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Carcinoma Tissues (carcinoma + tissue)
Kinds of Carcinoma Tissues Selected AbstractsDifferent roles of proteolipids and 70-kDa subunits of V-ATPase in growth and death of cultured human cellsGENES TO CELLS, Issue 6 2003Hong Zhan Background: The vacuolar-type proton-translocating adenosine triphosphatase (V-ATPase) plays important roles in cell growth and tumour progression. V-ATPase is composed of two distinct structures, a hydrophilic catalytic cytosolic sector (V1) and a hydrophobic transmembrane sector (V0). The V1 sector is composed of 5,8 different subunits with the structure A3B3C1D1E1F1G1H1. The V0 sector is composed of 5 different subunits with the structure 1161381191166. The over-expression of 16-kDa proteolipid subunit of V-ATPase in the perinuclear region of the human adventitial fibroblasts promotes phenotypic modulation that contributes to neointimal formation and medial thickening. A relationship between oncogenicity and the expression of the 16-kDa proteolipid has also been suggested in human pancreatic carcinoma tissue. Results: We found that the mRNA levels of the 16-kDa proteolipid but not of the 70-kDa subunit of V-ATPase in human myofibroblasts were more abundant in serum-containing medium (MF(+) cells) than serum-free medium (MF(,) cells). In HeLa cells, the levels of mRNA and protein of the 16-kDa, 21-kDa or 70-kDa were clearly suppressed when the corresponding anti-sense oligonucleotides were administered to the culture medium. The growth rate and viability (mostly due to necrosis) of HeLa cells were reduced markedly by the 16-kDa and 21-kDa anti-sense, but little by the 70-kDa anti-sense, and not at all by any sense oligonucleotides. The localization of 16-kDa/21-kDa proteolipid subunits was different from that of the 70-kDa subunit in HeLa cells. Conclusion: These results suggest that the 16-kDa and 21-kDa proteolipid subunits of the V0 sector play crucial roles in growth and death of cultured human cells. Our results may provide new insights into the mechanism and therapeutic implications for vessel wall hyperplasia and tumorigenesis. [source] Method optimisation for peptide profiling of microdissected breast carcinoma tissue by matrix-assisted laser desorption/ionisation-time of flight and matrix-assisted laser desorption/ionisation-time of flight/time of flight-mass spectrometryPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 10 2005Arzu Umar Abstract Appropriate methods for the analysis of microdissected solid tumour tissues by matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF MS) are not yet well established. Optimisation of sample preparation was performed first on undissected tissue slices, representing ,200,000 cells, which were solubilised either in urea containing buffer, trifluoroethanol/NH4HCO3, 0.1% sodium dodecyl sulphate (SDS) or in 0.1% RapiGest solution, then trypsin digested and analysed by MALDI-TOF MS. Solubilisation in 0.1% SDS resulted in detection of the highest number of sample specific peak signals. Interestingly, there was little overlap in detectable peaks using the different buffers, implying that they can be used complementarily to each other. Additionally, we fractionated tryptic digests on a monolithic high-performance liquid chromatography column. Fractionation of tryptic digest from whole tissue sections resulted in a four-fold increase in the total number of peaks detected. To prove this principle, we used 0.1% SDS to generate peptide patterns from 2000 microdissected tumour and stromal cells from five different breast carcinoma tumours. The tumour and stroma specific peaks could be detected upon comparison of the peptide profiles. Identification of differentially expressed peaks by MALDI-TOF/TOF MS was performed on fractionated tryptic digests derived from a whole tissue slice. In conclusion, we describe a method that is suitable for direct peptide profiling on small amounts of microdissected cells obtained from breast cancer tissues. [source] Geminin predicts adverse clinical outcome in breast cancer by reflecting cell-cycle progressionTHE JOURNAL OF PATHOLOGY, Issue 2 2004Michael A Gonzalez Abstract Geminin inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance (MCM) proteins onto DNA. The present study has investigated whether the frequency of geminin