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Sample records for carcinoma cells expressing

  1. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma*

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    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado Filho, Carlos D'Apparecida Santos

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment. PMID:27828631

  2. Transitional cell carcinoma express vitamin D receptors

    DEFF Research Database (Denmark)

    Hermann, G G; Andersen, C B

    1997-01-01

    Recently, vitamin D analogues have shown antineoplastic effect in several diseases. Vitamin D analogues exert its effect by interacting with the vitamin D receptor (VDR). Studies of VDR in transitional cell carcinoma (TCC) have not been reported. The purpose of the present study was therefore.......05). Similarly, also tumor grade appeared to be related to the number of cells expressing the receptor. Normal urothlium also expressed VDR but only with low intensity. Our study shows that TCC cells possess the VDR receptor which may make them capable to respond to stimulation with vitamin D, but functional...... studies of vitamin D's effect on TCC cells in vitro are necessary before the efficacy of treatment with vitamin D analogues in TCC can be evaluated in patients....

  3. Expression and function of FERMT genes in colon carcinoma cells.

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    Kiriyama, Kenji; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Kubo, Terufumi; Tamura, Yasuaki; Kanaseki, Takayuki; Takahashi, Akari; Nakazawa, Emiri; Saka, Eri; Ragnarsson, Charlotte; Nakatsugawa, Munehide; Inoda, Satoko; Asanuma, Hiroko; Takasu, Hideo; Hasegawa, Tadashi; Yasoshima, Takahiro; Hirata, Koichi; Sato, Noriyuki

    2013-01-01

    Invasion into the matrix is one of hallmarks of malignant diseases and is the first step for tumor metastasis. Thus, analysis of the molecular mechanisms of invasion is essential to overcome tumor cell invasion. In the present study, we screened for colon carcinoma-specific genes using a cDNA microarray database of colon carcinoma tissues and normal colon tissues, and we found that fermitin family member-1 (FERMT1) is overexpressed in colon carcinoma cells. FRRMT1, FERMT2 and FERMT3 expression was investigated in colon carcinoma cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that only FERMT1 had cancer cell-specific expression. Protein expression of FERMT1 was confirmed by western blotting and immunohistochemical staining. To address the molecular functions of FERMT genes in colon carcinoma cells, we established FERMT1-, FERMT2- and FERMT3-overexpressing colon carcinoma cells. FERMT1-overexpressing cells exhibited greater invasive ability than did FERMT2- and FERMT3-overexpressing cells. On the other hand, FERMT1-, FERMT2- and FERMT3-overexpressing cells exhibited enhancement of cell growth. Taken together, the results of this study indicate that FERMT1 is expressed specifically in colon carcinoma cells, and has roles in matrix invasion and cell growth. These findings indicate that FERMT1 is a potential molecular target for cancer therapy.

  4. Expression of Pol(t) in tissues and cell lines of transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To explore the expression of DNA polymerase iota in transitional cell carcinoma cells and tissues; Methods: RT-PCR was applie to detect the expression of polymerase iota in BIU87 and T24 cells, then the expression of polymerase iota was also detected in the same way in transitional cell carcinoma which was derived from clinical bladder carcinoma and renal pelvic carcinoma. Results: The expression of Polt was low in bladder normal membrana mucosa but significantly elevated in transitional cell carcinoma cells. Compared with the expression of polymerase iota in bladder normal mucous membranes, the expression of polymerase iota was significantly increased in transitional cell carcinoma tissue (P<0.01)and associated with the grade of transitional cell carcinoma. Conclusion: The significantly increased expression of polymerase iota may be associated with the generation and development of transitional cell carcinoma, even with its high heterogenicity.

  5. PRL-3 expression in nasal sinus squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zi-Hui Chen; Min-Ying Li

    2016-01-01

    Objective:To investigate the relationship between liver regeneration phosphatase-3 (PRL-3) with differentiation extent of nasal sinus squamous cell carcinoma, and molecular biological effects on the pathogenesis of nasal sinus squamous cell carcinoma to comprehend its relevance, so as to make early diagnosis of patients, and to give guidance to the prognosis. Methods:Immunohistochemistry was used to detect PRL-3 in 30 cases of different degrees of sinus nasal squamous cell carcinoma. 20 cases of normal nasal cavity of mucosa tissues were set as control. Results:The PRL-3 in all levels of sinonasal squamous cell carcinoma tissues, there was a significant difference compared with the normal nasal mucosa (P<0.05), squamous cell carcinoma and its expression increased with the grade with enhanced trend. Conclusions:PRL-3 expression increased significantly in sinonasal squamous cell carcinoma than in nasal polyp tissue, showed that it may be associated with squamous cell carcinoma of nasal sinus squamous cell carcinoma, may be the early event.

  6. The Expression of p53 and Cox-2 in Basal Cell Carcinoma, Squamous Cell Carcinoma and Actinic Keratosis Cases

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    Ülker KARAGECE YALÇIN

    2012-05-01

    Full Text Available Objective: The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship.Material and Method: 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostaining by p53 and COX-2 was performed on sections of the paraffin blocks.Results: p53 expression was observed in 98% of basal cell carcinoma, 88.9% of squamous cell carcinoma and all actinic keratosis cases. p53 expression was also noted in non-dysplastic appearing epithelium in actinic keratosis cases. COX-2 expression was seen in 90, 100 and 88.9% of the basal cell carcinoma, squamous cell carcinoma and actinic keratosis groups, respectively. Skin appendages, inflammatory cells and vascular structures were also stained by COX-2 besides tumor tissue. COX-2 expression increased by the p53 expression increase in basal cell carcinoma and squamous cell carcinoma. p53 and COX-2 expressions were not related in terms of tumor type in the BCC and were not related in terms of differentiation in SCC.Conclusion: The existence of p53 expression in actinic keratosis cases has supported the idea that p53 plays a role in the early steps of carcinogenesis in skin cancers. The fact that the expression of COX-2 increases in line with the increase of p53 expression in basal cell carcinoma and squamous cell carcinoma cases indicates that COX-2 expression may be affected by p53

  7. Expression of stromelysin 3 in basal cell carcinomas.

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    Cribier, B; Noacco, G; Peltre, B; Grosshans, E

    2001-01-01

    Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

  8. Expression of cyclooxygenase-2 in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jian-Gang Jiang; Dao-Wen Wang; Jiang-Bo Tang; Chun-Lian Chen; Bao-Xing Liu; Xiang-Ning Fu; Zhi-Hui Zhu; Wei Qu; Katherine Cianflone; Michael P. Waalkes

    2004-01-01

    AIM: To determine whether cyclooxygenase-2 (COX-2) was expressed in human esophageal squamous cell carcinoma.METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, immunohistochemistry and immunofluorescence were used to assess the expression level of COX-2 in esophageal tissue.RESULTS: COX-2 mRNA levels were increased by >80-fold in esophageal squamous cell carcinoma when compared to adjacent noncancerous tissue. COX-2 protein was present in 21 of 30 cases of esophageal squamous cell carcinoma tissues, but was undetectable in noncancerous tissue. Immunohistochemistry was performed to directly show expression of COX-2 in tumor tissue.CONCLUSION: These results suggest that COX-2 may be an important factor for esophageal cancer and inhibition of COX-2 may be helpful for prevention and possibly treatment of this cancer.

  9. Gene expression profile of renal cell carcinoma clear cell type

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    Marcos F. Dall’Oglio

    2010-08-01

    Full Text Available PURPOSE: The determination of prognosis in patients with renal cell carcinoma (RCC is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT. MATERIALS AND METHODS: We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1 low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2 high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3 metastatic RCC-CCT. Normal renal tissue was used as control. RESULTS: After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. CONCLUSION: These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.

  10. Reduced expression of Slit2 in renal cell carcinoma.

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    Ma, Wei-Jie; Zhou, Yu; Lu, Dan; Dong, Dong; Tian, Xiao-Jun; Wen, Jie-Xi; Zhang, Jun

    2014-01-01

    Slit2, initially identified as an important axon guidance molecule in the nervous system, was suggested to be involved in multiple cellular processes. Recently, Slit2 was reported to function as a potential tumor suppressor in diverse tumors. In this study, we systematically analyzed the expression level of Slit2 in renal cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2 mRNA and protein expression were significantly down-regulated in renal cell carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation dramatically induced Slit2 expression in cancer cell lines with weak expression of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation was observed in 8 out of 38 patients (21.1 %), which was well correlated with the down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor suppressor in RCC, which is down-regulated in RCC partially due to promoter methylation.

  11. GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas.

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    Abdou, Asmaa Gaber; Eldien, Marwa Mohammad Serag; Elsakka, Daliah

    2015-09-01

    Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

  12. Expression and clinical significance of sulfiredoxin expression in cervical squamous cell carcinoma tissue

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    Xiao-yan CHEN

    2015-10-01

    Full Text Available Objective To inquire into the expression and its clinical significance of sulfiredoxin (Srx in cervical squamous cell carcinoma tissue. Methods SABC immunohistochemical method was used to detect the expression levels of Srx in specimens of 104 cervical squamous cell carcinoma and the corresponding adjacent tissues, 15 cervical intraepithelial neoplasm (CIN Ⅲ, and 20 normal cervical squamous cell epithelium tissue. The relationship between the expression of Srx protein and clinical pathological parameters of the cancer was also analyzed. Results The positive expression rates of Srx in CIN Ⅲ and cervical squamous cell carcinoma [73.3%(11/15 and 82.7%(86/104, respectively] were significantly higher than that in normal cervical tissue [35.0%(7/20, χ2=17.778, P=0.000]. Meanwhile, Srx expression in cervical cancer specimens was significantly higher than that in normal adjacent tissues (χ2=56.224, P=0.000. The positive expression of Srx in cervical squamous cell carcinoma was significantly correlated with lymph node metastasis, the depth of cancer invasion, and the infiltration of blood vessels (P0.05. Conclusion The higher expression of Srx protein might be a valuable marker for the early diagnosis and evaluation of prognosis in patients with cervical squamous cell carcinoma. DOI: 10.11855/j.issn.0577-7402.2015.08.11

  13. Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

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    Chen, Yao-Tseng; Panarelli, Nicole C; Piotti, Kathryn C; Yantiss, Rhonda K

    2014-05-01

    Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

  14. Expression of lactate dehydrogenase C correlates with poor prognosis in renal cell carcinoma.

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    Hua, Yibo; Liang, Chao; Zhu, Jundong; Miao, Chenkui; Yu, Yajie; Xu, Aimin; Zhang, Jianzhong; Li, Pu; Li, Shuang; Bao, Meiling; Yang, Jie; Qin, Chao; Wang, Zengjun

    2017-03-01

    Lactate dehydrogenase C is an isoenzyme of lactate dehydrogenase and a member of the cancer-testis antigens family. In this study, we aimed to investigate the expression and functional role of lactate dehydrogenase C and its basic mechanisms in renal cell carcinoma. First, a total of 133 cases of renal cell carcinoma samples were analysed in a tissue microarray, and Kaplan-Meier survival curve analyses were performed to investigate the correlation between lactate dehydrogenase C expression and renal cell carcinoma progression. Lactate dehydrogenase C protein levels and messenger RNA levels were significantly upregulated in renal cell carcinoma tissues, and the patients with positive lactate dehydrogenase C expression had a shorter progression-free survival, indicating the oncogenic role of lactate dehydrogenase C in renal cell carcinoma. In addition, further cytological experiments demonstrated that lactate dehydrogenase C could prompt renal cell carcinoma cells to produce lactate, and increase metastatic and invasive potential of renal cell carcinoma cells. Furthermore, lactate dehydrogenase C could induce the epithelial-mesenchymal transition process and matrix metalloproteinase-9 expression. In summary, these findings showed lactate dehydrogenase C was associated with poor prognosis in renal cell carcinoma and played a pivotal role in the migration and invasion of renal cell carcinoma cells. Lactate dehydrogenase C may act as a novel biomarker for renal cell carcinoma progression and a potential therapeutic target for the treatment of renal cell carcinoma.

  15. Clear cell papillary renal cell carcinoma: micro-RNA expression profiling and comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma.

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    Munari, Enrico; Marchionni, Luigi; Chitre, Apurva; Hayashi, Masamichi; Martignoni, Guido; Brunelli, Matteo; Gobbo, Stefano; Argani, Pedram; Allaf, Mohamad; Hoque, Mohammad O; Netto, George J

    2014-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. Micro-RNAs (miRNAs) are small noncoding RNAs that play a crucial role in regulating gene expression and are involved in various biological processes, including cancer development. To better understand the biology of this tumor, we aimed to analyze the miRNA expression profile of a set of CCPRCC using microarray and quantitative reverse transcription-polymerase chain reaction. A total of 15 cases diagnosed as CCPRCC were used in this study. Among the most differentially expressed miRNA in CCPRCC, we found miR-210, miR-122, miR-34a, miR-21, miR-34b*, and miR-489 to be up-regulated, whereas miR-4284, miR-1202, miR-135a, miR-1973, and miR-204 were down-regulated compared with normal renal parenchyma. To identify consensus of differentially regulated miRNA between CCPRCC, CCRCC, and PRCC, we additionally determined differential miRNA expression using 2 publically available microarray data sets from the NCBI Gene Expression Omnibus database (GSE41282 and GSE3798). This comparison revealed that the miRNA expression profile of CCPRCC shows some overlapping characteristics between CCRCC and PRCC. Moreover, CCPRCC lacks dysregulation of important miRNAs typically associated with aggressive behavior. In summary, we describe the miRNA expression profile of a relatively infrequent type of renal cancer. Our results may help in understanding the molecular underpinning of this newly recognized entity.

  16. The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites.

    Science.gov (United States)

    Ly, Thai Yen; Walsh, Noreen M; Pasternak, Sylvia

    2012-04-01

    Most Merkel cell carcinomas display pure neuroendocrine differentiation (pure Merkel cell carcinoma), whereas a minority show combined neuroendocrine and nonneuroendocrine elements (combined Merkel cell carcinoma). Recent identification of Merkel cell polyomavirus DNA and Merkel cell polyomavirus large T antigen expression in a proportion of Merkel cell carcinomas has suggested viral-induced oncogenesis. To date, Merkel cell polyomavirus immunohistochemistry has shown an absence of viral large T antigen expression in combined Merkel cell carcinoma as well as select non-Merkel cell carcinoma cutaneous lesions and visceral neuroendocrine tumors. In our series, we aimed to further characterize the frequency and pattern of Merkel cell polyomavirus large T antigen expression by CM2B4 immunohistochemistry in primary and metastatic Merkel cell carcinoma (pure Merkel cell carcinoma and combined Merkel cell carcinoma) and various non-Merkel cell carcinoma lesions from patients with Merkel cell carcinoma, patients without Merkel cell carcinoma, and individuals with altered immune function. Merkel cell polyomavirus large T antigen was detected in 17 (63%) of 27 pure Merkel cell carcinomas and absent in all 15 (0%) combined Merkel cell carcinomas. Furthermore, complete concordance (100%) of Merkel cell polyomavirus large T antigen expression was observed in 10 cases of primary Merkel cell carcinoma and subsequent tumor metastases. We also evaluated 70 non-Merkel cell carcinoma lesions including 15 cases each of pulmonary and gastrointestinal neuroendocrine tumors. All 70 non-Merkel cell carcinoma lesions were negative for Merkel cell polyomavirus by CM2B4 immunohistochemistry, irrespective of any known Merkel cell carcinoma diagnosis and immune status. In summary, our identification of Merkel cell polyomavirus large T antigen expression in a subset of Merkel cell carcinoma and lack of findings in combined Merkel cell carcinomas and non-Merkel cell carcinoma lesions concur with

  17. Microarray gene expression profiling and analysis in renal cell carcinoma

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    Sadhukhan Provash

    2004-06-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

  18. Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas.

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    Yeasmin, Shamima; Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Ishikawa, Masako; Katagiri, Atsuko; Iida, Kouji; Nakayama, Naomi; Otuski, Yoshiro; Kobayashi, Hiroshi; Nakayama, Satoru; Miyazaki, Kohji

    2012-04-01

    This study examined the biological and clinical significance of NAC1 (nucleus accumbens associated 1) expression in both cervical squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. Using immunohistochemistry, the frequency of positive NAC1 expression in adenocarcinomas/adenosquamous carcinomas (31.0%; 18/58) was significantly higher than that in squamous cell carcinomas (16.2%; 12/74) (P = .043). NAC1 gene amplification was identified by fluorescence in situ hybridization in 5 (7.2%) of 69 squamous cell carcinomas. NAC1 amplification was not identified in the adenocarcinomas (0%; 0/58). Positive NAC1 expression was significantly correlated with shorter overall survival in squamous cell carcinomas (P NAC1 expression in squamous cell carcinomas was an independent prognostic factor for overall survival after standard radiotherapy (P = .0003). In contrast to squamous cell carcinomas, positive NAC1 expression did not correlate with shorter overall survival in adenocarcinomas/adenosquamous carcinomas (P = .317). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in the cervical cancer cell lines TCS and Hela P3, which normally lack NAC1 expression. These findings indicate that NAC1 overexpression is critical to the growth and survival of cervical carcinomas irrespective of histologic type. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, cervical carcinoma patients with NAC1 expression may benefit from a targeted therapy irrespective of histologic type.

  19. Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

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    Thomas C. Wehler

    2008-01-01

    Full Text Available Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P=.039, tumor dedifferentiation (P = .0005, and low hemoglobin (P = .039. In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma.

  20. Regulation of osteoprotegerin expression by Notch signaling in human oral squamous cell carcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    Jeeranan Manokawinchoke; Thanaphum Osathanon; Prasit Pavasant

    2016-01-01

    Objective: To investigate the influence of Notch signaling on osteoprotegerin (OPG) expression in a human oral squamous cell carcinoma cell line. Methods: Activation of Notch signaling was performed by seeding cells on Jagged1 immobilized surfaces. In other experiments, a γ-secretase inhibitor was added to the culture medium to inhibit intracellular Notch signaling. OPG mRNA and protein were determined by real-time PCR and ELISA, respectively. Finally, publicly available microarray database analysis was performed using connection up- or down-regulation expression analysis of microarrays software. Results: Jagged1-treatment of HSC-4 cells enhanced HES1 and HEY1 mRNA expres-sion, confirming the intracellular activation of Notch signaling. OPG mRNA and protein levels were significantly suppressed upon Jagged1 treatment. Correspondingly, HSC-4 cells treated with a γ-secretase inhibitor resulted in a significant reduction of HES1 and HEY1 mRNA levels, and a marked increase in OPG protein expression was observed. These results implied that Notch signaling regulated OPG expression in HSC-4 cells. However, Jagged1 did not alter OPG expression in another human oral squamous cell carcinoma cell line (HSC-5) or a human head and neck squamous cell carcinoma cell line (HN22). Conclusions: Notch signaling regulated OPG expression in an HSC-4 cell line and this mechanism could be cell line specific.

  1. Regulation of osteoprotegerin expression by Notch signaling in human oral squamous cell carcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    Jeeranan Manokawinchoke; Thanaphum Osathanon; Prasit Pavasant

    2016-01-01

    Objective: To investigate the influence of Notch signaling on osteoprotegerin(OPG)expression in a human oral squamous cell carcinoma cell line.Methods: Activation of Notch signaling was performed by seeding cells on Jagged1 immobilized surfaces. In other experiments, a g-secretase inhibitor was added to the culture medium to inhibit intracellular Notch signaling. OPG m RNA and protein were determined by real-time PCR and ELISA, respectively. Finally, publicly available microarray database analysis was performed using connection up- or down-regulation expression analysis of microarrays software.Results: Jagged1-treatment of HSC-4 cells enhanced HES1 and HEY1 m RNA expression, confirming the intracellular activation of Notch signaling. OPG m RNA and protein levels were significantly suppressed upon Jagged1 treatment. Correspondingly, HSC-4 cells treated with a g-secretase inhibitor resulted in a significant reduction of HES1 and HEY1 m RNA levels, and a marked increase in OPG protein expression was observed.These results implied that Notch signaling regulated OPG expression in HSC-4 cells.However, Jagged1 did not alter OPG expression in another human oral squamous cell carcinoma cell line(HSC-5) or a human head and neck squamous cell carcinoma cell line(HN22).Conclusions: Notch signaling regulated OPG expression in an HSC-4 cell line and this mechanism could be cell line specific.

  2. Expression of squamous cell carcinoma markers and adenocarcinoma markers in primary pulmonary neuroendocrine carcinomas.

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    Masai, Kyohei; Tsuta, Koji; Kawago, Mitsumasa; Tatsumori, Takahiro; Kinno, Tomoaki; Taniyama, Tomoko; Yoshida, Akihiko; Asamura, Hisao; Tsuda, Hitoshi

    2013-07-01

    Recent clinical trials have revealed that accurate histologic typing of non-small cell lung cancer is essential. Until now, squamous cell carcinoma (SQC) and adenocarcinoma (ADC) markers have not been thoroughly analyzed for pulmonary neuroendocrine carcinomas (NECs). We analyzed the expression of 8 markers [p63, cytokeratin (CK) 5/6, SOX2, CK7, desmocollin 3, thyroid transcription factor-1 (8G7G3/1 and SPT24), and napsin A] in 224 NECs. SOX2 (76.2%) had the greatest expression for NECs. CK5/6 (1.4%), desmocollin 3 (0.5%), and napsin A (0%) were expressed less or not at all in NECs. Although our investigated markers have been reported useful for differentiating between SQC and ADC, some of them were also present in a portion of pulmonary NECs. In our study, CK5/6 and desmocollin 3 were highly specific markers for SQC, and napsin A was highly specific for ADC. These markers are recommended for diagnosis of poorly differentiated non-small cell lung cancer.

  3. Expression and significance of PTEN and PCNA in human laryngeal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    李长青; 文莲姬; 金春顺; 崔树勋

    2004-01-01

    Objective: To elucidate the expression and significance of PTEN and PCNA in human laryngeal squamous cell carcinoma. Methods: Immunochemical method was used to study 60 cases of laryngeal carcinoma, 20 cases of normal laryngeal tissues which were closely adjacent to carcinoma and 10 cases of normal laryngeal tissues. Results: It was showed that PTEN gene was expressed in 85 % laryngeal carcinoma tissues. The percentage of lymph node metastasis of laryngeal carcinoma which were negative or positive of PTEN protein was 77.8 % and 33.3 % respectively, and the difference was significance ( P < 0.05). Conclusion: Expression of PTEN in laryngeal carcinoma was different from that of normal laryngeal tissues. It may play a role but not important in the tumorigenesis and development of laryngeal carcinoma.

  4. Pulmonary Large Cell Carcinoma Displays High Expression of EMMPRIN and VEGF

    Institute of Scientific and Technical Information of China (English)

    Yushuang Zheng; Miao Yu; Huachuan Zheng; Yifu Guan; Yasuo Takano

    2008-01-01

    OBJECTIVE To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) in lung carcinomas,and to clarify their roles in carcinoma progression.METHODS Expression of EMMPRIN and VEGF was examined with tissue microarrays (TMAs) of lung carcinomas (n = 181),and their suppression in adjacent normal lung samples (n = 40) were determined by immunohistochemistry.The results were compared with clinicopathological findings for the same tumors.RESULTS Both EMMPRIN and VEGF were occasionally expressed in pseudostratified columnar epithelium and frequently in lung carcinomas.Histologically,EMMPRIN and VEGF displayed higher levels in large (LCC) cell carcinomas than adenocarcinoma (AD),squamous (SQ) and small cell carcinomas (SCC) (P < 0.05).EMMPRIN was more highly expressed in SQ as compared with AD (P < 0.05),while the converse was true for VEGF (P < 0.05).Binding was generally more intense for EMMPRIN in samples from male compared to female patients (P < 0.05),whereas the latter tended to exhibit more VEGF expression (P < 0.05).Positive associations of VEGF expression with the TNM stage and amounts of EMMPRIN were noted in the lung carcinomas (P < 0.05).CONCLUSION EMMPRIN and VEGF possibly contribute to physiological repair of normal lung and histogenesis of lung carcinoma.Both proteins might be involved in the molecular basis for differences in the incidence of lung carcinoma between men and women.

  5. Expression of claudin-5 in canine pancreatic acinar cell carcinoma - An immunohistochemical study.

    Science.gov (United States)

    Jakab, Csaba; Rusvai, Miklós; Gálfi, Péter; Halász, Judit; Kulka, Janina

    2011-03-01

    Claudin-5 is an endothelium-specific tight junction protein. The aim of the present study was to detect the expression pattern of this molecule in intact pancreatic tissues and in well-differentiated and poorly differentiated pancreatic acinar cell carcinomas from dogs by the use of cross-reactive humanised anticlaudin-5 antibody. The necropsy samples taken from dogs included 10 nonneoplastic pancreatic tissues, 10 well-differentiated pancreatic acinar cell carcinomas, 10 poorly differentiated pancreatic acinar cell carcinomas, 5 intrahepatic metastases of well-differentiated and 5 intrahepatic metastases of poorly differentiated acinar cell carcinomas. A strong lateral membrane claudin-5 positivity was detected in exocrine cells in all intact pancreas samples. The endocrine cells of the islets of Langerhans and the epithelial cells of the ducts were negative for claudin-5. The endothelial cells of vessels and lymphatic channels in the stroma of the intact pancreas showed strong membrane positivity for this claudin. All well-differentiated exocrine pancreas carcinomas and all poorly-differentiated pancreatic acinar cell carcinoma samples showed a diffuse loss of claudin-5 expression. The claudin-5-positive peritumoural vessels and lymphatic channels facilitated the detection of vascular invasion of the claudin-5-negative cancer cells. In liver metastasis samples, the pancreatic carcinomas were negative for claudin-5. It seems that the loss of expression of claudin-5 may lead to carcinogenesis in canine exocrine pancreatic cells.

  6. Expression of CIDE proteins in clear cell renal cell carcinoma and their prognostic significance.

    Science.gov (United States)

    Yu, Ming; Wang, Hui; Zhao, Jun; Yuan, Yuan; Wang, Chao; Li, Jing; Zhang, Lijun; Zhang, Liying; Li, Qing; Ye, Jing

    2013-06-01

    Clear cell renal cell carcinoma (ccRCC) is the major and aggressive subtype of renal cell carcinoma. It is known to derive its histologic appearance from accumulation of abundant lipids and glycogens. The cell death-inducing DFF45-like effector (CIDE) family has been characterized as the lipid droplet proteins involved in the metabolism of lipid storage droplets. The purpose of this study was to evaluate the expression of CIDE proteins in ccRCC cells and to investigate their prognostic significance. We examined consecutive patients with sporadic ccRCC, who underwent nephrectomy, to measure their mRNA and protein expression of CIDE proteins. We found that Cidec and ADRP expression were significantly up-regulated in ccRCC, compared with normal kidney tissues. Cideb was down-regulated. We also found that Cideb was expressed more in low-grade ccRCC than in high-grade tumors. To further clarify the relationship between Cideb expression and patient prognosis, we evaluated 57 ccRCC patients followed up for 120 months. Reduced ccRCC Cideb expression was associated with a higher Fuhrman nuclear grade. Patients with high Cideb expression had better overall survival rate than those with low expression (p < 0.05). Cideb expression was an independent predictor of survival (p = 0.001). Although the biologic function of Cideb in ccRCC remains unknown, the expression level of Cideb might be a novel predictor of prognosis in ccRCC.

  7. Nuclear ß catenin expression is related to unfavourable outcome in oropharyngeal and hypopharyngeal squamous cell carcinoma

    OpenAIRE

    Pukkila, M; Virtaniemi, J; Kumpulainen, E; Pirinen, R; Johansson, R.; Valtonen, H; Juhola, M; Kosma, V.

    2001-01-01

    Aims—To investigate the expression of α, ß, and γ catenins in oropharyngeal and hypopharyngeal squamous cell carcinoma and their relations to each other, as well as to clinical data, tumour differentiation, and prognosis.

  8. Expression of the alpha 6 beta 4 integrin by squamous cell carcinomas and basal cell carcinomas: possible relation to invasive potential?

    DEFF Research Database (Denmark)

    Rossen, K; Dahlstrøm, K K; Mercurio, A M;

    1994-01-01

    We have studied the expression of alpha 6 beta 4 integrin, a carcinoma laminin receptor in ten squamous cell carcinomas (SCCs) and ten basal cell carcinomas (BCCs) of the skin in order to examine whether changes in alpha 6 beta 4 integrin expression may be related to invasive and metastatic...... the expression of the alpha 6 and the beta 4 subunits paralleled each other, showing an increased intensity and loss of polarity. The BCCs, however, showed consistently decreased expression of both the alpha 6 and the beta 4 subunits. The results of our study, as well as those of other studies, support...

  9. β-catenin expression pattern in primary oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    CAI Zhi-gang; SHI Xiao-jian; GAO Yan; WEI Ming-jie; WANG Cun-yu; YU Guang-yan

    2008-01-01

    Background β-catenin, a 92 kDa protein that binds to the cytoplasmic tail of E-cadherin, has an essential role in intercellular adhesion and signal transduction. Aberrant expression of β-catenin has been associated with progression and metastasis of various human cancers. The aim of this study was to elucidate the expression pattem of β-catenin in primary oral squamous cell carcinoma and examine the correlation between β-catenin expression and tumor differentiation, histological grade and lymph node status as well as its clinical significances.Methods Seventy-six patients with oral squamous cell carcinoma and sixteen metastatic lymph nodes were studied.The β-catenin expression was determined by immunohistochemical staining. The correlation with clinical, histological data was analyzed statistically.Results Normal oral epithelium showed strong β-catenin expression at the cell membrane, but no cytoplasmic or nuclear expression. Different degrees of reduced expression of β-catenin at the cell membrane were found in 54 cases with squamous cell carcinoma (71%). Cytoplasmic β-catenin expression was found in 17 tumors (22.4%). Three caseswere found with nuclear β-catenin expression. In sixteen lymph nodes with metastatic squamous cell carcinoma,negative β-catenin expression at the cell membrane was seen in 13 tumors (81.2%) and weak expression in 3 tumors (18.8%). Statistical analysis showed that there was an inverse correlation between β-catenin expression and lymph node status and histological grade of tumors.Conclusions Reduced β-catenin expression at the cell membrane is clearly associated with lymph node metastasis. A reduced expression of β-catenin may constitute a hallmark of aggressive biological behavior of squamous cell carcinoma.

  10. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  11. Reduced expression of β-catenin inhibitor Chibby in colon carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Marion M Schuierer; Elisabeth Graf; Ken-Ichi Takemaru; Wolfgang Dietmaier; Anja-Katrin Bosserhoff

    2006-01-01

    AIM: To analyse the Chibby expression and its function in colon carcinoma cell lines and colorectal carcinoma (CRC).METHODS: Chibby expression levels were investigated by quantitative RT-PCR in a panel of seven different colon carcinoma cell lines. By sequencing, we analysed mutational status of Chibby. To test whether Chibby exhibited effects on β-catenin signalling in colon carcinoma cells, we transfected SW480 cells with Chibby expression plasmid and, subsequently, analysed activity of β-catenin and tested for alterations in cellular phenotype. In addition, we examined Chibby mRNA levels in samples of colorectal carcinomas and adjacent normal tissues by using quantitative RT-PCR and hybridised gene chips with samples from CRC and normal tissues.RESULTS: Chibby mRNA expression was strongly downregulated in colon carcinoma cell lines in comparison to normal colon epithelial cells and no mutation in any of the examined colon carcinoma cell lines was found. Further, we could show that Chibby inhibited β-catenin activity in TOPflash assays when over-expressed in SW480 cells. Proliferation and invasion assays with Chibby transfected SW480 cells did not reveal profound differences compared to control cells. In contrast to these in vitro data, quantitative RT-PCR analyses of Chibby mRNA levels in CRC tumor samples did not show significant differences to specimens in adjacent non-cancerous tissue.Consistent with these findings, gene chips analysing tissue samples of tumors and corresponding normal tissue did not show altered Chibby expressionCONCLUSION: Altered Chibby expression might beobserved in vitro in different colon carcinoma cell lines.However, this finding could not be confirmed in vitro in CRC tumors, indicating that Chibby is not likely to promote CRC tumor development or progression. As Chibby is an important inhibitor of β-catenin signalling, our data implicate that the usability of colon carcinoma cell lines for in vitro studies analysing the Wnt

  12. Bladder squamous cell carcinomas express psoriasin and externalize it to the urine

    DEFF Research Database (Denmark)

    Celis, J E; Rasmussen, H H; Vorum, H;

    1996-01-01

    PURPOSE: To report a single biomarker, psoriasin (Mr 11.0 kd, pI 6.2), a calcium binding protein which is expressed largely by stratified squamous epithelia and is externalized to the urine of bladder squamous cell carcinoma (SCC) bearing patients. MATERIALS AND METHODS: Protein expression profiles...... identified from 100 samples of patients with suspected transitional cell carcinoma (TCC). The protein profiles of the 4 SCCs (56-1, grade III, T4; 181-1, grade I, T3; 219-1, grade III, T3 and 239-1, grade not determined, T2-4) resembled that of keratinocytes, suggesting that these cells express an early...

  13. Down-regulation of vimentin expression inhibits carcinoma cell migration and adhesion.

    Science.gov (United States)

    McInroy, Lorna; Määttä, Arto

    2007-08-17

    Vimentin is a type III Intermediate filament protein that is expressed frequently in epithelial carcinomas correlating with invasiveness and poor prognosis. We have analysed migration and adhesion to collagenous matrix of a panel of carcinoma cell lines. In vitro invasiveness was highest in vimentin-positive SW480 colon cancer and MDA-MB-231 breast cancer cells and the role of vimentin in these cell lines was investigated by RNA interference. Down-regulation of vimentin expression resulted in impaired migration in both scratch-wound experiments and in invasion assays through cell culture inserts coated with collagen gel. Compromised migration was observed in both cell lines, whereas cell attachment assays revealed impaired adhesion to fibrillar collagen in MDA-MB-231 cells while the adhesion of vimentin-ablated SW480 cells, that express both vimentin and keratin intermediate filaments was not affected. In conclusion, ablation of vimentin expression inhibits migration and invasion of colon and breast cancer cell lines.

  14. The Expression and Significance of RKIP in Lung Squamous Cell Carcinoma Tissues

    Directory of Open Access Journals (Sweden)

    Haiyuan XU

    2011-03-01

    Full Text Available Background and objective Raf kinase inhibitory protein (RKIP belongs to the phosphatidylethanolamine binding protein (PEBP family. RKIP is an endogenous inhibitor of the Raf-1-MEK1/2-ERK1/2 signaling pathway, NFkappaB signaling pathway and G protein coupled receptors signaling pathway. The aim of this study is to explore the expression of RKIP in lung squamous cell carcinoma, and the relationship between RKIP expression and clinical pathology of lung squamous cell carcinoma. Methods The expression of RKIP mRNA was detected in 56 lung squamous cell carcinoma tissues and adjacent cancer tissues by RT-PCR. The expression level of RKIP protein was detected by Western blot. The positive rates of RKIP expression in cancer tissues and adjacent cancer tissues were analyzed. Results RKIP mRNA positive expression rate in cancer tissues was significantly lower than that in adjacent cancer tissues (P < 0.05. The positive rate of RKIP mRNA expression in the cancer tissues with lymph node metastasis was significantly lower than that without lymph node metastasis (P < 0.05. RKIP mRNA expression has no remarkable correlation with age, sex, tumor differentiation and size (P > 0.05. RKIP protein expression in the cancer tissues was significantly lower than that in adjacent cancer tissues (P < 0.05. Conclusion The deficiency of RKIP expression is positively correlated with carcinogenesis and invasion metastasis of lung squamous cell carcinoma.

  15. Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas.

    Science.gov (United States)

    Pryor, Jennifer G; Simon, Rochelle A; Bourne, Patricia A; Spaulding, Betsy O; Scott, Glynis A; Xu, Haodong

    2009-02-01

    Merkel cell carcinoma is an uncommon and aggressive primary cutaneous neuroendocrine carcinoma with a high rate of recurrence and metastasis. Optimal management is controversial; consequently, it is imperative to identify the signaling pathways involved in the pathogenesis of Merkel cell carcinoma so that effective therapeutic targeting agents can be developed. We previously reported that K homology domain-containing protein overexpressed in cancer is expressed in high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. The K homology domain-containing protein overexpressed in cancer (KOC), also known as L523S and IMP-3, is an insulin-like growth factor II messenger RNA-binding protein that promotes tumor cell proliferation by enhancing insulin-like growth factor II protein expression. Expression of KOC in Merkel cell carcinoma has not been investigated. We studied 20 Merkel cell carcinomas by immunohistochemistry using a monoclonal antibody against L523S/KOC. Of 20 Merkel cell carcinomas, 18 (90%) overexpressed KOC, with 11 (55%) overexpressing KOC in greater than 90% of tumor cells, 3 (15%) overexpressing KOC in 50% to 90% of tumor cells, 3 (15%) overexpressing KOC in 10% to 50% of tumor cells, and 1 (5%) overexpressing KOC in less than 10% of tumor cells. The immunostaining intensity was variable, with moderate to strong staining in 14 cases and weak staining in the remaining 4. Extent of expression of K homology domain-containing protein overexpressed in cancer predicted metastasis (P = .04) and was weakly correlated with increased tumor size (P = .08). In conclusion, Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer with an expression pattern similar to high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. We propose K homology domain-containing protein overexpressed in cancer as a potential target molecule for the treatment of high

  16. RASSF1A expression inhibits cell growth and enhances cell chemosensitivity to mitomycin in BEL-7402 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    GUAN Hong-geng; XUE Wan-jiang; QIAN Hai-xin; ZHOU Xiao-jun; QIN Lei; LAN Jing

    2009-01-01

    Background The antitumor role of Ras association domain family 1A (RASSFIA) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSFIA in hepatoceliular carcinoma, and study the mechanisms of cell apoptosis induced by RASSFIA.Methods After stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Westem blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.Results Wild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatJn treatment.Conclusion Wild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.

  17. Survivin promotes the invasion of human colon carcinoma cells by regulating the expression of MMP‑7.

    Science.gov (United States)

    Gao, Fei; Zhang, Yuqin; Yang, Feng; Wang, Peng; Wang, Wenjun; Su, Yan; Luo, Weiren

    2014-03-01

    Increased expression levels of survivin are crucial for invasion activity in several types of human cancer, including colon carcinoma. However, the molecular mechanisms whereby survivin regulates cancer invasion have not been completely elucidated. To the best of our knowledge, this study is the first to investigate the role of matrix metalloprotease‑7 (MMP‑7) in cell invasion that is induced by survivin by using in vitro assays, including western blot, immunofluorescence and qPCR analyses. The results demonstrated that the ectopic expression of survivin significantly promoted the invasive activity of colon carcinoma cells (SW620 and HCT‑116) and resulted in increased levels of MMP‑7 activation. By contrast, the small interfering RNA (siRNA)‑based knockdown of survivin markedly reduced cell migration and led to a dose‑dependent decrease in MMP‑7 expression levels. Compared with the controls, knockdown of MMP‑7 by siRNA in colon carcinoma cells led to reduced invasion ability, whereas no obvious changes were observed when MMP‑7 expression was silenced in survivin‑overexpressing colon carcinoma cells. These findings demonstrate that MMP‑7 is crucial for survivin‑mediated invasiveness, suggesting that the survivin‑mediated MMP‑7 signaling pathway is a potential therapeutic target for the treatment of colon carcinoma.

  18. Expression of Caspase-3 in Laryngeal Squamous Cell Carcinoma and its Relationship with Cell Apoptosis

    Institute of Scientific and Technical Information of China (English)

    YU Yuan-chen; ZHONG Zhao-kun; LI Ji-xia; YU Chuan-ting

    2015-01-01

    Objective:To investigate the expression of Caspase-3 in laryngeal squamous cell carcinoma (LSCC) and its relationship with cell apoptosis. Methods: The expression of Caspase-3 protein in 43 LSCC tissues and 21 vocal cord polyp tissues was detected using immunohistochemical SP method; the apoptosis of LSCC was measured by in situ end-labeling (TUNEL) assay, and the relationships between Caspase-3 expression and clinicopathological features as well as cell apoptosis in LSCC tissue were analyzed. Results:The positive rate of Caspase-3 expression in LSCC tissue was lower than in vocal cord polyp tissue dramatically, with statistical significance (51.2%vs. 85.7%,P=0.007). Caspase-3 expression in LSCC tissue was closely related to the tumor differentiated degrees, clinical staging and presence or absence of lymph node metastasis (P=0.009, 0.001, 0.018) instead of the gender, age and tumor size (P>0.05). The apoptosis index (AI) of Caspase-3 was (4.31±0.49)% in LSCC tissue, while (24.28±1.07)% in vocal cord polyp tissue. Significant difference was presented between two groups by comparison to the AI (P<0.001). Spearman correlation analysis displayed that Caspase-3 expression in LSCC tissue had a signiifcantly positive correlation with the number of positive TUNEL cells (r=0.435,P=0.000). Conclusion: Low expression of Caspase-3 protein might promote the tumorigenesis and progression by reducing the apoptosis of tumor cells, and detection to its protein can be considered as an important index for judging the differentiation, clinical staging, inifltration and metastasis of laryngeal carcinoma.

  19. EXPRESSION OF ANNEXIN I IN TUMORIGENESIS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    吕宁; 薛丽燕; 林冬梅; 谢永强; 温芃; 何祖根

    2004-01-01

    Objective: To detect the expression of annexin I in esophageal squamous cell carcinoma and precursor lesions,and evaluate its effect on the tumorigenesis. Methods: The immunohistochemistry S-P method was used to determine the expression of annexin I in 135 cases of esophageal squamous cell carcinoma, in which precursor lesions were found in some cases, and in the corresponding normal controls. Results: Of 135 cases, 35 (25.9%) were strongly positive, 60 (44.4%) were weakly positive and 40 (29.6%)negative, while in the corresponding normal controls, 129(95.6%) were strongly positive, 6 (6.4%) weakly positive.The expression of annexin I was decreased in esophageal squamous cell carcinoma (P<0.0001), and the degree and rate of the decrease did not show correlation with age,gender, differentiation, and lymph node metastasis (P>0.05).The expression of annexin I was also decreased in the lesions of dysplasia and carcinoma in situ, with 2 (4.3%) strongly positive, 17 (37.0%) weakly positive and 27(58.7%) negative (P<0.0001). Conclusion: Annexin I may be useful in early detection of esophageal squamous cell carcinoma and in evaluation of predisposition for the risk of cancerization of precursor lesions.

  20. EXPRESSION OF EPIDERMAL GROWTH FACTOR RECEPTOR IN DIFFERENT SALIVARY ADENOID CYSTIC CARCINOMA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    MA Jie; ZONG Zhi-hong; WANG Zhao-yuan

    2005-01-01

    Objective: To investigate the expression of epidermal growth factor receptor, a receptor tyrosine protein kinase, in the subcellular fractions of human salivary adenoid cystic carcinoma cell lines SACC-83 and SACC-LM. Methods: Low metastatic and high metastatic cells of the adenoid cystic carcinoma, SACC-83 and SACC-LM, were cultured. Their subcellular fractions were extracted. The expression of epidermal growth factor receptor was detected with Western blot method, and the results of protein expression were quantitatively analyzed by FluorChem V2.0 software. Results: The results of Western blot analysis indicated that, EGFR expression on the membrane of SACC-83 cells was significantly higher than that of SACC-LM cells, but its expression in cytoplasm was significantly less in the former than the later (P<0.01). In SACC-83 cell line, EGFR was over-expressed in membrane (P<0.01), but in SACC-LM cell line, EGFR was over-expressed in cytoplasm (P<0.01). Conclusion: The results suggest that the obtaining of metastasis ability is related to the high expression of EGFR protein in cytoplasm, so the molecular targeting therapy to EGFR may be an ideal treatment for the invasion and metastasis of salivary adenoid cystic carcinoma.

  1. Correlation between Grade in Transitional Cell Carcinoma (TCC and Expression of Epidermal Growth Factor Receptor (EGFR

    Directory of Open Access Journals (Sweden)

    MR Jallali Nadoushan

    2007-08-01

    Full Text Available Background: The present study was undertaken to investigate the correlation of Epidermal Growth Factor Receptor (EGFR expression with grade of Transitional Cell Carcinoma (TCC. Methods: Tumor samples of 75 patients from Mostafa Khomaini Hospital with Transitional Cell Carcinoma of the bladder were analyzed by immunohistochemistry for expression of EGFR. In this context, we assigned the bladder tumors a grade accord¬ing WHO classification. Results analyzed for possible correlation with the expression status of the Epidermal Growth Factor Receptor (EGFR. Results: This cross-sectional study showed that all grades of Transitional Cell Carcinoma expressed EGFR, and 14 cases were LMP (18.9% which 10 cases among them had negative cells according EGFR point of view(71.4% and 4 cases had re¬ported positive (28.6%. Thirty five cases were low grade (46.7% which 18 cases among them had reported negative cells (51.4% and 17 cases had positive cells (48.6%. Twenty six cases were high grade (34.7% that 9 cases among them had reported negative cells (34.6%. Seventeen cases had positive cells (65.4%. Mann-Witney test showed relation between grade and expression of EGFR (P<0.05. Conclusions: This study showed that expression of EGFR is correlated with grade of tumor.

  2. The expression of glucose regulated protein-94 in colorectal carcinoma cells treated by sodium butyrate

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at G0/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.

  3. The expression of glucose regulated protein—94 in colorectal carcinoma cells treated by sodium butyrate

    Institute of Scientific and Technical Information of China (English)

    WUYIDI; JINDANSONG

    2000-01-01

    The expression of glucose regulated protein 94 (GPR94) during the treatment of human colorectal carcinoma cell lineClone A cells with codium butyrate was studied.Dodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at G0/G1 stage and cell differentiation as observed by morphological changes,MTT and flow cytometry assays,as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays.The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.

  4. Gender specific expression of tumor suppressor PKCd versus oncogenic PKCn in renal cell carcinoma

    OpenAIRE

    Brenner, Walburgis; Färber, Gloria; Jan G. Hengstler; Herget, Thomas; Thüroff, Joachim W.; Wiesner, Christoph

    2003-01-01

    Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was ex...

  5. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  6. Expression of Caveolin-1 in tongue squamous cell carcinoma by quantum dots

    Directory of Open Access Journals (Sweden)

    J. Xue

    2010-04-01

    Full Text Available Quantum dots (QDs are a new class of fluorescent probes to detect biomarker expression. The role of caveolin-1 (Cav-1 in tongue squamous cell carcinoma (TSCC is still unknown. This study aimed to investigate the expression profile of Cav-1 in carcinogenesis and development of TSCC by QDs immunofluorescence histochemistry (QDs-IHC and discuss the relationship between the Cav-1 expression and the clinicopathological outcomes. QDs-IHC was used to detect Cav-1 expression in tissue microarrays including normal tongue mucosa (NTM; n=10, hyperplastic tongue mucosa (HTM; n=10, tongue pre-cancer lesions (TPL; n=15 and primary tongue squamous cell carcinoma (PTSCC; n=61. Correlations between the Cav-1 expression and clinicopathologic variables were evaluated statistically. Cells positive for Cav-1 were clearly detected and bright images were obtained in a fine, granular pattern at the cell membrane and cytoplasm using QDs-IHC. The rate of Cav-1 immunoreactivity increased progressively from NTM (0%, HTM (0%, TPL (36% to PTSCC (74%. When compared with each other, there was statistical significance among PTSCC, TPL and NTM as well as among PTSCC, TPL and HTM. Moreover, Cav-1 expression level in PTSCC was correlated positively with clinical stage and histologic grade. QDs-IHC could accurately detect protein location in tongue mucosa. An increased expression of Cav-1 in the stepwise carcinogenesis from NTM, HTM, TPL to PTSCC suggested that Cav-1 might be an oncogene in the development of tongue squamous cell carcinoma.

  7. Expression of thymidylate synthase and glutathione-stransferase π in patients with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-Xing Huang; Feng-Yue Li; Wei Xiao; Zheng-Xiang Song; Rong-Yu Qian; Ping Chen; Eeva Salminen

    2009-01-01

    AIM: To investigate the expression of thymidylate synthase (TS) and glutathione-s-transferase π (GST-π) in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS: Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma (ESCC) tissue sections from 102 patients (median age, 58 years) and in 28 normal esophageal mucosa (NEM) samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS: The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples (P < 0.05). The expression level of TS was not only significantly lower in well-differentiated (21.88%) than in poorly-differentiated carcinomas (51.43%, P < 0.05), but was also significantly higher in samples from male patients (46.51%) than from female patients (18.75%, P < 0.05). GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples (P < 0.05). The expression level of GST-π was also significantly higher in welldifferentiated carcinomas (65.63%) than in poorlydifferentiated carcinomas (35.00%, P < 0.05). CONCLUSION: The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of TS and reduced expression of GST-π.

  8. Expression of E-Cadherin in Oral Squamous Cell Carcinoma is Associated with Clinical Prognosis

    Institute of Scientific and Technical Information of China (English)

    Jianming Zhang; Wei Zhang; Ping Gao; Yanqiu Li; Changyi Li; Sakan Maeda

    2006-01-01

    OBJECTIVE To investigate the correlation of E-cadherin expression with clinicopathological parameters and prognosis of patients with oral squamous cell carcinoma.METHODS We examined the expression of the protein E-cadherin in 43 oral squamous cell carcinoma (SCC) surgical speciments by SABC immunohistochemistry.RESULTS There was a significant correlation between the level of Ecadherin expression and tumor stage (P=0.024), invasive pattern (P=0.009) and lymph node metastasis (P=0.023). No relation was found with age (P=0.084), sex (P=1.356) and differentiation (P=0.877). Using the Kaplan-Meier method we demonstrated that those cases which showed E-cadherin expression (-) or (+) had a significantly poorer prognosis compared those cases which showed expression (++) or (+++) (P= 0.0146).CONCLUSION E-cadherin, is an important indicator of clinical diagnoses and prognositic marker for oral SCC patients.

  9. Relation between parthenolideinduced cytotoxicity and COX—2 expression in nasopharyngeal carcinoma cell

    Institute of Scientific and Technical Information of China (English)

    LinYL; OngCN

    2002-01-01

    To investigate the potential anti-tumor effects and its relative its relative mechanism of active component in chrysanthemum,on human nasopharyngeal carcinoma(NPC).Parthenolide(PN) was used as tested substance and exposed to NPC cell lines,CNE1 and CNE2.Cell toxicity indexes and cyclooxygenase-2(COX-2) expression were determined.Results showed that in CNE1 cells,with high level COX-2,there were significant cytotoxicities after PN-treated.However,there were not inducible effects on CNE2 cells with low level COX-2.It was indicated that PN could induce cytotoxicity in NPC cell,which correlated with its intracellular COX-2 expression.

  10. Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

    Directory of Open Access Journals (Sweden)

    Karagoz Filiz

    2010-06-01

    Full Text Available Abstract Background The aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF and phosphatase and tensin homolog deleted in chromosome ten (PTEN, angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx. Methods We examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored. Results The tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively. While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128, there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006 and lymph node metastasis (p = 0.048 but not cartilage invasion (p = 0.129. MVD was significantly higher in high-grade tumors (p = 0.003 but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204. There was also no significant relationship between PTEN and VEGF expression (p = 0.161 and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively. Conclusions Increased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.

  11. Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Swati Saawarn

    2012-01-01

    Full Text Available Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC. Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

  12. Clinical significance of expression of Klotho and β-Catenin in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    汤小伟

    2013-01-01

    Objective To investigate the clinical significance of expression of Klotho and β-Catenin in esophageal carcinoma. Methods Tissue microarray technique and immunohistochemistry were used to examine Klotho and β-Catenin expression in 75 esophageal carcinoma tissue

  13. Interdependence of Gemcitabine Treatment, Transporter Expression, and Resistance in Human Pancreatic Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Wolfgang Hagmann

    2010-09-01

    Full Text Available Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU alters the cellular transporter expression profile and that modulation of the expression of multidrug resistance protein 5 (MRP5; ABCC5 influences the chemoresistance of these tumor cells. Here, we studied the influence of acute and chronic gemcitabine treatment on the expression of relevant uptake and export transporters in pancreatic carcinoma cells by reverse transcription-polymerase chain reaction (RT-PCR, quantitative RT-PCR, and immunoblot analyses. The specific role of MRP5 in cellular gemcitabine sensitivity was studied by cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure to gemcitabine (12 nM for 3 days did not alter the messenger RNA (mRNA expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1 (ENT1, whereas high dosages of the drug (20 µM for 1 hour elicited up-regulation of these transporters in most cell lines studied. In cells with acquired gemcitabine resistance (up to 160 nM gemcitabine, the mRNA or protein expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to 40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either MRP5-overexpressing (HEK and PANC-1 or MRP5-silenced (PANC1/shMRP5 cells indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data not only on drug-induced alterations of transporter expression relevant for gemcitabine uptake and export but also on the link between gemcitabine sensitivity and MRP5 expression may lead to improved strategies of future chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.

  14. HIF1-Alpha Expression Predicts Survival of Patients with Squamous Cell Carcinoma of the Oral Cavity

    Science.gov (United States)

    dos Santos, Marcelo; Mercante, Ana Maria da Cunha; Louro, Iúri Drumond; Gonçalves, Antônio José; de Carvalho, Marcos Brasilino; da Silva, Eloiza Helena Tajara; da Silva, Adriana Madeira Álvares

    2012-01-01

    Background Oral squamous cell carcinoma is an important cause of death and morbidity wordwide and effective prognostic markers are still to be discovered. HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors survival. The relationship between HIF1α expression, tumor progression and treatment response in head and neck cancer is still poorly understood. Patients and Methods In this study, we investigated HIF1α expression by immunohistochemistry in tissue microarrays and its relationship with clinical findings, histopathological results and survival of 66 patients with squamous cell carcinoma of the lower mouth. Results Our results demonstrated that high HIF1α expression is associated with local disease-free survival, independently from the choice of treatment. Furthermore, high expression of HIF1α in patients treated with postoperative radiotherapy was associated with survival, therefore being a novel prognostic marker in squamous cell carcinoma of the mouth. Additionally, our results showed that MVD was associated with HIF1α expression and local disease relapse. Conclusion These findings suggest that HIF1α expression can be used as a prognostic marker and predictor of postoperative radiotherapy response, helping the oncologist choose the best treatment for each patient. PMID:23028863

  15. Reversing effect of exogenous WWOX gene expression on malignant phenotype of primary cultured lung carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yu-long; LI Yue-chuan; SHOU Feng; LIU Chang-qi; PU Yong; TANG Hua

    2010-01-01

    Background Whether WW domain containing oxidoreductase (WWOX) gene is a tumor-suppressor is still controversial. Some researchers found that the transcription of the WWOX gene was lacking not only in tumor tissues but also in non-tumorous tissues and sometimes in normal tissues. Hence it is important to explore the role of the expression of the exogenous WWOX gene in the proliferation and apoptosis of primary cultured lung carcinoma cells. Methods Lipofection technique was used to determine primary cultured lung carcinoma cells containing the highly expressed exogenous WWOX gene and primary cultured cells with vectors as controls. An animal model of lung cancer was made by subcutaneous implantation of tumor cells into nude mice. RT-PCR, Western blotting, flow cytometry, and TUN EL were used to detect the transcription, expression of the exogenous gene and the effect of the expression of targeted genes on the proliferation and apoptosis of the primary cultured lung carcinoma cells. Results The growth, clone formation rate (CFR) ((5.33±1.53)%) of the primary lung cancer cells transfected with the WWOX gene, tumor size and weight were significantly lower than those of the non-transfected lung cancer cells (CFR: (14.33±1.53)%) and the primary lung cancer cells transfected with blank plasmids (CFR: (11.00±1.73)%, P<0.05). The apoptosis level of primary lung cancer cells transfected with the WWOX gene ((40.72±5.20)%) was significantly higher than that of the non-transfected lung cancer cells ((2.76±0.02)%) and the primary lung cancer cells transfected with blank plasmids ((2.72±0.15)%, P<0.05). Conclusion The expression of the exogenous WWOX gene can significantly inhibit the proliferation of lung cancer cells and induce their apoptosis, suggesting that the WWOX gene possesses tumor-suppressing effect.

  16. Expression signature in peripheral blood cells for molecular diagnosis of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Braakhuis, B J M; Graveland, A P; Dijk, F; Ylstra, B; van Wieringen, W N; Leemans, C R; Brakenhoff, R H

    2013-07-01

    Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis due to the development of locoregional recurrences, distant metastases, and second primary tumors. There is an urgent need for biomarkers that enable detection and monitoring of the disease to provide adequate therapeutic strategies. In this study, we have investigated markers in peripheral blood cells (PBC) of 28 HNSCC patients who underwent surgery by means of expression profiling. Our hypothesis is that nucleated blood cells circulate continuously, also pass the tumor, and change their expression profile in response to tumor cell factors. For comparison, we enrolled a control group of 11 patients who underwent surgery in the head and neck region for non-HNSCC reasons. A set of 2949 genes was found to be statistically different between the groups (P < 0.05, false discovery rate-corrected) and the most prominently different pathways were EIF2, EIF4, and mTOR signaling. These preliminary results are promising and warrant further studies on the definitive role of PBC gene expression as a biomarker for HNSCC detection and monitoring.

  17. Over-expression of LPTS-L in hepatocellular carcinoma cell line SMMC-7721 induces crisis

    Institute of Scientific and Technical Information of China (English)

    Cheng Liao; Mu-Jun Zhao; Jing Zhao; Di Jia; Hai Song; Zai-Ping Li

    2002-01-01

    AIM: To evaluate the function of the longer transcripts LPTS-Lin hepatocellular carcinoma cell line SMMC-7721.METHODS: SMMC-7721 cells were transfected with LPTSL expression construct and stably transfected cells were selected by G418. Multiple single clones formed and were checked for their phenotype. In the study of the effect on telomerase activity of LPTS-Lin vitro, GST-LPTS-L fusion protein was expressed in E.coli and purified by glutathioneagarose column. Telomeric repeat amplification protocol (TRAP) assays were performed to study the influence of telomerase activity in SMMC-7721 cells.RESULTS: Over-expression of LPTS-L induced SMMC-7721 cells into crisis. LPTS-L could inhibit the telomerase activity in SMMC-7721 cellsin vitro.CONCLUSION: LPTS-L is a potent telomeraseinhibitor. Over-expression of LPTS-L can induce hepatoma cells into crisis due to the reduction of telomerase activity.

