• Journal of Ginseng Research
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• v.46 no.1
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• pp.167-174
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• 2022

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites of ginseng, performs a broad spectrum of anti-tumor effects. Our aims are to search out new strategies to enhance anti-tumor effects of natural products, including 20(S)-PPD. In recent years, fasting has been shown to be multi-functional on tumor progression. Here, the effects of fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored. Methods: CCK-8 assay, trypan blue dye exclusion test, imagings photographed by HoloMonitorTM M4, transwell assay and flow cytometry assay were performed for functional analyses on cell proliferation, morphology, migration, invasion, apoptosis, necrosis and cell cycle. The expressions of genes on protein levels were tested by western blot. Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD. Results: We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro. In fasting-mimicking culturing medium, the apoptosis and necrosis induced by 20(S)-PPD increased and more cells were arrested at G0-G1 phase. Meanwhile, invasion and migration of cells were decreased by down-regulating the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in fasting-mimicking medium. Furthermore, the in vivo study confirmed that intermittent fasting enhanced the tumor growth inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side effects. Conclusion: Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7965-7970
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• 2014

One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

• IMMUNE NETWORK
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• v.16 no.5
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• pp.305-310
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• 2016

In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone expressing heterodimeric IL-12 as a single chain (mb-scIL-12 tumor clone). The stimulatory effect of mb-scIL-12 on the proliferation of ConA-activated splenocytes was higher than that of mbIL-12 p35 in vitro. However, the stimulatory effect of mbIL-12 p35 was equivalent to that of recombinant soluble IL-12 (3 ng/ml). Interestingly, both tumor clones (mbIL-12 p35 and mb-scIL-12) showed similar tumorigenicity and induction of systemic anti-tumor immunity in vivo, suggesting that tumor cell expression of the membrane-bound p35 subunit is sufficient to induce anti-tumor immunity in our tumor vaccine model.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2289-2293
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• 2013

MicroRNAs (miRNAs) are small, non-coding RNAs that are critical regulators of various diseases. MicroRNA-20a (miR-20a) and microRNA-203 (miR-203) have previously shown significant alteration in a range of cancers. In this study, the expression levels of miR-20a and miR-203 in 100 cervical cancer tissues were detected by qRT-PCR and compared to patient matched-nontumor cervical tissues. Correlations between expression level and clinicopathologic characteristics of cervical cancer were also analyzed. Finally, we studied the effect of miR-20a and miR-203 on cell proliferation in cervical cancer cell lines by MTT. We found that the expression level of miR-20a (P<0.001) was significantly higher in cervical cancer patients than in healthy controls, while that of miR-203 (P<0.001) was lower. Aberrant expression of miR-20a was correlated with lymph node metastasis (LNM), histological grade and tumor diameter, but down-regulated miR-203 was correlated with LNM only. Furthermore, we found that over-expression of miR-203 decreased cell proliferation, while reduction of miR-20a also prevented tumor progression. Our results support the involvement of miR-20a and miR-203 in cervical tumorigenesis. We propose that miRNAs might be used as therapeutic agents for cervical cancer.

• Journal of Nutrition and Health
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• v.53 no.4
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• pp.369-380
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• 2020

Purpose: It has been previously reported that breast tumor incidence, growth, and metastasis are stimulated by high-fat diet but reduced by caloric restriction. However, few studies have elucidated the effects of dietary change from a high-fat diet after breast cancer initiation. Therefore, in this study, we attempted to provide practical assistance to breast cancer prevention and management by investigating the effects of dietary change from a high-fat diet to normal diet on breast cancer growth and metastasis. Methods: The experimental animals were divided into 2 groups (high-fat diet control [HFC] group and diet restriction [DR] group) and consumed a high-fat diet for 8 weeks. 4T1 cells were transplanted into subcutaneous fat or tail vein to measure the growth and metastasis of breast cancer. The HFC and DR groups continuously ingested either high-fat diet or AIG-93G diet for 5 weeks or 3 weeks, respectively. Cell proliferation and apoptosis markers from tumor tissues were analyzed by Western blot analysis. The data were analyzed using the SPSS 25.0 package program. Results: The results show that the DR group significantly reduced breast tumor initiation, growth, and tumor tissue weight compared to the HFC group. The DR group suppressed tumor growth by decreasing proliferation and inducing apoptosis through down-regulation of Bcl-xL and up-regulation of caspase-3 activity. Furthermore, the DR group significantly reduced numbers of metastasized tumors in lung tissues. Conclusion: These results suggest that dietary change from a high-fat diet to normal diet decreased breast growth by reducing cell proliferation and inducing apoptosis and metastasis. Taken together, these results indicate that dietary change to a low-fat and balanced diet might suppress breast tumor growth and metastasis even after tumor diagnosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.602-609
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• 2010

