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Cancer Tissues (cancer + tissue)
Kinds of Cancer Tissues Terms modified by Cancer Tissues Selected AbstractsChemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune responseCANCER SCIENCE, Issue 11 2007Keiichi Koizumi The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8+ and CD4+ T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. (Cancer Sci 2007; 98: 1652,1658) [source] Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004Julie E. Goodman Abstract Nitric oxide (NO·), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO· can activate p53, which can result in anti-carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO· induced p53 activation in vitro and found that NO· induced p53 accumulation and phosphorylation, particularly at ser-15, via ATM and ATR kinases, which then led to cell cycle arrest at G2/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53-P-ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM-2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C , A:T transitions at the CpG site of codon 248 and C:G , T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5-methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO· and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3,9, 2004. Published 2004 Wiley-Liss, Inc. [source] Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fluidsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Weizhu Zhu Abstract The assessment of DNA had demonstrated altered methylation in malignant compared to benign breast tissue. The purpose of our study was to (i) confirm the predictive ability of methylation assessment in breast tissue, and (ii) use the genes found to be cancer predictive in tissue to evaluate the diagnostic potential of hypermethylation assessment in nipple aspirate fluid (NAF) and mammary ductoscopic (MD) samples. Quantitative methylation specific (qMS)-PCR was conducted on three specimen sets: 44 malignant (CA) and 34 normal (NL) tissue specimens, 18 matched CA, adjacent normal (ANL) tissue and NAF specimens, and 119 MD specimens. Training and validation tissue sets were analyzed to determine the optimal group of cancer predictive genes for NAF and MD analysis. NAF and MD cytologic review were also performed. Methylation of CCND -2, p16, RAR -, and RASSF-1a was significantly more prevalent in tumor than in normal tissue specimens. Receiver operating characteristic curve analysis demonstrated an area under the curve of 0.96. For the 18 matched CA, ANL and NAF specimens, the four predictive genes identified in cancer tissue contained increased methylation in CA vs. ANL tissue; NAF samples had higher methylation than ANL specimens. Methylation frequency was higher in MD specimens from breasts with cancer than benign samples for p16 and RASSF-1a. In summary, i) routine quantitative DNA methylation assessment in NAF and MD samples is possible, and ii) genes hypermethylated in malignant breast tissue are also altered in matched NAF and in MD samples, and may be useful to assist in early breast cancer detection. [source] Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progressionINTERNATIONAL JOURNAL OF CANCER, Issue 6 2009Hiroshi Fujimoto Abstract There is growing evidence that tumor-associated macrophages (TAMs) promote tumor growth and dissemination. Many individual reports have focused on the protumor function of molecules linked to the recruitment of macrophages, but little is known about which factor has the strongest impact on recruitment of macrophages in breast cancer. To elucidate this question, we performed RT-PCR using species-specific primers and evaluated tumoral and stromal mRNA expression of macrophage chemoattractants separately in human breast tumor xenografts. The correlation between the tumoral or stromal chemoattractant mRNA expression including monocyte chemoattractant protein-1 (MCP-1) (CCL2), MIP-1, (CCL3), RANTES (CCL5), colony-stimulating factor 1, tumor necrosis factor ,, platelet-derived growth factor (PDGF)-BB and macrophage infiltration were compared. There was significant positive correlation between stromal MCP-1 expression and macrophage number (r = 0.63), and negative correlation between tumoral RANTES expression and macrophage number (r = ,0.75). However, no significant correlation was found for the other tumoral and stromal factors. The interaction between the tumor cells and macrophages was also investigated. Tumor cell,macrophage interactions augmented macrophage-derived MCP-1 mRNA expression and macrophage chemotactic activity in vitro. Treatment of immunodeficient mice bearing human breast cancer cells with a neutralizing antibody to MCP-1 resulted in significant decrease of macrophage infiltration, angiogenetic activity and tumor growth. Furthermore, immunohistochemical analysis of human breast cancer tissue showed stromal MCP-1 had a significant correlation with relapse free survival (p = 0.029), but tumoral MCP-1 did not (p = 0.105). These findings indicate that stromal MCP-1 produced as a result of tumor,stromal interactions may be important for the progression of human breast cancer and macrophages may play an important role in this tumor,stroma interaction. © 2009 UICC. [source] DHPLC is superior to SSCP in screening p53 mutations in esophageal cancer tissuesINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Osamu Yamanoshita Abstract Mutations of the p53 tumor-suppressor gene universally occur on exons 5,8 in human cancer. We analyzed these mutations in esophageal cancer tissue from 207 patients in