• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.37-44
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• 2017

Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that $kr{\ddot{u}}ppel$-like factor 8 (KLF8) is essential for tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with $TNF{\alpha}$ significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by $TNF{\alpha}$ stimulation in an ERK-dependent manner. The promoter region of KLF8 contained putative Sp1, KLF4, and $NF{\kappa}B$ binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8. The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8. Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, $SM22{\alpha}$, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and $SM22{\alpha}$ concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA. Stimulation of VSMCs with $TNF{\alpha}$ enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and $SM22{\alpha}$, thereby reduced the contractility in response to the stimulation of angiotensin II. These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.92-100
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• 2000

Purpose :This study was performed to determine the optimal treatment velum of Patients treating with radiation therapy for intracranial germ cell tumor. Materials and Methods : From 1993 to 1998, 19 patients with intracranial germ cell tumors treated by gamma knife radiosurgery were analyzed. The location of tumor was as follows; 9 cases on pineal region, 1 case on suprasellar region, and 9 cases of multiple lesion. 7 patients were pathologically verified; 5 cases of germ cell tumor and 2 cases of non germinomatous germ cell tumor. Tumor volume was ranged from 2.4 cm$^{3}$ to 74 cm$^{3}$. Irradiation dose was 10 Gy to 20 Gy with 50% isodose curve. Follow up period was 10 months to 54 months. Results : Recurrences were observed in 14 cases among 19 (74%) patients. Complete remission and partial remission were achieved in 2 (11%) and 10 (53%) respectively. No response was observed in 7 (36%). 2 cases were recurred within original tumor bed. 6 cases were recurred beyond but contiguous with tumor bed. Ventricular relapses separated from pretreatment tumor bed were 3. Spinal recurrences were 4. Among 8 recurred cases of which tumor volume is smaller than 20 cm$^{3}$, 2 were recurred within original tumor bed, 4 were recurred beyond but contiguous with tumor bed, and 1 spinal recurrence. Meanwhile, 6 cases of which tumor volume larger than 20 cm3, 1 case was recurred beyond but contiguous with tumorbed, 2 ventricular recurrences separated with original tumor bed, and 3 spinal recurrences. 5 cases which did not show any recurrence sign showed characteristics of single lesion, tumor volume smaller than 20 cm$^{3}$ and normal tumor marker. All of 4 cases of spinal recurrences happened in the case having ventricular invasion or lesion. Among 9 cases having multiple lesion, only 3 cases recurred within original tumor bed or around tumor bed, the other 6 cases recurred separated from pretreatment tumor bed. Conclusion : Gamma knife radiosurgery is not recommended for the treatment of intracranial germ cell tumor. It is because of small treatment volume and inadequate radiation dose that are characteristics of gamma knife radiosurgery. Tumor volume, ventricular invasion or ventricular lesion in multiple lesion are important factors to be considered for the wide field radiation therapy Tumor volume smaller than 20 cm$^{3}$, single lesion, no ventricular lesion or invasion, and normal tumor marker are ideal indications for small involved field radiation therapy. Prophylactic spinal irradiation seems to be necessary when there is ventricular lesion, ventricular invasion, and multiple lesions. When the tumor volume is larger than 20 cm$^{3}$, multiple lesions, abnormal tumor marker, and whole ventricular irradiation or partial brain irradiation would be possible and neoadjuvant chemotherapy would be most beneficial in these group.

• BMB Reports
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• v.45 no.11
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• pp.629-634
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• 2012

The human glycoprotein, stanniocalcin 2 (STC2) plays multiple roles in several tumor types, however, its function and clinical significance in hepatocellular carcinoma (HCC) remain unclear. In this study, we detected STC2 expression by quantitative real-time PCR and found STC2 was upregulated in HCC tissues, correlated with tumor size and multiplicity of HCC. Ectopic expression of STC2 markedly promoted HCC cell proliferation and colony formation, while silencing of endogenous STC2 resulted in a reduced cell growth by cell cycle delay in G0/G1 phase. Western blot analysis demonstrated that STC2 could regulate the expression of cyclin D1 and activate extracellular signal-regulated kinase 1/2 (ERK1/2) in a dominant-positive manner. Transwell chamber assay also indicated altered patterns of STC2 expression had an important effect on cell migration. Our findings suggest that STC2 functions as a potential oncoprotein in the development and progression of HCC as well as a promising molecular target for HCC therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.247-255
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• 2007

The bone morphogenic protein(BMP) can promote migration and growth of mesenchymal cells and initiate process for bone and cartilage formation. Cartilage-derived morphogenic protein(CDMP)-1 and -2 belong to the bone morphogenetic protein family in the transforming growth factor(TGF)-${\beta}$ superfamily. Although pleomorphic adenoma of the salivary glands is an epithelial tumor, it frequently shows ectopic cartilaginous formation with biomolecular studies. The mechanism of pathogenesis in cartilaginous formation is still controversy. We examined the expression and localization of CDMP-1 and -2, in comparison with the localization of cartilaginous matrix proteins, in human normal salivary glands and 20 cases of pleomorphic adenoma using immunohistochemical methods. The results were followed. 1. CMP-1 was immunolocalized in the striated ducts and the intercalated ducts, but not expressed in excretory duct, CDMP-2 was not expressed in the normal salivary glands. 2. CMP-1 was immunolocalized in the ductal cell and cuboidal neoplastic myoepithelial cells around the chondroid areas of the pleomorphic adenomas, whereas these molecules were not localized in the spindle-shaped neoplastic myoepithelial cells of the myxoid element in these tumors. CDMP-2 was expressed neither in normal salivary glands nor in any elements of the pleomorphic adenomas. 3. In transmission electron microscopic view, the tumor cells are composed of modifed myoepithelial cells between hyaline and myxoid stroma. 4. In Immuno-blot analysis, strong overexpression of CDMP-1 was frequently seen in pleomorphic adenomas, but the level of CDMP-2 was expressed minimally in pleomorphic adenoma. From the these results, it should be suggested that undifferentiated neoplastic myoepithelial cells around the chondroid areas expressed CDMP-1 and suggested that this molecule may play a role in the differentiation of neoplastic myoepithelial cells in pleomorphic adenoma, but not CDMP-2.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5691-5694
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• 2012