  18. Expression of interleukin-6 is downregulated by 17-(allylamino)-17-demethoxygeldanamycin in human prostatic carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Ke-hung TSUI; Tsui-hsia FENG; Wen-chi HSIEH; Phei-lang CHANG; Horng-heng JUANG

    2008-01-01

    Aim: Interleukin-6 (IL-6) is a pleiotropic cytokine that is associated with tumor metastasis and prostate cancer. We evaluated the mechanism and effect of 17-(allylamino)-17-demethoxygeldanamycin (17AAG), a novel inhibitor of heat shock protein 90 (Hsp90), on the IL-6 gene expression in human prostatic carcinoma (PC-3) cells. Methods: Quantitative IL-6 and IL-6 receptor (IL-6R) expressions were assessed using RT-PCR. The deregulation of 17AAG and phor-bol 12-myristate 13-acetate (PMA) on the IL-6 gene was determined by ELISA and transient gene expression assays using an IL-6 reporter vector. Results: Although the IL-6R is ubiquitously expressed by prostatic epithelium cells, the IL-6 expression is only found in advanced prostatic carcinoma cells, such as PC-3 and DU145. Further studies using RT-PCR indicated that 17AAG downregulated the gene expression of IL-6. ELISA and the transient gene expression assay revealed that 17AAG blocked the stimulation of PMA of IL-6 gene expression in PC-3 cells. The PMA-induced IL-6 gene expression is dependent on the NF-κB response element. However, the effect of 17AAG appears to be mediated via a region located at -149 to +8 bp upstream of the transcriptional starting site of the IL-6 gene, and might not be through the NF-κB signaling pathway. Conclusion: The present study reveals that IL-6 is transcriptionally downregulated in human prostatic carcinoma cells in response to 17AAG. This result suggests the presence of a novel Hsp90 mediation pathway that is involved in the deregulation on the transcription of the human IL-6 gene in human prostate cancer.

  19. The relationship between Interleukin 18 expression in laryngeal squamous cell carcinoma and clinical pathology as well as the effect of cetuximab on its expression

    Institute of Scientific and Technical Information of China (English)

    Xiu-Ping Liao; Nian Lyu; Sen-Lan Long

    2015-01-01

    Objective:To explore the relationship between Interleukin 18 (IL-18) expression in laryngeal squamous cell carcinoma and clinical pathology as well as the effect of cetuximab on its expression.Methods:40 cases of patients with laryngeal squamous cell carcinoma from January 2010 to June 2014 were chosen as the research group; 40 cases of patients with vocal cord polyp and 40 healthy volunteers were chosen as the control group. Statistical analysis was carried out on clinical pathology of laryngeal squamous cell carcinoma. IL-18, IFN-γ, TNF-αand IL-6 levels in peripheral blood mononuclear cells before and after cetuximab application were detected.Results:Detected IL-18 values of laryngeal squamous cell carcinoma group were higher than those of adjacent cancer tissue and vocal cord polyps; IL-18 positive rate (75.0%) of laryngeal squamous cell carcinoma group was higher than that of adjacent cancer tissue (47.5%) and polyp tissue (37.5%); IL-18 expressions of laryngeal squamous cell carcinoma group were related to primary lesion staging, differentiation degree and lymph node metastasis; before cetuximab application, IL-18 levels were significantly higher than those of the control group, and after cetuximab application, IL-18 levels significantly decreased than before. Differences were statistically significant; after cetuximab application, IFN-γ, TNF-αand IL-6 levels in PBMCs supernatant of patients with laryngeal squamous cell carcinoma were significantly lower than before. Differences were statistically significant.Conclusion:IL-18 can be highly expressed in laryngeal squamous cell carcinoma; IL-18 expression is involved in the occurrence and progress of laryngeal squamous cell carcinoma; IL-18 is possible to be involved in the occurrence and progress of laryngeal squamous cell carcinoma through regulating expressions of IFN-γ, TNF-α and IL-6, etc; IL-18 can be used as a target of laryngeal squamous cell carcinoma treatment, and cetuximab can inhibit IL-18

  20. Prostaglandin E₂ receptor EP2 mediates Snail expression in hepatocellular carcinoma cells.

    Science.gov (United States)

    Cheng, Shan-Yu; Zhang, Hai; Zhang, Min; Xia, Shu-Kai; Bai, Xiao-Ming; Zhang, Li; Ma, Juan; Rong, Rong; Wang, Yi-Pin; Du, Ming-Zhan; Wang, Jie; Chen, Meng; Shi, Feng; Yang, Qin-Yi; Leng, Jing

    2014-05-01

    Prostaglandin E2 (PGE2) has been shown to influence cell invasion and metastasis in several types of cancer, including hepatocellular carcinoma (HCC). however, the molecular mechanisms underlying it remain to be further elucidated. Snail, as one of key inducers of epithelial-mesenchymal transition (EMT), plays pivotal roles in HCC invasion and metastasis. The present study was designed to evaluate the possible signaling pathways through which PGE2 regulates Snail protein expression in HCC cell lines. PGE2 markedly enhanced Huh-7 cell invasion and migration ability by upregulating the expression level of Snail protein, and EP2 receptor played an important role in this process. Src, EGFR, Akt and mTOR were all activated and involved in the regulation of snail protein expression. Our findings suggest that PGE2 could upregulate the expression level of Snail protein through the EP2/Src/EGFR/Akt/mTOR pathway in Huh-7 cells, which promotes HCC cell invasion and migration.

  1. p63 and E-cadherin Expression in Canine Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Mestrinho, L A; Pissarra, H; Faísca, P B; Bragança, M; Peleteiro, M C; Niza, M M R E

    2015-07-01

    The expression of p63 and E-cadherin was studied in 22 oral squamous cell carcinomas in the dog according to immunohistochemical techniques. The association between these markers and clinicopathologic parameters was assessed. All tumor cells studied showed enhanced p63 expression. Regarding E-cadherin expression, 17 of 22 cases (77.3%) showed decreased immunoreactivity, and in 13 of 22 cases (59.1%), its expression was cytoplasmic. Neither p63 nor E-cadherin expression patterns were associated with tumor size, bone invasion, or lymph node metastasis. p63 score was related to proliferating cell nuclear antigen proliferative index (P = .020). A statistically significant correlation between the expression patterns of these 2 markers was noted (P = .026). Furthermore, they were related with tumor grade. An atypical p63 labeling and a cytoplasmic E-cadherin staining were statistically related with a higher tumor grade (P = .022 and P = .017, respectively). These findings suggest that changes in p63 and E-cadherin expression are frequent events in oral squamous cell carcinoma in dogs.

  2. Prostate specific antigen gene expression in androgen insensitive prostate carcinoma subculture cell line.

    Science.gov (United States)

    Tsui, Ke-Hung; Feng, Tsui-Hsia; Chung, Li-Chuan; Chao, Chun-Hsiang; Chang, Phei-Lang; Juang, Horng-Heng

    2008-01-01

    A novel prostate cancer cell line (PC-J) was isolated from an androgen independent non-prostate specific antigen (non-PSA) producing carcinoma cell line. The homologous correlation between PC-J and PC-3 was determined by short tandem repeat analysis. The PSA promoter activity was detected by transient expression assay in the PC-J and LNCaP cells but not in androgen insensitive PC-3 cells. When the PC-J cells were cotransfected with androgen receptor, androgen receptor coactivators and PSA reporter vector cells, the reporter assays indicated that nuclear receptor coactivator 4 (NCOA4) but not androgen receptor activator 24 (ARA24) increased the sensitivity and maximum stimulation of dihydrotestosterone (DHT)-inducing PSA promoter activity. The RT-PCR assays revealed that the expression of several tumor markers, including interleukin-6, prostate stem cell antigen (PSCA), prostate epithelium-specific Ets transcription factor (PDEF) and matriptase, was lower in the PC-J cells than in the PC-3 cells. This cell model elucidated the regulation of PSA expression and enabled comparison of the gene profile at different stages of metastasis in prostatic carcinoma.

  3. Identification of differentially expressed genes in two new human bladder carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To screen and identify differentially expressed genes in two new human urothelial carcinoma cell lines, BLS-211 and BLX. Methods Suppression subtractive hybridization (SSH) was used to createa subtracted library, and clones were sequenced. Results Totally 13 over-expressed genes in BLX and 9 in BLS-211 cells were obtained, respectively. Among them, 18 were known genes and 4 were new ESTs (Expressed Sequence Tag), and were collected by GenBank dbEST database (The access number was EB390424-7). Conclusion SSH is a powerful method for the identification of differentially expressed genes. The differential expression of some BCG-associated genes in different cells may be related to the different responses to clinical BCG therapy. The identified new ESTs can be cloned for full length to further study their functions.

  4. COX-2 mRNA expression in esophageal squamous cell carcinoma (ESCC) and effect by NSAID.

    Science.gov (United States)

    Liu, X; Li, P; Zhang, S-T; You, H; Jia, J-D; Yu, Z-L

    2008-01-01

    To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

  5. Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis

    Directory of Open Access Journals (Sweden)

    Nakamura Shinichiro

    2011-01-01

    Full Text Available Abstract Background Runt-related transcription factor 3 (RUNX3 is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC. Methods RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results RUNX3 protein expression was frequently inactivated in the HCC cell lines (91% and tissues (90%. RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

  6. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Almstrup, K; Nielsen, J E

    2005-01-01

    AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG......; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring...

  7. Membrane androgen binding sites are preferentially expressed in human prostate carcinoma cells

    Directory of Open Access Journals (Sweden)

    Delakas Dimitrios

    2003-01-01

    Full Text Available Abstract Background Prostate cancer is one of the most frequent malignancies in males. Nevertheless, to this moment, there is no specific routine diagnostic marker to be used in clinical practice. Recently, the identification of a membrane testosterone binding site involved in the remodeling of actin cytoskeleton structures and PSA secretion, on LNCaP human prostate cancer cells has been reported. We have investigated whether this membrane testosterone binding component could be of value for the identification of prostate cancer. Methods Using a non-internalizable testosterone-BSA-FITC analog, proven to bind on membrane sites only in LNCaP cells, we have investigated the expression of membrane testosterone binding sites in a series of prostate carcinomas (n = 14, morphologically normal epithelia, taken from areas of the surgical specimens far from the location of the carcinomas (n = 8 and benign prostate hyperplasia epithelia (n = 10. Isolated epithelial cells were studied by flow cytometry, and touching preparations, after 10-min incubation. In addition, routine histological slides were assayed by confocal laser microscopy. Results We show that membrane testosterone binding sites are preferentially expressed in prostate carcinoma cells, while BPH and non-malignant epithelial cells show a low or absent binding. Conclusions Our results indicate that membrane testosterone receptors might be of use for the rapid routine identification of prostate cancer, representing a new diagnostic marker of the disease.

  8. Expression of midkine and its clinical significance in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-Jia Ren; Qing-Yun Zhang

    2006-01-01

    AIM: To investigate the expression of midkine in esophageal squamous cell carcinoma (ESCC) and analyze its relationship with clinicopathological features.METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of midkine mRNA and protein in EC109 cells, respectively. Then the expression of midkine in 66 cases of ESCC samples were detected by immunohistochemistry using monoclonal antibodies against human midkine. RESULTS: Midkine was expressed in EC109 cell by RTPCR and immunocytochemistry. The immunoreactivity was detected in 56.1% (37/66) of the ESCC samples.The expression of midkine was found in cytoplasm of tumor cells. Notably, the intensity of midkine was stronger at the area abundant in vessels and the invading border of the tumors. Midkine was more intensely expressed in well differentiated tumors (76.9%)than in moderately and poorly differentiated tumors (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant correlation between midkine expression and gender, age, clinical stage, lymph node metastasis or survival in ESCC.CONCLUSION: Midkine is overexpressed in ESCC. It may play a role in tumor angiogenesis and invasion.The expression of midkine is correlated with tumor cell differentiation in ESCC. The more poorly tumor cells differentiate, the weaker midkine expresses.

  9. Fibrolamellar carcinoma of the liver: composition of the extracellular matrix and expression of cell-matrix and cell-cell adhesion molecules.

    Science.gov (United States)

    Scoazec, J Y; Flejou, J F; D'Errico, A; Fiorentino, M; Zamparelli, A; Bringuier, A F; Feldmann, G; Grigioni, W F

    1996-11-01

    We have analyzed the composition of the tumor stroma and the expression of cell-matrix and cell-cell adhesion molecules in 11 cases of fibrolamellar carcinoma of the liver (FLC), in comparison with 34 cases of hepatocellular carcinoma and 8 cases of focal nodular hyperplasia. Fibrolamellar carcinoma was characterized by the presence of large amounts of tenascin in tumor stroma and by the scarce expression of basement membrane components at the contact of neoplastic clusters. Like normal hepatocytes, neoplastic cells constantly expressed the alpha1 integrin chain, lacked the beta4 integrin chain, and coexpressed E-cadherin and the hepatocyte N-related cadherin. Abnormalities in the expression of cell adhesion molecules, including altered cadherin expression, alphaV integrin chain induction, and CD44 expression, were detected in the majority of cases. The composition of the tumor stroma and the pattern of expression of cell adhesion molecules in fibrolamellar carcinoma were reminiscent of those observed in grade III and grade IV hepatocellular carcinomas. Our results therefore show that, despite its slow local growth and good prognosis, fibrolamellar carcinoma expresses many characteristics usually associated with clinically aggressive malignancies. Further studies are needed to identify the factors responsible for the apparent dissociation between clinical behavior and biological characteristics in this tumor.

  10. Gene expression profiles at different stages of human esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jin Zhou; Li-Qun Zhao; Mo-Miao Xiong; Xiu-Qin Wang; Guan-Rui Yang; Zong-Liang Qiu; Min Wu; Zhi-Hua Liu

    2003-01-01

    AIM: To characterize the gene expression profiles in differentstages of carcinogenesis of esophageal epithelium.METHODS: A microarray containing 588 cancer relatedgenes was employed to study the gene expression profileat different stages of esophageal squamous cell carcinomaincluding basal cell hyperplasia, high-grade dysplasia,carcinoma in situ, early and late cancer. Principle componentanalysis was performed to search the genes which wereimportant in carcinogenesis.RESULTS: More than 100 genes were up or down regulatedin esophageal epithelial cells during the stages of basal cellhyperplasia, high-grade dysplasia, carcinoma in situ, earlyand late cancer. Principle component analysis identified aset of genes which may play important roles in the tumordevelopment. Comparison of expression profiles betweenthese stages showed that some genes, such as P160ROCK,JNK2, were activated and may play an important role inearly stages of carcinogenesis. CONCLUSION: These findings provided an esophagealcancer-specific and stage-specific expression profiles,showing that complex alterations of gene expression underliethe development of malignant phenotype of esophagealcancer cells.

  11. Increased expression of the matrix metalloproteinase 2 in differentiating Tera 2 human embryonal carcinoma cells.

    Science.gov (United States)

    Tienari, J; Pertovaara, L; Saksela, O; Lehtonen, E; Vartio, T

    1994-01-15

    Secretion of proteolytic enzymes by cells has been implicated in tissue remodeling during embryonic development as well as in invasive neoplastic diseases. We studied the regulation of type-IV-collagenase activity in Tera 2 human embryonal carcinoma cells, which in the undifferentiated state proliferate rapidly and are tumorigenic. The undifferentiated cells produced relatively low levels of matrix-metalloproteinase-2 (MMP-2) activity. This activity was not markedly affected by exogenous basic fibroblast growth factor (bFGF) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA), even though the plasminogen activator activity of the cells was increased by these agents. Tera 2 cells can be induced by retinoic acid to differentiate into quiescent cells, of which many express neuronal characteristics. The type-IV-collagenase activity of the cells increased markedly during the differentiation. This increase was mainly due to increased expression of MMP-2. Expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was not markedly affected by the differentiation of Tera 2 cells. The results show that in the Tera 2 cell system, increased expression of MMP-2 is characteristic of the differentiated derivatives. This is in contrast with many other model systems, where increased type-IV-collagenase activity is associated with the malignant phenotype. This pattern of regulation may reflect the facts that Tera 2 cells resemble early embryonic cells and that their differentiation mimics related cell-differentiation processes in the developing embryo.

  12. Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Liang-Hui Shi; Xiao-Qun Zhu; Guo-Hai Zhao; Ya-Bin Xia; Yi-Sheng Zhang

    2006-01-01

    AIM: To investigate the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in gastric carcinoma and its clinical significance and to explore its relationship with cell proliferation.METHODS: Expressions of IGFBP-2 and Ki-67 in 118cases of gastric carcinoma and 40 cases of normal gastric mucosa were detected by EnVision immunohistochemical technique.RESULTS: Expression of IGFBP-2 in gastric carcinoma was higher than that in normal gastric mucosa (P 0.05). Fxpression of IGFBP-2 in aclvancecl gastric carcinoma was higher than that in early gastric carcinoma (P < 0.05). Expression of IGFBP-2 in gastric carcinoma with lymph node metastasis was higher than that without lymph node metastasis (P < 0.01).IGFBP-2 expression was a positively related to the clinical stage of gastric carcinoma (P < 0.01). There was a positive correlation between IGFBP-2 and Ki-67 (P < 0.05).CONCLUSION: IGFBP-2 may be involved in carcinogenesis and progression of gastric carcinoma by promoting cell proliferation.

  13. RASSF1A protein expression and correlation with clinicopathological parameters in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Machtens Stefan

    2008-09-01

    Full Text Available Abstract Background Epigenetic silencing of RAS association family 1A (RASSF1A tumor suppressor gene occurs in various histological subtypes of renal cell carcinoma (RCC but RASSF1A protein expression in clear cell RCC as well as a possible correlation with clinicopathological parameters of patients has not been analyzed at yet. Methods 318 primary clear cell carcinomas were analyzed using tissue microarray analysis and immunohistochemistry. Survival analysis was carried out for 187 patients considering a follow-up period of 2–240 month. Results Expression of RASSF1A was found to be significantly decreased in tumoral cells when compared to normal tubular epithelial cells. RASSF1A immunopositivity was significantly associated with pT stage, group stage and histological grade of tumors and showed a tendency for impaired survival in Kaplan-Meier analysis. Conclusion While most tumors demonstrate a loss of RASSF1A protein, a subset of tumors was identified to exhibit substantial RASSF1A protein expression and show increased tumor progression. Thus RCC tumorigenesis without depletion of RASSF1A may be associated with an adverse clinical outcome.

  14. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Nicolas, E-mail: simplissimus@gmx.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de [Department of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Splittstoesser, Vera, E-mail: Veri.sp@web.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de [Department of Internal Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg (Germany); Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de [Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

  15. The expression of calretinin and cytokeratins in canine acanthomatous ameloblastoma and oral squamous cell carcinoma.

    Science.gov (United States)

    Fulton, A; Arzi, B; Murphy, B; Naydan, D K; Verstraete, F J M

    2014-12-01

    Oral squamous cell carcinoma (OSCC) and canine acanthomatous ameloblastoma (CAA) represent two epithelium-derived neoplasms that affect the oral cavity of dogs. The expression of cytokeratins (CKs) and calretinin has been previously established in the canine tooth bud and odontogenic tumours. The aim of this study was to characterize the CK and calretinin expression profile of OSCC in comparison to CAA and canine tooth bud tissues. Samples from 15 OSCC and 15 CAA cases, as well as 6 tooth buds and 2 normal gingival tissues were examined. OSCC CK expression was consistent with the CK expression profile of CAA and canine tooth bud tissue. Calretinin was positively expressed in 10 of 15 OSCC cases, with 5 cases demonstrating high staining intensity. Only 2 of 15 CAA cases demonstrated mild-moderate staining intensity. The statistically significant difference in staining pattern and intensity of calretinin in OSCC and CAA can help distinguish between these two tumour types.

  16. Altered expression of heat shock proteins in embryonal carcinoma and mouse early embryonic cells.

    Science.gov (United States)

    Morange, M; Diu, A; Bensaude, O; Babinet, C

    1984-04-01

    In a previous paper, we have shown that in the absence of stress, mouse embryonal carcinoma cells, like mouse early embryo multipotent cells, synthesize high levels of 89- and 70-kilodalton heat shock proteins (HSP)(O. Bensaude and M. Morange, EMBO J. 2:173-177, 1983). We report here the pattern of proteins synthesized after a short period of hyperthermia in various mouse embryonal carcinoma cell lines and early mouse embryo cells. Among the various cell lines tested, two of them, PCC4-Aza R1 and PCC7-S-1009, showed an unusual response in that stimulation of HSP synthesis was not observed in these cells after hyperthermia. However, inducibility of 68- and 105-kilodalton HSP can be restored in PCC7-S-1009 cells after in vitro differentiation triggered by retinoic acid. Similarly, in the early mouse embryo, hyperthermia does not induce the synthesis of nonconstitutive HSP at the eight-cell stage, but induction of the 68-kilodalton HSP does occur at the blastocyst stage. Such a transition in the expression of HSP has already been described for Drosophila melanogaster and sea urchin embryos and recently for mouse embryos. It may be a general property of early embryonic cells.

  17. Heat shock protein 70 expression in relation to apoptosis in primary bladder transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    HE Ling-feng; GUAN Kao-peng; YE Hai-yun; REN Liang; YAN Zheng; WANG Shen-wu; HOU Shu-kun

    2005-01-01

    @@ Bladder carcinoma is the most common tumor in the urinary system. In 1996, a sample investigation showed that bladder carcinoma, in which more than 90% was mainly primary bladder transitional cell carcinoma (BTCC), was one of the ten highest mortality malignant tumors in China. Bladder carcinoma represented 2% of all malignant tumors and has the fifth most common malignancy in men in Europe and North America.1

  18. The Effect of Nano-apatite on the Expression of Telomerase Gene of Human Hepatocellular Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the effect of nano- apatite on the expression of the telomerase gene of human hepatocellular carcinoma cell lines and further explore the mechanism of the nano-apatite inhibiting cancer cells. Using the hybridization in situ method to detect the expression of the telomerase gene of human hepatocellular carcinoma cells treated with the nano- apatite for 4 h at 37 ℃. The hybridization in situ showed that the cytoplasm of the positive cells was stained in nigger-brown. The positive cell rate of the control group was 88.49% , the cisplatin group was 25.6% , the nano-apatite group was 63.6% . The activity oftelomerase gene was both obviously declined comparing with the control group and the difference had significance (p < 0.05, p < 0.01 ). The nanoapatite obviously inhabit the expression of the telomerase gene of human hepatocellular carcinoma cells.

  19. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Calmon, Marilia Freitas [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil); Sichero, Laura [Molecular Biology Laboratory, Centre for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo (Brazil); Boccardo, Enrique [Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo., São Paulo (Brazil); Villa, Luisa Lina [Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo (Brazil); Rahal, Paula, E-mail: rahalp@yahoo.com.br [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil)

    2016-09-15

    Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

  20. Effect of miR-451-mediated regulation of MIF expression on cell proliferation in human colon carcinoma cell line LoVo

    Institute of Scientific and Technical Information of China (English)

    孔帅

    2013-01-01

    Objective To investigate the effect of miR-451-mediated regulation of macrophage migration inhibitory factor(MIF) expression on cell proliferation in human colon carcinoma cell line LoVo.Methods A lentiviral vector

  1. Mast cell density and the context of clinicopathological parameters and expression of p185,estrogen receptor,and proliferating cell nuclear antigen in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-AnJiang; You-YuanZhang; He-ShengLuo; Shou-FuXing

    2002-01-01

    AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.

  2. Expression of SART-1 mRNA in canine squamous cell carcinomas.

    Science.gov (United States)

    Takaishi, Yumi; Yoshida, Yukari; Nakagaki, Kazuhide; Fujita, Michio; Taniguchi, Akiko; Orima, Hiromitsu

    2008-12-01

    SART-1, a squamous cell carcinoma (SCC) antigen recognized by cytotoxic T lymphocytes, has been useful in human cancer therapy. The SART-1(259) peptide is a potential candidate for vaccine. The present study examined an orthologue of the mRNA coding this peptide in canine SCCs. Specimens were obtained from seven canine patients with SCC, and the mRNA was isolated from the samples. The SART-1 and beta-actin genes were amplified by reverse-transcription polymerase chain reaction, using the isolated mRNA as a template. Canine SART-1 was amplified in six of the seven specimens, while beta-actin was detected in all the samples. In dogs, carcinomas expressing SART-1 could be a target for cytotoxic T lymphocyte mediated immunotherapy.

  3. Elevated maspin expression is associated with better overall survival in esophageal squamous cell carcinoma (ESCC.

    Directory of Open Access Journals (Sweden)

    Yang Wang

    Full Text Available Tumor suppressor maspin is a differentially regulated gene in the progression of many types of cancer. While the biological function of maspin in blocking tumor invasion and metastasis is consistent with the loss of maspin expression at the late stage of tumor progression, the differential expression and the biological significance of maspin in early stage of tumor progression appear to be complex and remain to be elucidated. In the current study, we examined the expression of maspin in 84 esophageal squamous cell carcinoma (ESCC cases (stages I-III and 55 non-tumor adjacent esophageal tissue specimens by immunohistochemical (IHC staining. The correlation of maspin with clinicopathological parameters was analyzed. Compared to normal esophageal squamous tissue where 80% (47/55 of the cases expressed maspin at a low to moderate level, all ESCC specimens (100% (84/84 were positive for maspin expression at a moderate to high level. ESCC with low or moderate maspin expression had significantly shorter postoperative survival rates compared to those that had high maspin expression (p<0.001. Since the correlation of maspin with ESCC histology and the correlation of maspin with ESCC prognosis seem to be at odds, we further investigated the biological function of maspin in ESCC using the established ESCC cell lines. The expression of maspin in five human esophageal squamous cancer cell lines (T12, E450, KYSE150, EC109, and KYSE510 was examined by the Western blot. ESCC cell line KYSE510 that did not express maspin and was stably transfected by maspin cDNA or an empty vector. The resulting transfected cells were characterized in vitro. Maspin expression significantly inhibited cell proliferation, motility and matrigel invasion. Taken together, our data suggest that the transient up-regulation of maspin in the early development of ESCC may be a defense mechanism against further transition towards more malignant phenotypes, ultimately slowing down ESCC tumor

  4. Elevated maspin expression is associated with better overall survival in esophageal squamous cell carcinoma (ESCC).

    Science.gov (United States)

    Wang, Yang; Sheng, Shijie; Zhang, Jianzhi; Dzinic, Sijana; Li, Shaolei; Fang, Fang; Wu, Nan; Zheng, Qingfeng; Yang, Yue

    2013-01-01

    Tumor suppressor maspin is a differentially regulated gene in the progression of many types of cancer. While the biological function of maspin in blocking tumor invasion and metastasis is consistent with the loss of maspin expression at the late stage of tumor progression, the differential expression and the biological significance of maspin in early stage of tumor progression appear to be complex and remain to be elucidated. In the current study, we examined the expression of maspin in 84 esophageal squamous cell carcinoma (ESCC) cases (stages I-III) and 55 non-tumor adjacent esophageal tissue specimens by immunohistochemical (IHC) staining. The correlation of maspin with clinicopathological parameters was analyzed. Compared to normal esophageal squamous tissue where 80% (47/55) of the cases expressed maspin at a low to moderate level, all ESCC specimens (100% (84/84)) were positive for maspin expression at a moderate to high level. ESCC with low or moderate maspin expression had significantly shorter postoperative survival rates compared to those that had high maspin expression (pESCC histology and the correlation of maspin with ESCC prognosis seem to be at odds, we further investigated the biological function of maspin in ESCC using the established ESCC cell lines. The expression of maspin in five human esophageal squamous cancer cell lines (T12, E450, KYSE150, EC109, and KYSE510) was examined by the Western blot. ESCC cell line KYSE510 that did not express maspin and was stably transfected by maspin cDNA or an empty vector. The resulting transfected cells were characterized in vitro. Maspin expression significantly inhibited cell proliferation, motility and matrigel invasion. Taken together, our data suggest that the transient up-regulation of maspin in the early development of ESCC may be a defense mechanism against further transition towards more malignant phenotypes, ultimately slowing down ESCC tumor progression.

  5. Differential expression of Yes-associated protein is correlated with expression of cell cycle markers and pathologic TNM staging in non-small-cell lung carcinoma.

    Science.gov (United States)

    Kim, Jin Man; Kang, Dong Wook; Long, Liang Zhe; Huang, Song-Mei; Yeo, Min-Kyung; Yi, Eunhee S; Kim, Kyung-Hee

    2011-03-01

    Yes-associated protein, a downstream effector of the Hippo signaling pathway, has been linked to progression of non-small-cell lung carcinoma. The aim of this study was to investigate expression of Yes-associated protein in lung adenocarcinoma and squamous cell carcinoma. Associations of Yes-associated protein expression with clinicopathologic parameters, expression of cell cycle-specific markers, and epidermal growth factor receptor gene amplification were also analyzed. In a univariate analysis of the 66 adenocarcinomas, high nuclear expression of Yes-associated protein was significantly correlated with expression of cyclin A and mitogen-activated protein kinase. Multivariate analysis, including age and sex, showed that cyclin A expression was independently correlated with nuclear expression of Yes-associated protein in adenocarcinomas. Furthermore, high nuclear expression of Yes-associated protein was also a significant predictor of epidermal growth factor receptor gene amplification for adenocarcinoma. For the 102 squamous cell carcinomas, univariate analysis revealed that high cytoplasmic expression of Yes-associated protein was correlated with the low pathologic TNM staging (stage I) and histologic grading. Multivariate analysis, including age and sex, showed that cytoplasmic expression of Yes-associated protein was an independent predictor of low pathologic TNM staging. These results indicate that nuclear overexpression of Yes-associated protein contributes to pulmonary adenocarcinoma growth and that high cytoplasmic expression of Yes-associated protein is an independent predictor of low pathologic TNM staging and histologic grading. The differential effects of Yes-associated protein expression patterns in adenocarcinomas and squamous cell carcinomas suggest that Yes-associated protein may play important roles in different pathways in distinct tumor subtypes. These observations may, therefore, lead to new perspectives on therapeutic targeting of these tumor

  6. Inhibition of TGF-β and EGF pathway gene expression and migration of oral carcinoma cells by mucosa-associated lymphoid tissue 1

    OpenAIRE

    Ohyama, Y.; Kawamoto, Y.; Chiba, T.; Maeda, G.; Sakashita, H; Imai, K.

    2013-01-01

    Background: Expression of mucosa-associated lymphoid tissue 1 (MALT1) is inactivated in oral carcinoma patients with worse prognosis. However, the role in carcinoma progression is unknown. Unveiling genes under the control of MALT1 is necessary to understand the pathology of carcinomas. Methods: Gene data set differentially transcribed in MALT1-stably expressing and -marginally expressing oral carcinoma cells was profiled by the microarray analysis and subjected to the pathway analysis. Migra...

  7. Characteristics of HCV replication and expression in a cultured human liver carcinoma cell line in vitro

    Institute of Scientific and Technical Information of China (English)

    SONG Zhi-qing; HAO Fei; MIN Feng; LIU Dao-jian

    2001-01-01

    Objective: To establish a cell culture system to support HCV long-term replication in vitro. Methods: A human hepatoma cell line 7721 was tested for its susceptibility to HCV by incubating with a serum from chronic hepatitis C patient. Cells and supernatant of the culture medium were harvested at various time-phases during the culturing periods. The presence of HCV RNA, the expression of HCV antigens in cells and/or supematant were examined with RT-PCR, in situ hybridization and immunohistochemistry respectively. Results: It was found that the intracellular HCV RNA was first detected on the 2nd day after culture, and then could be intermittently detected in both cells and supernatant over a period of at least 3 months after culture. HCV NS3, CP10 antigens were expressed in the cells. The fresh cells could be infected with the supernatant from cultured infected cells and the transmission of viral genome from HCV-infected 7721 cells to peripheral blood mononuclear cells (PBMCs) was also observed. Conclusion: Our findings suggest that the human liver carcinoma cell line7721 is not only susceptible to HCV but also can support its long replication in vitro. This cell line with HCV infection in vitro can serve as a useful tool for the study of the mechanism of HCV infection and replication, the evaluation of antiviral agents, and the primary selection of neutralization assays and HCV vaccine development.

  8. Identification of differentially expressed radiation-induced genes in cervix carcinoma cells using suppression subtractive hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Sang; Lee, Young Sook; Lee, Jeung Hoon; Lee, Woong Hee; Seo, Eun Young; Cho, Moon June [Chungnam National University, Daejeon (Korea, Republic of)

    2005-03-15

    A number of genes and their products are induced early or late following exposure of cells to ionizing radiation. These radiation-induced genes have various effects of irradiated cells and tissues. Suppression subtractive hybridization (SSH) based on PCR was used to identify the differentially expressed genes by radiation in cervix carcinoma cells. Total RNA and poly (A){sup +} mRNA were isolated from irradiated and non-irradiated HeLa cells. Forward-and reverse-subtracted cDNA libraries were constructed using SSH. Eighty-eight clones of each were used to randomly select differentially expressed genes using reverse Northern blotting (dot blot analysis). Northern blotting was used to verify the screened genes. Of the 176 clones, 10 genes in the forward-subtracted library and 9 genes in the reverse-subtracted library were identified as differentially expressed radiation-induced genes by PCR-select differential screening. Three clones from the forward-subtracted library were confirmed by Northern blotting, and showed increased expression in a dose-dependent manner, including a telomerase catalytic subunit and sodium channel-like protein gene, and an ESTs (expressed sequence tags) gene. We identified differentially expressed radiation-induced genes with low-abundance genes with SSH, but further characterization of theses genes are necessary to clarify the biological functions of them.

  9. Expression Profile of Metastasis-associated Genes in Esophageal Squamous Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Pei; LING Zhiqiang; YANG Hongyan; HUANG Youtian; ZHAO Mingyao; ZHENG Zhimin; DONG Ziming

    2006-01-01

    The differentially expressed genes between esophageal squamous cell carcinoma (ESCC)with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened out. Expression array was used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 cases of human ESCC. The lymphatic metastasis-associated genes were screened by bioinformatics between ESCC with or without lymphatic metastasis. The results showed that 43 (4.85%) genes significantly differed between the ESCC with and without lymphatic metastasis (P<0.05), of which 18(2.03%)were upregulated and 25 (2.82 %) down-regulated. The up-regulated genes were involved in cell adhesion molecules and cell membrane receptors and the down-regulated genes were mostly cell cycle regulators and intracellular signaling molecules. It was suggested that lymphatic metastasis-associated genes were screened by gene chip, which was helpful to understand the molecular mechanism of ESCC lymphatic metastasis and lymphatic metastasis-associated genes might be used as diagnostic markers and therapeutic targets for lymphatic metastasis.

  10. Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma

    DEFF Research Database (Denmark)

    Jacobsen, Benedikte; Santoni-Rugiu, Eric; Illemann, Martin

    2012-01-01

    in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti-C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased......The protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor, is a potential new biomarker in non-small cell lung cancer, with high levels of expression recently shown to correlate to poor survival of adenocarcinoma patients. In this study, C4.4A immunoreactivity...... finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical...

  11. Expression, purification and serological analysis of hepatocellular carcinoma associated antigen HCA587 in insect cells

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Hong-Yan Wu; Xiao-Ping Qian; Yan Li; Wei-Feng Chen

    2003-01-01

    AIM: In order to assess hepatocellular carcinoma associated antigen HCA587 as a potential target for immunotherapy,the Bac-to-Bac expression system was used to express recombinant protein HCA587 in insect cells.METHODS: The cDNA encoding HCA587 gene was cloned into donor vector pFasBacHtb and recombinant pFasBac Htb587 was transformed into competent cells DH10Bac.Recombinant Bacmid-587 was transfected into Sf9 insect cells using CELLFECTIN, Recombinant HCA587 protein was produced in Sf9 insect cells after infection with recombinant baculovirus, and was purified using Ni-NTA resin. Sera from HCC patients were also screened using recombinant protein HCA587.RESULTS: The molecular weight of the recombinant protein HCA587 expressed in insect cells was approximately 43kd.Western blot results proved the recombinant protein HCA587had the similar antigenicity with its native counterpart.Serological analysis told that the rate of seroreactivity to HCA587 was not high in HCC patients.CONCLUSION: The recombinant protein HCA587 was successfully expressed and purified using Bac-to-Bac expression system. It paved the way for generation of specific antibody and investigation of immunohistochemical analysis and immune responses of HCC in the future.

  12. The expression sequence tag is an effective method for screening DNA segments that predict urinary bladder transitional cell carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Yang PS

    2014-09-01

    Full Text Available Pei-Shan Yang,1,* Yu-Chao Hsu,1,2,* Yu-Hsiang Lin,1,2 Cheng-Pang Hou,1,2 Chien-Lun Chen,1,2 Phei-Lang Chang,1–3 Horng-Heng Juang,3,4 Ke-Hung Tsui1–3 1Department of Urology, Chang Gung Memorial Hospital at Linkou, Taiwan, Republic of China; 2School of Medicine, Chang Gung University, Taiwan, Republic of China; 3Bioinformation Center, Chang Gung Memorial Hospital, Taiwan, Republic of China; 4Department of Anatomy, School of Medicine, Chang Gung University, Taiwan, Republic of China; Kwei-Shan, Tao-Yuan, Taiwan, Republic of China *These authors contributed equally to this workPurpose: We validated the use of expression sequence tags (ESTs as an effective method of screening for DNA segments that could predict urothelial cell carcinoma and for identifying ESTs with such predictive value.Patients and methods: From 2004 to 2009, eleven patients were enrolled in this study: six with high-grade bladder carcinoma and five with low-grade bladder carcinoma. ESTs were used to screen for differential gene expression in a high-grade cell line (MGH-U1 and in a premalignant cell line (MGH-U4. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction were used to validate the degree of EST expression and the prognostic value of ESTs.Results: Apoferritin H subunit (FTH1 protein exhibited increased expression in high-grade bladder carcinoma compared with that seen in low-grade carcinoma. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction both supported the higher expression of FTH1 in high-grade urothelial carcinoma.Conclusion: ESTs are useful for detecting the FTH1 protein, which predicts the prognosis of patients with bladder carcinoma.Keywords: expression sequence tag, transitional cell carcinoma, FTH1

  13. Irradiated fibroblasts promote epithelial–mesenchymal transition and HDGF expression of esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Ci-Hang; Wang, Xin-Tong [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Ma, Wei [Department of Radiation Oncology, Cancer Hospital, Genaral Hospital of Ningxia Medical University, Yinchuan 750000 (China); Wang, Na-Na; Nesa, Effat un; Wang, Jian-Bo; Wang, Cong; Jia, Yi-Bin; Wang, Kai [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Tian, Hui [Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan 250012 (China); Cheng, Yu-Feng, E-mail: qlcyf1965@126.com [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2015-03-06

    Recent evidence suggested that nonirradiated cancer-associated fibroblasts (CAFs) promoted aggressive phenotypes of cancer cells through epithelial–mesenchymal transition (EMT). Hepatoma-derived growth factor (HDGF) is a radiosensitive gene of esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the effect of irradiated fibroblasts on EMT and HDGF expression of ESCC. Our study demonstrated that coculture with nonirradiated fibroblasts significantly increased the invasive ability of ESCC cells and the increased invasiveness was further accelerated when they were cocultured with irradiated fibroblasts. Scattering of ESCC cells was also accelerated by the supernatant from irradiated fibroblasts. Exposure of ESCC cells to supernatant from irradiated fibroblasts resulted in decreased E-cadherin, increased vimentin in vitro and β-catenin was demonstrated to localize to the nucleus in tumor cells with irradiated fibroblasts in vivo models. The expression of HDGF and β-catenin were increased in both fibroblasts and ESCC cells of irradiated group in vitro and in vivo models. Interestingly, the tumor cells adjoining the stromal fibroblasts displayed strong nuclear HDGF immunoreactivity, which suggested the occurrence of a paracrine effect of fibroblasts on HDGF expression. These data suggested that irradiated fibroblasts promoted invasion, growth, EMT and HDGF expression of ESCC. - Highlights: • Irradiated CAFs accelerated invasiveness and scattering of ESCC cell lines. • Irradiated CAFs promoted EMT of ESCC cells. • Irradiated fibroblasts induced nuclear β-catenin relocalization in ESCC cells. • Irradiated fibroblasts increased HDGF expression in vitro and in vivo.

  14. Adenovirus vector expressing mda-7 selectively kills hepatocellular carcinoma cell line Hep3B

    Institute of Scientific and Technical Information of China (English)

    Xin-Bo Xue; Kun Chen; Cong-Jun Wang; Jian-Wei Zheng; Yuan Yu; Zhi-Hai Peng; Zai-De Wu

    2008-01-01

    BACKGROUND: Melanoma differentiation associated gene-7 (mda-7) is a novel tumor suppressor gene, which has suppressor activity in a broad spectrum of human cancer cells both in vitro and in vivo through activation of various intracellular signaling pathways. In this study, we investigated the potential effect of mda-7 on human hepatocellular carcinoma (HCC) in vitro. METHODS: Cells from the human HCC cell line Hep3B and the human liver cell line L-02 were assigned to three groups. One was cultured in Dulbecco's modiifed Eagle's medium without serum (control). The others were transfected with adenovirus expressing the mda-7 gene (Ad.mda-7) or adenovirus vector serving as negative control (Ad.vec). The expression of MDA-7 and Bcl-2 proteins in Hep3B and L-02 cells was conifrmed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. The methyl thiazolyl tetrazolium colorimetric assay and lfow cytometry were used to assess tumor cell proliferation and the cell cycle. Hoechst and Annexin-V/propidium iodide staining were used to study mda-7 gene expression in Hep3B and L-02 cells. The expression of MDA-7, Bcl-2 and Bax proteins were detected by Western blotting. RESULTS: The mda-7 gene was expressed in Hep3B and L-02 cells. The protein concentrations of MDA-7 in supernatants were 790 and 810 pg/ml, respectively. mda-7 induced Hep3B growth suppression and apoptosis, compared with Ad.mda-7 and control (P CONCLUSIONS: mda-7 selectively induces growth inhibi-tion and apoptosis in the HCC cell line Hep3B but not in the normal liver cell line L-02 via downregulating the anti-apoptosis protein Bcl-2. It could be an ideal gene for gene therapy in HCC.

  15. Effect of androgen withdrawal on activation of ERKs and expression of cell cycle regulation molecules in human prostate carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    YE Ding-wei; LI Hui; TSENG Jane; CHAUVIN Priscilla; QIAN Song-xi; ZHENG Jia-fu; SUN Ying-hao; MA Yong-jiang

    2002-01-01

    Objective: To explore the possible mechanisms of growth regression of human androgen dependentprostate carcinoma cells caused by androgen withdrawal. Methods: After 24 h of treatment with 1×10-9mol/L dihydrotestosterone (DHT), the expression of phosphorylated ERK proteins and cell cycle regulationmolecules including CDK2, CDK4, CDK6 and P27kip1 in human androgen dependent prostate carcinoma cellline LNCaP was measured by Western blot analysis 0 h, 8 h and 24 h of after androgen withdrawal. Humanandrogen independent prostate carcinoma cell line PC-3 was also examined as control. Results: Down-regula-tion of phosphorylated ERK, CDK2, CDK4 and CDK6 and up-regulation of P27kip1 were found initially inLNCaP cell line 8 h after androgen withdrawal. The levels of phosphorylated ERK and CDKs decreased con-tinuously and reached the lowest after 24 h, while continuous elevation of P27kip1 was detected thereafter to 24h. No expression change of phosphorylated ERK, CDKs and P27kip1 were detected in PC-3 cell line. Conclu-sion: The androgen withdrawal can cause ERKs activation decrease and cell cycle regulation moleculeschanges, which may be one of the mechanisms for inhibited growth of androgen dependent prostate carcinomaafter androgen ablation by either operative or medicine methods.

  16. Enhanced expression of ANO1 in head and neck squamous cell carcinoma causes cell migration and correlates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Christian Ruiz

    Full Text Available Head and neck squamous cell carcinoma (HNSCC has the potential for early metastasis and is associated with poor survival. Ano1 (Dog1 is an established and sensitive marker for the diagnosis of gastrointestinal stromal tumors (GIST and has recently been identified as a Ca(2+ activated Cl(- channel. Although the ANO1 gene is located on the 11q13 locus, a region which is known to be amplified in different types of human carcinomas, a detailed analysis of Ano1 amplification and expression in HNSCC has not been performed. It is thus still unclear how Ano1 contributes to malignancy in HNSCC. We analyzed genomic amplification of the 11q13 locus and Ano1 together with Ano1-protein expression in a large collection of HNSCC samples. We detected a highly significant correlation between amplification and expression of Ano1 and showed that HNSCC patients with Ano1 protein expression have a poor overall survival. We further analyzed the expression of the Ano1 protein in more than 4'000 human samples from 80 different tumor types and 76 normal tissue types and detected that besides HNSCC and GISTs, Ano1 was rarely expressed in other tumor samples or healthy human tissues. In HNSCC cell lines, expression of Ano1 caused Ca(2+ activated Cl(- currents, which induced cell motility and cell migration in wound healing and in real time migration assays, respectively. In contrast, knockdown of Ano1 did not affect intracellular Ca(2+ signaling and surprisingly did not reduce cell proliferation in BHY cells. Further, expression and activity of Ano1 strongly correlated with the ability of HNSCC cells to regulate their volume. Thus, poor survival in HNSCC patients is correlated with the presence of Ano1. Our results further suggest that Ano1 facilitates regulation of the cell volume and causes cell migration, which both can contribute to metastatic progression in HNSCC.

  17. Promoter methylation and expression of CDH1 and susceptibility and prognosis of eyelid squamous cell carcinoma.

    Science.gov (United States)

    Wang, Yong-Qiang; Yuan, Ye; Jiang, Shan; Jiang, Hua

    2016-07-01

    Eyelid skin tumors are the most frequent type of cancer in ophthalmology. And, eyelid squamous cell carcinoma (SCC) accounts for a large part of it. CDH1 encodes E-cadherin, a glycoprotein that plays an important part in cell-cell interaction. Loss of CDH1 function was suspected to be associated with tumorigenesis. Methylation of CDH1 promotors can alter the expression of its protein and is also considered as a contributor to various cancers. In this study, CDH1 methylation and expression profile as well as prognosis of 38 cases of eyelid SCC and the corresponding adjacent tissues were analyzed to clarify the role of CDH1 methylation in SCC carcinogenesis and prognosis. Methylation was detected by PCR, and CDH1 expression was evaluated by immunohistochemistry. We observed that CDH1 methylation is significantly correlated with decreased CDH1 protein expression in eyelid SCC patients. Patients with methylation and low expression of CDH1 are significantly associated with advanced and aggressive phenotypes. Therefore, CDH1 methylation and CDH1 expression are both independent prognostic factors for prognosis of eyelid SCC patients.

  18. CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases.

    Science.gov (United States)

    Mir, Hina; Singh, Rajesh; Kloecker, Goetz H; Lillard, James W; Singh, Shailesh

    2015-04-30

    Lung cancer (LuCa) is the leading cause of cancer-related deaths worldwide regardless of the gender. High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined. Here, we present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of LuCa. CXCR6 expression was significantly higher in two subtypes of NSCLC (adenocarcinomas-ACs and squamous cell carcinoma-SCCs) as compared to non-neoplastic tissue. Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls. Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients. Biological significance of this axis was validated using SCC and AC cell lines. Expression of CXCR6 was higher in AC cells, which also showed higher migratory and invasive potential than SCC. Differences in migratory and invasive potential between AC and SCC were due to differential expression of metalloproteinases following CXCL16 stimulation. Hence, our findings suggest clinical and biological significance of CXCR6/CXCL16 axis in LuCa, which could be used as potential prognostic marker and therapeutic target.

  19. Expression of Plasminogen Activator Inhibitor-2 is Negatively Associated with Invasive Potential in Hepatocellular Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    Ye Jin; Li Zhou; Ke-min Jin; Bao-cai Xing

    2013-01-01

    Objective To investigate the association between plasminogen activator inhibitor (PAI)-2 expression and invasive potential in hepatocellular carcinoma (HCC) cells. Methods The HCC cell lines with high,low,and non-metastatic potentials,namely MHCC97-H,MHCC97-L,and SMMC-7721 respectively,were cultured in vitro. Matrigel invasion assay and Western blot of PAI-2 protein expression were conducted. Results The number of invaded cells in MHCC97-L was significantly higher than that in SMMC-7721 (P=0.005),whereas that in MHCC97-H was higher than in MHCC97-L (P=0.017) and SMMC-7721 (P=0.001). Contrarily,PAI-2 protein expression was gradually reducing from SMMC-7721,MHCC97-L,to MHCC97-H (MHCC97-H vs. MHCC97-L,P<0.001; MHCC97-H vs. SMMC-7721,P=0.001; MHCC97-L vs. SMMC-7721,P=0.001). The Pearson's correlation analysis revealed a significant negative association between invaded cell number and PAI-2 expression (r=?0.892,P=0.001). Conclusion PAI-2 expression may be negatively associated with the invasive potential of HCC.

  20. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute;

    2004-01-01

    in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported......Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly...

  1. Expression of the WT1 gene -KTS domain isoforms suppresses the invasive ability of human lung squamous cell carcinoma cells.

    Science.gov (United States)

    Moriya, Shogo; Takiguchi, Masaki; Seki, Naohiko

    2008-02-01

    Although the WT1 gene was originally isolated as a tumor suppressor gene from Wilms' tumor, oncogenic roles for WT1 have been reported in several tumors. Here, we present new findings of high levels of WT1 expression associated with the suppression of lymph node metastasis in patients with human lung squamous cell carcinoma (SCC). We investigated the effect of down-regulated WT1 gene expression on the invasive phenotype of the SCC cell line RERF-LC-AI. Invasive ability was enhanced in WT1-specific siRNA-transfected cells, and a WT1 target gene p21(Waf1/Cip1) was isolated by comprehensive gene expression analysis. As several isoforms are produced from the WT1 gene, we isolated eight major WT1 isoforms from a cDNA library and cloned each variant into an expression vector. Luciferase reporter assays revealed that p21(Waf1/Cip1) expression was enhanced only by the WT1 cDNA variants that included a three-amino acid deletion (-KTS). Our results suggested that the -KTS-containing variants of WT1 are directly involved in the regulation of p21(Waf1/Cip1) expression and the subsequent suppression of lymph node metastasis in human lung squamous cell carcinoma.

  2. The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion.

    Science.gov (United States)

    Ping, Ji-Gen; Wang, Fei; Pu, Jin-Xian; Hou, Ping-Fu; Chen, Yan-Su; Bai, Jin; Zheng, Jun-Nian

    2016-09-01

    Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of renal cell carcinoma (RCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 307 cases of RCC tissues and 34 normal renal tissues. The Cul1 expression was increased significantly in RCC and was correlated with renal carcinoma histology grade (P = 0.007), tumor size (P = 0.013), and pT status (P = 0.023). Also, we found that silencing of Cul1 leads to increased expression of p21 and p27 that could inhibit the cyclin D1 and cyclin E2 expressions and arrest cell cycle at the G1 phase. Furthermore, knockdown of Cul1 inhibits RCC cell migration and invasion abilities by up-regulating the expression of TIMP-1 which could inhibit the expression of MMP-9. Finally, using bioluminescence imaging, we found that Cul1 knockdown significantly reduced the tumor growth in vivo. Cul1 may constitute a potential therapeutic target in RCC.

  3. Osteopontin expression in salivary gland carcinomas

    DEFF Research Database (Denmark)

    Bjørndal, Kristine; Larsen, Stine R; Godballe, Christian;

    2011-01-01

    J Oral Pathol Med (2010) Background:  In several cancer types, osteopontin (OPN) expression has been correlated with tumor progression and prognosis. Two earlier studies have examined OPN expression in salivary gland carcinomas with contradictory results. Methods:  One hundred and seventy......-five patients with a primary salivary gland carcinoma diagnosed from January 1, 1990 to December 31, 2005 were identified in the local pathology register, Odense University Hospital. Criteria as documented by Allred et al. were used to assess OPN immunostaining that was performed on surgical specimens. Results......:  Osteopontin was expressed in all salivary gland carcinomas. Adenoid cystic carcinomas had the highest mean sum score (7.3) and a significantly higher proportion of carcinomas with high OPN sum score than both mucoepidermoid carcinoma and acinic cell carcinoma. Correlation of OPN expression with known...

  4. PD-1/PD-L1 expression in chromophobe renal cell carcinoma: An immunological exception?

    Science.gov (United States)

    Erlmeier, Franziska; Hartmann, Arndt; Autenrieth, Michael; Wiedemann, Max; Ivanyi, Philipp; Steffens, Sandra; Weichert, Wilko

    2016-11-01

    Immune checkpoint inhibitors targeting the inhibitory cross talk between tumor and immune cells have been approved for therapy in renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known on PD-1/PD-L1 expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-1 and PD-L1 expression in chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimen was analyzed for PD-1 and PD-L1 expression by immunohistochemistry. Expression data were correlated with clinic-pathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis, thereof 25 (30.9 %) and 11 (13.6 %) patients were positive for PD-1(+) tumor-infiltrating mononuclear cells (TIMCs) and tumoral PD-L1(+) expression, respectively. No significant associations were found for PD-1(+) TIMC or tumoral PD-L1(+) expression and clinical attributes. In addition, no differences in 5- and 10-year overall survival for PD-1(-) TIMC compared to PD-1(+) TIMC (90.5 and 72.2 vs. 100 and 75 %; p = 0.41) and for PD-L1(-) tumors compared to PD-L1(+) tumors (91.9 and 76.4 vs. 100 and 50 %; p = 0.48) were observed. In conclusion, to our knowledge this is the first study to evaluate the prognostic impact of PD-1 and PD-L1 in chRCC. PD-L1 does seem to be expressed in a minority of all chRCC, likewise only a minority of chRCC was infiltrated by PD-1-positive inflammatory cells. Neither PD-1(+) TIMC nor tumoral PD-L1(+) expression was associated with parameters of aggressiveness or survival.

  5. Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Wusheng

    2012-01-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC, the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB, normal differentiated squamous epithelium (ND, and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and

  6. Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

    Directory of Open Access Journals (Sweden)

    Fabjani Gerhild

    2008-01-01

    Full Text Available Abstract Background Many cancer cells produce interleukin-6 (IL-6, a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.e. IL-1β, prostaglandin E2, 17β-estradiol, and 1,25-dihydroxyvitamin D3, on expression and synthesis of the cytokine at different stages of tumour progression. Methods We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the IL-6 gene promoter. Results IL-6 mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10-7 M reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the IL-6 promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the IL-6 gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-myc proto-oncogene expression. These effects were inhibited by 10-8 M 1,25-dihydroxyvitamin D3. Conclusion In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally

  7. RNA interference by expression of short hairpin RNAs suppresses bcl-xL gene expression in nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Fang LIU; Cheng-wei HE; Yue-fei ZHANG; Ke-yuan ZHOU

    2005-01-01

    Aim: To evaluate a new plasmid mediated RNA interference (RNAi) system and investigate whether knock-down of bcl-xL by short hairpin RNA (shRNA) can induce apoptosis of human nasopharyngeal carcinoma (NPC) cell line CNE-2Z in vitro. Methods: The plasmid containing mU6 promoter was subcloned to yield the pmU6 plasmid, recombinant plasmid expressing shRNA targeting bcl-xL gene was designed and constructed, and were co-transfected cells with green fluorescence protein expressing plasmid. Flow cytometry was used to evaluate transfection efficiency, and RT-PCR and Western blot were applied to analyze bcl-xL mRNA and protein levels, respectively. Results: The shRNA expressed by the recombi nant plasmid efficiently suppressed bcl-xL gene expression and induced apoptosis .of NPC cells in vitro. Conclusion: The recombinant plasmid can sufficiently mediate RNAi in CNE-2Z cells, and knock-down of the bcl-xL expression by shRNA significantly induced apoptosis in CNE-2Z cells. The results suggest this new system, mediated RNAi can be used as a tool for the study of gene function and gene therapy.

  8. Survivin expression in canine epidermis and in canine and human cutaneous squamous cell carcinomas.

    Science.gov (United States)

    Bongiovanni, Laura; Colombi, Isabella; Fortunato, Carmine; Della Salda, Leonardo

    2009-10-01

    Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is ubiquitously expressed during tissue development, undetectable in most normal tissues, but re-expressed in most cancers, including skin malignancies. Expression of survivin was evaluated retrospectively in 19 canine cutaneous squamous cell carcinomas (SCCs; one in situ; 16 well differentiated; one invasive, one lymph node metastasis) and 19 well differentiated SCCs from human beings. Seven specimens of normal canine skin were included. Immunohistochemical expression of full-length survivin was determined using a commercially available antibody. In addition, apoptotic rate [Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labelling index (TUNEL) index] and mitotic index (MI), counting mitoses in 10 high power fields (HPF), were determined. Scattered survivin positive nuclei were identified in the epidermal basal cell layer of normal canine skin. Nuclear survivin expression was identified in 18 of 19 human and in all canine SCCs, mainly along the base of the tumour cell population. Cytoplasmic survivin expression was rarely observed in human SCCs and in 84.2% of canine SCCs. The TUNEL index ranged from 0.1 to 2.6 in human beings and from 7.5 to 69.4 in dogs, while MIs ranged from 0 to 4 in human beings and dogs. No correlation was found between survivin expression and apoptotic or mitotic rates. Canine and human tumours showed similar nuclear survivin expression, indicating similar functions of the molecule. We demonstrated survivin expression in normal adult canine epidermis. Increased nuclear survivin expression in pre-neoplastic and neoplastic lesions demonstrates a possible association of survivin with development of SCCs in human beings and dogs.