China using 2 methods, single-strand conformation polymorphism (SSCP), one of the most frequently used methods, and the recently developed denaturing high-performance liquid chromatography (DHPLC), and compared their sensitivity and efficiency. Exons 5,8 of p53 were amplified from esophageal cancer tissue genomes, screened for fragments of mutations and polymorphisms by SSCP and DHPLC in a blind study and confirmed by direct sequencing to detect the mutations and polymorphisms. The numbers detected by DHPLC were greater than those detected by SSCP, though the rate of mutations and polymorphisms was lower in SSCP than in DHPLC, which appeared to detect smaller mutations (substitutions and 1 bp insertions/deletions). Of the mutations with substitutions detected by DHPLC but not by SSCP, 50% substituted adenosine for other nucleotides, suggesting that these mutations are often missed when SSCP is used. According to these data, the sensitivity of SSCP and DHPLC was 81% and 97%, respectively, and the specificity was 97% and 85%, respectively. Our results suggest that DHPLC may be recommended over SSCP when screening gene mutations. Thus, rates of p53 mutations and polymorphisms in esophageal cancer tissue in Chinese patients were 49% and 41% by DHPLC and SSCP, respectively. © 2004 Wiley-Liss, Inc. [source] Application of differential display, with in situ hybridization verification, to microscopic samples of breast cancer tissueINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2003Ruey Ho Kao Summary., The technique of differential display (DD) has been used widely to identify potentially interesting overexpressed or repressed genes in a variety of compared samples. When used in studying tissue samples, it inevitably confronts problems of limited amount of input material and cell-type heterogeneity. We report here the application of in situ hybridization as a method of confirmatory test for DD as well as definition of cell type expressing differential cDNA. This procedure employed material derived from a single case of human mammary, grade III, infiltrating ductal carcinoma, using free-hand microdissection, where we have compared gene expression profiles in invasive tumour with those in adjacent normal tissue. A total of 21 cDNAs were found to be differentially expressed between the two tissue types; 11 upregulated in the tumour sample and 10 upregulated in the normal sample. Six cDNAs were utilized as probes for in situ hybridization analysis of a further five cases of comparably staged breast cancer. One of these clones, 11AT1, which was found to be homologous to Hsc70, was shown to be overexpressed in tumour cells relative to adjacent normal stroma and to benign glandular epithelium in all five cases; an increase in expression was further confirmed at protein level by immunohistochemistry. The study demonstrated the applicability of in situ hybridization as a screening test in DD strategy for studying tissue material and a reasonable technique combination of identifying changes in gene expression associated with tumour development. [source] Expression of vascular endothelial growth factor in renal cell carcinoma is correlated with cancer advancementJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2003Ching-Chiang Yang Abstract Vascular endothelial growth factor (VEGF) functions as a regulator of neovascularization in malignant cells. VEGF as a mitogen is thought to alter renal cell carcinoma formation and tumor progression. We investigated the expression of the VEGF gene in order to evaluate its clinical significance in renal cell carcinoma. Tissue samples from 198 patients with renal cell carcinoma were examined with an immunohistochemical stain for the expression of the VEGF gene. The expression rate was compared to 34 normal renal cortical samples obtained from renal surgery from noncancer patients. There were significant differences between normal renal cortex (0%) and cancer tissue (54.5%) in positive staining of VEGF protein (P<0.001). With the progression of tumor grade, the positive rate of VEGF gene expression significantly increased. The expression rate of the VEGF gene in the advanced group, such as with lymph node involvement or vein invasion, was greater than that in the locally confined group (P<0.001). The results revealed that expression of the VEGF gene is proportional to the formation and progression of renal cell carcinoma, which may allow VEGF to be used as a prognostic marker for renal cell carcinoma. J. Clin. Lab. Anal. 17:85,89, 2003. © 2003 Wiley-Liss, Inc. [source] Expression of VEGF and its receptors Flt and KDR in gastric cancerJOURNAL OF DIGESTIVE DISEASES, Issue 4 2001Dongping Liu OBJECTIVE: The purpose of the present study was to investigate the correlation between the expression of vascular endothelial growth factor (VEGF), the expression of its receptors, Flt and KDR, and the biological behavior of gastric cancer. METHODS: Sixty cases of gastric cancer that had been diagnosed by surgery and pathology were studied with the method of semiquantitative reverse transcriptase,polymerase chain reaction (RT-PCR), to determine the expression of VEGF, Flt and KDR in gastric cancer tissue. RESULTS: The positive rates of VEGF, Flt and KDR in gastric cancer were 73.3, 86.7 and 80.0%, respectively. In pericancerous tissue, the rates were 43.3, 33.0 and 30.0%, respectively. There were significant differences between the groups with and without lymph node metastasis (P < 0.01). For gastric cancer patients with lymphatic metastasis, the positive rates for VEGF, Flt and