Ectopic expression of CDX2 in the stomach is closely associated with chronic Helicobacter pylori (H. pylori) infection and intestinal metaplasia. Whether CDX2 has tumor suppression or tumorigenesis potential remains to be elucidated. In this study, we investigated the association between the CDX2 G543C polymorphism (silent mutation) and the risk for H. pylori-induced gastric atrophy and cancer as well as H. pylori infection, using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The frequency of the minor allele was the same as previously reported in China, but different from that reported in England. CDX2 G543C was not associated with risk of H. pylori infection, gastric atrophy, or gastric cancer, although the point estimate for non-cardiac differentiated gastric cancer as compared to controls with gastric atrophy was 2.22 (95%CI=0.17-29.4). In conclusion, our results indicate that the CDX2 G543C polymorphism is unlikely to affect the H. pylori infection-gastric atrophy-gastric cancer sequence.

• Journal of Yeungnam Medical Science
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• v.5 no.2
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• pp.189-193
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• 1988

Adenosquamous carcinoma of stomach is a mixed glandular-epidermoid tumor where both components are neoplastic. Its incidence is extremely rare. The five theories on the origin of squamous components are 1) island of ectopic squamous epithelium in the gastric mucosa, 2) squamous metaplasia of gastric epithelium, 3) squamous differentiation in a preexisting adenocarcinoma, 4) endothelial cell differentiated toward squamous elements, and 5) totipotential undifferentiated cells of the gastric mucosa. We experienced three cases of adenosquamous carcinoma. Case 1 was a 71-year-old female patient. ; an ulcerative lesion was present in the pylorus, measuring 5cm in diameter. Case 2 was a 57-year-old male patient. ; an ulcerative lesion is present in the pylorus, measuring 6 em in diameter. Case 3 was a 58-year-old female patient. ; an ulcerative lesion was present in the body and fundus, measuring 10cm in diameter. Microscopic examination revealed a mixed malignant squamous and adenomatous component.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5057-5061
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• 2016

The present study was conducted to assess error rates with diagnosis using intra-operative frozen sections, and to indicate ways to increase overall performance. Over a period of two years, 227 cases were biopsied intra-operatively. Errors were observed in 14 cases. Four of these were sampling errors, one by a pathologist and three by surgeons. In seven cases incorrect interpretations were made. Epithelial dysplasia was observed on definitive histology in two cases which was not reported intra-operatively. One case was of ectopic thyroid. In cases of oral cancer where sentinel lymph nodes were sampled, immunohistochemistry for cytokeratin was performed to facilitate identification of micrometastasis. Only single case displayed tumor deposits which was not evident morphologically. Resection margins were reported in seventy eight cases. Some 18% (14/50) benefited from revision of margins; overall sensitivity of intra-operative frozen sections for marginal status was 71.4%, with a specificity of 90.3%. Overall sensitivity was 75% and specificity was 97.5%. Careful observation, pathologist experience and knowledge of limitations help in improving the overall diagnostic outcome.

• Molecules and Cells
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• v.38 no.11
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• pp.959-965
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• 2015

Inducible and reversible gene silencing in desired types of cells is instrumental for deciphering gene functions using cultured cells or in vivo models. However, efficient conditional gene knockdown systems remain to be established. Here, we report the generation of an inducible expression system for short hairpin RNA (shRNA) targeted to PTEN, a well-documented dual-specificity phosphatase involved in tumor suppression and ontogenesis. Upon induction by doxycycline (DOX), the reverse tetracycline transcriptional activator (rtTA) switched on the concomitant expression of GFP and a miR-30 precursor, the subsequent processing of which released the embedded PTEN-targeted shRNA. The efficacy and reversibility of PTEN knockdown by this construct was validated in normal and neoplastic cells, in which PTEN deficiency resulted in accelerated cell proliferation, suppressed apoptosis, and increased invasiveness. Transgenic mice harboring the conditional shRNA-expression cassette were obtained; GFP expression and concurrent PTEN silencing were observed upon ectopic expression of rtTA and induction with Dox. Therefore, this study provides novel tools for the precise dissection of PTEN functions and the generation of PTEN loss of function models in specific subsets of cells during carcinogenesis and ontogenesis.

• Molecules and Cells
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• v.42 no.1
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• pp.17-27
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• 2019

Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors. However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes by USP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.

• BMB Reports
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• v.55 no.2
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• pp.72-80
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• 2022

Odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, detect odorants in the nose. In addition, ORs were recently shown to be expressed in many nonolfactory tissues and cells, indicating that these receptors have physiological and pathophysiological roles beyond olfaction. Many ORs are expressed by tumor cells and tissues, suggesting that they may be associated with cancer progression or may be cancer biomarkers. This review describes OR expression in various types of cancer and the association of these receptors with various types of signaling mechanisms. In addition, the clinical relevance and significance of the levels of OR expression were evaluated. Namely, levels of OR expression in cancer were analyzed based on RNA-sequencing data reported in the Cancer Genome Atlas; OR expression patterns were visualized using t-distributed stochastic neighbor embedding (t-SNE); and the associations between patient survival and levels of OR expression were analyzed. These analyses of the relationships between patient survival and expression patterns obtained from an open mRNA database in cancer patients indicate that ORs may be cancer biomarkers and therapeutic targets.