• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7501-7508
• /
• 2013

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.

• Nutrition Research and Practice
• /
• 제9권6호
• /
• pp.628-636
• /
• 2015

BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.

• 대한기관식도과학회지
• /
• 제2권2호
• /
• pp.200-212
• /
• 1996

The clinical staging systems for oral squamous cell carcinoma is limited as a prognostic indicatior because of different biological characteristics of cancer in this region and variable microenvironment depending on subsites, there have been study to determine prognosis by evaluating malignancy, that is the nature of tumor cells. Many studies have been tried to determine prognostic indicator in various malignancies for the evaluation of differentiation capacity and the expression of oncogene product. EGF make a role in cellular growth and differentiation and to be essential in cellular survival. EGFR is an intergral membrane protein, stimulate cellular differentiation and hormonal secretion, and has structural homology with V-erb-B transforming protein. Recent reports have demonstrated that EGFR is overexpressed in stomach, breast, vagina, dermis, head and neck, genitourinary and lung tumors, and possibly used as a tumor marker. In head and neck region, most of studies were mainly carried out on laryngeal squamous cell carcinoma. In the present study, immunohistochemical study for EGFR and C-erb-B2 gene in paraffin sections of 45 squamous cell carcinoma in oral cavity was performed to evaluate the presense of EGFR and C- erb-B2 gene in this lesion, to evaluate them as a prognostic indicator by analysing the correlation between these expression and subsites, primary stages, clinical stages, pathologic grades, neck node metastasis, recurrences and treatment results, and to determine relation between EGFR and C-erb-B2 gene.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권7호
• /
• pp.3043-3050
• /
• 2015

The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.

• IMMUNE NETWORK
• /
• 제5권4호
• /
• pp.215-220
• /
• 2005

Background: Transforming growth factor-${\beta}$ (TGF-${\beta}1$) directs class switch recombination (CSR) to IgA isotype, which is a predominant antibody in mucosal surfaces. Although IgA is preferentially committed in mucosal lymphoid tissues, it is not definitely established whether hallmarks of IgA CSR such as IgA germ-line transcripts (GLT ${\alpha}$), post-switch transcripts (PST ${\alpha}$) and circle transcripts (CT ${\alpha}$) are readily expressed in such tissues. Therefore, we compared the expression of these transcripts among mouse Peyer's patches (PP), mesenteric lymph nodes (MLN), and spleen. Methods: Levels of GLTs, PSTs and CTs were measured by RT-PCR in isolated PPs, MLNs and spleen cells. Results: GLT ${\alpha}$ and PST ${\alpha}$ were well expressed in PP and MLN cells but in spleen cells. Similar patterns were observed in the expression of GL ${\gamma}$2b and PST ${\gamma}$2b. On the other hand, these transcripts were only inducible in spleen cells upon stimulated with LPS and TGF-${\beta}1$. In addition, CT${\alpha}$ and CT${\gamma}$2b were detected in PP cells. Conclusion: PP B cells readily express IgA GLT, PST, and CT. Overall expression patterns of these transcripts were similar in MLN cells. Thus, these results suggest that microenvironment of PP and MLN influences spontaneous IgA CSR, which lacks in systemic lymphoid tissues such as spleen.

• 한국환경보건학회지
• /
• 제37권2호
• /
• pp.94-101
• /
• 2011

Objectives: The purpose of this study is to evaluate the noise exposures of firefighters according to their time-dependent activity patterns. Methods: Personal exposure levels were measured for six days and nights using noise dosimeters; three days and nights for on-duty tasks, the other days and nights for off-duty activities. Results: The total amount of time spent in the workplace was 13,677 min (67%), outside areas 4,833 min (23%), in transit 1,002 min (5%), and other indoor area 807 min (4%) during a working period. However, during off-days they spent 10,858 min (76%) at home, 1,382 min (10%) outdoors, 1,225 min (9%) other indoors, and 493 min (3%) in transit. As a result of individual exposure levels, TWA did not exceed 90 dBA of the occupational exposure limit for the majority of the firefighters, whereas the levels of Lmax were 119 dBA, which were higher than the noise levels of firefighters in USA. Sometimes during dispatching the levels of Lpeak exceeded the ACGIH exposure standard (140 dBC). The Leq levels in transit were higher than the levels in home and other indoors even though the activity time is short. Conclusions: This paper characterized the noise exposure patterns of firefighters in Korea. We suggest that special noise sources, including sirens and speaker phones, should be readjusted to reduce noise exposure.