  9. Expression of Bcl-2 inhibited Fas-mediated apoptosis in human hepatocellular carcinoma BEL-7404 cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Apoptosis plays an important role in embryonic development, tissue remodeling, immune regulation and tumor regression. Two groups of molecules (Bcl-2 family and"Death factor"family) are involved in regulating apoptosis. In order to know about the effect of Bcl-2 on apoptosis induced by Fas, a typical member of"Death factor" family, the transfection experiments with expression vectors pcDNA3-fland pcDNA3-bcl-2 were performed in BEL-7404 cells, a human hepatocellular carcinoma cell line which expresses endogenous Fas, but not FasL and Bcl2. The data showed that the expression of FasL in pcDNA3fl transfected hepatoma cells obviously induced the apoptosis of the cells. However, the overexpression of Bcl-2 in pcDNA3bcl-2 transfected 7404/b-16 cells counteracted pcDNA3-fltransient transfection mediated apoptosis. Further study by cotransfection experiments indicated that Bid but not Bax (both were pro-apoptotic proteins of Bcl-2 family) blocked the inhibitory effect of Bcl-2 on Fas-mediated apoptosis. These results suggested that Fas-mediated apoptosis in human hcpatoma cells is possibly regulated by Bcl-2 family proteins via mitochondria pathway.

  10. Human Papillomaviruses, p16INK4a and Akt expression in basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Paolini Francesca

    2011-11-01

    Full Text Available Abstract Background The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC, is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC. The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients. Methods The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample. Results No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%, HPV100 (11,5% and HPV15 (11,5% all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3% with the highest percentages (> 30% of positive cells detected in 8 cases. A statistically significant (p = 0,012 increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%; in particular in HPV positive samples over-expressing p16INK4a. Conclusions Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15. The association of these viruses with the up

  11. The expression and clinical significance of metastasis suppressor gene and matrix metalloproteinase-2 in esophageal squamous cell of carcinoma.

    Science.gov (United States)

    Guo, Xiao-Qi; Li, Xing-Ya

    2016-07-01

    To investigate the expression and clinical significance of metastasis suppressor gene and matrix metalloproteinase-2 in esophageal squamous cell of carcinoma. choose 30 cases of specimens of esophageal squamous cell carcinoma which are removed in surgery and confirmed by pathology and 30 cases of specimens of normal esophageal mucosa. Use immunohistochemistry SP method to detect the expression of nm23-H1, MMP-2 protein in esophageal squamous cell carcinoma and normal esophageal mucosal. The positive rate of nm23-H1 protein in esophageal squamous cell carcinoma was 43.3% (13/30), while that in normal esophageal mucosa was 100% (30/30), which has a significant difference between them (χ2=22. 083, P0.05), but it was related to the degree of tumor differentiation, depth of invasion and lymph node metastasis (P0.05); The expression of nm23-H1 and MMP-2 in esophageal squamous cell carcinoma was negatively correlated. nm23-H1 and MMP-2 have played a role in the development of esophageal cancer, which can promote the occurence of distant metastasis; The loss of expression of nm23-H1 may be related to cut end residual cancer; nm23-H1 and MMP-2 may be as an indicator for esophageal cancer metastasis and prognosis.

  12. Expression of SKP2 Protein in Non-small Cell Lung Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To study the expressive characteristics of SKP2 protein in non-small cell lung carcinoma and it is affection to NSCLC patients' prognosis. Methods: The expression of SKP2 protein was detected in 89 NSCLC, 5 benign lung neoplasmas, 5 normal bronchus and lung tissues by Tissue Chip and immunohistochemistry technology.Results: The positive rate of SKP2 protein staining was (23.52±13.57)% in NSCLC tissues, significantly higher than that in benign lung neoplasmas, normal brochus and lung tissues (2.91±1.27)% (P=0.0000<0.001). The expressive level of SKP2 protein in NSCLC tissues was closely related to cell differentiation (P1=0.000<0.001),but not to age, sex, smoking history, pathological type, site, size, lymph node metastasis and TNM stage (each P1>0.05). The survival analysis displayed that the NSCLC patients' 5 years survival rate was lower in positive expression group than that in negative expression group (P1=0.042/0.031<0.05; r=-0.186, P2=0.000<0.001).Conclusion: The positive expression of SKP2 protein may play an enhancement role in the occurrence and development of NSCLC. Moreover, it may be a bad indicator to NSCLC patients' prognosis.

  13. E-cadherin and c-Met expression in actinic cheilits and lip squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    A Martínez

    2011-12-01

    Full Text Available Objective: The aim of this study was to assess epithelial expression of E-cadherin and c-Met in normal lip, in actinic cheilitis and lip squamous cell carcinoma. Study Design: Biopsies of normal lip vermillion (NL, n=18, actinic cheilitis (AC, n=37, and lip SCC (n=22 were processed for E-cadherin and c-Met immunodetection. Epithelial and tumor cell expression was scored for each sample considering staining intensity and percentage. Results: E-cadherin expression was significantly reduced in AC and lip SCC as compared to normal lip (P<0.05, with a significant reduction in lip SCC as compared to AC (P=0.003. Expression of c-Met was significantly higher in AC and lip SCC as compared to NL (P<0.05, with a significant increase in lip SCC as compared to AC (P<0.0001. Conclusion: The results showed that epithelial E-cadherin expression is reduced and c-Met expression is increased as lip carcinogenesis progresses, suggesting that these proteins may be useful markers of malignant transformation.

  14. Molecular classification of basal cell carcinoma of skin by gene expression profiling.

    Science.gov (United States)

    Jee, Byul A; Lim, Hyoseob; Kwon, So Mee; Jo, Yuna; Park, Myong Chul; Lee, Il Jae; Woo, Hyun Goo

    2015-12-01

    Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The classical BCC showed the enriched expression and transcription signature with the activation of Wnt and Hedgehog signaling pathways, which were well known key features of BCC. By contrast, the SCC-like BCC was enriched with immune-response genes and oxidative stress-related genes. Network analysis revealed the PLAU/PLAUR as a key regulator of SCC-like BCC. The normal-like BCC showed prominent activation of metabolic processes particularly the fatty acid metabolism. The existence of these molecular subtypes could be validated in an independent dataset, which demonstrated the three subgroups of BCC with distinct functional enrichment. In conclusion, we suggest a novel molecular classification of BCC providing insights on the heterogeneous progression of BCC.

  15. Cell proliferation, apoptosis and the related regulators p27, p53 expression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhao Jing; Ke-Jun Nan; Mei-Long Hu

    2005-01-01

    AIM: To investigate the expression of cell apoptosis,proliferation and the related regulators p27, p53 in hepatocellular carcinoma (HCC).METHODS: The expression of p27, p53, proliferating cell nuclear antigen (PCNA) and apoptosis in 47 HCC specimens and 42 surrounding non-cancerous tissues were detected by the immunohistochemistry and terminal deoxy-nudeotidyl transferase-mediated nick end labeling (TUNEL) technique.Meanwhile, the clinical significance of them was analyzed combining with the clinicopathological factors and followup data.RESULTS: (1) The average proliferating index and apoptotic index in HCC were significantly higher than that in adjacent liver tissues. The proliferating index was associated with extrahepatic metastasis. The apoptotic index was significantly lower in TNM stage Ⅰ-Ⅱ than in stage Ⅲ-Ⅳ. The proliferating index of groups with p53-/p27+ was significantly lower than that in group with p53+/p27- (P = 0.030); (2) The level of p27 in the cytoplasmic fraction was higher in non-tumoral liver tissues and was associated with clinical stage; (3) Survival analysis showed advanced stage (P = 0.031) and with extrahepatic metastasis (P = 0.045) was significantly associated with shorter survival. In addition, the prognosis of patients with p53-/p27+ was longer than that of patients with p53+/p27- (P = 0.0356).CONCLUSION: The p53 mutation and decreased p27 expression might be involved in the imbalance of proliferation and apoptosis in HCC. Cytoplasmic displacement might lead to the inactivation of p27 protein in HCC cells and acts early during carcinogenesis of HCC. The combined examination of p27, and p53 expression allows reliable estimation of prognosis for patients with primary hepatic carcinoma.

  16. IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study

    Science.gov (United States)

    Soddu, S.; Di Felice, E.; Cabras, S.; Castellanos, M.E.; Atzori, L.; Faa, G.; Pilloni, L.

    2013-01-01

    The protein insulin-like growth factor II mRNA binding protein 3 (IMP-3) is an important factor for cell migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP-3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. The purpose of this study is to compare IMP-3 immunostaining in cutaneous squamous cell tumors and determine whether IMP-3 can aid in the differential diagnosis of these lesions. To our knowledge, IMP-3 expression has not been investigated in skin squamous cell proliferations thus far. Immunohi-stochemical staining for IMP-3 was performed on slides organized by samples from 67 patients, 34 with keratoacanthoma (KA) and 33 with primary cutaneous squamous cell carcinoma (SCC) (16 invasive and 17 in situ). Seventyfour percent of KAs (25/34) were negative for IMP-3 staining, while 57% of SCCs (19/33) were positive for IMP-3 staining. The percentage of IMP-3 positive cells increased significantly in the invasive SCC group (P=0.0111), and particularly in the SCC in situ group (P=0.0021) with respect to the KA group. IMP-3 intensity staining was significantly higher in invasive SCCs (P=0.0213), and particularly in SCCs in situ (P=0.008) with respect to KA. Our data show that IMP-3 expression is different in keratoacanthoma with respect to squamous cell carcinoma. IMP-3 assessment and staining pattern, together with a careful histological study, can be useful in the differential diagnosis between KA e SCC. PMID:23549465

  17. THE APOPTOSIS OF EXPERIMENTAL COLORECTAL CARCINOMA CELLS INDUCED BY PEPTIDOGLYCAN OF BIFIDOBACTERIUM AND THE EXPRESSION OF APOPTOTIC REGULATING GENES

    Institute of Scientific and Technical Information of China (English)

    WANG Li-sheng; PAN Ling-jia; SHI Li; SUN Yong; ZHANG Ya-li; ZHOU Dian-yuan

    1999-01-01

    Objective: To explore the antitumor mechanisms of whole peptidoglycan of bifidobacterium. Methods: The apoptotic cells and the positive expression of bcl-2 and bax oncoprotein were studied nude mice transplantation tumors of colorectal carcinoma by employing in situ end labeling technique and immunohistochemical staining. Results:The apoptotic cell density, the positive rate and the staining intensity of bax oncoprotein of the transplantation tumor of colorectal carcinoma in the whole peptidoglycan injection group were significantly higher when compared with the tumor control group. The positive rate of bcl-2 oncoprotein in the whole peptidoglycan injection group was obviously lower than that in the tumor control group (P<0.01).Conclusion: Whole peptidoglycan of Bifidobacterium bifidum could induce cell apoptosis of nude mice transplantation tumors of colorectal carcinoma by downregulating the expression of the bcl-2 gene and upregulating the expression of the bax gene.

  18. Expression of aquaporin-1 in SMMC-7221 liver carcinoma cells promotes cell migration

    Institute of Scientific and Technical Information of China (English)

    LI Yongming; FENG Xuechao; YANG Hong; MA Tonghui

    2006-01-01

    Migration of tumor cells is a crucial step in tumor invasion and metastasis. Here we provide evidence that aquaporin expression is involved in tumor cell migration. RT-PCR, immunofluorescence and Western blot analysis demonstrated the AQP1 protein expression on the plasma membrane of SMMC-7221 human hepatoma cells. SMMC-7221 cell clones with high (SMMC-7221hPf) and low (SMMC-7221/Pf) water permeability were identified by functional assays with corresponding high and low AQP1 expression. Cell migration rate was remarkably higher in SMMC-7221hPf cells than SMMC-7221/Pf cells, assessed by Boyden chamber and wound healing assays, whereas cell growth and adhesion were not different. Adenovirus-mediated AQP1 expression in SMMC-7221/Pf cells increased their water permeability and migration rate. These results provide the first evidence that aquaporin-mediated membrane water permeability enhances tumor cell migration and may be associated with tumor invasion and metastasis.

  19. Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma

    Directory of Open Access Journals (Sweden)

    Alessandra Mangolini

    2014-01-01

    Full Text Available Renal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs, which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma.

  20. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O. [Lab. de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne (Switzerland); Knebel Doeberitz, M. von [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Inst. fuer Virusforschung

    1998-02-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [Deutsch] Das Ziel dieser Studie lag darin, die Rolle der HPV-18-Gene E6 und E7 in bezug auf die Strahlenempfindlichkeit von menschlichen Zervixkarzinomzellen zu untersuchen. Wir verwendeten zwei menschliche Zervixkarzinomzellinien, C4-1 und SW 756, in welchen die Expression der viralen Gene HPV 18 E6 und E7 mit Dexamethason moduliert werden kann: In C4-1 bewirkt die Behandlung mit Dexamethason eine Erhoehung der Expression dieser Gene, in SW 756 eine Verminderung. Die Wirkung auf die Wachstumsfaehigkeit der Zellen und auf die Wachstumshemmung durch die Bestrahlung wurde unter Verwendung eines klonogenen Assays bestimmt. Dexamethason bewirkte eine erhoehte Wachstumsfaehigkeit der C4-1 Zellen, ohne die Wachstumsfaehigkeit der SW-756-Zellen zu beeinflussen, wie schon frueher beschrieben. Die Resistenz beider Zellinien gegenueber Bestrahlung wurde erhoeht. Somit besteht in den C4-1-Zellen eine Korrelation der Expression der viralen Gene mit der Zunahme der Strahlenresistenz, wogegen in den SW-756-Zellen die Abnahme der Expression im Gegensatz zu

  1. Expression of survivin and matrix metalloproteinases in adenocarcinoma and squamous cell carcinoma of the uterine cervix.

    Science.gov (United States)

    Yoshida, Hiroyuki; Sumi, Toshiyuki; Hyun, Yooji; Nakagawa, Eri; Hattori, Kanae; Yasui, Tomoyo; Morimura, Mina; Honda, Ken-Ichi; Nakatani, Tatsuya; Ishiko, Osamu

    2003-01-01

    Cervical cancer can be classified into two histological types: squamous cell carcinoma (SCA) and adenocarcinoma (ACA). Reportedly ACA has poorer prognoses, metastasizes more easily to lymph nodes, and is more resistant to radiotherapy than SCA. To clarify the cause of characteristic differences between these histological types, we examined the expressions of apoptosis inhibiting and tumor-invasion related factors in both histological types. We reviewed the 34 cases of cervical cancer (17 ACA, 17 SCA) that had surgery as their initial treatment at Osaka City University Medical School Hospital between 1996 and 2001. The differences of survivin, and matrix metalloproteinase (MMP-2, and MMP-7) expressions between both histological types were immunohistochemically assayed, and the correlation between the expression of each protein and clinicopathological characteristics was analyzed. Survivin was expressed significantly stronger in ACA cases (p=0.035). The number of patients who expressed MMP-2 and MMP-7 simultaneously was significantly higher in SCA cases (p=0.039). MMP-2 and MMP-7 had tendencies to be expressed stronger in SCA (p=0.057 and p=0.084, respectively). These results suggest that the differences of the expression of survivin (an apoptosis inhibiting factor), MMP-2, and MMP-7 (tumor-invasion related factors) between ACA and SCA were causes of the characteristic differences between the two histological types.

  2. Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma.

    Science.gov (United States)

    Lu, Meng; Wu, Jiao; He, Feng; Wang, Xi-Long; Li, Can; Chen, Zhi-Nan; Bian, Huijie

    2015-02-01

    Overexpression of CD147/basigin in hepatic cells promotes the progression of hepatocellular carcinoma (HCC). Whether CD147 also expressed in liver non-parenchymal cells and associated with HCC development was unknown. The aim of the study was to explore time-dependent cell expression patterns of CD147 in a widely accepted N-diethylnitrosamine/phenobarbital (DEN/PB)-induced HCC mouse model. Liver samples collected at month 1-12 of post-DEN/PB administration were assessed the localization of CD147 in hepatocytes, endothelial cells, hepatic stellate cells, and macrophages. Immunohistochemistry analysis showed that CD147 was upregulated in liver tumors during month 1-8 of DEN/PB induction. Expression of CD147 was positively correlated with cytokeratin 18, a hepatocyte marker (r = 0.7857, P = 0.0279), CD31 (r = 0.9048, P = 0.0046), an endothelial cell marker, and CD68, a macrophage marker (r = 0.7619, P = 0.0368). A significant correlation was also observed between CD147 and alpha-smooth muscle actin (r = 0.8857, P = 0.0333) at DEN/PB initiation and early stage of tumor formation. Immunofluorescence and fluorescence in situ hybridization showed that CD147 co-expressed with cytokeratin 18, CD31, alpha-smooth muscle actin, and CD68. Moreover, there existed positive correlations between CD147 and microvessel density (r = 0.7857, P = 0.0279), CD147 and Ki-67 (r = 0.9341, P = 0.0022) in the development of DEN/PB-induced HCC. In conclusion, our results demonstrated that CD147 was upregulated in the liver parenchymal and mesenchymal cells and involved in angiogenesis and tumor cell proliferation in the development of DEN/PB-induced HCC.

  3. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S;

    2008-01-01

    Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship...

  4. Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun Nan; Zhi-Ping Ruan; Zhao Jing; Hai-Xia Qin; Hong-Yan Wang; Hui Guo; Rui Xu

    2005-01-01

    AIM: To evaluate the expression of fragile histidine triad (FHIT) gene protein, product of a candidate tumor suppressor,and to investigate the relationship between FHIT, cell apoptosis and proliferation, and pathological features of primary hepatocellular carcinoma (HCC).METHODS: Forty-seven HCC and ten normal liver specimens were collected during surgical operation between 2001and 2003. FHIT and proliferating cell nuclear antigen (PCNA)expression were detected by immunohistochemistry, and apoptotic level was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay on the tissue sections.RESULTS: All normal liver tissues showed a strong expression of FHIT, whereas 28 of 47 (59.6%) carcinomas showed a significant loss or absence of FHIT expression (P = 0.001).The proportion of reduced FHIT expression in those carcinomas at stages Ⅲ-Ⅳ (70.6%) and in those with extrahepatic metastasis (86.7%) showed an increasing trend compared with those at stages Ⅰ-Ⅱ (30.8%, P= 0.013) and those without metastasis (46.9%, P = 0.010) respectively. Apoptotic incidence in advanced TNM stage carcinoma and those with positive FHIT expression was higher than that in early stage carcinoma (P = 0.030) and in those with negative FHIT expression (P = 0.044) respectively. The proliferating potential of hepatocellular carcinoma was associated with FHIT expression (P = 0.016) and the aggressive feature (P = 0.019). Kaplan-Meier analysis demonstrated that the survival time of these 47 patients correlated with TNM stage,FHIT expression and metastasis.CONCLUSION: There is marked loss or absence of FHIT expression, as well as abnormal apoptosis-proliferation balance in HCC. FHIT may play an important role in carcinogenesis and development of HCC.

  5. COX-1 and COX-2 expression in feline oral squamous cell carcinoma.

    Science.gov (United States)

    Hayes, A; Scase, T; Miller, J; Murphy, S; Sparkes, A; Adams, V

    2006-01-01

    This study demonstrated immunohistochemically the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2 immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear; it was demonstrated in a small proportion (tissues showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1 immunolabelling was less intense than nuclear labelling in neoplastic tissue. In the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent. The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling was significantly higher in neoplastic tissue than in adjacent normal oral mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but the clinical and pathophysiological significance of this finding remains to be determined.

  6. Anti-apoptotic signature in thymic squamous cell carcinomas - functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

    Directory of Open Access Journals (Sweden)

    Bei eHuang

    2013-12-01

    Full Text Available The molecular pathogenesis of thymomas and thymic carcinomas (TCs is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCC with a custom made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

  7. Expression of vascular cell adhesion molecule-1 facilitates angiogenesis in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yongbin Ding; Tianson Xia; Guoyu Chen; Jianguo Xia

    2006-01-01

    Objective: To investigate the relationship between the expression of VCAM-1 and oncogenesis, tumor angiogenesis and metastasis in gastric carcinoma. Methods: Using RT-PCR and immunohistochemistry technique, the expression of VCAM-1 were detected in specimens from 44 patients with gastric cancer, 8 with ulcer. Microvessel density (MVD) was also counted by endothelial cells immunostained with monoclonal antibodies CD34. In addition, Circulating sVCAM-1 concentrations were measured by an enzyme linked immunosorbent assay. Results:Of 44 gastric cancer tumor tissues, 36were detected the ex pressions of VCAM-1 mRNA. The rates of VCAM-1 mRNA in the primary gastric cancer tissues were significantly higher than those in the para-cancerous tissues and benign ulcer tissues (P < 0.05). The VCAM-1 posithoseive isolates had more lymph node metastases than that of VCAM-l-negative ones (P < 0.05). MVD of positive VCAM-1 expression tissues were higher than those of negative VCAM-1 (P < 0.05). Circulating sVCAM-1 levels decreased significantly after operation (P < 0.05). Furthermore, the levels of sVCAM-1 were positively correlated with the expressions of VCAM-1 in the tumor tissues (r = 0.64, P <0.05). Conclusion: Expressions of VCAM-1 mRNA was closely related to oncogenesis, tumor angiogenesis and metastasis in gastric carcinoma. The concentration of sVCAM-1 may be considered as an effective mark of tumor burden of gastric cancer.

  8. EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survival.

    Science.gov (United States)

    Monteiro, Luís Silva; Delgado, Maria Leonor; Ricardo, Sara; Garcez, Fernanda; do Amaral, Barbas; Pacheco, José Júlio; Lopes, Carlos; Bousbaa, Hassan

    2014-01-01

    The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P = 0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression (P = 0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS) (P = 0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

  9. Expression of epithelial-mesenchymal transition markers at the invasive front of oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Liana Cristina Melo Carneiro COSTA

    2015-04-01

    Full Text Available Oral squamous cell carcinoma (OSCC is one of the most common malignances. In epithelial-mesenchymal transition (EMT, epithelial cells switch to mesenchymal-like cells exhibiting high mobility. This migratory phenotype is significant during tumor invasion and metastasis. Objective : The aim of this study is to evaluate the expression of the EMT markers E-cadherin, N-cadherin and vimentin in OSCC. Material and Methods : Immunohistochemical detection of E-cadherin, N-cadherin and vimentin was performed on 20 OSCC samples. Differences in the expression of each protein at the invasive front (IF and in the central/superficial areas (CSA of the tumor were assessed. Differences in the expression of each protein at the IF of both histologically high- and low-invasive OSCCs were evaluated. Associations among expression of proteins at the IF were assessed. Correlations between the expression levels of each protein at the IF and the tumor stage and clinical nodal status were also evaluated. Results : Reduced expression of E-cadherin was detected in 15 samples (75%. E-cadherin expression was reduced at the IF when compared to the CSA and in high-invasive tumors when compared to low-invasive tumors. All samples were negative for N-cadherin, even though one sample showed an inconspicuous expression. Positive expression of vimentin was observed in 6 samples (30%. Nevertheless, there was no difference in vimentin expression between the IF and the CSA regions or between the low- and high-invasive tumors. Furthermore, no association was observed among protein expression levels at the IF. Finally, no correlations were observed between each protein’s expression levels and tumor stage or clinical nodal status. Conclusions : Reduced E-cadherin expression at the IF and its association with histological invasiveness suggest that this protein is a noteworthy EMT marker in OSCC. Although vimentin was also detected as an EMT marker, its expression was neither limited to

  10. p53 protein expression in corneal squamous cell carcinomas of dogs

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    Lucas Bahdour Cossi

    2015-06-01

    Full Text Available Ocular tumors play an increasing concern in veterinary ophthalmology. Corneal squamous cell carcinoma is unfrequent in dogs, and by this way it has little studies. Studies that investigated the carcinogenesis mechanisms wich could help to the development of ocular squamous cell carcinoma (SCC in dog are rare. The aim of this work was to identify by immunohistochemical techniques, the p53 protein expression in the spontaneous dog corneal SCC. For this work, were used five cases of corneal SCC and one case of actinic keratitis. The sections were obtained from paraffin-wax blocks and submitted to histopathological and immunohistochemical analysis. All the six samples showed immunolabeling to cytokeratin and p53 protein. These results support the conclusions that the immunoreactivity of p53 protein by immunohistochemistry is present in canine corneal SCC suppporting its role in carcinogenesis of this tumor, but not provides prognostic indicators in cases of SCC corneal in dog; and can be a association of exposure to solar radiation with the possible mutation of the TP53 gene.

  11. Immunohistochemical Expression of Cyclooxygenase-2 in Urinary Bladder Transitional Cell Carcinomas

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    F Niki

    2012-07-01

    Full Text Available Background: Transitional Cell Carcinoma (TCC is the most common type of urinary bladder cancer. Cyclooxygenase-2 (COX-2, a key enzyme in prostaglandins biosynthesis, has been introduced as a new candidate for targeted therapy in this cancer. In this study, we investigated the expression of COX-2 in urinary bladder TCCs and its relationship with clinicopathological parameters such as tumor grade and stage. Methods: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Pathology reports of patients with definite diagnosis of urinary bladder TCCs who had undergone Transurethral Resection (TUR were reviewed and 40 cases were selected. Subsequently, COX-2 expression was assessed immunohistochemically by the examination of paraffin embedded tissue blocks. Staining in more than 5% of tumor cells was considered as positive expression. Results: COX-2 was expressed in 52.5% of the patients. High-grade tumors revealed a higher (87.5% COX-2 expression versus other grades of the lesions and there was a statistically significant difference in COX-2 expression between them (P<0.001. Patients age was also related to the expression of this marker (P=0.03. In contrast, this marker did not correlate with other characteristics including gender, lymphatic invasion or tumor stage. In addition, perineurial or vascular invasions were not detected in any of the patients. Conclusion: COX-2 expression was seen in more than half of our patients and it had a marked relation to tumor differentiation. Accordingly, this molecule may be a useful tumor marker in the assessment of urinary bladder cancers.

  12. Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium

    Science.gov (United States)

    Cartularo, Laura; Laulicht, Freda; Sun, Hong; Kluz, Thomas; Freedman, Jonathan H.; Costa, Max

    2015-01-01

    Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the earth’s crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24 hours; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181 genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, and cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24 hours indicated a reduction in global levels of histone methylation and acetylation that persisted 72 hours post-treatment. PMID:26314618

  13. WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression

    Science.gov (United States)

    Li, Fu-Jun; Wang, Xin-Juan; Zhou, Xiao-Li

    2016-01-01

    Background WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC) cells. Methods In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells. In addition, the role of MMP-2 in the WISP-1-mediated growth regulation was also investigated. Results It was demonstrated that the WISP-1 expression was upregulated at both mRNA and protein levels in 15 of 21 SGC tumor tissues, compared to the non-tumor tissues (five of 21), associated with the lymph node dissection and bone invasion. The in vitro CCK-8 assay and colony-forming assay demonstrated that the exogenous WISP-1 treatment or the WISP-1 overexpression promoted the growth of A-253 cells. In addition, we confirmed that the WISP-1 overexpression upregulated the MMP-2 expression in A-253 cells with the gain-of-function and loss-of-function strategies, and that the MMP-2 knockdown attenuated the WISP-1-mediated growth promotion of A-253 cells. Conclusion We found that WISP-1 was overexpressed in the human SGCs, and the WISP-1 overexpression promoted the salivary gland cell proliferation via upregulating MMP-2 expression. Our study recognized the oncogenic role of WISP-1 in human SGCs, which could serve as a potential target for anticancer therapy. PMID:27799801

  14. Relation Between Fluorodeoxyglucose Uptake and Glucose Transporter 1 Expression in Gastric signet Ring Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Bong Hoi; Song, Hee Sung; An, Young Sil; Han, Sang Uk; Kim, Jang Hee; Yoon, Joon kee [Ajou Univ. School of medicine, Suwon (Korea, Republic of)

    2011-03-15

    Gastic signet ring cell carcinoma (GSRC) is known to have low fluorodeoxyglucose (FDG) uptake. The aim of the study was to investigate the relation between FDG uptake and glucose transporter (GLUT) 1 expression and clinicopathologic parameters in cases of GSRC. Forty patients (28 men, mean age 54{+-}12 years) with histologically confirmed GSRC who underwent pre operative [{sup 18}F]FDG PET/CT were enrolled. Maximum standardized uptake values (SUVmax) were compared with clinicopathologic parameters and GLUT 1 expression. Cases were divided based on GLUT 1 expression in tumor tissues into a membranous group (n=17) and a cytoplasmic group (n=23). Mean SUVmax was significantly higher in the membranous group than in the cytoplasmic group (6.06{+-}2.79 vs, 3.67{+-}1.54, P=0.03). Gastric wall invasion, depth of invasion, extent of LN metastasis, overall stage, and tumor size were found to be related to SUVmax. On the other hand, age, sex, and the presence of distant metastasis were not related to SUVmax. Multiveriate analysis revealed that membranous GLCT 1 expression and the extent of LN metastasis independently predicted high FDG uptake. This study demonstrates that high FDG uptake is mediated by membranous GLUT 1 expression in GSRC.

  15. Correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Xiaoping Huang; Jun Qi; Cai Yan; Xin Xu; Yaling Han; Mingrong Wang

    2008-01-01

    Androgen-induced proliferation shutoff gene AS3, also known as APRIN, is a growth inhibitory gene that is in itially implicated inprostate cancer. This gene is required for androgen-dependent growth arrest and is a primary target for 1,25(OH)2D3 and androgens. Alle-lic loss at AS3 locus has been linked to a variety of cancers. However, the correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma (ESCC) is not well established. In this study, the genomic and expression alterations of AS3 in ESCC and their clinical significance are evaluated. Loss of beterozygosity (LOH) analysis using an AS3 intragenic mierosatellite marker D13S171 revealed 72% allelic loss at AS3 locus in ESCC, which is significantly correlated with higher pathological grade (P=0.042).RT-PCR examination showed that AS3 mRNA obviously decreased in 44% tumors and its down-regulation was correlated with the sex of patients (P=0.03). Furthermore, the correlation between genomic and expression alterations of AS3 gene was analyzed in 18 ESCC specimens, which indicated that the consistency between allelic loss and decreased mRNA expression of AS3 was relatively poor. The results of this study indicate that the aberrant expression of AS3 may be involved in the tumorigenesis of esophagus and is responsible for the male predominance of ESCC.

  16. Expression of GLTSCR2/Pict-1 in squamous cell carcinomas of the skin.

    Science.gov (United States)

    Kim, Jee-Youn; Cho, Young-Eun; Park, Jae-Hoon; Lee, Sun

    2013-11-01

    The most important cause of cutaneous squamous cell carcinomas (SCC) is DNA damage induced by exposure to solar UV irradiation. DNA damage induced by UV irradiation is sensed by early DNA damage response (DDR) proteins. Recently, GLTSCR2 has been suggested to play a role in UV light-induced DDR. To explore the role of GLTSCR2 in the development of cutaneous SCC, we investigated the molecular mechanism underlying GLTSCR2 inactivation in response to UV irradiation. We analyzed cutaneous SCC (n=42), basal cell carcinomas (BCC; n=26), and normal skin tissue samples (n=36) and compared GLTSCR2 expression between tumor and normal tissues, using immunohistochemistry. Next, to investigate the effects of UV irradiation on GLTSCR2, we performed immunocytochemistry, RT-PCR, immunoblotting, half-life assay for GLTSCR2, and comet assay after UV irradiation in primary keratinocytes. GLTSCR2 expression in SCC was significantly lower than that of normal skin tissue (pUV irradiation. UV irradiation accelerated degradation of GLTSCR2 through proteasomal pathway. Knockdown of GLTSCR2 resulted in marked decrease in γH2AX foci after UV exposure. Furthermore, comet assay showed that DNA damage after UV exposure persists longer in GLTSCR2 knocked-down cells. Our data show that GLTSCR2 is downregulated in SCC of the skin and that UV light exposure decreases the stability of GLTSCR2 and sensitizes keratinocytes to DNA damage. Therefore, our data suggest that GLTSCR2 might be involved in the development and/or progression of SCC of the skin.

  17. Immunohistochemical evaluation of E-cadherin expression in basal cell carcinoma of the skin

    Directory of Open Access Journals (Sweden)

    Vladimír Bartoš

    2015-08-01

    Full Text Available Introduction: E-cadherin is important cell-cell adhesion molecule, that plays a crucial role in the maintenance of tissue microarchitecture. In many human malignancies, reduced or loss of E-cadherin production in neoplastic cells correlates with tumor dedifferentiation and acquisition of the invasive and metastatic potential. In contrast to most other cancers, basal cell carcinoma (BCC of the skin possess some unique features, such as slow local growth, strong stroma-dependency, and virtual absence of metastases. Aim: In the present study, we immunohistochemically evaluated expression of E-cadherin in a set of cutaneous BCCs. Material and methods: Study group consisted of 41 primary BCCs cathegorized into non-infiltrative subroup (superfical and nodular subtypes and infiltrative subroup (nodular-infiltrative and infiltrative subtypes. Results: E-cadherin was expressed in all tumor specimens with variable quantitative range and intensity. There were 19 cases (46.3 % with preserved and 22 cases (53.7 % with reduced E-cadherin expression. In superficial, nodular, nodular-infiltrative and infiltrative BCC subtypes, reduced E-cadherin immunoreactivity was found in 40 % (2/5, 56.2 % (9/16, 54.5 % (6/11 and 55.5 % (5/9, respectively. We did not confirm a significant correlation between expression of E-cadherin and both given, non-infiltrative and infiltrative BCC subgroup. None of the tumors examined showed apparent decreasing immunostaining intensity in tumor tissue with increasing depth of invasion. There were not convincing differences either between the central and peripheral parts of tumor mass, or in the vertical dimension. Conclusions: Reduction of E-cadherin expression per se does not seem to directly contribute to the acqusition of more aggressive phenotype in cutaneous BCC. This may represent another peculiarity, by which BCC differs from the most other epithelial malignancies and reflect a distinct tumor biology.

  18. Association of mu-opioid receptor expression with lymph node metastasis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Y-F; Xu, Q-X; Liao, L-D; Xu, X-E; Wu, J-Y; Wu, Z-Y; Shen, J-H; Li, E-M; Xu, L-Y

    2015-01-01

    The mu-opioid receptor (MOR), a membrane-bound G protein-coupled receptor, is the main target for opioids in the nervous system. MOR1 has been found in several types of cancer cells and reported to be involved in tumor progression and metastasis. However, the expression and clinical significance of MOR1 in esophageal squamous cell carcinoma (ESCC) remain unclear. In our study, the expression of MOR1 was confirmed in ESCC cell lines (KYSE180, KYSE150, and EC109) by Western blot. MOR1 was also detected on tissue microarrays of ESCC samples in 239 cases using immunohistochemical staining. We found that MOR1 was mainly located in the cytoplasm and occasionally occurred in the membrane or nucleus of ESCC cells. Moreover, results indicated that MOR1 expression in the cytoplasm was associated with lymph node metastasis (R = 0.164, P = 0.008, Kendall's tau-b-test). No more associations were found between MOR1 expression status and other clinical parameters. However, no statistical significant differences were found between MOR1 expression in the cytoplasm, nucleus/membrane, and the overall survival of ESCC patients (P = 0.848; P = 0.167; P = 0.428, respectively, log-rank test). Our results suggest that the cytoplasmic MOR1 may be a high-risk factor for lymph node metastasis of ESCC patients. We also hypothesize that MOR1 agonists used in ESCC patients should be prudent, and opioid receptor antagonists may be novel therapeutic drugs for ESCC patients.

  19. Impact of increased erythropoietin receptor expression and elevated serum erythropoietin levels on clinicopathological features and prognosis in renal cell carcinoma

    OpenAIRE

    ITO, KEIICHI; YOSHII, HIDEHIKO; ASANO, TAKAKO; HORIGUCHI, AKIO; Sumitomo, Makoto; Hayakawa, Masamichi; ASANO, TOMOHIKO

    2012-01-01

    Erythropoietin (EPO) expression and EPO receptor (EpoR) expression have been demonstrated in various malignant tumors. EPO-EpoR signaling can activate several downstream signal transduction pathways that enhance tumor aggressiveness. The present study was undertaken to evaluate the impact of overexpression of EpoR and elevated serum EPO (sEPO) levels on the clinicopathological features and prognosis of patients with renal cell carcinoma (RCC). EpoR expression was evaluated immunohistochemical...

  20. Immunohistochemical expression of Bcl-2 in oral epithelial dysplasia and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    S Juneja

    2015-01-01

    Full Text Available BACKGROUND: The B cell lymphoma-2 gene is a proto-oncogene whose protein product inhibits apoptosis. Its role is associated with keeping cells alive, but not by stimulating them to proliferation, as other proto-oncogenes do. Increased expression of protein product of Bcl-2 gene appears in the early phase of carcinogenesis leading to apoptosis impairment and in consequence to the progression of neoplastic changes. OBJECTIVE: To evaluate and compare the expression of Bcl-2 protein in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. MATERIALS AND METHODS: Sixty cases of formalin-fixed paraffin-embedded archival specimens comprising of 30 cases of leukoplakia with oral epithelial dysplasia and 30 cases of OSCC were taken for immunohistochemical analysis using monoclonal antibody against anti-human Bcl-2 oncoprotein. RESULTS: Immunostaining for Bcl-2 protein was identified in basal and parabasal layers as granular cytoplasmic staining in oral epithelial dysplasia. In OSCC, Bcl-2 immunoreactivity was most prominent in the peripheral cells of the infiltrating tumor islands which diminished toward the center in well-differentiated and moderately differentiated OSCC, whereas stronger and more diffuse expression of Bcl-2 oncoprotein was seen in poorly differentiated OSCC. Overall positivity of 26.7% (8/30 was observed in oral epithelial dysplasia and 30% (9/30 in OSCC in this study. INTERPRETATION AND CONCLUSION: Altered expression of Bcl-2 oncoprotein may be an early molecular event which leads to prolonged cell survival, increased chances of accumulation of genetic alterations, and subsequent increase in malignant transformation potential.

  1. Gene Expression Differences Predict Treatment Outcome of Merkel Cell Carcinoma Patients

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    Loren Masterson

    2014-01-01

    Full Text Available Due to the rarity of Merkel cell carcinoma (MCC, prospective clinical trials have not been practical. This study aimed to identify biomarkers with prognostic significance. While sixty-two patients were identified who were treated for MCC at our institution, only seventeen patients had adequate formalin-fixed paraffin-embedded archival tissue and followup to be included in the study. Patients were stratified into good, moderate, or poor prognosis. Laser capture microdissection was used to isolate tumor cells for subsequent RNA isolation and gene expression analysis with Affymetrix GeneChip Human Exon 1.0 ST arrays. Among the 191 genes demonstrating significant differential expression between prognostic groups, keratin 20 and neurofilament protein have previously been identified in studies of MCC and were significantly upregulated in tumors from patients with a poor prognosis. Immunohistochemistry further established that keratin 20 was overexpressed in the poor prognosis tumors. In addition, novel genes of interest such as phospholipase A2 group X, kinesin family member 3A, tumor protein D52, mucin 1, and KIT were upregulated in specimens from patients with poor prognosis. Our pilot study identified several gene expression differences which could be used in the future as prognostic biomarkers in MCC patients.

  2. Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma

    Science.gov (United States)

    Jeong, Dae Cheon; Han, Myoung-Eun; Kim, Ji-Young; Liu, Liangwen; Jung, Jin-Sup; Oh, Sae-Ock

    2017-01-01

    Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage. Furthermore, Kaplan-Meier and multivariate regression analysis showed that reduction in the mRNA expression of ZHX1 was associated with poorer survival. Taken together, the present study shows loss of ZHX1 is correlated with ccRCC progression and suggests it is an independent prognostic marker in ccRCC. PMID:28152006

  3. Expression of Yes-associated protein 1 gene and protein in oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Song-ying; HU Ji-an; WANG Hui-ming

    2013-01-01

    Background Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the oral and maxillofaoial region.Yes-associated protein 1 (YAP1) has been implicated as a bona fide oncogene in solid tumors.We seek to elucidate the role of YAP1 in OSCC tissue.Methods We identified YAP1 gene and protein overexpression in 30 OSCC patients and 10 normal oral mucosa tissues by immunohistochemistry,Western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results In the normal oral mucosa by immunohistochemical staining,YAP1 mainly located in both the cytoplasm and nucleus mainly the nuclei of the basal cells.In OSCC,the expression of YAP1 translocated from the nucleus to cytoplasm;YAP1 being mainly located in both the cytoplasm and nucleus of the adjacent mucosa.The expression of YAP1 gradual increased in normal oral mucosa,tumor adjacent mucosa and low grade,middle grade,high grade OSCC tissue by Western blotting.Significant difference was found between the expressions of the normal oral mucosa and OSCC tissue (P <0.05).The coincidence was detected between the normal oral mucosa and OSCC tissue by RT-PCR (P <0.05).Conclusions YAP1 is involved in the carcinogenesis and development of OSCC.There is a transformation between nucleus and cytoplasm.

  4. Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas

    DEFF Research Database (Denmark)

    Le, Quynh-Thu; Kong, Christina; Lavori, Phillip W;

    2007-01-01

    PURPOSE: To investigate the expression pattern of hypoxia-induced proteins identified as being involved in malignant progression of head-and-neck squamous cell carcinoma (HNSCC) and to determine their relationship to tumor pO(2) and prognosis. METHODS AND MATERIALS: We performed immunohistochemical...

  5. Decreased gene expression of human beta-defensin-1 in the development of squamous cell carcinoma of the oral cavity.

    NARCIS (Netherlands)

    Wenghoefer, M.H.; Pantelis, A.; Dommisch, H.; Reich, R.; Martini, M.; Allam, J.P.; Novak, N.; Berge, S.; Jepsen, S.; Winter, J.

    2008-01-01

    The aim of this study was to investigate the gene expression of human beta-defensin-1, -2, -3 (hBD-1, -2, -3), interleukin-1beta, tumour necrosis factor-alpha and cyclooxygenase-2 in oral squamous cell carcinoma (OSCC) compared to benign and premalignant lesions as well as healthy controls. Biopsies

  6. Immunohistochemical expression of budding uninhibited by benzimidazole related 1 in leukoplakia and oral squamous cell carcinoma

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    Taneeru Sravya

    2016-01-01

    Full Text Available Background: Budding uninhibited by benzimidazole related 1 (BUBR1 is an important protein in the mitotic spindle assembly checkpoint. Alterations in expression of BUBR1 have been reported in many premalignant and malignant lesions. Aim: To compare the expression of BUBR1 with respect to the normal mucosa and degree of dysplasia in oral leukoplakia (OL and also with respect to different histopathological grades of oral squamous cell carcinoma (OSCC. Materials and Methods: Neutral buffered formalin-fixed and paraffin-embedded biopsy specimens 30 each of normal, OL and OSCC tissue were included in this study. The expression of BUBR1 was detected using immunohistochemistry (IHC. The scores obtained were subjected to ANOVA test. Results: Significant correlation was found in immunostaining between normal, dysplasia and OSCC groups with a P value of 0.00001. The expression of BUBR1 was significant when compared with different degrees of dysplasia and in different histopathological grades of OSCC with a P value of 0.00001. Conclusion: Higher IHC scores were obtained with increased histopathological grades of OL and OSCC suggesting its role as a prognostic indicator.

  7. Altered expression of SIRT gene family in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Lai, Chi-Chih; Lin, Pai-Mei; Lin, Sheng-Fung; Hsu, Cheng-Hsien; Lin, Hsin-Ching; Hu, Ming-Luen; Hsu, Cheng-Ming; Yang, Ming-Yu

    2013-06-01

    Head and neck squamous cell carcinoma (HNSCC) include a group of malignant neoplasms that arise from the upper aerodigestive tract and represent the seventh most common cause of cancer-related death. The overall 5-year survival rates have not significantly improved for decades in spite of the advances in the field of oncology and surgery, encouraging further research on factors that might modify disease prognosis. The silent information regulator (SIR) genes (Sirtuins) play key roles in cellular stress and are associated with aging-related diseases including cancer. Currently, seven human sirtuin (SIRT1-7) genes have been identified, but the roles of SIRT genes in HNSCC are still uncertain. Therefore, in this study, we used real-time quantitative reverse transcription-polymerase chain reaction to investigate the expressions of the seven SIRT genes in human HNSCC tissues to assess the changes in cancerous and noncancerous parts and the correlation with different tumor behaviors. Our results demonstrated that the expression levels of SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly downregulated in cancerous tissues compared with noncancerous tissues (all pSIRT1, SIRT2, SIRT3, SIRT5, and SIRT7 showed downregulation in advanced stages in respect to early stages (pSIRT genes expression may contribute to the development of cancer and trigger the neoplastic disease to more advanced stages. Our study indicates that SIRT genes expression could help in the diagnosis and represent a prognostic biomarker in HNSCC.

  8. N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma

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    Ludwig Behnes Carl

    2012-08-01

    Full Text Available Abstract Background Papillary renal cell carcinoma (RCC represents a rare tumor, which is divided, based on histological criteria, into two subtypes. In contrast to type I papillary RCC type II papillary RCC shows a worse prognosis. So far, reliable immunohistochemical markers for the distinction of these subtypes are not available. Methods In the present study the expression of N(neural-, E(epithelial-, P(placental-, und KSP(kidney specific-cadherin was examined in 22 papillary RCC of histological type I and 18 papillary RCC of histological type II (n = 40. Results All papillary RCC type II displayed a membranous expression for N-cadherin, whereas type I did not show any membranous positivity for N-cadherin. E-cadherin exhibited a stronger, but not significant, membranous as well as cytoplasmic expression in type II than in type I papillary RCC. A diagnostic relevant expression of P- and KSP-cadherin could not be demonstrated in both tumor entities. Conclusion Thus N-cadherin represents the first immunhistochemical marker for a clear cut differentiation between papillary RCC type I and type II and could be a target for therapy and diagnostic in the future. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2011556982761733

  9. Expressão de marcadores de proliferação celular e apoptose em carcinoma basocelular Markers expression of cell proliferation and apoptosis in basal cell carcinoma

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    Marília de Pádua Dornelas Corrêa

    2009-12-01

    Full Text Available FUNDAMENTOS: O carcinoma basocelular é o câncer mais comum em humanos. Estudos que utilizam recursos da biologia molecular e genética, associados à histomorfologia, permitem a identificação de fatores de risco no desenvolvimento de lesões mais recorrentes e agressivas. OBJETIVO: Correlacionar a expressão dos marcadores de apoptose (p53 e Bcl-2 e proliferação celular (Ki-67 e PCNA com os indicadores histológicos de gravidade do tumor. MÉTODOS: Estudaram-se cinco amostras das formas nodular, morfeiforme e superficial, respectivamente, e um grupo-controle com três pacientes livres de lesão. Empregou-se o teste de Mann-Whitney na comparação da expressão desses marcadores com a forma de apresentação do carcinoma basocelular. RESULTADOS: Verificou-se que a marcação do Bcl-2 foi expressiva nos CBCs ditos agressivos (variantes morfeiforme e nodular. Dos tumores estudados, 66,7% (n = 10 indicaram fortemente o p53. Nossos resultados mostram maior expressão do Ki-67 no carcinoma basocelular nodular e superficial, sem expressão nos controles. O PCNA mostrou forte marcação em todos os tipos de tumores e nos controles. CONCLUSÃO: Os achados nos permitem concluir que o Bcl-2 e o p53 apresentam tendência para diagnosticar gravidade do carcinoma basocelular e o Ki-67, por seu comportamento variável, não pode ser considerado como marcador de gravidade, assim como o PCNA, que não foi um bom marcador de proliferação celular.BACKGROUND: - Basal cell carcinoma is the most common form of human cancer. Studies employing molecular and genetic biology techniques, associated with histomorphology, lead to the identification of risk factors in the development of more recurring and aggressive lesions. OBJECTIVE - To correlate markers expression of apoptosis (p53 and bcl-2 and cell proliferation (Ki-67 and PCNA with histological indicators of tumor severity. METHODS - Five samples of the nodular, morpheaform and superficial types of carcinoma

  10. NAC1, a potential stem cell pluripotency factor expression in normal endometrium, endometrial hyperplasia and endometrial carcinoma.

    Science.gov (United States)

    Ishikawa, Masako; Nakayama, Kentaro; Yeasmin, Shamima; Katagiri, Atsuko; Iida, Kouji; Nakayama, Naomi; Miyazaki, Kohji

    2010-05-01

    The purpose of this study was to investigate the role of NAC1 in the development of endometrial cancer. NAC1 expression and localization were assessed with immunohistochemistry in the normal cyclic human endometrium, hyperplastic endometrium, and endometrial cancer. Expression of NAC1 in the glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases, endometrial hyperplasia, and endometrial carcinoma. NAC1 expression was down-regulated during endometrial carcinogenesis. There were significant correlations between positive NAC1 expression and pathological grade (P=0.037). No significant associations were found between NAC1 expression and the other clinicopathological characteristics including patient age, FIGO staging, depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, menopause, or body mass index. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and JHEM2 cell lines, all of which overexpressed NAC1. Ectopic overexpression of the NAC1 gene stimulated cell proliferation in the HEC1B, and JHEM1 endometrial cancer cell lines, which have lower endogenous NAC1 expression. Endometrial carcinomas with NAC1 overexpression are clinically aggressive, high-grade carcinomas. Therefore, detection of NAC1 overexpression in endometrial cancers may identify patients who will benefit from NAC1 targeted therapy.

  11. Expressão de metaloproteinases de matriz e de seus inibidores teciduais em carcinomas basocelulares Expression of matrix metalloproteinasis and their tissue inhibitors in basal cell carcinoma

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    Rosy Iara Maciel de Azambuja Ribeiro

    2008-04-01

    Full Text Available INTRODUÇÃO: Aproximadamente 80% das neoplasias malignas de pele não-melanomas são carcinomas basocelulares (CBC. Apesar das raras metástases, esses tumores são localmente agressivos. As metaloproteinases de matriz (MMPs, especialmente as MMP-2 e 9, são importantes no processo de invasão. Em contrapartida, os inibidores teciduais das MMPs (TIMPs têm como principal função a inibição dessas enzimas. OBJETIVO: Investigar a associação de variáveis clinicopatológicas de pacientes portadores de CBC com a expressão de MMP-2, MMP-9, TIMP-1 e TIMP-2. MATERIAL E MÉTODOS: Foram selecionados 31 casos de CBC, sendo então obtidos, retrospectivamente, os dados referentes a idade, sexo e tamanho da lesão. Cortes histológicos das lesões foram submetidos a reação imuno-histoquímica pela técnica estreptavidina-biotina-peroxidase para detecção dos antígenos de interesse. Índices de imunomarcação foram construídos e comparados com os dados previamente obtidos. RESULTADOS: Observou-se correlação significativa entre idade e tamanho da lesão (R = 0,532; p = 0,008. Não foram observadas correlações significativas entre as outras variáveis e a expressão imuno-histoquímica dos antígenos de interesse. CONCLUSÃO: A expressão das metaloproteinases e de seus inibidores teciduais não parece ser influenciada pelos parâmetros investigados. Estudos adicionais são necessários para melhor compreensão de sua associação com o comportamento biológico do CBC.INTRODUCTION: Approximately 80% of non-melanoma skin neoplasias are basal cell carcinomas (BCC. Although metastasis is rare, BBC carcinomas are locally aggressive tumors. Matrix metalloproteinases (MMPs, mainly MMP-2 and MMP-9, play an important role on the invasion process. On the other hand, tissue inhibitors of MMPs (TIMPs have the main function of inhibiting these enzymes. OBJECTIVE: To investigate the association of clinical-pathological variables of BCC patients with the

  12. Expression of Wnt and Notch pathway genes in a pluripotent human embryonal carcinoma cell line and embryonic stem cell.

    Science.gov (United States)

    Walsh, James; Andrews, Peter W

    2003-01-01

    Embryonal carcinoma (EC) cells, the pluripotent stem cells of teratocarcinomas, show many similar-ities to embryonic stem (ES) cells. Since EC cells are malignant but their terminally differentiated derivatives are not, understanding the molecular mechanisms that regulate their differentiation maybe of value for diagnostic and therapeutic purposes. We have examined the expression of multiple components of two developmentally important cell-cell signalling pathways, Wnt and Notch, in the pluripotent human EC cell line, NTERA2, and the human ES cell line, H7. Both pathways have well-documented roles in controlling neurogenesis, a process that occurs largely in response to retinoicacid (RA) treatment of NTERA2 cultures and spontaneously in H7 cultures. In NTERA2, many ofthe genes tested showed altered transcriptional regulation following treatment with RA. These include members of the frizzled gene family (FZDI, FZD3, FZD4, FZD5, FZD6), encoding receptors forWnt proteins, the Frizzled Related Protein family (SFRPI, SFRP2, FRZB, SFRP4), encoding solubleWnt antagonists and also ligands and receptors of the Notch pathway (Dlkl, Jaggedl; Notchl, Notch2, Notch3). Few differences were found in the repertoire of Wnt and Notch pathway genes expressed by NTERA2 EC cells and H7 ES cells. We present a model in which interactions between and regulation of Wnt and Notch signalling are important in maintaining EC/ES stem cells and also controlling their differentiation.

  13. Study on Translational Medicine of RUNX3 Expression in Oral Precancerous Lesions and Squamous Cell Carcinoma

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    Ramamurthy Mustafa

    2016-03-01

    Full Text Available Objective: To explore the expression and distribution characteristics of RUNX3 in the pathological process of oralsquamous cell carcinoma (OSCC as well as its correlation with clinicopathological features. Methods: Fifteen cases of normal oral mucosal tissues, 37 cases of OSCC tissues and 21 cases of precancerous lesion tissues were respectively collected. The expression and distribution characteristics of RUNX3 were detected using immunohistochemical method, and its relationship with each clinicopathological feature of OSCC was analyzed. Results: The positive rates of RUNX3 expression in normal oral mucosal tissues, precancerous lesion tissues and OSCC tissues were 100% (15/15, 95.24% (20/21 and 54.05% (20/37, and their average optical densities were (0.391±0.07, (0.369±0.03 and (0.263±0.01, respectively. The differences were statistically significant by comparison to the positive rates of RUNX3 expression and their average optical densities in normal oral mucosal tissue, precancerous lesion tissue and OSCC tissue (P<0.01. There was no statistical significance regarding RUNX3 expression in the patients with different gender, age and presence or absence of lymph node metastasis (P>0.05, but the difference was statistically significant among the patients with different pathological gradings (P=0.012. Conclusion: The expression of RUNX3 in normal oral mucosal tissues, precancerous lesion tissues and OSCC tissues gradually shows a down-regulating tendency and its frequency of abnormal localization is on the rise. The expression of RUNX3 is closely associated with the degree of histological differentiation. All of these findings indicate that RUNX3, an important action factor in the occurrence and progression of OSCC, can be considered as a key biological indicator for early diagnosis, judgment of malignant degree and prognostic monitoring.

  14. Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma

    Science.gov (United States)

    Kim, Ryul; Keam, Bhumsuk; Kwon, Dohee; Ock, Chan-Young; Kim, Miso; Kim, Tae Min; Kim, Hak Jae; Jeon, Yoon Kyung; Park, In Kyu; Kang, Chang Hyun; Kim, Dong-Wan; Kim, Young Tae; Heo, Dae Seog

    2016-01-01

    AIM To investigate the expression and prognostic role of programmed death ligand-1 (PD-L1) in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed. RESULTS Tumor tissues from 67 ESCC patients (33.5%) were PD-L1-positive. Positive p16 expression was observed in 21 specimens (10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens (21.0%). Although PD-L1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PD-L1-positivity (OR = 2.34, 95%CI: 1.16-4.72, P = 0.017). PD-L1 expression was not significantly associated with a change in overall survival (P = 0.656). In contrast, the locoregional relapse rate tended to increase (P = 0.134), and the distant metastasis rate was significantly increased (HR = 1.72, 95%CI: 1.01-2.79, P = 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative ESCC. CONCLUSION PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC. PMID:27729745

  15. Expression of Cyclin D1 and P16 in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Dey, Biswajit; Raphael, Vandana; Khonglah, Yookarin; GiriLynrah, Kyrshanlang

    2015-10-01

    BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the lethal cancers with a high incidence rate in Asia. Many genes including cyclin D1 and p16 play important role in its carcinogenesis. We aimed to analyze the expressions of cyclin D1 and p16 with the various clinicopathological characteristics of ESCC. METHODS We examined 30 biopsy samples of ESCC for cyclin D1 and p16 protein expressions using immunohistochemistry. Immunointensity was classified as no immunostaining (-), weakly immunostaining (+), weak immunostaining (++) and strongly positive immunostaining (+++). RESULTS Out of the 30 cases, positive expression of cyclin D1 was detected in 26 cases (86.7%). The percentage of tumors with invasion to the adventitia (88.2%), lymph node metastasis (87.5%), and tumors which were poorly differentiated (92.9%) were higher in cyclin D1 positive tumors than in the cyclin D1 negative tumors. However no significant association was found between cyclin D1 expression and the different clinicopathological parameters.There were 22 cases of ESCC (73.3 %) which showed negativity for p16. The percentage of tumors with invasion to the adventitia (82.4%) and poorly differentiated tumors (92.9%) were higher in the p16 negative tumors than in the p16 positive tumors. There was significant association between the histological grade and p16 expression (p=0.012). However, there were no significant association with regard to site, size and lymph node status of the tumors and p16 expression. CONCLUSION The study shows that alterations of cyclin D1 and p16 play an important role in ESCC. Loss of p16 expression was associated with poor differentiation.