expression predicts clinical outcome in breast cancer. Immunohistochemistry was used first to examine geminin expression in normal and malignant breast tissue (n = 67). Correlations with cell-cycle parameters, pathological features, and clinical outcome were then determined using an invasive breast carcinoma tissue microarray (n = 165). Breast carcinomas were scanned for mutations (n = 61) and copy number imbalances (n = 241) of the geminin gene. Finally, the cell cycle distribution of geminin in breast cancer cells was investigated in vivo and in vitro. Despite a putative tumour suppressor function, it was found that increased geminin expression is a powerful independent indicator of adverse prognosis in invasive breast cancer. Both poor overall survival (p = 0.0002) and the development of distant metastases (p = 0.005) are predicted by high geminin expression, which performs better in this patient cohort than traditional factors currently used to determine prognosis and appropriate therapy. No mutations or deletions of the geminin gene and no evidence that a high frequency of protein expression is related to gene amplification were found. It is shown that geminin is expressed from S to M phase in breast carcinoma tissue and cell lines, disappearing at the metaphase,anaphase transition. While MCM proteins identify all non-quiescent cells, geminin identifies the sub-fraction that have entered S phase, but not exited mitosis, thereby indicating the rate of cell-cycle progression. It is suggested that this explains its unexpected value as a prognostic marker in breast cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Activation of Signal Transducers and Activators of Transcription 3 and Overexpression of its Target Gene CyclinD1 in Laryngeal Carcinomas,THE LARYNGOSCOPE, Issue 11 2008Bin Liu MD Abstract Objectives/Hypothesis: Constitutive activation of signal transducers and activators of transcription (STAT) 3 has been observed in many solid tumors including head and neck squamous cell carcinoma. Expression and activation of STAT3 in laryngeal carcinoma have not been fully understood. The study aims to investigate the expression and activation of STAT3 in laryngeal carcinoma, the relationship between activated STAT3 and its downstream target gene CyclinD1 and the related clinicopathological factors of activated STAT3. Study Design: Prospective. Methods: Sixty-four samples of laryngeal squamous cell carcinoma and 12 samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and reverse transcriptase-polymerase chain reaction. Statistical analysis was performed using SPSS. Results: The overexpression of both STAT3 and CyclinD1 mRNA was observed in all samples of laryngeal squamous cell carcinoma. The mRNA levels of STAT3 and CyclinD1 in carcinoma tissue were 2.1- and 2.3-fold higher than those in control mucosa, respectively; the differences were statistically significant (P < .01). The overexpression of STAT3, p-STAT3, and CyclinD1 protein was also observed in all tumor samples. The protein levels of STAT3, p-STAT3, and CyclinD1 in carcinoma tissue were 1.6-, 4.5-, and 2.0-fold higher than those in control mucosa respectively; the differences were statistically significant (P < .01). There was a positive correlation between p-STAT3 protein and CyclinD1 mRNA (Pearson correlation coefficient = 0.827, P < .01). There were significant correlations between the overexpression of p-STAT3 protein and clinical T stage (P < .01), and tumor size (P < .05). The p-STAT3 protein level of patients in T1, T2 was higher than that of patients in T3, T4. The p-STAT3 protein level of patients with tumor size within 20 mm was higher than that of patients with tumor size more than 20 mm. Conclusions: High expression and activation of STAT3 exist in laryngeal carcinomas. Activated STAT3 may take effect on promoting transcription of its downstream target gene CyclinD1. The role of activation of STAT3 in laryngeal carcinogenesis needs further research. [source] Intestinal tumor and agmatine (decarboxylated arginine)CANCER, Issue 4 2004Low content in colon carcinoma tissue specimens, inhibitory effect on tumor cell proliferation in vitro Abstract BACKGROUND The polyamine system is a promising target for anticancer therapy. Ideally, an antineoplastic compound affecting this system should inhibit both ornithine