• Title/Summary/Keyword: Epithelial differentiation

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Diagnostic Usefulness and Limitation of Fine Needle Aspiration Cytology of Lymph Node - Analysis of 176 Cases Confirmed by Biopsy - (림프절 세침흡인 세포검사의 진단적 유용성과 한계 - 생검으로 확진한 176 예의 분석 -)

  • Kim, Hee-Sung;Kim, Dae-Soo;Oh, Young-Lyun;Ko, Young-Hyeh;Ree, Howe-J.
    • The Korean Journal of Cytopathology
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    • v.10 no.1
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    • pp.35-42
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    • 1999
  • The accuracy of fine needle aspiration cytology(FNAC) of the lymph node was investigated through a review of 176 FNAC cases and the corresponding biopsies. We chose 157 FNAC cases after the exclusion of 19 inadequate ones. Sensitivity of malignancy was 94.0%, specificity 100%, false negativity 6.0%, and false positivity 0.0%. The overall diagnostic accuracy was 96.8%. Sensitivity of metastatic carcinoma was 98.0% and that of malignant lymphoma was 87.9%. False negative cases included one metastatic carcinoma and four malignant lymphomas. The aspirates of metastatic carcinoma with false negativity exhibited a diffuse smear of keratin debris without viable cells, which led to the difficulty in differentiation from benign epithelial cyst. The cases of malignant lymphoma with false negative diagnosis were two Hodgkin diseases, one Lennert's lymphoma, and one peripheral T cell lymphoma in the histologic sections. On the analysis of 39 cases of tuberculosis, 17 cases(43.6%) were diagnosed as tuberculosis, 4(10.3%) as granulomatous lymphadenitis, 3(7.7%) as necrotizing lymphadenitis, and 15(38.5%) as reactive hyperplasia or pyogenic inflammation. Sensitivity of tuberculosis was 53.9%. In conclusion, lymph node FNAC is an excellent non-invasive diagnostic tool for the diagnosis of metastatic carcinoma. The diagnostic accuracy of malignant lymphoma could be improved with flow cytometry or polymerase chain reaction for antigen receptor genes. For the FNAC diagnosis of tuberculosis, AFB stain, culture, and PCR would be helpful as adjuvant techniques.

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Hypermethylation of Promoter Region of LATS1 - a CDK Interacting Protein in Oral Squamous Cell Carcinomas - a Pilot Study in India

  • Reddy, Vijaya Ramakrishna;Annamalai, Thangavelu;Narayanan, Vivek;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1599-1603
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    • 2015
  • Background: Epigenetic silencing of tumor suppressor genes due to promoter hypermethylation is one of the frequent mechanisms observed in cancers. Hypermethylation of several tumor suppressor genes involved in cell cycle regulation has been reported in many types of tumors including oral squamous cell carcinomas. LATS1 (Large Tumor Suppressor, isoform 1) is a novel tumor suppressor gene that regulates cell cycle progression by forming complexes with the cyclin dependent kinase, CDK1. Promoter hypermethylation of the LATS1 gene has been observed in several carcinomas and also has been linked with prognosis. However, the methylation status of LATS1 in oral squamous cell carcinomas is not known. As oral cancer is one of the most prevalent forms of cancer in India, the present study was designed to investigate the methylation status of LATS1 promoter and associate it with histopathological findings in order to determine any associations of the genetic status with stage of differentiation. Materials and Methods: Tumor chromosomal DNA isolated from biopsy tissues of thirteen oral squamous cell carcinoma biopsy tissues were subjected to digestion with methylation sensitive HpaII enzyme followed by amplification with primers flanking CCGG motifs in promoter region of LATS1 gene. The PCR amplicons were subsequently subjected to agarose gel electrophoresis along with undigested amplification control. Results: HpaII enzyme based methylation sensitive PCR identified LATS1 promoter hypermethylation in seven out of thirteen oral squamous cell carcinoma samples. Conclusions: The identification of LATS1 promoter hypermethylation in seven oral squamous cell carcinoma samples (54%), which included one sample with epithelial dysplasia, two early invasive and one moderately differentiated lesions indicates that the hypermethylation of this gene may be one of the early event during carcinogenesis. To the best of our knowledge, this is the first study to have explored and identified positive association between LATS1 promoter hypermethylation with histopathological features in oral squamous cell carcinomas.