  16. Piroxicam inhibits Masitinib-induced cyclooxygenase 2 expression in oral squamous cell carcinoma cells in vitro.

    Science.gov (United States)

    Rathore, Kusum; Alexander, Mary; Cekanova, Maria

    2014-08-01

    Development and characterization of animal models for human cancers is important for the improvement of diagnosis and therapy. The oral squamous cell carcinoma (OSCC) of domestic animals resembles human OSCC in many aspects; thus, cell lines derived from OSCC of cats and dogs are a valuable model for human OSCC. We characterized 1 feline OSCC (FeOSCC-Sidney) and 1 canine OSCC (K9OSCC-Abby) cell line and compared their characteristics with human OSCC cell line hSCC-25. We calculated the doubling time of the new OSCC cell lines and evaluated the expression profiles of cancer-related markers and cell-cycle proteins such as c-kit, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, epidermal growth factor receptor, cyclooxygenase (COX)-1, COX-2, and p27 by immunocytochemistry and Western blot analysis. We evaluated the effects of novel receptor tyrosine kinase inhibitor (Masitinib, AB1010) and the nonsteroidal anti-inflammatory drug piroxicam on the previously mentioned OSCC cells. Interestingly, AB1010 increased expression levels of COX-2 in all tested OSCCs. Cotreatment of piroxicam with Masitinib significantly inhibited cell proliferation of OSCC as compared to either drug alone through the c-kit and AKT signaling pathways. Piroxicam inhibited Masitinib-induced COX-2 expression in all tested OSCCs. Therefore, targeting these two signaling pathways simultaneously was more efficient for inhibition of OSCCs across these species.

  17. Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase.

    Science.gov (United States)

    Yoon, Cheol-Yong; Shim, Young-Jun; Kim, Eun-Ho; Lee, Ju-Han; Won, Nam-Hee; Kim, Jeong-Hun; Park, In-Sun; Yoon, Duck-Ki; Min, Bon-Hong

    2007-02-15

    Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ASS, which enables tumor cells to recycle citrulline to arginine. Thus, we examined the expression levels of ASS in various cancer cells and found that it is low in renal cell carcinoma (RCC) cells, rendering the cells highly sensitive to arginine deprivation by ADI treatment. Immunohistochemical analysis revealed that in biopsy specimens from RCC patients (n = 98), the expression of ASS is highly demonstrated in the epithelium of normal proximal tubule but not seen in tumor cells. Furthermore, RCC cells treated with ADI showed remarkable growth retardation in a dose dependent manner. ADI also exerted in vivo antiproliferative effect on the allografted renal cell carcinoma (RENCA) tumor cells and prolonged the survival of tumor-bearing mice. Histological examination of the tumors revealed that tumor angiogenesis and vascular endothelial growth factor (VEGF) expression were significantly diminished by ADI administration. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of RCC in ways of inhibitions of arginine availability and neovascularization.

  18. Expressão de glicoesfingolipídeos no carcinoma espinocelular do trato aerodigestivo superior Glycosphingolipid expression in squamous cell carcinoma of the upper aerodigestive tract

    Directory of Open Access Journals (Sweden)

    Marcilio Ferreira Marques Filho

    2006-02-01

    Full Text Available Os glicoesfingolipídios (GSLs são importantes componentes da membrana celular, organizados em microdomínios, relacionados a receptores de membrana e comportamento anti-social da célula neoplásica como crescimento descontrolado, invasão e ocorrência de metástases. OBJETIVO: Como a expressão de GSLs no carcinoma espinocelular (CEC é tema pouquíssimo estudado decidiu-se realizar estudo prospectivo visando avaliar a expressão de GSLs no CEC do trato aerodigestivo superior. MÉTODO: Coletou-se 33 amostras de CEC e mucosa normal e GSLs extraídos e purificados por cromatografia de fase reversa em coluna de C-18 e hidrólise alcalina em metanol. Os GSLs foram quantificados por densitometria das placas de cromatografia de alta resolução em camada delgada coradas com orcinol. RESULTADOS: Observou-se aumento significativo de GSLs no CEC (3,57µg/mg em comparação à mucosa normal (1,92µg/mg, principalmente do monosialogangliosídeo (GM3, trihexosilceramida (CTH, dihexosilceramida (CDH, globosídeo (Gb4. A expressão de monohexosilceramida (CMH foi semelhante no CEC e na mucosa normal. O aumento do GM3 no CEC foi demonstrado por métodos imunoquímicos empregando-se MAb DH2 (anti-GM3. Analisando-se os carboidratos do CMH por cromatografia gasosa acoplado a espectrômetro de massa constatou-se que a mucosa normal expressa glucosilceramida e o CEC glucosilceramida e galactosilceramida. CONCLUSÃO: O aumento de GSLs no tecido tumoral pode representar alterações dos microdomínios da membrana celular resultantes do processo de transformação maligna, responsáveis por uma maior interação célula-célula e célula-matriz aumentando seu potencial de infiltração e metástase, possibilitando o emprego dos GSLs e de MAbs no diagnóstico e no tratamento do CEC, a exemplo do que ocorre no melanoma.Glycosphingolipids are integral constituents of cellular membrane, arranged in rafts, and with neoplasic cell anti-social behavior, like uncontrolled

  19. Gene Expression Patterns in Ovarian Carcinomas

    Science.gov (United States)

    Schaner, Marci E.; Ross, Douglas T.; Ciaravino, Giuseppe; Sørlie, Therese; Troyanskaya, Olga; Diehn, Maximilian; Wang, Yan C.; Duran, George E.; Sikic, Thomas L.; Caldeira, Sandra; Skomedal, Hanne; Tu, I-Ping; Hernandez-Boussard, Tina; Johnson, Steven W.; O'Dwyer, Peter J.; Fero, Michael J.; Kristensen, Gunnar B.; Børresen-Dale, Anne-Lise; Hastie, Trevor; Tibshirani, Robert; van de Rijn, Matt; Teng, Nelson N.; Longacre, Teri A.; Botstein, David; Brown, Patrick O.; Sikic, Branimir I.

    2003-01-01

    We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers. PMID:12960427

  20. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Skakkebaek, N E

    1994-01-01

    Carcinoma-in-situ of the testis (CIS) is the precursor of invasive germ cell tumours. It is believed that CIS cells may originate from early fetal gonocytes. Recently, the proto-oncogene c-kit has been implicated as crucial for the development and migration of primordial germ cells. In this study......, CIS and overtly invasive human male germ cell tumours were analysed immunohistochemically for expression of the c-kit proto-oncogene protein product. Testicular tissue samples from 36 patients with various types of testicular germ cell neoplasia and 19 control specimens were stained using an indirect...... in 61% of the samples while focal expression was observed in 39% of the samples studied. No expression of c-kit was detected in non-seminomas or in normal testicular germ cells. High expression of the proto-oncogene in CIS cells supports the hypothesis of their origin from primordial germ cells...

  1. The Relationship between Apoptosis and the Expression of Proliferating Cell Nuclear Antigen and the Clinical Stages in Gastric Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5±3.7) % and (49.8±15.9) % respectively, and the rate of AI/PI was 0.13±0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer (P<0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage Ⅱ to Ⅳ (P<0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.

  2. COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tie-Jun Li; Jun Cui

    2013-01-01

    Objective:To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Methods: The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC. Results: The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM (P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP (P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM (P<0.01). The COX-2 expression was associated with clinical stage (P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis (P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC. Conclusions:The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.

  3. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2012-02-01

    BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance\\/loss of heterozygosity (AI\\/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI\\/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

  4. Study on Translational Medicine of RUNX3 Expression in Oral Precancerous Lesions and Squamous Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ramamurthy Mustafa; Shabil Mohamed Rajaraman

    2016-01-01

    Objective: To explore the expression and distribution characteristics of RUNX3 in the pathological process of oral squamous cell carcinoma (OSCC) as well as its correlation with clinicopathological features. Methods: Fifteen cases of normal oral mucosal tissues, 37 cases of OSCC tissues and 21 cases of precancerous lesion tissues were respectively collected. The expression and distribution characteristics of RUNX3 were detected using immunohistochemical method, and its relationship with each clinicopathological feature of OSCC was analyzed. Results: The positive rates of RUNX3 expression in normal oral mucosal tissues, precancerous lesion tissues and OSCC tissues were 100% (15/15), 95.24% (20/21) and 54.05% (20/37), and their average optical densities were (0.391±0.07), (0.369±0.03) and (0.263±0.01), respectively. The differences were statistically signiifcant by comparison to the positive rates of RUNX3 expression and their average optical densities in normal oral mucosal tissue, precancerous lesion tissue and OSCC tissue (P0.05), but the difference was statistically signiifcant among the patients with different pathological gradings (P=0.012). Conclusion: The expression of RUNX3 in normal oral mucosal tissues, precancerous lesion tissues and OSCC tissues gradually shows a down-regulating tendency and its frequency of abnormal localization is on the rise. The expression of RUNX3 is closely associated with the degree of histological differentiation. All of these findings indicate that RUNX3, an important action factor in the occurrence and progression of OSCC, can be considered as a key biological indicator for early diagnosis, judgment of malignant degree and prognostic monitoring.

  5. Expression of CD44 and P53 in renal cell carcinoma: Association with tumor subtypes

    Directory of Open Access Journals (Sweden)

    Farahnaz Noroozinia

    2014-01-01

    Full Text Available Renal cell carcinoma (RCC is a common malignancy of the kidney and accurate prediction of prognosis is valuable for the design of adjuvant therapy and counseling and effective scheduling of follow-up visits. Molecular genetic investigations of CD44 and P53 in RCC may be helpful in this regard. We studied the CD44 and P53 expressions semi-quantitatively on paraffin-embedded specimens of 64 RCC patients (37 male/27 female who underwent surgery from 2003 to 2008 by immunohistochemistry and analyzed the correlation of P53 and CD44 expression in RCC and outcome. Thirteen of 64 (20.3% specimens were P53 positive, 30/64 (46.9% were CD44 positive and five tumors with positive P53 expressed CD44 protein (P = 0.5. A statistically significant correlation was not found between CD44 and P53 expression (P = 0.5 and age (P = 0.07, sex (P= 0.3, tumor size (P = 0.7, grade (P = 0.23, vascular invasion (P = 1.00 and ureteral invasion (P = 1.00. Furthermore, a significant correlation was not found between P53 expression with age (P = 0.3, sex (P = 0.7, tumor size (P = 0.7, grade (P = 0.1, vascular inva-sion (P = 1.00 and ureteral invasion (P = 1.00. According to our findings, only P53 expression is generally accompanied by non-conventional subtype tumor.

  6. Rat hepatic stellate cells alter the gene expression profile and promote the growth, migration and invasion of hepatocellular carcinoma cells.

    Science.gov (United States)

    Wang, Zhi-Ming; Zhou, Le-Yuan; Liu, Bin-Bin; Jia, Qin-An; Dong, Yin-Ying; Xia, Yun-Hong; Ye, Sheng-Long

    2014-10-01

    The aim of the present study was to examine the effects of activated hepatic stellate cells (HSCs) and their paracrine secretions, on hepatocellular cancer cell growth and gene expression in vitro and in vivo. Differentially expressed genes in McA-RH7777 hepatocellular carcinoma (HCC) cells following non-contact co-culture with activated stellate cells, were identified by a cDNA microarray. The effect of the co-injection of HCC cells and activated HSCs on tumor size in rats was also investigated. Non-contact co-culture altered the expression of 573 HCC genes by >2-fold of the control levels. Among the six selected genes, ELISA revealed increased protein levels of hepatic growth factor, matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9). Incubation of HCC cells with medium conditioned by activated HSCs significantly increased the proliferation rate (Pprofile of HCC cells and affected their growth, migration and invasiveness. The results from the present study indicate that the interaction between the activated HSCs and HCC has an important role in the development of HCC.

  7. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    Energy Technology Data Exchange (ETDEWEB)

    Melchers, Lieuwe J., E-mail: l.j.melchers@umcg.nl [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Clausen, Martijn J.A.M. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Mastik, Mirjam F. [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Slagter-Menkema, Lorian [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Laan, Bernard F.A.M. van der [Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wal, Jacqueline E. van der; Vegt, Bert van der [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Roodenburg, Jan L.N. [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schuuring, Ed [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    2014-10-01

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was optimized on formalin-fixed, paraffin-embedded tissue using glioblastoma tissue. It was compared with EGFR and EGFRvIII RNA expression using a specific reverse transcription–polymerase chain reaction also optimized for formalin-fixed, paraffin-embedded tissue. Tissue microarrays including 531 HNSCCs of various stages with complete clinicopathologic and follow-up data were tested for the presence of EGFRvIII. Results: None of the 531 cases showed EGFRvIII protein expression. Using an immunohistochemistry protocol reported by others revealed cytoplasmic staining in 8% of cases. Reverse transcription–polymerase chain reaction for the EGFRvIII transcript of the 28 highest cytoplasmic staining cases, as well as 69 negative cases, did not show expression in any of the tested cases, suggesting aspecific staining by a nonoptimal protocol. Conclusions: The EGFRvIII mutation is not present in HNSCC. Therefore, EGFRvIII does not influence treatment response in HNSCC and is not a usable clinical prognostic marker.

  8. Differential expression of microRNA clusters in bladder transitional cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Feng Xu; Zhifeng Wei; Zhengyu Zhang; Jingping Ge; Peng Xie; Hongqing Ma; Jianping Gao; Wen Cheng

    2013-01-01

    Objective: The aim of the study was to investigate the differential expression of microRNAs (miRNAs) in bladder transitional cell carcinoma (BTC). Methods: Fresh tissues were obtained from patients with BTC (9 cases; 3 cases with grade I, 3 cases with grade II, 3 cases with grade III) and those with normal bladder mucosa (3 cases) and stored in liquid nitrogen. Total RNA was extracted using TRizol reagent and RNA was quantified and quality control was performed. miRNA probes were labeled with Hy3TM fluorescence, then hybridized with a miRCURYTM array labeling kit. miRNA arrays were scanned and analyzed and the scanned result was validated using reverse transcription-polymerase chain reaction (RT-PCR). Results: In four groups of differentially expressed genes obtained from grade I, grade II, grade III, and grade I + grade II + grade III BTC tissues compared with normal bladder mucosa, hsa-miR-29b-1* was upregulated, and hsa-miR-923 and hsa-miR-300 were downregulated. The hsa-miR-29b-1*, hsa-miR-300, and hsa-miR-923 findings were confirmed by real-time RT-PCR. Conclusion: Genes that were differentially expressed between BTC and normal bladder mucosa may be involved in the pathogenesis and development of BTC, and may be useful for further studies of BTC-related genes.

  9. Increased expression of the PRL-3 gene in human oral squamous cell carcinoma and dysplasia tissues.

    Science.gov (United States)

    Hassan, Nur Mohammad Monsur; Hamada, Jun-ichi; Kameyama, Takeshi; Tada, Mitsuhiro; Nakagawa, Koji; Yoshida, Shoko; Kashiwazaki, Haruhiko; Yamazaki, Yutaka; Suzuki, Yukiko; Sasaki, Akira; Nagatsuka, Hitoshi; Inoue, Nobuo; Moriuchi, Tetsuya

    2011-01-01

    Phosphatase of regenerating liver (PRL) belongs to a class of the protein tyrosine phosphatase family, which is known so far to consist of 3 members, PRL-1, PRL-2, and PRL-3. The aim of this study was to uncover the role of PRL genes in development of oral malignancy. We analyzed expression levels of the 3 PRL genes in 50 human oral squamous cell carcinomas (OSCCs), 11 dysplasia and 12 normal mucosa tissues by a real-time RT-PCR method. PRL-3 but not PRL-1 or PRL-2 expressions were significantly higher in OSCC and dysplasia than in normal mucosa tissues. Additionally, PRL-3 expressions were significantly higher in OSCC tissues harboring dominant-negative p53 or recessive p53 mutation than in those harboring wild-type p53. These results suggest that PRL-3 plays a role in oral cancer development and can be useful as a marker of pre-malignant and malignant lesion of oral mucosa.

  10. Over-expressed Genes Detected by Suppression Subtractive Hybridization in Carcinoma Derived From Transformed 16HBE Cells Induced by BPDE

    Institute of Scientific and Technical Information of China (English)

    SHE-JUAN AN; JIA-KUN CHEN; LI-LI LIU; YAN-FENG ZHAO; XUE-MIN CHEN

    2005-01-01

    Objective To screen the over differentially expressed genes in carcinoma induced by BPDE-transformed 16HBE cells (16HBE-C cells). Methods The suppression subtractive hybridization (SSH) method was performed to profile differentially expressed genes between 16HBE-C cells and 16HBE cells. The cDNA fragments of differentially expressed genes were inserted into TA cloning vector and transformed competent E. coli strain. Positive clones were randomly picked up and identified by the colony PCR method. Dot blot was used to test the same source with the tester. The differentially expressed cDNA fragments were sequenced and compared with known genes and EST database in Genbank. Results Eight known genes were over-expressed in 16HBE-C cells including eukaryotic translation elongation factor 1 alpha 1, HIF-1 responsive RTP801, ribosomal protein L10 (RPL10), ribosomal protein S29 (RPS29), mitochondrion related genes, and laminin receptor 1. Three differentially expressed cDNA fragments could not be matched to the known genes but to the EST database. Conclusion The SSH method can detect differentially expressed genes between 16HBE-C and 16HBE cells. BPDE-induced carcinogenesis may be related to alteration of at least eight known genes and three unknown genes. These expression data provide a clue to further cloning novel genes and studying functions in BPDE-induced carcinoma.

  11. Expression of Hypoxia Inducible Factor-1α and Its Relationship to Apoptosis and Proliferation in Human Laryngeal Squamous Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    俞琳琳; 刘洋; 崔永华

    2004-01-01

    To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used to detect the expression of HIF-1α and PCNA. Tunnel technique was used to detect in situ cell apoptosis in LSCC. Our results showed that the expression of HIF-1α was related to the clinical stages of cancer and lymph node metastasis (P<0. 05). The relationship between HIF-1α and PCNA was statistically significant (P<0.05) and no relationship was found between HIF-1α and apoptosis (P>0.05) It is concluded that HIF-1α plays a role in the carcinogenesis of laryngeal carcinoma and is correlated with proliferation, but bears no relationship with the apoptosis of tumor cells in LSCC.

  12. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  13. Clinical significance of costimulatory molecule B7-H3 expression on CD3+T cells in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    MAO Yong; SUN Jing; WANG Wei-peng; ZHANG Xue-guang; HUA Dong

    2013-01-01

    Background B7-H3 has been widely studied in the context of tumor progression in recent years,and behaves as a tumor cell marker in a variety of tumors including colorectal carcinoma.The mechanism of B7-H3 in tumor progression is complicated and not clear yet.Studies have revealed that B7 family molecules are expressed on infiltrated lymphocytes as well as tumor cells in tumor microenvironment,which indicates that different expression pattern may lead to different clinical outcomes.Methods The expression of B7-H3 was detected in tissues of 98 colorectal carcinoma patients by using immunohistochemistry.Then the expression of B7-H3 on CD3+ T lymphocytes isolated from fresh cancer tissues of 12 colorectal carcinoma patients was analyzed by flow cytometry assay.The relationship between the expression of B7-H3 on CD3+ T lymphocytes and patients' clinical pathological parameters was demonstrated with statistical analysis.Results Patients with more CD3+ T cell infiltration survived much longer than patients with less CD3+ T cell infiltration (P <0.05); B7-H3 was highly expressed by infiltrating CD3+ T lymphocytes in colorectal carcinoma tissues.The expression of B7-H3 was found to be significantly related with lymph node metastasis status (P <0.05),but not with the patient's gender,age,tumor size,differentiation degree,depth of tumor invasion,Dukes' stage,distant metastasis and whether or not mucinous adenocarcinoma was present (P >0.05).Moreover,the survival time of patients with low expression of B7-H3 was obviously longer than those of high B7-H3 expression patients,but the seven-year survival rate showed no difference between the high and low B7-H3 expression patients (P >0.05).Conclusion The negative costimulatory molecule B7-H3 on infiltrating CD3+ T lymphocytes in colorectal carcinoma bears importance in the clinical pathological progress and prognosis of colorectal carcinoma.

  14. EXPRESSION OF A MUTANT hTERT IN HUMAN BLADDER CARCINOMA CELL LINE T24 AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    符伟军; 洪宝发; 黄君健; 徐兵; 高江平; 王晓雄; 黄翠芬

    2004-01-01

    Objective: To construct a mutant pEGFP- hTERT expression vector, to observe its steady expression in transfected human bladder carcinoma cell line T24 and its role in molecular regulatory mechanisms of telomerase, and to provide a new target gene for bladder cancer. Methods: PCR amplification was performed by using primers based on the known gene sequence of hTERT. PCR production was cloned into plasmid pGEMT-T easy and the sequence of mutant hTERT gene was analyzed. A recombinant mutant hTERT vector (pEGFP-hTERT) was constructed at the EcoR I and Sal I sites of the pEGFP-C1 vector. After transfecting the fusion gene into bladder carcinoma cell line T24 by calcium phosphate-DNA coprecipitation, the steady expression of GFP-hTERT fusion protein was tested by fluorescent light microscopy. The proliferation changes of bladder carcinoma cell line T24 were detected by light microscopy and senescence correlated β-galactosidase staining. Results: Identification of pEGFP-hTERT by enzyme digestion showed that mutant hTERT fragment had been cloned into EcoR I and Sal I sites of the pEGFP-C1 vector. The steady expression of GFP-hTERT fusion protein was localized in the nucleus of transfected cells. Expression of senescence-associated β-galactosidase in transfected cells gradually increased with extended cultured time and cell growth was suppressed. Conclusion: The mutant-type hTERT gene suppresses the proliferation of bladder carcinoma cell line T24 by competitive effect on telomerase activity. This suggests that hTERT gene might be a suitable gene target for bladder cancer therapy.

  15. Knockdown of survivin gene expression by RNAi induces apoptosis in human hepatocellular carcinoma cell line SMMC-7721

    Institute of Scientific and Technical Information of China (English)

    Sheng-Quan Cheng; Wen-Liang Wang; Wei Yan; Qing-Long Li; Li Wang; Wen-Yong Wang

    2005-01-01

    AIM: To investigate the survivin gene expression in human hepatocellular carcinoma cell line SMMC-7721 and the effects of survivin gene RNA interference (RNAi) on cell apoptosis and biological behaviors of SMMC-7721 cells.METHODS: Eukaryotic expression vector of survivin gene RNAi and recombinant plasmid pSuppressorNeo-survivin (pSuNeo-SW), were constructed by ligating into the vector,pSupperssorNeo (pSuNeo) digested with restriction enzymes Xba I and Sa/I and the designed double-chain RNAi primers. A cell model of SMMC-7721 after treatment with RNAi was prepared by transfecting SMMC-7721 cells with the lipofectin transfection method. Strept-avidinbiotin-complex (SABC) immunohistochemical staining and RT-PCR were used to detect survivin gene expressions in SMMC-7721 cells. Flow cytometry was used for the cell cycle analysis. Transmission electron microscopy was performed to determine whether RNAi induced cell apoptosis, and the method of measuring the cell growth curve was utilized to study the growth of SMMC-7721 cells before and after treatment with RNAi.RESULTS: The eukaryotic expression vector of survivin gene RNAi and pSuNeo-SW, were constructed successfully. The expression level of survivin gene in SMMC-7721 cells was observed. After the treatment of RNAi, the expression of survivin gene in SMMC-7721 cells was almost absent,apoptosis index was increased by 15.6%, and the number of cells was decreased in G2/M phase and the cell growth was inhibited.CONCLUSION: RNAi can exert a knockdown of survivin gene expression in SMMC-7721 cells, and induce apoptosis and inhibit the growth of carcinoma cells.

  16. Evaluation of the Selenotranscriptome Expression in Two Hepatocellular Carcinoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Stefano Guariniello

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common type of liver cancer and is still one of the most fatal cancers. Hence, it needs to identify always new putative markers to improve its diagnosis and prognosis. Since the selenium is able to fight the oxidative damage which is one of the major origins of cell damage as well as cancer, we have recently focused our attention on selenoprotein family and their involvement in HCC. In the present paper we have carried out a global analysis of the selenotranscriptome expression in HepG2 and Huh7 cells compared to the normal human hepatocytes by reverse transcription-qPCR (RT-qPCR. Our data showed that in both cells there are three downregulated (DIO1, DIO2, and SELO and ten upregulated (GPX4, GPX7, SELK, SELM, SELN, SELT, SELV, SEP15, SEPW1, and TrxR1 genes. Additionally, interactomic studies were carried out to evaluate the ability of these down- and upregulated genes to interact between them as well as to identify putative HUB nodes representing the centers of correlation able to exercise a direct control over the coordinated genes.

  17. Expression and inducibility of UDP-glucuronosyltransferase 1As in MCF-7 human breast carcinoma cells.

    Science.gov (United States)

    Hanioka, Nobumitsu; Iwabu, Hiroyuki; Hanafusa, Hiroyuki; Nakada, Shintaro; Narimatsu, Shizuo

    2012-03-01

    UDP-glucuronosyltransferases (UGTs) are conjugation enzymes, which are regulated in a tissue-specific manner by endogenous and environmental factors. In this study, we focused on UGT1A isoforms broadly expressed in hepatic and extrahepatic tissues and examined the expression and inducibility of UGT1As (UGT1A1 and UGT1A3-1A10) in MCF-7 cells (human breast carcinoma cell line). Reverse transcription polymerase chain reaction (RT-PCR) analysis demonstrated that UGT1A1, UGT1A6 and UGT1A9 mRNAs as well as the mRNAs of transcriptional regulators (AhR, aryl hydrocarbon receptor; Arnt, AhR nuclear translocator; ERα, oestrogen receptor α; ERβ, oestrogen receptor β; and GR, glucocorticoid receptor) are expressed in MCF-7 cells. UGT1A6 mRNA level in MCF-7 cells was significantly increased to 1.9 times by β-naphthoflavone (BNF), whereas UGT1A1 and UGT1A9 mRNA levels were not affected by BNF. There were no significant changes in the mRNAs of UGT1A1, UGT1A6 and UGT1A9 in MCF-7 cells by treatment with phenobarbital (PB) and dexamethasone (DEX) in MCF-7 cells. The kinetics of 7-ethyl-10-hydroxycamptothecin (SN-38), 5-hydroxytryptamine (5-HT) and 4-methylumbelliferone (4-MU) glucuronidation by microsomes from control and BNF-treated MCF-7 cells fitted with the Michaelis-Menten model, and the V(max) and CL(int) values were significantly increased to 7.5-8.5 times and 5.9-10.4 times by BNF treatment, respectively. These findings suggest that BNF induces UGT1A6 in MCF-7 cells and that the increase may be mediated by AhR but not pregnane X receptor (PXR)/constitutive androstane receptor (CAR). The information gained in this study should help predict and assess the toxicity of environmental chemicals.

  18. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

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    Magaldi, Thomas G.; Almstead, Laura L. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Bellone, Stefania [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Prevatt, Edward G. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Santin, Alessandro D. [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States); DiMaio, Daniel, E-mail: daniel.dimaio@yale.edu [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Department of Therapeutic Radiology, Yale School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040 (United States); Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States)

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  19. MicroRNA Expression Profiling in Clear Cell Renal Cell Carcinoma: Identification and Functional Validation of Key miRNAs.

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    Haowei He

    Full Text Available This study aims to profile dysregulated microRNA (miRNA expression in clear cell renal cell carcinoma (ccRCC and to identify key regulatory miRNAs in ccRCC.miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452 and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429 were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3' untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes.This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429 may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

  20. Up-regulated manganese superoxide dismutase expression increases apoptosis resistance in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    HU Hai; WANG Ming-rong; LUO Man-li; DU Xiao-li; FENG Yan-bin; ZHANG Yu; SHEN Xiao-ming; XU Xin; CAI Yan; HAN Ya-ling

    2007-01-01

    Background Esophageal cancer is one of the most common malignancies in the world.In order to identify the proteins associated with esophageal squamous cell carcinomas(ESCC),we analyzed the protein profiles of ESCC cases with tumor and matched adjacent normal tissues.Methods Two-dimensional electrophoresis(2-DE)was carried out to analyze the protein profiles.Dysregulated protein spots were identified by Matrix-Assisted Laser Desorption Ionization Time-of-Flight(MALDI-TOF)and verified by liquid chromatography/electrospray ionization ion trap-mass spectrometry/mass spectrometry(LC-ESI-IT MS).RT-PCR and immunohistochemistry on tissue microarray were performed to confirm the gene dysregulation in esophageal cancerous tissues.RNA interference (RNAi)was used to knock down the gene expression in ESCC cell lines.Apoptosis assay with annexin V-FITC/PI staining was conducted and cells were analyzed by flow cytometry.Results 2-DE showed that two protein spots with approximate molecular weights and different pl were elevated in 12 out of 18 ESCCs as compared to the corresponding normal tissues.Both the two spots were identified as MnSOD by MALDI-TOF and were verified by LC-ESI-IT MS.MnSOD overexpression was detected in 14 tumors out of 24 cases by RT-PCR and 52 tumors out of 116 cases by immunohistochemistry comparing to normal epithelia.siRNA-mediated silencing of MnSOD in KYSE450 and KYSE150 cell lines revealed that MnSOD protected ESCC cells from apoptosis induced by ultraviolet(UV)and doxorubicin(DOX).Conclusions These findings suggest that there existed two isoforms of MnSOD protein in normal and tumor esophageal tissues.MnSOD was overexpressed in ESCC and its up-regulation in esophageal cancer cells was associated with apoptosis resistance.

  1. Expressão de marcadores de proliferação celular e apoptose no carcinoma espinocelular de pele e ceratose actínica Expression of cell proliferation and apoptosis biomarkers in skin spinocellular carcinoma and actinic keratose

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    Marilho Tadeu Dornelas

    2009-10-01

    Full Text Available FUNDAMENTOS: O câncer de pele é o mais frequente tipo de câncer humano e mostra aumento de sua incidência. Em muitos casos, antes do surgimento do carcinoma, instala-se uma lesão precursora, ceratose actínica, podendo evoluir para carcinoma espinocelular. Estudos buscam determinar os parâmetros com significado prognóstico na predição daqueles tumores que terão comportamento mais agressivo. OBJETIVO: Avaliar a expressão dos marcadores de proliferação celular (PCNA, Ki-67 e apoptose (p53, Bcl-2, em portadores de carcinoma espinocelular e ceratose actínica. MÉTODO: Foram estudadas amostras de 30 pacientes: sendo dez portadores do carcinoma espinocelular; dez de ceratose actínica e dez indivíduos livres de lesões submetidos à blefaroplastia. RESULTADOS: A proteína p53 foi expressa em todos os casos estudados, embora apresentassem padrões quantitativos diferentes. O Bcl-2 foi expresso em baixa intensidade. Em seis casos de ceratose actínica, nas peles de blefaroplastia, e negativo nos casos de carcinoma espinocelular. O PCNA exibiu expressão intensa, em todas as amostras. O Ki-67 apresentou expressão variável, nos casos de carcinoma e de ceratose, e negativo na pele de pálpebra. CONCLUSÃO: A expressão do Ki-67 e a não-expressão de Bcl-2, no grupo CEC, indica intensificação da atividade proliferativa. Ao passo que, a maior expressão de p53 e Bcl-2, no grupo CA, sugere imortalização celular.BACKGROUND: Skin cancer is the most frequent type of human cancer and has shown an increase in its incidence. In many cases, before the onset of the carcinoma, there might be a precursor lesion - actinic keratosis, which can develop into squamous cell carcinoma. Studies have been carried out in order to etermine the parameters that have prognostic significance in predicting those tumors which have more aggressive behavior. OBJECTIVE: To evaluate the expression of markers of cell proliferation (PCNA, Ki-67 and apoptosis (p53,Bcl-2

  2. Increase of bcl-2 Protein Expression in Aggressive Basal Cell Carcinoma of Head and Neck

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    Cláudia CAZAL

    2006-09-01

    Full Text Available Objective: The aim of this study was to verify the bcl-2 protein expression in 22 cutaneous basal cell carcinomas (BCC of the head and neck, and to compare it with its aggressive behavior. Method: Tumors were histologically classified in non-aggressive (BCC 1 and aggressive (BCC 2 and then submitted to the immunohistochemistry technique with the streptavidin-biotin peroxidase method using the anti-bcl-2 antibody. Results: After proceeding to morphological analysis, sixteen tumors (72.7% were considered aggressive and six (27.3% non-aggressive. Immunohistochemistry analysis showed that thirteen (59.1% lesions were positive staining and nine (40.9% were negative to the bcl-2 protein. Considering the positive lesions, 12 (92.3% were aggressive and one (7.7% non-aggressive. The relation between bcl-2 protein staining and the tumor aggressiveness was statistically significant (p<0.05 - Fisher's exact Test. Conclusion: The results suggest a relationship between the bcl-2 protein expression and the histological aggressiveness grade in the BCC of the head and neck group studied may exist.

  3. Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression

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    Xiao, Can [Department of Occupational Medicine and Environmental Health, School of Public Health, Soochow University, Suzhou 215123 (China); Department of Stomatology, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Wang, Lili; Zhu, Lifang [Department of Stomatology, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Zhang, Chenping, E-mail: zhang_cping@163.com [Department of Head and Neck Tumors, Shanghai Ninth People’s Hospital Affiliated Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhou, Jianhua [Department of Occupational Medicine and Environmental Health, School of Public Health, Soochow University, Suzhou 215123 (China)

    2014-11-28

    Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCC inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.

  4. Transformation analysis of oral epithelial dysplasia to carcinoma in-situ and squamous cell carcinoma by p53 expression and gene mutations

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    Mei Syafriadi

    2009-06-01

    Full Text Available Background: It is known that oral squamous epithelial dysplasia (SED and carcinoma in-situ (CIS are precancerous lesion and it could transform to squamous cell carcinoma (SCC. We had reported p53-Protein Over-Expression and Gene Mutational of Oral CIS, such as basaloid, verrucous, and acanthothic/atrophic types, but demarcated between SED to CIS and CIS to SCC and how their transformation is still unclear. It is considered that their molecular behavior related one another. Purpose: To understand the molecular behavior of them we examined p53 exon 5-8 gene mutation and their protein expression in the sequential cases. Methods: Using 10 cases formalin–fixed paraffin sections that composed SED appearance, CIS and SCC in the same case were subjected to P53 immunohistochemistry. Then all cases were subjected to p53 gene mutations analysis. By laser capturing microdissection dysplasia part, CIS part and SCC part were cutted, and followed by direct sequencing of PCR product for exon 5-8. Result: SED p53-protein over-expression in some cells, and the expression was increased to CIS and SCC. Mutational analysis for p53 gene showed that 60% of p53 gene mutation in CIS also found in SCC, therefore SCC had additional mutation in other exon of p53 gene. While no particular mutations were found in SED part of all cases. Conclusion: Carcinoma in-situ is a squamous cell carcinoma eventhough not invasive yet, but squamous epithelial dysplasia is an early step to malignancy. It needs other genes examination to know any genes are involved in the precancerous to cancer transformation process.

  5. Effect of Cerium on Expression and Activity of MMP-9 from Human Carcinoma of Bladder Cell Line

    Institute of Scientific and Technical Information of China (English)

    李瑾; 胡国武; 欧阳砥; 牛瑞芳; 周永洽; 申泮文

    2004-01-01

    The effects of Ce4+ on cell survival,expression and activity of matrix metalloproteinase-9(MMP-9)with MTT colorimetry and gelatin zymography assays in human bladder carcinoma cell line was studied.The results indicate that the lower concentration of Ce4+(0.01 mmol*L-1)has no influence on cell growth,but inhibits extremely expression of MMP-9 and increases its activity,whereas the higher concentration of Ce4+(1.0 mmol*L-1)can inhibit all of them.The results raise the possibility that Ce4+ may have beneficial effects in attenuating invasion and metastasis of malignant tumors.

  6. Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma

    Science.gov (United States)

    Marote, Georgina; Abramo, Francesca; McKay, Jenny; Thomson, Calum; Beltran, Mariana; Millar, Michael; Priestnall, Simon; Dobson, Jane; Costantino-Casas, Fernando; Petrou, Terry; McGonnell, Imelda M.; Davies, Anthony J.; Weetman, Malcolm; Garden, Oliver A.; Masters, John R.; Thrasivoulou, Christopher; Ahmed, Aamir

    2016-01-01

    Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (ptissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease. PMID:27559731

  7. DLEC1 Expression Is Modulated by Epigenetic Modifications in Hepatocelluar Carcinoma Cells: Role of HBx Genotypes

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    Niu, Dandan; Feng, Huixing; Chen, Wei Ning, E-mail: WNChen@ntu.edu.sg [School of Chemical and Biomedical Engineering, Nanyang Technological University (Singapore)

    2010-09-16

    Deleted in Lung and Esophageal Cancer 1 (DLEC1) is a functional tumor suppressor gene (TSG). It has been found to be silenced in a variety of human cancers including hepatocellular carcinoma (HCC). The silencing of DLEC1 can be modulated by epigenetic modifications, such as DNA hypermethylation and histone hypoacetylation. In the case of HCC, hepatitis B virus X protein (HBx) has been implicated in methylation of target promoters resulting in the down-regulation of tumor suppressor genes, which in turn contributes to the development of HCC. In the present study, we first established a cell system in which epigenetic modifications can be modulated using inhibitors of either DNA methylation or histone deacetylation. The cell system was used to reveal that the expression of DLEC1 was upregulated by HBx in a genotype-dependent manner. In particular, HBx genotype A was found to decrease DNA methylation of the DLEC1 promoter. Our results have provided new insights on the impact of HBx in HCC development by epigenetic modifications.

  8. IL-6 upregulation contributes to the reduction of miR-26a expression in hepatocellular carcinoma cells

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    Zhang, Yafei [People' s Liberation Army, Department of Oncology, Wuhan General Hospital of Guangzhou Command, Wuhan (China); Third Military Medical University, Department of Gastroenterology, Southwest Hospital, Chongqing (China); Zhang, Bicheng [People' s Liberation Army, Department of Oncology, Wuhan General Hospital of Guangzhou Command, Wuhan (China); Zhang, Anran [Third Military Medical University, Department of Gastroenterology, Southwest Hospital, Chongqing (China); Li, Xiaohua [Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xi' an (China); Liu, Jian; Zhao, Jie; Zhao, Yong; Gao, Jianfei [People' s Liberation Army, Department of Oncology, Wuhan General Hospital of Guangzhou Command, Wuhan (China); Fang, Dianchun [Third Military Medical University, Department of Gastroenterology, Southwest Hospital, Chongqing (China); Rao, Zhiguo [People' s Liberation Army, Department of Oncology, Wuhan General Hospital of Guangzhou Command, Wuhan (China)

    2012-09-28

    A recent study showed that miR-26a is downregulated in hepatocellular carcinoma tissues and that this downregulation is an independent predictor of survival. Interestingly, the same study also reported that miR-26a downregulation causes a concomitant elevation of IL-6 expression. Because miR-26a expression was found to be transcriptionally downregulated by oncogene c-Myc in various cancers, and the expression of c-Myc was increased by IL-6 stimulation, we hypothesized that IL-6 contributes to reduction of miR-26a in hepatocellular carcinoma. Serum IL-6 was measured by ELISA and miR-26a was detected by qRT-PCR. The data of 30 patients with hepatocellular carcinoma who had undergone surgical tumor resection revealed that serum IL-6 could be considered to be a predictor of survival up to 5 years for hepatocellular carcinoma patients (log-rank test, P < 0.05). We observed that the serum IL-6 concentration was inversely correlated with miR-26a expression in cancerous tissues (Pearson correlation test, r = -0.651, P < 0.01). Furthermore, by in vitro experiments with HepG2 cells, we showed that IL-6 stimulation can lead to miR-26a suppression via c-Myc activation, whereas in normal hepatocyte LO2 cells incubation with IL-6 had no significant effect on miR-26a expression. Taken together, these results indicate that miR-26a reduction in hepatocellular carcinoma might be due to IL-6 upregulation.

  9. Expression of the fibroblast growth factor 4 (FGF-4) gene is regulated by serum in Tera-2 embryonal carcinoma cells.

    Science.gov (United States)

    Lucas, J; Knobloch, T; Lang, J

    1996-02-01

    Expression of the fibroblast growth factor 4 (FGF-4) gene is tightly regulated during mammalian development. Dysregulation of FGF-4 gene expression results in cell transformation and tumorigenesis. It is therefore pertinent to investigate the regulatory mechanisms which control expression of FGF-4. In an initial attempt to identify exogenous factors other than retinoic acid which might control FGF-4 expression, we have investigated the response of endogenous FGF-4 to serum in a number of embryonal carcinoma and embryonic stem cell lines. We have identified a human embryonal carcinoma cell line (Tera-2) in which the FGF-4 gene can be induced by serum. In Tera-2 cells made quiescent by serum deprivation, expression of the FGF-4 gene is repressed. Subsequent addition of serum reactivates FGF-LC expression and further addition of cycloheximide results in superinduction of mRNA suggesting that FGF-4 may be classified as an early response gene. It is suggested that this observation may be explained, at least in part, by the stage of differentiation of the Tera-2 cells.

  10. Differential expression of ETS family transcription factors in NCCIT human embryonic carcinoma cells upon retinoic acid-induced differentiation.

    Science.gov (United States)

    Park, Sung-Won; Do, Hyun-Jin; Ha, Woo Tae; Han, Mi-Hee; Song, Hyuk; Uhm, Sang-Jun; Chung, Hak-Jae; Kim, Jae-Hwan

    2014-01-01

    E26 transformation-specific (ETS) transcription factors play important roles in normal and tumorigenic processes during development, differentiation, homeostasis, proliferation, and apoptosis. To identify critical ETS factor(s) in germ cell-derived cancer cells, we examined the expression patterns of the 27 ETS transcription factors in naive and differentiated NCCIT human embryonic carcinoma cells, which exhibit both pluripotent and tumorigenic characteristics. Overall, expression of ETS factors was relatively low in NCCIT cells. Among the 27 ETS factors, polyomavirus enhancer activator 3 (PEA3) and epithelium-specific ETS transcription factor-1 (ESE-1) exhibited the most significant changes in their expression levels. Western blot analysis confirmed these patterns, revealing reduced levels of PEA3 protein and elevated levels of ESE-1 protein in differentiated cells. PEA3 increased the proportion of cells in S-phase and promoted cell growth, whereas ESE-1 reduced proliferation potential. These data suggest that PEA3 and ESE-1 may play important roles in pluripotent and tumorigenic embryonic carcinoma cells. These findings contribute to our understanding of the functions of oncogenic ETS factors in germ cell-derived stem cells during processes related to tumorigenesis and pluripotency.

  11. Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells

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    Weng Yuan-Yuan

    2008-10-01

    Full Text Available Abstract Background CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs. Tumor cells adhesion to extracellular matrix (ECM proteins is the first step to the tumor metastasis. MMPs degrade the ECM to promote tumor metastasis. The aim of this study is to investigate the effects of small interfering RNA (siRNA against CD147 (si-CD147 on hepatocellular carcinoma cells' (SMMC-7721 architecture and functions. Methods Flow cytometry and western blot assays were employed to detect the transfection efficiency of si-CD147. Confocal microscopy was used to determine the effects of si-CD147 on SMMC-7721 cells' cytoskeleton. Invasion assay, gelatin zymography and cell adhesion assay were employed to investigate the effects of si-CD147 on SMMC-7721 cells' invasion, gelatinase production and cell adhesive abilities. Western blot assay was utilized to detect the effects of si-CD147 on focal adhesion kinase (FAK, vinculiln and mitogen-activated protein kinase (MAPK expression in SMMC-7721 cells. Results Downregulation of CD147 gene induced the alteration of SMMC-7721 cell cytoskeleton including actin, microtubule and vimentin filaments, and inhibited gelatinase production and expression, cells invasion, FAK and vinculin expression. si-CD147 also blocked SMMC-7721 cells adhesion to collagen IV and phosphorylation level of SAPK/JNKs. SAPK/JNKs inhibitor SP600125 inhibited gelatinase production and expression. Conclusion CD147 is required for normal tumor cell architecture and cell invasion. Downregulation of CD147 affects HCC cell structure and function. Moreover, the alteration of cell behavior may be related to SAPK/JNK Pathway. siRNA against CD147 may be a possible new approach for HCC gene therapy.

  12. Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System

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    Therese Featherston

    2016-09-01

    Full Text Available Aim We have recently identified and characterized cancer stem cell (CSC subpopulations within moderately differentiated buccal mucosal squamous cell carcinoma (MDBMSCC. We hypothesized that these CSCs express components of the renin-angiotensin system (RAS.Methods 3,3-Diaminobenzidine (DAB immunohistochemical (IHC staining was performed on formalin-fixed paraffin-embedded MDBMSCC samples to investigate the expression of the components of the RAS: pro(renin receptor (PRR, angiotensin converting enzyme (ACE, angiotensin II receptor 1 (ATIIR1 and angiotensin II receptor 2 (ATIIR2. NanoString mRNA gene expression analysis and Western Blotting (WB were performed on snap-frozen MDBMSCC samples to confirm gene expression and translation of these transcripts, respectively. Double immunofluorescent (IF IHC staining of these components of the RAS with the embryonic stem cell markers OCT4 or SALL4 was performed to demonstrate their localization in relation to the CSC subpopulations within MDBMSCC.Results DAB IHC staining demonstrated expression of PRR, ACE, ATIIR1 and ATIIR2 in MDBMSCC. IF IHC staining showed that PRR was expressed by the CSC subpopulations within the tumor nests, the peri-tumoral stroma and the endothelium of the microvessels within the peri-tumoral stroma. ATIIR1 and ATIIR2 were localized to the CSC subpopulations within the tumor nests and the peri-tumoral stroma, while ACE was localized to the endothelium of the microvessels within the peri-tumoral stroma. WB and NanoString analyses confirmed protein expression and transcription activation of PRR, ACE and ATIIR1 but not of ATIIR2, respectively.

  13. Gene expression profile of oral squamous cell carcinomas from Sri Lankan betel quid users.

    Science.gov (United States)

    Suhr, Mai Lill; Dysvik, Bjarte; Bruland, Ove; Warnakulasuriya, Saman; Amaratunga, Asoka N; Jonassen, Inge; Vasstrand, Endre N; Ibrahim, Salah O

    2007-11-01

    Oral squamous cell carcinoma (OSCC) is one of the major health problems in Sri Lanka and the disease is associated with the habit of Betel Quid (BQ) chewing. Using 35k oligo microarrays, we analyzed the gene expression profile of 15 Sri Lankan patients diagnosed with OSCCs and pair-wised normal controls and correlated the findings with the clinicopathological data. Following the recording of the scanned array images and data analysis, results for selected candidate genes were verified using QRT-PCR. Upon analysis, a total of 263 genes [71 (27%) of unknown functions previously not reported in OSCCs and 192 (73%) of known functions] were found as differentially expressed between tumors and controls. For the genes with known functions, 66 (34%; such as COL4A1, MMP1, MMP3, PLAU, SPARC and KRT19) were previously reported in OSCC and for the remaining 126 (66%; such as CD47, APOL3, RRAGC, BPIL1 and AZGP1) this is the first report in OSCCs. Hierarchical clustering of the differentially expressed 263 genes grouped the samples into several clusters with the larger one being dominated by tumors of stage 3 and 4. Two cases (a verrucous SCC and an advanced SCC), did not cluster with any of the other samples. We found two main biological pathways (cell communication and integrin-mediated cell adhesion) and 5 gene ontology categories (transcription regulator activity, structural molecule activity, intracellular signaling, cytoskeleton and signal transduction) of relevance to the OSCCs examined. Results from the QRT-PCR verified the results from the microarray experiment. This study provides valuable information on gene expression profile of OSCCs of habitual users of BQ from Sri Lanka. Of particular interest were the list of genes of known and unknown functions and the two biological pathways that we suggest as candidate genes in oral cancers associated with BQ chewing in Southeast Asia, in particular Sri Lanka. The suggested candidate genes might be used as molecular biomarkers

  14. Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Sugiyama Takayuki

    2011-07-01

    Full Text Available Abstract Background Improving the treatment of renal cell carcinoma (RCC will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7, also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC, overexpress FABP7. The abundant expression of FABP7 in primary RCCs compared to certain RCC-derived cell lines may allow the definition of the molecular components of FABP7's regulatory system. Results We determined FABP7 mRNA levels in six RCC cell lines. Two were highly expressed, whereas the other and the embryonic kidney cell line (HEK293 were weakly expressed FABP7 transcripts. Western blot analysis of the cell lines detected strong FABP7 expression only in one RCC cell line. Promoter activity in the RCC cell lines was 3- to 21-fold higher than that of HEK293. Deletion analysis demonstrated that three FABP7 promoter regions contributed to upregulated expression in RCC cell lines, but not in the HEK293 cell. Competition analysis of gel shifts indicated that OCT1, OCT6, and nuclear factor I (NFI bound to the FABP7 promoter region. Supershift experiments indicated that BRN2 (POU3F2 and NFI bound to the FABP7 promoter region as well. There was an inverse correlation between FABP7 promoter activity and BRN2 mRNA expression. The FABP7-positive cell line's NFI-DNA complex migrated faster than in other cell lines. Levels of NFIA mRNA were higher in the HEK293 cell line than in any of the six RCC cell lines. In contrast, NFIC mRNA expression was lower in the HEK293 cell line than in the six RCC cell lines. Conclusions Three putative FABP7 promoter regions drive reporter gene expression in RCC cell lines, but not in the HEK293 cell line. BRN2 and NFI may be key

  15. p21WAF1/Cip1 expression is associated with cell differentiation but not with p53 mutations in squamous cell carcinomas of the larynx.

    Science.gov (United States)

    Nadal, A; Jares, P; Cazorla, M; Fernández, P L; Sanjuan, X; Hernandez, L; Pinyol, M; Aldea, M; Mallofré, C; Muntané, J; Traserra, J; Campo, E; Cardesa, A

    1997-10-01

    p21WAF1/Cip1 is a recently identified gene involved in cell cycle regulation through cyclin-CDK-complex inhibition. The expression of this gene in several cell lines seems to be induced by wild-type, but not mutant, p53. p21WAF1/Cip1 expression has been studied at both mRNA and protein levels in a series of 49 normal mucosae and squamous cell carcinomas of the larynx. A significant association was found between mRNA and protein expression in tumours (P global S-phase of the carcinomas. p53 mutations (exons 5-9) were found in ten carcinomas with p21WAF1/Cip1 expression, but no p53 mutations were detected in three p21WAF1/Cip1-negative tumours. In conclusion, p21WAF1/Cip1 expression is frequently upregulated in squamous cell carcinomas of the larynx and is associated with tumour cell differentiation. p21WAF1/Cip1 expression in these tumours is independent of p53 gene mutations.

  16. Head and Neck Squamous Cell Carcinomas Do Not Express EGFRvIII

    NARCIS (Netherlands)

    Melchers, Lieuwe J; Clausen, Martijn J A M; Mastik, Mirjam F; Slagter-Menkema, Lorian; Langendijk, Johannes A; van der Laan, Bernard F A M; van der Wal, Jacqueline E; van der Vegt, Bert; Roodenburg, Jan L N; Schuuring, Ed

    2014-01-01

    Purpose: To assess the prevalence of EGFRvIII, a specific variant of EGFR (epidermal growth factor receptor), in 3 well-defined cohorts of head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Immunohistochemistry for the specific detection of EGFRvIII using the L8A4 antibody was opt

  17. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR

    Directory of Open Access Journals (Sweden)

    Kristiansen Glen

    2007-06-01

    Full Text Available Abstract Background Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in various studies were examined with regard to their usefulness as reference genes. Results The expression of the potential reference genes was examined in matched malignant and non-malignant tissue specimens from 25 patients with clear cell renal cell carcinoma. Quality assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a mean RNA integrity number of 8.7 for all samples. The between-run variations related to the crossing points of PCR reactions of a control material ranged from 0.17% to 0.38%. The expression of all genes did not depend on age, sex, and tumour stage. Except the genes TATA box binding protein (TBP and peptidylprolyl isomerase A (PPIA, all genes showed significant differences in expression between malignant and non-malignant pairs. The expression stability of the candidate reference genes was additionally controlled using the software programs geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by normalizing the target gene ADAM9 using these two most stably expressed genes in comparison with up- and down-regulated housekeeping genes of the panel. Conclusion Our study demonstrated the suitability of the two housekeeping genes PPIA and TBP as endogenous reference genes when comparing malignant tissue samples with adjacent normal tissue samples from clear cell renal cell carcinoma. Both genes are recommended as reference genes for relative gene quantification in gene profiling studies either as single gene or preferably in combination.

  18. Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder.

    Science.gov (United States)

    Junqueira-Neto, Susana; Vieira, Filipa Q; Montezuma, Diana; Costa, Natália R; Antunes, Luís; Baptista, Tiago; Oliveira, Ana Isabel; Graça, Inês; Rodrigues, Ângelo; Magalhães, José S; Oliveira, Jorge; Henrique, Rui; Jerónimo, Carmen

    2015-07-01

    Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets.

  19. Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Rancés Blanco

    2013-01-01

    Full Text Available At present, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs for a better understanding of tumor biology and genetics of lung tumors. For this reason, we evaluated the tissue expression of carcinoembryonic antigen (CEA and ior C2 (a cell surface O-linked glycoprotein carbohydrate chain TAA in lung carcinomas, as well as its correlation with a variety of clinicopathological features. The tissue expression of CEA was evidenced in 22/43 (51.16% lung carcinomas and it was correlated with mitotic activity, cell pleomorphism indexes, and age of patients. The expression of ior C2 was observed in 15/43 (34.88% tumors but no correlation with the clinicopathological features mentioned above was obtained. No correlation between both CEA and ior C2 antigens expression and the overall survival (OS of non-small-cell lung cancer patients was also observed. However, CEA-negative patients displayed higher OS rates as compared with positive ones (69.74 versus 58.26 months. Our results seem to be in agreement with the role of CEA expression in tumor cell proliferation, inhibition of cell polarizations and tissue architecture distortion. The significance of ior C2 antigen in these malignancies and it potential use in diagnosis, prognosis, and/or immunotherapy must be reevaluated.

  20. Expression of laminin-5 and integrins in actinic cheilitis and superficially invasive squamous cell carcinomas of the lip.

    Science.gov (United States)

    Peixoto da-Silva, Janaína; Lourenço, Silvia; Nico, Marcello; Silva, Filomena H; Martins, Marília Trierveiler; Costa-Neves, Adriana

    2012-10-15

    The progression of carcinogenesis entails the detachment of cells, invasion and migration of neoplastic cells. Alterations in epithelial adhesion and basement membrane proteins might mediate the early stages of carcinogenesis. This study investigated the expression of adhesion molecules and the basement membrane protein laminin-5 in actinic cheilitis (AC) and incipient squamous cell carcinoma of the lower lip to understand early photocarcinogenesis. Ln-5γ2 chain as well as α3, β1 subunits of α3β1 heterodimer and β4 subunit of integrin α6β4 were evaluated by immunohistochemistry in 16 cases of AC and 16 cases of superficially invasive squamous cell carcinoma (SISCC). Most AC cases showed reduced expression of β1, β4 and α3 integrins, and SISCCs lacked β1, β4 and α3 integrins in the invasive front. AC cases were negative for the Ln-5γ2 chain. Five cases of SISCC (31%) showed heterogeneous Ln-5γ2 chain expression in the invasive front of the tumor. Integrin β1, β4 and α3 expression is lost during the early stages of lip carcinogenesis. Expression of Ln-5γ2 in the invasive front in cases and its correlation with tumor progression suggest that it mediates the acquisition of the migrating and invading epithelial cell phenotype.

  1. Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Kawakami, Hisato; Okamoto, Isamu; Terao, Kyoichi; Sakai, Kazuko; Suzuki, Minoru; Ueda, Shinya; Tanaka, Kaoru; Kuwata, Kiyoko; Morita, Yume; Ono, Koji; Nishio, Kazuto; Nishimura, Yasumasa; Doi, Katsumi; Nakagawa, Kazuhiko

    2013-12-01

    Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074-0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese.

  2. Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

    Science.gov (United States)

    Zeng, Rong; Huang, Jun-Peng; Li, Xu Feng; Xiong, Wei-Bin; Wu, Gang; Jiang, Zhao-Jing; Song, Shu-Jie; Li, Ji-Qiang; Zheng, Yan-Fang; Zhang, Ji-Ren

    2016-04-01

    EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.

