• Title/Summary/Keyword: Tumor differentiation

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Interaction of HIV-1 Core p24 Antigen with Human Monocytic Cell Line THP1 Results in TNF-${\alpha}$ Dependent Secretion of Matrix Metalloproteinase-9

  • Sung, Ji-Hye;Yoo, Seung-Hee;Park, Hae-Kyung;Chong, Young-Hae
    • The Journal of the Korean Society for Microbiology
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    • v.35 no.1
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    • pp.9-18
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    • 2000
  • Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

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Platelet Indices May be Useful in Discrimination of Benign and Malign Endometrial Lesions, and Early and Advanced Stage Endometrial Cancer

  • Kurtoglu, Emel;Kokcu, Arif;Celik, Handan;Sari, Seher;Tosun, Migraci
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5397-5400
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    • 2015
  • Background: The aim of this study was to investigate the predictive value of white blood cells (WBC), the neutrophil to lymphocyte ratio (NLR), platelet indices including mean platelet volume (MPV), platelet distribution width (PDW), platelet crit (PCT) and platelet to lymphocyte ratio (PLR) in discrimination between benign and malign endometrial lesions, and early and advanced stage endometrial adenocarcinomas. Materials and Methods: Data for 105 patients undergoing total abdominal or vaginal hysterectomy for benign uterine diseases and 114 patients surgically staged for endometrium adenocarcinoma at Ondokuz Mayis University, Department of Gynecology and Obstetrics, between 2008 and 2014, were collected. Parameters were preoperative and postoperative complete blood counts in the week prior to surgery with differentials including WBC, platelet count, platelet indices (MPV, PCT, PDW), NLR and PLR. Pathologic evaluations for both benign and malign endometrium lesions, grade of endometrium adenocarcinoma, tumor stage, presence of lymphovascular space invasion (LVI) were retrospectively analyzed. Results: Regarding definitive factors in discriminating patients with endometrium cancer from those with benign diseases, MPV was significantly increased in the malign group whereas there was a significant decrease in the PDW value compared to the benign group. The best cut-off value in differentiation of the benign and malign groups, malign cases were found to increase over the value of 7.54 for MPV, and under 37.8 for PDW. When definitive factors in discrimination of early stage endometrium cancer from advanced stage disease and LVI in the malign group were evaluated according to the ROC analysis, no significant relation was detected between blood parameters and the stage and the LVI of the disease. Conclusions: MPV and PDW may have predictive value in the discrimination of benign and malign endometrium diseases. Nevertheless, since there have been few reports on this topic, further large-scale prospective studies are necessary.

The Clinicopathological Significance of Bmi-1 Expression in Pathogenesis and Progression of Gastric Carcinomas

  • Lu, Hang;Sun, Hong-Zhi;Li, Hua;Cong, Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3437-3441
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    • 2012
  • Background: Oncogenic Bmi-1 (B-lymphoma Moloney murine leukemia virus insertion region-1) belongs to the Polycomb-group (PcG) family of proteins and plays an important role in the regulation of proliferation, senescence, cell cycle and apoptosis, chromosome stability, activation of gene transcription. Methods: To clarify the roles of Bmi-1 in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) and real-time RT-PCR in gastric carcinomas, dysplasia, intestinal metaplasia (IM), and gastritis with a comparison of its expression with clinicopathological parameters of carcinomas. Results: There was gradually increased Bmi-1 protein expression from gastritis, IM, dyplasia to carcinoma (p<0.001). Bmi-1 expression was positively linked to tumor size, depth of invasion, lymph node metastasis and worse prognosis of carcinomas (p<0.001), but not to age or sex of carcinoma patients (p>0.05). There was higher Bmi-1 protein expression in intestinal-type carcinomas than diffuse-type ones (p<0.001). At mRNA level, Bmi-1 protein expression was increased from gastritis, IM, dysplasia and carcinoma (p<0.001). Bmi-1 overexpression was observed in gastric carcinoma with larger diameter, deeper invasion, lymph node metastasis, and intestinal-type carcinoma (p<0.05). Conclusion: These findings indicate that up-regulated Bmi-1 expression is positively linked to pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviors and prognosis of gastric carcinomas.

Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

  • Lei, Yuan-Yuan;Wang, Wei-Jia;Mei, Jin-Hong;Wang, Chun-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8539-8548
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    • 2014
  • Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

Roles for Paraoxonase but not Ceruloplasmin in Peritoneal Washing Fluid in Differential Diagnosis of Gynecologic Pathologies

  • Yildirim, Mustafa;Demirpence, Ozlem;Kaya, Vildan;Suren, Dinc;Karaca, Mehmet;Evliyaoglu, Osman;Yilmaz, Necat;Gunduz, Seyda
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6233-6237
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    • 2014
  • Background: Intraperitoneal spread of gynecologic cancers is a major cause of mortality and morbidity and often presents with malignant ascites. Microscopic tumor spread can be demonstrated by a peritoneal wash cytology and help assess the prognosis of the disease. In our study, the roles of paraoxonase and ceruloplasmin, measured in peritoneal washing fluid of patients operated for gynecologic pathologies in differential diagnosis was investigated. Materials and Methods: Patients operated for malign or benign gynecologic pathologies in Antalya Education and Research Hospital Gynecology Clinic between 2010-2012 were included in the study. Samples were obtained during surgery. Results: A statistically significant difference was detected between patients with benign and malign diseases with regards to PON1 levels measured in peritoneal washing fluid (p:0.044), the average values being $64.2{\pm}30.8$ (Range 10.8-187.2) and $41.4{\pm}21.4$ (Range 10.4-95.5), respectively. No significant variation was evident for ceruloplasmin. Conclusions: Paraoxonase levels measured in peritoneal washing fluid may contribute to the differentiation of malign-benign diseases in gynecologic pathologies.

A Study on the Mechanism of Oxidative Stress, Screening of Protective Agents and Signal Transduction of Cell Differentiation in Cultured Osteoblast and Osteoclast Damaged by Reactive Oxygen Species

  • Park Seung-Taeck;Jeon Seung-Ho
    • Biomedical Science Letters
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    • v.11 no.3
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    • pp.319-326
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    • 2005
  • It is well known that oxidative stress of reactive oxygen species (ROS) may be a causative factor in the pathenogenesis of bone disorder on osteoblast or osteoclast. The purpose of this study was to evaluate the cytotoxicity of oxidative stress, protective effect of glutamate receptor antagoinst against ROS-induced osteotoxicity, secretion of tumor necrosis factor $(TNF)-\alpha$ and the expression of c-fos gene in the cultured rat osteoblasts and osteoclasts. Cell viability by MTS assay or !NT assay, activity of glutathione peroxidase (GPx), lipid peroxidation (LPO) activity, protein synthesis by sulforhodamine B (SRB) assay, alkaline phosphatase (ALP) activity, lactate dehydrogenase (LDH) activity, MTS assay for NMDA (N-methyl-D-aspartate) receptor antagonist or AMPA/kainate receptor antagonist, measurement for $TNF-\alpha$, and c-fos gene expression were performed after these cells were treated with or without various cocentrations of xanthine oxidase (XO), hypoxanthine (HX), D-2-amino-5-phosphonovaleric acid (APV), 7-chlorokynurenic acid (CKA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. In this study, XO/HX showed decreased cell viability and glutathione peroxidase (GPx) activity, but it showed increased LPO activity, $TNF-\alpha$ secretion and c-fos expression. APV and CKA incresed protein sythesis and ALP activity. While, CNQX or DNQX did not show any protective effect in LDH activity or cell viability. From these results, XO/HX showed cytotoxic effect in cultured rat osteoblast or osteoclast, and also NMDA receptor antagonist such as APV or CKA was effective in blocking XO/HX-induced osteotoxicity in these cultures.

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Neural Transdifferentiation: MAPTau Gene Expression in Breast Cancer Cells

  • Lara-Padilla, E;Miliar-Garcia, A;Gomez-Lopez, M;Romero-Morelos, P;Bazan-Mendez, CI;Alfaro-Rodriguez, A;Anaya-Ruiz, M;Callender, K;Carlos, A;Bandala, C
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1967-1971
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    • 2016
  • Background: In tumor cells, aberrant differentiation programs have been described. Several neuronal proteins have been found associated with morphological neuronal-glial changes in breast cancer (BCa). These neuronal proteins have been related to mechanisms that are involved in carcinogenesis; however, this regulation is not well understood. Microtubule-associated protein-tau (MAP-Tau) has been describing in BCa but not its variants. This finding could partly explain the neuronal-glial morphology of BCa cells. Our aim was to determine mRNA expression of MAP-tau variants 2, 4 and 6 in breast cancer cell lines. Materials and Methods: Cultured cell lines MCF-10A, MDA-MB-231, SKBR3 and T47D were observed under phase-contrast microscopy for neural morphology and analyzed for gene expression of MAP-Tau transcript variants 2, 4 and 6 by real-time PCR. Results: Regarding morphology like neural/glial cells, T47D line shown more cells with these features than MDA-MB-231 and SKBR. In another hand, we found much greater mRNA expression of MAP-Tau transcript variants 2, and to a lesser extent 4 and 6, in T47D cells than the other lines. In conclusion, regulation of MAP-Tau could bring about changes in cytoskeleton, cell morphology and motility; these findings cast further light on neuronal transdifferentiation in BCa.

