• Molecules and Cells
• /
• v.38 no.2
• /
• pp.112-121
• /
• 2015

Ectopic expression of $14-3-3{\zeta}$ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of $14-3-3{\zeta}$ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how $14-3-3{\zeta}$ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that $14-3-3{\zeta}$ is overexpressed. In OSCC cells, $14-3-3{\zeta}$ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, $14-3-3{\zeta}$ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-${\gamma}$ (IFN-${\gamma}$) and lipopolysaccharide (LPS). Furthermore, supernatants from $14-3-3{\zeta}$ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with $14-3-3{\zeta}$ and its disruption relieved the inhibition induced by $14-3-3{\zeta}$ in tumor inflammation. Taken together, our studies provide evidence that $14-3-3{\zeta}$ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.

• Tuberculosis and Respiratory Diseases
• /
• v.63 no.2
• /
• pp.165-172
• /
• 2007

Background: The pathogenesis of lung cancer includes the accumulation of multiple genetic abnormalities. The CREB-binding protein(CBP) is one of several transcriptional co-activators among various sequence-specific DNA-binding transcription factors. CBP is involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis that are suspected of contributing to tumorigenesis. The goal of this study was to evaluate CBP expression in a series of human lung tissues containing normal epithelium, premalignant lesions(hyperplasia and dysplasia) and squamous cell carcinomas. Materials and Methods: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by use of a monoclonal anti-CBP antibody. CBP expression was compared in samples from 120 patients with premalignant and malignant histological types including 20 metaplastic specimens, 40 dysplastic specimens, and 60 squamous cell carcinomas in the lung. Results: CBP expression was seen in 35% (7/20) of the metaplastic specimens. 65% (26/40) of the dysplastic specimens, and 70% (42/60) of the squamous cell carcinomas (p<0.05). According to celluar atypism, CBP expression was 50% (10/20) of the low-grade dysplastic specimens and 80% (16/20) of the high-grade dysplastic specimens(p <0.01). By cellular differentiation, CBP expression was seen in 95% (19/20) of the well differentiated squamous cell carcinomas, 85% (17/20) of the moderately differentiated carcinomas and 30% (6/20) of the poorly differentiated lesions (p <0.05). Conclusion: These results suggest that CBP may have an important role in malignant transformation of precancerous lung lesions and may be a marker for malignancy.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.23 no.2
• /
• pp.71-84
• /
• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Korean Journal of Clinical Laboratory Science
• /
• v.36 no.2
• /
• pp.193-198
• /
• 2004

PET/CT combines the functional information from a positron emission tomography (PET) exam with the anatomical information from a computed tomography (CT) exam into one single exam. A CT scan uses a combination of x-rays and computers to give the radiologist a non-invasive way to see inside your body. One advantage of CT is its ability to rapidly acquire two-dimensional pictures of your anatomy. Using a computer these 2-D images can be presented in 3-D for in-depth clinical evaluation. A PET scan detects changes in the cellular function - how your cells are utilizing nutrients like sugar and oxygen. Since these functional changes take place before physical changes occur, PET can provide information that enables your physician to make an early diagnosis. The PET exam pinpoints metabolic activity in cells and the CT exam provides an anatomical reference. When these two scans are fused together, your physician can view metabolic changes in the proper anatomical context of your body. PET/CT offers significant advantages including more accurate localization of functional abnormalities, and the distinction of pathological from normal physiological uptake, and improvements in monitoring treatment. A PET/CT scan allows physicians to measure the body's abnormal molecular cell activity to detect cancer (such as breast cancer, lung cancer, colorectal cancer, lymphoma, melanoma and other skin cancers), brain disorders (such as Alzheimer's disease, Parkinson's disease, and epilepsy), and heart disease (such as coronary artery disease).

• Korean Journal of Korean Medical Institute of Dermatology and Aesthetics
• /
• v.1 no.1
• /
• pp.53-90
• /
• 2005