  3. Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Romilda Cardin

    2012-05-01

    Full Text Available Abstract Background MicroRNAs expression has been extensively studied in hepatocellular carcinoma but little is known regarding the relationship, if any, with inflammation, production of reactive oxygen species (ROS, host’s repair mechanisms and cell immortalization. This study aimed at assessing the extent of oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG in different phases of the carcinogenetic process, in relation to DNA repair gene polymorphism, telomeric dysfunction and to the expression of several microRNAs, non-coding genes involved in post-transcriptional regulation, cell proliferation, differentiation and death. Methods Tissue samples obtained either at surgery, [neoplastic (HCC and adjacent non-cancerous cirrhotic tissues (NCCT] at percutaneous or laparoscopic biopsy (patients with HCV or HBV-related hepatitis or patients undergoing cholecystectomy were analysed for 8-OHdG (HPLC-ED, OGG1 (a DNA repair gene polymorphism (PCR-RFLP, telomerase activity, telomere length (T/S, by RT-PCR, Taqman microRNA assay and Bad/Bax mRNA (RT-PCR. Fifty-eight samples from 29 HCC patients (obtained in both neoplastic and peritumoral tissues, 22 from chronic hepatitis (CH and 10 controls (cholecystectomy patients - CON were examined. Results Eight-OHdG levels were significantly higher in HCC and NCCT than in CH and CON (p=0.001. Telomerase activity was significantly higher in HCC than in the remaining subgroups (p=0.002; conversely T/S was significantly lower in HCC (p=0.05. MiR-199a-b, -195, -122, -92a and −145 were down-regulated in the majority of HCCs while miR-222 was up-regulated. A positive correlation was observed among 8-OHdG levels, disease stage, telomerase activity, OGG1 polymorphisms and ALT/GGT levels. In HCC, miR-92 expression correlated positively with telomerase activity, 8-OHdG levels and Bad/Bax mRNA. Conclusions The above findings confirm the accumulation, in the progression of chronic liver damage to HCC, of a ROS

  4. Expression and Clinical Significance of CD147 and MMP-2 
in Squamous Cell Carcinoma and Adenocarcinoma of the Lungs

    Directory of Open Access Journals (Sweden)

    Siwen WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that CD147 was an extracellular matrix metalloproteinase inducer reportedly involved in the invasion and metastasis of malignancies. The aim of this study is to investigate CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs and to analyze their clinical significance. Methods Tissue samples from 55 patients with squamous cell carcinoma and adenocarcinoma of the lungs and their corresponding non-cancerous tissues were examined for CD147 and MMP-2 expression using immunohistochemistry. Results The positive expression rates of CD147 and MMP-2 in the squamous cell carcinoma and adenocarcinoma among the lung tissues were significantly higher than those in the corresponding normal lung tissues. Moreover, the CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs were related to lymph node metastasis and TNM stages (P<0.05, but not to age, gender and histologic type (P>0.05. MMP-2 expression was highly correlated with CD147 expression. Conclusion CD147 and MMP-2 expression is correlated with the invasion and metastasis of squamous cell carcinoma and adenocarcinoma of the lungs and may be used as objective markers for predicting the behavior of squamous cell carcinoma and adenocarcinoma of the lungs.

  5. Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates with human oesophageal squamous cell carcinoma.

    Science.gov (United States)

    van der Watt, Pauline J; Zemanay, Widaad; Govender, Dhirendra; Hendricks, Denver T; Parker, M I; Leaner, Virna D

    2014-08-01

    The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models. Immunohistochemistry revealed that Crm1 expression was significantly elevated in oesophageal tumour tissues compared to normal tissues and its localisation shifted from predominantly nuclear to nuclear and cytoplasmic. Real‑time RT‑PCR revealed that Crm1 expression was elevated at the mRNA level. To determine the functional significance of elevated Crm1 expression in oesophageal cancer, its expression was inhibited using siRNA, and a significant decrease in cell proliferation was observed associated with G1 cell cycle arrest and the induction of apoptosis. Similarly, leptomycin B (LMB) treatment resulted in the effective killing of oesophageal cancer cells at nanomolar concentrations. Normal oesophageal epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA and LMB. Together, this study reveals that Crm1 expression is increased in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells.

  6. CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sweeny, Larissa, E-mail: larissasweeny@gmail.com [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States); Liu, Zhiyong; Bush, Benjamin D.; Hartman, Yolanda [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States); Zhou, Tong [Department of Medicine, Division of Immunology and Rheumatology, 1825 University Boulevard, Shelby Biomedical Research Building 302, Birmingham, Alabama (United States); Rosenthal, Eben L., E-mail: oto@uab.edu [Department of Surgery, University of Alabama, Division of Otolaryngology-Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, Alabama (United States)

    2012-08-15

    The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis. -- Highlights: Black-Right-Pointing-Pointer We investigated AGR2 in head and neck squamous cell carcinoma for the first time. Black-Right-Pointing-Pointer We explored the relationship between AGR2 and CD147 for the first time. Black-Right-Pointing-Pointer AGR2 and CD147 appear to co-localize in head and squamous cell carcinoma samples. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 reduced migration and invasion in vitro. Black-Right-Pointing-Pointer Knockdown of both AGR2 and CD147 decreased metastasis in vivo.

  7. Similar Squamous Cell Carcinoma Epithelium microRNA Expression in Never Smokers and Ever Smokers.

    Science.gov (United States)

    Kolokythas, Antonia; Zhou, Yalu; Schwartz, Joel L; Adami, Guy R

    2015-01-01

    The incidence of oral tumors in patients who never used mutagenic agents such as tobacco is increasing. In an effort to better understand these tumors we studied microRNA (miRNA) expression in tumor epithelium of never tobacco users, tumor epithelium of ever tobacco users, and nonpathological control oral epithelium. A comparison of levels among 372 miRNAs in 12 never tobacco users with oral squamous cell carcinoma (OSCC) versus 10 healthy controls was made using the reverse transcription quantitative polymerase chain reaction. A similar analysis was done with 8 ever tobacco users with OSCC. These comparisons revealed miR-10b-5p, miR-196a-5p, and miR-31-5p as enriched in the tumor epithelium in OSCC of both never and ever tobacco users. Examination of The Cancer Genome Atlas (TCGA) project miRNA data on 305 OSCCs and 30 controls revealed 100% of those miRNAs enriched in never smoker OSCCs in this patient group were also enriched in ever smoker OSCCs. Nonsupervised clustering of TCGA OSCCs was suggestive of two or four subgroups of tumors based on miRNA levels with limited evidence for differences in tobacco exposure among the groups. Results from both patient groups together stress the importance of miR196a-5p in OSCC malignancy in both never and ever smokers, and emphasize the overall similarity of miRNA expression in OSCCs in these two risk groups. It implies that there may be great similarity in etiology of OSCC in never and ever smokers and that classifying OSCC based on tobacco exposure may not be helpful in the clinic.

  8. Expression of Wnt11 and Rock2 protein with clinical characteristics of esophageal squamous cell carcinoma in Kazakh and Han patients

    OpenAIRE

    LIU Dong; Zhou, Keming; Li, Qiaoxin; Deng, Feiyan; Ma, Yuqing

    2015-01-01

    Background: Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a very poor outcome in China. Wnt11 and Rock2, new identified proteins highly associated with metastasis of many cancers, which were never reported in esophageal squamous cell carcinoma (ESCC). Here we measured the expression levels of Wnt11 and Rock2 in tissues from 265 patients with ESCC. Immunohistochemical staining was employed to detect the correlation of Wnt11 and Rock2 expression with clinicopath...

  9. EFFECT OF MATRINE ON EXPRESSION OF HCCR1 AND HCCR2 PROTEINS IN CULTURAL HUMAN HEPATOCELLULAR CARCINOMAS CELLS

    Institute of Scientific and Technical Information of China (English)

    GENG Dong-jin; CHEN Jun-hao; CHEN Lei-lei; GU Xiang-fang; ZHANG Le; HAN Li; LIU Yong

    2005-01-01

    Objective: To explore the effects of matrine on HCCR1 and HCCR2 expression in cultural human hepatocellular carcinomas (HCC) cells at the level of gene and protein. Methods: Three methods, representational difference analysis(RDA) of cDNA, microarrays and fluorescence in situ hybridization (FISH) were used to detect levels of mRNA and protein expression of HCCR1 and HCCR-2 before and after treatment of matrine. Results: Matrine had inhibitory effect on the mRNA and protein expression of HCCR1 and HCCR2 in cultural HCC cells. Conclusion: Matrine has inhibitory effect on gene transcription, protein expression of HCCR1 and HCCR2 in cultural HCC cells.

  10. Effects of Cyclin D1 Antisense Oligodeoxyneucleotides on the Growth and Expression of G1 Phase Regulators in Gastric Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    帅晓明; 韩高雄; 王国斌

    2003-01-01

    To investigate the effects of Cyclin D1 antisense oligodeoxyneucleotides (ASODN) on the growth, cell cycle progression and expression of G1 phase regulators in human gastric carcinoma cell lines SGC7901 and HS746T, phosphorothioate-modified Cyclin D1 ASODN were encapsulated by LipofectAMINE2000 and transfected into gastric carcinoma cells. Dose-dependent inhibitory effects were induced by Cyclin D1 ASODN in two gastric carcinoma cell lines. Treatment of gastric carcinoma cells with 0.2 μmol/L Cyclin D1 ASODN for 24 h could significantly inhibit their growth in vitro and in vivo, reduce expression of Cyclin DlmRNA to 26.3 % (SGC7901) and 17.3 %(HS746T) respectively. The percentage of cells in G0/G1 phase was increased as revealed by flow cytometry. Immunohistochemical staining showed that the expression of p21 was increased and the expression of Cyclin D1 and pRb was decreased in the two cell lines; the expression of p27 was increased in HS746T, but unchanged in SGC7901. Cyclin D1 ASODN could inhibit the growth and the expression of Cyclin D1 mRNA in gastric carcinoma cells, influence the cell cycle and expression of its regulators.

  11. Second Intron of Mouse Nestin Gene Directs its Expression in Pluripotent Embryonic Carcinoma Cells through POU Factor Binding Site

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang JIN; Li LIU; Hua ZHONG; Ke-Jing ZHANG; Yong-Feng CHEN; Wei BIAN; Le-Ping CHENG; Nai-He JING

    2006-01-01

    Nestin, an intermediate filament protein, is expressed in the neural stem cells of the developing central nervous system. This tissue-specific expression is driven by the neural stem cell-specific enhancer in the second intron of the nestin gene. In this study, we showed that the mouse nestin gene was expressed in pluripotent embryonic carcinoma (EC) P19 and F9 cells, not in the differentiated cell types. This cell typespecific expression was conferred by the enhancer in the second intron. Mutation of the conserved POU factor-binding site in the enhancer abolished the reporter gene expression in EC cells. Oct4, a Class V POU factor, was found to be coexpressed with nestin in EC cells. Electrophoretic mobility-shift assays and supershift assays showed that a unique protein-DNA complex was formed specifically with nuclear extracts of EC cells, and Oct4 protein was included. Together, these results suggest the functional relevance between the conserved POU factor-binding site and the expression of the nestin gene in pluripotent EC cells.

  12. Expression of MTLC gene in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Guang-Bin Qiu; Li-Guo Gong; Dong-Mei Hao; Zhi-Hong Zhen; Kai-Lai Sun

    2003-01-01

    AIM: To investigate the expression of c-myc target from laryngeal cancer cells (MTLC) gene in gastric carcinoma (GC)tissues and the effect of MTLC over-expression on gastric carcinoma cell line BGC823.METHODS: RT-PCR was performed to determine the expression of MTLC mRNA in GC and matched control tissues.BGC823 cells were transfected with an expression vector pcDNA3.1-MTLC by liposome and screened by G418. Growth of cells expressing MTLC was observed daily by manual counting. Apoptotic cells were determined by TdT-mediated dUTP nick-end labeling (TUNEL) assay.RESULTS: The expression of MTLC mRNAs was downregulated in 9(60%) of 15 cases of GC tissues. The growth rates of the BGC823 cells expressing MTLC were indistinguishable from that of control cells. A marked acceleration of apoptosis was observed in MTLC-expressing cells.CONCLUSION: MTLC was down-regulated in the majority of GC tissues and could promote apoptosis of GC cell lines,which suggests that MTLC may play an important role in the carcinogenesis of gastric carcinoma.

  13. pRB expression in esophageal mucosa of individuals at high risk for squamous cell carcinoma of the esophagus

    Institute of Scientific and Technical Information of China (English)

    Simone S Contu; Paulo C Contu; Daniel C Damin; Renato B Fagundes; Fabiano Bevilacqua; Aline S Rosa; Jo(a)o C Prolla; Luis F Moreira

    2007-01-01

    AIM: To investigate the pRb expression in a large group of patients with history of chronic exposure to the main risk factors for development of squamous cell carcinoma of the esophagus.METHODS: One hundred and seventy asympto matic individuals at high risk for esophageal squamous cell carcinoma (consumption of more than 80 g of ethanol and 10 cigarettes/d for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa. As a control group, specimens of esophageal mucosa obtained from 20 healthy subjects were also studied. Immunohistochemical assessment of the tissues was performed using a monoclonal antibody anti-pRB protein.RESULTS: Absence of the pRB staining, indicating loss of RB function, was observed in 33 (19.4%) of the individuals at risk for esophageal cancer, but in none of the healthy controls (P < 0.02). Loss of pRb expression increased in a stepwise fashion according to the severity of the histological findings (P < 0.005): normal mucosa (11/97 or 11.3%), chronic esophagitis (17/60 or 28.3%), low-grade dysplasia (3/10 or 30%), high-grade dysplasia 1/2 or 50%) and squamous cell carcinoma (1/1 or 100%).CONCLUSION: Our findings suggest that abnormal expression of the pRB protein may be implicated in the process of esophageal carcinogenesis. Additional studies are warranted to define the role of the pRBprotein as a biomarker for development of esophageal squamous cell carcinoma in individuals at high risk for this malignancy.

  14. Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-hua; WEI Wei; XU Hao; WANG Yan-yan; WU Wen-xi

    2007-01-01

    Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells.Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA.The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells.Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

  15. Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Pedicini Piernicola

    2012-08-01

    Full Text Available Abstract Purpose To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr and the reduction of the effective doubling time (TD during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC. Methods A survey of the published papers comparing 3-years of local regional control rate (LCR for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr, respectively. By obtaining the TD from the above analysis and the sub-sites’ potential doubling time (Tpot from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif, was estimated. Results The averages of TD were 77 (27-9095% days in LEGFr and 8.8 (7.3-11.095% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites’ TD were 5.9 (6.6, 5.9 (6.6, 4.6 (6.1, 14.3 (12.9 days, with respect to literature immunohistochemical (flow cytometry data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29, 0.33 (0.29, 0.42 (0.31, 0.14 (0.15 Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed. Conclusions A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck

  16. Immunohistochemical profile of the penile urethra and differential expression of GATA3 in urothelial versus squamous cell carcinomas of the penile urethra.

    Science.gov (United States)

    Chaux, Alcides; Han, Jeong S; Lee, Stephen; Gonzalez-Roibon, Nilda; Sharma, Rajni; Burnett, Arthur L; Cubilla, Antonio L; Netto, George J

    2013-12-01

    The penile urethra has a distinctive morphology not yet fully characterized by immunohistochemistry. In addition, both urothelial and squamous cell carcinomas have been reported in the penile urethra, and the distinction between these 2 tumors might be difficult. The purposes of this study are to assess the histology and immunohistochemical profile (CK20, CK7, p63, and GATA3) of the penile urethra and to assess the usefulness of Trans-acting T-cell-specific transcription factor (GATA3) and human papillomavirus detection in distinguishing urothelial versus squamous cell carcinomas. Normal penile urethra was evaluated in 11 total penectomies. The penile urethra was lined by 2 cell layers: a superficial single layer of CK7+, CK20-, and p63- columnar cells and a deep stratified layer of CK7-, CK20-, and p63+ cubical cells. Both layers were GATA3+, supporting urothelial differentiation. In addition, 2 tissue microarrays and 6 surgical specimens of primary tumors of the penile urethra (3 urothelial and 3 squamous cell carcinomas) were evaluated for GATA3 expression. In the tissue microarrays, 22 of 25 upper tract urothelial carcinomas and 0 of 38 penile squamous cell carcinomas were GATA3+. In the surgical specimens, GATA3 was positive in all urothelial carcinomas and negative in all squamous cell carcinomas. Human papillomavirus was detected in 2 of 3 squamous cell carcinomas and in 0 of 3 of the urothelial carcinomas. In conclusion, the penile urethra is covered by epithelial cells that are unique in morphology and immunohistochemical profile. In addition, our study suggests that GATA3 and human papillomavirus detection are useful markers for distinguishing urothelial carcinomas from squamous cell carcinomas of the penile urethra.

  17. Expression of E-selectin, integrin β1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance

    Institute of Scientific and Technical Information of China (English)

    Jin-Jing Ke; Qin-Shu Shao; Zhi-Qiang Ling

    2006-01-01

    AIM: To study the expression levels of E- selectin, integrin β1 and immunoglobulin supperfamily memberintercellular adhesion molecule-1 (ICAM-1) in human gastric carcinoma cells, and to explore the relationship between these three kinds of cell adhesion molecules and gastric carcinoma.METHODS: The serum contents of E-selectin, integrin β1 and ICAM-1 were detected by enzyme-linked immunosorbent assay (ELISA), in 47 healthy individuals (control group) and in 57 patients with gastric carcinoma (gastric carcinoma group) respectively prior to operation and 7 d after operation.RESULTS: The serum E-selectin, ECAM-1 and integrin β1were found to be expressed in both control and gastric carcinoma groups. However, they were highly expressed in patients with gastric carcinoma patients before operation or with unresectable tumours. The expression levels of ICAM-1 and integrin β1 were significantly higher in gastric carcinoma patients than in controls (P <0.01). A comparison of the E-selectin levels between the two groups showed statistically insignificant differnce (P = 0.64) In addition, the expression levels were all decreased substantially in the postoperative patients subjected to radical resection of the tumours, indicating that the high level expressions of these compounds might be the important factor for predicting the prognosis of these patients.CONCLUSION: Serum E-selectin, ICAM-1 and integrin β1 expression levels are probably related to the metastasis and relapse of gastric cancer.

  18. Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma

    OpenAIRE

    Kawakami, Hisato; Okamoto, Isamu; Terao, Kyoichi; Sakai, Kazuko; SUZUKI, MINORU; Ueda, Shinya; Tanaka, Kaoru; Kuwata, Kiyoko; Morita, Yume; Ono, Koji; Nishio, Kazuto; Nishimura, Yasumasa; Doi, Katsumi; Nakagawa, Kazuhiko

    2013-01-01

    Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methyla...

  19. Prognostic relevance of β-catenin expression in T2-3N0M0 esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Dong-Rong; Situ; Tie-Hua; Rong

    2010-01-01

    AIM: To study the expression of β-catenin in esophageal squamous cell carcinoma (ESCC) at stage T2-3N0M0 and its relation with the prognosis of ESCC patients. METHODS: Expression of β-catenin in 227 ESCC speci-mens was detected by immunohistochemistry (IHC). A reproducible semi-quantitative method which takes both staining percentage and intensity into account was applied in IHC scoring, and receiver operating char-acteristic curve analysis was used to select the cut-off score for high or low IHC reactivity...

  20. Expression of p27Kip1 and E-cadherin in Head and Neck Squamous Cell Carcinoma of Indonesian Patients.

    Science.gov (United States)

    E I, Auerkari; V, Joewono; D R, Handjari; A T, Sarwono; A W, Suhartono; K, Eto; M A, Ikeda

    2014-01-01

    Cancer cells exhibit characteristic damage of DNA and its expression. The expression of the tumor suppressors E-cadherin and p27(Kip1) has been tested on 57 head and neck squamous cell carcinomas (HNSCC) of Indonesian subjects. HNSCC tumor samples including both primary and (unrelated) nodal cases were obtained from the archives of Indonesian hospitals, in accordance with acknowledged ethical requirements. Only modest correlation was found between reduced expression of E-cadherin or p27(Kip1) with increased malignancy of primary and nodal growth. The observed strong correlation regardless of malignancy between the expressed levels of E-cadherin and p27(Kip1) suggests that also in combination these would not help to better predict the outcome of HNSCC.

  1. TGF-β1 promotes the migration and invasion of bladder carcinoma cells by increasing fascin1 expression.

    Science.gov (United States)

    Zhang, Naiwen; Bi, Xiaojun; Zeng, Yu; Zhu, Yuyan; Zhang, Zhe; Liu, Yang; Wang, Jianfeng; Li, Xuejie; Bi, Jianbin; Kong, Chuize

    2016-08-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that is reported to regulate cellular motility and invasive capability during tumor progression. Fascin1, an actin-bundling protein, increases cell motility, migration and adhesion. To investigate the function of TGF-β1 and test whether fascin1 is an important mediator of the tumor response to TGF-β1 in bladder carcinoma cells, real-time RT-PCR and western blot analysis were used to test changes in fascin1 expression after TGF-β1 (10 ng/ml) treatment in T24 and BIU87 cells. Small interfering RNA (siRNA) technique was performed to silence fascin1. Cell viability and biological behavior changes were evaluated by cell growth (MTT), wound-healing and Matrigel invasion assays. In the present study, we found that the mRNA and protein levels of fascin1 in the T24 and BIU87 cells were significantly increased after 10 ng/ml TGF-β1 treatment (pTGF-β1. The findings suggested that TGF-β1 can promote invasion and migration of T24 and BIU87 bladder carcinoma cells, and the increase in fascin1 expression may be the key point of this impact of TGF-β1.

  2. Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated PD-L1 Expression

    Science.gov (United States)

    Xu, Chunxiao; Fillmore, Christine M.; Koyama, Shohei; Wu, Hongbo; Zhao, Yanqiu; Chen, Zhao; Herter-Sprie, Grit S.; Akbay, Esra A.; Tchaicha, Jeremy H.; Altabef, Abigail; Reibel, Jacob B.; Walton, Zandra; Ji, Hongbin; Watanabe, Hideo; Jänne, Pasi A.; Castrillon, Diego H.; Rustgi, Anil K.; Bass, Adam J.; Freeman, Gordon J.; Padera, Robert F.; Dranoff, Glenn; Hammerman, Peter S.; Kim, Carla F.; Wong, Kwok-Kin

    2014-01-01

    SUMMARY Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that biallelic inactivation of Lkb1 and Pten in the mouse lung leads to SCC that recapitulates the histology, gene expression, and microenvironment found in human disease. Lkb1;Pten null (LP) tumors expressed the squamous markers KRT5, p63 and SOX2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. SCA1+NGFR+ fractions were enriched for tumor-propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and NGFR+ cells in human SCCs highly expressed Pd-ligand-1 (PD-L1), suggesting a mechanism of immune escape for TPCs. PMID:24794706

  3. Effects of Meloxicam on Vascular Endothelial Growth Factor and Angiopoietin-2 Expression in Colon Carcinoma Cell Line HT-29

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ning; TAO Kaixiong; HUANG Tao

    2007-01-01

    To investigate the effect of meloxicam, a selected NSAIDs, on cell growth, expression of VEGF and angiopointin-2 (Ang-2) protein in HT-29 cell line, cultured HT-29 cells were treated with meloxicam of various concentrations for various lengths of time. The proliferation of HT-29 was detected by cell counting kit-8 (CCK-8), the cell cycle was determined by flow cytometer and the levels of VEGF and Ang-2 protein in supernatants were examined by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of VEGF and Ang-2 in cultured HT-29 were determined by real-time quantitative reverse-transcription polymerase chain reaction. Our results showed that treatment of meloxicam of different concentrations and for various lengths of time had a cytotoxicic effect on the cell proliferation of HT-29 cells in a concentration-dependant and time-dependant manner. Cell cycle analysis showed that the cells were mainly blocked in G0/G1 phase. The VEGF and Ang-2 protein levels in supematants of the culture medium were decreased gradually in a concentration-dependent or time-dependent fashion. The mRNA expression of cox-2, VEGF and Ang-2 showed a gradual and concentration-dependent reduction. It is concluded that meloxicam can reduce the expression of VEGF and Ang-2 at the protein and mRNA level in colon carcinoma cell line.

  4. miR-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Cañueto, J; Cardeñoso-Álvarez, E; García-Hernández, J L; Galindo-Villardón, P; Vicente-Galindo, P; Vicente-Villardón, J L; Alonso-López, D; De Las Rivas, J; Valero, J; Moyano-Sáez, E; Fernández-López, E; Mao, J H; Castellanos-Martín, A; Román-Curto, C; Pérez-Losada, J

    2016-12-11

    Cutaneous squamous cell carcinoma is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as poor-prognosis diseases, and therefore it is important to identify new markers to better predict its clinical evolution. Here, we identified the expression pattern of miRNAs at different stages of skin cancer progression in a panel of murine skin cancer cell lines. We determined that miR-203 and miR-205 are differentially expressed in this panel, and evaluated their potential use as biomarkers of prognosis in human tumours. MiR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. MiR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. MiR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. This work highlights the utility of miRNA-205 and miRNA-203 as prognostic markers in cutaneous squamous cell carcinoma. This article is protected by copyright. All rights reserved.

  5. Construction of a plasmid coding for green fluorescent protein tagged cathepsin L and data on expression in colorectal carcinoma cells

    Directory of Open Access Journals (Sweden)

    Tripti Tamhane

    2015-12-01

    Full Text Available The endo-lysosomal cysteine cathepsin L has recently been shown to have moonlighting activities in that its unexpected nuclear localization in colorectal carcinoma cells is involved in cell cycle progression (Tamhane et al., 2015 [1]. Here, we show data on the construction and sequence of a plasmid coding for human cathepsin L tagged with an enhanced green fluorescent protein (phCL-EGFP in which the fluorescent protein is covalently attached to the C-terminus of the protease. The plasmid was used for transfection of HCT116 colorectal carcinoma cells, while data from non-transfected and pEGFP-N1-transfected cells is also shown. Immunoblotting data of lysates from non-transfected controls and HCT116 cells transfected with pEGFP-N1 and phCL-EGFP, showed stable expression of cathepsin L-enhanced green fluorescent protein chimeras, while endogenous cathepsin L protein amounts exceed those of hCL-EGFP chimeras. An effect of phCL-EGFP expression on proliferation and metabolic states of HCT116 cells at 24 h post-transfection was observed.

  6. Expressão do colágeno I em carcinomas epidermóides da cavidade oral Collagen type I expression in squamous cell carcinoma of the oral cavity

    Directory of Open Access Journals (Sweden)

    Gabriela Botelho Martins

    2003-03-01

    Full Text Available A matriz extracelular no carcinoma epidermóide da cavidade oral sofre modificações qualitativas e quantitativas durante a sua progressão. Estas alterações parecem possibilitar os processos de invasão e metástase que caracterizam as neoplasias malignas e são mais evidentes na interface tumor-hospedeiro. No nosso estudo, 23 biópsias incisionais de carcinomas epidermóides de diversas localizações da cavidade oral foram classificadas segundo o sistema de graduação histológica preconizado por Anneroth et al.¹ (1987. Foram utilizadas as colorações pela H. E. e a do tipo picrosirius, específica para colágeno. A expressão imuno-histoquímica do colágeno tipo I foi analisada em lesões com diferentes escores histológicos de malignidade. Pôde-se concluir que o colágeno apresenta diferentes padrões morfológicos, histoquímicos e imuno-histoquímicos em lesões com altos e baixos escores de malignidade.An analysis of the extracellular matrix at the invasive front of squamous cell carcinoma of the oral cavity may improve the understanding of tumour cell matrix interactions during malignancy growth. Alterations in collagen I expression may influence cellular invasion and metastasis. In this work, 23 cases of squamous cell carcinoma were submitted to the Anneroth's malignancy grading system¹. H. E. and sirius red staining were used. Immunohistochemical expression of collagen type I protein was observed in different malignancy scores. As a result, it was observed that the extracellular matrix in squamous cell carcinoma of the oral cavity shows different patterns of collagen I expression in low and high scores of malignancy.

  7. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  8. Inducible nitric oxide synthase expression is related to angiogenesis, bcl-2 and cell proliferation in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    彭佳萍; 郑树; 孝作祥; 张苏展

    2003-01-01

    In this study, we examined the expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) by immunohistochemical staining in 76 tissue sections collected from hepatocellular carcinoma (HCC) patients undergoing hepatectomy. Microvascular density (MVD) was determined by counting endothelial cells immunostained using anti-CD34 antibody. We performed DNA-flow cytometric analyses to elucidate the impact of iNOS and VEGF expression on the cell cycle of HCC. Most of the HCC cells that invaded stroma were markedly immunostained by iNOS antibody. The iNOS stain intensity of the liver tissue close to the tumor edge was stronger than that of HCC tissue, and the strongest was the hepatocytes closer to the tumor tissue. However, iNOS expression in 10 normal hepatic samples was undetectable. VEGF positive expression ratio was 84.8% in iNOS positive expression cases, and the ratio was 35.3% in negative cases. There was significant correlation (P=0.000) between iNOS and VEGF expression. Moreover, iNOS expression was significantly associated with bcl-2 and MVD, but without p53 expression. DNA-flow cytometric analyses showed that combined expression of iNOS and VEGF had significant impact on the cell cycle in HCC. PI (Proliferating Index) and SPF (S-phase fraction) in the combined positive expression of iNOS and VEGF group was significantly higher than that in the combined negative group. The present findings suggested that iNOS expression was significantly associated with angiogenesis, bcl-2 and cell proliferation of HCC.

  9. High Expression of LAMP3 Is a Novel Biomarker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Xiaoyu Liao

    2015-07-01

    Full Text Available Lysosomal-associated membrane protein 3 (LAMP3, identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC is still unknown. In the current study, mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR. LAMP3 protein expression in 46 paired cancerous and normal tissues was detected by immunohistochemistry (IHC. Then, DNA copy number was examined to observe its potential correlation with mRNA expression. The results showed that both mRNA and protein expression level of LAMP3 was significantly higher in cancerous tissues compared with normal controls (p < 0.001. LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037. Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17–3.09, p = 0.010 and disease-free survival (HR = 1.80, 95% CI = 1.18–2.74, p = 0.006. In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.

  10. Expressions and the clinical significances of p53,p57(Kip2) and CD68 in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Geng Su; Zhongming Tang; Qiurong Mo; Wei Wen

    2013-01-01

    Objective: The aim of our study was to investigate the expression of p53, p57(Kip2) and CD68 in esophageal squamous cell carcinoma (ESCC) and their correlation with the biological behavior of ESCC. Methods: The protein expressions of p53, p57(Kip2) and CD68 were detected in 51 cases of ESCC with S-P immunohistochemical method. Results: The total positive rate of those proteins was p53 64.71%, CD68 58.82% and p57(Kip2) 45.09% respectively in ESCC. The positive expression rate of p57(Kip2) was significantly lower in the positive p53 of ESCC than in the negative p53 (P 0.05). Conclusion: There are significant negative correlations between p57(Kip2) and p53, CD68 protein expression and related to biological behavior. Multy predictors are better guide to patients than single predictor.

  11. Identification of c-Yes expression in the nuclei of hepatocellular carcinoma cells: involvement in the early stages of hepatocarcinogenesis.

    Science.gov (United States)

    Nonomura, Takako; Masaki, Tsutomu; Morishita, Asahiro; Jian, Gong; Uchida, Naohito; Himoto, Takashi; Izuishi, Kunihiko; Iwama, Hisakazu; Yoshiji, Hitoshi; Watanabe, Seishiro; Kurokohchi, Kazutaka; Kuriyama, Shigeki

    2007-01-01

    It is thought that the subcellular distribution of Src-family tyrosine kinases, including c-Yes binding to the cellular membrane, is membranous and/or cytoplasmic. c-Yes protein tyrosine kinase is known to be related to malignant transformation. However, the expression patterns of c-Yes in hepatocellular carcinoma (HCC) remains unknown. In the present study, we report that c-Yes is expressed not only in the membrane and cytoplasm, but also in the nuclei of cancer cells in some human HCC tissues and in a human HCC cell line. We examined the expression and localization of c-Yes in human HCC cell lines (HLE, HLF, PLC/PRF/5 and Hep 3B) by Western blotting and immunohistochemical analyses; we also examined the expression of c-Yes by immunohistochemistry and Western blotting in the tissues of various liver diseases, including 39 samples from HCC patients. We used an antibody array to detect proteins that bind to nuclear c-Yes in PLC/PRF/5 cell line. c-Yes was found to be expressed in the membranes and cytoplasm of HLE, HLF and Hep 3B HCC cells; it was also detected in the nuclei in addition to the membranes and cytoplasm of PLC/PRF/5 HCC cells. HCC with nuclear c-Yes was detected in 5 of 39 cases (13.0%), and nuclear c-Yes expression was not detected in normal, chronic hepatitis or cirrhotic livers. All HCCs with nuclear c-Yes expression were well-differentiated, small tumors at the early stages. In the PLC/PRF/5 cell line, the nuclear localization of c-Yes with cyclin-dependent kinase 1 was confirmed by a protein antibody array. In conclusion, nuclear c-Yes expression was found in cancer cells at the early stages of hepatocarcinogenesis, suggesting that nucleus-located c-Yes may be a useful marker to detect early-stage HCC.

  12. Differential expression of thromboxane synthase in prostate carcinoma: role in tumor cell motility.

    Science.gov (United States)

    Nie, Daotai; Che, Mingxin; Zacharek, Alex; Qiao, Yan; Li, Li; Li, Xinglin; Lamberti, Mario; Tang, Keqin; Cai, Yilong; Guo, Yande; Grignon, David; Honn, Kenneth V

    2004-02-01

    Arachidonic acid metabolism through cyclooxygenase, lipoxygenase, or P-450 epoxygenase pathways can generate a variety of eicosanoids. Thromboxane synthase (TxS) metabolizes the cyclooxygenase product, prostanglandin H(2), into thromboxane A(2) (TXA(2)), which can cause vessel constriction, platelet activation, and aggregation. Here we demonstrate that human prostate cancer (PCa) cells express enzymatically active TxS and that this enzyme is involved in cell motility. In human PCa cell lines, PC-3, PC-3M, and ML-2 cells expressed higher levels of TxS than normal prostate epithelial cells or other established PCa cell lines such as DU145, LNCaP, or PPC-1. We cloned and sequenced the full-length TxS cDNA from PC-3 cells and found two changes in the amino acid residues. Immunohistochemical analysis of tumor specimens revealed that expression of TxS is weak or absent in normal differentiated luminal, or secretory cells, significantly elevated in less differentiated or advanced prostate tumors, and markedly increased in tumors with perineural invasion. TxS expressed in PC-3 cells was enzymatically active and susceptible to carboxyheptal imidazole, an inhibitor of TxS. The biosynthesis of TXA(2) in PC-3 cells was dependent on COX-2, and to a lesser extent, COX-1. Treatment of PC-3 cells with a COX-1 selective inhibitor, piroxicam, reduced TXA(2) synthesis by approximately 40%, while the COX-2 specific inhibitor NS398 reduced TXA(2) production by approximately 80%. Inhibition of TxS activity or blockade of TXA(2) function reduced PC-3 cell migration on fibronectin, while having minimal effects on cell cycle progression or survival. Finally, increased expression of TxS in DU145 cells increased cell motility. Our data suggest that human PCa cells express TxS and that this enzyme may contribute to PCa progression through modulating cell motility.

  13. Inhibition of invasiveness and expression of epidermal growth factor receptor in human colorectal carcinoma cells induced by retinoic acid

    Institute of Scientific and Technical Information of China (English)

    SUNBAODONG; JINDANSONG

    1995-01-01

    Human amniotic basement membrane (HABM) model and agarose drop explant method were used to investigate the effects of retinoic acid(RA) on the invasive ness and adhesiveness to the basement membrane,and the migration of a highly invasive human colorectal cancer cell line CCL229.Results showed that 5×106 MRA markedly reduced the in vitro invasiveness and adhesiveness to the HABM,and the migration of the CCL229 cells.In addition,to elucidate the relation between expression of epidermal growth factor receptor(EGFR) and the invasiveness of the colorectal carcinoma cells,two well-differentiated,but with different invasiveness colorectal cancer cell lines were compared at mRNA level for expression of EGFR by using EGFR cDNA probe labeled with digoxigenin(DIG). Expression of EGFR was shown to be markedly higher in the highly invassive CCL229 cells than that in the low invasive CX-1 cells.Furthermore,expression of EGFR in RA treated CCL229 cells gradually decreased with time,the level being the lowest on day 6 of the RA treatment.

  14. Alteration of cadherin isoform expression and inhibition of gap junctions in stomach carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To explore cell malignant phenotype correlated changes of cell surface adhesion molecules and cell-cell communication in carcinogenesis, human stomach transformed and cancer cell lines were investigated. Expressions of E-cadherin, N-cadherin, ?-catenin, ?-catenin as well as gap junction (GJ) protein Cx32 were studied by utilization of immunoblotting, immunocytochemical and fluorescent dye transfer methods. Mammalian normal stomach mucosal cells expressed E-cadherin but not N-cadherin. E-cadherin immunofluorescence was detected at cell membranous adherens junctions (AJ) where colocalization with immunofluorescent staining of inner surface adhesion plaque proteins ?- and ?-catenins was observed. The existence of E-cadherin/ catenin (?-, ?-) protein complexes as AJ was suggested. In transformed and stomach cancer cells E-cadherin was inhibited, instead, N-cadherin was expressed and localized at membranous AJ where co-staining with ?- and ?-catenin fluorescence was observed. Formation of N-cadherin/catenin (?-, ?-) protein complex at AJs of transformed and cancer cells was suggested. The above observations were further supported by immunoblotting results. Normal stomach muscosal and transformed cells expressed Cx32 at membranous GJ and were competent of gap junction communication (GJIC). In stomach cancer cells, Cx32 was inhibited and GJIC was defective. The results suggested that changes of signal pathways mediated by both cell adhesion and cell communication systems are associated intracellular events of stomach carcinogenesis. The alteration of cadherin isoform from E- to N-cadherin in transformed and stomach cancer cells is the first report.

  15. Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

    Science.gov (United States)

    Choi, Y-W; Bae, S M; Kim, Y-W; Lee, H N; Kim, Y W; Park, T C; Ro, D Y; Shin, J C; Shin, S J; Seo, J-S; Ahn, W S

    2007-01-01

    Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

  16. miR-208-3p promotes hepatocellular carcinoma cell proliferation and invasion through regulating ARID2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Peng; Wu, Dingguo; You, Yu; Sun, Jing; Lu, Lele; Tan, Jiaxing; Bie, Ping, E-mail: bieping2010@163.com

    2015-08-15

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associated with HCC cell progression and may provide a new target for liver cancer treatment. - Highlights: • miR-208-3p was highly expressed and directly repressed the expression of ARID2 in HCC. • miR-208-3p contributed to HCC cell progression both in vitro and in vivo. • Over-expression of ARID2 inhibited the HCC cell proliferation and invasion. • Restoration of ARID2 partly reversed the the effect of miR-208-3p down-regulation on HCC cells. • Newly regulatory pathway: miR-208-3p mediated the repression of ARID2 by TGFβ1 in HCC cells.

  17. Effects of downregulation of SIRT3 expression on proliferation and apoptosis in esophageal squamous cell carcinoma EC9706 cells and its molecular mechanisms.

    Science.gov (United States)

    Yang, Mei; Yang, Chunsong; Pei, Yuhua

    2014-01-01

    To investigate the effect of downregulation of SIRT3 expression on cell proliferation and invasion in esophageal squamous cell carcinoma (ESCC) EC9706 cells, and to explore its possible molecular mechanisms, we transfected siRNA targeting SIRT3 into EC9706 cells, and then divided cells into three groups: untreated, control siRNA and SIRT3 siRNA groups. The expression levels of SIRT3 protein were detected in different groups by western blotting. The effect of SIRT3 siRNA on cell proliferation was investigated using the CCK-8 kit. The changes of cell apoptosis were examined by flow cytometry. Finally, the expression levels of cell proliferation and apoptosis related proteins such as p21, Bcl-2 and Bax were determined by western blotting. SIRT3 siRNA effectively down-regulated the expression of SIRT3 protein in EC9706 cells, and the reduced expression of SIRT3 significantly inhibited cell proliferation and induced cell apoptosis. Most notably, the SIRT3 depletion markedly increased the expressions of p21 and Bax proteins but reduced Bcl-2 protein expression. The proliferation inhibition and apoptosis of EC9706 cells mediated by SIRT3 downregulation may be closely associated with the expression levels of p21, Bcl-2 and Bax proteins.

  18. Induction of PD-L1 expression by epidermal growth factor receptor–mediated signaling in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang W

    2017-02-01

    Full Text Available Wencheng Zhang,1 Qingsong Pang,1 Cihui Yan,2 Qifeng Wang,3 Jingsong Yang,3 Shufei Yu,3 Xiao Liu,3 Zhiyong Yuan,1 Ping Wang,1 Zefen Xiao3 1Department of Radiation Oncology, 2Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Purpose: The purpose of this study was to investigate the potential effect of activation of epidermal growth factor receptor (EGFR signaling pathway on the expression of programmed death-ligand 1 (PD-L1 in esophageal squamous cell carcinoma (ESCC cells with EGFR overexpression. Methods: Flow cytometry and Western blot methods were used to assess PD-L1 expression on ESCC cells when EGFR signaling pathway was activated by epidermal growth factor (EGF with or without EGFR-specific inhibitor AG-1478, and then EGFR signaling array was applied to analyze the potential signaling pathways involved. Results: This study found that PD-L1 expression increased significantly in an EGFR-dependent manner by the activation of EGFR signaling and decreased sharply when EGFR signaling was blocked. The upregulated expression of PD-L1 was not associated with EGFR-STAT3 signaling pathway, but may be affected by EGFR–PI3K–AKT, EGFR–Ras–Raf–Erk, and EGR–PLC-γ signaling pathways. Conclusion: The expression of PD-L1 can be regulated by EGFR signaling activation in ESCC, which indicates an important role for EGFR-mediated immune escape and potential molecular pathways for EGFR-targeted therapy and immunotherapy. Keywords: epidermal growth factor receptor, programmed death-ligand 1, esophageal squamous cell carcinoma, immune checkpoint

  19. SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Srisuttee, Ratakorn [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Koh, Sang Seok [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Jhun, Byung Hak [Department of Applied Nanoscience, Pusan National University, Busan 609-735 (Korea, Republic of); Horio, Yoshiyuki [Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556 (Japan); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. Black-Right-Pointing-Pointer Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. Black-Right-Pointing-Pointer Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of {beta}-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

  20. Immunohistochemical expression of ARID1A in penile squamous cell carcinomas: a tissue microarray study of 112 cases.

    Science.gov (United States)

    Faraj, Sheila F; Chaux, Alcides; Gonzalez-Roibon, Nilda; Munari, Enrico; Cubilla, Antonio L; Shih, Ie-Ming; Netto, George J

    2015-05-01

    ARID1A, a member of the chromatin remodeling genes family, has been suggested as a novel tumor suppressor gene in gynecologic malignancies. However, its role in penile cancer has yet to be determined. This study assesses the immunohistochemical expression of ARID1A in penile squamous cell carcinoma (SCC) and its association with pathologic features, human papillomavirus (HPV) status, and previously reported mammalian target of rapamycin pathway markers in the same cohort. Four tissue microarrays were constructed from 112 cases of formalin-fixed, paraffin-embedded penile SCC from Paraguay. Each tumor was sampled 3 to 12 times. ARID1A expression was evaluated by immunohistochemistry using a polyclonal rabbit anti-ARID1A (BAF250A) antibody. An H score was calculated in each spot as the sum of expression intensity (0-3+) by extent (0%-100%). Median H score per case was used for statistical analysis. ARID1A expression was observed in all cases, ranging from 3% to 100% of tumor cells (median, 95%). In 96 cases (86%), ARID1A expression was observed in 90% or more tumor cells. HPV DNA was detected in 20 (38%) of 52 analyzed samples. There was a significant trend of association between ARID1A and histologic grade. ARID1A expression was not associated with histologic subtype (P = .61) or HPV status (P = .18). ARID1A expression decreased with decreasing levels of PTEN expression (P = .01). ARID1A was expressed in penile SCC, in most cases at high levels. A significant trend of association was found between histologic grade and ARID1A expression, with lower ARID1A expression, lower histologic grades, and decreased PTEN expression.

  1. Immunohistochemical expression of ARID1A in penile squamous cell carcinomas: a tissue microarray study of 112 cases☆

    Science.gov (United States)

    Faraj, Sheila F.; Chaux, Alcides; Gonzalez-Roibon, Nilda; Munari, Enrico; Cubilla, Antonio L.; Shih, Ie-Ming; Netto, George J.

    2015-01-01

    Summary ARID1A, a member of the chromatin remodeling genes family, has been suggested as a novel tumor suppressor gene in gynecologic malignancies. However, its role in penile cancer has yet to be determined. This study assesses the immunohistochemical expression of ARID1A in penile squamous cell carcinoma (SCC) and its association with pathologic features, human papillomavirus (HPV) status, and previously reported mammalian target of rapamycin pathway markers in the same cohort. Four tissue microarrays were constructed from 112 cases of formalin-fixed, paraffin-embedded penile SCC from Paraguay. Each tumor was sampled 3 to 12 times. ARID1A expression was evaluated by immunohistochemistry using a polyclonal rabbit anti-ARID1A (BAF250A) antibody. An H score was calculated in each spot as the sum of expression intensity (0-3+) by extent (0%-100%). Median H score per case was used for statistical analysis. ARID1A expression was observed in all cases, ranging from 3% to 100% of tumor cells (median, 95%). In 96 cases (86%), ARID1A expression was observed in 90% or more tumor cells. HPV DNA was detected in 20 (38%) of 52 analyzed samples. There was a significant trend of association between ARID1A and histologic grade. ARID1A expression was not associated with histologic subtype (P = .61) or HPV status (P = .18). ARID1A expression decreased with decreasing levels of PTEN expression (P = .01). ARID1A was expressed in penile SCC, in most cases at high levels. A significant trend of association was found between histologic grade and ARID1A expression, with lower ARID1A expression, lower histologic grades, and decreased PTEN expression. PMID:25776029

  2. CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis

    Directory of Open Access Journals (Sweden)

    Ferrari Angelo

    2012-03-01

    Full Text Available Abstract Background Mammary tumours frequently develop in female domestic cats being highly malignant in a large percentage of cases. Chemokines regulate many physiological and pathological processes including organogenesis, chemotaxis of inflammatory cells, as well as tumour progression and metastasization. In particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the regulation of metastatic potential of neoplastic cells, including breast cancer. The aim of this study was the immunohistochemical defininition of the expression profile of CXCR4 in primary and metastatic feline mammary carcinomas and the evaluation of the role of SDF-1 in feline mammary tumour cell proliferation. Results A total of 45 mammary surgical samples, including 33 primary tumours (31 carcinomas and 2 adenomas, 6 metastases, and 4 normal mammary tissues were anlyzed. Tumor samples were collected from a total number of 26 animals, as in some cases concurrent occurrence of neoplasm in more than one mammary gland was observed. Tissues were processed for standard histological examination, and all lesions were classified according to the World Health Organization criteria. CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score evaluating both the number of positive cells and the intensity of staining. Six primary, fibroblast-free primary cultures were obtained from fresh feline mammary carcinomas and characterized by immunofluorescence for CXCR4 and malignant mammary cell marker expression. SDF-1-dependent in vitro proliferative effects were also assayed. CXCR4 expression was observed in 29 out of 31 malignant tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than in the respective primary tumours. In 2 benign lesions analyzed, only the single basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal tissue did

  3. FasL EXPRESSION IN HUMAN COLON CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:The Fas and Fas ligand (FasL) play an important role in maintaining immune privilege on malignant tumors. In present study, we investigated the expression of FasL in SW480 and LS174 human colon carcinoma cell lines and twenty primary colon carcinoma specimens. Methods: The expression of FasL in human colon carcinoma cell lines and primary colon carcinomas specimens was detected by immunohistochemistry and Reverse Transcription-PCR (RT-PCR). Results: We found that all of detected human colon carcinoma cell lines and primary colon carcinoma specimens constitutively expressed FasL at the mRNA and protein level. However, the expression of FasL was not found in normal colon epithelial cells. Conclusion: The expression of FasL may occur during malignant transformation from normal colon epithelial cells to colon carcinoma cells. Our results suggest that tumor cells kill cytotoxic T lymphocytes (CTLS) and natural killer (NK) cells by expression of FasL. It may be a new mechanism for tumor cells to escape the host's immune surveillance. The expression of FasL may contribute to the formation of colon carcinomas.

  4. Protein p 16INK4A expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix

    Directory of Open Access Journals (Sweden)

    Gupta Ruchi

    2010-01-01

    Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well recognized. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to up regulation of p16 INK4A , a CDK inhibitor, which is a biomarker for HPV infection. We investigated p16 expression in CIN and invasive squamous cell carcinoma (SCC which has not been reported in the Indian population previously. Materials and Methods: Retrospective analysis of 100 cases with 20 cases each of histologically normal cervical epithelium, CIN1, 2, 3 and invasive SCC for p16 expression was performed by immunohistochemistry using commercially available mouse monoclonal antibody to p16 (clone 6H12. Statistical Analysis: For differences in expression among groups, statistical analysis was carried out using ANOVA and post hoc test of Scheffe. Results: p16 immunoreactivity was found to be both nuclear and/or cytoplasmic. The normal cervical epithelium was predominantly negative for p16 (18/20. There was a progressive increase of p16 expression with the grade of CIN. In CIN 1, two cases (20% showed nuclear and nucleocytoplasmic positivity respectively. In contrast, diffuse strong nuclear or nucleocytoplasmic expression was observed in 45 and 55% cases of CIN 2 and CIN 3 respectively. All except one squamous cell carcinoma stained strongly positive for p16. The difference in expression between CIN 2/3 and SCC versus normal cervix was found highly significant (p is equal to 0.008 and p less than 0.001. Conclusions: p16 expression correlates excellently with the grade of CIN and is a sensitive marker of cervical intraepithelial neoplasia.

  5. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

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    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  6. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells

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    Yao, Qing; Xu, Hui; Zhang, Qian-Qian; Zhou, Hui [Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-Sen University, Guangzhou 510275 (China); Qu, Liang-Hu, E-mail: lssqlh@mail.sysu.edu.cn [Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-Sen University, Guangzhou 510275 (China)

    2009-10-23

    MicroRNAs are involved in cancer-related processes. The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer. However, the function of miR-21 is unknown in cervical carcinomas. In this study, we found that the inhibition of miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4. We also provide direct evidence that PDCD4-3'UTR is a functional target of miR-21 and that the 18 bp putative target site can function as the sole regulatory element in HeLa cells. These results suggest that miR-21 may play an oncogenic role in the cellular processes of cervical cancer and may serve as a target for effective therapies.

  7. Xanthohumol, a prenylated chalcone derived from hops, inhibits proliferation, migration and interleukin-8 expression of hepatocellular carcinoma cells.

    Science.gov (United States)

    Dorn, Christoph; Weiss, Thomas S; Heilmann, Jörg; Hellerbrand, Claus

    2010-02-01

    Xanthohumol, the major prenylated chalcone found in hops, is well known to exert anti-cancer effects, but information regarding the impact on hepatocellular carcinoma (HCC) cells and potential adverse effects on non-tumorous hepatocytes is limited. Here, we show that xanthohumol at a concentration of 25 microM induced apoptosis in two HCC cell lines (HepG2 and Huh7). Furthermore, xanthohumol repressed proliferation and migration, as well as TNF induced NF-kappaB activity and interleukin-8 expression in both cell lines at even lower concentrations. In contrast, xanthohumol concentrations up to 100 microM did not affect viability of primary human hepatocytes in vitro. In summary, our data showed that xanthohumol can ameliorate different pro-tumorigenic mechanisms known to promote HCC progression, indicating its potential as promising therapeutic agent that selectively affects cancer cells.

  8. Relationship between expression of 5-fluorouracil metabolic enzymes and 5-fluorouracil sensitivity in esophageal carcinoma cell lines.

    Science.gov (United States)

    Ando, T; Ishiguro, H; Kuwabara, Y; Kimura, M; Mitsui, A; Sugito, N; Mori, R; Ogawa, R; Katada, T; Fujii, Y

    2008-01-01

    5-Fluorouracil (5-FU) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC). Gene expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), has recently been investigated in order to predict the 5-FU sensitivity of several cancers. We examined the relationship between such gene expression and 5-FU sensitivity in 25 ESCC cell lines. TS, DPD, TP and OPRT mRNA levels were assessed by real-time polymerase chain reaction. The 50% inhibitory concentrations (IC50) of 5-FU in 25 ESCC cell lines were determined by cell proliferation assay. IC50 values for 5-FU ranged from 1.00 to 39.81 micromol/L. There were significant positive correlations between IC50 and TS mRNA expression (R(2) = 0.5781, P IC50 and TP or OPRT mRNA expression. TS and DPD mRNA expression levels may be useful indicators in predicting the anti-tumor activity of 5-FU in ESCC.

  9. Suprabasal expression of Ki-67 as a marker for the severity of oral epithelial dysplasia and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Nidhi Dwivedi

    2013-01-01

    Full Text Available Background: Transition of the normal oral epithelium to dysplasia and to malignancy is featured by increased cell proliferation. To evaluate the hypothesis of distributional disturbances in proliferating and stem cells in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. Aim: To evaluate layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC. Materials and Methods: Thirty histologically confirmed cases of oral epithelial dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were immunohistochemically examined and nuclear expression of Ki-67 was counted according to basal, parabasal, and suprabasal layers in epithelial dysplasia and number of positive cells per 100 cells in OSCC as labeling index (LI. Results: Suprabasal expression of Ki-67 increased according to the severity of epithelial dysplasia and the difference was statistically significant ( P < 0.001. The mean Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for OSCC and 13.6 for normal buccal mucosa. Conclusion: The results of the present study demonstrate the use of proliferative marker Ki-67 in assessing the severity of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective criteria for determining the severity of epithelial dysplasia and histological grading of OSCC.

  10. Versican expression in myoepithelial cells from carcinomas in canine mixed mammary tumors.

    Science.gov (United States)

    Damasceno, Karine A; Bertagnolli, Angélica C; Estrela-Lima, Alessandra; Rabelo, Bruna S; Campos, Liliane C; Ribeiro, Lorena G R; Cassali, Geovanni D

    2014-04-01

    The matrix of canine mixed mammary tumors (CMMTs) consists of proliferating spindle cells of possible myoepithelial origin, as well as myxomatous tissue, cartilage matrix and/or bone. Among the multiple components of this tumor extracellular matrix, versican probably plays a prominent role due to its importance in tumor progression, cell proliferation and differentiation. However, there are few data related to a possible association between versican expression and the state of myoepithelial cell differentiation in CMMTs. Using immunohistochemistry and histochemistry, the objective of this study was to evaluate the expression of versican, sulfated proteoglycans and mucopolysaccharides in myoepithelial cells at different stages of differentiation and to explore a potential relationship with p63 and α-smooth muscle actin (SMA) expression. A significant difference in versican expression was observed among the different stages of myoepithelial cell differentiation with an inverse correlation between versican and p63/SMA expression. These results suggest that at an early stage of proliferation, myoepithelial cells acquire a phenotype consistent with a role in chondrogenesis. Moreover, myoepithelial cells showed an affinity for safranin and periodic acid-Schiff staining at different stages of proliferation supporting the myoepithelial origin of spindle cells from CMMTs.

  11. Expression analysis of Stat3 in human lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Hong; HAN Yi-ping

    2002-01-01

    Objective: To analyze the relationship of Stat3 expression with clinical stages, tissue types, p53and proliferation cell nuclear antigen (PCNA) in human lung carcinoma, and to evaluate the role of Stat3 in the pathogenesis of lung carcinoma. Methods: Immunohistochemical method were used to detected Stat3,p53 and PCNA in different tissues of patients (n= 42) with lung carcinoma who accepted neither radiotherapy nor chemotherapy. Results: The positive rate of Stat3 was 81.0% in lung carcinoma and its expression level was related to the tissue type but not to T, N or the clinical stage. The expression level of Stat3 in non-small cell lung carcinoma (NSCLC) was higher than that in small cell lung carcinoma (SCLC). A positive correlation of the expression of Stat3 with that of p53 and PCNA was identified. Conclusion: The expression level of Stat3 is abnormal in lung carcinoma. Stat3 may be involved in the regulation of p53 gene in lung carcinoma cell, it may accelerate the proliferation of lung carcinoma cells and play an important role in the pathogenesis of lung carcinoma.

  12. Antitumor Activity and Immune Enhancement of Murine Interleukin-23 Expressed in Murine Colon Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    Baoen Shan; Jingsheng Hao; Qiaoxia Li; Masatoshi Tagawa

    2006-01-01

    Interleukin (IL)-23, a cytokine composed of p19 and the p40 subunit of IL-12, can enhance the proliferation of memory T cells and production of IFN-γ from activated T cells. It can also induce antitumor effects in murine model. To further evaluate the antitumor activity and immune enhancement of IL-23 in vivo, murine colon carcinoma cells retrovirally transduced with mIL-23 gene were injected subcutaneously (s.c.) into BALB/c mice.Survival time and tumor volume were observed. LDH release assay, [3H]-TdR incorporation assay and ELISA were used to determine CTL activity, proliferation of splenocytes and level of cytokines, respectively. Number of dendritic cells (DCs) was analyzed by flow cytometry (FCM). IL-23 secreted by Colon26/IL-23 cells suppressed the growth of tumor and prolonged the survival time of mice, enhanced proliferation of splenocytes, CTL activity, and number of DCs. IL-23 also promoted the production of Th1 cytokines such as IFN-γ, IL-12 and TNF-o. However,the level of IL-4 was not enhanced significantly. These data suggested that IL-23 secreted by tumor cells can induce antitumor activity by enhancing immune response.

  13. Subcellular Expression of Mammary Serine Proteinase Inhibitor (MASPIN in Locally Advance Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Samina Zaheer

    2014-08-01

    Conclusions: MASPIN expression was observed in the majority of OSCC. However, it was localized to the cytoplasm of tumor cells in all cases. Loss of MASPIN expression was observed more frequently in poorly differentiated cancers. [J Interdiscipl Histopathol 2014; 2(4.000: 213-216

  14. Expression and phosphorylation of stathmin correlate with cell migration in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Liu, Fei; Sun, Yu-Lin; Xu, Yang; Liu, Fang; Wang, Li-Shun; Zhao, Xiao-Hang

    2013-02-01

    Microtubules play extensive roles in cellular processes, including cell motility. Stathmin is an important protein which destabilizes microtubules. The essential function of stathmin is closely associated with its phosphorylation status. Stathmin is overexpressed in many human cancers and has a significant relationship with clinical characteristics such as grade, tumor size and prognosis. We demonstrated that stathmin was overexpressed in ESCC tissues using both 2-DE and immunohistochemistry analysis. In addition, overexpression of stathmin was significantly correlated with histological grade in ESCC. However, no correlation was found with age, gender and lymph node metastasis. Knockdown of stathmin with siRNA impaired cell migration in KYSE30 and KYSE410 cells. When EC0156 cells were treated with paclitaxel, stathmin was stably phosphorylated and migration was impaired. These observations suggest that stathmin may have a more important function in ESCC development and migration. The present study provides further understanding of the importance of stathmin in ESCC therapy or diagnosis.

