, SOS. As lung was the metastasis site of SOS, the weight of lung was measured to determine the degree of metastasis inhibition by the L. plantarum cell lysate feeding. The rats fed with cell lysate for one week showed a remarkable inhibition of lung metastasis by 63%(before) and 46%(after), respectively. These results indicate that the feeding of L. plantarum cell lysate to mouse or rat can induce a strong stimulation of mucosal or systemic immune system and these effects results in an efficient antitumor activity.

• Journal of Mushroom
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• v.20 no.3
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• pp.93-101
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• 2022

Cordyceps militaris mycelium extracts containing high amounts of cordycepin were evaluated in vitro for their anti-inflammatory and tumor cell growth-inhibitory activities. All extracts dose dependently inhibited the increased production of inflammatory mediators including reactive oxygen species (ROS), nitric oxide (NO), and 𝛽-hexosaminidase in lipopolysaccharide (LPS)-stimulated inflammatory cells. All extracts were evaluated for anti-proliferative activity against normal RBL-2H3 cells and diverse types of cancer cell lines, including HCT, MC5-7, U-87MG, AGS, and A549 cells. The extract showed the strongest growth inhibition (IC₅₀ = 28.13 ㎍/mL) relative to vehicle-treated control cells against fibrosarcoma (MC5-7). We have demonstrated anti-inflammatory activity of C. militaris via inhibition of NO, ROS production, and 𝛽-hexosaminidase release in activated cells. C. militaris mycelium extract was also evaluated mechanistically and found to exert six types of anti-cancer activity, confirming its pharmacological potential. Our study suggests C. militaris use as a potential source of anti-inflammatory and anti-cancer agents. C. militaris may also be considered a functional food.

• BMB Reports
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• v.53 no.6
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• pp.291-298
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• 2020

Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.6
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• pp.528-534
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• 2005

Angiogenesis is important for the growth and metastasis of solid tumors. Some growth factors, inflammatory cytokines, and angiogenin are known to promote tumor angiogenesis. Among them, Vascular endothelial growth factor (VEGF) is the most intriguing factor in regard to tumor angiogenesis. Inhibition of VEGF activity by neutralizing antibodies or by the introduction of dominant negative VEGF receptors into endothelial cells of tumor-associated blood vessels resulted in the inhibition of tumor growth and in tumor regression, indicating that VEGF is a major initiator of tumor angiogenesis. VEGF promotes angiogenesis through their receptors, Flt-1 and Flk-1/KDR. on vascular endothelial cells. These two receptors were usually believed to be expressed specifically on vascular endothelial cell. Several reports have now shown that VEGF is not only significantly associated with microvessel density but also has prognostic value in both node-negative and node-positive oral squamous cell carcinoma. For many years several histologic features of the neoplasms are being considered when assessing the influence of malignancy grading on recurrence and prognosis. Among the characteristics investigated, degree of keratinization, nuclear pleomorphism, mode of invasion, microscopic depth of invasion, intravascular invasion, lymphocyte infiltration, and number of mitoses have been considered as important prognostic factors. So, this study was conducted to evaluate the correlation of vascular endothelial growth factor expression with malignancy in paraffin-embedded biopsy specimens from 11 patients with tongue cancers. Our results showed that high immunoreactivity specimens of VEGF expression were significantly lower keratinization degree and more pronounced nuclear pleomorphism than in low immunoreactivity specimens. Thus, VEGF expression could be used as a prognostic marker in tongue cancer.