KDR were 90.3, 80.6 and 96.8%, respectively; for patients without lymphatic metastasis, the rates were 51.7, 41.3 and 55.1%; there were significant differences between the groups with and without lymph node metastasis (P < 0.01). The positive rates of VEGF and KDR in well-differentiated gastric cancer were 40.0 and 46.7%, markedly lower than those of the poorly differentiated and undifferentiated gastric cancer groups. The rate of positive expression of Flt in the well-differentiated gastric cancer group was 73.3%. There was no significant difference between this rate and that of the poorly differentiated and undifferentiated groups (87.5%). The positive expression of VEGF, Flt and KDR was unrelated to the depth of infiltration. CONCLUSIONS: There are some correlations between VEGF, Flt and KDR and the biological behavior of gastric cancer. Knowing where they are expressed at high rates may be of help in evaluating the prognosis of gastric cancer. [source] Reduced expression of CD9 in oral squamous cell carcinoma: CD9 expression inversely related to high prevalence of lymph node metastasisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2001Jingo Kusukawa Abstract: Because CD9 is implicated in cell growth, cell adhesion and cell motility, altered CD9 expression might be involved in cancer invasion and metastasis. We have studied the immunolocalization of CD9 in oral squamous cell carcinoma (SCC). Sections prepared from paraffin-embedded specimens from patients with SCC of the oral cavity were stained with a monoclonal anti-CD9 antibody by means of the streptoavidin biotin method. Significant reduction or complete loss of CD9 expression was observed in cancer cells at the periphery of the cancer nests in the advancing front of invading tumor. Among 78 cases of oral SCCs examined, 46 (59.0%) cases were completely negative for CD9 expression. Loss of CD9 expression in cancer tissue strongly correlated with a high incidence of cervical lymph node metastasis and poorer prognosis (P=0.001). Thus a close examination of CD9 in SCC tissue would be useful for the prognosis of patients with oral carcinoma. [source] Low Ki-67 proliferation index is an indicator of poor prognosis in gastric cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Hee Eun Lee MD Abstract Background and Objectives We designed this study to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Methods Gastric cancer tissue from 245 patients were immunostained for Ki-67. Ki-67 PI was defined as the percentage of tumor cells positive for Ki-67. In addition, we have previously evaluated the expressions of nine epithelial mesenchymal transition (EMT)-related proteins. The relationship between Ki-67 PI and clinicopathologic parameters, patient survival, and EMT data were sought. Results Low Ki-67 PI was correlated with poorly differentiated histology (P,=,0.034), an advanced T stage (P,<,0.001), and lymph node metastasis (P,=,0.011). Also, the low PI group was found to have a significantly worse prognosis than the high PI group (P,=,0.003, log-rank test). Multivariate analysis revealed that Ki-67 PI remained as an independent prognostic factor (hazard ratio (95% CI),=,0.670 (0.450,0.999)). Furthermore, greater expressional changes of EMT-related proteins were found to be significantly associated with low Ki-67 PI (P,=,0.025). Conclusions These findings suggest that Ki-67 PI is an effective tool for predicting survival in gastric cancer. In addition, we found that an invasive property presented as EMT-related protein expressional changes was inversely correlated with a proliferative activity in gastric cancer. J. Surg. Oncol. 2010;102:201,206. © 2010 Wiley-Liss, Inc. [source] Expression of cyclooxygenase-2 in primary and remnant gastric carcinoma: Comparing it with p53 accumulation, Helicobacter pylori infection, and vascular endothelial growth factor expressionJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2002Atsushi Kawabe MD Abstract Background and Objectives Cyclooxygenase-2 (COX-2) expression may contribute to the synthesis of prostanoids, which have been related to carcinogenesis and tumor progression. It is well known that the gastric remnant is at greater risk of the development of gastric cancer than is the whole stomach; incidence rates for gastric cardia adenocarcinoma are rising in the United States and Europe. Our objective was to determine the involvement of COX-2 in primary and remnant gastric cancer tissues as well as in adjacent noncancerous mucosa. Methods We investigated the expression of COX-2 in 91 human gastric cancer tissue and adjacent noncancerous mucosa samples (40 remnant gastric cancer, 37 gastric cardia cancer, and 14 gastric corpus and antrum cancer), using immunohistochemistry. In addition, p53 expression, Helicobacter pylori infection, and vascular endothelial growth factor in the tissues were evaluated by immunohistochemical staining and compared with COX-2 expression. Results There were no significant differences in clinicopathological data in the gastric cancer tissues. There was a significant relation between the expression of COX-2 and p53 in gastric cancer tissues (P,=,0.0048). However, vascular endothelial growth factor expression and Helicobacter pylori infection showed no correlation with the expression of COX-2. In the case of adjacent noncancerous mucosa, the positive rate of COX-2 expression was significantly higher in the remnant gastric cancers (75.0%) than in the primary gastric cancers (25.5%) (P,<,0.0001). Conclusions This information may help in the analysis of the carcinogenesis of gastric cancer; there is also a possibility that the COX-2 selective inhibitor to the remnant gastric cancer has a chemopreventive effect. J. Surg. Oncol. 