This study was carried out to investigate the anti-cancer effects of Gunbibosinhangam-tang (GBHT I) and Gunbibosinhangam-tang-gamibang (GBHT II, GBHT III) on solid tumor and immune cells. The animals were divided into 4 groups ; Control, no treatment. GBHT I, treatment with GBHT itself. GBHT II, treatment with GBHT increased the quantity of Hedyotis Diffusae twice. GBHT III, treatment with GBHT increased the quantity of Hedyotis Diffusae four times. We investigated the effects of GBHT on proliferation of solid tumor cells (S-180), thymocytes, splenocytes in vitro in order to examine cytotoxicity for S-180 and immuno-stimulating activities. The experiments that is about solid tumor weight and survival rate in tumor bearing mice were performed also. As compared with the control group, treatments with GBHT II and GBHT III suppressed the proliferation of S-180 effectively. Treatments with all experimental groups accelerated the proliferation of thymocytes and splenocytes significantly. In addition, GBHT III was significantly decreased on solid tumor weight and increased on survival rate in tumor bearing mice. Based upon these results, we suggest that GBHT and GBHT-gamibang have both anti-cancer effects for S-180 and immuno-stimulating activities for thymocytes and splenocytes. Therefore, we conclude that GBHT and Hedyotis Diffusae is useful to treat the patients with cancer.

• Proceedings of the KSME Conference
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• 2002.08a
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• pp.711-712
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• 2002

A numerical study of a hemodynamical model for the tumor angiogenesis is carried out. The tumor angiogenesis process is comprised of a sequence of events; secretion of tumor angiogenesis factor(TAF) from the solid tumor, degradation of the basement membrane of nearby blood vessels, migration and proliferation of the endothelial cells. The model takes into account the effect of TAF concentration and endothelial cell density, and their conservation equations are represented as a set of one-dimensional initial boundary value problems. These equations are discretized by using a finite difference method in which the second order schemes both in time and in space are used. The effects of the parameters contained in the model are Investigated extensively through the numerical simulation of the discretized model. The result for the typical case compares very well with the known result.

• Korean Journal of Bronchoesophagology
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• v.8 no.1
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• pp.87-91
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• 2002

Solitary fibous tumor of pleura is a rare and slow vowing neoplasm. The histogenesis of this tumor is thought as mesenchymal origin by immunohistochemical and ultrastructural bases. This case report is of a 69-year-old female who presented severe dyspnea and orthopnea with long-term history. Preoperative chest X-ray an chest CT revealed huge and hemithorax-occupying heterogenous mass and cardiomegaly. She underwent surgical resection and a 22 X 18 X 10 cm sized visceral pleural based mass was evacuated. Histologic findings of tumor showed patternless proliferation in a fibrocollagenous and well vasculized stroma. Immnohistochemical staining revealed strong positive in CD34, that are compatible with solitary fibrous tumor of pleura. The patient was discharged without any complications and no evidence of recurrence was found after 2 years.

• BMB Reports
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• v.52 no.7
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• pp.415-423
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• 2019

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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• pp.106-114
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• 2018

Angiogenesis is the new blood vessel formation process and has known to a fundamental event of tumor growth and metastasis. Especially, vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the crucial regulators of angiogenesis in tumor. VEGF-A is one of the VEGF family and binds to endothelial cell specific VEGFR1 and VEGFR2, which are associated with tumor growth and tumor angiogenesis. $VEGF_{121}$ is more tumorigenic isomer of VEGF-A. Targeted VEGF or VEGFR molecular imaging has been widely used to enable diagnosis and monitoring of proliferation and development of angiogenic tumors. Therefore, in this review, we have focused on the radioligands with $VEGF_{121}$ for angiogenesis of tumor.