Mutational Analysis of Prohibitin - A Highly Conserved Gene in Indian Female Breast Cancer Cases

  • Najm, Mohammad Zeeshan;Akhtar, Md. Salman;Ahmad, Istaq;Sadaf, Sadaf;Mallick, Mohd Nasar;Kausar, Mohd Adnan;Chattopadhyay, Shilpi;Ahad, Amjid;Zaidi, Shuaib;Husain, Syed Akhtar;Siddiqui, Waseem Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5113-5117
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    • 2012
  • Prohibitin (PHB) is a chaperone protein which is highly conserved evolutionarily. It shows significant homology with the Drosophila cc gene which is considered important for development and differentiation of Drosophila melanogaster. Investigations have revealed an involvement of PHB in cellular proliferation and development, apoptosis, signal transduction, mitochondrial function and regulation of the estrogen and androgen receptors. Therefore, we conducted the present study to analyze mutations in the highly conserved region in Indian female breast cancer patients. Conventional PCR-SSCP and Automated DNA sequencing were performed with a total of 105 breast cancer samples along with adjacent normal tissue. Of the total, 14.2% (15/105) demonstrated a mutation status of prohibitin observed in our study population. We identified a novel missense mutation (Thr>Ser), a novel deletion of T nucleotide in an intron adjacent to intron-exon boundary and a previously determined missense mutation (Val>Ala). A statistically significant correlation was obtained which suggested that prohibitin may be associated with tumor development and/or progression of at least some proportion of breast cancers.

Craniopharyngiomas : Radiological Differentiation of Two Types

  • Lee, In Ho;Zan, Elcin;Bell, W. Robert;Burger, Peter C.;Sung, Heejong;Yousem, David M.
    • Journal of Korean Neurosurgical Society
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    • v.59 no.5
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    • pp.466-470
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    • 2016
  • Objective : To determine imaging features that may separate adamantinomatous and papillary variants of craniopharyngiomas given that tumors with adamantinomatous signature features are associated with higher recurrence rates, morbidity, and mortality. We specifically reviewed calcification on CT, T1 bright signal intensity, and cystic change on T2 weighted images for differentiating these two types. Methods : We retrospectively reviewed the MRI and CT studies in 38 consecutive patients with pathologically proven craniopharyngiomas between January 2004 and February 2014 for the presence of calcification on CT scans, bright signal intensity on T1 weighted images, and cystic change on T2 weighted images. Results : Of the 38 craniopharyngiomas, 30 were adamantinomatous type and 8 were papillary type. On CT scans, calcification was present in 25 of 38 tumors. All calcified tumors were adamantinomatous type. Twenty four of 38 tumors had bright signal intensity on T1 weighted images. Of these 24 tumors, 22 (91.7%) were adamantinomatous and 2 were papillary type. Cystic change on T2 weighted images was noted in 37 of 38 tumors; only 1 tumor with papillary type did not show cystic change. Conclusion : T1 bright signal intensity and calcification on CT scans uniformly favor the adamantinomatous type over papillary type of craniopharyngioma in children. However, these findings are more variable in adults where calcification and T1 bright signal intensity occur in 70.6% and 58.8% respectively of adult adamantinomatous types of craniopharyngiomas.

Relationship between EGFR Over-expression and Clinicopathologic Characteristics in Squamous Cell Carcinoma of the Esophagus: A Meta-analysis

  • Wang, Jun;Yu, Jin-Ming;Jing, Shao-Wu;Guo, Yin;Wu, Ya-Jing;Li, Na;Jiao, Wen-Peng;Wang, Li;Zhang, Yan-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5889-5893
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    • 2014
  • Over-expression of epidermal growth factor receptor (EGFR) has been identified as a common feature associated with clinical outcome in many types of cancer, including squamous cell carcinoma of the oesophagus (SCCO). However, the clinical importance of EGFR over-expression in SCCO remains unsettled as conflicting results exist. Therefore we carried out the present meta-analysis of published studies for clarification. A total of 13 studies including 1, 150 patients were enrolled. EGFR over-expression was positive in 722 of these cases. With EGFR over-expression, patients had higher depth of invasion, vascular invasion, and poor prognosis. However, expression had no relation with degree of differentiation, histological grade, lymph node metastasis, clinical stage or lymphatic invasion. EGFR over-expression is probably a valuable predictor for the T stage, vascular invasion and OS, and it could be used as a poor prognosis indicator for the esophageal SCC patients. Targeting therapy to EFGR should be considered to the combined treatment in SCCO.