2002;80:79,88. © 2002 Wiley-Liss, Inc. [source] Fluorescence staining of human ovarian cancer tissue following application of 5-aminolevulinic acid: Fluorescence microscopy studiesLASERS IN SURGERY AND MEDICINE, Issue 5 2006Martin C. Löning Abstract Background and Objectives Application of 5-aminolevulinic acid (ALA) for fluorescence-guided second-look laparoscopy has been shown to be a promising new procedure in the early diagnosis of ovarian carcinoma metastases. However, for assessing the reliability of this method, information on the microscopic distribution of protoporphyrin IX (PP IX) in the tissue is needed. Additionally, the selectivity of PP IX uptake is essential for a potential photodynamic therapy (PDT) of ovarian cancer metastases. Study Design/Materials and Methods Thirty-six patients with epithelial ovarian cancer and two patients suffering from fallopian tube carcinoma underwent a laparoscopic second-look procedure 5 hours after the application of ALA. In 17 patients 36 fluorescence-guided biopsies were taken from fluorescing and non-fluorescing tissues for further evaluation. Fluorescence microscopy and digital image processing were utilized to determine the presence of PP IX fluorescence. Results A specificity of 88% and a sensitivity of 100% with a negative predictive value of 100% and a positive predictive value of 91% were calculated for PP IX fluorescence on a microscopic level as marker for ovarian cancer metastases. Conclusions On a microscopic scale, ALA-induced PP IX fluorescence is confined to ovarian cancer tumor tissue sparing stromal tissues. Lasers Surg. Med. © 2006 Wiley-Liss, Inc. [source] Prognostic and predictive value of HER2/neu oncogene in breast cancerMICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2002Shahla Masood Abstract Assessment of HER2/neu oncogene has been used as both a prognostic and predictive marker for breast cancer. However, the choice of the best method to assess the status of HER2/neu oncogene in breast cancer tissue remains controversial. A variety of techniques are available to detect HER2/neu gene amplification and overexpression. Tissue-based detection methods by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) offers a clear advantage over other approaches. FISH is a costly and relatively difficult assay and yet appears to be a better predictor of response to Herceptin® (Trastuzumab) therapy and patient outcome. IHC is less expensive and is easier to perform; however, it suffers from a high rate of false negativity and positivity as well as inter-observer variability among pathologists. Suggestions have been made to use IHC as a screening procedure followed by confirmation by FISH in selected cases. Considering the importance of an accurate assessment of HER2/neu oncogene in selecting therapy, a better alternative may be to use FISH as the primary testing for HER2/neu oncogene. Herceptin® therapy is associated with several side effects and is expensive. Thus, in the long term, it may be more cost-effective to use the FISH procedure and reduce the possibility of under-treatment or over-treatment of breast cancer patients. In addition, assessment of HER2/neu oncogene on every newly diagnosed early breast carcinoma may not be necessary. Metastatic lesions, when they occur, can be sampled by fine needle aspiration biopsy or core needle biopsy for assessment of HER2/Neu status. Microsc. Res. Tech. 59:102,108, 2002. © 2002 Wiley-Liss, Inc. [source] Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopyNMR IN BIOMEDICINE, Issue 4 2010Beathe Sitter Abstract Absolute quantitative measures of breast cancer tissue metabolites can increase our understanding of biological processes. Electronic REference To access In vivo Concentrations (ERETIC) was applied to high resolution magic angle spinning MR spectroscopy (HR MAS MRS) to quantify metabolites in intact breast cancer samples. The ERETIC signal was calibrated using solutions of creatine and TSP. The largest relative errors of the ERETIC method were 8.4%, compared to 4.4% for the HR MAS MRS method using TSP as a standard. The same MR experimental procedure was applied to intact tissue samples from breast cancer patients with clinically defined good (n,=,13) and poor (n,=,16) prognosis. All samples were examined by histopathology for relative content of different tissue types and proliferation index (MIB-1) after MR analysis. The resulting spectra were analyzed by quantification of tissue metabolites (,-glucose, lactate, glycine, myo-inositol, taurine, glycerophosphocholine, phosphocholine, choline and creatine), by peak area ratios and by principal component analysis. We found a trend toward lower concentrations of glycine in patients with good prognosis (1.1,µmol/g) compared to patients with poor prognosis (1.9,µmol/g, p,=,0.067). Tissue metabolite concentrations (except for ,-glucose) were also found to correlate to the fraction of tumor, connective, fat or glandular tissue by Pearson correlation analysis. Tissue concentrations of ,-glucose correlated to proliferation index (MIB-1) with a negative correlation factor (,0.45, p,=,0.015), consistent with increased energy demand in proliferating tumor cells. By analyzing several metabolites simultaneously, either in ratios or by metabolic profiles analyzed by PCA, we found that tissue metabolites correlate to patients' prognoses and health status five years after surgery. This study shows that the diagnostic and prognostic potential in MR metabolite analysis of breast cancer tissue is greater when combining multiple metabolites (MR Metabolomics). Copyright © 2010 John Wiley & Sons, Ltd. [source] Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using 1H and 31P magic angle spinning MRS of intact tissueNMR IN BIOMEDICINE, Issue 2 2009Sonali S. De Silva Abstract The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n,=,5), cervical intraepithelial neoplasia (CIN; mild, n,=,5; moderate/severe, n,=,40), and invasive cancer (n,=,23). 