Journal of Pathology and Translational Medicine

Original Articles

Paricalcitol prevents MAPK pathway activation and inflammation in adriamycin-induced kidney injury in rats: Amanda Lima Deluque, Lucas Ferreira de Almeida, Beatriz Magalhães Oliveira, Cláudia Silva Souza, Ana Lívia Dias Maciel, Heloísa Della Coletta Francescato, Cleonice Giovanini, Roberto Silva Costa, Terezila Machado Coimbra; J Pathol Transl Med. 2024;58(5):219-228. Published online August 27, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.12

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Background
Activation of the mitogen-activated protein kinase (MAPK) pathway induces uncontrolled cell proliferation in response to inflammatory stimuli. Adriamycin (ADR)-induced nephropathy (ADRN) in rats triggers MAPK activation and pro-inflammatory mechanisms by increasing cytokine secretion, similar to chronic kidney disease (CKD). Activation of the vitamin D receptor (VDR) plays a crucial role in suppressing the expression of inflammatory markers in the kidney and may contribute to reducing cellular proliferation. This study evaluated the effect of pre-treatment with paricalcitol on ADRN in renal inflammation mechanisms.
Methods
Male Sprague-Dawley rats were implanted with an osmotic minipump containing activated vitamin D (paricalcitol, Zemplar, 6 ng/day) or vehicle (NaCl 0.9%). Two days after implantation, ADR (Fauldoxo, 3.5 mg/kg) or vehicle (NaCl 0.9%) was injected. The rats were divided into four experimental groups: control, n = 6; paricalcitol, n = 6; ADR, n = 7 and, ADR + paricalcitol, n = 7.
Results
VDR activation was demonstrated by increased CYP24A1 in renal tissue. Paricalcitol prevented macrophage infiltration in the glomeruli, cortex, and outer medulla, prevented secretion of tumor necrosis factor-α, and interleukin-1β, increased arginase I and decreased arginase II tissue expressions, effects associated with attenuation of MAPK pathways, increased zonula occludens-1, and reduced cell proliferation associated with proliferating cell nuclear antigen expression. Paricalcitol treatment decreased the stromal cell-derived factor 1α/chemokine C-X-C receptor type 4/β-catenin pathway.
Conclusions
Paricalcitol plays a renoprotective role by modulating renal inflammation and cell proliferation. These results highlight potential targets for treating CKD.

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Perirenal fat differs in patients with chronic kidney disease receiving different vitamin D-based treatments: a preliminary study
Ana Checa-Ros, Antonella Locascio, Owahabanun-Joshua Okojie, Pablo Abellán-Galiana, Luis D’Marco
BMC Nephrology.2025;[Epub] CrossRef

The importance of histomorphological features and ERG expression in the diagnosis of malignancy in cases with atypical small acinar proliferation: Gizem Teoman, Ayten Livaoglu, Hatice Kucuk, Afs ¸ın Rahman Murtezaoglu; J Pathol Transl Med. 2024;58(3):134-140. Published online May 14, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.18

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Abstract PDF: Background
Atypical small acinar proliferation (ASAP) cases typically require rebiopsy, which are invasive and associated with increased risk of complications. Our aim in this study was to determine the importance of laboratory and histological findings and E-26 transformation-specific-related gene (ERG) expression in the diagnosis of malignancy.
Methods
Between March 2016 and March 2022, 84 patients who were diagnosed with ASAP on biopsy or rebiopsy were included in the study. Clinical-laboratory features of age, serum prostate-specific antigen level, and histopathological features were compared and included multifocality, number of suspicious acini, nuclear enlargement, nucleolar prominence, hyperchromasia, cytoplasmic amphophilia, luminal amorphous acellular secretion, crystalloid presence, infiltrative appearance, inflammation, atrophy, α-methyl acyl-CoA racemase, p63, and/or high molecular weight cytokeratin were analyzed. In addition, ERG expression was evaluated immunohistochemically.
Results
Statistically significant correlation was found between nucleolar prominence, nuclear hyperchromasia, crystalloid presence, infiltrative pattern, and prostate cancer (p < .001). In 19 of 84 cases (22.6%) ERG was positive in the nucleus. Prostate cancer was diagnosed at rebiopsy in 15 of the 19 ERG-positive cases (78.9%). A statistically significant correlation was found between ERG positivity and prostate cancer (p= .002).
Conclusions
Our findings suggest that evaluation of these markers during initial transrectal ultrasound biopsies may decrease and prevent unnecessary prostate rebiopsy.