EXPRESSION OF CARTILAGE DERIVED MORPHOGENIC PROTEIN IN PLEOMORPHIC ADENOMA (다형성선종에서 연골유래형성단백의 발현)

  • Lee, Hwang-Jae;Kim, Chul-Hwan;Kim, Kyung-Wook
    • 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.

THE EFFECTS OF IRRADIATION AND CALCIUM-DEFICIENT DIET ON DENTIN AND CEMENTUM FORMATION OF RAT MOLAR (방사선조사와 저칼슘식이가 백서구치의 상아질과 백악질형성에 미치는 영향에 관한 실험적 연구)

  • Shin Jae-Chang;Hwang Eui-Hwan;Lee Sang-Rae
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.28 no.1
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    • pp.87-109
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    • 1998
  • The present study was designed to elucidate the effects of the Co-60 γ irradiation and/or calcium­deficient diet on the dentin and cementum formation of rat molar. The pregnant three-week old Sprague­Dawley rats were used for the study. The experimental group was divided into two groups, irradiation/normal diet group and irradiation/calcium-deficient diet group. The control group was non­irradiation/normal diet group. The abdomen of the rats at the 19th day of pregnancy were irradiated with single absorbed dose of 350cGy. The rat pups were sacrificed on the 14th day after delivery and the maxillae including molar tooth germ were taken. The specimens including the 1st molar tooth germ were prepared to make tissue sections for light and transmission electron microscopy. Some of tissue sections for light microscopy were stained immunohistochemically with anti-fibronectin antibody. The results were as follows; 1. The Hertwig's epithelial root sheath cells, which are related to the differentiation of the tooth-forming cells, showed irregular cellular arrangement, decrease of intercellular junctional complex, and decreased immunoreactivity to the fibronectin after irradiation. These were more severe in the irradiation/calcium-deficient diet group. 2. The cementoblasts at the cementum-forming area showed chromatin clumpings after irradiation. The immu noreactivity to the fibronectin was weaken after irradiation, especially irradiation/calcium-deficient diet group. 3. The odontoblasts at the dentin-forming area showed increase of lysosomes in the cytoplasm and destruction of intercellular junctional complex. The irradiation/calcium-deficient diet group showed decrease of number and density of the electron dense particles and a large number of vacuoles scattered in the dentin matrix. The immunoreactivity was weaken.

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Chondroid Syringomas arising on the Nasal Dorsum and the Upper Lip: Two Cases of Report (비배부와 상구순에 발생한 연골모양 땀샘종 2례)

  • Kim, Eui Sik;Cho, Sung Hoo;Yoo, Sung In;Noh, Bok Kyun;Hwang, Jae Ha;Kim, Kwang Seog;Lee, Sam Yong;Choi, Yoo Duck
    • Archives of Plastic Surgery
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    • v.34 no.4
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    • pp.504-507
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    • 2007
  • Purpose: Chondroid syringoma, previously known as 'mixed tumor of the skin', is a rare benign tumor. It usually presents an asymptomatic solitary firm intradermal or subcutaneous slowly growing nodule. It occurs frequently in the head and neck region of middle-aged men. We would like to report an uncommon chondroid syringoma about the clinical and histologic presentation. about the clinical and histologic presentation. Methods: We experienced two cases of chondroid syringoma on the nose and the upper lip, each other. Both masses were totally excised with clear margin. Results: On histologic examination, the masses showed a biphasic pattern-an epithelial component exhibiting apocrine/eccrine differentiation and a stromal component exhibiting myxoid/collagenous change-consistent with the diagnosis of chondroid syringoma. There have been no evidence of recurrence and malignant transformation during postoperative follow-up. Conclusion: There is no one distinctive clinical feature that is specific for chondroid syringoma. However, it should be included in the differential diagnosis of a solid nodule in head and neck region with long standing duration, such as epidermal inclusion cyst, pilomatrixoma, dermoid cyst, sebaceous cyst, neurofibroma, and basal cell carcinoma.