1H HR-MAS MRS data were acquired using a Bruker Avance 11.74,T spectrometer (Carr,Purcell,Meiboom,Gill sequence; TR,=,4.8,s; TE,=,135,ms; 512 scans; 41,min acquisition). 31P HR-MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a 1H-decoupled pulse-acquire sequence (TR,=,2.82,s; 2048 scans; 96,min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P,=,0.0001) and phosphocholine (P,=,0.002) in tissue from patients with cancer than from patients with high-grade dyskaryosis, but no differences between non-cancer groups. Division by histology of the sample also showed increases in choline (P,=,0.002) and phosphocholine (P,=,0.002) in cancer compared with high-grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P,=,0.0001). Estimated concentrations of alanine (P,=,0.01) and creatine (P,=,0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non-cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non-cancer patients (P,=,0.0001). Estimated concentrations of choline-containing metabolites increased from pre-invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue. Copyright © 2008 John Wiley & Sons, Ltd. [source] High-resolution magic angle spinning MRS of breast cancer tissueNMR IN BIOMEDICINE, Issue 5 2002Beathe Sitter Abstract High-resolution magic angle spinning (HR MAS) may develop into a new diagnostic tool for studying intact tissue samples, and several types of cancer have been investigated with promising results. In this study HR MAS spectra of breast cancer tissue from 10 patients have been compared to conventional high-resolution spectra of perchloric acid extracts of the same tissue type. The HR MAS spectra show resolution comparable to spectra of extracts, and two-dimensional techniques lead to identification of a majority of the constituents. More than 30 different metabolites have been detected and assigned. To our knowledge this is the most detailed assignment of biochemical components in intact human breast tissue. The spectra of intact breast cancer tissue differ from perchloric acid extracts by the presence of lipids and fewer signals in the low field region. HR MAS analysis of intact breast tissue specimens is a rapid method, providing spectra with resolution where relative quantification of the majority of the detected metabolites is possible. Copyright © 2002 John Wiley & Sons, Ltd. [source] Downregulation of Krüppel-like factor 9 in human colorectal cancerPATHOLOGY INTERNATIONAL, Issue 6 2008Ling Kang Mammalian Sp and Krüppel-like factors (KLF), a family of zinc finger-containing transcription factors, are involved in growth control, proliferation, apoptosis and angiogenesis of a wide variety of tissues and cells. Several KLF have been linked to various types of human cancers, but the relationship between Krüppel-like factor 9 (KLF9) and colorectal cancer has not been explored. The purpose of the present study was to investigate KLF9 expression in human colorectal cancer tissue. KLF9 mRNA was detected on quantitative real-time reverse transcriptase,polymerase chain reaction (Q-PCR). Of the 50 cancerous tissues examined, 86% (43/50) expressed lower levels of KLF9 mRNA than individually matched normal mucosa (P < 0.0001). On western blot, reduced or absent expression of KLF9 protein was observed in 65% (13/20) of the samples (P < 0.01). A total of 81% (35/43) of normal samples had expression of KLF9 protein, whereas its protein was detected in only 9% (4/43) of tumor tissues (P < 0.001) on tissue microarray. These results indicate that KLF9 may be involved in the carcinogenesis of human colorectal cancer. [source] Apoptosis regulators Fau and Bcl-G are down-regulated in prostate cancerTHE PROSTATE, Issue 14 2010Mark R. Pickard Abstract BACKGROUND The molecular control of cell death through apoptosis is compromised in prostate cancer cells, resulting in inappropriate cell survival and resistance to cytotoxic therapy. Reduced expression of the functionally connected apoptosis-regulators and candidate tumor suppressors Fau and Bcl-G has recently been implicated in oncogenesis in other tissues. The present study examines the hypothesis that reduced expression of these genes may be involved in prostate cancer. METHODS Fau and Bcl-G mRNA levels were determined by real time RT-PCR in two independent prostate tissue collections. In experiments in vitro, Fau and Bcl-G levels in prostate cancer cell lines were reduced using RNA interference and the effects on sensitivity to UVC irradiation were determined. RESULTS Fau and Bcl-G mRNA levels were both lower in prostate cancer tissue than in normal prostate and Benign Prostate Hyperplasia. Active down-regulation of Fau and Bcl-G expression in vitro resulted in decreased sensitivity to UVC-induced cytotoxicity. Simultaneous down-regulation of Fau and Bcl-G produced a decrease in sensitivity which was similar to either gene alone. CONCLUSIONS Fau and Bcl-G mRNA levels are both decreased in prostate cancer. In prostate cancer cell lines in vitro such