• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.93-99
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• 2008

Human cyclin D3 gene (CCND3) located on 6p21.1 is important for the regulation of the G1-S phase transition of the cell cycle by modulating the activity of the cyclin-dependent kinases Cdk4 and Cdk6. Because little is known about the effect of cyclin D3 in various human cancers, we evaluated the intricate relationship between expression of cyclin D3 and the process of HCC development using immunohis tochemistry and TUNEL assay on 43 paraffin embedded tissues. Cyclin D3 immunoreactivity was more frequently observed in the tumors with high histologic grade and the tumors with metastasis, and more frequently expressed in HCCs with cirrhotic background and gain of 6p21.1 when compared with those with non-neoplastic tissue. Apoptotic cells were more common in tumor with cirrhotic background, amplification of 6p21.1 and expression of cyclin D3 when compared with HCCs with lower level of cyclin D3 expression. Also, we observed that some of the cyclin D3 positive cell and apoptotic cell were co-localized. From these results, it is suggested that over-expression of cyclin D3 may contribute to more rapid cell turn-over in the background of HCC, and balance between proliferation and apoptosis is a role in the progression of HCC with cirrhotic background.

• Journal of Chest Surgery
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• v.55 no.1
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• pp.95-97
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• 2022

A cardiac calcified amorphous tumor (CAT) is a rare non-neoplastic mass of the heart with histological characteristics comprising calcification and amorphous fibrous material. Little is known regarding the incidence, symptoms, and therapeutic strategies for CAT. Echocardiography and computed tomography were performed on a 48-year-old man who had a cardiac mass that was accidentally discovered on admission to a local hospital for a fracture related to a trauma that occurred 1 month prior. After surgery, a histological examination resulted in the diagnosis of a cardiac CAT. The patient was discharged without postoperative complications on the 12th day after surgery.

• Journal of Gastric Cancer
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• v.13 no.4
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• pp.232-241
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• 2013

Purpose: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. Materials and Methods: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. Results: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. Conclusions: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5433-5438
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• 2012

Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.297-304
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• 2016

Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7295-7300
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• 2013

Lung cancer is the most common cause of cancer-related death in the world. The main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the latter including squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma. NSCLCs account for about 80% of all lung cancer cases. Microcephalin (MCPH1), also called BRIT1 (BRCT-repeat inhibitor of hTERT expression), plays an important role in the maintenance of genomic stability. Recently, several studies have provided evidence that the expression of MCPH1 gene is decreased in several different types of human cancers. We evaluated the expression of protein MCPH1 in 188 lung cancer and 20 normal lung tissues by immunohistochemistry. Positive MCPH1 staining was found in all normal lung samples and only some cancerous tissues. MCPH1-positive cells were significantly lower in lung carcinoma compared with normal tissues. Furthermore, we firstly found that MCPH1 expression in lung adenocarcinoma is higher than its expression in squamous cell carcinoma. Change in MCPH1 protein expression may be associated with lung tumorigenesis and may be a useful biomarker for identification of pathological types of lung cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.5
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• pp.293-297
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• 2003

Florid cemento-osseous dysplasia (FCOD) is a benign, non-neoplastic lesion characterized by multiple sclerosing masses only within jawbones. It is frequently confused with chronic diffuse sclerosing osteomyelitis (CDSO) in previous literatures. In our study, two cases of FCOD were examined to know the characteristics of their calcifying tissues. The first case was non-infected, while the second case was severely infected, displaying the typical features of CDSO in clinico-radiologic findings. The infected FCOD case showed a lot of bacterial colonies in the main lesion with relatively rare inflammatory reaction. The globular cementum-like materials of FCOD showed woven bone pattern and was positive for Alcian blue stain, and also positive for the antibodies of ameloblastin, bone morphogenetic protein (BMP) -2 and -4. On the other hands, in the immunostains of matrix metalloproteinase (MMP) -3, -9, -10, and $TNF-{\alpha}$, macrophage infiltrated in the FCOD lesion was rarely observed. These data suggest that the cementum-like materials of FCOD contain various matrix proteins, and that the cementum-like materials are relevant to the overgrowth of the bacterial colonies by inhibition of the regional inflammatory reactions.