Itch E3 Ubiquitin Ligase Positively Regulates TGF-β Signaling to EMT via Smad7 Ubiquitination

  • Park, Su-Hyun;Jung, Eun-Ho;Kim, Geun-Young;Kim, Byung-Chul;Lim, Jae Hyang;Woo, Chang-Hoon
    • Molecules and Cells
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    • v.38 no.1
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    • pp.20-25
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    • 2015
  • TGF-${\beta}$ regulates pleiotropic cellular responses including cell growth, differentiation, migration, apoptosis, extracellular matrix production, and many other biological processes. Although non-Smad signaling pathways are being increasingly reported to play many roles in TGF-${\beta}$-mediated biological processes, Smads, especially receptor-regulated Smads (R-Smads), still play a central mediatory role in TGF-${\beta}$ signaling for epithelial-mesenchymal transition. Thus, the biological activities of R-Smads are tightly regulated at multiple points. Inhibitory Smad (I-Smad also called Smad7) acts as a critical endogenous negative feedback regulator of Smad-signaling pathways by inhibiting R-Smad phosphorylation and by inducing activated type I TGF-${\beta}$ receptor degradation. Roles played by Smad7 in health and disease are being increasingly reported, but the molecular mechanisms that regulate Smad7 are not well understood. In this study, we show that E3 ubiquitin ligase Itch acts as a positive regulator of TGF-${\beta}$ signaling and of subsequent EMT-related gene expression. Interestingly, the Itch-mediated positive regulation of TGF-${\beta}$ signaling was found to be dependent on Smad7 ubiquitination and its subsequent degradation. Further study revealed Itch acts as an E3 ubiquitin ligase for Smad7 polyubiquitination, and thus, that Itch is an important regulator of Smad7 activity and a positive regulator of TGF-${\beta}$ signaling and of TGF-${\beta}$-mediated biological processes. Accordingly, the study uncovers a novel regulatory mechanism whereby Smad7 is controlled by Itch.

Anti-inflammatory effects of Hataedock with Coptidis Rhizoma and Glycyrrhiza Uralensis on Allergic Rhinitis through Regulating IL-4 Activation (알레르기성 비염에서 황련-감초 하태독법의 IL-4활성 조절을 통한 항염증효과)

  • Jung, A Ram
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.2
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    • pp.116-122
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    • 2019
  • The aim of this study is to evaluate the anti-inflammatory effect of Hataedock treatment using Coptidis Rhizome and Glycyrrhiza Uralensis (CG) mixed extract in allergic rhinitis induced NC/Nga mice. We divided NC/Nga mice into 3 groups as follows; allergic rhinitis-induced group after CG Hataedock treatment (CGT, n=10), no treatment group (Ctrl), allergic rhinitis elicited group (ARE). To induce allergic rhinitis, NC/Nga mice of 3 weeks age were sensitized on 7, 8 and 9week by Ovalbumin (OVA) antigen in intranasal space. Hataedock using CG extract was administered on week 3 in allergic rhinitis-induced group (CGT) after Hataedock treatment. To identify distribution of Interlukin (IL)-4, Cluster of differentiation 40 (CD40), high-affinity IgE receptor ($Fc{\varepsilon}RI$), substance P, Matrix metallopeptidase 9 (MMP-9), Nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65, Inducible nitric oxide synthase (iNOS) and Cycloxygenase-2 (COX-2), we used histological examination. CGT significantly inhibited IL-4 and CD40 response compared with ARE. The reduction of Th2 cytokine expression decreased inflammatory mediators such as $Fc{\varepsilon}RI$, substance P, MMP-9, $NF-{\kappa}B$ p65, iNOS and COX-2. Such immunological improvement induced reduction of respiratory epithelial damage and mucin secretion in goblet cell. These results indicate that Hataedock treatment suppresses allergic rhinitis through modulating of Th2 responses and diminishing various inflammatory mediators in nasal mucosal tissue. It might have potential applications for prevention and treatment of allergic rhinitis.