HDAC1 Expression in Invasive Ductal Carcinoma of the Breast and Its Value as a Good Prognostic Factor: Minseob Eom, Sung Soo Oh, Sayamaa Lkhagvadorj, Airi Han, Kwang Hwa Park; Korean J Pathol. 2012;46(4):311-317. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.311

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Abstract PDF

Background

Histone deacetylase 1 (HDAC1) is associated with the expression and function of estrogen receptors and the proliferation of tumor cells, and has been considered a very important factor in breast tumor progression and prognosis. Several studies have reported an association between HDAC1 expression and poorer prognosis in cancers including breast cancer, with a few exceptions. However, because of the dearth of studies on HDAC1 expression in breast cancer, its significance for breast cancer prognosis has not been well defined. Therefore, we examined HDAC1 expression in invasive ductal carcinoma (IDC), the most common breast cancer, and investigated its potential prognostic significance.

Methods

We used 203 IDC tissue samples. Immunohistochemical stains for HDAC1 and real-time polymerase chain reaction for HDAC1 mRNA were performed and the results were compared to generally well-established prognostic factors in breast cancer and patient survival rates.

Results

HDAC1 expression was significantly reduced in proportion to higher histologic grade, higher nuclear pleomorphism score, and higher mitotic counts, and with lower estrogen receptor expression. Furthermore, it was significantly associated with the survival rate.

Conclusions

HDAC1 expression is a good prognostic indicator in IDC.

Citations

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SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46‐mediated HDAC1 degradation
Zihan Zhang, Xiaoping Liu, Lei Li, Yang Yang, Jianguo Yang, Yue Wang, Jiajing Wu, Xiaodi Wu, Lin Shan, Fei Pei, Jianying Liu, Shu Wang, Wei Li, Luyang Sun, Jing Liang, Yongfeng Shang
The EMBO Journal.2021;[Epub] CrossRef
The Impact of Androgen Receptor and Histone Deacetylase 1 Expression on the Prognosis of Ductal Carcinoma In Situ
Choong Man Lee, Il Yong Chung, Yangsoon Park, Keong Won Yun, Hwi Gyeong Jo, Hye Jin Park, Hee Jin Lee, Sae Byul Lee, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn, Jisun Kim
Journal of Breast Cancer.2020; 23(6): 610. CrossRef
Prognostic and clinical significance of histone deacetylase 1 expression in breast cancer: A meta-analysis
Weiqiang Qiao, Heyang Liu, Ruidong Liu, Qipeng Liu, Ting Zhang, Wanying Guo, Peng Li, Miao Deng
Clinica Chimica Acta.2018; 483: 209. CrossRef
HDAC1 triggers the proliferation and migration of breast cancer cells via upregulation of interleukin-8
Zhaohui Tang, Sijuan Ding, Honglin Huang, Pengfei Luo, Bohua Qing, Siyuan Zhang, Ruoting Tang
Biological Chemistry.2017; 398(12): 1347. CrossRef
Identification of novel histone deacetylase 1 inhibitors by combined pharmacophore modeling, 3D-QSAR analysis, in silico screening and Density Functional Theory (DFT) approaches
Sanjay K. Choubey, Richard Mariadasse, Santhosh Rajendran, Jeyakanthan Jeyaraman
Journal of Molecular Structure.2016; 1125: 391. CrossRef
The Potential of Histone Deacetylase Inhibitors in Breast Cancer Therapy
Namita Chatterjee, Martin Tenniswood
Breast Cancer Management.2015; 4(2): 85. CrossRef

Expression of Survivin in Gastric Carcinoma and its Relation to Tumor Cell Proliferation and Apoptosis.: Wan Sik Lee, Sung Bum Cho, Jong Sun Rew, Jae Hyuk Lee, Chang Soo Park, Young Eun Joo; Korean J Pathol. 2009;43(4):329-334.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.329

