• Title/Summary/Keyword: neoplastic

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Overview of Transforming Growth Factor β Superfamily Involvement in Glioblastoma Initiation and Progression

  • Nana, Andre Wendindonde;Yang, Pei-Ming;Lin, Hung-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.6813-6823
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    • 2015
  • Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

Interchange with Art Contained in the Works of Yves Saint Laurent (이브 생 로랑(Yves Saint Laurent) 작품에 수용된 예술과의 교류)

  • Kim, Sun-Young
    • The Research Journal of the Costume Culture
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    • v.19 no.2
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    • pp.283-295
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    • 2011
  • This study deals with the interchange with art that is contained in the works of Yves Saint Laurent, and it is disclosed through his works that modern fashion is part of expressive art while pursuing creative function as a work of art. The study has been performed on the basis of the references, the pictures of his works and interviews posted in domestic and overseas fashion magazines such as Vogue, Fashion News, Mode & Mode, Gap, Collections, etc. Regarding the scope of this study, it specifically deals with works he created from 1958 until 2002, when he announced his last collection. The results of the study show that with respect to Post-Impressionism, his works were greatly affected by van Gogh(who had used colors as active media in depicting his internal mental state) which gave birth to gorgeous and handicraft-like 'Couture-style clothes'. With respects to Fauvism, the works of Matisse also had an impact on Yves Saint Laurent, who added a sense of fauvism in his works through the use of colors, motif, or full reproduction of images from paintings. We see the influence of cubism upon Laurent when we examine his works of 'clothes with artistic value,' which utilized applique, beaded decoration, patchwork, embroidered patterns, relief-like ornaments, etc. using motif or objet much as we see in the works of Picasso and Braque, artists who expressed a new dimension of the formative arts. Laurent's use of neoplasticism, or plainness of painting, demonstrates a new formative art on the three-dimensional human body by using the works of Mondrian, which consist of black lines and primary colors, although generally Laurent's 'neoplastic'works differed from the works of Mondrian by more actively utilizing the lines and colors when designing dress and its ornament. In addition, the paintings and poems of surrealism artists and poets were directly used in the clothes or their images were sometimes borrowed. In order to express respect toward the spirit of surrealism and its artists, the human body motifs such as lips and eyes(which were frequently used by the surrealism artists) were applied to embroidery, printing and beaded decoration. Finally, being inspired by such Pop artists as Andy Warhol, Roy Lichtenstein and Tom Wesselman, Laurent further emphasized the aesthetic value of the popular consumer image in his own work, resulting in the wide recognition of the designs of Yves Saint Laurent as representing the new wave of the Pop Art school.

Marsupialization of the Nictitating Membrane Cyst Following Cherry Eye Repair in a Dog

  • Kim, Sunhyo;Kang, Seon-mi;Susanti, Lina;Kim, Boyun;Park, Yoonji;Shim, Jaeho;Go, Seokmin;Lee, Eunji;Seo, Kangmoon
    • Journal of Veterinary Clinics
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    • v.37 no.3
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    • pp.149-152
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    • 2020
  • One-year-old male Cocker Spaniel dog was referred for the third eyelid enlargement and inflammation in the left eye (OS). It gradually swelled for 2 weeks after the cherry eye repair by conjunctival mucosa pocket procedure at a private animal clinic. Routine ophthalmic examinations including neuro-ophthalmic examination, Schirmer tear test, intraocular pressure and corneal fluorescein staining were all normal. No lesions were found on slit lamp biomicroscopy and indirect ophthalmoscopy except for third eyelid swelling in the OS. Ultrasonography revealed cystic structure within the OS nictitating membrane. Fluid from the cyst was aspirated and there were no microorganisms or neoplastic changes. Surgical intervention was performed under general anesthesia. On the day of the surgery, there was a deep corneal ulcer in the OS, which had not existed before. Ventral palpebral surface of the third eyelid was incised horizontally to the shaft of the T-shaped hyaline cartilage. And then, a full thickness of the cystic wall was incised and marsupialized. Additionally, a direct suture was performed on the ulcerated cornea. Topical and systemic antibiotics and anti-inflammatory drugs were prescribed. One month after the surgery, the third eyelid swelling and the discharge were improved. Marsupialization of the nictitating membrane cyst relieved the swelling of the third eyelid and inflammation. It could be a simple but effective surgical intervention for the cystic complication of conjunctival mucosa pocket procedure in dogs.