  15. Prokineticin 2/Bv8 is expressed in Kupffer cells in liver and is down regulated in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To study the implication of prokineticin 1 (PK1/EG VEGF) and prokineticin 2 (PK2/Bv8) in hepatocellular carcinoma angiogenesis. METHODS: The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF (an angiogenesis marker), vWF (an endothelial cell marker) and to CD68 (a monocyte/macrophage marker). Furthermore, the mRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochemistry and immunocytochemistry.RESULTS:PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/Bv8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC, as expected. In addition, out of all isolated liver cells examined, only Kupffer cells (liver resident macrophages) express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.CONCLUSION:In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.

  16. Increasing matrix stiffness upregulates vascular endothelial growth factor expression in hepatocellular carcinoma cells mediated by integrin β1.

    Science.gov (United States)

    Dong, Yinying; Xie, Xiaoying; Wang, Zhiming; Hu, Chao; Zheng, Qiongdan; Wang, Yaohui; Chen, Rongxin; Xue, Tongchun; Chen, Jie; Gao, Dongmei; Wu, Weizhong; Ren, Zhenggang; Cui, Jiefeng

    2014-02-14

    Matrix stiffness as a novel regulation factor involves in modulating the pathogenesis of hepatocellular carcinoma (HCC) invasion or metastasis. However, the mechanism by which matrix stiffness modulates HCC angiogenesis remains unknown. Here, using buffalo rat HCC models with different liver matrix stiffness backgrounds and an in vitro cell culture system of mechanically tunable Collagen1 (COL1)-coated polyacrylamide gel, we investigated the effects of different matrix stiffness levels on vascular endothelial growth factor (VEGF) expression in HCC cells and explored its regulatory mechanism for controlling HCC angiogenesis. Tissue microarray analysis showed that the expression levels of VEGF and CD31 were gradually upregulated in tumor tissues with increasing COL1 and lysyl oxidase (LOX) expression, indicating a positive correlation between tumor angiogenesis and matrix rigidity. The expression of VEGF and the phosphorylation levels of PI3K and Akt were all upregulated in HCC cells on high-stiffness gel than on low-stiffness gel. Meanwhile, alteration of intergrin β1 expression was found to be the most distinctive, implying that it might mediate the response of HCC cells to matrix stiffness simulation. After integrin β1 was blocked in HCC cells using specific monoclonal antibody, the expression of VEGF and the phosphorylation levels of PI3K and Akt at different culture times were accordingly suppressed and downregulated in the treatment group as compared with those in the control group. All data suggested that the extracellular matrix stiffness stimulation signal was transduced into HCC cells via integrin β1, and this signal activated the PI3K/Akt pathway and upregulated VEGF expression. This study unveils a new paradigm in which matrix stiffness as initiators to modulate HCC angiogenesis.

  17. Co-expression of heat shock protein 70 and glucose-regulated protein 94 in human gastric carcinoma cell line BGC-823

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Wang; Jing Liao; Guo-Zhen Liu; Xing-Cui Wang; Hong-Wei Shang

    2005-01-01

    AIM: To investigate the co-expression and significance of heat shock protein 70 (HSP70) and glucose-regulatedprotein 94 (grp94) in human gastric carcinoma cell line BGC-823.METHODS: The expression and localization of HSP70 and grp94 in human gastric carcinoma cell line BGC-823 were determined by immunocytochemistry and indirect immunofiuorescence cytochemical staining. Flow cytometry was used to analyze the correlation between expression of HSP70, grpg4 and cell cycle in BGC-823 cell line.RESULTS: Gastric cancer cell line BGC-823 expressed high level of HSP70 and grp94. The positive rate of HSP70 and grp94 was 84.9±4.94% and 79.6±5.16%, respectively. Bothof them were stained in cell plasma. There was a significant difference compared with control group (1.9±0.94%,P<0.01). During the cell cycle, HSP70 and grp94 were continuously expressed in BGC-823.CONCLUSION: HSP70 and grp94 are highly expressed in human gastric carcinoma BGC-823 cells through the whole cell cycle. There is no relationship between expression of HSP70, grp94 and cell cycle.

  18. Expression of SKP2 Protein in Lung Carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jun; YANG Chun-lu; ZHANG Huan; DING Wei-zhong; LIU Zhi-ping; LIU Jing-yi

    2008-01-01

    Objective:To study the expressive characteristics of SKP2 protein in lung carcinoma and its implication for prognosis.Methods:The expression of SKP2 protein was detected in 89 non small cell lung carcinoma,13 small cell lung carcinoma,10 lung benign lesion tissues by Tissue Chip and Immunohistochemistry technology.Results:The positive rate of SKP2 protein staining was(23.52±13.57)% in non small cell lung carcinoma and (53.85+12.26)% in small cell lung carcinoma,which were significantly higher than(2.91±1.27)% in lung benign lesion tissues.It was highest in small cell lung carcinoma and lowest in lung benign lesion tissues,with a significant difference between them(P=0.000).The expressive level of SKP2 protein in lung carcinoma tissues was closely related to cell differentiation,lymph node metastasis and pathological types,but not to age,sex,smoking history,tumor site and size,and TNM staging.The survival analysis revealed that the 5-year survival rate of lung carcinoma patients was lower in SKP2 protein positive expression group than that in negative expression group(P1=0.003/0.002;r=-0.275,P2=0.005).Conclusion:The positive expression of SKP2 protein is higher in lung carcinoma than in lung benign lesion tissues.in particular,much higher in small cell lung carcinoma.In lung carcinoma,its expressive level was closely related to cell differentiation,lymph node metastasis and pathological types.Moreover,it may be an independent factor to prognosis of patients with lung carcinoma.

  19. Matrix Metalloproteinase-2, Squamous Cell Carcinoma Antigen, and Tissue Polypeptide-Specific Antigen Expression in Egyptian Patients with Cervical Carcinoma: Relationship with Prognosis

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    Maha Imam Ahmed

    2004-01-01

    Full Text Available Matrix metalloproteinases (MMPs, a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA, and tissue polypeptide – specific antigen (TPS in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA, we analyzed 50 patients with cervical carcinoma (CC and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR and 95% confidence interval (CI for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9] and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]. Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]. Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach.

  20. Mast cell density and the context of clinicopathological parameters and expression of p185, estrogen receptor, and proliferating cell nuclear antigen in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-An Jiang; You-Yuan Zhang; He-Sheng Luo; Shou-Fu Xing

    2002-01-01

    AIM: To investigate the relationship between the mast cell density (MCD) and the context of clinicopathological parameters and expression of p185, estrogen receptor (ER), and proliferating cell nuclear antigen (PCNA) in gastric carcinoma.METHODS: Mast cell, p185, ER, and PCNA were detected using immunohistochemical S-P labeling method. Mast cell was counted in tissue of gastric carcinoma and regional lymph nodes respectively, and involved lymph nodes (TLN) were examined as usual.RESULTS: MCD was significantly related to both age and depth of penetration (χ2=4.688,P<0.05 for age and χ2=9.350,P<0.01 for depth of penetration) between MCD>21/0.03 mm2 and MCD≤21/0.03 mm2 in 100 patients; MCD in 1-6 ILN group patients was significantly higher than that in 7-15 TLN or >15 TLN group patients (u=6.881, 8.055, P<0.01);There were significant differences intergroup in positive expression rate of p185, ER and PCNA between MCD >21/0.03 mm2 and MCD≤21/0.03 mm2 in 100 patients.CONCLUSION: Mast cell may have effect on inhibiting invasive growth of tumor, especially in the aged patients; The number of mast cells, in certain degree, may predicate the number of involved lymph nodes, which is valuable for assessment of prognosis; MCD was related to the expression of p185, ER, and PCNA in gastric carcinoma. Tt suggests that mast cell accumulation may inhibit the proliferation and the dissemination of the gastric carcinoma.

  1. Expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder.

    Science.gov (United States)

    Ai, Xing; Zhang, Xu; Wu, Zhun; Ma, Xin; Ju, Zhenghua; Wang, Baojun; Shi, Taoping

    2007-02-01

    The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (PMRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P>0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (PMRP-1/CD9 expression was statistically significant (r=0.316, PMRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

  2. Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402

    Institute of Scientific and Technical Information of China (English)

    Dong Hong ZHAO; Jian Jun HONG; Shi Ying GUO; Run Lin YANG; Jun YUAN; Chuan Jun WEN; Kai Ya ZHOU; Chao Jun LI

    2004-01-01

    Wnt signaling pathway is essential for development and tumorigenesis,however,this signaling pathway in the progress of hepatocellular carcinoma (HCC) remains unclear. In this paper,we studied the function of human T-cell transcription factor-4 (TCF4),a key factor of Wnt signaling pathway,on the proliferation of HCC cell line. We showed that the expression of TCF4 mRNA in HCC cell line BEL-7402 was higher than that in immortalized normal liver cell line L02. Blockage of Wnt pathway by △NTCF4,a dominant negative TCF4,could suppress BEL-7402 cells growth and decrease the expression of cyclin D1 and c-myc,two of target genes of Wnt pathway. On the other hand,stimulating Wnt pathway by introducing a degradation-resistant β-catenin S37A could increase BEL-7402 cells proliferation. But all the treatments had no effect on L02 cells. Our data indicated that TCF4 might be another key factor in Wnt pathway involved in HCC cells proliferation and TCF4 could be an effective therapeutic target for suppressing the growth of hepatocellular cancers.

  3. Induction of PD-L1 expression by epidermal growth factor receptor–mediated signaling in esophageal squamous cell carcinoma

    Science.gov (United States)

    Zhang, Wencheng; Pang, Qingsong; Yan, Cihui; Wang, Qifeng; Yang, Jingsong; Yu, Shufei; Liu, Xiao; Yuan, Zhiyong; Wang, Ping; Xiao, Zefen

    2017-01-01

    Purpose The purpose of this study was to investigate the potential effect of activation of epidermal growth factor receptor (EGFR) signaling pathway on the expression of programmed death-ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) cells with EGFR overexpression. Methods Flow cytometry and Western blot methods were used to assess PD-L1 expression on ESCC cells when EGFR signaling pathway was activated by epidermal growth factor (EGF) with or without EGFR-specific inhibitor AG-1478, and then EGFR signaling array was applied to analyze the potential signaling pathways involved. Results This study found that PD-L1 expression increased significantly in an EGFR-dependent manner by the activation of EGFR signaling and decreased sharply when EGFR signaling was blocked. The upregulated expression of PD-L1 was not associated with EGFR-STAT3 signaling pathway, but may be affected by EGFR–PI3K–AKT, EGFR–Ras–Raf–Erk, and EGR–PLC-γ signaling pathways. Conclusion The expression of PD-L1 can be regulated by EGFR signaling activation in ESCC, which indicates an important role for EGFR-mediated immune escape and potential molecular pathways for EGFR-targeted therapy and immunotherapy.

  4. Expression and role of Tie-2 in rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the expression of Tie-2 in rectal carcinoma and its relationship with invasion and metastasis in rectal carcinoma.Materials S-P immunohistochemical assay was used to detect the expression of Tie-2 in 40 cases of rectal carcinoma and 10 cases of normal rectal tissues.Results Tie-2 was mainly localized in the cytoplasm and nucleus of vascular endothelial cells in cancerous tissues and partly in the cytoplasm of some cancerous cells.The expression of Tie-2 in rectal carcinoma was signi...

  5. HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

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    Bitu Carolina

    2012-04-01

    Full Text Available Abstract Background HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. Methods In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA containing 127 oral squamous cell carcinomas (OSCC was performed to determine the prognostic role of HOXA1 expression. Results We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026. Conclusion Our findings indicate that HOXA1 may contribute to oral carcinogenesis

  6. MicroRNA expression and regulation in human ovarian carcinoma cells by luteinizing hormone.

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    Juan Cui

    Full Text Available BACKGROUND: MicroRNAs have been widely-studied with regard to their aberrant expression and high correlation with tumorigenesis and progression in various solid tumors. With the major goal of assessing gonadotropin (luteinizing hormone, LH contributions to LH receptor (LHR-positive ovarian cancer cells, we have conducted a genome-wide transcriptomic analysis on human epithelial ovarian cancer cells to identify the microRNA-associated cellular response to LH-mediated activation of LHR. METHODS: Human ovarian cancer cells (SKOV3 were chosen as negative control (LHR- and stably transfected to express functional LHR (LHR+, followed by incubation with LH (0-20 h. At different times of LH-mediated activation of LHR the cancer cells were analyzed by a high-density Ovarian Cancer Disease-Specific-Array (DSA, ALMAC™, which profiled ∼ 100,000 transcripts with ∼ 400 non-coding microRNAs. FINDINGS: In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a. By incorporating the dramatic expression changes observed in mRNAs, strong microRNA/mRNA regulatory pairs were predicted through statistical analyses coupled with collective computational prediction. The role of each microRNA was then determined through a functional analysis based on the highly-confident microRNA/mRNA pairs. CONCLUSION: The overall impact on the transcriptome-level expression indicates that LH may regulate apoptosis and cell growth of LHR+ SKOV3 cells, particularly by reducing cancer cell proliferation, with some microRNAs involved in regulatory roles.

  7. Antiproliferative factor regulates connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells

    Science.gov (United States)

    Matika, Christina A.; Wasilewski, Melissa; Arnott, John A.; Planey, Sonia Lobo

    2012-01-01

    Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis (IC)—a chronic, painful bladder disease of unknown etiology. APF inhibits the proliferation of normal bladder epithelial and T24 bladder carcinoma cells in vitro by binding to cytoskeleton-associated protein 4 (CKAP4) and altering the transcription of genes involved in proliferation, cellular adhesion, and tumorigenesis; however, specific molecular mechanisms and effector genes that control APF's antiproliferative effects are unknown. In this study, we found that there was a 7.5-fold up-regulation of connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells treated with APF. Western blot revealed a dose-dependent increase in CCN2 protein levels, with secretion into the culture medium after APF treatment. CCN2 overexpression enhanced APF's antiproliferative activity, whereas CCN2 knockdown diminished APF-induced p53 expression. Using a luciferase reporter construct, we found that APF treatment resulted in fivefold activation of the CCN2 proximal promoter and, of importance, that small interfering RNA–mediated knockdown of CKAP4 inhibited CCN2 upregulation. In addition, we demonstrate that CKAP4 translocates to the nucleus and binds to the CCN2 proximal promoter in an APF-dependent manner, providing evidence that CCN2 regulation by APF involves CKAP4 nuclear translocation and binding to the CCN2 promoter. PMID:22438586

  8. The Relationship of Expression of bcl-2, p53, and Proliferating Cell Nuclear Antigen (PCNA) to Cell Proliferation and Apoptosis in Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    朱朝辉; 邢诗安; 程平; 李国胜; 杨郁; 曾甫清; 鲁功成

    2004-01-01

    To investigate the relationship of bcl-2, p53, proliferating cell nuclear antigen (PCNA) to cell proliferation, apoptosis and pathological parameters, the patterns of cell growth and turnover in renal cell carcinoma (RCC), formalin-fixed and paraffin-embedded tissue blocks from 34 patients with RCC were examined. Cell proliferation activity was detected by PCNA immunostaining and the proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy- nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Expressions of bcl-2 and p53 were assessed immunohistochemically. Our results showed that the PI ranged from 6.0 % to 24.0 % (median 12.3 %) and theAI from 2.0 % to 8.0 % (median 5.4 %) in RCC. The expression of the bcl-2 protein was demonstrated in 15 cases (44.1 %); the expression of the p53 protein, however, was seen in only 3 case. bcl-2 positivity was not associated with PI or AI or any pathological parameters. There were close associations between PI and tumor grade and stage, and a significant relationship between AI and the tumor grade of RCC. Our study suggests that bcl-2 positivity was not associated with PI or AI or any pathological parameters. There are close associations between PI and AI and tumor grade and stage of RCC. Active cell proliferation may be accompanied by frequent apoptosis in RCC.

  9. Uncoupling of PUMA Expression and Apoptosis Contributes to Functional Heterogeneity in Renal Cell Carcinoma - Prognostic and Translational Implications.

    Science.gov (United States)

    Zhou, Xiaoguang; Li, Jielin; Marx, Christina; Tolstov, Yanis; Rauch, Geraldine; Herpel, Esther; Macher-Goeppinger, Stephan; Roth, Wilfried; Grüllich, Carsten; Pahernik, Sascha; Hohenfellner, Markus; Duensing, Stefan

    2015-12-01

    Renal cell carcinoma (RCC) is characterized by a profound disruption of proapoptotic signaling networks leading to chemo- and radioresistance. A key mediator of DNA damage-induced apoptosis is the BH3-only protein PUMA. Given its central role in proapoptotic signaling, we analyzed a series of more than 600 precision-annotated primary RCC specimens for PUMA protein expression. We found a reduced expression of PUMA in 22.6% of RCCs analyzed. Unexpectedly, however, PUMA deficiency was not associated with more aggressive tumor characteristic as expected. Instead, a reduced PUMA expression was associated with a lower TNM stage, lower histopathologic grade, and more favorable cancer-specific patient survival. A direct correlation in a separate patient cohort revealed a profound disconnection between PUMA expression and apoptosis as exemplified by the fact that the tumor with the highest level of apoptotic cells was PUMA deficient. In a series of in vitro studies, we corroborated these results and discovered the highest propensity to undergo apoptosis in an RCC cell line with virtually undetectable PUMA expression. At the same time, PUMA expression was not necessarily associated with stronger apoptosis induction, which underscores the striking functional heterogeneity of PUMA expression and apoptosis in RCC. Collectively, our findings suggest that PUMA-independent mechanisms of cell death exist and may play an important role in suppressing malignant progression. They underscore the functional heterogeneity of RCCs and suggest that PUMA expression alone may not be a suitable predictive biomarker. A better understanding of alternative proapoptotic pathways, however, may help to design novel therapeutic strategies for patients with advanced RCC.

  10. Clinical significance of serum expression of GROβ in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Qiao-Mei Dong; Jin-Qiang Zhang; Qian Li; Jacqueline C Bracher; Denver T Hendricks; Xiao-Hang Zhao

    2011-01-01

    AIM: To determine the association between serum levels of growth-related gene product β (GROβ) and clinical parameters in esophageal squamous cell carcinoma (ESCC). METHODS: Using enzyme-linked immunosorbent assay, serum GROβ levels were measured in ESCC patients (n = 72) and healthy volunteers (n = 83). The association between serum levels of GROβ and clinical parameters of ESCC was analyzed statistically. RESULTS: The serum GROβ levels were much higher in ESCC patients than in healthy controls (median: 645 ng/L vs 269 ng/L, P < 0.05). Serum GROβ levels were correlated positively with tumor size, lymph node metastasis, and tumor-node-metastasis (TNM) staging, but not with gender or the histological grade of tumors in ESCC patients. The sensitivity and specificity of the assay for serum GROβ were 73.61% and 56.63%, respectively. CONCLUSION: GROβ may function as an oncogene product and contribute to tumorigenesis and metastasis of ESCC.

  11. Influences of survivin expression on cisplatin sensitivity of tongue squamous cell carcinoma in vitro and in vitro

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang Huang; Jian Hui Xu; Chao Bin Pan; Bin Zhang; Jian Guang Wang; Xi Qiang Liu; Lei Tao Zhang

    2008-01-01

    @@ Tongue squamous cell carcinoma (TSCC) is the most common malignancy in oral and maxillofacial region. Liking other tumors in the body, it is a genetic disorder that is strongly linked to imbalance between cell proliferation and apoptosis.

  12. CONSTRUCTION OF ACTIVE RECOMBINANT CASPASE-3 EUKARYOTIC EXPRESSION PLA SMID AND EFFECT OF r-CASPASE-3 ON APOPTOSIS OF PANCREATIC CARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To construct active recombinant cas pa ses-3 gene(r-caspases-3)eukaryotic expression plasmid and observe the apoptos is inducing activity of r-caspase-3 in pancreatic carcinoma cells. Methods pcDNA3.1(+)/r-caspase-3 was constructed and pan creatic carcinoma cells(PC-Ⅱ)were transfected with the pcDNA3.1(+)/r-caspases -3 by liposomes(LipofectAMINE).The expression of r-Caspase-3 mRNA in pancreat ic carcinoma cells was detected by reverse transcription process of the polymera se chain reaction(RT-PCR), and the signs of apoptosis were examined in pancreat ic carcinoma cells by the methods of the DNA electrophoresis and flow cytometry analysis(FACS).Results The sequence inserted in pBlueSKM/r-Caspase-3 p lasmid was coincident with that of the r-caspases-3. The evaluation result of pcDNA3.1(+)/r-caspases-3 through enzyme cutting was correct. A 894bp strap was observed by RT-PCR after pancreatic carcinoma cells being transfected with the pcDNA3.1(+)/r-caspases-3 by liposomes. No strap was found in control groups. A characteristic DNA ladder was observed in pancreatic carcinoma cells DNA elect r ophoresis, and transparent hypodiploid karyotype peak was found by FACS. Conclusion The plasmid of pcDNA3.1(+)/r-Caspase-3 was c onstructed successfully, the expression of r-Caspase-3 mRMA in pancreatic carc inoma cells was confirmed by RT-PCR, and pcDNA3.1(+)/r-Caspase-3 can induce a poptosis in pancreatic carcinoma cells.

  13. Ghost cell odontogenic carcinoma.

    NARCIS (Netherlands)

    Nazaretian, S.P.; Schenberg, M.E.; Simpson, I.; Slootweg, P.J.

    2007-01-01

    Ghost cell odontogenic carcinoma (GCOC) is the malignant counterpart of calcifying cystic odontogenic tumour and dentinogenic ghost cell tumour. This is the case of a middle-aged male who presented with a slow-growing maxillary tumour. He was asymptomatic until pain symptoms developed prior to initi

  14. HLA class I expression in bladder carcinomas.

    Science.gov (United States)

    Cabrera, T; Pedrajas, G; Cozar, J M; Garrido, A; Vicente, J; Tallada, M; Garrido, F

    2003-10-01

    HLA class I molecules are frequently lost in a large variety of human carcinomas, possibly because of T-cell immune selection of major histocompatibility complex class I deficient tumor variants. We report that this phenomenon is also a frequent event in bladder carcinomas. Of a total of 72 bladder carcinomas, 72% of the tumors had at least one alteration in HLA class I expression. These altered HLA class I phenotypes were classified as total HLA class I loss (25%; phenotype I); HLA-A or/and HLA-B locus-specific loss (12%; phenotype III); and HLA class I allelic loss (35%; phenotype II or IV). Comparison of histopathological parameters with HLA class I expression showed a statistically significant relationship with the degree of differentiation and tumor recurrence.

  15. Effects of vitamin E succinate on the expression of Fas and PCNA proteins in human gastric carcinoma cells and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Lan Zhao; Yao Li; Yu-Juan Shan; Li-Jie Wu

    2004-01-01

    AIM: To investigate the effects of vitamin E succinate (VES) on the expression of Fas and PCNA proteins as well as its clinical significance in human gastric carcinoma, and to explore the mechanism of VES-induced inhibition of gastric carcinoma cell growth.METHODS: Immunohistochemical methods were used to detect Fas and PCNA expression both in human gastric cancer SGC-7901 cells treated with VES at different doses and in human gastric carcinoma tissues.RESULTS: After the SGC-7901 cells were treated with VES at 5, 10, 20 mg/L for 48 h, the positive rates of Fas expression were 16%, 27% and 48%, respectively, significantly increased compared to that of control group (P<0.05); while the positive rates of PCNA expression in groups treated with different doses of VES were 20%, 18% and 7%, respectively, which were significantly decreased compared to that of the control group (P<0.05). In human gastric carcinoma tissues, the Fas positive expression rate was 42.4%(25/59), which declined with the decrease in the degree of tumor differentiation (P<0.05) and with the existence of lymph node metastasis (P<0.001). While the PCNA positive expression rate was 91.5%(54/59), no relationship was observed between PCNA expression and clinicopathologic parameters.CONCLUSION: VES inhibited the growth of gastric cancer cells by inducing Fas expression and inhibiting PCNA expression.It is, therefore, considered that the expression of Fas and PCNA genes, through tumor cell apoptosis and proliferation,respectively, may be useful as a clinical predictive index in the application of VES to gastric carcinoma therapy, where as Fas may be of more value than PCNA.

  16. Subungual squamous cell carcinoma*

    Science.gov (United States)

    Padilha, Carolina Barbosa de Sousa; Balassiano, Laila Klotz de Almeida; Pinto, Julyana Calegari; de Souza, Flávia Crespo Schueler; Kac, Bernard Kawa; Treu, Curt Mafra

    2016-01-01

    Although subungual squamous cell carcinoma is rare, it is the most common primary malignant neoplasms in this location. The higher incidence occurs in the fingernails, but involvement of the toenails is also possible. Subungual squamous cell carcinoma often looks like other more common benign lesions, such as fungal infection, onychomycosis, or viral wart. These factors, together with a general lack of awareness of this disease among physicians, often result in delayed diagnosis. Therefore, it is underdiagnosed, with few reports in the literature. The authors present a case of a man with a diagnosis of subungual squamous cell carcinoma in the hallux, without bone involvement, which was submitted to the appropriate surgical treatment. PMID:28099608

  17. Expression of COX-2, CD44v6 and CD147 and relationship with invasion and lymph node metastasis in hypopharyngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Qing Yang

    Full Text Available To assess the expression of COX-2,CD44v6 and CD147 in hypopharyngeal squamous cell carcinomas and the three biomarkers correlation with tumor invasion and lymph node metastasis of Chinese people. 101 cases of surgically excised primary tumor were included in this study, and 40 tissues of epithelium adjacent to carcinoma were used as controls. We characterized the immunohistochemical expression of COX-2, CD44v6, and CD147 in 141 formalin-fixed, paraffin-embedded tissues, and measured the mean optical density (OD of the positive area to identify the expression of the three bio-markers and relationship with tumor invasion and lymph node metastasis. Our study demonstrates that the expression of the COX-2 and CD147 were significantly increased in carcinoma tissues compared to the epithelium adjacent to carcinoma. We also observed that the expression of COX-2, CD44v6, and CD147 were significantly associated with T classification, lymph node metastasis and clinical stage. There was strong significant correlation among the three biomarkers as well. Additionally, we indicated that recurrence and ≥ P50 level of COX-2 expression had an independent prognostic effect on prognosis. In conclusion, the three biomarkers play important roles in tumor invasion and lymph node metastases and might be valuable indicators of tumor metastasis in hypopharyngeal squamous cell carcinoma.

  18. Survivin mRNA expression in urine as a biomarker for patients with transitional cell carcinoma of bladder

    Institute of Scientific and Technical Information of China (English)

    HOU Jian-quan; HE Jun; WEN Duan-gai; CHEN Zi-xing; ZENG Jian

    2006-01-01

    @@ Transitional cell carcinoma (TCC) of bladder is the most common malignant tumor in uropoiesis system. Up to date, there is still lack of an ideal marker for the diagnosis of TCC except CT and MRI imaging and cystoscopy. Cystoscopy is an invasive examination, which increases the possibility of urinary tract infection. Urine cytology has low sensitivity (21%-40%) in diagnosis of bladder cancer, especially for those with medium or high differentiation. The specificity is often affected by factors such as specimen collection, urinary tract infection, etc. Detecting the expression of survivin mRNA in urine by real time-PCR is simple in specimen collection and is sensitive and relatively specific, which provides a simple and noninvasive diagnostic method for TCC. Moreover it allows comparing the gene expression levels at different stages and grades of TCC, which can help define malignancy degree of TCC.

  19. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

    Science.gov (United States)

    Ali, Maged M.; El Shorbagy, Shereen; Abdelbary, Abeer M.; Abdelaziz, Lobna A.; Salim, Reham A.; Abdel Wahab, Khaled M.

    2017-01-01

    Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC). Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p < 0.001), number of tumors, lymph node metastasis, and tumor size (p < 0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively). High NEDD9 and p38 detection had a worse 3-year OS (p = 0.041 and <0.001, respectively). By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients' outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC. PMID:28194179

  20. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ola A. Harb

    2017-01-01

    Full Text Available Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC. Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9 is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p<0.001, number of tumors, lymph node metastasis, and tumor size (p<0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively. High NEDD9 and p38 detection had a worse 3-year OS (p=0.041 and <0.001, respectively. By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients’ outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.

  1. Largescale Transcriptomics Analysis Suggests Over-Expression of BGH3, MMP9 and PDIA3 in Oral Squamous Cell Carcinoma.

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    Yuan He

    Full Text Available Oral squamous cell carcinoma (OSCC has been reported as the most prevalent cancer of the head and neck region, while early diagnosis remains challenging. Here we took a comprehensive bioinformatics study on microarray data of 326 OSCC clinical samples with control of 165 normal tissues. The cell interaction pathways of ECM-receptor interaction and focal adhesion were found to be significantly regulated in OSCC samples. Further analysis of the topological properties and expression consistency identified that three hub genes in the gene interaction network, MMP9, PDIA3 and BGH3, were consistently up-expressed in OSCC samples. When being validated on additional microarray datasets of 41 OSCC samples, the validation rate of over-expressed BGH3, MMP9, and PDIA3 reached 90%, 90% and 84% respectively. At last, immuno-histochemical assays were done to test the protein expression of the three genes on newly collected clinical samples of 35 OSCC, 20 samples of pre-OSCC stage, and 12 normal oral mucosa specimens. Their protein expression levels were also found to progressively increase from normal mucosa to pre-OSCC stage and further to OSCC (ANOVA p = 0.000, suggesting their key roles in OSCC pathogenesis. Based on above solid validation, we propose BGH3, MMP9 and PDIA3 might be further explored as potential biomarkers to aid OSCC diagnosis.

  2. LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway

    Science.gov (United States)

    Xiao, Deshen; Lai, Weiwei; Pan, Yu; Jiang, Yiqun; Chen, Ling; Mao, Chao; Zhou, Jian; Xi, Sichuan; Cao, Ya; Liu, Shuang; Tao, Yongguang

    2016-01-01

    Basal cell carcinomas (BCC) of the skin are the most common of human cancers. The noncanonical NF-κB pathway is dependent on IKKα. However, the role of IKKα in BCC has not been elucidated. We show here that IKKα is expressed in the nucleus in BCC and non-malignant diseases. Nuclear IKKα could directly bind to the promoters of inflammation factors and LGR5, a stem cell marker, in turn, upregulating LGR5 expression through activation of STAT3 signaling pathway during cancer progression. Activation of STAT3 signaling pathway contributes LGR5 expression in dependent of IKKα after the interplay between STAT3 and IKKα. Meanwhile knockdown of IKKα inhibits tumor growth and transition of epithelial stage to mescheme stage. Taken together, we demonstrate that IKKα functions as a bone fide chromatin regulator in BCC, whose promoted expression contributes to oncogenic transformation via promoting expression stemness- and inflammatory- related genes. Our finding reveals a novel viewpoint for how IKKα may involve in BCCs tumor progression in the inflammatory microenvironment. PMID:27049829

  3. Largescale Transcriptomics Analysis Suggests Over-Expression of BGH3, MMP9 and PDIA3 in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    He, Yuan; Shao, Fangyang; Pi, Weidong; Shi, Cong; Chen, Yujia; Gong, Diping; Wang, Bingjie; Cao, Zhiwei; Tang, Kailin

    2016-01-01

    Oral squamous cell carcinoma (OSCC) has been reported as the most prevalent cancer of the head and neck region, while early diagnosis remains challenging. Here we took a comprehensive bioinformatics study on microarray data of 326 OSCC clinical samples with control of 165 normal tissues. The cell interaction pathways of ECM-receptor interaction and focal adhesion were found to be significantly regulated in OSCC samples. Further analysis of the topological properties and expression consistency identified that three hub genes in the gene interaction network, MMP9, PDIA3 and BGH3, were consistently up-expressed in OSCC samples. When being validated on additional microarray datasets of 41 OSCC samples, the validation rate of over-expressed BGH3, MMP9, and PDIA3 reached 90%, 90% and 84% respectively. At last, immuno-histochemical assays were done to test the protein expression of the three genes on newly collected clinical samples of 35 OSCC, 20 samples of pre-OSCC stage, and 12 normal oral mucosa specimens. Their protein expression levels were also found to progressively increase from normal mucosa to pre-OSCC stage and further to OSCC (ANOVA p = 0.000), suggesting their key roles in OSCC pathogenesis. Based on above solid validation, we propose BGH3, MMP9 and PDIA3 might be further explored as potential biomarkers to aid OSCC diagnosis.

  4. Expression of long non-coding RNA-HOTAIR in oral squamous cell carcinoma Tca8113 cells and its associated biological behavior

    Science.gov (United States)

    Liu, Huawei; Li, Zhiyong; Wang, Chao; Feng, Lin; Huang, Haitao; Liu, Changkui; Li, Fengxia

    2016-01-01

    As a long noncoding RNA, HOX transcript antisense intergenic RNA (HOTAIR) is highly expressed in many types of tumors. However, its expression and function in oral squamous cell carcinoma (OSCC) cells and tissues remains largely unknown. We herein studied the biological functions of HOTAIR in OSCC Tca8113 cells. Real-time quantitative PCR showed that HOTAIR, p21 and p53 mRNA expressions in doxorubicin (DOX)-treated or γ-ray-irradiated Tca8113 cells were up-regulated. Knockdown of p53 expression inhibited DOX-induced HOTAIR up-regulation, suggesting that DNA damage-induced HOTAIR expression may be associated with p53. Transfection and CCK-8 assays showed that compared with the control group, overexpression of HOTAIR promoted the proliferation of Tca8113 cells, while interfering with its expression played an opposite role. Flow cytometry exhibited that HOTAIR overexpression decreased the rate of DOX-induced apoptosis. When HOTAIR expression was inhibited by siRNA, the proportions of cells in G2/M and S phases increased and decreased respectively. Meanwhile, the rate of DOX-induced apoptosis rose. DNA damage-induced HOTAIR expression facilitated the proliferation of Tca8113 cells and decreased their apoptosis. However, whether the up-regulation depends on p53 still needs in-depth studies. PMID:27904675

  5. Construction of a hepatocellular carcinoma cell line that stably expresses stathmin with a Ser25 phosphorylation site mutation.

    Science.gov (United States)

    Du, J; Tao, Z H; Li, J; Liu, Y K; Gan, L

    2015-10-05

    We constructed hepatocellular carcinoma (HCC) cells that stably express stathmin with a Ser25 phosphorylation site mutation (stathmin S25A). We used the polymerase chain reaction for site-directed mutagenesis, constructed a stathmin S25A plasmid, and verified the results by restriction enzyme cleavage and sequencing technology. Using the liposome transfection method, stathmin wild-type and S25A HCCLM6 cells were established, which were identified by western blotting. The sequencing report of the stathmin S25A plasmid showed that stathmin serine at position 25 had mutated into alanine. Stable cells transfected with stathmin wild-type and S25A plasmids were constructed. Using western blotting, we confirmed that the expression level of stathmin pS25 in the stathmin S25A cells was reduced than that in the stathmin wild-type and HCCLM6 control cells (P stathmin S25A HCCLM6 cells, which offer an experimental model for further investigation of the molecular mechanism of stathmin phosphorylation in hepatocarcinogenesis.

  6. Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma

    Science.gov (United States)

    León, Xavier; Bothe, Carolina; García, Jacinto; Parreño, Matilde; Alcolea, Sonia; Quer, Miquel

    2015-01-01

    The presence of IL-1 in human cancers is associated with aggressive tumor biology but its prognostic value is unknown. We studied whether IL-1α expression is a prognostic marker of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). IL-1α mRNA and protein levels were determined in tumor samples and cancer cell lines using RT-PCR and ELISA. The effects of constitutive IL-1α expression by tumor lines were characterized. IL-1α mRNA and protein secretion were higher in tumor samples from patients who later developed distant metastasis than in patients who did not. By using distant metastasis as a dependent variable, patients were classified into two categories of IL-1α transcript-levels. The high-IL-1α group had a significantly lower five-year distant metastasis-free survival than the low-IL-1α group [70.0% (CI 95%: 55.9-84.1%) vs 94.7% (CI 95%:90.2-99.2%)]. When IL-1α transcript-levels were combined with clinical factors related to tumor metastasis, the predictive power of the model increased significantly. Additionally, transcript levels of IL-1α correlated significantly with those of the IL-1 family genes and genes related to the metastatic process. IL-1 treatment of microvascular endothelial cells increased adhesion of HNSCC cells but no differences were found based on constitutive IL-1α expression by tumor cells. Nevertheless, IL-1α produced by tumor cells effectively increased their transmigration across the endothelium. We found a significant relationship between IL-1α expression and development of distant metastasis in HNSCC patients. IL-1α expression could help to define a subset of patients at high risk of distant metastasis who could benefit from adjuvant treatment. PMID:26460957

  7. Increased Expression of Serglycin in Specific Carcinomas and Aggressive Cancer Cell Lines

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    Angeliki Korpetinou

    2015-01-01

    Full Text Available In the present pilot study, we examined the presence of serglycin in lung, breast, prostate, and colon cancer and evaluated its expression in cell lines and tissues. We found that serglycin was expressed and constitutively secreted in culture medium in high levels in more aggressive cancer cells. It is worth noticing that aggressive cancer cells that harbor KRAS or EGFR mutations secreted serglycin constitutively in elevated levels. Furthermore, we detected the transcription of an alternative splice variant of serglycin lacking exon 2 in specific cell lines. In a limited number of tissue samples analyzed, serglycin was detected in normal epithelium but was also expressed in higher levels in advanced grade tumors as shown by immunohistochemistry. Serglycin staining was diffuse, granular, and mainly cytoplasmic. In some cancer cells serglycin also exhibited membrane and/or nuclear immunolocalization. Interestingly, the stromal cells of the reactive tumor stroma were positive for serglycin, suggesting an enhanced biosynthesis for this proteoglycan in activated tumor microenvironment. Our study investigated for first time the distribution of serglycin in normal epithelial and cancerous lesions in most common cancer types. The elevated levels of serglycin in aggressive cancer and stromal cells may suggest a key role for serglycin in disease progression.

  8. Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas

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    Abbruzzese Claudia

    2012-01-01

    Full Text Available Abstract Background Lung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC, which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member. Methods By means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history. Results mRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters. Conclusions This explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.

  9. Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Liu, J; Yang, X Y; Shi, W J

    2014-01-08

    Non-small cell lung carcinoma, NSCLC, accounts for 80-85% of lung cancers. NSCLC can be mainly divided into two types: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The purpose of our study was to identify and differentiate the pathogenesis of ADC and SCC at the molecular level. The gene expression profiles of ADC and SCC were downloaded from Gene Expression Omnibus under accession No. GSE10245. Accordingly, differentially expressed genes (DEGs) were identified by the limma package in R language. In addition, DEGs were functionally analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A total of 4124 DEGs were identified, including CDK1, CDK2, CDK4, and SKP2. The DEGs were mainly involved in 16 pathways related to cell proliferation, cell signal transduction and metabolism. We conclude that the molecular mechanisms of ADC and SCC are considerably different, and that they are involved in immune response, cell signal transduction, metabolism, cell division, and cell proliferation. Therefore, the two diseases should be treated differently. This study offers new insight into the diagnosis and therapy of these two types of lung cancer.

  10. Expression of peanut agglutinin-binding mucin-type glycoprotein in human esophageal squamous cell carcinoma as a marker

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    Balakrishnan Ramathilakam

    2003-11-01

    Full Text Available Abstract Background The TF (Thomson – Friedenreich blood group antigen behaves as an onco-foetal carcinoma-associated antigen, showing increased expression in malignancies and its detection and quantification can be used in serologic diagnosis mainly in adenocarcinomas. This study was undertaken to analyze the sera and tissue level detectable mucin-type glycoprotein (TF-antigen by Peanut agglutinin (PNA and its diagnostic index in serum as well tissues of human esophageal squamous cell carcinoma as marker. Results We examined 100 patients for serological analysis by Enzyme Linked Lectin Assay (ELISA and demonstrated a sensitivity of 87.5%, specificity of 90% and a positive predictive value of 95%. The immuno-histochemical localization of TF antigen by Fluorescence Antigen Technique (FAT in 25 specimens of normal esophageal squamous epithelium specimens and 92 specimens with different grades of, allowed a quicker and more precise identification of its increased expression and this did not correlate with gender and tumor size. There was a positive correlation between membrane bound TF antigen expression with different histological progression, from well differentiated to poorly differentiated, determined by PNA binding. Specimens showed morphological changes and a pronounced increase in PNA binding in Golgi apparatus, secretory granules of the cytosol of well differentiated and an increased cell membrane labeling in moderately and poorly differentiated, when compared with ESCC and normal tissues. Conclusion The authors propose that the expression of TF-antigen in human may play an important role during tumorigenesis establishing it as a chemically well-defined carcinoma-associated antigen. Identification of the circulating TF-antigen as a reactive form and as a cryptic form in the healthy individuals, using PNA-ELLA and Immunohistochemical analysis of TF antigen by FAT is positively correlated with the different histological grades as a simple

  11. Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiang; ZHAO Yu-pei; LIAO Quan; HU Ya; XU Qiang; ZHOU Li; SHU Hong

    2011-01-01

    Background Thymidylate synthase (TS) is a key regulatory enzyme for de novo DNA synthesis.TS activity is also an important determinant of the response to chemotherapy with fluoropyrimidine prodrugs,and its expression may be affected by gene polymorphisms.In this study,we investigated the associations between polymorphisms of the TS gene and its protein expression,and the implications on the efficacy of 5-fluorouracil (5-FU) in pancreatic cancer cells.Methods Genotypes based on the 28-bp TS tandem repeat for pancreatic cell lines were determined by electrophoretic analysis of PCR products.A single nucleotide polymorphism (SNP) at nucleotide 12 of the second 28-bp repeat of the 3R allele was determined by nucleotide sequencing.The chemosensitivity of pancreatic carcinoma cells to 5-FU in vitro was evaluated using Cell Counting Kit-8 (CCK-8).TS protein expression was analyzed by Western blotting.Results Seven pancreatic carcinoma cell lines had different genotypes in terms of the 28-bp TS tandem repeat,as follows:homozygous 2R/2R (T3M4 and BxPC-3 cells),heterozygous 2R/3R (AsPC-1,Capan-1,and SU86.86),and homozygous 3R/3R (PANC-1 and COLO357).The optical density ratio of genotypes 3R/3R,2R/2R and 2R/3R was 1.393±0.374,0.568±0.032 and 0.561±0.056,respectively.Cells with the 2R/3R or 3R/3R genotypes were further analyzed for the G to C SNP at nucleotide 12 of the second 28-bp repeat of the 3R allele,yielding heterozygous 2R/3Rc (AsPC-1,Capan-1,and SU86.86),homozygous 3Rg/3Rg (COLO357) and homozygous 3Rc/3Rc (PANC-1).The optical density ratio of homozygous 3Rg/3Rg cells and homozygous 3Rc/3Rc cells was 1.723±0.062 and 1.063±0.134,respectively,and this difference was statistically significant (P <0.05).Cells with the 2R/2R and 2R/3R genotypes of TS were hypersensitive to 5-FU in vitro as compared with those with the 3R/3R cells.Conclusions Polymorphisms in the TS gene influenced its protein expression and affected sensitivity of 5-FU in seven pancreatic cancer cell

  12. Hepatitis B Virus X Upregulates HuR Protein Level to Stabilize HER2 Expression in Hepatocellular Carcinoma Cells

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    Chao-Ming Hung

    2014-01-01

    Full Text Available Hepatitis B virus- (HBV- associated hepatocellular carcinoma (HCC is the most common type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very complicated and HBV-encoded X protein (HBx has been reported to play the most important role in this process. Activation of downstream signal pathways of epidermal growth factor receptor (EGFR family is known to mediate HBx-dependent HCC tumor progression. Interestingly, HER2 (also known as ErbB2/Neu/EGFR2 is frequently overexpressed in HBx-expressing HCC patients and is associated with their poor prognosis. However, it remains unclear whether and how HBx regulates HER2 expression. In this study, our data showed that HBx expression increased HER2 protein level via enhancing its mRNA stability. The induction of RNA-binding protein HuR expression by HBx mediated the HER2 mRNA stabilization. Finally, the upregulated HER2 expression promoted the migration ability of HBx-expressing HCC cells. These findings deciphered the molecular mechanism of HBx-mediated HER2 upregulation in HBV-associated HCC.

  13. Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Susilowati, Heni [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Okamura, Hirohiko [Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Hirota, Katsuhiko, E-mail: hirota@dent.tokushima-u.ac.jp [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Shono, Masayuki [Support Center for Advanced Medical Sciences, The University of Tokushima, Tokushima 770-8504 (Japan); Yoshida, Kaya [Department of Fundamental Oral Health Science, School of Oral Health and Welfare, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Murakami, Keiji [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Tabata, Atsushi; Nagamune, Hideaki [Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506 (Japan); Haneji, Tatsuji [Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Miyake, Yoichiro [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan)

    2011-01-07

    Research highlights: {yields} ILY leads to the accumulation of [Ca{sup 2+}]i in the nucleus in HuCCT1 cells. {yields} ILY induced activation of NFAT1 through a calcineurin-dependent pathway. {yields} Calcineuri/NFAT pathway is involved in EGR-1 expression in response to ILY treatment. -- Abstract: Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellular calcium ([Ca{sup 2+}]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-{kappa}B translocation in human hepatic HepG2 cells, ILY did not affect NF-{kappa}B localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca{sup 2+}]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells.

  14. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment

    Science.gov (United States)

    Hirai, Mariko; Kitahara, Hiroko; Kobayashi, Yutaka; Kato, Koroku; Bou-Gharios, George; Nakamura, Hiroyuki; Kawashiri, Shuichi

    2017-01-01

    Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly. PMID:27922697

  15. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  16. Visualization-aided classification ensembles discriminate lung adenocarcinoma and squamous cell carcinoma samples using their gene expression profiles.

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    Ao Zhang

    Full Text Available INTRODUCTION: The widespread application of microarray experiments to cancer research is astounding including lung cancer, one of the most common fatal human tumors. Among non-small cell lung carcinoma (NSCLC, there are two major histological types of NSCLC, adenocarcinoma (AC and squamous cell carcinoma (SCC. RESULTS: In this paper, we proposed to integrate a visualization method called Radial Coordinate Visualization (Radviz with a suitable classifier, aiming at discriminating two NSCLC subtypes using patients' gene expression profiles. Our analyses on simulated data and a real microarray dataset show that combining with a classification method, Radviz may play a role in selecting relevant features and ameliorating parsimony, while the final model suffers no or least loss of accuracy. Most importantly, a graphic representation is more easily understandable and implementable for a clinician than statistical methods and/or mathematic equations. CONCLUSION: To conclude, using the NSCLC microarray data presented here as a benchmark, the comprehensive understanding of the underlying mechanism associated with NSCLC and of the mechanisms with its subtypes and respective stages will become reality in the near future.

  17. EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN PRIMARY NON-SMALL CELL LUNG CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lijian; YANG Guoli; XIE Yuquan; XU Weiguo

    1999-01-01

    Objective: Tumor growth depends on angiogenesis.The aim of this paper is to clarify the relationship between the expression of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) and the angiogenesis, or growth, or invasion and prognostic value in Non-Small Cell Lung Cancer (NSCLC).Methods: Microvessei quantification and expression of VEGF was performed immunohistochemically, using multiclonal antibodies against endothelial protein factor Ⅷ-related antigen (F-Ⅷ antigen, or factor Ⅷ) for evaluating the angiogenesis; against VEGF antigen for the expression of VEGF. Results: A total of 53 patients with NSCLC after the radical resection were evaluated.The patients with high and low expression of VEGF were 33 and 20, respectively. A significant higher microvessel density (MVD) was observed in the tumors with high expression of VEGF compared with the tumors with low expression of it (12.17±2.57/mm2 vs 6.01±1.161/mm2, rank sum test, P<0.01). There were 29patients with lymphonodes metastasis in the high expression VEGF/VPF (29/33, 87.88%) group, and 9patients in the low (9/20, 45%) group. There was good correlation between MVD and expression of VEGF (chisquare tests, P<0.001). The overall 5 years survival for 53 patients was 20.75±5.78%; that of the high expression of the VEGF group was 3.03±2.98%; that of the low group was 36.36±13.94%, by Log rank test, P=0.0001.The difference between them had a high significance.There was good correlation between the survival and the expression of VEGF. By the COX's proportional hazard model analysis, the expression of VEGF and MVD was considered to be an independent marker of the prognosis in non-small cell lung cancer. Conclusion: the expression of VEGF has a significant correlation with MVD, growth, invasion, and lymph node metastasis. The increasing of the node metastasis and the size of tumor accompanied the increasing of VEGF/VPF. The cancer patient with higher VEGF and MVD expression might

  18. Identification of Differentially Expressed Genes in Metastatic and Non-Metastatic Nasopharyngeal Carcinoma Cells by Suppression Subtractive Hybridization

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    Xu-Yu Yang

    2005-01-01

    Full Text Available Background & Objective: Nasopharyngeal carcinoma (NPC is an epithelial neoplasm with high occurrence rates in southern China. The disease often metastasizes to regional lymphnodes at a very early stage. Local recurrences and metastasis occur frequently in patients with NPC and are a leading cause of death, despite improvements on treatment modalities. The molecular mechanism underlying the metastasis of nasopharyngeal carcinoma remains poorly understood, however, and requires additional elucidation. The aim of this study was to explore possible NPC gene candidates that may play key roles in NPC metastasis. Methods: Subtractive suppression hybridization (SSH was performed to isolate differentially expressed clones between the metastatic 5-8F and non-metastatic 6-10B nasopharyngeal carcinoma cell lines. Differentially expressed clones were screened and confirmed by reverse Northern blotting. The sequences of cDNA fragments were subsequently analyzed and compared to known sequences in Genbank. Results & Discussion: The SSH library contained thousands of positive clones. Random analysis of 300 clones by PCR demonstrated that 269 clones contained inserted fragments. Reverse Northern blot confirmed that 20 out of 192 clones examined were significantly up-regulated in the 5-8F cell line. Among these 20 clones, 16 were previously identified genes (flotilin-2, ezrin, pim-3, fli-1, mel, neugrin, znf216, ASB1, raly, UBE2A, keratin6A, TMED7, EIF3S9, FTL, two ribosomal proteins RPL21 and RPL16, two were predicted genes (c9orf74 and MDS006, and two sequences shared no homology with known genes listed in GenBank and may represent novel genes. The proposed functions of the genes identified in this study include cell signal transduction, cell survival, transcription regulation, cell mobility, protein synthesis, and DNA damage repair. Flotillin-2, fli-1, pim-3 and ezrin have previously been reported to be associated with tumor metastasis and progression. The

  19. EXPRESSION OF c-erbB-2, p53, p16 IN SQUAMOUS CELL CARCINOMA OF ANTERIOR TONGUE IN CHINA POPULATION

    Institute of Scientific and Technical Information of China (English)

    张宗敏; 徐震纲; 唐平章; 李爱东; 王争; 赵清正

    2004-01-01

    Objective: Aberrant expression of c-erbB-2, p53, p16 has been found in oral squamous cell carcinoma. We therefore examined expression of these proteins in squamous cell carcinoma of the anterior tongue and compared their relationship with clinical stages and prognosis. Methods: Seventy-six patients with squamous cell carcinoma of the anterior tongue never treated before were obtained from Cancer Hospital, CAMS. Archive tissues of carcinoma and paracarcinoma were examined for c-erbB-2, p53 and p16 expression by immunohistochemistry.Results: The rates of immunopositive staining of c-erbB-2,p53 and p16 were 64.5%, 61.8% and 23.7% respectively; the positive rates in paracarcinoma mucosa were 19.7%, 22.6% and 55.3% respectively. Overexpression of c-erbB-2 was significantly correlated with short overall survival,metastasis and staging. Overexpression of paracarcinoma p53 was significantly correlated with local recurrence.Conclusion. c-erbB-2 may be used as a prognosis marker for the patients with squamous cell carcinoma of the anterior tongue and p53 as a recurrence marker.

  20. Altered β-catenin expression related to cancer progression on actinic cheilitis and squamous cell carcinoma of the lip.

    Science.gov (United States)

    Schussel, Juliana L; Pinto, Décio Dos Santos; Martins, Marília Trierveiler

    2011-02-01

    β-Catenin is a bifunctional protein related to cell adhesion and gene transcription when activated by Wnt pathway. Altered expression of β-catenin was related to loss of differentiation, more aggressive phenotype, increase of tumor invasion, and poor prognosis in a number of different cancers. Actinic cheilitis is caused by excessive exposure to ultraviolet radiation and has a high potential to suffer malignant transformation into squamous cell carcinoma (SCC) of the lip, the most frequent oral malignancy. Studies of oral cancer have shown the correlation of β-catenin expression and oral SCC prognosis, and loss of membrane expression may be considered as a potential marker for early tumor recurrence. Thirty-five cases of actinic cheilitis and 12 cases of SCC of the lip were select and submitted to immunohistochemical staining using β-catenin antibody. β-Catenin was positive on the membrane for all cases. Eighty-five percent of actinic cheilitis cases showed cytoplasmatic staining, and 22% nuclear staining. Eighty-three percent of SCC was positive for β-catenin, and none of them had nuclear staining. Cytoplasmatic and nuclear staining of β-catenin on studied cases point to pathway alterations. Results demonstrated that β-catenin expression is altered on epithelial dysplasia, and it is related to degree of alterations.

  1. Integrin β4 promotes cell invasion and epithelial-mesenchymal transition through the modulation of Slug expression in hepatocellular carcinoma

    Science.gov (United States)

    Li, Xiao-Long; Liu, Lin; Li, Dan-Dan; He, Ya-Ping; Guo, Le-Hang; Sun, Li-Ping; Liu, Lin-Na; Xu, Hui-Xiong; Zhang, Xiao-Ping

    2017-01-01

    Integrin β4 (ITGB4) is a transmembrane receptor involved in tumorigenesis and the invasiveness of many cancers. However, its role in hepatocellular carcinoma (HCC), one of the most prevalent human cancers worldwide, remains unclear. Here, we examined the involvement of ITGB4 in HCC and explored the underlying mechanisms. Real-time PCR and immunohistochemical analyses of tissues from 82 patients with HCC and four HCC cell lines showed higher ITGB4 levels in tumor than in adjacent non-tumor tissues and in HCC than in normal hepatic cells. Silencing of ITGB4 repressed cell proliferation, colony forming ability and cell invasiveness, whereas ectopic expression of ITGB4 promoted the proliferation and invasion of HCC cells and induced epithelial to mesenchymal transition (EMT) in parallel with the upregulation of Slug, as shown by transwell assays, WB and immunocytochemistry. Knockdown of Slug reduced cell viability inhibited invasion and reversed the effects of ITBG4 overexpression on promoting EMT, and AKT/Sox2-Nanog may also be involved. In a xenograft tumor model induced by injection of ITGB4-overexpressing cells into nude mice, ITGB4 promoted tumor growth and metastasis to the lungs. Taken together, our results indicate that ITGB4 plays a tumorigenic and pro-metastatic role mediated by Slug and suggest IGTB4 could be a prognostic indicator or a therapeutic target in patients with HCC. PMID:28084395

  2. Extrapulmonary small cell carcinoma.

    NARCIS (Netherlands)

    Heijden, E. van der; Heijdra, Y.F.

    2005-01-01

    This article reviews the recent literature on extrapulmonary small cell carcinomas. Until now, only four cases have been published in the English literature, two of those in the Southern Medical Journal. Sharing the information on diagnosis and treatment of these cases is important for better unders

  3. Expression of Vascular Endothelial Growth Factor and Cyclooxygenase-2 in Laryngeal Squamous Cell Carcinoma and Its significance

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to study the expressions of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in human laryngeal squamous cell carcinoma (LSCC) and its significance,the expression of VEGF mRNA and COX-2 mRNA in 62 cases of LSCC and 54 adjacent noncancerous laryngeal tissues and 9 normal human laryngeal mucous tissues was detected by using techniques of semi-quantitative RT-PCR. It was found that the expression level of VEGF and COX-2 mRNA was significantly increased in LSCC as compared with that in the normal human laryngeal mucous tissues (both P<0.01), and the expression level of VEGF and COX-2 mRNA were significantly increased in stage Ⅲ + Ⅳ tissues of LSCC as compared with the stage Ⅰ + Ⅱ tissues of LSCC (P <0. 01). There was a high positive correlation between VEGF and COX-2 expression in LSCC (r=0. 756,P<0.01). These data raise the possibility that VEGF and COX-2 may play key roles in the growth, invasion and metastasis of LSCC.

  4. Podoplanin expression in tumor-free resection margins of oral squamous cell carcinomas: an immunohistochemical and fractal analysis study.

    Science.gov (United States)

    Margaritescu, C; Raica, M; Pirici, D; Simionescu, C; Mogoanta, L; Stinga, A C; Stinga, A S; Ribatti, D

    2010-06-01

    Podoplanin is involved in tumorigenesis and cancer progression in head and neck malignancies and its expression is not restricted to lymphatic vessel endothelium. The aim of this study was to establish podoplanin expression in the tumor-free resection margins of oral squamous cell carcinomas (OSCCs) and to evaluate the geometric complexity of the lymphatic vessels in oral mucosa by utilizing fractal analysis. As concerns the podoplanin expression in noncancerous tissue, forty tumor-free resection margins from OSCCs were investigated utilizing immunohistochemistry for D2-40 antibody and image densitometry analysis. Podoplanin expression was extremely low in basal cells, especially in resection margins of OSCCs developed in the lower lip regions. However, a highly variable D2-40 expression in tumor-free resection margins associated with hyperplastic or dysplastic lesions was identified. Moreover, podoplanin expression also extended to the basal layer of the lower lip skin appendages, the myoepithelial cells of acini and ducts of minor salivary glands, and other structures from the oral cavity. As concerns the study of the density and complexity of oral lymphatic vessels architecture by means of immunohistochemistry (D2-40, CD31 and Ki-67 antibodies) and fractal analysis, we demonstrated that in normal oral mucosa the geometry of the lymphatic vessels was less complex at the level of the lower lip compared to the anterior part of the oral floor mucosa or the tongue. A comparative analysis between the normal and pathological aspects revealed statistically significant differences between the fractal dimension (FD) of the vessels' outline, especially in the tongue. Fractal analysis proved an increasing lymphatic network complexity from normal to premalignant oral mucosal lesions, providing additional prognostic information in oral malignant tumors.