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Abstract PDF

BACKGROUND
Survivin, a novel antiapoptotic gene has been linked with tumor development and progression in various human carcinomas including gastric carcinomas. The aim of this study was to evaluate the expression of survivin in gastric carcinoma and its correlation with tumor cell proliferation and apoptosis. METHODS: Expression of survivin was evaluated immunohistochemically in 84 surgically resected gastric carcinomas. Tumor cell apoptosis was evaluated with terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), and Ki-67 immunostaining was used for evaluation of tumor cell proliferation. RESULTS: Expression of survivin was noted in 53.6% of the gastric carcinomas, and was significantly associated with depth of invasion, status of lymph node metastasis or tumor stage (p=0.022, 0.034, 0.040, respectively). There was an inverse correlation between survivin expression and apoptotic index (p=0.015). But there was no significant correlation between survivin expression and Ki-67 labeling index (p=0.430). CONCLUSIONS: These results suggest that survivin expression may contribute to tumor development and progression by inhibiting apoptosis in human gastric carcinoma.

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Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression
SOO-AH KIM, RAN HONG
Oncology Letters.2014; 7(5): 1589. CrossRef

Case Reports

Giant Cell Tumor-like Proliferation Associated with Renal Staghorn Calculi: A Case Report.: Han Seong Kim, Mee Joo, Sun Hee Chang, Ji Eun Kwak, Sang Hwa Shim, Sung Yong Cho; Korean J Pathol. 2009;43(2):182-184.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.182

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Abstract PDF

A 62-year-old man with left flank pain and hematuria was shown to have a staghorn stone in left renal pelvis. Grossly, renal pelvis and calyces were markedly dilated with cystic and hemorrhagic degeneration and renal parenchyma was atrophied. A tumor-like mass was located in a hemorrhagic cyst of the renal upper pole. This mass consisted of giant cells and stromal cells mimicking a giant cell tumor of bone. This giant cell tumor-like proliferation may represent a response to hemorrhage into a cystic cavity. Recognition of this finding is important to avoid the over-diagnosis of neoplastic lesions.

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Imaged guided surgery during arteriovenous malformation of gastrointestinal stromal tumor using hyperspectral and indocyanine green visualization techniques: A case report
Tristan Wagner, Onur Mustafov, Marielle Hummels, Anders Grabenkamp, Michael N Thomas, Lars Mortimer Schiffmann, Christiane J Bruns, Dirk L Stippel, Roger Wahba
World Journal of Clinical Cases.2023; 11(23): 5530. CrossRef

Bizarre Parosteal Osteochondromatous Proliferation: A report of five cases.: Bohng Hee Kim, Yong Koo Park, Youn Wha Kim, Moon Ho Yang; Korean J Pathol. 1996;30(8):733-738.

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Abstract PDF: Bizarre parosteal osteochondromatous proliferation was first described in 1983, when Nora and his collegues reported 35 examples of a proliferative lesion involving bones of the hands and the feet. In 1993, Meneses reported 65 cases of this condition. A fourth of all the reported cases involved the long bones. It is important to identify the clinical, roentgenographic, and histologic characteristic to seperate it from other entities because it is a benign lesion with atypical microscopic features with a tendency to recur. Roentgenograms show a calcific mass attached to the underlying cortex having a broad base. Histologically, the lesion exhibites proliferative activity, irregular bony cartilaginous interfaces, and enlarged, bizarre, and binucleated chondrocytes. We reviewed the bone tumors, diagnosed in the KyungHee University Hospital, dated from 1984 to 1994. Five cases were revised to Nora's lesion, all of which were previously diagnosed as osteochondroma. The ages of the patients ranged from 12 to 57 years (median, 19 years), and all of them were males. Two cases involved the bones of hands and feet (metacarpal and talus), and 3 cases involved the long bones (humerus, fibula, and ulna). One lesion involving the humerus has a recurrence. No metastasis had been reported.

Clear Cell Meningioma.: Hee Jeung Cha, Soo Kee Min, Joon Mee Kim, Young Chae Chu; Korean J Pathol. 1997;31(8):782-787.