A Case of Diffuse Infiltrative Lymphocytosis Syndrome Associated with Human Immunodeficiency Virus Infection (사람면역결핍바이러스 감염에 동반된 미만성 침윤성 림프구 증가 증후군 1예)

  • Kwon, Sun Ok;Park, Won Wo;Lee, Hyun Kyung;Lee, Sung Soon;Kang, Youn Kyung;Lee, Young Min;Lee, Hyuk Pyo;Kim, Joo In;Choi, Soo Jeon;Yum, Ho Kee
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.3
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    • pp.289-293
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    • 2006
  • Diffuse infiltrative lymphocytosis syndrome is an autoimmune syndrome that is characterized by the oligoclonal expansion of CD8+ T-lymphocytes in response to human immunodeficiency virus (HIV) antigens. The clinical manifestations include bilateral enlargement of the parotid glands, lymphocytic interstitial pneumonitis, lymphocytic hepatitis, neurological involvement and systemic lymphadenopathies. In addition to a positive HIV test, the diagnostic histopathological findings are CD8+ T-lymphocytic infiltrations in the lymphnodes, liver, lung, muscle and the salivary or lacrimal glands without granulomatous or neoplastic involvement. We report a case of pulmonary involvement of diffuse infiltrative lymphocytosis syndrome that was associated with a human immunodeficiency virus infection.

Expression of Matrix Metalloproteinase-9 and Fibroblast Growth Factor in Squamous Cell Carcinoma of the Head and Neck and Metastaric Cervical Lymph Node (두경부 편평 세포암의 원발 병소와 전이 경부 림프절에서 Matrix Metalloproteinase-9와 Basic Fibroblast Growth Factor의 발현)

  • Rho Young-Soo;Hwang Joon-Sik;Kim Jin;Kim Jin-Hwan;Cho Sung-Jin;Shin Hyung-Sik
    • Korean Journal of Head & Neck Oncology
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    • v.20 no.1
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    • pp.13-18
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    • 2004
  • Objectives: Cancer lethality is usually the result of local invasion and metastasis of neoplastic cell from the primary tumor. Because of their ability to degrade extracellular matrix components, matrix metalloproteinases (MMPs) and basic fibroblast growth factor (bFGF) have been implicated in the breakdown of basement membrane and underlying stroma, thereby facilitating tumor growth and invasion. It has been well established that MMPs and bFGF expression correlate with cervical lymph node metastasis, but studies on expression in the metastatic cervical lymph node itself are not enough. We have analyzed matrix metalloproteinases (MMPs) and basic fibroblast growth factor (bFGF) in squamous cell carcinoma of the head and neck and metastatic cervical lymph node, and evaluated their relationship and clinicophathologic significance. Material and Methods: 20 cases of squamous cell carcinoma of the head and neck were entered on the study of immunohistochemical stains for MMP-9 and bFGF in the obtained tissue from primary tumor and metastatic cervical lymph node. We analyzed the relationship between MMP-9, bFGF expression of the primary tumor and metastatic node with age, sex, T-stage, N-stage, histologic grade, pathologic stage and disease free survival. Results: Expression of MMP-9 and bFGF in cancer cell and metastatic lymph node was higher than that in normal cell and lymph node. According to histologic differentiation, expression of MMP-9 of the metastatic cervical lymph node was higher than primary tumor. Considering to other clinicopathologic factor, no statistical significance was seen in MMP-9 and bFGF. Conclusion: We found that expression of MMP-9 is higher in the metastatic lymph node than primary tumor in the poorly differentiated squamous cell carcinoma. But we don't find out the statistical significance in relation between bFGF and clinical factors. So we guess that some different mechanism of MMP-9 and bFGF in Head & Neck squamous cell carcinoma exist. Further studies will be necessary to establish their pathogenesis in the Head and Neck cancer.

Efficacy of Fine Needle Aspiration Cytology of Salivary Gland Diseases (타액선 질환에 대한 세침흡인세포검사의 유용성)

  • Park Min-Hyun;Lee Seung-Sin;Choi Byung-Yoon;Kim In-Sang;Choi Seung-Ho;Ko Tae-Yong;Kim Kwang-Hyun;Sung Myung-Whun
    • Korean Journal of Head & Neck Oncology
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    • v.16 no.1
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    • pp.42-45
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    • 2000
  • Background and Objectives: To review efficacy of the fine-needle aspiration cytology(FNAC) in patients with salivary glands lesions. Materials and Methods: From January 1994 through June 1999, FNACs and surgical biopsies were carried out on 109 patients with salivary gland diseases. The medical records were reviewed retrospectively. Benign tumor was found in 81 patients, and malignant tumor was in 19 patients. Nine patients had inflammatory lesion. Results: In 6 of 109 cases the aspiration was inadequate. Of the remaining 103 patients, FNAC correctly diagnosed 87 lesions(84.5%). For benign tumor lesions, the accuracy was 91%(71/78), and for malignant lesions 55.6%(10/18). The accuracy for inflammatory lesions was 85.7%(6/7). Regarding the capacity to discriminate between neoplastic and nonneoplastic lesions, sensitivity, specificity and total diagnostic accuracy were 99%, 85.7% and 84.5% respectively. Regarding the capacity to discriminate between malignant and benign tumors, sensitivity and specificity were 55.6% and 97.4% respectively. FNACs misdiagnosed malignant tumors as benign lesions in eight patients, in which three were with adenoid cystic carcinomas. Carcinoma ex pleomorphic adenoma, malignant lymphoma and mucoepidermoid carcinoma 'were others. Conclusion: FNAC showed high accuracy to diagnose benign lesions in salivary gland diseases. But the accuracy was rather low for malignant lesions. If a salivary gland lesion was suspected for malignant tumor, other diagnostic methods such as tissue biopsy should be seriously considered.