  5. Prognostic Significance of Decreased Expression of Six Large Common Fragile Site Genes in Oropharyngeal Squamous Cell Carcinomas

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    Ge Gao

    2014-12-01

    Full Text Available Common fragile sites (CFSs are large regions with profound genomic instability that often span extremely large genes a number of which have been found to be important tumor suppressors. RNA sequencing previously revealed that there was a group of six large CFS genes which frequently had decreased expression in oropharyngeal squamous cell carcinomas (OPSCCs and real-time reverse transcriptase polymerase chain reaction experiments validated that these six large CFS genes (PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT had decreased expression in most of the tumor samples. In this study, we investigated whether the decreased expression of these genes has any clinical significance in OPSCCs. We analyzed the six CFS large genes in 45 OPSCC patients and found that 27 (60% of the OPSCC tumors had decreased expression of these six genes. When we correlated the expression of these six genes to each patient’s clinical records, for 11 patients who had tumor recurrence, 10 of them had decreased expression of almost all 6 genes. When we divided the patients into two groups, one group with decreased expression of the six genes and the other group with either slight changes or increased expression of the six genes, we found that there is significant difference in the incidence of tumor recurrence between these two groups by Kaplan-Meier plot analysis (P < .05. Our results demonstrated that those OPSCC tumors with decreased expression of this select group of six large CFS genes were much more likely to be associated with tumor recurrence and these genes are potential prognostic markers for predicting tumor recurrence in OPSCC.

  6. Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

    Directory of Open Access Journals (Sweden)

    Jia W

    2016-08-01

    Full Text Available Wei Jia,1 Wei Wang,1 Chu-shu Ji,1 Jun-yang Niu,2 Ya-jing Lv,1 Hang-cheng Zhou,2 Bing Hu1 1Department of Medical Oncology, 2Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Background: Both periostin (PN and epidermal growth factor receptor (EGFR can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. Patients and methods: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS and overall survival (OS. Results: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044, differentiation grade (P=0.003, venous invasion (P=0.010, invasion depth (P=0.007, lymphatic metastasis (P=0.000, and tumor stage (P=0.000. The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000, invasion depth (P=0.022, and tumor stage (P=0.000. Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000 and DFS (P=0.000, which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS

  7. Identification of Molecular Tumor Markers in Renal Cell Carcinomas with TFE3 Protein Expression by RNA Sequencing

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    Dorothee Pflueger

    2013-11-01

    Full Text Available TFE3 translocation renal cell carcinoma (tRCC is defined by chromosomal translocations involving the TFE3 transcription factor at chromosome Xp11.2. Genetically proven TFE3 tRCCs have a broad histologic spectrum with overlapping features to other renal tumor subtypes. In this study,we aimed for characterizing RCC with TFE3 protein expression. Using next-generation whole transcriptome sequencing (RNA-Seq as a discovery tool, we analyzed fusion transcripts, gene expression profile, and somatic mutations in frozen tissue of one TFE3 tRCC. By applying a computational analysis developed to call chimeric RNA molecules from paired-end RNA-Seq data, we confirmed the known TFE3 translocation. Its fusion partner SFPQ has already been described as fusion partner in tRCCs. In addition, an RNAread-through chimera between TMED6 and COG8 as well as MET and KDR (VEGFR2 point mutations were identified. An EGFR mutation, but no chromosomal rearrangements, was identified in a control group of five clear cell RCCs (ccRCCs. The TFE3 tRCC could be clearly distinguished from the ccRCCs by RNA-Seq gene expression measurements using a previously reported tRCC gene signature. In validation experiments using reverse transcription-PCR, TMED6-COG8 chimera expression was significantly higher in nine TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in 24 ccRCCs (P<.001 and 22 papillaryRCCs (P<.05-.07. Immunohistochemical analysis of selected genes from the tRCC gene signature showed significantly higher eukaryotic translation elongation factor 1 alpha 2 (EEF1A2 and Contactin 3 (CNTN3 expression in 16 TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in over 200 ccRCCs (P < .0001, both.

  8. MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma.

    Science.gov (United States)

    Bujas, T; Marusic, Z; Peric Balja, M; Mijic, A; Kruslin, B; Tomas, D

    2011-03-21

    In the present study we analyzed immunohistochemical expression of MAGE-A 3/4 and NY-ESO-1 in 55 samples of esophageal squamous cell carcinomas (ESCC) and their respective lymph node metastases. To our knowledge this is the first study to assess and compare the expression of these antigens in ESCC lymph node metastases. Fifty (90.9%) primary ESCC were positive for MAGE-A 3/4 and 53 (96.6%) were positive for NY-ESO-1. MAGE-A 3/4 was expressed in all lymph node metastases and the intensity of expression was high in a majority of cases. NY-ESO-1 was negative in 2 (7.1%) lymph nodes metastases, while the reaction was predominantly moderate in the positive group. In primary tumors MAGE-A 3/4 showed a significantly higher intensity of expression compared to NY-ESO-1 (P=0.047), while in lymph node metastases the intensity of expression was not significantly different (P=0.387). Primary tumors with and without lymph node metastases showed no significant differences in MAGE-A 3/4 (P=0.672) and NY-ESO-1 (P=0.444) expression. Intensity of MAGE-A 3/4 (P=0.461) and NY-ESO-1 (P=0.414) expression in primary tumors was not significantly different compared to the expression in their respective lymph nodes metastases. Expression of MAGE-A 3/4 in primary tumors showed significant positive correlation with primary tumor expression of NY-ESO-1 (P=0.021) but no significant correlation with the expression of MAGE-A 3/4 in lymph node metastases (P=0.056). Expression of NY-ESO-1 in primary tumors showed significant positive correlation with the expression of NY-ESO-1 in lymph node metastases (P=0.001) and significant negative correlation with patients’ age (PESO-1 in primary tumors and lymph node metastases showed no significant correlation with prognostic parameters such as tumor grade and TNM stage (P>0.05). We have shown different levels of MAGE-A 3/4 and NY-ESO-1 expression in almost all specimens of primary tumor and lymph node metastases, suggesting that ESCC may be possible target

  9. Construction of a fusion protein expression vector MK-EGFP and its subcellular localization in different carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Li-Cheng Dai; Di-Yong Xu; Xing Yao; Li-Shan Min; Ning Zhao; Bo-Ying Xu; Zheng-Ping Xu; Yong-Liang Lu

    2006-01-01

    AIM: To construct an expression plasmid encoding human wild-type midkine (MK) and enhanced green fluorescence protein (EGFP) fusion protein (MK-EGFP), and to analyze the subcellular localization of MK in different carcinoma cell lines.METHODS: Two kinds of MK coding sequences with or without signal peptide were cloned into plasmid pEGFP-N2, and the recombinant plasmids constructed were introduced into HepG2, MCF7 and DU145 cells,respectively, by transfection. With the help of laser scanning confocal microscopy, the expression and subcellular localization of MK-GFP fusion protein could be detected.RESULTS: Compared with the GFP control, in which fluorescence was detected diffusely over the entire cell body except in the nucleolus, both kinds of fusion protein MK-GFP were localized exclusively to the nucleus and accumulated in the nucleolus in the three kinds of cancer cell lines.CONCLUSION: This study reveals the specific nucleolar translocation independent of signal peptide, which may be involved in the mechanism that MK works. It provides valuable evidence for further study on the functions of MK in nucleus and its possible mechanisms, in which ribosomal RNA transcription and ribosome assembly are involved.

  10. Reference genes for gene expression analysis by real-time reverse transcription polymerase chain reaction of renal cell carcinoma

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Pedersen, Shona; Kristensen, Søren Risom;

    2011-01-01

    Differentiation between malignant renal cell carcinoma and benign oncocytoma is of great importance to choose the optimal treatment. Accurate preoperative diagnosis of renal tumor is therefore crucial; however, existing imaging techniques and histologic examinations are incapable of providing an ...

  11. Cholesterol affects gene expression of the Jun family in colon carcinoma cells using different signaling pathways.

    Science.gov (United States)

    Scheinman, Eyal J; Rostoker, Ran; Leroith, Derek

    2013-07-15

    Hyperlipidemia and hypercholesterolemia have been found to be important factors in cancer development and metastasis. However, the metabolic mechanism and downstream cellular processes following cholesterol stimulation are still unknown. Here we tested the effect of cholesterol on MC-38 colon cancer cells. Using Illumina gene array technology we found a number of genes that were differentially expressed following short term (20-40 min) and longer term (between 2 and 5h) cholesterol stimulation. Three genes were consistently increased at these time points; c-Jun, Jun-B and the chemokine CXCL-1. We have previously shown that cholesterol stimulation leads to PI3K/Akt phosphorylation, and now demonstrated that cholesterol inhibits ERK1/2 phosphorylation; both effects reversed when cholesterol is depleted from lipid rafts using methyl-β-cyclodextrin (MBCD). In addition, vanadate, an inhibitor of phosphatases, reversed the cholesterol inhibition of ERK1/2 phosphorylation. Specific inhibition of p-Akt by wortmannin did not affect cholesterol's stimulation of the expression of c-Jun and Jun-B, however the vanadate effect of increasing p-ERK1/2, inhibited c-Jun expression, specifically, and the MBCD effect of increasing p-ERK and inhibiting p-Akt reduced c-Jun expression. In contrast MBCD and vanadate both enhanced Jun-B gene expression in the presence of cholesterol and elevation of ERK phosphorylation. Thus there is apparently, a differential signaling pathway whereby cholesterol enhances gene expression of the Jun family members.

  12. Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Chaiyarit, Ponlatham; Utrawichian, Akasith; Leelayuwat, Chanvit;

    2012-01-01

    . Materials and methods Saliva samples were from 23 healthy subjects and 23 OSCC patients. Tissue samples were collected from 32 normal oral mucosa (NOM) and 32 OSCC biopsy specimens. ELISA and immunohistochemical methods were used to evaluate the expression of TFF1, TFF2, and TFF3 in saliva and oral mucosal......Objectives The aims of our study were to determine levels of trefoil factor (TFF) peptides in saliva and oral mucosal tissues from patients with oral squamous cell carcinoma (OSCC), and to evaluate whether individual members of TFFs (TFF1, TFF2, and TFF3) might act as biomarkers of disease...... progression in OSCC. Quantification of TFF levels in saliva may not be optimal in terms of diagnostic or predictive value for OSCC derived from oral mucosa....

  13. Detection of HPV DNA and immunohistochemical expression of cell cycle proteins in oral carcinoma in a population of brazilian patients

    Directory of Open Access Journals (Sweden)

    Rosilene Calazans Soares

    2008-10-01

    Full Text Available This study investigated the presence of human papillomavirus (HPV DNA and viral types in 33 cases of oral squamous cells carcinoma (OSCC and compared the immunohistochemical expression of the cell-cycle markers p21 and pRb between cases of the disease with and without HPV. DNA was extracted from paraffin-embedded tissue and amplified by PCR for the detection of HPV DNA. Viral typing was performed by dot blot hybridization. Immunohistochemistry was performed by the streptavidinbiotin technique. HPV DNA was detected in 11 (33.33% of the 33 cases. The prevalent viral type was HPV 18 (81.81%. A significant association was observed between the presence of HPV and immunohistochemical expression of pRb, but not between p21 expression and the presence of the virus. The low frequency of detection of HPV DNA in OSCC suggests a possible participation of the virus in the development and progression of only a subgroup of these tumors.

  14. E-cadherin expression and prognosis of head and neck squamous cell carcinoma: evidence from 19 published investigations

    Directory of Open Access Journals (Sweden)

    Ren X

    2016-04-01

    Full Text Available Xusheng Ren,1,2 Jianning Wang,2 Xuefen Lin,1,3 Xuxia Wang1,3 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Shandong University, 2Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, 3Shandong Province Key Laboratory of Oral Tissue Regeneration, Stomatological Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China Objective: The objective of this study was to review the published literature and investigate whether E-cadherin gene is a prognostic factor in head and neck squamous cell carcinoma by conducting a meta-analysis.Methods: Studies were identified from the databases Embase, Medline, and Cochrane Library by using the keywords “E-cadherin gene” and “head and neck cancer”. Overall survival (OS and disease-free survival (DFS were the primary outcome measurements.Results: Our literature review identified 1,458 articles; 19 studies with a total number of 2,012 cases were eligible for inclusion in the meta-analysis. The hazard ratio (HR for OS of patients with decreased expression of E-cadherin gene was 0.57 (95% CI =0.37, 0.89; P=0.000. However, statistical heterogeneity was unacceptably high (I2=74.5%, P=0.000. After sensitivity analysis, heterogeneity became acceptable, and the effect measure was still significant (I2=7.0%; HR =0.52; 95% CI =0.40, 0.66; P=0.000. The HR for DFS was 0.53 (95% CI =0.42, 0.67; P=0.000.Conclusion: This meta-analysis showed clear evidence that high E-cadherin gene expression is a positive prognostic factor of head and neck squamous cell carcinoma, resulting in better OS and DFS. However, this conclusion must be interpreted with caution due to a few limitations. Keywords: E-cadherin gene, prognosis, head and neck squamous cell carcinoma, immunohistochemistry 

  15. Enhanced expression of PD-L1 in oral squamous cell carcinoma-derived CD11b(+)Gr-1(+) cells and its contribution to immunosuppressive activity.

    Science.gov (United States)

    Fuse, Hiroki; Tomihara, Kei; Heshiki, Wataru; Yamazaki, Manabu; Akyu-Takei, Rie; Tachinami, Hidetake; Furukawa, Ken-Ichiro; Sakurai, Kotaro; Rouwan, Moniruzzaman; Noguchi, Makoto

    2016-08-01

    Cancer is often associated with dysregulation of both the humoral and cellular immune response, which in some instances is believed to result from changes in immune cell populations. For example, immunosuppressive CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been shown to proliferate in the tumor microenvironment and surrounding tissues, highlighting the relationship between tumor growth and impairment of the immune response. However, the role of myeloid-derived suppressor cells in cancer progression has not been fully characterized because these cells are heterogeneous with properties influenced by the type and location of the tumor. Here, we show that CD11b(+)Gr-1(+) cells are elevated in the peripheral blood, spleen, and tumor of mice with oral squamous cell carcinoma. The phenotype and function of these cells varied depending on the tissue of origin. In particular, CD11b(+)Gr-1(+) cells in tumors expressed PD-L1 more abundantly than those in other tissues. Accordingly, CD11b(+)Gr-1(+) cells from tumors, but not from the spleen, suppressed T cell proliferation in vitro. The results suggest that tumor-derived or immune factors result in the accumulation of phenotypically and functionally diverse populations of CD11b(+)Gr-1(+) cells in mice with oral squamous cell carcinoma. The data also indicate that PD-L1 expression in CD11b(+)Gr-1(+) cells contributes to immune suppression, implying that targeting both myeloid-derived suppressor cells and PD-L1 would be an effective immunotherapeutic strategy against oral cancer.

  16. A comparative Analysis by SAGE of Gene Expression Profiles of Esophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma

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    Jantine W. P. M. van Baal

    2008-01-01

    Full Text Available Esophageal adenocarcinoma (EA and esophageal squamous cell carcinoma (ESCC are the two main types of esophageal cancer. Despite extensive research the exact molecular basis of these cancers is unclear. Therefore we evaluated the transcriptome of EA in comparison to non-dysplastic Barrett’s esophagus (BE, the metaplastic epithelium that predisposes for EA, and compared the transcriptome of ESCC to normal esophageal squamous epithelium. For obtaining the transcriptomes tissue biopsies were used and serial analysis of gene expression (SAGE was applied. Validation of results by RT-PCR and immunoblotting was performed using tissues of an additional 23 EA and ESCC patients. Over 58,000 tags were sequenced. Between EA and BE 1013, and between ESCC and normal squamous epithelium 1235 tags were significantly differentially expressed (p < 0.05. The most up-regulated genes in EA compared to BE were SRY-box 4 and Lipocalin2, whereas the most down-regulated genes in EA were Trefoil factors and Annexin A10. The most up-regulated genes in ESCC compared to normal squamous epithelium were BMP4, E-Cadherin and TFF3. The results could suggest that the BE expression profile is closer related to normal squamous esophagus then to EA. In addition, several uniquely expressed genes are identified.

  17. Sulindac modulates secreted protein expression from LIM1215 colon carcinoma cells prior to apoptosis.

    Science.gov (United States)

    Greening, David W; Ji, Hong; Kapp, Eugene A; Simpson, Richard J

    2013-11-01

    Colorectal cancer (CRC) is a major cause of mortality in Western populations. Growing evidence from human and rodent studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) cause regression of existing colon tumors and act as effective chemopreventive agents in sporadic colon tumor formation. Although much is known about the action of the NSAID sulindac, especially its role in inducing apoptosis, mechanisms underlying these effects is poorly understood. In previous secretome-based proteomic studies using 2D-DIGE/MS and cytokine arrays we identified over 150 proteins released from the CRC cell line LIM1215 whose expression levels were dysregulated by treatment with 1mM sulindac over 16h; many of these proteins are implicated in molecular and cellular functions such as cell proliferation, differentiation, adhesion, angiogenesis and apoptosis (Ji et al., Proteomics Clin. Appl. 2009, 3, 433-451). We have extended these studies and describe here an improved protein/peptide separation strategy that facilitated the identification of 987 proteins and peptides released from LIM1215 cells following 1mM sulindac treatment for 8h preceding the onset of apoptosis. This peptidome separation strategy involved fractional centrifugal ultrafiltration of concentrated cell culture media (CM) using nominal molecular weight membrane filters (NMWL 30K, 3K and 1K). Proteins isolated in the >30K and 3-30K fractions were electrophoretically separated by SDS-PAGE and endogenous peptides in the 1-3K membrane filter were fractioned by RP-HPLC; isolated proteins and peptides were identified by nanoLC-MS-MS. Collectively, our data show that LIM1215 cells treated with 1mM sulindac for 8h secrete decreased levels of proteins associated with extracellular matrix remodeling (e.g., collagens, perlecan, syndecans, filamins, dyneins, metalloproteinases and endopeptidases), cell adhesion (e.g., cadherins, integrins, laminins) and mucosal maintenance (e.g., glycoprotein 340 and mucins 5AC, 6

  18. Use of the EGP-2/Ep-CAM promoter for targeted expression of heterologous genes in carcinoma derived cell lines

    NARCIS (Netherlands)

    McLaughlin, PMJ; Trzpis, M; Kroesen, BJ; Helfrich, W; Terpstra, P; Dokter, WHA; Ruiters, MHJ; de Leij, LF; Harmsen, MC

    2004-01-01

    EGP-2, also known as Ep-CAM, is expressed at high levels on the surface of most carcinomas and is therefore considered an attractive target for anticancer strategies. To explore the mechanisms regulating the expression of EGP-2, sequences 3.4 kb upstream of the transcription start site were isolated

  19. Expression of angiostatin cDNA in human gallbladder carcinoma cell line GBC-SD and its effect on endothelial proliferation and growth

    Institute of Scientific and Technical Information of China (English)

    Ding-Zhong Yang; Jing He; Ji-Cheng Zhang; Zuo-Ren Wang

    2006-01-01

    AIM: To explore the influence of angiostatin up-regulation on the biologic behavior of gallbladder carcinoma cells in vitro and in vitro, and the potential value of angiostatin gene therapy for gallbladder carcinoma.METHODS: A eukaryotic expression vector of pcDNA3.1(+) containing murine angiostatin was constructed and identified by restriction endonuclease digestion and sequencing. The recombinant vector pcDNA3.1-angiostatin was transfected into human gallbladder carcinoma cell line GBC-SD with Lipofectamine 2000, and paralleled with the vector and mock control. The resistant clone was screened by G418 filtration. Angiostatin transcription and protein expression were examined by RT-PCR,immunofluorescence and Western-blot. The supernatant was collected to treat endothelial cells. Cell proliferation and growth in vitro were observed under microscope.RESULTS: Murine angiostatin Cdna was successfully cloned into the eukaryotic expression vector pcDNA3.1(+). After 14 d of transfection and selection with G418,macroscopic resistant cell cloning was formed in the experimental group transfected with pcDNA 3.1(+)-angiostatin and vector control. But untreated cells died in the mock control. Angiostatin was detected by RT-PCR and protein expression was detected in the experimental group by immunofluorescence and Western-blot. Cell proliferation and growth in vitro in the three groups were observed respectively under microscope. No significant difference was observed in the growth speed of GBCSD cells between groups that were transfected with and without angiostatin. After treatment with supernatant,significant differences were observed in endothelial cell (ECV-304) growth in vitro. The cell proliferation and growth were inhibited.CONCLUSION: Angiostatin does not directly inhibit human gallbladder carcinoma cell proliferation and growth in vitro, but the secretion of angiostatin inhabits endothelial cell proliferation and growth.

  20. Telomerase inhibition decreases alpha-fetoprotein expression and secretion by hepatocellular carcinoma cell lines: in vitro and in vivo study.

    Directory of Open Access Journals (Sweden)

    Roula Tahtouh

    Full Text Available Alpha-fetoprotein (AFP is a diagnostic marker for hepatocellular carcinoma (HCC. A direct relationship between poor prognosis and the concentration of serum AFP has been observed. Telomerase, an enzyme that stabilizes the telomere length, is expressed by 90% of HCC. The aim of this study was to investigate the effect of telomerase inhibition on AFP secretion and the involvement of the PI3K/Akt/mTOR signaling pathway. Proliferation and viability tests were performed using tetrazolium salt. Apoptosis was determined through the Annexin V assay using flow cytometry. The concentrations of AFP were measured using ELISA kits. The AFP mRNA expression was evaluated using RT-PCR, and cell migration was evaluated using a Boyden chamber assay. The in vivo effect of costunolide on AFP production was tested in NSG mice. Telomerase inhibition by costunolide and BIBR 1532 at 5 and 10 μM decreased AFP mRNA expression and protein secretion by HepG2/C3A cells. The same pattern was obtained with cells treated with hTERT siRNA. This treatment exhibited no apoptotic effect. The AFP mRNA expression and protein secretion by PLC/PRF/5 was decreased after treatment with BIBR1532 at 10 μM. In contrast, no effect was obtained for PLC/PRF/5 cells treated with costunolide at 5 or 10 μM. Inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP concentration. In contrast, the MAPK/ERK pathway appeared to not be involved in HepG2/C3A cells, whereas ERK inhibition decreased the AFP concentration in PLC/PRF/5 cells. Modulation of the AFP concentration was also obtained after the inhibition or activation of PKC. Costunolide (30 mg/kg significantly decreased the AFP serum concentration of NSG mice bearing HepG2/C3A cells. Both the inhibition of telomerase and the inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP production of HepG2/C3A and PLC/PRF/5 cells, suggesting a relationship between telomerase and AFP expression through the PI3K

  1. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

    Science.gov (United States)

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

  2. CD44 and MMP-2 expression in urothelial carcinoma

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    Gülgün ERDOĞAN

    2008-09-01

    Full Text Available Aim: CD44, one of the adhesion molecules, is thought to play an important role in cell-cell and cell-matrix interactions. Matrix metalloproteinases are degradative enzymes that remodel extracellular components. In this study the relation of MMP-2 and CD44 expressions with the histologic classification and the pathologic stage of urothelial carcinoma was revealed using immunohistochemistry.Material and Methods: Thirty-nine patients with urothelial carcinoma of the bladder were studied. The histological classification was performed according to WHO criteria. Patients were grouped as infiltrating urothelial carcinoma, low grade non-invasive papillary urothelial carcinoma, and high grade non-invasive papillary urothelial carcinoma. The pathological staging was done according to the TNM classification. Immunohistochemical staining using CD44 and MMP-2 antibodies was performed on tissue blocks.Results: CD44 immunoreactivity was detected in 77% (30/39 of the tumours which was significantly higher in non-invasive papillary urothelial carcinomas, low grade non-invasive papillary urothelial carcinomas, high grade infiltrating urothelial carcinomas (p≥0.05. MMP-2 expression was observed in 69% (27 of 39 of the tumours. There were no significant differences in MMP-2 expression between various histologic subtypes and noninvasive and infiltrative tumours.Conclusion: In conclusion, higher expression of CD44 is inversely correlated with infiltrative potential of urothelial carcinoma. These results should be supported by further studies.

  3. Expression level of pre-B-cell leukemia transcription factor 2 (PBX2) as a prognostic marker for gingival squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying QIU; Zhu-ling WANG; Shu-qing JIN; Yu-fei PU; Satoru TOYOSAWA; Katsuyuki AOZASA; Eiichi MORII

    2012-01-01

    Objective:In this study,we investigated the interrelationship between clinicopathologic findings and pre-B-cell leukemia transcription factor 2 (PBX2) expression in gingival squamous cell carcinoma (GSCC).Methods:Expression level of PBX2 was immunohistochemically examined in 66 GSCC subjects (30 men and 36 women) with ages ranging from 42 to 85 (median 64.5) years,in which staining intensity in tumor cells was categorized as either weaker (level 1) or equal to/stronger (level 2) than that in the endothelial cells.Results:PBX2 expression is correlated with valosin-containing protein (VCP) expression.Univariate and multivariate analyses revealed a high level of PBX2 expression to be a poor prognosticator for disease-free survival (DFS) and overall survival (OS),and PBX2 expression was an independent prognostic factor for both DFS and OS in GSCC.Conclusions:PBX2 expression level in GSCC is prognostic.PBX2 may be a useful marker to identify the potential for progression in GSCC.

  4. Clinical significance and prognostic value of TRIM24 expression in esophageal squamous cell carcinoma

    Science.gov (United States)

    Chi, Jun; Yang, Qing; Xie, Xiao-Feng; Yang, Xian-Zi; Zhang, Mei-Yin; Wang, Hui-Yun; Xu, Guo-Liang

    2016-01-01

    Tripartite motif-containing 24 (TRIM24), a member of the transcription intermediary factor 1 family, is defined as a co-regulator with several nuclear receptors, such as RARα. TRIM24 has been reported to be involved in many cancers. In this study, we aimed to investigate the expression pattern and prognostic significance of TRIM24 and its relationship with RARα in esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR and western blot. Immunohistochemistry staining shows that the reduced TRIM24 protein is associated with lymph node metastasis (P=0.024), advance pathological TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated TRIM24 protein predicts longer overall survival and disease-free survival (both P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI, 0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve prediction of survival of pTNM stage in ESCC patients, especially in stage I and II. However, no significant relationship was found between TRIM24 and RARα expression levels. In conclusion, reduced TRIM24 protein is associated with poor survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC. PMID:27689360

  5. Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis

    DEFF Research Database (Denmark)

    Giwercman, Alexander; Andrews, P W; Jørgensen, N;

    1993-01-01

    Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell neoplasia would be strengthened by the finding of antigenic...

  6. Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders

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    Aline Correa Abrahao

    2011-02-01

    Full Text Available Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16INK4a in potentially malignant disorders (PMD of the oral mucosa (with varying degrees of dysplasia and in oral squamous cell carcinomas (OSCC to correlate them with the expression of telomerase (hTERT. Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16INK4a expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16INK4a expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16INK4a and hTERT.

  7. Resistance of renal cell carcinoma to sorafenib is mediated by potentially reversible gene expression.

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    Liang Zhang

    Full Text Available PURPOSE: Resistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells. EXPERIMENTAL DESIGN: Mice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice. RESULTS: Despite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib. CONCLUSIONS: In two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment.

  8. Nevoid basal cell carcinoma syndrome

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    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  9. THE EXPRESSION OF CONNEXIN GENES IN NASOPHARYNGEAL CARCINOMA CELLS AND THE EFFECT OF RETINOIC ACID ON THE REGULATION OF THOSE GENES

    Institute of Scientific and Technical Information of China (English)

    JIANG Ning; BIN Liang-hua; TANG Xiang-na; ZHOU Ming; ZENG Zhao-yang; Li Gui-yuan

    1999-01-01

    Objective: To detect which members in the connexin gene family are expressed in nasopharyngeal carcinoma (NPC) cell line HNE1, and the mechanism by which those genes are specifically switched on and off during retinoic acid (RA) induction. Methods: Establishing the cell growth curves of NPC cells. Observing the effect of RA on connexin genes by Northern hybridization. Results: Two genes Cx46 and Cx37, belonging to the connexin gene family, were expressed in HNE, The down-regulation of Cx46 and Cx37, up-regulation of RARa and growth inhibition was observed in HNE1, after exposure to RA. The gene expression and cell growth in HNE1 cells was restored after removal of RA. Conclusion: Two members of the connexin gene family: Cx37 and Cx46 were expressed in HNE1 cells, RA can inhibit the expression of those two genes mediated by RARa, and the effects of RA on HNE1 are reversible.

  10. Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy

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    Slaby Ondrej

    2010-07-01

    Full Text Available Abstract Background MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies have shown altered expression levels of several microRNAs in renal cell carcinoma. Methods We examined the expression levels of selected microRNAs in 38 samples of conventional renal cell carcinoma (RCC and 10 samples of non-tumoral renal parenchyma using TaqMan real-time PCR method. Results The expression levels of miRNA-155 (p Conclusions We have confirmed previous observations obtained by miRNA microarray analysis using standardized real-time PCR method. For the first time, we have identified a prognostic significance of miRNA-106b, which, after validation on a larger group of patients, maybe useful as a promising biomarker in patients with RCC.

  11. NES1基因在结肠癌细胞中表达及意义%The expression and significance of NES1 in colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    饶雪峰; 刘伟中; 吴鹤立; 赵辉; 肖冬生

    2014-01-01

    目的:探讨NES1基因在结肠癌细胞中表达及意义。方法用RT-PCR方法检测NES1mRNA在正常结肠细胞、结肠癌细胞株HT29、HCT116表达情况。结果 NES1在结肠癌细胞株中表达较正常结肠黏膜细胞明显增高。结论 NES1基因在结肠癌的发生发展中起重要作用,这为选用NES1作为结肠癌治疗靶点提供了实验依据及理论基础。%Objective To investigate the expression of NES1 in colon carcinoma cells and its significance. Methods The ex-pression of NES1mRNA in clon carcinoma cells and human colon cell was detected by RT-PCR technique. Results The expres-sion of NES1mRNA in colon carcinoma cell lines HT29 and HCT116 was significantly higher (P<0.05). Conclusion NES1 may play an important role of occurrence and development of colon carcinoma.

  12. Expression microarray analysis reveals alternative splicing of LAMA3 and DST genes in head and neck squamous cell carcinoma.

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    Ryan Li

    Full Text Available Prior studies have demonstrated tumor-specific alternative splicing events in various solid tumor types. The role of alternative splicing in the development and progression of head and neck squamous cell carcinoma (HNSCC is unclear. Our study queried exon-level expression to implicate splice variants in HNSCC tumors.We performed a comparative genome-wide analysis of 44 HNSCC tumors and 25 uvulopalatopharyngoplasty (UPPP tissue samples at an exon expression level. In our comparison we ranked genes based upon a novel score-the Maximum-Minimum Exon Score (MMES--designed to predict the likelihood of an alternative splicing event occurring. We validated predicted alternative splicing events using quantitative RT-PCR on an independent cohort.After MMES scoring of 17,422 genes, the top 900 genes with the highest scores underwent additional manual inspection of expression patterns in a graphical analysis. The genes LAMA3, DST, VEGFC, SDHA, RASIP1, and TP63 were selected for further validation studies because of a high frequency of alternative splicing suggested in our graphical analysis, and literature review showing their biological relevance and known splicing patterns. We confirmed TP63 as having dominant expression of the short DeltaNp63 isoform in HNSCC tumor samples, consistent with prior reports. Two of the six genes (LAMA3 and DST validated by quantitative RT-PCR for tumor-specific alternative splicing events (Student's t test, P<0.001.Alternative splicing events of oncologically relevant proteins occur in HNSCC. The number of genes expressing tumor-specific splice variants needs further elucidation, as does the functional significance of selective isoform expression.

  13. Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival.

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    Yink Heay Kong

    Full Text Available Oral squamous cell carcinoma (OSCC is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clinical outcome can reflect the biological events that promote cancer's aggressive behavior, and these can serve as molecular markers for improved patient management and survival. To this end, epithelial-mesenchymal transition (EMT is a major process that promotes tumor invasion and metastasis, making EMT-related proteins attractive diagnostic biomarkers and therapeutic targets. In this study, we used immunohistochemistry to study the expression of a panel of transcription factors (TWIST1, SNAI1/2, ZEB1 and ZEB2 and other genes intimately related to EMT (CDH1 and LAMC2 at the invasive tumor front of OSCC tissues. The association between the expression of these proteins and clinico-pathological parameters were examined with Pearson Chi-square and correlation with survival was analyzed using Kaplan Meier analysis. Our results demonstrate that there was a significant differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and normal oral mucosa (NOM. Specifically, CDH1 loss was significantly associated with Broder's grading, while diffused LAMC2 was similarly associated with non-cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC was significantly associated with poorer overall survival, particularly in patients without detectable lymph node metastasis. This study demonstrates that EMT-related proteins are differentially expressed in OSCC and that the co-expression of TWIST1 and ZEB2 could be of clinical value in identifying patients with poor survival for appropriate patient management.

  14. HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome.

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    Anders Näsman

    Full Text Available HPV-DNA positive (HPVDNA+ oropharyngeal squamous cell carcinoma (OSCC has better clinical outcome than HPV-DNA negative (HPVDNA- OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS, disease-specific survival (DSS and overall survival (OS in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT or radiotherapy (RT alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

  15. PPI Network Analysis of mRNA Expression Profile of Ezrin Knockdown in Esophageal Squamous Cell Carcinoma

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    Bingli Wu

    2014-01-01

    Full Text Available Ezrin, coding protein EZR which cross-links actin filaments, overexpresses and involves invasion, metastasis, and poor prognosis in various cancers including esophageal squamous cell carcinoma (ESCC. In our previous study, Ezrin was knock down and analyzed by mRNA expression profile which has not been fully mined. In this study, we applied protein-protein interactions (PPI network knowledge and methods to explore our understanding of these differentially expressed genes (DEGs. PPI subnetworks showed that hundreds of DEGs interact with thousands of other proteins. Subcellular localization analyses found that the DEGs and their directly or indirectly interacting proteins distribute in multiple layers, which was applied to analyze the shortest paths between EZR and other DEGs. Gene ontology annotation generated a functional annotation map and found hundreds of significant terms, especially those associated with cytoskeleton organization of Ezrin protein, such as “cytoskeleton organization,” “regulation of actin filament-based process,” and “regulation of actin cytoskeleton organization.” The algorithm of Random Walk with Restart was applied to prioritize the DEGs and identified several cancer related DEGs ranked closest to EZR. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile of Ezrin knockdown for future examination of the roles and mechanisms of Ezrin.

  16. Function of the integrin alpha 6 beta 1 in metastatic breast carcinoma cells assessed by expression of a dominant-negative receptor

    DEFF Research Database (Denmark)

    Shaw, L M; Chao, C; Wewer, U M;

    1996-01-01

    The involvement of the alpha 6 beta a integrin, a laminin receptor, in breast carcinoma progression needs to be addressed rigorously. We report that a human breast carcinoma cell line, MDA-MB-435, known to be highly invasive and metastatic, expresses three potential integrin laminin receptors...... function that involved expression of a cytoplasmic domain deletion mutant of the beta 4 integrin subunit by cDNA transfection. Stable transfectants of MDA-MB-435 cells that expressed this mutant beta 4 subunit were inhibited dramatically in their ability to adhere and migrate on laminin matrices......, and their capacity to invade Matrigel was reduced significantly. These findings support the hypothesis that alpha 6 beta 1 is important for breast cancer progression. Moreover, this approach is a powerful method that should be useful in assessing the role of alpha 6 beta 1 in other cells....

  17. Downregulation of retinoic acid receptor-β2expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Zhong-Min Liu; Fang Ding; Ming-Zhou Guo; Li-Yong Zhang; Min Wu; Zhi-Hua Liu

    2004-01-01

    AIM: To study the role of hypermethylation in the loss ofretinoic acid receptorβ2(RARβ2) in esophageal squamous cell carcinoma (ESCC).METHODS: The role of hypermethylation in RAR,β2 gene silencing in 6 ESCC cell lines was determined by methylationspecific PCR (MSP), and its methylation status was compared with RARβ2 mRNA expression by RT-PCR. The MSP results were confirmed by bisulfite sequencing of RARβ2promoter regions. RESULTS: Methylation was detected in 4 of the 6 cell lines, and the expression of RARβ2was markedly downregulated in 3 of the 4 methylated cell lines. The expression of RARβ2was restored in one RARβ2-downregulated cell line with the partial demethylation of promoter region of RARβ after 5aza-2'-deoxycytidine (5-aza-dc) treatment.CONCLUSION: The methylation of the 5' region may play an important role in the downregulation of RARβ2 in someESCC cell lines, suggesting that multiple mechanisms contribute to the loss of RARβ2expression in ESCC cell lines. This study may have clinical applications for treatment and prevention of ESCC.

  18. Apigenin suppresses GLUT-1 and p-AKT expression to enhance the chemosensitivity to cisplatin of laryngeal carcinoma Hep-2 cells: an in vitro study.

    Science.gov (United States)

    Xu, Ying-Ying; Wu, Ting-Ting; Zhou, Shui-Hong; Bao, Yang-Yang; Wang, Qin-Ying; Fan, Jun; Huang, Ya-Ping

    2014-01-01

    Glucose transporter-1 (GLUT-1) and PI3K/Akt are known to be closely involved in resistance to chemotherapy. Co-targeted therapy reducing GLUT-1 expression and PI3K/Akt pathway activity may overcome the chemoresistance of human cancers. Apigenin may inhibit the expression of GLUT-1 and the PI3K/Akt pathway. We hypothesized that over-expression of GLUT-1 and p-Akt was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether apigenin inhibited GLUT-1 and p-Akt, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin. Real-time RT-PCR and Western blotting confirmed the presence of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins in Hep-2 cells. We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with such expression. Apigenin markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth. This effect was concentration- and time-dependent. Thus apigenin may significantly reduce the levels of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins, in cisplatin-treated Hep-2 cells, in a concentration- and time-dependent manner. To conclude, overexpression of GLUT-1 mRNA may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Apigenin may enhance the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of GLUT-1 and p-Akt expression.

  19. Renal cell carcinoma-infiltrating natural killer cells express differential repertoires of activating and inhibitory receptors and are inhibited by specific HLA class I allotypes.

    Science.gov (United States)

    Schleypen, Julia S; Von Geldern, Marion; Weiss, Elisabeth H; Kotzias, Nicole; Rohrmann, Karl; Schendel, Dolores J; Falk, Christine S; Pohla, Heike

    2003-10-10

    Among tumor-infiltrating lymphocytes (TILs) directly isolated from renal cell carcinomas (RCCs), we found substantial numbers of natural killer (NK) cells in most tumor tissues. They could be identified reliably in situ with an antibody directed against the activating receptor (AR) NKp46 that is exclusively expressed by all NK cells. NK-enriched TILs (NK-TILs) showed cytotoxicity against major histocompatibility complex (MHC) class I-negative cell lines. The ability to detect lysis of target cells was dependent on the percentage of NK cells within the TILs, and cytotoxicity was only observed after overnight activation with low-dose interleukin-2 (IL-2). Infiltrating NK cells were found to express various inhibitory receptors (IRs); among these the CD94/NKG2A receptor complex was overrepresented compared to the autologous peripheral blood mononuclear cell (PBMC) population. Other IRs were underrepresented, indicating that NK subpopulations vary in their tumor-infiltrating capacity. IRs expressed by NK-TILs are functional since receptor engagement with MHC class I ligands presented by human leukocyte antigen (HLA)-transfected target cell lines was able to inhibit NK-mediated cytotoxicity. NK-TILs were also able to lyse autologous or allogeneic tumor cell lines in vitro. This activity correlated with low HLA class I surface expression since lysis could be inhibited by interferon (IFN)-gamma-expressing RCC transductants that displayed a higher surface density of HLA class I molecules. Therefore, NK cells infiltrating tumor tissues have an inherent ability to recognize transformed cells, but they require cytokine activation and are sensitive to inhibition by IR ligands.

  20. In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head and neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumour cells

    DEFF Research Database (Denmark)

    Hald, J; Rasmussen, N; Claesson, Mogens Helweg

    1994-01-01

    A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well with their abi......A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well...... with their ability to expand in vitro in the presence of high-dose interleukin-2 (2000 U/ml). High MHC class I antigen expression on tumour cells was found to be positively correlated with p53 overexpression, suggesting that p53-derived peptides, wild-type or mutated ones, presented by MHC class I antigens......, are potential targets for MHC-restricted cytotoxic T cells in head and neck squamous cell carcinomas. However, lack of correlation between peritumoural T cell infiltration in vivo and T cell expansion in vitro, on the one hand, and p53 overexpression on tumour cells, on the other hand, suggests absence of p53...

  1. Identification of novel microRNAs regulating HLA-G expression and investigating their clinical relevance in renal cell carcinoma

    Science.gov (United States)

    Jasinski-Bergner, Simon; Reches, Adi; Stoehr, Christine; Massa, Chiara; Gonschorek, Evamaria; Huettelmaier, Stefan; Braun, Juliane; Wach, Sven; Wullich, Bernd; Spath, Verena; Wang, Ena; Marincola, Francesco M.; Mandelboim, Ofer; Hartmann, Arndt; Seliger, Barbara

    2016-01-01

    The non-classical human leukocyte antigen G (HLA-G) is expressed at a high frequency in renal cell carcinoma (RCC) and is associated with a higher tumor grade and a poor clinical outcome. This might be caused by the HLA-G-mediated inhibition of the cytotoxicity of T and NK cells. Therefore a selective targeting of HLA-G might represent a powerful strategy to enhance the immunogenicity of RCC lesions. Recent studies identified a number of HLA-G-regulating microRNAs (miRs) and demonstrated an inverse expression of some of these miRs with HLA-G in RCC in vitro and in vivo. However, it was postulated that further miRs might exist contributing to the tightly controlled selective HLA-G expression. By application of a miR enrichment assay (miTRAP) in combination with in silico profiling two novel HLA-G-regulatory miRs, miR-548q and miR-628-5p, were identified. Direct interactions of both miRs with the 3′ untranslated region of HLA-G were confirmed with luciferase reporter gene assays. In addition, qPCR analyses and immunohistochemical staining revealed an inverse, expression of miR-628-5p, but not of miR-548q to the HLA-G protein in primary RCC lesions and cell lines. Stable overexpression of miR-548q and miR-628-5p caused a downregulation of HLA-G mRNA and protein. This leads in case of miR-548q to an enhanced NK cell-mediated HLA-G-dependent cytotoxicity, which could be reverted by ILT2 blockade suggesting a control of the immune effector cell activity at least by this miR. The identification of two novel HLA-G-regulatory miRs extends the number of HLA-G-relevant miRs tuning the HLA-G expression and might serve as future therapeutic targets. PMID:27057628

  2. Identification of novel microRNAs regulating HLA-G expression and investigating their clinical relevance in renal cell carcinoma.

    Science.gov (United States)

    Jasinski-Bergner, Simon; Reches, Adi; Stoehr, Christine; Massa, Chiara; Gonschorek, Evamaria; Huettelmaier, Stefan; Braun, Juliane; Wach, Sven; Wullich, Bernd; Spath, Verena; Wang, Ena; Marincola, Francesco M; Mandelboim, Ofer; Hartmann, Arndt; Seliger, Barbara

    2016-05-01

    The non-classical human leukocyte antigen G (HLA-G) is expressed at a high frequency in renal cell carcinoma (RCC) and is associated with a higher tumor grade and a poor clinical outcome. This might be caused by the HLA-G-mediated inhibition of the cytotoxicity of T and NK cells. Therefore a selective targeting of HLA-G might represent a powerful strategy to enhance the immunogenicity of RCC lesions. Recent studies identified a number of HLA-G-regulating microRNAs (miRs) and demonstrated an inverse expression of some of these miRs with HLA-G in RCC in vitro and in vivo. However, it was postulated that further miRs might exist contributing to the tightly controlled selective HLA-G expression.By application of a miR enrichment assay (miTRAP) in combination with in silico profiling two novel HLA-G-regulatory miRs, miR-548q and miR-628-5p, were identified. Direct interactions of both miRs with the 3' untranslated region of HLA-G were confirmed with luciferase reporter gene assays. In addition, qPCR analyses and immunohistochemical staining revealed an inverse, expression of miR-628-5p, but not of miR-548q to the HLA-G protein in primary RCC lesions and cell lines. Stable overexpression of miR-548q and miR-628-5p caused a downregulation of HLA-G mRNA and protein. This leads in case of miR-548q to an enhanced NK cell-mediated HLA-G-dependent cytotoxicity, which could be reverted by ILT2 blockade suggesting a control of the immune effector cell activity at least by this miR. The identification of two novel HLA-G-regulatory miRs extends the number of HLA-G-relevant miRs tuning the HLA-G expression and might serve as future therapeutic targets.

  3. Activating transcription factor 4 mediates a multidrug resistance phenotype of esophageal squamous cell carcinoma cells through transactivation of STAT3 expression.

    Science.gov (United States)

    Zhu, Hongwu; Chen, Xiong; Chen, Bin; Chen, Bei; Fan, Jianyong; Song, Weibing; Xie, Ziying; Jiang, Dan; Li, Qiuqiong; Zhou, Meihua; Sun, Dayong; Zhao, Yagang

    2014-11-01

    Multidrug resistance (MDR) is a major challenge to the clinical treatment of esophageal cancer. The stress response gene activating transcription factor 4 (ATF4) is involved in homeostasis and cellular protection. However, relatively little is known about the expression and function of ATF4 in esophageal squamous cell carcinoma (ESCC) MDR. In this study, we investigate the potential role and mechanisms of ATF4 in ESCC MDR. We demonstrated that overexpression of ATF4 promotes the MDR phenotype in ESCC cells, while depletion of ATF4 in the MDR ESCC cell line induces drug re-sensitization. We also demonstrated that ATF4 transactivates STAT3 expression by directly binding to the signal transducers and activators of transcription 3 (STAT3) promoter, resulting in MDR in ESCC cells. Significantly, inhibition of STAT3 by small interfering RNA (siRNA) or a selective inhibitor (JSI-124) reintroduces therapeutic sensitivity. In addition, increased Bcl-2, survivin, and MRP1 expression levels were observed in ATF4-overexpressing cells. In conclusion, ATF4 may promote MDR in ESCC cells through the up-regulation of STAT3 expression, and thus is an attractive therapeutic target to combat therapeutic resistance in ESCC.

  4. Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma

    Science.gov (United States)

    Li, Xin; Liang, Liming; De Vivo, Immaculata; Tang, Jean Y.; Han, Jiali

    2016-01-01

    Genome-wide association studies (GWASs) have primarily focused on the association between individual genetic markers and risk of disease. We applied a novel approach that integrates skin expression-related single-nucleotide polymorphisms (eSNPs) and pathway analysis for GWAS of basal cell carcinoma (BCC) to identify potential novel biological pathways. We evaluated the associations between 70,932 skin eSNPs and risk of BCC among 2,323 cases and 7,275 controls of European ancestry, and then assigned them to the pathways defined by KEGG, GO, and BioCarta databases. Three KEGG pathways (colorectal cancer, actin cytoskeleton, and BCC), two GO pathways (cellular component disassembly in apoptosis, and nucleus organization), and four BioCarta pathways (Ras signaling, T cell receptor signaling, natural killer cell-mediated cytotoxicity, and links between Pyk2 and Map Kinases) showed significant association with BCC risk with p-value<0.05 and FDR<0.2. These pathways also ranked at top in sensitivity analyses. Two positive controls in KEGG, the hedgehog pathway and the BCC pathway, showed significant association with BCC risk in both main and sensitivity analyses. Our results indicate that SNPs that are undetectable by conventional GWASs are significantly associated with BCC when tested as pathways. Biological studies of these gene groups suggest their potential roles in the etiology of BCC. PMID:27367190

  5. ASSESSMENT OF PROLIFERATIVE POTENTIAL OF TUMOR CELLS USING KI-67 EXPRESSION AND MORPHOMETRICAL ANALYSIS FOR PROGNOSTICATION OF ORAL SQUAMOUS CELL CARCINOMAS

    Directory of Open Access Journals (Sweden)

    Rakheja Mahima, Singh Pratyush, Shergill Ankur K, Guddattu Vasudeva,Solomon Monica C

    2015-09-01

    Full Text Available Background: Cancer cells exhibit a characteristic intrinsic ability of uncontrolled cell proliferation which plays a vital role in tumor development and progression. The Ki-67 antigen expression is strictly associated with cell proliferation which detects the cells entering the cell cycle. In addition, computer aided image analysis provides an objective and highly reproducible histological evaluation of OSCC. Assessment of Ki-67 expression along with morphometry may help in early and precise diagnosis and prognostication of OSCC. Aims: To correlate the ki-67 expression and the morphometrical parameters of oral squamous cell carcinomas and to assess the efficacy of the correlation in OSCC prognostication. Methods and material: OSCC cases (n=105 were examined immuno histochemically using Ki-67 antigen The nuclear area (NA, cell area (CA, nuclear perimeter (NP and cell perimeter (CP assessed using “image J 1.34 software”. The data was statistically analyzed. Results: Highly significant correlation was found between Ki-67 expression and the advancing grades of OSCC (p<.0001. NA (p=0.025, CA (p<.0001, NP (p=.027 and CP (p<.0001 of poorly differentiated OSCC were significantly lower than well differentiated and moderately differentiated OSCC. Follow up analysis revealed nuclear area and cell area to be higher in the recurrent cases than the non recurrent ones. Conclusion: Assessment of Ki-67 expression and morphometry help in early and precise diagnosis and prognostication of OSCC. A correlation between Ki-67 expression and morphometrical analysis could not be ascertained in this study. Further studies with a larger sample number may provide more definitive results.

  6. Colocalization of carbonic anhydrase 9 expression and cell proliferation in human head and neck squamous cell carcinoma.

    NARCIS (Netherlands)

    Hoogsteen, I.J.; Marres, H.A.M.; Wijffels, K.I.E.M.; Rijken, P.F.J.W.; Peters, J.P.W.; Hoogen, F.J.A. van den; Oosterwijk, E.; Kogel, A.J. van der; Kaanders, J.H.A.M.

    2005-01-01

    PURPOSE: Tumor cells undergo a variety of biological changes under sustained hypoxic conditions, allowing cells to survive and retain their clonogenic potential. The purpose of this study is to relate the expression of the hypoxia marker carbonic anhydrase 9 (CA9) to the uptake of iododeoxyuridine (

  7. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.

    Science.gov (United States)

    Davis, Drew G; Siddiqui, Momin T; Oprea-Ilies, Gabriela; Stevens, Keith; Osunkoya, Adeboye O; Cohen, Cynthia; Li, Xiaoxian Bill

    2016-01-01

    GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation.

  8. Expression of biomarkers (p53, transforming growth factor alpha, epidermal growth factor receptor, c-erbB-2/neu and the proliferative cell nuclear antigen) in oropharyngeal squamous cell carcinomas

    OpenAIRE

    1999-01-01

    Using immunohistochemistry, expression of p53, transforming growth factor-alpha (TGF-α), epidermal growth factor receptor (EGFR), c-erbB-2/neu and proliferating cell nuclear antigen (PCNA) was examined in 26 fresh frozen tissue specimens of oropharyngeal squamous cell carcinomas (SCCs). p53 gene mutations were examined by polymerase chain reaction (PCR)/DNA sequencing methods in 22 carcinomas. The findings were examined for correlations with patients’ clinicopathological parameters. Expressio...

  9. Comparing the expression of myoepithelial cell markers CD10 and smooth muscle actin with the estrogen receptor status in the invasive carcinoma breast: An immunohistochemical study

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    Gaurav Arora

    2013-01-01

    Full Text Available Background: Breast cancer is the most frequent cancer in females throughout the world. Around 20% of breast carcinomas are estrogen receptor alpha (ER-negative. Thus, theoretically this negativity could be either the result of down-regulation of ER expression in the tumor cells, or the result of the tumor being derived from cells which normally lack that expression. Normal basal, including myoepithelial cells of the breast is ER-negative. CD10 and smooth muscle actin (SMA are used as markers for the demonstration of these basal cells. Aims: To compare the expression of positive staining for CD10 and SMA in ER-negative and ER-positive invasive breast carcinomas. Materials and Methods: The study was performed on 40 paraffin-embedded tissues of already diagnosed cases of invasive breast carcinomas with known ER status, i.e., thirty ER-negative and ten ER-positive cases. Expression of CD10 and SMA was demonstrated using avidin-biotin-peroxidase complex (ABC technique. Tumor was considered to be positive for both markers only when more than 10% of tumor cells were stained positive. Results: Overall, CD10 tumor cell staining was seen in eight, 23.3% (7/30 ER-negative cases and in 10% (1/10 ER-positive cases. Also the staining intensity was considered to be strong. SMA tumor cell staining was seen in only 6.7% (2/30 ER-negative cases and the staining intensity was considered to be moderate. Percentages of positively stained tumor cells varied between 13% to 72% and 23% to 45% for CD10 and SMA, respectively. Conclusion: CD10 is a better marker when compared to SMA, as it is expressed in more number of cases and gives strong positivity in tumor cells. Higher expression of CD10 and SMA is correlated with higher tumor grade and ER negativity.

  10. Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation

    Directory of Open Access Journals (Sweden)

    Zeng Zhen

    2012-12-01

    Full Text Available Abstract Background Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to “downstage” patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs, has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence. Methods Formalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE. Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0–3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen. Results TACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040. None of the other markers predicted recurrence. Conclusion High pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of

  11. Vismodegib in basal cell carcinoma.

    Science.gov (United States)

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  12. Analysis of differentially expressed mitochondrial proteins in chromophobe renal cell carcinomas and renal oncocytomas by 2-D gel electrophoresis

    Directory of Open Access Journals (Sweden)

    Maria V. Yusenko, Thomas Ruppert, Gyula Kovacs

    2010-01-01

    Full Text Available Renal oncocytomas (RO and chromophobe renal cell carcinomas (RCC display morphological and functional alterations of the mitochondria. Previous studies showed that accumulation of mitochondria in ROs is associated with somatic mutations of mitochondrial DNA (mtDNA resulting in decreased activity of the respiratory chain complex I, whereas in chromophobe RCC only heteroplasmic mtDNA mutations were found. To identify proteins associated with these changes, for the first time we have compared the mitochondrial proteomes of mitochondria isolated from ROs and chromophobe RCCs as well as from normal kidney tissues by two-dimensional polyacrylamide gel electrophoresis. The proteome profiles were reproducible within the same group of tissues in subsequent experiments. The expression patterns within each group of samples were compared and 81 in-gel digested spots were subjected to nanoLC-MS/MS-based identification of proteins. Although the list of mitochondrial proteins identified in this study is incomplete, we identified the downregulation of NDUFS3 from complex I of the respiratory chain and upregulation of COX5A, COX5B, and ATP5H from complex IV and V in ROs. In chromophobe RCCs downregulation of ATP5A1, the alpha subunit of complex V, has been observed, but no changes in expression of other complexes of the respiratory chain were detected. To confirm the role of respiratory chain complex alterations in the morphological and/or functional changes in chromophobe RCCs and ROs, further studies will be necessary.

  13. Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Ferdous Rastgar Jazii; Zahra Najafi; Reza Malekzadeh; Thomas P Conrads; Abed Ali Ziaee; Christian Abnet; Mansour Yazdznbod; Ali Asghar Karkhane; Ghasem H Salekdeh

    2006-01-01

    AIM: To assess the proteome of normal versus tumor tissue in squamous cell carcinoma of the esophagus(SCCE) in Iranian patients and compare our results with former reports by using proteomics.METHODS: Protein was extracted from normal and tumor tissues. Two dimensional electrophoresis was carried out and spots with differential expression were identified with mass spectrometry. RNA extraction and RT-PCR along with immunodetection were performed.RESULTS: Fourteen proteins were found whose expression levels differed in tumor compared to normal tissues. Mass spectrometric analysis resulted in the identification of β-tropomyosin (TMβ), myosin light chain 2 (and its isoform), myosin regulatory light chain 2,peroxyredoxin 2, annexin I and an unknown polypeptide as the down regulated polypeptides in tumor tissue. Heat shock protein 70 (HSP70), TPM4-ALK fusion oncoprotein 2, myosin light polypeptide 6, keratin I, GH16431p and calreticulin were the up-regulated polypeptides found in tumor tissue. Several of these proteins, such as TMβ,HSP70, annexin I, calreticulin, TPM4-ALK and isoforms of myosins, have been well recognized in tumorigenesis of esophageal or other types of cancers.CONCLUSION: Our study not only supports the involvement of some of the formerly reported proteins in SCCE but also introduces additional proteins found to be lost in SCCF, including TMβ.

  14. Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas.