• Tuberculosis and Respiratory Diseases
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• v.66 no.5
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• pp.380-384
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• 2009

Drug-induced subacute cutaneous lupus erythematosus (SCLE) is associated with use of the following classes of medications: anti-hypertensives, anti-cholesterolemia, anti-psychotics, and anti-inflammatory drugs. Docetaxel is an anti-neoplastic agent, which is widely used for treatment of non-small cell lung cancer. Few cases of docetaxel-induced SCLE have been reported in the medical literature. Here, we report the case of a 58-year-old female patient who developed drug-induced SCLE after administration of docetaxel. After 4 cycles of chemotherapy with docetaxel and cisplatin, erythematous skin eruptions developed on the patient's face. Skin biopsies of the eruptions were remarkable for interfacing dermatitis with basement membrane thickening. Immunofluorescent study revealed characteristic features of SCLE, including granular deposition of IgM, C3, and apoptotic bodies along the basement membrane. The skin eruptions resolved gradually after cessation of drug and with the use of topical corticosteroids.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7513-7516
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• 2015

Background: Pyogenic granuloma is a common non-neoplastic connective tissue proliferation. ICAM-1 and VCAM-1 are vascular adhesion molecules and CD34 is a marker for evaluation of angiogenesis. The purpose of this study was to compare the immunohistochemical expression of ICAM-1, VCAM-1 & CD34 in oral pyogenic granuloma and normal gingiva. Materials and Methods: This study was performed on thirty five formalin-fixed, paraffin embedded samples of gingival pyogenic granuloma. Also we used thirty five paraffined blocks of normal gingiva as control group which were taken from crown lengthening surgery. We employed immunohistochemistry staining for our prepared microscopic slides using monoclonal mouse anti-human antibodies against ICAM-1 (CD54), VCAM-1 (CD106) and CD34. Slides were examined under light microscope and then the mean amount of stained vessels also known as microvascular density (MVD) in highly vascularized areas (hot spots) was measured. Paired t-test and repeated measures ANOVA were used to compare the difference between quantitative variables and Chi-square test for qualitative variables in different groups. Pearson correlation coefficient was used to compare relations between quantitative variables. P<0.05 was considered significant. Results: The mean of MVD for ICAM-1, VCAM-1 and CD34 was significantly higher in pyogenic granuloma than normal gingiva (p<0.001 & p<0.001 & p<0.001, respectively). Expression of CD34 in pyogenic granuloma was significantly higher than ICAM-1 and VCAM-1 (P<0.001). Besides, expression of ICAM-1 in normal gingiva, was significantly lower than two other markers (p<0.001). Conclusions: Regarding the results, it seems that ICAM-1, VCAM-1 and CD34 are useful biomarkers in evaluation of vascular and inflammatory lesions such as gingival pyogenic granuloma and the results indicate the role of these biomarkers in pathogenesis of oral pyogenic granuloma.

• Journal of Life Science
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• v.19 no.11
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• pp.1514-1521
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• 2009

To evaluate the feasibility of cathepsin-B levels in preoperatively screening patients with thyroid cancer, we assigned these patients to either the thyroid cancer group (n=32) or the nodular hyperplasia group (n=7). Five healthy volunteers served as controls (n=5). We quantified cathepsin-B expressions in cancerous lesions with follicular carcinoma and hyperplastic lesions with nodular hyperplasia, and compared the degrees to those of normal thyroid tissue, which was obtained from matched contralateral lobe. The activity of serum cathepsin B was significantly higher in patients with thyroid carcinoma ($284.87{\pm}79.32$, ${\times}10^{-2}\;mU$) and those with nodular hyperplasia ($255.45{\pm}95.68$, ${\times}10^{-2}\;mU$) than compared to normal control ($168.94{\pm}15.10$, ${\times}10^{-2}\;mU$) (p<0.05). Based on the results of immunoassay, the concentrations of cathepsin B in the thyroid cancer group ($15.50{\pm}7.86\;ng/ml$) and the nodular hyperplasia group ($17.64{\pm}7.49\;ng/ml$) were higher than those of the control group ($4.85{\pm}0.61\;ng/ml$). The degree of cathepsin-B mRNA expression was significantly higher in cancerous or hyperplastic lesions than normal thyroid tissues from matched contralateral lobe with follicular carcinoma or non-neoplastic thyroid disease. Our results indicate that the activity of serum cathepsin B is a useful indicator in screening patients with nodular hyperplasia or neoplastic thyroid disease and it may be involved in the abnormal proliferation of cells.