decarboxylase and the polyamine transporter, and toxicity should be mild. Agmatine, decarboxylated L -arginine, appears to be such a compound. METHODS Adenosine triphosphate levels and the protein content of cell populations in culture were identified as surrogate markers for cell count. Agmatine content in cells and tissue specimens was measured by high-performance liquid chromatography. Antizyme levels were estimated by Western blotting. RESULTS Agmatine inhibited the proliferation of six human intestinal tumor cell lines in a concentration-dependent manner; this inhibition probably was attributable to an interaction between agmatine and the intracellular polyamine system. Consistent with the inverse relation between cell proliferation and agmatine concentration was the finding that agmatine content in human colon carcinoma tissue was approximatly one-half as great as it was in adjacent macroscopically normal tissue. CONCLUSIONS The results of the current study were compatible with the hypothesis that agmatine possesses antineoplastic action against intestinal tumor cells. It is likely that this activity is attributable to agmatine's regulatory role in polyamine homeostasis. Cancer 2004. © 2004 American Cancer Society. [source] Interleukin-10 expression significantly correlates with minor CD8+ T-cell infiltration and high microvessel density in patients with gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 8 2006Teruhisa Sakamoto Abstract We aimed to investigate the relationships between interleukin-10 (IL-10) expression and both the clinicopathological findings and prognoses in patients with gastric cancer and to compare IL-10 expression with microvessel (MV) density and CD8+ T lymphocyte infiltration to evaluate its effects on angiogenesis and immune responses in gastric cancer. IL-10 expression was determined in gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR) or immunohistochemical procedures. Two of 7 normal gastric tissues showed IL-10 mRNA expression, while its expressions were confirmed in all advanced gastric carcinoma tissues examined (n = 11) by RT-PCR. Immunohistochemical staining demonstrated that IL-10 expression was detected in 52 (47.7%) of 109 cases. There was a close correlation between IL-10 expression and MV density. IL-10 expression inversely correlated with CD8+ T-lymphocyte infiltration. The prognoses of patients whose tumors expressed IL-10 were significantly worse than those of patients whose tumors did not express IL-10. Multivariate analysis indicated IL-10 expression was an independent prognostic factor. IL-10 might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric cancer. © 2005 Wiley-Liss, Inc. [source] Suppression of the TIG3 tumor suppressor gene in human ovarian carcinomas is mediated via mitogen-activated kinase-dependent and -independent mechanismsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Kristina Lotz Abstract The TIG3 gene is a retinoic acid inducible class II tumor suppressor gene downregulated in several human tumors and malignant cell lines. Diminished TIG3 expression correlates with decreased differentiation whereas forced expression of TIG3 suppresses oncogenic signaling pathways and subsequently induces differentiation or apoptosis in tumor cells. Analysis of TIG3 mRNA expression in a large set of cDNA pools derived from matched tumor and normal human tissues showed a significant downregulation of TIG3 in 29% of the cDNA samples obtained from ovarian carcinomas. Using in situ hybridization, we demonstrated expression of TIG3 in the epithelial lining of 7 normal ovaries but loss of TIG3 expression in 15/19 of human ovarian carcinoma tissues. In SKOV-3, CAOV-3 and ES-2 ovarian carcinoma cell lines, downregulation of TIG3 mRNA was reversible and dependent on an activated MEK-ERK signaling pathway. Re-expression of TIG3 mRNA in these cells upon specific interference with the MEK-pathway was correlated with growth inhibition of the cells. In OVCAR-3 and A27/80 ovarian carcinoma cells, TIG3 suppression is MEK-ERK independent, but expression could be reconstituted upon interferon gamma (IFN,) induction. Overexpression of TIG3 in A27/80 ovarian carcinoma cells significantly impaired cell growth and despite increased mRNA levels, TIG3 protein was hardly detectable. These results suggest that TIG3 is negatively regulated by