• Title/Summary/Keyword: epithelial stage

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Relationship Between Prognosis and Neutrophil: Lymphocyte and Platelet:Lymphocyte Ratios in Patients with Malignant Pleural Mesotheliomas

  • Cihan, Yasemin Benderli;Ozturk, Ahmet;Mutlu, Hasan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2061-2067
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    • 2014
  • Background: It has been demonstrated that neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios are associated with prognosis in cancer patients. The aim of this study was to investigate whether pretreatment white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, basophil and eosinophil counts, LDH level, NLR and PLR are associated with prognosis in patients with malignant pleural mesothelioma (MPM). Materials and Methods: We retrospectively reviewed files of 50 patients who were managed with a diagnosis of MPM between 2005 and 2010. Demographic and clinical characteristics, treatments, response to treatment and prognostic factors were evaluated, along with relationships between pretreatment blood parameters and prognosis. Results: Overall, 38 men and 12 women were included to the study. Mean age was $61.5{\pm}9.4$ years (range: 39-83 years). There was advanced disease in 86% (n=43) and the histological type was epithelial mesothelioma in the majority (82%). Of the cases, 17 (34%) received radiotherapy, while 42 cases underwent first- and second-line chemotherapy, with cisplatin plus pemetrexed as the most commonly used regimen. In the assessment after therapy, it was found that there was complete response in 4 cases (8%), partial response in 10 cases (20%), stable disease in 17 cases (34%) and progression in 19 cases (38%). Median follow-up was 10 months (range: 10 day-30 months). Median overall survival was found to be 20.7 months while median progression-free survival as 10 months. In univariate and multivariate analyses, it was found that factors significantly affecting overall survival included stage (p=0.030), response to treatment (p=0.026) and monocyte count (p=0.004), while factors affecting disease-free survival included NLR (p=0.018), response to treatment (p=0.001), and PLR score (p=0.003). Conclusions: Overall and disease-free survival was found to be better in cases with a WBC count<8.000, platelet count<300,000, and low NLR and PLR scores in malignant pleural mesothelioma.

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 Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

  • Alikanoglu, Arsenal Sezgin;Gunduz, Seyda;Demirpence, Ozlem;Suren, Dinc;Gunduz, Umut Riza;Sezer, Cem;Yildiz, Mustafa;Yildirim, Mustafa
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4387-4392
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    • 2015
  • Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well-known adhesion effect.

A Study on the Differentiation and Acetylcholinesterase Activity of the Developing Rat Retina (발생중인 흰쥐 망막의 분화 및 Acetylcholinesterase 활성에 관한 연구)

  • Kim, Wan-Jong;Choi, Jun-Sub
    • Applied Microscopy
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    • v.27 no.2
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    • pp.131-144
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    • 1997
  • The present study was carried out to investigate the processes of the ultrastructural differentiation and the acetylcholinesterase (AChE) activities of the developing rat retina. The results are as follows. The retina of fetal rat on the 13th day of gestation showed the early stage of differentiation. Briefly, there appeared dividing chromosomes, the plentiful free ribosomes, and the high ratio of nucleus to cytoplasm. The reaction products by AChE were localized at the membrane of endoplasmic reticulum and on the outer membrane of nucleus. Ultrastructures and AChE activities in the retina of the fetal rats on the 18th day of gestation were similar to those of the prior stages, except the appearence of rough endoplasmic reticulum and Golgi apparatus. According to the ultrastructural observations, the rat retina was still in immature state at birth, but the pigment epithelial cells were fully differentiated, e. g. the increase of melanin granules, the development of mitochondria and Golgi apparatus. The AChE activity was weekly detected. The differentiated retinal layers and the outer segment of photoreceptor cells were observed on the 7th postnatal day. And the pigment epithelium appeared to be fully differentiated. On the 14th postnatal day, rat retina were completely differentiated. In other words, the rat retina was characterized by the prominent outer segments, phagocytosed residues in the pigment epithelium, and the localization of reaction products by AChE in the synapses. In conclusion, the differentiation of rat retina is charaterized by the changes of cell shape, the increase of retinal layers, and the alterations of AChE activities. It seems that rat retina is to be functional from 2 weeks of birth onward, coinciding with the eye opening of the juvenile rats.

