• BMB Reports
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• v.48 no.3
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• pp.127-128
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• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.513-521
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• 2000

Background : TNF may play an important role(central mediator) in the development of an acute respiratory distress syndrome. Since TNF induced lung injury in the acute respiratory distress syndrome and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of TNF on the regulation of surfactant protein A, B and C mRNA accumulation. Methods : The effects of TNF on gene expression of surfactant protein A, B, and C were analyzed using filter hybridization, 12 and 24 hours after intravenous injection of TNF in rats. Results : 1. The accumulation of SP-A mRNA in the TNF treated group (12 and 24 hours after TNF injection) was significantly decreased by 22.9% and 27.4%, respectively, compared to the control group (P<.025, P<.025). 2. The accumulation of SP-B mRNA in 24 hours after TNF treated group was significantly decreased by 20.5% compared to that of the control group(P<.01). 3. The accumulation of SP-C mRNA in 12 hours after TNF treated group was significantly decreased by 31% the compared to that of the control group(P<.01). Conclusions : These findings indicate the marked inhibitory effects of tumor necrosis factor on surfactant proteins expression in vivo. This finding. in turn, supports the idea of inhibitory effects of tumor necrosis factor on surfactant proteins expression as it relates to pathogenesis of acute respiratory distress syndrome.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.608-612
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• 2002

The twelve-protostane analogues were synthesized from alisol B 23-acetate and assessed for their in vitro antitumor activity against six different human and murine tumor cell lines. Of the compounds synthesized, 23S-acetoxy-24R(25)-epoxy-11$\beta$,23S-dihydroxyprotost-13(17)-en-3-hy-droxyimine (12) exhibited significant cytotoxic activities against A549, SK-OV3, B16-F10, and HT1080 tumor cells with $ED_{50}/$ values of 10.0, 8.7 ,5.2, and 3.1 ${\mu}g$/ml, respectively. Furthermore, 23S-acetoxy-13(17),24R(25)-diepoxy-11$\beta$-hydroxyprotost-3-one (5), 13(17),24R(25)-diepoxy-11$\beta$, 23S-dihydroxyprotostan-3-one (6), 24R,25-epoxy-11$\beta$,23S-dihydroxyprotost-13(17)-en-3-one (7), and 11$\beta$,23S,24R,25-tetrahydroxyprotost-13(17)-en-3-one (9) showed moderate cytotoxic activities against 816-F10 and HT1080 tumor cells. These results mean that a hydroxyimino group at C-3 position in the protostane-type terpene enhances cytotoxic activity.

• Korean Journal of Plant Tissue Culture
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• v.26 no.1
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• pp.31-35
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• 1999

Morphological characteristic during formation of tobacco crown gall tumor and genetic tumor, and their differential response to growth regulator were investigated in in vitro culture. Crown gall tumor was induced from tumor tissue transformed by infecting Agrobacterium tumefaciens C58. Genetic tumor was induced from tumor tissue which was induced spontaneously from reciprocal interspecific hybrids between Nicotiana glauca (2n=24) and Nicotiana langsdorffii (2n=18). Morphological characteristic of crown gall tumor, genetic tumor, and teratoma shoot was very similar, and they were actively proliferated on hormone-free medium. Typical tumor callus and teratoma shoot formed from crown gall tumor on the hormone-free medium. On the contrary, tumor callus derived from genetic tumor formed as a crown gall tumor callus on the medium supplemented with 0.5 mg/L of 2,4-D, and lots of teratoma shoots without any root formed on the hormone-free medium. Root development from the teratoma shoots was hardly obtained on the medium with IAA, GA and active carbon. However, teratoma shoots with roots, as normal shoots, were initiated occasionally on the hormone-free medium. These shoots also formed new genetic tumor on the stem, which leaves formed lots of teratoma shoot on the hormone-free medium in in vitro culture.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8823-8828
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• 2014

Objective: To explore the most appropriate treatment for patients with hepatocellular cancer (HCC) >10 cm by using the Barcelona Clinic Liver Cancer (BCLC) classification. Materials and Methods: A total of 124 HCC patients undergoing surgery were selected. Disease-free survival (DFS), overall survival (OS) and prognostic factors were respectively assessed. Results: This study showed that the cumulative 1-, 3-, 5-year survival rates were 79.7%, 59.8% and 41.6% in BCLC-A patients, 76.2%, 9.5% and 0% in BCLC-B patients and 44.9%, 0% and 0% in BCLC-C patients, respectively. The 1-, 3-, 5-year DFS rates were 49%, 24.5% and 9.1% in BCLC-A patients, 7.5%, 0% and 0% in BCLC-B patients, respectively. No BCLC-C patients survived 1 year after surgery. Multivariate analysis indicated that hepatitis B surface antigen (HBsAg), vascular invasion, intra-hepatic metastasis, curative resection, tumor rupture and pathologic differentiation were independent prognostic factors. Conclusions: Surgery is effective and safe for patients with HCC >10 cm with sufficient hepatic reserve.