down-regulation results in reduced sensitivity to UVC-induced cytotoxicity, consistent with the putative roles of these genes as candidate prostate tumor suppressors. The absence of an additive effect when Fau and Bcl-G were down-regulated simultaneously is consistent with the two genes acting in the same apoptosis pathway, for example, with the pro-apoptotic effects of Fau being mediated through modulation of Bcl-G. Prostate 70: 1513,1523, 2010. © 2010 Wiley-Liss, Inc. [source] Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissueTHE PROSTATE, Issue 8 2009Thomas J. Walton Abstract BACKGROUND Real-time quantitative RT-PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ER,) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. METHODS Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT-PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ER,), estrogen receptor alpha (ER,), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann,Whitney U -test. Correlation coefficients were analyzed using Spearman's test. RESULTS Significant positive correlations were seen when AR and AR-dependent PSA, and ER, and ER,-dependent PGR were compared, indicating a representative population of RNA transcripts. ER, gene expression was significantly over-expressed in the cancer group compared with benign controls (P,<,0.01). In contrast, PGR expression was significantly down-regulated in the cancer group (P,<,0.05). There were no significant differences in AR, ER, or PSA expression between the groups. This study represents the first to show an upregulation of ER, gene expression in laser microdissected prostate cancer specimens. CONCLUSIONS In concert with recent studies the findings suggest differential production of ER, splice variants, which may play important roles in the genesis of prostate cancer. Prostate 69: 810,819, 2009. © 2009 Wiley-Liss, Inc. [source] Protein tyrosine phosphatase PTP1B is involved in neuroendocrine differentiation of prostate cancerTHE PROSTATE, Issue 11 2006Chengyu Wu Abstract BACKGROUND Prostate cancer (PC) contains a minor component of neuroendocrine (NE) cells that may stimulate androgen-independent growth of the tumor. The mechanism of neuroendocrine differentiation remains unknown. METHODS The expression of PTP1B, a protein tyrosine phosphatase, was studied in LNCaP cells induced to show neuroendocrine phenotype by androgen withdrawal. Wild-type PTP1B and its dominant-negative mutant were transfected into LNCaP cells to study their effects on neuroendocrine differentiation. In vivo expression of PTP1B in human prostate cancer was studied by immunohistochemistry. RESULTS Androgen withdrawal of LNCaP cells led to increased expression of PTP1B with a corresponding increase in its tyrosine phosphatase activity. Overexpression of PTP1B in LNCaP cells led to neuroendocrine differentiation while expression of its dominant-negative mutant inhibited neuroendocrine differentiation. Immunohistochemical study showed that PTP1B was exclusively expressed in neuroendocrine cells of human prostate cancer tissue. Conclusion Our findings suggest that PTP1B plays an important role in neuroendocrine differentiation, and therefore, may possibly be involved in the progression of prostate cancer. Prostate © 2006 Wiley-Liss, Inc. [source] Methylation of the ASC gene promoter is associated with aggressive prostate cancerTHE PROSTATE, Issue 7 2006Rachael L. Collard Abstract Background The aim of this study was to investigate the methylation status of apoptosis-associated speck-like protein containing a CARD (ASC; TMS1; PYCARD) in prostate cancer cell lines and human tissues and to determine if those findings correlate with the clinicopathological features of prostate cancer. Methods Genomic DNA was isolated from prostate cell lines and microdissected tissues, bisulfite converted and analyzed by methylation specific polymerase chain reaction (MSP). Expression of ASC in prostate cancer cell lines treated with or without methylation inhibitors was determined by quantitative or qualitative RT-PCR. Results ASC gene expression was silenced or reduced in five prostate cancer cell lines and correlated with methylation status. Treatment of MDAPCa2b prostate cancer cells with the methylation inhibitors 5-aza-2-deoxycitidine and Zebularine reactivated expression of ASC. Of 58 prostate cancer specimens, methylation of the ASC promoter region was present in 65% of primary cancer tissue, 64% (7/11) of cancer-associated high grade-prostatic intraepithelial neoplasia (HG-PIN), and 28% of normal-appearing but adjacent to tumor prostate tissue. While ASC methylation was not related to Gleason score (P,=,0.46) or pathological stage (P,=,0.75), there was a significantly higher frequency of ASC methylation in the adjacent normal tissue for patients with biochemical recurrence (P,=,0.0383). Conclusions Methylation of the ASC gene promoter is both a frequent and early event in prostate cancer carcinogenesis. Surprisingly, methylation of the adjacent normal tissue occurs significantly more often in patients who later undergo biochemical recurrence, suggesting a role for inactivation of the ASC gene in the initial stages of aggressive disease. Prostate © 2006 Wiley-Liss, Inc. [source] Expression of androgen receptor coactivators in normal and cancer prostate tissues and cultured cell linesTHE PROSTATE, Issue 3 2003C. Mestayer Abstract BACKGROUND In prostate cancer cell lines, androgen receptor (AR) coactivators modulate the transcriptional activity of AR. However, very little is known about their expression in normal prostate