• Molecules and Cells
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• v.42 no.7
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• pp.530-545
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• 2019

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive $CD133^+/CD24^-$ cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1879-1883
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• 2014

Background: The relationship between obesity and prostate cancer aggressiveness is controversial in recent studies, partly because BMI is the only generally applied marker of obesity. Our study aimed at evaluating the correlation of periprostatic fat (PF) on magnatic resonance imaging (MRI) and adipocytokines with prostate cancer aggressiveness. Patients and method: A total of 184 patients who underwent radical retropubic prostatectomy (RRP) were analyzed retrospectively; different fat measurements on MRI slices and levels of adipocytokines were compared with the clinical and pathologic factors using SSPS ver.13.0. Result: The PF rates showed a statistically significant variation (p=0.019, 0.025) among groups, that is to say, more adipose tissue was distributed in periprostatic areas of high risk patients. Logistic regression analysis adjusted for age revealed a statistically association between the PF, the ratio and the risk of having high-risk disease (p=0.031, 0.024). The levels of IL-6, leptin and c-reactive protein (CRP) significantly increased with the aggressiveness of prostate cancer, and also with PF and its ratio. The strongest correlation was seen between IL-6 and PF (Pearson r coefficient=0.67, P<0.001). No association was observed between adipocytokines and BMI. Conclusion: Periprostatic adiposity not only affects prostate cancer aggressiveness, but also influences the secretion of adipocytokines. IL-6, PF and CRP have promoting effects on progression of prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.201-205
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• 2016

Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.141-141
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• 2003

Ras expression has been suggested as a marker for tumor aggressiveness of breast cancer, including the degrees of invasion and tumor recurrence. We previously showed that p38 MAPK is a key signaling molecule differentially regulated by H-ras and N-ras, leading to H-ras-specific cell invasive and migrative phenotypes in human breast epithelial cells (Cancer Res.: 63, 5454-5461, 2003).(omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.170.2-170.2
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• 2003

Ras expression has been suggested as a marker for tumor aggressiveness of breast cancer, including the degrees of invasion and tumor recurrence. We previously showed that p38 MAPK is a key signaling molecule differentially regulated by H-ras and N-ras, leading to H-ras-specific cell invasive and migrative phenotypes in human breast epithelial cells (Cancer Res: 63, 5454-5461, 2003). In this study, we further investigated the role of p38 MARK pathway in the induction of metastatic potential in MCF10A cells as a "gain of function" study. (omitted)

• Korean Journal of Veterinary Pathology
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• v.2 no.2
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• pp.85-94
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• 1998

This study was performed to evaluate whether the loss or overexpression of Rb, and overexpression of p53 were prognostic indicators for bladder neoplasia, 52 tumor specimens from transitional cell carcinoma of the urinary bladder were from 42 male and 10 female patients whose age ranged from 30 to 83 years old(mean age; 63,5 years old), This group included 36 superficial and 16 invasive stage bladder tumors, and grades 16-25, p53 was significantly associated with tumor stage and grade(p＜0,05 in each), but not with tumor recurrence. Loss of Rb gene expression or Rb overexpression was correlated with stage, but not grade. These results suggested that changes of Rb and p53 expression might play an important role in assessing the aggressiveness of human neoplasms.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.54-54
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• 2003

Malignant fibrous histiocytomas (MFHs) is the most common type of soft tissue sarcoma in the old animal with a aggressiveness, a high local recurrence rate and significant metastatic rate, which associated with a poor prognosis. In most histologic and immunohistological studies, the tumor cells raised from a fibroblastic and/or myofibroblastic phenotype, presumably from undifferentiated mesenchymal cell origin. MFHs are usually firm and invasive, arising in the subcutis; metastasis depends on tumor grade (many are grade 3) [1,2]. The primary tumor cells are pleomorphic, varying in appearance from fusiform to round. Often nucleoli are prominent and irregular [5]. Extracellular amorphous eosinophilic material may be prominent and likely represents reactive collagen production by the tumor [5]. (omitted)

• The Journal of the Korean bone and joint tumor society
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• v.10 no.1
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• pp.39-44
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• 2004

A Giant cell tumor of bone has unusual characteristics of pulmonary metastasis as well as local aggressiveness. Clinical courses of pulmonary metastasis of benign giant cell tumor vary including rapid growth, continuously slow growth or spontaneous regression. We report a case of extensive pulmonary metastasis of giant cell tumor of bone, which regressed spontaneouly.

• The Journal of the Korean bone and joint tumor society
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• v.7 no.2
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• pp.73-79
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• 2001

Giant cell tumor is usually found around the knee joint, especially in the distal femur or proximal tibia. Despite being classified as benign, it has unusual biological behavior of local aggressiveness and tend to have severely destructive lesion and develop rare pulmonary metastasis. Therefore, when the patient is presented to the physician with an expansile lytic lesion of challenging clinicopathologic entity extending to subchondral bone, the physician faces up to difficulties in treatment. We report a case of 25 years old patient having recurrent giant cell tumor in the right distal femur which developed metastasis to lung. The primary bone lesion was treated with local curettage and fillings with methylmethacrylate, but when he returned to the hospital two years later, the recurrence had developed with lung metastasis.

• Molecules and Cells
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• v.37 no.1
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• pp.17-23
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• 2014

We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or ${\beta}$-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. We demonstrated that Sp1 protein or mRNA expression is induced by Bcl-w using Western blotting or RT-PCR, respectively, and markedly elevated in high-grade glioma specimens compared with low-grade glioma tissues using tissue array. However, relationship between Bcl-w-related signaling and aggressive characteristic of GBM is poorly characterized. This study suggested that Bcl-w-induced Sp1 activation promoted expression of glioma stem-like cell markers, such as Musashi, Nanog, Oct4 and sox-2, as well as neurosphere formation and invasiveness, using western blotting, neurosphere formation assay, or invasion assay, culminating in their aggressive behavior. Therefore, Bcl-w-induced Sp1 activation is proposed as a putative marker for aggressiveness of GBM.