• Archives of Pharmacal Research
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• v.24 no.4
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• pp.323-326
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• 2001

Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

• The Korean Journal of Zoology
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• v.26 no.2
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• pp.69-81
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• 1983

The biological effect of hyperthermia on the SCK tumor cells in vitro were analyzed in several respects. A comparision of the survival curve of SCK tumor cells in vitro and in vivo following hyperthermia demonstrated that the cytocidal effect of heating is far greater on the cells in vivo than on the cells in vitro. The pH change in the SCK tumor upon being heated at $43.5^\\circC$ started out at 7.05 and increased to 7.18 during the first 7 min of heating and then rapidly declined to 6.67 by 30 min. Contrary to the decrease in pH in the heated tumors, the pH in the muscle increased significantly when heated to $43.5-45.0^\\circC$. Following hyperthermia at $43.5^\\circC$ for 30 min, a maximum increase in the lactic acid content in the tumor and liver was observed at 1 hr and 3 hr, respectively. The increase in the tumor was followed by a gradual decrease below the control level, whereas the increase in the liver was maintained at quite a steady level for 24 hr. The hyperthermia at $43.5^\\circC$ for 1 hr exhibited a general tendency that high molecular proteins decrease markedly, whereas most of low molecular proteins increase. The most prominent change was that the heat shock protein 70K increased significantly along with other low molecular proteins in heat shocked cells.

• Journal of Nutrition and Health
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• v.24 no.3
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• pp.149-156
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• 1991

To determine the effect of dietary fat and calorie level on protein kinase C(PKC) activity in mouse epidermal cells, female BALB/C mice (4weeks of age) were placed on high (24.6% ), moderate(5%) fat or calorie-restricted diets for at least 4 weeks. Diets were formulated on a nutrient/kcal basis such that the mice consumed the same amounts of protein. vitamins, minerals and fiber per kcal. PKC was assayed by the procedure of Wise et at. An apparent increase of PKC activity was observed from the aminal fed high fat diet when compared with the aminal fed moderate fat diet. PKC activity was decreased 40% by calorie restriction. In summary levels of dietary fat may contribute to mechanism of tumor promotion by increasing PKC activity in the mouse skin model.

• Natural Product Sciences
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• v.23 no.1
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• pp.35-39
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• 2017

D-chiro-inositol (DCI) is a secondary messenger in insulin signal transduction. It is produced in vivo from myo-inositol via action of epimerase. In this study, we evaluated antitumor activity of DCI against human breast cancer both in vitro and in vivo. In order to determine the inhibitory effects of DCI on growth of human breast cancer cells (MDA-MB-231), two different assessment methods were implemented: MTT assay and mouse xenograft assay. MTT assay demonstrated downturn in cell proliferation by DCI treatment (1, 5, 10, 20 and 40 mM) groups by 18.3% (p < 0.05), 17.2% (p < 0.05), 17.5% (p < 0.05), 18.4% (p < 0.05), and 24.9% (p < 0.01), respectively. Also, inhibition of tumor growth was investigated in mouse xenograft model. DCI was administered orally at the dose of 500 mg/kg and 1000 mg/kg body weight to treat nude mouse for 45 consecutive days. On the 45th day, tumor growth of DCI (500 mg/kg and 1000 mg/kg) groups was suppressed by 22.1% and 67.6% as mean tumor volumes were $9313.8{\pm}474.1mm^3$ and $3879.1{\pm}1044.1mm^3$, respectively. Furthermore, breast cancer stem cell (CSC) phenotype ($CD44^+/C24^-$) was measured using flow cytometry. On the 46th day, CSC ratios of DCI (500 mg/kg) and co-treatment with doxorubicin (4 mg/kg) and DCI (500 mg/kg) group decreased by 24.7% and 53.9% (p < 0.01), respectively. Finally, from tumor recurrence assay, delay of 5 days in the co-treatment group compared to doxorubicin (4 mg/kg) alone group was observed. Based on these findings, we propose that DCI holds potential as an anti-cancer drug for treatment of breast cancer.

• Archives of Pharmacal Research
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• v.17 no.2
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• pp.115-118
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• 1994

This paper describes the isolation of isoguanosine from Croton tiglium L. and its cytotoxic effect anginst several tumor cell lines in culture and newly reports that isoguanosine has an antitumor activity against implanted S-180 ascitic turmor mice. Isoguanosine is effective at the dose of $24mg/kg/day{\times}5$, with T/C value of 168%. Isoguanosine inhibits the gorwth of S-180 and Ehrich solid tumor in mice at the optimal doses of $96\; mg/kg/day{\times}12$ and $48\;mg/kg/day{\times}12$, with 1-T/C values of 65% and 60% respecively.