an activated MEK-ERK signaling pathway. Further mechanisms must interfere with TIG3 expression that are independent of MEK and partially include interferon-responsive components. © 2005 Wiley-Liss, Inc. [source] Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodesINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Yasuhiko Kitadai Abstract The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes. © 2005 Wiley-Liss, Inc. [source] Replication efficiency and sequence analysis of full-length hepatitis B virus isolates from hepatocellular carcinoma tissuesINTERNATIONAL JOURNAL OF CANCER, Issue 5 2002Xu Lin Abstract Prolonged replication of hepatitis B virus (HBV) in liver tissues of hepatitis B patients has been considered as an important risk factor for the development of malignancy. Few studies on full-length HBV sequencing in association with the replication efficiency of isolates from HCC tissues have been reported. To study the structural and functional genomics of HBV isolates from Chinese hepatocellular carcinoma (HCC) patients, full-length HBV genomes were amplified from 6 HBV-marker positive HCC tissues and used to transfect HepG2 cells. Five of 6 isolates showed high replicative efficiency. All isolates were of genotype C and "hot-spots" mutations were detected in the B cell and T helper (Th) cell epitopes of the envelope and the core region. In addition, the X region of 2 isolates contained a stop-codon mutation that was predicted to result in a truncated X protein. High replicative HBV immune escape mutants that persist in infected hepatocytes could be 1 of the important factors to initiate pathological processes for the development of HCC in Chinese patients. © 2002 Wiley-Liss, Inc. [source] Chemokine receptor expression in non-melanoma skin cancerJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2008Jeff Basile Background:, Previous studies suggest that chemokines and chemokine receptors have a role in the metastatic process. A correlation exists between the specific expression of these chemoattractive, pro-inflammatory cytokines and the ability of cancer to disseminate. Prior studies have shown that in metastatic melanoma and squamous cell carcinoma of the head and neck upregulation of CXC (,) chemokine receptor (CXCR)4 and CC (,) chemokine receptor (CCR)7 expression is accompanied by downregulation of the chemokine receptor CCR6. However, the expression patterns of CCR6, CCR7 and CXCR4 in non-melanoma skin cancer have yet to be elucidated. Methods:, The expression patterns of CCR6, CCR7 and CXCR4 were determined using an immunohistochemical approach on formalin-fixed, paraffin-embedded normal, pre-cancerous actinic (solar) keratosis, squamous cell carcinoma and basal cell carcinoma tissues. Results:, Analysis of chemokine receptor expression showed downregulation of CCR6 and upregulation of CCR7 and CXCR4 in potentially metastatic non-melanoma skin cancer, invasive squamous cell carcinoma, but this pattern did not exist in non-melanoma skin cancer with no metastatic potential, basal cell carcinoma; or actinic keratosis, when compared with normal skin. Conclusions:, Chemokine receptor expression may influence the biological behavior of non-melanoma skin cancer. The exact mechanism by which this occurs requires further study. [source] Elevated expression of bisecting N -acetylglucosaminyltransferase-III gene in a human fetal hepatocyte cell line by hepatitis B virusJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2004JAE-KYOUNG SHIM Abstract Background and Aim:, UDP-N-acetylglucosamine: ,-D-mannoside ,-1,4 N-acetylglucosaminyltransferase III (GnT-III) is a key enzyme in N-glycan biosytnesis. Human GnT-III enzyme activity was found to be elevated in the serum of patients with hepatomas and liver cirrhosis and in hepatocellular carcinoma tissues. Therefore, to understand the relationship between the elevation in GnT-III activity and hepatitis B viral (HBV) hepartocarcinogenesis, we investigated GnT-III gene expression in the HBV-infected cells. Methods:, A cell line, HFH-T1, producing HBV was produced by natural infection of human fetal hepatocytes. A 170-bp band corresponding to the pre-S1 region of HBV was detected in the culture medium by polymerase chain reaction. Virions were also isolated from the culture medium by sucrose density gradient centrifugation. The