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Abstract PDF: Clear cell meningioma is a recently recognized morphologically unique entity. It shows no sex predilection, affects primarily the lumbar region, and the cerebellopontine angle. Despite its benign appearance, it may be aggressive, particularly in intracranial cases. All lesions are moderately cellular, with the exception of stromal hyalinization. The tumor consists largely of a sheet- like or somewhat lobular pattern of polygonal cells, the cytoplasm of which is clear. No close association is noted between the recurrence or the clinical outcome and factors such as mitotic activity, the PCNA index, and the DNA ploidy status. But the MIB-1 proliferation index is appreciably higher in recurrent tumors. We experienced a case of clear-cell meningioma showing a characteristic histologic finding. A 39-year-old man was admitted due to the recent onset of right-sided, facial-nerve palsy, left hemiparesis and general weakness. A CT scan of the head showed a well defined mass in the petroclival area. After surgical resection, the patient was in good condition, but 1 year later symptoms recurred. A CT scan of the head showed a huge, recurrent petroclival tumor with adhesion to the surrounding brain parenchyme.

Original Articles

Characteristics of the Immortalized Human B-cells by Epstein-Barr Virus.: Ho Jong Jeon, Bong Nam Choi, Yoon Kyeong Oh; Korean J Pathol. 1997;31(9):832-846.

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Abstract PDF: Human lymphoblastoid B-cell lines immortalized by Epstein-Barr virus (EBV) were established from peripheral blood of patients with acute myeloblastic and chronic lymphocytic leukemia and chronic fatigue syndrome. The sera of patients with acute myeloblastic and chronic lymphocytic leukemia did not show antibodies to Epstein-Barr viral capsid antigen (VCA), but serum of a patient with chronic fatigue syndrome disclosed antibodies to VCA (IgG, IgM), and EBNA was demonstrated in peripheral blood mononuclear cells by polymerase chain reaction. The established cell lines were mature B-cell phenotypes with polyclonal proliferation in early passage and no evidence for commitment to other lineages. The immortalized cells by EBV were designated as CSUP-1 and CSUP-2 (from acute myeloblastic leukemia, FAB classification M2 and M1), CSUP-3 (from chronic lymphocytic leukemia) and CSUP-4 (from a patient with chronic fatigue syndrome). The CSUP-1, 2, 3, and 4 grew in suspension forming clumps with a doubling time of 38 to 49 hours. Colony formation was not recognized in plate. By light and electron microscopic examination, the immortalized cells showed features of lymphoblastoid to plasmacytoid lymphocytes, and multinucleated giant cells. The lymphoblastoid cells showed scanty cytoplasm with poorly developed organelles. Immunophenotypic analyses of CUSP-1, 2, 3, and 4 with monoclonal antibodies by flow cytometry showed B-cell phenotype with polyclonal proliferation in early passage. Epstein-Barr virus nuclear antigen was confirmed in the extracted DNAs from immortalized cells by polymerase chain reaction. DNA analysis showed a normodiploid stemline with a DNA index of 1.12. The established cells were strongly reactive for CD10, CD30 (Ki-1) in early passage, and bcl-2 and c-myc onco-protein in early and late passage. Karyotypic analysis of CSUP-1, 2, 3 and 4 showed 46, XY or 46, XX. No tumorigenesis in heterotransplanted SCID mouse was recognized. This immortalized cells by EBV should be a valuable cell lines to study the pathogenesis of EBV-related malignant lymphoma.

The Relation between Cell Proliferation and Apoptosis According to the Histologic Types in Chemically Induced Rat Mammary Tumorigenesis.: Tae Jung Jang, Woo Hee Jung, Kwang Gil Lee; Korean J Pathol. 1998;32(3):174-185.