Purpose: Contents of astragaloside I, II and IV, cytotoxicity, anticancer activity, immunomodulatory activity and antioxidant capacity were to be compared as a function of the cultivated years as one, three, five and seven years. Method: Major components of Astragali membranacei Radix were separated as astragaloside I, astragaloside II, astragaloside IV by HPLC analysis. Cytotoxicity and anticancer activities were measured by MTT and SRB assay. For immunomodulatory activity, the secretion of IL -6 and $TNF-{\alpha}$, NK cell activation and macrophage activation were observed as well as kinetics of responding to human T cells by a microphysiometer. In vitro antioxidant activities were measured by several radical scavenging activities of superoxide anion radican, DPPH, LDL and linoleic acid. For in vivo activity, the activation of SOD, GSH-px, catalase, ALDH and ADH was measured as well the relative weight of liver. Result : 1. For HPLC analysis, the contents of all of astragaloside I, astragaloside II, astragaloside IV were in order of three, five, one and seven years. 2. The cytotoxicity of normal human lung cell line, HEL299 showed lower than 18% in adding 0.25 mg/ml, and 28.9% in adding 1.0 mg/ml of water extract of seven year root. For methanol extracts, three year root showed highest cytotoxicity as 35.2 % and there was no difference between the cultivated years. 3. For anticancer activities, methanol extracts of one and three year roots showed relatively high inhibition of human stomach cancer cells, AGS, breast cancer cells, MCF-7, lung cancer cells, A549 and liver cancer cell, Hep3B as well as high selectivities. 4. The water extract of seven year root could yield high secretion of IL-6 from both human Band T cells while the methanol extracts of three and five year roots secreted high amounts of IL-6 and $TNF-{\alpha}$ from both Band T cells. 5. As a result of in vitro antioxidant activities, both water and methanol extracts from five and seven year roots showed high activities for superoxide anion radical scavenging activity, inhibiting linoleic acid peroxide and contents of total phenols. 6. For in vivo tests, Mn-SOD and GSH-px activities and weight of liver were better in adding seven year root. For ALDH activity one year root was better and for ADH activity five year root. Overall speaking, seven year root showed relatively better antioxidant activities. Conclusion:There was difference of the contents of astragaloside I, astragaloside II, astragaloside IV according to cultivation year. Methanol extract showed better activities of anticancer and immune activation rather than water extract Interestingly enough, for methanol extracts, overall activities were improved as the cultivation year increased. There might be further investigation required for the clinical uses of the results as several biological activities varied according to the cultivated year of Astragali membranacei Radix.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.1
• /
• pp.255-260
• /
• 2012

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

• The Korean Journal of Cytopathology
• /
• v.1 no.1
• /
• pp.111-120
• /
• 1990

Small cell neuroendocrine carcinoma of the uterine cervix is a distinct subtype of cervical cancer that appears analogous to oat cell carcinoma and carcinoid tumors of the lung. It has been assumed to be derived from the neural crest via argyrophilic cells in the normal endocervix. We have recently encountered a case of small cell neuroendocrine carcinoma of the uterine cervix coexisting with adenocarcinoma which was argyrophil negative. A 66-year-old multiparous woman was admitted because of vaginal bleeding for 2 months. Cervicovaginal smear revealed several scattered clusters and sheets of monotonous small cells with some peripheral palisading in the background of hemorrhage and necrosis. Radical hysterectomy specimen revealed an ulcerofungating tumor on endocervical canal which was composed of two components. Major component of the tumor was made up of monomorphic population of small oval-shaped tumor cells arranged in sheets and partly in acinar structures or trabecular fashion. Other component was adenocarcinoma, endocervical well-differentiated type. Argyrophilia was present on the Grimelius stain and immunohistochemical studies revealed diffuse positivity to neuron-specific enolase and carcinoembryonic antigen. Electron microscopic examination showed clusters of small round to oval cells, which had a few well-formed desmosomes and several membrane-bound, dense-core neurosectetory granules.

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

• International Journal of Oral Biology
• /
• v.46 no.2
• /
• pp.85-93
• /
• 2021

Asarum sieboldii Miq. (Aristolochiaceae) is a perennial herbaceous plant and has been used as traditional medicine for treating diseases, cold, fever, phlegm, allergies, chronic gastritis, and acute toothaches. Also, it has various biological activities, such as antiallergic, antiinflammatory, antinociceptive, and antifungal. However, the anticancer effect of A. sieboldii have been rarely reported, except anticancer effect on lung cancer cell (A549) of water extracts of A. sieboldii. This study investigated the anticancer activity of methanol extracts of A. sieboldii (MeAS) and the underlying mechanism in human FaDu hypopharyngeal squamous carcinoma cells. MeAS inhibited FaDu cells grown dose-dependently without affecting normal cells (L929), as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and live and dead assay. In addition, concentration of MeAS without cytotoxicity (0.05 and 0.1 mg/mL) inhibited migration and colony formation. Moreover, MeAS treatment significantly induced apoptosis through the proteolytic cleavage of caspase-3, -7, -9, poly (ADP-ribose) polymerase, and downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by fluorescence-activated cell sorting analysis, 4'6-diamidino-2-phenylindole stain, and western blotting. Altogether, these results suggest that MeAS exhibits strong anticancer effects by suppressing the growth of oral cancer cells and the migration and colony formation via caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeAS can serve as a natural chemotherapeutic for human oral cancer.

• Journal of Applied Biological Chemistry
• /
• v.59 no.2
• /
• pp.133-136
• /
• 2016

An acetone extract in the cortex of Ulmus pumila L. was prepared to evaluate its anti-oxidative and anti-proliferative activities. The free radical scavenging activity ($EC_{50}=36.7{\mu}g/mL$) and reducing power ($EC_{50}=53.2{\mu}g/mL$) proportionally increased according to the extract concentration. The acetone extract possessed a potent anti-proliferative activity against human non-small cell lung cancer (A549, $GI_{50}=74.3{\mu}g/mL$) and human colon cancer (SNU-C4, $GI_{50}=92.8{\mu}g/mL$) cells in a dose-dependent manner, but was less effective with human normal cells (L132, human embryonic lung epithelial cell).