tissue and during progression to cancer. METHODS AR and coactivators ARA54, ARA55, ARA70, and SRC1 RNA were analyzed by RT-PCR in normal and tumoral tissues of the same prostate, in prostate cell lines, and after hormonal treatments of prostate epithelial cells. RESULTS AR-coactivators were expressed in normal and tumoral tissues and in cultured prostate cells; only ARA55 expression was decreased in tumoral relative to normal tissue of all seven prostates analyzed. It was not expressed in LNCaP and DU145 cancer cells and low in PNT2 immortalized cells in which all coactivator's expression were down regulated by DHT and up regulated by E2. In addition, coactivator's expression was increased in hyperplastic relative to normal prostate fibroblasts. CONCLUSIONS ARA55 is both an AR coactivator and a focal adhesion protein (Hic-5). Its role in the progression of prostate carcinoma may therefore involve these two different functions. Its decrease in cancer tissue suggests that it plays a different role than that expected, namely, facilitate cell proliferation and therefore mobility and metastasis. Prostate 56: 192,200, 2003. © 2003 Wiley-Liss, Inc. [source] Stereologic estimation of the total numbers, the composition and the anatomic distribution of lymphocytes in cone biopsies from patients with stage I squamous cell carcinoma of the cervix uteri,APMIS, Issue 12 2007BETTINA S. NEDERGAARD The aim of this study was to present a method to obtain basic biological data on the in situ cellular immune response towards cancer. Using stereology, we estimated the density and frequency of immune cells of 10 different phenotypes in cone biopsies from 20 patients with FIGO stage I cervical squamous cell carcinoma. The anatomic distribution of immune cells with respect to intraepithelial, periepithelial or stromal compartments was recorded in normal epithelium, dysplastic epithelium and carcinoma. We estimated the number of immune cells per cancer cell, and the 3D total number of immune cells, inside cancer tissue. The tumor volume was estimated in 3D and corrected for shrinkage occurring during tissue processing. We found more immune cells in cancer compared to dysplasia and normal epithelia. A median total number of 278 ? 103 CD3+, 69.1 ? 103 CD4+ and 113 ? 103 CD8+ cells were present in the cancers. A median number of 63 CD3+, 11 CD4+ and 29 CD8+ cells were present per cancer cell. The average volume of tumors in stage IA was significantly smaller than that of stage IB. This method was found to be usable and of potential value in clinical pathology research, and for development and evaluation of immunotherapy. [source] Expression of the endogenous, nicotinic acetylcholine receptor ligand, SLURP-1, in human colon cancerAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2008A. Pettersson Summary 1,Secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is a recently discovered endogenous ligand at the ,7 subunit of the nicotinic acetylcholine receptors. Previous reports have shown that SLURP-1 is expressed in normal human keratinocytes seemingly with a pro-apoptotic function. Conversely, such expression was markedly attenuated in transformed cells and it was suggested that the molecule could convey protection against malignant transformation. 2,In this study, we demonstrated the mRNA expression (by RT-PCR) and protein expression (by Western blotting and immunocytochemistry) of SLURP-1 in the human colon cancer cell line, HT-29. 3,Furthermore, we demonstrated the expression of SLURP-1 (by immunohistochemistry) in tumour cells of human colon cancer tissue, and, to a greater extent, in immune and smooth muscle cells of adjacent, macroscopically tumour-free colon tissue. 4,The current findings suggest that SLURP-1 participates in the regulation of gut immune functions and motility, as well as possibly playing a role in colon carcinogenesis/cancer progression. [source] Characterisation of normal and cancer stem cells: One experimental paradigm for two kinds of stem cellsBIOESSAYS, Issue 9 2009Jean-François Mayol Abstract The characterisation of normal stem cells and cancer stem cells uses the same paradigm. These cells are isolated by a fluorescence-activated cell sorting step and their stemness is assayed following implantation into animals. However, differences exist between these two kinds of stem cells. Therefore, the translation of the experimental procedures used for normal stem cell isolation into the research field of cancer stem cells is a potential source of artefacts. In addition, normal stem cell therapy has the objective of regenerating a tissue, while cancer stem cell-centred therapy seeks the destruction of the cancer tissue. Taking these differences into account is critical for anticipating problems that might arise in cancer stem cell-centred therapy and for upgrading the cancer stem cell paradigm accordingly. [source] DNA content in the diagnostic biopsy for benign-adjacent and cancer-tissue areas predicts the need for treatment in men with T1c prostate cancer undergoing surveillance in an expectant management programmeBJU INTERNATIONAL, Issue 3 2010Sumit Isharwal Study Type , Prognosis (case series)Level of Evidence 4 OBJECTIVE To assess the DNA content in benign-adjacent and cancer-tissue areas of a diagnostic biopsy, to predict which patients would subsequently develop an unfavourable biopsy necessitating treatment for prostate cancer in the expectant management (EM) programme. PATIENTS AND METHODS Of 71 patients who had benign-adjacent and cancer-tissue areas of diagnostic biopsies