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Abstract PDF: Balancing the rates of cell proliferation and cell death is important in maintaining normal tissue homeostasis. The relationship among apoptosis, cell proliferation and factors influencing apoptosis according to the histologic types in chemically induced mammary tumorigenesis appears important in understanding the pathogenesis of breast carcinoma. In this study, we investigated alterations in the kinetics of cell proliferation and apoptosis during rat mammary tumorigenesis induced by 7, 12-dimethylbenzanthracene (DMBA) and we related these changes to the expressions of bcl-2, p53, and TGF-beta. Seven-week-old female Sprague-Dawley rats were divided into an experimental group (20 mg/ml DMBA by oral intubation) and a control group. The results were as follows. 1. In the experimental group, breast tumors occurred in twenty two of fifty nine rats(37.3%, 22/59), and the total number of tumors was 100 (4.5 2.0/rat). The histological classification was infiltrating ductal carcinomas (n=5), ductal carcinomas with focal invasion (n=10), intraductal carcinomas (n=36), adenomas accompanied with intraductal proliferation (n=35), intraductal proliferation (n=9), and adenomas (n=5); 2. The differentiation of terminal end bud into alveolar bud (AB) in the experimental group was significantly lower than that of the control group (p<0.05); 3. BrdU labeled tumor cells were mainly located at the peripheral portion of tumor cell nests. BrdU labeling indices were highest in ductal carcinomas, less pronounced in intraductal proliferation, and lowest in adenomas, whereas apoptosis levels were highest in adenomas, less pronounced in intraductal proliferation, and lowest in ductal carcinomas (p<0.05); 4. p53 protein was not expressed in any breast tumors. Although the expression of bcl-2 protein was highest in infiltrating and focal infiltrative ductal carcinomas (58.3%), compared with adenomas, intraductal proliferation, and intraductal carcinomas (p<0.05), the extent of its expression was less than 1% of all tumor cells; 5. TGF-beta was mainly expressed in the central portion of tumor cell nests rather than in peripheral portion, and TGF-beta immunoreactive tumor cells displayed good differentiation and did not reveal BrdU immunoreactivity. TGF-beta labeling index of infiltrating and focal infiltrative ductal carcinomas was significantly higher than that of intraductal carcinomas, intraductal proliferation, and adenomas (p<0.05). Based on these results, it is thought that high cell proliferation and the suppression of apoptosis are closely associated with DMBA-induced rat mammary carcinogenesis. However, the suppression of apoptosis is not related to p53 mutation, bcl-2, and TGF-beta. TGF-beta seems to be reversely related to tumor cell proliferation but closely associated with the progression of the tumor, especially an invasion of breast carcinomas.

The Role of Cell Proliferation and Apoptosis in the Cardiac Development.: Eo Jin Kim, Hyo Soo Kim, Jeong Wook Seo; Korean J Pathol. 1998;32(12):1049-1057.

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Abstract: The functional and morphologic cardiac developments are determined by the morphogenesis, growth and remodeling of the heart resulted from the cell proliferation and apoptosis. We studied the distribution of the proliferation and apoptotic activity of myocardial cells according to the developmental stages in embryos of C57bl/6 mice. Serial histologic sections were stained with PCNA and TUNEL method and were analyzed with image analyzer (BMI, Seoul). The ventricular myocardium of an embryonic heart could be divided into trabecular, inner compact and outer compact layers. Proliferation indices at layers of the left ventricular myocardium on embryonal days (ED) 13, 14, 16, 17 and 18 were 19.9%/47.4%/60.4%, 16.1%/45.8%/60.3%, 24.6%/45.6%/38.1%, 23.3%/17.7%/18.3% and 31.2%/28.0%/19.4% (trabecular/ inner compact/ outer compact) and the right ventricle, 11.0%/34.4%/60.5%, 23.0%/44.0%/69.0%, 29.2%/42.9%/35.1%, 30.4%/30.5%/22.3% and 32.4%/28.4%/16.3%. The apoptotic indices of the left ventricle/VIF were 0.23%/3.66% on ED 13-14, 0.42%/1.31% on ED 16 and 0.05%/0.60% on ED 17-18. The results show that the proliferation of the myocytes was maximal at the outer compact layer on ED 13 and 14 but lowest on ED 17 and 18. This decrease was more pronounced at the left ventricle. The innermost trabecular layer showed a constant proliferation activity of 11.0-32.4%. The presence of spatiotemporal differences in the cell proliferation reveals regional regulation in the developmental timing of cardiac development. Functional maturation is considered to be responsible for the change of proliferation activity. The apoptosis was most frequent and intense in the VIF and crux throughout the periods of each embryonal day where as rarely seen in the ventricular myocardium, especially in the trabecular layer of myocardium. These findings suggest that the apoptosis plays the role in the development of atrioventricular, ventriculoarterial septation and valve formation. Our results also reveal that the participation of apoptosis in formation of the trabeculation can be denied.