synthesis of both ,-fetoprotein and albumin as an indicator that these cells were functional hepatocytes and the extent of differentiation was examined. Polymerase chain reaction and Western blot analysis using a monoclonal antibody, GT273, which was prepared using human aglycosyl recombinant GnT-III were used for HBV DNA and GnT-III detection. Results:, Two types of HBV-related particles were secreted into the culture medium; one was a Dane particle (40 nm in size) containing HBV DNA and the other was a subviral hepatitis B surface antigen particle (20 nm in size) that did not contain the viral genome. The secretion from the cell line was diminished by the number of passages and, thus, this cell was renamed as HFH-T2. A decreased level of the HBV was secreted from the cells after a rest period. HFH-T2 cells showed a weak staining for ,-fetoprotein and a moderate staining for albumin in the cytoplasm around the nucleus. High levels of a 0.7 kb DNA fragment originating from GnT-III DNA were detected in HFH-T2 cells. Western blot analysis using a monoclonal antibody, GT273, whixh was prepared using human aglycosyl recombinant GnT-III showed a single band, corresponding to Mr 63 kDa, whereas aglycosyl GnT-III showed a band at Mr 53 kDa, with a molecular weight difference of about 10 kDa. This indicates that HFH-T2 cells express glycosylated GnT-III. GnT-III activities were 347.2 ± 53.6 pmol/mg of protein/h in HFH-T2, 276 ± 26.3 in Hep3B, 252.5 ± 23.3 in HepG2 and 30.7 ± 3.4 in NIH-3T3. GnT-III activity was higher in HFH-T2 cells than in the hepatoma cell lines, Hep3B and HepG2. Conclusion:, A human fetal hepatocyte cell line was transformed by infection with HBV and the cell line expressed high levels of GnT-III as the levels of secretion of HBV decreased. The decrease in HBV secretion from HFH-T2 cells could be due to a high level of expression of GnT-III. Such a cell line could be used to investigate relationships between HBV infection and glycosyltransferase gene expression. Furthermore, this cell line will be useful in future studies on the effect of the expression of GnT-III on other glycosyltransferase. [source] Frequent integration of precore/core mutants of hepatitis B virus in human hepatocellular carcinoma tissuesJOURNAL OF VIRAL HEPATITIS, Issue 2 2000Zhong The development of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) frequently follows persistent HBV infection and may arise in individuals who are hepatitis B e antigen (HBeAg) negative, indicating the possible presence of precore/core mutants. It is unclear whether precore/core mutants are associated with tumour development or are selected for after chromosomal integration of the wild-type viral DNA. We studied the status and sequence variation of the precore/core region of HBV in 56 patients with HBV-associated HCC and in various corresponding non-tumour tissues by Southern blot analysis, polymerase chain reaction and direct sequencing. Southern blot showed that integrated HBV DNA existed in 43 of 56 HCC tissues. Sequence analysis revealed mutations in 65% of the HCC (26/40) and 45% (14/31) of the corresponding non-tumour tissues. The mutation at nucleotide (nt) 1896, known to prevent HBeAg synthesis, was detected in 40% (16/40) of the tumours and in 35.4% (11/31) of the non-tumour tissues. Other mutations were found at nt 1899 (eight of 40 in HCC; three of 31 in non-tumour tissues), nt 1898 (seven of 40 in HCC; two of 31 in non-tumour tissues), nt 1912 (seven of 40 in HCC; none of 31 in non-tumour tissues) and nt 1886 (three of 40 in HCC; none of 31 in non-tumour tissues). To determine whether this finding merely reflected the prevalence of such mutants in this geographical region, HBV DNA from the sera of patients (also in this region) with acute and chronic hepatitis were sequenced. The nt 1896 mutant was found in 5.6% (one of 18) of patients with acute hepatitis B and in 22.8% (nine of 35) of patients with chronic hepatitis B. However, the nt 1898 mutation was not found in any of these sera. The precore/core mutant was observed with increasing frequency from acute hepatitis to chronic hepatitis, non-tumour and HCC, and this difference in frequency was significant between HCC and acute hepatitis B groups (P < 0.01), suggesting that the precore/core mutant or hepatocytes harbouring this mutant may be under