available, 39 developed unfavourable biopsies (Gleason score ,7, Gleason pattern 4/5, three or more cores positive for cancer, >50% of any core involved with cancer), while 32 maintained favourable biopsies on annual surveillance examination (median follow-up 3.7 years). DNA content was measured on Feulgen-stained biopsy sections using an automatic imaging system (AutoCyteTM, TriPath Imaging Inc, Burlington, NC, USA). Cox proportional-hazard regression and Kaplan-Meier plots were used to identify significant predictors for unfavourable biopsy conversion. RESULTS Univariately, DNA content measurements i.e. an excess of optical density (OD) in the benign-adjacent tissuer area, and the sd of the OD in the cancer tissue were significant, with a hazard ratio and 95% confidence interval of 2.58 (1.17,5.68; P = 0.019) and 5.36 (1.89,15.24; P = 0.002), respectively, for predicting unfavourable biopsy conversion that required intervention. Also, several other DNA content measurements in benign-adjacent and cancer-tissue areas showed a trend to statistical significance. Further, benign-adjacent excess of OD (3.12, 1.4,6.95; P = 0.005) and cancer sd of OD (5.88, 2.06,16.82; P = 0.001) remained significant in the multivariate model to predict unfavourable biopsy conversion. Patients with benign-adjacent excess of OD > 25.0 and cancer sd of OD of >4.0 had the highest risk for unfavourable biopsy conversion (P < 0.001). CONCLUSIONS DNA content measurements in the benign-adjacent and cancer-tissue areas appear to be useful for predicting unfavourable biopsy conversion (a recommendation for intervention) on annual surveillance examinations in the EM programme. [source] The effect of serotonin and serotonin antagonists on bladder cancer cell proliferationBJU INTERNATIONAL, Issue 3 2006EMAD J. SIDDIQUI OBJECTIVE To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3). MATERIALS AND METHODS HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT1A, 5HT1B, 5HT1D, 5HT2, 5HT3 and 5HT4). After 72 h, cell viability was assessed using the crystal violet assay. The presence of 5HT receptor subtypes on HT1376 cells and sections of human bladder cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS 5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10,8m as compared to the control at 72 h. At 10,4m, 5HT1A antagonist (NAN-190 hydrobromide) and 5HT1B antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT1A and 5HT1B receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT1A and 5HT1B receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION 5HT1A and to a greater extent 5HT1B antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT1A and 5HT1B receptors. These results highlight the potential use of 5HT1A and 5HT1B antagonists in the treatment of bladder cancer. [source] A clinicopathological study of the expression of extracellular matrix components in urothelial carcinomaBJU INTERNATIONAL, Issue 4 2005Elli Ioachim OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27,89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. [source] Establishing a national tissue bank for surgically harvested cancer tissueBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2004K. Knox Surgeons have a part to play [source] Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancerCANCER, Issue 8 2008Aurelia Noske MD Abstract BACKGROUND The human nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) mediates the nuclear export of proteins and messenger RNAs and, thus, is an important regulator of subcellular distribution of key molecules. Whereas cell-biologic studies have suggested a fundamental role for CRM1 in the regulation of mitosis, the expression of this protein in human tumor tissue has not been investigated to date. METHODS In this study, the expression of CRM1 was analyzed in a cohort of 88 ovarian tumors and 12 ovarian cell lines for the first time to the authors' knowledge. RESULTS Immunohistochemistry revealed increased nuclear (52.7%) and cytoplasmic (56.8%) expression of CRM1 in 74 carcinomas compared with the expression revealed in borderline tumors and benign lesions. Similarly, CRM1 expression was increased in ovarian cancer cell lines compared with human ovarian surface epithelial cells. Cytoplasmic CRM1 expression was related significantly to advanced tumor stage (P = .043), poorly differentiated carcinomas (P = .011), and higher mitotic rate (P = .008). Nuclear CRM1 was associated significantly with cyclooxygenase-2 (COX-2) expression (P = .002) and poor overall survival (P = .01). Because it was demonstrated previously that blocking of CRM1 by leptomycin B (LMB) contributes to the inhibition of nuclear export, the authors used a set of mechanistic assays to study the effects of CRM1 inhibition in cancer cells. Treatment of OVCAR-3 cells with LMB revealed a significant reduction of cell proliferation and increased apoptosis as well as suppressed interleukin-1,-induced COX-2 expression. CONCLUSIONS The current results indicated that CRM1 is expressed in a subpopulation of ovarian carcinomas with aggressive behavior and is related to poor patient outcome. A correlation also was demonstrated between CRM1 and COX-2 expression in ovarian cancer tissue. Furthermore, the treatment of ovarian cancer cells with LMB revealed a reduction in COX-2 expression. Therefore, the authors suggest that CRM1 may be an interesting biomarker for the assessment of patient prognosis and a molecular target for anticancer treatment. Cancer 2008. © 2008 American Cancer Society. [source] | ||||||||||||||||||||||||||||||||||