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Antigenic localities in the tissues of Payagonimus westermani by developmental stages using immunogoldlabeling method (면역황금표식법을 이용한 폐흡충의 발육단계별 충체조직내 항원성 부위에 관한 연구)

  • 임한종;김수진
    • Parasites, Hosts and Diseases
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    • v.30 no.1
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    • pp.1-14
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    • 1992
  • In order to observe the antigenic localization in the tissues of Paragonimus westermani of deve- lopmental stages, immunogoldlabeling method was applied using serum of the cats which were infected with isolated metacercariae from Cambaroides similis. The sectioned worm tissues from orch developmental stage were embedded in Lowicryl HM20 medium, stained with infected semi IgG and protein A gold complex(particle size: 12 nm) and observed by electron microscopy. In the young adult worm tissue of 4 weeks after infection with metacercariae, the gold particles were specifically concentrated on the tegumental syncytium and cytoplasm of the tegumental cells as well as the secretory granules in the parenchymal tissue. The antigenic materials in the adult worm tissue were specifically concentrated on the secretory granules in the parenchymal tissue, the cytoplasm between granules in the vitelline gland and the epithelial lamella in the lumen of the caecum.

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Expression of pituitary adenylate cyclase activating polypeptide in the adult rat testis by in situ hybridization and immunohistochemistry (In situ hybridization법과 면역조직화학적법을 이용한 성숙한 흰쥐고환에서의 pituitary adenylate cyclase activating polypeptide의 발현)

  • Koh, Phil-ok;Kwak, Soo-dong
    • Korean Journal of Veterinary Research
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    • v.41 no.1
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    • pp.1-6
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    • 2001
  • Pituitary adenyl ate cyclase activating polypeptide (PACAP) was originally isolated from the ovine hypothalamus and stimulated cAMP production in anterior pituitary cells. It is known that PACAP stimulates cAMP accumulation and contributes to the spermatogenesis and steroidogenesis in rat testis. The principal aim of this study is to determinate the distribution of PACAP mRNA and protein in adult rat testis. For this study, we used in situ hybridization and immunohistochemistry techniques in adult rat testis. PACAP mRNA was stage specifically expressed in seminiferous tubules. Positive signals of PACAP mRNA were detected in the developing germ cells at stages HI-VII of the epithelial cycle. The strongest signals of PACAP mRNA and protein were detected in round spermatids at stages V to early VII of the cycle. These results demonstrate that PACAP which is synthesised in the developing germ cells contributes to the spermatogenesis in rat testis. Thus, we suggest that PACAP plays a critical role in the function of testis.

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Studies on the cloning of calves by nuclear transplantation II. Efficient embryo cloning under oocyte activation, cell cycle regulation of donor nuclei and optimal culture conditions (핵이식을 이용한 복제송아지 생산에 관한 연구 II. 효율적인 복제수정란 생산을 위한 난자의 활성화, 공여핵의 세포주기조절 및 적정 배양조건)

  • Hwang, Woo-suk;Roh, Sang-ho;Lee, Byeong-chun
    • Korean Journal of Veterinary Research
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    • v.37 no.3
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    • pp.639-645
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    • 1997
  • The objectives of the present study were improvements in the efficiency of developmental rates to morula and blastocyst stages to produce a large number of genetically identical nuclear transplanted embryos. The oocytes collected from slaughterhouse ovaries were matured 24h in TCM199+10% FBS and exposed to $39^{\circ}C$ or room temperature to allow cytoplasmic maturation and gain activation competence. Donor embryos were treated for 12h with $10{\mu}g/ml$ nocodazole or $0.05{\mu}g/ml$ demicolcine to synchronize the cell cycle stage at 26h after the onset of culture. The blastomeres and recipient oocytes were fused by electrofusion. The cloned embryos were then cultured in various conditions to allow further development. In the treatment of oocyte activation and cell cycle regulation of donor nuclei, the room temperature exposure and nocodazole treatment group had significant effect on the developmental rates to morula/blastocyst(21.7% vs 12.1~16.7%), but had no significant effect on the fusion rates between donor blastomeres and recipient oocytes. The developmental rates of bovine nuclear transplanted embryos appeared to be higher significantly in mTALP medium under 5% $O_2$ condition and in TCM199 with bovine oviduct epithelial cell under 20% $O_2$ condition(22.2%) than other groups. In embryo transfer of nuclear transplanted embryos, there were no significant differences in calving rates between the use of excellent and good grade donor embryos.