immune selection and that such mutations may facilitate integration and subsequent tumour development. [source] Disturbance of circadian gene expression in hepatocellular carcinomaMOLECULAR CARCINOGENESIS, Issue 12 2008Yueh-Min Lin Abstract Circadian rhythm plays an important role in the regulation of digestive system. The human circadian rhythm is controlled by at least nine circadian genes. The aims of this study are to understand the expression of the circadian genes between hepatocellular carcinoma tissues and nontumor tissues, and to explore the possible mechanism(s) contributing to the difference. We analyzed differential expression of the 9 circadian genes in 46 hepatocellular carcinoma and paired noncancerous tissues by real-time quantitative RT-PCR and immunohistochemical detection. We also tested the possible regulatory mechanism(s) by direct sequencing and methylation PCR analysis. Our results showed that decreased expression levels of PER1, PER2, PER3, CRY2, and TIM in hepatocellular carcinomas were observed. Decreased-expression of these genes was not caused by genetic mutations, but by several factors, such as promoter methylation, overexpression of EZH2 or other factors. The downexpression of more circadian genes may result in disturbance of cell cycle, and it is correlated with the tumor size. Downregulation of circadian genes results in disturbance of circadian rhythm in hepatocellular carcinoma which may disrupt the control of the central pacemaker and benefit selective survival of cancerous cells and promote carcinogenesis. © 2008 Wiley-Liss, Inc. [source] In situ estrogen production and its regulation in human breast carcinoma: From endocrinology to intracrinologyPATHOLOGY INTERNATIONAL, Issue 11 2009Hironobu Sasano The great majority of breast carcinomas arising in postmenopausal women are estrogen dependent or positive for estrogen receptor (ER) in carcinoma cells despite markedly low plasma or circulating estrogen concentrations. In these patients, biologically active estrogens are locally produced from circulating inactive steroids including adrenal androgens in an intracrine mechanism in the breast cancer tissues and confer estrogenic activities on carcinoma cells. A series of enzymes are involved in this intra-tumoral or in situ production of estrogens in breast carcinoma tissues but aromatase, a member of the cytochrome P450 family, is a key enzyme of estrogen production through conversion from circulating adrenal androgens in estrogen-dependent postmenopausal breast cancer. It then becomes important to identify the sites of this estrogen production. There has been, however, controversy regarding intra-tumoral localization of aromatase in breast carcinoma, especially whether intra-tumoral production of estrogens through aromatase occurs in carcinoma or stromal cells. The enzyme was demonstrated to be expressed in both carcinoma and stromal cells in breast carcinoma tissues on immunohistochemistry with a well-characterized mAb 677 and combined laser capture microdissection/qualitative reverse transcriptase,polymerase chain reaction. Intra-tumoral aromatase in both of these cell types was subsequently demonstrated to be induced by carcinoma,stromal interactions associated with carcinoma invasion in breast tissue. The signals through various nuclear receptors, especially estrogen-related receptor-, in carcinoma cells and liver receptor homologue-1 in adipocytes adjacent to carcinoma invasion, in conjunction with various cytokines and/or growth factors, play pivotal roles in this induction of intra-tumoral aromatase. This increased aromatase subsequently results in increased in situ estrogen concentrations of breast cancer. Aromatase inhibitors are currently established as the gold standard for the treatment for ER-positive breast carcinoma but resistance to the therapy still remains to be solved by other modes of suppression of intra-tumoral estrogen production. [source] Peroxisome proliferator-activated receptor gamma in human prostate carcinomaPATHOLOGY INTERNATIONAL, Issue 5 2009Yasuhiro Nakamura Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily of transcription factors. Peroxisome proliferator-activated receptor gamma (PPAR,) plays an important role in the regulation of lipid homeostasis, adipogenesis, insulin resistance, and development of various