Detection Rate of Helicobacter Pylori in Gastric Adenocarcinoma and Effect of Helicobacter Pylori Infection on Proliferative Activity of Gastric Epithelium.: Young Lyun Oh, Geung Hwan Ahn; Korean J Pathol. 1999;33(8):581-588.

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Abstract PDF: Helicobacter pylori infection has been shown to be associated with gastric carcinoma. However, despite the frequent detection of seropositivity for H. pylori and histologic detection in biopsy specimen, histologic detection rate of H. pylori in surgical specimens has been low. In this study, we investigated the prevalence of H. pylori infection in gastrectomy specimens bearing gastric adenocarcinoma and compared it with both endoscopic biopsy and serologic results. H. pylori infection was identified by Giemsa stain in the mucosa stripped from the tumor, body, and antrum in 61 gastrectomy specimens. We evaluated the effect of H. pylori infection on gastric mucosal cell proliferation by using monoclonal antibody for Ki-67. H. pylori detection rate using Giemsa stain was higher in gastrectomy specimens (67.3%) compared to that (48.1%) of biopsy specimens (p=0.006). The detection rate was higher in body than that of antrum or tumor site in the same patients (p=0.001). The H. pylori seropositivity was 60.5% and relatively nonspecific. The mean value of Ki-67 labeling index in the H. pylori-positive group was higher than that in the H. pylori-negative group (p<0.05). The increase in gastric epithelial cell proliferation was not influenced by the location of the tumor or the site of the specimen. The results suggest that the actual prevalence of H. pylori infection in patients with gastric carcinoma is considerably higher than that evaluated on endoscopic biopsy specimens. In addition, the increased cell proliferation in the H. pylori-positive group suggests some evidence that H. pylori may be involved in gastric carcinogenesis.

Epidermal Growth Factor Receptor Expression and Cell Proliferation in Renal Cell Carcinoma.: Ji Shin Lee, Jong Jae Jung, Min Cheol Lee, Chang Soo Park; Korean J Pathol. 2000;34(4):273-279.

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Abstract PDF: The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is a possible cause of increased tumor cell proliferation and has recently been proposed as a prognostic parameter in some tumors. Expression of EGFR was studied immunohistochemically in 62 cases of human renal cell carcinomas to evaluate their possible prognostic roles. We also examined the correlation between EGFR expression and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). Fifty-six cases (90.3%) expressed EGFR, with staining largely confined to the cell membrane and cytoplasm. Staining intensity of EGFR was directly correlated with nuclear grade (p=0.000) and TNM stage (p=0.015). PCNA index was significantly higher in EGFR-positive tumors than in EGFR- negative tumors. There was a statistically significant positive correlation between PCNA index and increasing staining intensity of EGFR (p=0.000). In univariate survival analysis, EGFR expression was significantly associated with shortened survival. However, EGFR expression was not an independent prognostic factor by multivariate analysis. These findings suggest that EGFR expression may be an important cause of tumor cell proliferation in renal cell carcinoma and further studies are needed to evaluate whether EGFR expression analysis provides independent prognostic information.

Study on the Function of NAG-1 in Hepatocellular and Gastric Carcinoma Cells.: Tae Jung Jang; Korean J Pathol. 2007;41(4):244-251.