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Fine Structure of the Epithelial Apoptosis in the Anuran Tadpole Rana nigromaculata (참개구리(Rana nigromaculata) 유생기 상피 세포사의 미세구조)

  • Lee, Hye-Won;Moon, Myung-Jin
    • Applied Microscopy
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    • v.40 no.2
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    • pp.81-88
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    • 2010
  • The fine structural characteristics of the apoptotic cells in the cutaneous epithelium of the anuran tadpole of the black-spotted frog, Rana nigromaculata was examined using the TUNEL (Terminal deoxynucleotidyl transferase-mediated biotinylated d-Uridine triphosphate Nick End Labeling) staining technique and TEM (transmission electron microscopy) observations. The cutaneous epithelium of the tadpole was composed of stratified cuboidal cells and the apoptotic cell death was observed continuously during the tail degeneration stages from the Shumway stage number 31 to 33. The early apoptotic cells shown in the epithelium demonstrated condensation and margination of the chromatin material at the nuclear periphery, and nuclear breakdown and cytoplasmic condensation were followed. Subsequent cytoplasmic degeneration of the apoptotic cell were produced by membrane-bounded cell fragments with relatively well preserved organelles. Following the processes of autophagic degradation, the late apoptotic cells being phagocytosed by other surrounding cells. These nearby cells, presumptive intraepithelial macrophages, contain a variety of lysosomal residual bodies which fuses with other cell organelles or other cytoplasmatic material to form secondary lysosomes. They are soon transformed into lamellar shaped vesicles and finally disappeared during the process of degradation.

THE CLINICAL STUDY ON PAROTID GLAND TUMOR (이하선 종양의 임상적 연구)

  • Shin, Sang-Hun;Heo, June;Kim, Ki-Hyen;Chung, In-Kyo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.1
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    • pp.80-84
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    • 2000
  • Tumors of the parotid gland are the most frequently encountered salivary gland tumors. Knowledge of the histology and anatomy of the salivary gland is important when considering the histiogenesis of salivary gland tumors, requiring close cooperation between the pathologist and the surgeon. Most tumors are benign epithelial formations. Pleomorphic adenomas predominate. Superficial lobectomy is adequate treatment. When the tumor involves a deep lobe, total parotidectomy is indicated. Treatment of malignant tumors depends on the histology, its TNM stage and other factors. Total parotidectomy with lymph adectomy and radiotherapy are needed in case of high grade malignancy. In children, vascular neoplasias are the most frequent, followed by malignant tumors. Their histological features and treatment are the same as for adults. We reviewed 64 cases of the parotid tumors at Department of surgery, Dong-A University Hospital from July. 1990 to Jan. 1999 for the purpose of apprehension of parotid gland tumor by the clinical study and review. Over all sex ratio was 1:1.13(M:F), mean age was 38.9 years, mean size was 3.53cm. According to histologic findings of 64 cases, pleomorphic adenoma was 55(85.9%), Warthin's tumor was 3(4.7%), mucoepidermoid carcinoma was 3(4.7%), squamous cell carcinoma was 2(3.1%), acinic cell carcinoma was 1(1,6%). Post op. facial nerve palsy 16(25%), Frey's syndrome 11(17.2%) cases were happened. Hence, the clinical manifestation of pain, tenderness, facial N. palsy suggest malignant tumors.

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Validation of Neurotensin Receptor 1 as a Therapeutic Target for Gastric Cancer

  • Akter, Hafeza;Yoon, Jung Hwan;Yoo, Young Sook;Kang, Min-Jung
    • Molecules and Cells
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    • v.41 no.6
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    • pp.591-602
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    • 2018
  • Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.