organs. Agonists of PPAR, have been also reported to inhibit proliferation of prostate carcinoma cells as in other human malignancies, and these synthetic ligands have been used in differentiation-mediated therapy of various human carcinomas associated with high levels of PPAR,. The significance of PPAR, expression, however, was unknown in human prostate carcinoma tissues. The purpose of the present study was therefore to examine the immunolocalization of PPAR, in human prostate cancer tissues (40 cases) and correlate the findings with clinicopathological features of the patients in order to evaluate its possible biological significance. Twenty-nine patients were positive for PPAR, immunoreactivity (73%) and a significant inverse correlation was detected between PPAR, immunoreactivity, pT stage (P = 0.036), and serum concentration of prostate-specific antigen (P = 0.0004). In conclusion, PPAR, immunoreactivity is considered to be a new clinicopathological parameter of human prostate cancer. [source] Mutational analysis of caspase genes in prostate carcinomasAPMIS, Issue 4 2010MIN SUNG KIM Kim MS, Park SW, Kim YR, Lee JY, Lim HW, Song SY, Yoo NJ, Lee SH. Mutational analysis of caspase genes in prostate carcinomas. APMIS 2010; 118: 308,12. Evasion of apoptosis is one of the hallmarks of cancer. Of the components of apoptosis machinery, caspases are the main executioners of apoptosis that initiate and propagate the apoptosis, and finally degrade target molecules. Caspase-encoding genes have been reported to harbor inactivating mutations in many human cancers. However, mutational status of caspase genes in prostate carcinomas has not been identified. The aim of this study was to explore whether caspase genes are somatically mutated in prostate carcinomas. For this, we analyzed entire coding regions of 11 human caspase-encoding genes (CASP1,10 and 14) in 45 prostate carcinoma tissues by a single-strand conformation polymorphism (SSCP) assay. In this study, however, we detected no somatic mutation of CASP genes in the prostate carcinomas by the SSCP. This is the first report on systematic evaluation of caspase-encoding gene mutations in human prostate carcinomas, and our data indicate that CASP genes may not be mutated in prostate carcinomas. The data suggest that apoptosis evasion in prostate carcinoma may be dependent on other mechanisms besides genetic alteration of caspase-encoding genes. [source] Expression of NEDD-1, a PTEN regulator, in gastric and colorectal carcinomas,APMIS, Issue 9 2008SUNG SOO KIM Recent studies have disclosed that NEDD4-1 regulates PTEN activity by ubiquitination. NEDD4-1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4-1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4-1 in PTEN regulation in cancer cells, expression of NEDD4-1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4-1 expression in colorectal and gastric cancer tissues. We investigated NEDD4-1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4-1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4-1. There was no significant association of NEDD4-1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4-1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4-1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4-1 expression may play a role in colorectal and gastric cancer development. [source] Immunohistochemical and mutational analysis of FLASH in gastric carcinomas,APMIS, Issue 8 2007EUN GOO JEONG FLASH was initially identified as a pro-apoptotic protein that transmits an apoptosis signal during death receptor-induced apoptosis. Additionally, diverse biologic roles of FLASH, including TNF-induced NF-,B activation, cell-cycle progression and cell division, have been identified. Although such functions are important in cancer pathogenesis, little is known about the alterations of FLASH gene and FLASH protein expression in human cancers. In this study, we analyzed the expression of FLASH protein in 60 gastric adenocarcinomas by immunohistochemistry. We furthermore analyzed mutation of FLASH in exon 8, where two polyadenine tracts ((A)8 and (A)9) are present, by single-strand conformation polymorphism (SSCP) assay in 184 gastric adenocarcinomas. By immunohistochemistry, FLASH protein expression in cancer cells was detected positively in 42 gastric carcinoma tissues (70%), whereas its expression