Disruption of the Tff1 gene in mice using CRISPR/Cas9 promotes body weight reduction and gastric tumorigenesis

  • Kim, Hyejeong;Jeong, Haengdueng;Cho, Yejin;Lee, Jaehoon;Nam, Ki Taek;Lee, Han-Woong
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.257-263
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    • 2018
  • Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. Tff1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated Tff1-knockout (KO) mice, without a neomycin resistant ($Neo^R$) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our Tff1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established Tff1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that Tff1 expression influences gender differences.

New established cell lines from undifferentiated pleomorphic sarcoma for in vivo study

  • Eun-Young Lee;Young-Ho Kim;Md Abu Rayhan;Hyun Guy Kang;June Hyuk Kim;Jong Woong Park;Seog-Yun Park;So Hee Lee;Hye Jin You
    • BMB Reports
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    • v.56 no.4
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    • pp.258-264
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    • 2023
  • As a high-grade soft-tissue sarcoma (STS), undifferentiated pleomorphic sarcoma (UPS) is highly recurrent and malignant. UPS is categorized as a tumor of uncertain differentiation and has few options for treatment due to its lack of targetable genetic alterations. There are also few cell lines that provide a representative model for UPS, leading to a dearth of experimental research. Here, we established and characterized new cell lines derived from two recurrent UPS tissues. Cells were obtained from UPS tissues by mincing, followed by extraction or dissociation using enzymes and culture in a standard culture environment. Cells were maintained for several months without artificial treatment, and some cell clones were found to be tumorigenic in an immunodeficient mouse model. Interestingly, some cells formed tumors in vivo when injected after aggregation in a non-adherent culture system for 24 h. The tissues from in vivo study and tissues from patients shared common histological characteristics. Pathways related to the cell cycle, such as DNA replication, were enriched in both cell clones. Pathways related to cell-cell adhesion and cell-cell signaling were also enriched, suggesting a role of the mesenchymal-to-epithelial transition for tumorigenicity in vivo. These new UPS cell lines may facilitate research to identify therapeutic strategies for UPS.

Usefulness of p16INK4a Immunocytochemical staining for the Differentiation between Atrophy and ASCUS in Diagnosis of Uterine Cervical Cancer

  • Hye Ryoung Shin;Taekil Eom;Wan-Su Choi
    • Biomedical Science Letters
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    • v.29 no.3
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    • pp.144-151
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    • 2023
  • A Pap smear is the most important screening test for the diagnosis of cervical cancer. However, subjective judgment by the operator cannot be excluded, and replicability may greatly be reduced if uncertain specimens are examined. Examiners often experience difficulties in differentiating atrophy with inflammatory changes and ASCUS when diagnosing squamous epithelial lesions from a pap smear. Reports often vary between cytologists and pathologists, and misdiagnosis may result in delayed follow-ups and advanced diseases. Hence, auxiliary examinations are necessary when confusing results between atrophy and ASCUS are obtained. The importance of p16INK4a activation due to HPV infection, which is an important factor in the outbreak of cervical cancer, has been highlighted. Recent studies have reported that p16INK4a immunocytochemical staining and HPV high-risk type tests using liquid-based cervical specimens are effective to detect the presence of lesions of grade HSIL or higher in patients with ASC-H. However, no research exists on the utility of HPV and p16INK4a tests on the differential diagnosis of atrophy and ASCUS. This study focused on whether p16INK4a immunocytochemical staining and HPV tests can help diagnose borderline lesions between atrophy and ASCUS. The results reported that p16INK4a activation can significantly (P<0.001) differentiate atrophy from ASCUS in atrophic lesions infected with High risk-HPV. Therefore, it may be concluded that p16INK4a immunocytochemical staining is an effective auxiliary test in lesions infected with HR-HPV when atrophic lesions are difficult to differentiate by morphology. Such results are expected to help decide on adequate follow-up and treatment.