• BMB Reports
• /
• 제42권6호
• /
• pp.344-349
• /
• 2009

Angiogenesis is crucial for solid tumor growth. By secreting angiogenic factors, tumor cells induce angiogenesis. However, targeting these angiogenic factors for cancer therapy is not always successful, suggesting that other factors may be involved in tumor angiogenesis. This work shows that 25 protein spots were differentially expressed by two-dimensional gel electrophoretic analysis when HepG2 cells induced endothelial cell differentiation to tube in vitro, and most of them were upregulated. Twenty-one proteins were identified with MALDITOF-MS, and the other four were identified by LTQ-MS/MS. Keratins were identified as one class of these upregulated proteins. Further study indicated that the expression of keratin 17 in cultured endothelial cells is likely microenvironment regulated, because its expression can be induced by HepG2 cells and bFGF as well as serum in culture media. Increased expression of keratins in endothelial cells, such as keratin 17, may contribute to the angiogenesis induced by HepG2 cells.

• BMB Reports
• /
• 제40권3호
• /
• pp.341-348
• /
• 2007

Herpesvirus saimiri (HVS), a member of the $\delta$-herpesvirus family, encodes an oncoprotein called Saimiri Transforming Protein (STP) which is required for lymphoma induction in non-human primates. Previous study has shown that STP-C, an oncoprotein of HVS, activates NF-$\kappa$B signaling pathway. However, the detailed mechanism of STP-Cmediated NF-$\kappa$B activation has not been reported yet. We first report that STP-C interacts with TRAF6 protein in vivo and in vitro and further investigation shows that $Glu_{12}$ residue of STP-C is critical for binding to TRAF6. Introduction of ubiquitin together with STP-C augments NF-$\kappa$B activity compared to that of STP-C expression alone. STP-C expression further induces ubiquitination of endogenous TRAF6. In addition, either a deubiquitination enzyme, CYLD or a dominant negative E2-conjugation enzyme reduced NF-$\kappa$B activity in spite of the presence of STP-C, supporting that the interaction between STP-C and TRAF6 induces ubiquitination of TRAF6. NF-$\kappa$B activation by STP-C through the ubiquitinated TRAF6 causes the increased production of IL-8, an inflammatory chemokine and the enhanced expression of costimulatory molecule ICAM, which might ultimately contribute cellular transformation by the exposure of HVS-infected cells with inflammatory microenvironment and chronic activation.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권9호
• /
• pp.3917-3922
• /
• 2015

Curcumin, a lipid-soluble compound extracted from the plant Curcuma Longa, has been found to exert immunomodulatory effects via macrophages. However, most studies focus on the low bioavailability issue of curcumin by nano and microparticles, and thus the role of macrophages in the anticancer mechanism of curcumin has received little attention so far. We have previously shown the potential biocompatibility, biodegradability and anti-cancer effects of dendrosomal curcumin (DNC). In this study, twenty-seven BALB/c mice were equally divided into control as well as 40 and 80 mg/kg groups of DNC to investigate the involvement of macrophages in the antitumor effects of curcumin in a typical animal model of metastatic breast cancer. At the end of intervention, the tumor volume and weight were significantly reduced in DNC groups compared to control (P<0.05). Histopathological data showed the presence of macrophages in tumor and spleen tissues. Real-time PCR results showed that DNC increased the expression of STAT4 and IL-12 genes in tumor and spleen tissues in comparison with control (P<0.05), referring to the high levels of M1 macrophages. Furthermore treatment with DNC decreased STAT3, IL-10 and arginase I gene expression (P<0.05), indicating low levels of M2 macrophage. The results confirm the role of macrophages in the protective effects of dendrosomal curcumin against metastatic breast cancer in mice.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1305-1310
• /
• 2012

Breast cancer cells undergo transformation when they spread into surrounding tissues. Studies have shown that cancer cells undergo surface alterations and interact with the surrounding microenvironment during the invasion process. The aim of the present study was to analyse these cancer cell surface alterations and interactions of cancer cells and stroma. Twenty 1-methyl-1-nitrosourea-induced breast cancer samples taken from five rats were fixed in McDowell-Trump fixative and then washed in 0.1 M phosphate buffer. The samples were then treated with osmium tetroxide before being washed in distilled water and subsequently dehydrated through graded ethanols. The dehydrated samples were immersed in hexamethyldisilazane (HMDS), then following removal of excess HMDS, the samples were air dried at room temperature in a dessicator. The dried samples were mounted onto specimen stubs and coated with gold coater before being viewed under a scanning electron microscope. We detected the presence of membrane ruffles on the surface of cancer cells and the formation of unique surface membrane protrusions to enhance movement and adhesion to the surrounding stroma during the process of invasion. Advancing cancer cells demonstrated formation of lamellipodia and invadopodia. The stroma at the advancing edge was desmoplastic with many collagen fibres laid down near the cancer cells. Our data suggest that all of these abnormalities could act as hallmarks of invasiveness for breast cancer.