    Science.gov (United States)

    Bezerra, Stephania M; Chaux, Alcides; Ball, Mark W; Faraj, Sheila F; Munari, Enrico; Gonzalez-Roibon, Nilda; Sharma, Rajni; Bivalacqua, Trinity J; Burnett, Arthur L; Netto, George J

    2015-04-01

    Approximately 50% of penile squamous cell carcinomas (SCC) are associated with high-risk human papillomavirus (HR-HPV) infection. We evaluated the correlation of p16(INK4a) expression and HR-HPV with clinicopathological features and outcome in a cohort of patients with penile SCC. Two tissue microarrays were constructed from 53 invasive penile SCC at our hospital. p16(INK4a) expression was assessed by immunohistochemistry (CINtec Kit). High-risk human papillomavirus status was assessed by in situ hybridization (INFORM HPV III family 16 probe B cocktail). High-risk human papillomavirus was detected in 8 cases (15%), and p16(INK4a) overexpression was found in 23 cases (44%). Both markers showed a significant association with histologic subtype (P = .017 and P = .01, respectively) and lymphovascular invasion (P = .015 and P = .015, respectively). Regarding outcome analyses, neither HPV infection nor p16(INK4a) overexpression significantly predicted overall survival or cancer-specific survival using Cox proportional hazards regression model. High-risk human papillomavirus positivity and p16(INK4a) overexpression were significantly associated with histologic subtype and presence of lymphovascular invasion. Human papillomavirus status was not predictive of outcome in our cohort.

  15. Cyclin D1 expression in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tucci, S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Muglia, V.F. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Interna (Centro de Ciência da Imagem), Ribeirão Preto, SP, Brasil, Departamento de Medicina Interna (Centro de Ciência da Imagem), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Reis, R.B. Dos [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, G.E.B. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

  16. FADD Expression as a Prognosticator in Early-Stage Glottic Squamous Cell Carcinoma of the Larynx Treated Primarily With Radiotherapy

    NARCIS (Netherlands)

    Schrijvers, Michiel L.; Pattje, Wouter J.; Slagter-Menkema, Lorian; Mastik, Mirjam F.; Gibcus, Johan H.; Langendijk, Johannes A.; van der Wal, Jacqueline E.; van der Laan, Bernard F. A. M.; Schuuring, E.

    2012-01-01

    Purpose: We recently reported on the identification of the Fas-associated death domain (FADD) as a possible driver of the chromosome 11q13 amplicon and the association between increased FADD expression and disease-specific survival in advanced-stage laryngeal carcinoma. The aim of this study was to

  17. A genetic polymorphism affects the risk and prognosis of renal cell carcinoma: association with follistatin-like protein 1 expression

    Science.gov (United States)

    Liu, Yan; Han, Xue; Yu, Yongwei; Ding, Yibo; Ni, Chong; Liu, Wenbin; Hou, Xiaomei; Li, Zixiong; Hou, Jianguo; Shen, Dan; Yin, Jianhua; Zhang, Hongwei; Thompson, Timothy C.; Tan, Xiaojie; Cao, Guangwen

    2016-01-01

    Few single nucleotide polymorphisms (SNPs) associated with the risk of renal cell carcinoma (RCC) have been identified, yet genetic predisposition contributes significantly to this malignancy. We previously showed that follistatin-like 1 (FSTL1) was significantly down-regulated in clear cell RCC (ccRCC), in particular metastatic ccRCC. In the present study, we systemically investigated the associations of the 6 SNPs within FSTL1-coding genomic region with RCC risk and postoperative prognosis. Age- and gender-matched case-control study (417 vs 855) indicated that rs1259293 variant genotype CC was significantly associated with an increased risk of RCC, with an odds ratio of 2.004 (95% confidence internal [CI] = 1.190–3.375). Multivariate Cox regression analysis in 309 of 417 cases showed that rs1259293 genotype (CC vs TT + CT) independently predicted an unfavorable prognosis, with a hazard ratio of 2.531 (95% CI = 1.052–6.086). Expression of FSTL1 was significantly higher in adjacent renal tissues than in tumors, and significantly higher in the tissues with rs1259293 TT genotype than in those with rs1259293 TC+CC genotypes. rs1259293 C allele might generate a CTCF binding site that blocks trans-activation of FSTL1 expression. Our results indicate that rs1259293 is associated with an increased risk and unfavorable postoperative prognosis of RCC, possibly by down-regulating FSTL1 expression in renal tissues. PMID:27225192

  18. Cloning of Human Uroplakin Ⅱ Gene from Chinese Transitional Cell Carcinoma of Bladder and Construction of Its Eukaryotic Expression Vector

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To clone Uroplakin Ⅱ gene from Chinese transitional cell carcinoma (TCC) of bladder and construct its eukaryotic expression vector, the molecular cloning method was used to extract total RNA from a GⅢ/ T3N0M0 tissue sample of the bladder TCC patients. The primers were designed by Primer 5.0 software. Full length cDNA of Uroplakin Ⅱ gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), assayed by nucleic acid sequencing and then inserted between Xba Ⅰ and HindⅢ restrictive sites of eukaryotic expression vector pcDNA3.0. The recombinant was assayed by restricted enzyme digestion. Under the induction of Lipofectamine 2000, the recombinant was transfected into Uroplakin Ⅱ negative bladder cancer cell line EJ. Cellular expression levels of Uroplakin Ⅱ were detected by RT-PCR. The nucleic acid sequencing results indicated that Chinese Uroplakin Ⅱ cDNA (555 bp) was successfully cloned. The BLAST analysis demonstrated that the cloned sequence is 100 % homologous with sequences reported overseas. The GenBank accession number AY455312 was also registered. The results of restricted enzyme digestion indicated that eukaryotic vector pcDNA-UP Ⅱ for Uroplakin Ⅱ was successfully constructed.After being transferred with pcDNA-UPⅡ for 72 h, cellular Uroplakin Ⅱ mRNA levels were significantly improved (P<0.01). It is concluded that human Uroplakin Ⅱ gene was successfully cloned from Chinese TCC tissues, which provided a basis for further exploration of the roles of Uroplakin Ⅱ gene in TCC biological behaviors and potential strategies for targeted biological therapy of TCC.

  19. Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.

    Science.gov (United States)

    Zhang, Mingfeng; Liang, Liming; Morar, Nilesh; Dixon, Anna L; Lathrop, G Mark; Ding, Jun; Moffatt, Miriam F; Cookson, William O C; Kraft, Peter; Qureshi, Abrar A; Han, Jiali

    2012-04-01

    Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value <0.05 and false discovery rate (FDR) <0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.

  20. Expressão citofotométrica do marcador CD34 no carcinoma epidermóide de esôfago Citophotometric expression of CD34 in squamous cell carcinoma of the esophagus

    Directory of Open Access Journals (Sweden)

    Olímpia Alves Teixeira Lima

    2007-12-01

    clinical presentation, squamous cell carcinoma of the esophagus is well known to have one of the poorest prognoses, exhibiting high morbid-mortality rates. Molecular biology markers have been pointed out as great predictors in tumors diagnoses and staging. Angiogenesis, an essential event for tumor progression, can be studied using CD34 marker. AIM: To determine, by computerized image cytophotometric study, using SAMBA 4000, the expression of CD34 in squamous cell carcinoma of the esophagus and correlate the results with the clinical-pathological data (age, gender, differentiation tumor graduation, staging, size, tumor localization, depth, and lymph node metastases. METHODS: Twenty-nine recovery of sampled-tissue squamous cell carcinoma of the esophagus were evaluated using immunohistochemistry staining with anti-CD34 marker. Analysis of tumor expression marker was submitted to SAMBA reading using the following parameters: labeling index and optical density. Correlations among samples and statistical analysis were possible using SPSS program. RESULTS: The average labeling index for CD34 was 73,40% + 15,20 and as for optical density was 56,10 + 23,54 pixels. CD34 doe not show significant statistical correlation with clinical-pathological features considered (age, gender, differentiation tumor graduation, staging, size, tumor localization, depth, and lymph node metastases. CONCLUSION: CD34 marker demonstrates expression in squamous cell carcinoma of the esophagus, presenting a greater labeling index value than optical density. The respective tumor marker does not show correlation with the clinical-pathological features considered in the study.

  1. Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study

    Directory of Open Access Journals (Sweden)

    Wang Facheng

    2008-10-01

    Full Text Available Abstract Background p27Kip1 plays a major role as a negative regulator of the cell cycle. The regulation of p27Kip1 degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp 2 and cyclin-dependent kinase subunit (Cks 1. However, little is known regarding the prognostic utility of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma. Methods Immunohistochemistry was performed for p27Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. Results Immunoreactivity of p27Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P Kip1 levels (P = 0.006 and P Kip1 expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27Kip1 expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27Kip1 expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC. Conclusion Our results suggest that immunohistochemical expression levels of p27Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.

  2. Expression and Characterization of Catalytic Domain of T Cell Protein Tyrosine Phosphatase(ΔTC-PTP)——Immunohistochemical Study of ΔTC-PTP Expression in Non-small Cell Lung Carcinomas

    Institute of Scientific and Technical Information of China (English)

    ZHU Zhi-cheng; SUN Mei; ZHANG Xing-yi; LIU Ke-xiang; SHI Dong-lei; LI Jin-dong; SU Ji-quan; XU Yue-chi; FU Xue-qi

    2007-01-01

    This study objective was to express and characterize the catalytic domain of the human T cell protein tyrosine phosphatase(ΔTC-PTP) and to study immunohistochemically the expression of ΔTC-PTP in human non-small cell lung cancers. ΔTC-PTP gene was PCR amplified with the cDNA of human TC-PTP as template, and cloned into the pT7 expression vector. The recombinant pT7-ΔTC-PTP was expressed in E.coli Rosetta(DE3) host cells and purified. The enzymatic characteristics of ΔTC-PTP including enzyme activity and kinetics assay were measured. The antiserum was prepared by immunizing rabbit with the purified recombinant ΔTC-PTP. Rabbit polyclonal antibody against ΔTC-PTP was purified by PVDF immobilized antigen affinity chromatography. Immunohistochemical staining of lung cancer tissues was performed with antibody against ΔTC-PTP protein. ΔTC-PTP gene was correctly cloned, expressed, and purified. The recombinant ΔTC-PTP had a highly catalytic activity of PTPase. Squamous cell lung carcinoma showed a significantly higher expression rate of ΔTC-PTP(76.92%, 10/13) than adenocarcinoma(57.14%, 4/7) and normal lung tissue(20%, 1/5). This study represents the first demonstration that ΔTC-PTP is highly expressed in human squamous cell lung carcinomas. In addition, this study provides an important basis for further studying the biological function of TC-PTP and its relationship with lung carcinomas and other diseases.

  3. Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana [Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla (Mexico); Sandoval, Alejandro [School of Medicine FES Iztacala, National Autonomous University of Mexico (UNAM), Tlalnepantla (Mexico); Monroy, Alma; Felix, Ricardo [Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City (Mexico); Monjaraz, Eduardo, E-mail: emguzman@siu.buap.mx [Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla (BUAP), Puebla (Mexico)

    2010-12-03

    Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating the cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.

  4. Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells.

    Science.gov (United States)

    Hussain, Tajamul; Gupta, Sanjay; Adhami, Vaqar M; Mukhtar, Hasan

    2005-02-10

    Overexpression of cyclooxygenase (COX)-2 has been implicated in many pathologic conditions, including cancer. One practical inference of this finding is that sustained inhibition of COX-2 could serve as a promising target for prevention or therapy of cancer. Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells. Therefore, there is a need to define novel, nontoxic dietary constituents with proven chemopreventive effects through other pathways that also possess COX-2 but not COX-1 inhibitory activity. Recent studies on green tea and its major polyphenolic constituent (-)epigallocatechin-3-gallate (EGCG) have established its remarkable cancer preventive and some cancer therapeutic effects. Here, we show that EGCG inhibits COX-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate carcinoma cells. Based on our study, it is tempting to suggest that a combination of EGCG with chemotherapeutic drugs could be an improved strategy for prevention and treatment of prostate cancer.

  5. Clinico-pathological correlation of E-cadherin expression at the invasive tumor front of Indian oral squamous cell carcinomas: An immunohistochemical study

    Science.gov (United States)

    Mehendiratta, Monica; Solomon, Monica Charlotte; Boaz, Karen; Guddattu, Vasudeva; Mohindra, Aashima

    2014-01-01

    Background: Recent studies have indicated that although malignant cells at the invasive tumor front, bare morphological resemblance to the cells at central portion of the tumor, their molecular character differs significantly. E-cadherin is a cell-cell adhesion molecule that connects epithelial cells. This study attempts to correlate the E-cadherin expression at the invasive tumor front with tumor differentiation along with its clinico-pathological parameters. Materials and Methods: Immunohistochemical staining with E-cadherin was carried out on archival cases of primary oral squamous cell carcinomas (n = 30). The E-cadherin expression at the invasive tumor front was analyzed and was linked to clinico-pathological parameters including patient prognosis. Results: The downregulation of E-cadherin expression at the invasive tumor edge when compared with patient's prognosis yielded a significant correlation (P = 0.041) but its correlation with the degree of differentiation determined was not significant (P = 0.27). Also, its association with tumor size and lymph node status was negative. Conclusions: Loss of E-cadherin expression at the invasive tumor front is an important event in the progression of oral squamous cell carcinomas. Tumors with a loss of expression of E-cadherin are those which had a poor prognosis PMID:25328302

  6. Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy.

    Science.gov (United States)

    Kobayashi, Makoto; Ikezoe, Takayuki; Uemura, Yoshiki; Takeuchi, Tamotsu; Ueno, Hisayuki; Ohtsuki, Yuji; Taguchi, Hirokuni

    2007-06-01

    We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.

  7. Expression of Cell Cycle-associated Proteins p53, pRb, p16, p27, and Correlation With Survival: A Comparative Study on Oral Squamous Cell Carcinoma and Verrucous Carcinoma.

    Science.gov (United States)

    Vallonthaiel, Archana G; Singh, Manoj K; Dinda, Amit K; Kakkar, Aanchal; Thakar, Alok; Das, Satya N

    2016-03-01

    Verrucous carcinoma (VC) is a well-differentiated form of squamous cell carcinoma (SCC) with better prognosis. Differences in molecular pathogenesis between the 2 have not been well-characterized. We conducted this study to evaluate immunohistochemical expression of cell-cycle regulatory proteins p53, pRb, p16, and p27 in SCC and VC, compare the expression in these 2 neoplasms, and assess if these markers have any diagnostic or prognostic value. Sixty cases of SCC with and without lymph node metastasis and 31 cases of VC were studied. Immunohistochemical analysis for p53, pRb, p16, and p27 was performed and the results were analyzed. SCC was most frequent in tongue (52%), whereas VC in buccal mucosa (81%). Mean age of SCC patients was significantly lower than in VC. Majority of SCCs were in stage III and IV (63%), whereas VCs were in stage I and II (84%). p53 immunopositivity was more frequent in SCC (65%) than in VC (23%) (P≤0.001). VC had lower p53 as compared with well-differentiated SCC and SCC without lymph node metastasis. No significant difference was seen in pRb, p16, and p27 expression. Disease-free survival (DFS) at 1 year for SCC was 57% whereas it was 80% for VC (P=0.02). DFS and overall survival of SCC correlated with nodal status and stage; cell-cycle-associated protein expression had no association with DFS. To conclude, p53 immunoexpression differs in SCC and VC, suggesting different pathogenesis, and it may have some utility as an adjunct to morphology to differentiate between the 2. Expression of cell-cycle-associated proteins does not influence survival in SCC.

  8. E2F-Rb complexes assemble and inhibit cdc25A transcription in cervical carcinoma cells following repression of human papillomavirus oncogene expression

    DEFF Research Database (Denmark)

    Wu, L; Goodwin, E C; Naeger, L K;

    2000-01-01

    Expression of the bovine papillomavirus E2 protein in cervical carcinoma cells represses expression of integrated human papillomavirus (HPV) E6/E7 oncogenes, followed by repression of the cdc25A gene and other cellular genes required for cell cycle progression, resulting in dramatic growth arrest....... To explore the mechanism of repression of cell cycle genes in cervical carcinoma cells following E6/E7 repression, we analyzed regulation of the cdc25A promoter, which contains two consensus E2F binding sites and a consensus E2 binding site. The wild-type E2 protein inhibited expression of a luciferase gene...... linked to the cdc25A promoter in HT-3 cervical carcinoma cells. Mutation of the distal E2F binding site in the cdc25A promoter abolished E2-induced repression, whereas mutation of the proximal E2F site or the E2 site had no effect. None of these mutations affected the activity of the promoter...

  9. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    Science.gov (United States)

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy.

  10. Penis squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  11. Squamous cell carcinoma.

    Science.gov (United States)

    Webb, Julie L; Burns, Rachel E; Brown, Holly M; LeRoy, Bruce E; Kosarek, Carrie E

    2009-03-01

    Squamous cell carcinoma (SCC) is a relatively common, malignant neoplasm of dogs and cats that can arise in a variety of locations. The gross appearance of SCC can be variable and nonspecific, so definitive diagnosis requires microscopic examination of the tissue (cytology or histology). Several treatment modalities exist, but surgical excision, if possible, is regarded as the best treatment option. Early diagnosis and treatment of SCC are key because small, early-stage tumors are the most amenable to treatment and carry the best prognosis.

  12. MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Yamashita Shunichi

    2011-03-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is often diagnosed at later stages until they are incurable. MicroRNA (miR is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Methods Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Results Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2

  13. Correlation between vascular endothelial growth factor expression and presence of lymph node metastasis in advanced squamous cell carcinoma of the larynx

    Directory of Open Access Journals (Sweden)

    Rodrigo Gonzalez Bonhin

    2015-02-01

    Full Text Available Introduction: Squamous cell carcinoma is the most common neoplasm of the larynx, and its evolution depends on tumor staging. Vascular endothelial growth factor is a marker of angiogenesis, and its expression may be related to increased tumor aggressiveness, as evidenced by the presence of cervical lymphatic metastases. Objectives: To evaluate the expression of the vascular endothelial growth factor marker in non-glottic advanced squamous cell carcinoma of the larynx (T3/T4 and correlate it with the presence of cervical lymph node metastases. Methods: Retrospective clinical study and immunohistochemical analysis of vascular endothelial growth factor through the German scale of immunoreactivity in products of non-glottic squamous cell carcinomas. Results: This study analyzed 15 cases of advanced non-glottic laryngeal tumors (T3/T4, four of which exhibited cervical lymphatic metastases. There was no correlation between vascular endothelial growth factor expression and the presence of cervical metastases. Conclusion: Although vascular endothelial growth factor was expressed in a few cases, there was no correlation with the spread of cervical lymph metastases.

  14. Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. METHODS: In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients. RESULTS: In the first study investigating MDR-1 P-gp and MRP-1 protein expression patterns in renal cell carcinoma patients, high levels of expression of both efflux pumps are observed with 100% of tumours studied showing MDR-1 P-gp and MRP-1 positivity. CONCLUSION: Although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

  15. Signalling pathways involved in antitumoral effects of VIP in human renal cell carcinoma A498 cells: VIP induction of p53 expression.

    Science.gov (United States)

    Vacas, Eva; Muñoz-Moreno, Laura; Fernández-Martínez, Ana B; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2014-08-01

    Vasoactive intestinal peptide (VIP) decreases cell proliferation through PI3K signalling and prevents tumour progression in clear renal cell carcinoma (RCC). Here we analyzed the signalling pathways that mediate such VIP effects by using human RCC A498 cells. The effects of treatment with 1 μM VIP and/or specific protein kinase inhibitors such as H89, Wortmannin and PD98059 were studied by cell adhesion assay, ELISA of VEGF165 and ROS production assays. Semiquantitative RT-PCR and western blot were performed to study p53 expression. VIP increased cell adhesion and ROS production, and decreased VEGF165 secretion through PI3K signalling. Moreover, VIP increased nuclear expression of tumour suppressor p53. VIP effects could be blocked by cell incubation with a specific p53 inhibitor, cyclin pifithrin-α hydrobromide (CPFT-αH). In conclusion, this study provides a p53-dependent mechanism by which VIP regulates cell proliferation in RCC development. It supports a potential usefulness of VIP in new therapies of RCC.

  16. MicroRNA-17-5p post-transcriptionally regulates p21 expression in irradiated betel quid chewing-related oral squamous cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, S.Y. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Radiation-Oncology; HungKuang Univ., Taichung (China). Dept. of Biotechnology; Lin, K.C. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Oral and Maxillofacial Surgery; Chiou, J.F. [Taipei Medical Univ., Taipei (China). Dept. of Radiology; Taipei Medical Univ. Hospital, Taipei (China). Dept. of Radiation Oncology; Taipei Medical Univ. Hospital, Taipei (China). Dept. of Hospice and Palliative Center; Taipei Medical Univ. Hospital, Taipei (China). Cancer Center; Jeng, S.C. [Taipei Medical Univ. Hospital, Taipei (China). Dept. of Radiation Oncology; Cheng, W.H.; Chang, C.I. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Hemato-Ongology; Lin, W.C. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Div. of Thoracic Surgery; Wu, L.L. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Ophthalmology; Lee, H.L. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Radiation-Oncology; Chen, R.J. [National Taiwan Univ. Hospital and National Taiwan Univ., Taipei (China). Dept. of Obstetrics and Gynecology

    2013-08-15

    Background and purpose: Betel nut chewing is associated with oral cavity cancer in Taiwan. OC3 is an oral carcinoma cell line that was established from cells collected from a long-term betel nut chewer who does not smoke. After we found that microRNA-17-5p (miR-17-5p) is induced in OC3 cells, we used this cell line to examine the biological role(s) of this microRNA in response to exposure to ionizing radiation. Materials and methods: A combined SYBR green-based real-time PCR and oligonucleotide ligation assay was used to examine the expression of the miR-17 polycistron in irradiated OC3 cells. The roles of miR-17-5p and p21 were evaluated with specific antisense oligonucleotides (ODN) that were designed and used to inhibit their expression. Expression of the p21 protein was evaluated by Western blotting. The clonogenic assay and annexin V staining were used to evaluate cell survival and apoptosis, respectively. Cells in which miR-17-5p was stably knocked down were used to create ectopic xenografts to evaluate in vivo the role of miR-17-5p. Results: A radiation dose of 5 Gy significantly increased miR-17-5p expression in irradiated OC3 cells. Inhibition of miR-17-5p expression enhanced the radiosensitivity of the OC3 cells. We found that miR-17-5p downregulates radiation-induced p21 expression in OC3 cells and, by using a tumor xenograft model, it was found that p21 plays a critical role in increasing the radiosensitivity of OC3 cells in vitro and in vivo. Conclusion: miR-17-5p is induced in irradiated OC3 cells and it downregulates p21 protein expression, contributing to the radioresistance of OC3 cells. (orig.)

  17. ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells.

    Science.gov (United States)

    Léger, Karolin; Hopp, Ann-Katrin; Fey, Monika; Hottiger, Michael O

    2016-08-02

    ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27(Kip 1) protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27(Kip 1) stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism.

  18. Key peptide processing enzymes are expressed by a variant form of small-cell carcinoma of the lung.

    Science.gov (United States)

    North, W G; Du, J

    1998-01-01

    Small-cell carcinoma of the lung (SCCL) is a neuroendocrine tumor characterized by having the capacity to produce and secrete a number of small neuropeptides. These peptides serve the tumor as autocrine growth factors. SCCL is known to undergo a process of dedifferentiation to a variant (drug-resistant) form, and this process is associated with loss of marker enzymes such as neuron-specific enolase (NSE) and dopa decarboxylase (DDC). The current study was designed to discover if variant SCCL, represented by cell line NCI H82, retains some capacity to generate active neuropeptides (like vasopressin) from their precursors by continuing to express the three key classes of enzymes necessary for such conversions, namely prohormone convertases (PCs), carboxypeptidases (CPs), and peptidylglycine a-amidating monooxygenase (PAM). RT-PCR for mRNAs representing PC1, PC2, CPE, and PAM was performed on total RNA extracted from NCI H82. The primers selected for PCR and partial sequencing were synthetic 20, 21, 22, and 24 oligomers designed to yield products of 533, 880, 405, and 560 base pairs (bp) for PC1, PC2, CPE, and PAM, respectively. For the conditions used, we were able to demonstrate products for all four enzymes. Each of the four products generated were of the expected size. Cloning and sequencing of these products revealed that each had a structure identical to that published for the human form of the respective enzyme. Western analysis with antibodies against PC1, PC2, CPE, and PAM, provided evidence that mRNAs for the four enzymes are translated into proteins that could represent functional forms. Our findings therefore demonstrate that key enzymes involved in the generation of active neuropeptides, unlike the marker enzymes NSE and DDC, continue to be expressed by variant SCCL.

  19. A comparative analysis by SAGE of gene expression profiles of esophageal adenocarcinoma and esophageal squamous cell carcinoma

    NARCIS (Netherlands)

    van Baal, Jantine W. P. M.; Milana, Francesco; Rygiel, Agnieszka M.; Sondermeijer, Carine M. T.; Spek, C. Arnold; Bergman, Jacques J. G. H. M.; Peppelenbosch, Maikel P.; Krishnadath, Kausilia K.

    2008-01-01

    Esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC) are the two main types of esophageal cancer. Despite extensive research the exact molecular basis of these cancers is unclear. Therefore we evaluated the transcriptome of EA in comparison to non-dysplastic Barrett's esophag

  20. Krüppel-like factors 4 and 5 expression and their involvement in differentiation of oral carcinomas.

    Science.gov (United States)

    Shibata, Masaki; Chiba, Tadashige; Matsuoka, Takanori; Mihara, Nozomi; Kawashiri, Shuichi; Imai, Kazushi

    2015-01-01

    Proliferation-differentiation balance of epithelial cells is regulated by Krüppel-like factors (KLF) 4 and 5, and the unbalanced expression relates to carcinoma progression. However, little is known about the expression and role in oral carcinomas. This study examined expression of KLF4 and KLF 5 in the carcinomas by immunohistochemistry (n = 67) and the involvement in proliferation and differentiation of carcinoma cells. KLF4 was detected in keratinizing carcinoma cells and KLF5 in non-keratinizing cells. KLF4 staining declined in the patient with lymph node metastasis (P carcinoma progression through the dedifferentiation of carcinoma cells.

  1. Paraneoplastic hormones: parathyroid hormone-related protein (PTHrP) and erythropoietin (EPO) are related to vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma.

    Science.gov (United States)

    Feng, Chen-chen; Ding, Guan-xiong; Song, Ning-hong; Li, Xuan; Wu, Zhong; Jiang, Hao-wen; Ding, Qiang

    2013-12-01

    To investigate the correlation between parathyroid hormone-related protein (PTHrP), erythropoietin (EPO), and vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemical studies on PTHrP, EPO and VEGF were performed in 249 patients with ccRCC. Serum calcium level and haematocrit were analyzed. The expression of the factors and clinicopathological parameters were studied statistically for possible correlations. The incidence for hypercalcaemia and polycythaemia were 15.3% and 2.0% respectively. Expression of PTHrP, EPO, and VEGF were respectively related to advanced stage (P EPO and VEGF were correlated to tumour grade significantly. All factors were expressed higher in hypercalcaemic patients. PTHrP, EPO, and VEGF were positively correlated with each other in non-hypercalcaemic patients yet not in hypercalcaemic ones. PTHrP and EPO are related to VEGF expression and to the progression of ccRCC. This finding offers us new insight on the behaviour of ccRCC and offers possible targets in RCC treatment.

  2. Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

  3. EXPRESSIONS OF P53, PROLIFERATING CELL NUCLEAR ANITIGEN, BCL-2 PROTEIN AND THEIR SIGNIFICANCE IN SALIVARY ADENOID CYSTIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the effects of P53, PCNA, Bcl-2 protein and their relationship in salivary adenoid cystic carcinoma(SACC). Methods These proteins were examined by immunohistochemistry. Results Overexpressions of P53 and PCNA were revealed in ACC samples, they were higher than those in (polymorphous adenomas) PA, but expression of Bcl-2 protein was not different between ACC and PA. In 3 subtypes of ACC, expressions of 3 proteins were different. Conclusion Mutations of P53, Bcl-2 may be involed in the occurrence of SACC, expression of PCNA and mutation of P53 may coexist in the development of the SACC.

  4. The gene expression profiles of canine mammary cancer cells grown with carcinoma-associated fibroblasts (CAFs as a co-culture in vitro

    Directory of Open Access Journals (Sweden)

    Król Magdalena

    2012-03-01

    Full Text Available Abstract Background It is supposed that fibroblasts present in tumour microenvironment increase cancer invasiveness and its ability to metastasize but the mechanisms have not been clearly defined yet. Thus, the current study was designed to assess changes in gene expression in five various cancer cell lines grown as a co-culture with the carcinoma-associated fibroblasts (CAFs in vitro. Results A carcinoma-associated fibroblast cell line was isolated from a canine mammary cancer. Then, a co-culture of cancer cells with the CAFs was established and maintained for 72 hrs. Having sorted the cells, a global gene expression in cancer cells using DNA microarrays was examined. The analysis revealed an up-regulation of 100 genes and a down-regulation of 106 genes in the cancer cells grown as a co-culture with the CAFs in comparison to control conditions. The PANTHER binomial statistics tool was applied to determine statistically over-manifested pathways (p Conclusion The results of the current study showed that the co-culturing of cancer cells and the CAFs caused significant changes to the cancer gene expression. The presence of the CAFs in a microenvironment of cancer cells promotes adhesion, angiogenesis and EMT.

  5. Expression of placental protein 14 by the new endometrial cancer cell line MFE-280 in vitro and by endometrial carcinomas in vivo.

    Science.gov (United States)

    Hackenberg, R; Loos, S; Nia, A H; Kunzmann, R; Schulz, K D

    1998-01-01

    MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.

  6. Effects on Proliferation and Migration of the Human Colon Carcinoma Cell Line SW620 by Silencing of Hepatocyte Growth Factor Expression

    Institute of Scientific and Technical Information of China (English)

    Yi-tao JIA; Lei ZHANG; Yan LI; Ya-di WANG; Wei GUO; Lei CAO; Zhong-xin LI

    2010-01-01

    OBJECTIVE Hepatocyte growth factor (HGF) expression is closely related to the progression and poor prognosis of colorectal cancer patients. In this study, we investigated the effects on proliferation and migration of the human colon carcinoma cell line SW620 by silencing HGF expression. METHODS HGF was silenced using specifi c HGF α/β siRNA.The proliferation, migration, cell cycle and ultrastructure of SW620 cells were examined. RESULTS The transfection efficiency was 70%–80%. The expression rate of HGF in the experimental group was signifi cantly lower than that in the negative and blank control groups (P <0.05). The proliferation inhibition rate in the experimental group at 24, 48, 72 and 96 h after transfection was 14.2%, 50.2%, 39.5% and 23.2%, respectively. The migratory ability of cells in the experimental group was significantly inhibited compared with that in the negative control or blank control groups (58.2% vs. 2.1% or 0%, P < 0.05).CONCLUSION The application of RNA interference to silence the expression of HGF in the colon carcinoma cell line SW620 effectively inhibits the proliferation and migration of tumor cells.

  7. Influence of Ginkgo biloba extract on the proliferation, apoptosis of ACC-2 cell and Survivin gene expression in adenoid cystic carcinoma of lacrimal gland

    Institute of Scientific and Technical Information of China (English)

    Li-Xiao Zhou; Yu Zhu

    2012-01-01

    Objective: To explore the influence of extract of Ginkgo biloba (EGB) on the proliferation, apoptosis of ACC-2 cell and Survivin gene expression in adenoid cystic carcinoma (ACC) of lacrimal gland. Methods:ACC-2 cell in human with ACC of lacrimal gland was in vitro cultured. MTT method was used for cell proliferation detection. Annexin V/PI double-staining flow cytometer was used to detect cell apoptosis and cell cycle. Survivin gene expression was analyzed by RT-PCR and Western blotting. Results: EGB had inhibitory effect on the proliferation of ACC-2 cell with significant dose-effect relationship, and there was statistical difference when compared with the control group (P<0.01). The inhibitory concentration 50 % (IC50) is 88 mg/L. The flow cytometer test indicated that EGB can gradually increase ACC-2 cell in G0-G1 stage and decrease it in G2-M and S stage. With the increase of dose, the apoptosis rate of ACC-2 cell was obviously increased (P<0.05 or P<0.01). EGB had certain inhibitory effect on Survivin gene expression of ACC-2 cell, and Survivin gene expression was decreased with the increasing of the EGB concentration (P<0.01). Conclusions:EGB can effectively inhibit Survivin gene expression of ACC-2 cell in human with ACC of lacrimal gland, induce the apoptosis of ACC-2 cell and inhibit tumor cell proliferation.

  8. High-level expression of Notch1 increased the risk of metastasis in T1 stage clear cell renal cell carcinoma.

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    Qing Ai

    Full Text Available BACKGROUND: Although metastasis of clear cell renal cell carcinoma (ccRCC is basically observed in late stage tumors, T1 stage metastasis of ccRCC can also be found with no definite molecular cause resulting inappropriate selection of surgery method and poor prognosis. Notch signaling is a conserved, widely expressed signal pathway that mediates various cellular processes in normal development and tumorigenesis. This study aims to explore the potential role and mechanism of Notch signaling in the metastasis of T1 stage ccRCC. METHODOLOGY/PRINCIPAL FINDINGS: The expression of Notch1 and Jagged1 were analyzed in tumor tissues and matched normal adjacent tissues obtained from 51 ccRCC patients. Compared to non-tumor tissues, Notch1 and Jagged1 expression was significantly elevated both in mRNA and protein levels in tumors. Tissue samples of localized and metastatic tumors were divided into three groups based on their tumor stages and the relative mRNA expression of Notch1 and Jagged1 were analyzed. Compared to localized tumors, Notch1 expression was significantly elevated in metastatic tumors in T1 stage while Jagged1 expression was not statistically different between localized and metastatic tumors of all stages. The average size of metastatic tumors was significantly larger than localized tumors in T1 stage ccRCC and the elevated expression of Notch1 was significantly positive correlated with the tumor diameter. The functional significance of Notch signaling was studied by transfection of 786-O, Caki-1 and HKC cell lines with full-length expression plasmids of Notch1 and Jagged1. Compared to the corresponding controls, all cell lines demonstrated significant promotion in cell proliferation and migration while cell cycle remained unaffected. CONCLUSIONS/SIGNIFICANCE: High-level expression of Notch signaling increased the risk of metastasis in T1 stage ccRCC by stimulating the proliferation and migration of tumor cells, which may be helpful for the

  9. Epidermal growth factor receptor (EGFR mutations and expression in squamous cell carcinoma of the esophagus in central Asia

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    Abedi-Ardekani Behnoush

    2012-12-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC shows geographic variations in incidence, with high incidences (>50/105 person-years in central Asia, including North Eastern Iran (Golestan and Northern India (Kashmir. In contrast to Western countries, smoking does not appear to be a significant risk factor for ESCC in central Asia. In lung adenocarcinoma, activating mutations in the gene encoding epidermal growth factor receptor (EGFR are frequent in tumors of never smokers of Asian origin, predicting therapeutic sensitivity to Egfr-targeting drugs. Methods In this study 152 cases of histologically confirmed ESCC from Iran (Tehran and Golestan Province and North India (Kashmir Valley have been analyzed for EGFR mutation by direct sequencing of exons 18–21. Egfr protein expression was evaluated by immunohistochemistry in 34 samples from Tehran and HER2 mutations were analyzed in 54 cases from Kashmir. Results A total of 14 (9.2% EGFR variations were detected, including seven variations in exons. Among those, four (2.6% were already documented in lung cancers, two were reported as polymorphisms and one was a potentially new activating mutation. All but one variation in introns were previously identified as polymorphisms. Over-expression of Egfr was detected in 22/34 (65% of tested cases whereas no HER2 mutation was found in 54 cases from Kashmir. Conclusion Overall, EGFR mutations appear to be a rare event in ESCC in high incidence areas of central Asia, although a very small proportion of cases may harbor mutations predicting sensitivity to anti-Egfr drugs.

  10. Global Expression-Based Classification of Lymph Node Metastasis and Extracapsular Spread of Oral Tongue Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Xiaofeng Zhou

    2006-11-01

    Full Text Available Regional lymph node metastasis is a critical event in oral tongue squamous cell carcinoma (OTSCC progression. The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making for improved management of OTSCC patients. Global expressional profiles were obtained for 25 primary OTSCCs, where 11 cases showed lymph node metastasis (pN+ histologically and 14 cases were nonmetastatic (pN-. Seven of pN+ cases also exhibited extracapsular spread (ECS of metastatic nodes. Multiple expression indices were used to generate signature gene sets for pN+/- and ECS+/- cases. Selected genes from signature gene sets were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR. The classification powers of these genes were then evaluated using a logistic model, receiver operating characteristic curve analysis, leave-oneout cross-validation. qRT-PCR validation data showed that differences at RNA levels are either statistically significant (P<.05 or suggestive (P< .1 for six of eight genes tested (BMP2, CTTN, EEF1A1, GTSE1, MMP9, EGFR for pN+/- cases, for five of eight genes tested (BMP2, CTTN, EEF1A1, MMP9, EGFR for ECS+/- cases. Logistic models with specific combinations of genes (CTTN+MMP9+EGFR for pN and CTTN+EEFIA1+MMP9 for ECS achieved perfect specificity and sensitivity. Leave-one-out cross-validation showed overall accuracy rates of 85% for both pN and ECS prediction models. Our results demonstrated that the pN and the ECS of OTSCCs can be predicted by gene expression analyses of primary tumors.

  11. MiR-21 expression in the tumor stroma of oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Hedbäck, Nora; Jensen, David H; Specht, Lena;

    2014-01-01

    RNA-21 (miR-21) is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ...... hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC...... samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N...

  12. Expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine in esophageal squamous cell carcinoma and their relation to prognosis

    Institute of Scientific and Technical Information of China (English)

    Li-Yan Xue; Shuang-Mei Zou; Shan Zheng; Xiu-Yun Liu; Peng Wen; Yan-Ling Yuan; Dong-Mei Lin; Ning Lu

    2011-01-01

    Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 γ2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 γ2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 γ2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116 patients with advanced (stages II-IV) esophageal SCC using the tissue microarray-based immunohistochemistry and analyzed the correlation of the expressions with clinicopathologic characteristics and survival. We found that in normal esophageal tissues, laminin-5 γ2 chain was expressed in the basement membrane, whereas in esophageal SCC tissues, laminin-5 -γ2 chain was expressed in the cytoplasm of carcinoma cells, with a positive rate of 72.4‰. SPARC was not detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in 84.6‰ of esophageal SCC cases and in cancer cells in 7.8‰ of esophageal SCC cases. There was a significant correlation between laminin-5 γ2 chain and stromal SPARC expression in esophageal SCC (Spearman's rho = 0.423, P < 0.001). The expressions of both laminin-5 γ2 chain and stromal SPARC were correlated with survival (P = 0.032 and P = 0.034, respectively). In stage-Ⅱ esophageal SCC, the expression of laminin-5 γ2 chain was significantly correlated with survival (P = 0.023), while the expression of SPARC was not significantly correlated with survival (P = 0.154). Patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis than did those lacking elevated levels of laminin-5 γ2 chain expression and/or elevated levels of SPARC expression (P = 0.001). In stage-Ⅱ esophageal SCC, patients with elevated levels of laminin-5 γ2 chain and SPARC

  13. Tiam1 gene expression and its significance in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li Liu; De-Hua Wu; Yan-Qing Ding

    2005-01-01

    AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis.METHODS: Expressions of Tiam1 gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptasepolymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiam1 expression with the invasive ability was also analyzed.RESULTS: Tiam1 gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116,LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiam1 gene was highly related to the metastatic potential of colorectal carcinoma cells.CONCLUSION: Tiam1 gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

  14. Cyclooxygenase-2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinoma.

    Science.gov (United States)

    Moussa, Mona; Omran, Zeinab; Nosseir, Mona; Lotfy, Abeya; Swellam, Tarek

    2009-01-01

    Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins. It contributes to human carcinogenesis by various mechanisms. The aim of the current study was to elucidate the possible involvement of COX-2 in human bladder carcinoma by examining its expression on both urothelial and inflammatory cells in tissue biopsies and urine cytology samples of different urinary bladder lesions. A total of 65 patients were included in the study and were selected from cases admitted to Urology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. They represented seven control cases with almost normal-looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma (SqCC) (n=10). Immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections and urine cytology samples was performed for all cases using COX-2 (H-62): sc-7951, a rabbit polyclonal antibody. The study revealed positive COX-2 expression on the urothelial and inflammatory cells of cystoscopic biopsies from all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with 42.8% and 71.4% of normal controls, respectively. The score of urothelial COX-2 expression was sequentially up-regulated from normal to chronic cystitis (either pure or associated with premalignant changes) (pUrine cytology samples were positive for COX-2 in a comparable manner to that observed in cystoscopic biopsies. Accordingly, the results of the current study have provided new information in two aspects: First, is the possibility of using the differential COX-2 expression on both inflammatory and urothelial cells as markers for premalignant or malignant transformation; second, besides cystoscopy, urine cytology was found to have a high sensitivity for COX-2 expression and hence proved to be valuable in

  15. Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells

    DEFF Research Database (Denmark)

    Jørgensen, N; Rajpert-De Meyts, E; Graem, N;

    1995-01-01

    -like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first...

  16. Modulation of expression of the nuclear receptor NR0B2 (small heterodimer partner 1) and its impact on proliferation of renal carcinoma cells.

    Science.gov (United States)

    Prestin, Katharina; Olbert, Maria; Hussner, Janine; Isenegger, Tamara L; Gliesche, Daniel G; Böttcher, Kerstin; Zimmermann, Uwe; Meyer Zu Schwabedissen, Henriette E

    2016-01-01

    Mammalian nuclear receptors (NRs) are transcription factors regulating the expression of target genes that play an important role in drug metabolism, transport, and cellular signaling pathways. The orphan and structurally unique receptor small heterodimer partner 1 (syn NR0B2) is not only known for its modulation of drug response, but has also been reported to be involved in hepatocellular carcinogenesis. Indeed, previous studies show that NR0B2 is downregulated in human hepatocellular carcinoma, suggesting that NR0B2 acts as a tumor suppressor via inhibition of cellular growth and activation of apoptosis in this tumor entity. The aim of our study was to elucidate whether NR0B2 may also play a role in other tumor entities. Comparing NR0B2 expression in renal cell carcinoma and adjacent nonmalignant transformed tissue revealed significant downregulation in vivo. Additionally, the impact of heterologous expression of NR0B2 on cell cycle progression and proliferation in cells of renal origin was characterized. Monitoring fluorescence intensity of resazurin turnover in RCC-EW cells revealed no significant differences in metabolic activity in the presence of NR0B2. However, there was a significant decrease of cellular proliferation in cells overexpressing this NR, and NR0B2 was more efficient than currently used antiproliferative agents. Furthermore, flow cytometry analysis showed that heterologous overexpression of NR0B2 significantly reduced the amount of cells passing the G1 phase, while on the other hand, more cells in S/G2 phase were detected. Taken together, our data suggest that downregulation of NR0B2 may also play a role in renal cell carcinoma development and progression.

  17. Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas

    DEFF Research Database (Denmark)

    Mandel, U; Hassan, H; Therkildsen, M H

    1999-01-01

    Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc: polypeptide N -acetyl-galactosaminyltransferases (GalNAc-transferases). Individual GalNAc-transferases appear to have different functions and Northern analysis indicates that they are differently expressed in different organ...

  18. FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

    NARCIS (Netherlands)

    Koole, Koos; Clausen, Martijn J A M; van Es, Robert J. J.; van Kempen, Pauline M W; Melchers, Lieuwe J; Koole, Ron; Langendijk, Johannes A; van Diest, Paul J; Roodenburg, Jan L N; Schuuring, Ed; Willems, Stefan M

    2016-01-01

    INTRODUCTION: Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member protei

  19. FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

    NARCIS (Netherlands)

    Koole, Koos; Clausen, Martijn J. A. M.; van Es, Robert J. J.; van Kempen, Pauline M. W.; Melchers, Lieuwe J.; Koole, Ron; Langendijk, Johannes A.; van Diest, Paul J.; Roodenburg, Jan L. N.; Schuuring, Ed; Willems, Stefan M.

    2016-01-01

    Introduction Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member protein

  20. stathmin基因在喉鳞状细胞癌组织中的表达及意义%The expression stathmin gene in laryngeal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    张学聪; 曹华; 高冬玲

    2009-01-01

    Objective:To observe expression of stathmin gene in laryngeal squamous cell carcinoma(LSCC) and relation between expression of stathmin gene and occurance and development of LSCC.Method:The expression of the stathmin gene was determined in 35 LSCC of specimens and 18 normal laryngeal tissues(NLT) of specimens by in situ hybridizaion with Digoxigenin labled probe of stathmin mRNA.Result:Expression of stathmin gene was observed in 35 cases of laryneal squamous cell carcinoma tissue (positive rate, 69%) and positive signal was observed in both cytoplasm and nuclear. Among 18 cases of normal tissue, only 6 showed weak positive signal. There was significant difference in expression of stathmin gene between laryneal squamous cell carcinoma tissue and nomal tissue.Conclusion:Expreesion of stathmin gene may play a key role in the pathogenisis and development of laryneal squamous cell carcinoma. It may be a very important biotherapy target in the treatment of laryneal squamous cell carcinoma.%目的:探讨stathmin基因在人喉鳞状细胞细胞癌(LSCC)的表达及其与LSCC发生、发展之间的关系.方法:原位杂交方法检测stathmin mRNA在35例人LSCC组织及18例癌旁正常喉黏膜组织(NLT)中的表达情况.结果:在35例LSCC组织中有24例stathmin mRNA呈阳性表达(阳性率69%),阳性颗粒可见于细胞质及细胞核,18例NLT中6例呈弱阳性表达,差异有统计学意义(P<0.05).结论:stathmin基因在LSCC组织中高表达,stathmin基因高表达与LSCC组织的发生、发展有重要的相关性.

  1. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

    Science.gov (United States)

    Fadare, Oluwole; Liang, Sharon X

    2012-12-01

    Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear

  2. Expression and clinical significance of the Kv3.4 potassium channel subunit in the development and progression of head and neck squamous cell carcinomas.

    Science.gov (United States)

    Menéndez, Sofía Tirados; Rodrigo, Juan P; Allonca, Eva; García-Carracedo, Darío; Alvarez-Alija, Gustavo; Casado-Zapico, Sara; Fresno, Manuel F; Rodríguez, Carmen; Suárez, Carlos; García-Pedrero, Juana M

    2010-08-01

    The concept of ion channels as membrane therapeutic targets and diagnostic/prognostic biomarkers has attracted growing attention. We therefore investigated the expression pattern and clinical significance of the Kv3.4 potassium channel subunit during the development and progression of head and neck squamous cell carcinomas (HNSCCs). KCNC4 mRNA levels were determined by real-time RT-PCR in both HNSCC tissue specimens and derived cell lines. Kv3.4 protein expression was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 84 patients with laryngeal/pharyngeal squamous cell carcinomas and 67 patients with laryngeal dysplasias. Molecular alterations were correlated with clinicopathological parameters and patient outcome. Increased KCNC4 mRNA levels were found in 15 (54%) of 28 tumours, compared to the corresponding normal epithelia and varied mRNA levels were detected in 12 HNSCC-derived cell lines analysed. Increased Kv3.4 protein expression was observed in 34 (40%) of 84 carcinomas and also at early stages of HNSCC tumourigenesis. Thus, 35 (52%) of 67 laryngeal lesions displayed Kv3.4-positive staining in the dysplastic areas, whereas both stromal cells and normal adjacent epithelia exhibited negligible expression. No significant correlations were found between Kv3.4-positive expression in HNSCC and clinical data; however, Kv3.4 expression tended to diminish in advanced-stage tumours. Interestingly, patients carrying Kv3.4-positive dysplasias experienced a significantly higher laryngeal cancer incidence than did those with negative lesions (p = 0.0209). In addition, functional studies using HNSCC cells revealed that inhibition of Kv3.4 expression by siRNA leads to the inhibition of cell proliferation via selective cell cycle arrest at the G2/M phase without affecting apoptosis. Collectively, these data demonstrate for the first time that Kv3.4 expression is frequently increased during HNSCC tumourigenesis and correlated significantly with a

  3. Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients

    Directory of Open Access Journals (Sweden)

    Gallagher Michael F

    2009-12-01

    Full Text Available Abstract Background Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-like populations within malignancies. We aim to identify molecular mechanism associated with the generation of tumours with differing grades from malignant stem cell populations with different differentiation potentials. In this study we assessed microRNA (miRNA regulation in two populations of malignant Embryonal Carcinoma (EC stem cell, which differentiate (NTera2 or remain undifferentiated (2102Ep during tumourigenesis, and compared this to miRNA regulation in ovarian serous carcinoma (OSC patient samples. Methods miRNA expression was assessed in NTera2 and 2102Ep cells in the undifferentiated and differentiated states and compared to that of OSC samples using miRNA qPCR. Results Our analysis reveals a substantial overlap between miRNA regulation in 2102Ep cells and OSC samples in terms of miRNA biosynthesis and expression of mature miRNAs, particularly those of the miR-17/92 family and clustering to chromosomes 14 and 19. In the undifferentiated state 2102Ep cells expressed mature miRNAs at up to 15,000 fold increased levels despite decreased expression of miRNA biosynthesis genes Drosha and Dicer. 2102Ep cells avoid differentiation, which we show is associated with consistent levels of expression of miRNA biosynthesis genes and mature miRNAs while expression of miRNAs clustering to chromosomes 14 and 19 is deemphasised. OSC patient samples displayed decreased expression of miRNA biosynthesis genes, decreased expression of mature miRNAs and prominent clustering to chromosome 14 but not 19. This indicates that miRNA biosynthesis and levels of miRNA expression, particularly from chromosome 14, are tightly regulated both in progenitor cells and in tumour samples. Conclusion miRNA biosynthesis and

  4. Ziyuglycoside II-induced apoptosis in human gastric carcinoma BGC-823 cells by regulating Bax/Bcl-2 expression and activating caspase-3 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, A.K. [Department of General Surgery, Nanjing Medical University, Affiliated Hangzhou Hospital, Hangzhou (China); Zhou, H.; Xia, J.Z. [Department of General Surgery, Nanjing Medical University, Affiliated Wuxi Second Hospital, Wuxi (China); Jin, H.C. [Department of General Surgery, Nanjing Medical University, Affiliated Hangzhou Hospital, Hangzhou (China); Wang, K. [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Yan, J.; Zuo, J.B. [Department of General Surgery, Nanjing Medical University, Affiliated Wuxi Second Hospital, Wuxi (China); Zhu, X. [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Shan, T. [Department of General Surgery, Nanjing Medical University, Affiliated Wuxi Second Hospital, Wuxi (China)

    2013-08-13

    Ziyuglycoside II is an active compound of Sanguisorba officinalis L. that has anti-inflammation, antioxidation, antibiosis, and homeostasis properties. We report here on the anticancer effect of ziyuglycoside II on human gastric carcinoma BGC-823 cells. We investigated the effects of ziyuglycoside II on cell growth, cell cycle, and cell apoptosis of this cell line. Our results revealed that ziyuglycoside II could inhibit the proliferation of BGC-823 cells by inducing apoptosis but not cell cycle arrest, which was associated with regulation of Bax/Bcl-2 expression, and activation of the caspase-3 pathway. Our study is the first to report the antitumor potential of ziyuglycoside II in BGC-823 gastric cancer cells. Ziyuglycoside II may become a potential therapeutic agent against gastric cancer in the future.

  5. MiR-21 expression in the tumor stroma of oral squamous cell carcinoma: an independent biomarker of disease free survival.

    Directory of Open Access Journals (Sweden)

    Nora Hedbäck

    Full Text Available Oral squamous cell carcinoma (OSCC patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. MicroRNA-21 (miR-21 is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N-stage in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC.

  6. GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas.

    Science.gov (United States)

    Cimino-Mathews, Ashley; Subhawong, Andrea P; Illei, Peter B; Sharma, Rajni; Halushka, Marc K; Vang, Russell; Fetting, John H; Park, Ben Ho; Argani, Pedram

    2013-07-01

    GATA3 plays an integral role in breast luminal cell differentiation and is implicated in breast cancer progression. GATA3 immunohistochemistry is a useful marker of breast cancer; however, its use in specific subtypes is unclear. Here, we evaluate GATA3 expression in 86 invasive ductal carcinomas including triple-negative, Her-2, and luminal subtypes, in addition to 13 metaplastic carcinomas and in 34 fibroepithelial neoplasms. In addition, we report GATA3 expression in matched primary and metastatic breast carcinomas in 30 patients with known estrogen receptor (ER), progesterone receptor (PR), and Her-2 status, including 5 with ER and/or PR loss from primary to metastasis. Tissue microarrays containing 5 to 10 cores per tumor were stained for GATA3, scored as follows: 0 (0-5%), 1+ (6%-25%), 2+ (26%-50%), 3+ (51%-75%), and 4+ (>75%). GATA3 labeling was seen in 67% (66/99) of primary ductal carcinomas including 43% of triple-negative and 54% of metaplastic carcinomas. In contrast, stromal GATA3 labeling was seen in only 1 fibroepithelial neoplasm. GATA3 labeling was seen in 90% (27/30) of primary breast carcinomas in the paired cohort, including 67% of triple-negative carcinomas. GATA3 labeling was overwhelmingly maintained in paired metastases. Notably, GATA3 was maintained in all "luminal loss" metastases, which showed ER and/or PR loss. In conclusion, GATA3 expression is maintained between matched primary and metastatic carcinomas including ER-negative cases. GATA3 can be particularly useful as a marker for metastatic breast carcinoma, especially triple-negative and metaplastic carcinomas, which lack specific markers of mammary origin. Finally, GATA3 labeling may help distinguish metaplastic carcinoma from malignant phyllodes tumors.

  7. Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression

    NARCIS (Netherlands)

    B. Saltman; B. Singh; C.V. Hedvat; V.B. Wreesmann; R. Ghossein

    2006-01-01

    Background. Genetic screening studies suggest that genetic changes underlie progression from well differentiated, to anoplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression. Methods. Tissue microarrarys (TMAs)

  8. Effects of Tetrazanbigen on the Protein Expression in Human Hepatocellular Carcinoma Cell Line QGY-7701

    Institute of Scientific and Technical Information of China (English)

    Yonghua YUAN; Wei LI; Longjiang LI; Xiaolan YANG; Rong GU; Huabo LIU; Kaishun HUANG; Yu YU

    2009-01-01

    d per-oxiredoxin-1. These up-regulated or down-regulated proteins are mostly related to lipid metabolism. The TNBG antitumor mechanism is probably to influence tumor lipid metabolism, resulting in accu-mulation of LDs in tumor cells.

  9. Expression of PinX1 and hTERT in basal cell carcinoma and their implications

    Institute of Scientific and Technical Information of China (English)

    Long Qin; Jing Ge

    2015-01-01

    Objective This study aimed to investigate the expression and significance of PIN2/TERF1 interacting, telomerase inhibitor 1 (PinX1) and human telomerase reverse transcriptase (hTERT) in basal cel carcino-ma (BCC). Methods Real-time polymerase chain reaction and immunohistochemistry were performed to quantify the mRNA expressions and integrated optical density (IOD), respectively, of PinX1 and hTERT in BCC specimens (n = 30), as wel as in normal skin specimens (n = 15). Results The mRNA expression level and IOD of PinX1 in the BCC samples were both significantly lower than those in the control specimens (P 0.05). Conclusion Downregulation of PinX1 and upregulation of hTERT expression may be associated with the activation and maintenance of telomerases in the induction of BCC.

  10. Genomic Integration of High-Risk HPV Alters Gene Expression in Oropharyngeal Squamous Cell Carcinoma.

    Science.gov (United States)

    Walline, Heather M; Komarck, Christine M; McHugh, Jonathan B; Bellile, Emily L; Brenner, J Chad; Prince, Mark E; McKean, Erin L; Chepeha, Douglas B; Wolf, Gregory T; Worden, Francis P; Bradford, Carol R; Carey, Thomas E

    2016-10-01

    High-risk HPV (hrHPV) is the leading etiologic factor in oropharyngeal cancer. HPV-positive oropharyngeal tumors generally respond well to therapy, with complete recovery in approximately 80% of patients. However, it remains unclear why some patients are nonresponsive to treatment, with 20% of patients recurring within 5 years. In this study, viral factors were examined for possible clues to differences in tumor behavior. Oropharynx tumors that responded well to therapy were compared with those that persisted and recurred. Viral oncogene alternate transcripts were assessed, and cellular sites of viral integration were mapped and sequenced. Effects of integration on gene expression were assessed by transcript analysis at the integration sites. All of the tumors demonstrated active viral oncogenesis, indicated by expression of HPV E6 and E7 oncogenes and alternate E6 splicing. In the responsive tumors, HPV integration occurred exclusively in intergenic chromosome regions, except for one tumor with viral integration into TP63. Each recurrent tumor exhibited complex HPV integration patterns into cancer-associated genes, including TNFRSF13B, SCN2A, SH2B1, UBE2V2, SMOC1, NFIA, and SEMA6D Disrupted cellular transcripts were identified in the region of integration in four of the seven affected genes.

  11. Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma.

    Science.gov (United States)

    Martin, Tracey Amanda; Jiang, Wen Guo

    2014-01-01

    The tumor stem cell theory could explain how patients with metastatic disease show clinical relapse several months after starting treatment due to the survival of a small group of cells with unique characteristics. We examined the distribution and expression of a panel of stem cell markers in human breast cancer primary tumors. Human breast tissues were processed for immunohistochemistry, and RNA was extracted for analysis by quantitative-PCR. Immunohistochemical assay revealed that CD44 was strongly expressed in background endothelia and epithelia. CD133 expression was lost in tumor-associated endothelial cells. Conversely, CD49b was strongly stained in the tumors, associated vessels and ducts but was weakly stained in the background epithelia. q-PCR analysis revealed that CD44 and PSCA were reduced in patients with poor outcome (metastatic disease and death from breast cancer), with a marked reduction in ductal carcinoma, particularly with metastasis to bone although these did not reach significant difference. CD133 was significantly reduced in patients with metastatic disease and was also signif