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Gastrokine 1 Expression in the Human Gastric Mucosa Is Closely Associated with the Degree of Gastritis and DNA Methylation

  • Choi, Won Suk;Seo, Ho Suk;Song, Kyo Young;Yoon, Jung Hwan;Kim, Olga;Nam, Suk Woo;Lee, Jung Yong;Park, Won Sang
    • 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.

Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

  • Chang, Youjin;Kim, Seon Ye;Choi, Yun Jung;So, Kwang Sup;Rho, Jin Kyung;Kim, Woo Sung;Lee, Jae Cheol;Chung, Jin-Haeng;Choi, Chang-Min
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.3
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    • pp.95-103
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    • 2013
  • Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

PKHD1 Gene Silencing May Cause Cell Abnormal Proliferation through Modulation of Intracellular Calcium in Autosomal Recessive Polycystic Kidney Disease

  • Yang, Ji-Yun;Zhang, Sizhong;Zhou, Qin;Guo, Hong;Zhang, Ke;Zheng, Rong;Xiao, Cuiying
    • BMB Reports
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    • v.40 no.4
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    • pp.467-474
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    • 2007
  • Autosomal recessive polycystic kidney disease (ARPKD) is one of the important genetic disorders in pediatric practice. Mutation of the polycystic kidney and hepatic disease gene 1 (PKHD1) was identified as the cause of ARPKD. The gene encodes a 67-exon transcript for a large protein of 4074 amino acids termed fibrocystin, but its function remains unknown. The neoplastic-like in cystic epithelial proliferation and the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) axis overactivity are known as the most important characteristics of ARPKD. Since the misregulation of $Ca^{2+}$ signaling may lead to aberrant structure and function of the collecting ducts in kidney of rat with ARPKD, present study aimed to investigate the further mechanisms of abnormal proliferation of cystic cells by inhibition of PKHD1 expression. For this, a stable PKHD1-silenced HEK-293T cell line was established. Then cell proliferation rates, intracellular $Ca^{2+}$ concentration and extracellular signal-regulated kinase 1/2 (ERK1/2) activity were assessed after treatment with EGF, a calcium channel blocker and agonist, verapamil and Bay K8644. It was found that PKHD1-silenced HEK-293T cell lines were hyperproliferative to EGF stimulation. Also PKHD1-silencing lowered the intracellular $Ca^{2+}$ and caused EGF-induced ERK1/2 overactivation in the cells. An increase of intracellular $Ca^{2+}$ in PKHD1-silenced cells repressed the EGF-dependent ERK1/2 activation and the hyperproliferative response to EGF stimulation. Thus, inhibition of PKHD1 can cause EGF-induced excessive proliferation through decreasing intracellular $Ca^{2+}$ resulting in EGF-induced ERK1/2 activation. Our results suggest that the loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in ARPKD by modulation of intracellular $Ca^{2+}$.

Association of Selected Medical Conditions With Breast Cancer Risk in Korea

  • Jung, Sun Jae;Song, Minkyo;Choi, Ji-Yeob;Song, Nan;Park, Sue Kyung;Yoo, Keun-Young;Kang, Daehee
    • Journal of Preventive Medicine and Public Health
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    • v.46 no.6
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    • pp.346-352
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    • 2013
  • Objectives: To estimate the effect of medical conditions in the population of Korea on breast cancer risk in a case-control study. Methods: The cases were 3242 women with incident, histologically confirmed breast cancer in two major hospitals interviewed between 2001 and 2007. The controls were 1818 women each admitted to either of those two hospitals for a variety of non-neoplastic conditions. Information on each disease was obtained from a standardized questionnaire by trained personnel. Odds ratios (ORs) for each disease were derived from multiple logistic regression adjusted for age, age of menarche, pregnancy, age of first pregnancy, and family history of breast cancer. Results: Among all of the incident breast cancer patients, pre-existing diabetes (OR, 1.33; 95% confidence interval [CI], 0.99 to 1.78), hypertension (OR, 1.46; 95% CI, 1.18 to 1.83), thyroid diseases (OR, 1.26; 95% CI, 1.00 to 1.58), and ovarian diseases (OR, 1.70; 95% CI, 1.23 to 2.35) were associated with an increased risk of breast cancer when other factors were adjusted for. In a stratified analysis by menopausal status, pre-existing hypertension (pre-menopause OR, 0.80; 95% CI, 0.48 to 1.34 vs. post-menopause OR, 1.87; 95% CI, 1.44 to 2.43; p-heterogeneity <0.01) and ovarian disease (pre-menopause OR, 4.20; 95% CI, 1.91 to 9.24 vs. post-menopause OR, 1.39; 95% CI, 1.02 to 1.91; p-heterogeneity 0.01) showed significantly different risks of breast cancer. Conclusions: Our results suggest the possibility that medical conditions such as hypertension affect breast cancer development, and that this can differ by menopausal status. Our study also indicates a possible correlation between ovarian diseases and breast cancer risk.