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Abstract PDF: BACKGROUND
Nonsteroidal anti-inflammatory drug activated gene (NAG-1) has proapoptotic activities in the colon and also in gastric cancer cells that lack any endogenous COX-2 expression. Recent studies have suggested that the proa- poptotic activity of NAG-1 is cell type specific. I investigated the cell proliferation, invasiveness and apoptosis in Hep3B cells and SNU719 cells by determining the different expression levels of NAG-1. In addition, I examined the gene profile in the Hep3B cells that have a stable expression of NAG-1.
METHODS
SNU719 cells and several clones of Hep3B cells with a stable expression of NAG-1 were used. I reduced the expression level of NAG-1 via the RNAi method. An Agilent Human 22k microarray was used for studying the gene profile in Hep3B cells that had a stable expression of NAG-1.
RESULTS
The expression level of NAG-1 did not influence apoptosis, cell proliferation and invasiveness in Hep3B cells. There was no correlation between the reduction of the endogenous NAG-1 expression and cell proliferation, including invasiveness, in the SNU719 cells. However, a knocked-down NAG-1 expression protected against apoptosis in the SNU719 cells. The microarray analysis results showed that 0.25% (58/22,575) of the genes were induced or repressed more than three fold in the Hep3B cells that had a stable expression of NAG-1.
CONCLUSIONS
Proapoptotic activity of NAG-1 is found in gastric cancer cells, but not in hepatocellular cancer cells.

Expression of Survivin in Non-Small Cell Lung Carcinoma: Relationship to Tumor Biology and Prognosis in Surgically Treated Patients.: Min Jung Jung, Bong Kwon Chun; Korean J Pathol. 2005;39(3):151-157.

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Abstract PDF: BACKGROUND
Survivin, a novel member of inhibitor-of-apoptosis, is undetectable in most terminally differentiated nonproliferative adult tissue, but is overexpressed in some human malignancies. The survivin gene expression is repressed by binding of wild-type p53 with the survivin promotor. In this study, we investigated the prevalence of survivin expression, its association with p53 overexpression and proliferative index, and clinicopathological significance in non-small cell lung carcinomas (NSCLC).
METHODS
Immunohistochemical stainings were performed in 59 cases of primary NSCLC for survivin, p53 and Ki-67. Correlations between the survivin expression, p53 overexpression and Ki-67 labeling index were analyzed.
RESULTS
Survivin expression was detected in 47 carcinomas (80%) with nuclear immunoreactivity (56%). Survivin nuclear immunoreactivity revealed significantly worse prognosis in NSCLC patients (p=0.003), and correlated with lymph node metastasis (p=0.014), lymphovascular invasion (p=0.032), p53 overexpression, and Ki-67 labeling index (KI 24.2 +/- 6.9, p=0.045). Survivin expression was not correlated with histological type and pT status.
CONCLUSIONS
High incidence of survivin overexpression in NSCLC suggests that survivin is involved in lung carcinogenesis, and nuclear expression of survivin can be used as a poor prognostic predictor in NSCLC patients. Expression of mutant p53 seems to be a possible mechanism of survivin up-regulation in NSCLC.

Histologic and Immunohistochemical Study of Cutaneous Vascular Disorders.: Jai Hyang Go, Hoon Jin, Dong Hwan Shin, Kwang Gil Lee; Korean J Pathol. 1995;29(3):327-333.

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Abstract PDF: There is a wide array of designation for cutaneous vascular disorders based on clinical characteristics, histology, embryology, cellular biology, and hemodynamics. The cutaneous vascular disorders can be divided into hemangioma and vascular malformation according to the biologic classification based on cell kinetics i.e. endothelial hyperplasia. There are clinical and histologic differences between them. In this study, clinical, histologic and im-munohistochemical evaluations were attempted on 40 cases of cutaneous vascular disorders diagnosed the period between 1985 and 1993. The results are as follows: 1) Twenty-three out of forty cases were immunoreacive for proliferating cell nuclear antigen(PCNA). The lesions composed of capillary-sized blood vessels with endothelial hyperplasia were diffusely reactive, whereas those composed largely of dilated blood vessels with or without focal endothelial hyperplasia were only focally reactive. 2) Each groups of the classic classification contained both reactive and nonreactive cases except nevus flammeus and juvenfle hemangioma. 3) In contrast to the cases nonreactive for PCNA, those reactive for PCNA contained areas of proliferating small vessels, which showed reactivity for PCNA. In conclusion, the cutaneous vascular disorders diagnosed by the classic classification are heterogeneous in the pattern of the endothelial hyperplasia and the PCNA staining. Therefore it should be classified by the clinical and the histologic characteristics.

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