in epithelial cells of normal gastric mucosa was shown as no or very weak intensity. Mutational analysis detected one FLASH mutation in the gastric carcinomas (0.5%). The increased expression of FLASH in the malignant gastric epithelial cells compared to the normal mucosal epithelial cells suggests that FLASH expression may play a role in gastric tumorigenesis. Also, the data suggest that somatic mutation of FLASH is a rare event in gastric carcinomas. [source] Mutational analysis of salvador gene in human carcinomasAPMIS, Issue 6 2003NAM JIN YOO It is believed that clonal expansion and cancer growth is the result of the deregulation of proliferation and cell death. Recently, salvador, a molecule that can regulate both cell proliferation and cell death, was identified. It was also reported that human salvador (hWW45) is mutated in some cancer cell lines. However, there have been no data regarding salvador gene mutations in human cancer tissues. To explore the hypothesis that the salvador gene might be similarly mutated in human cancer tissues, we analyzed the entire coding region of the salvador gene for the detection of somatic mutations in a series of human cancer tissues, including carcinomas from stomach, colon, liver and lung. However, using SSCP analysis, no mutation in the coding and splicing regions could be detected in the cancers. The data presented here suggest that salvador is not frequently mutated in human carcinoma tissues and that the mutation might be tumor-type specific. [source] Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for ,3,1 integrinAPMIS, Issue 3 2000Jouni Lohi Interplay between laminin-5 (Ln-5) and its integrin (Int) receptors ,2,1, ,3,1 and ,6,4 has been implicated in the progression and invasion of carcinomas. In this study we found abundant immuno-reactivity for chains of Ln-5 (,3-,3-,2) and Ln-10 (,5-,1), as well as for type VII collagen, in basement membranes (BM) of colorectal adenomas. In carcinomas of all differentiation grades, Lns were seen in tumor BMs, whereas type VII collagen was almost absent. Ln-5 appeared to accumulate along the invading edges of carcinomas, while Ln-10 was mostly absent. Immunoreactivity for Ln ,1 chain, a component of Lns-1 and -3, was not seen in adenomas or carcinomas. Immunoreactivity for ,2, ,6, ,1 and ,4 Ints was found in all tumors and that for ,3 Int in all adenomas and most of the carcinomas, often in colocalization with Ln-5. Immunoblotting of carcinoma tissues showed that the ,2 chain of Ln-5 was present as typical Mr 105000 and 155000 isoforms. Immunoprecipitation experiments showed production of Ln-5 by cultured colon carcinoma cells. In quantitative cell adhesion experiments, function-blocking MAbs to ,3 and ,1 Int subunits, but not those to Int ,2 or ,6 subunits, significantly inhibited the adhesion of cells to Ln-5. Our results suggest that BM composition in colorectal adenomas reflects the properties of surface epithelial BM of colorectal mucosa. In invading carcinomas, trimeric Ln-5, produced by carcinoma cells, is a major BM component and the cells use the ,3,1 Int complex for adhesion to Ln-5. [source] Epstein-Barr virus infection in sarcomatoid renal cell carcinoma tissuesBJU INTERNATIONAL, Issue 1 2006Article first published online: 6 DEC 200 No abstract is available for this article. [source] Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism,CANCER, Issue 5 2006Ramy Ibrahim M.D. Abstract BACKGROUND To date, several mechanisms have been described by which malignant cells escape from the immune system. One of these is through the expression of FasL. The authors hypothesized that the Fas/FasL interaction enables cervical carcinoma cells to induce apoptosis of the cells of the immune system and thereby escape from them. METHODS The authors tested the expression of FASL on the surface of cervical carcinoma tissues. Next, they stained the same cervical tissues with anti-human leukocyte common antigen and TUNEL to identify apoptotic cells. An in vitro functional assay was then done to test if the FASL expressed on the surface of cervical carcinoma cell lines was or was not responsible for inducing apoptosis in T-cells. Finally, they compared the expression of FASL on normal and dysplastic cervical tissues. RESULTS Ninety-four percent of the cervical carcinoma tissues the authors tested expressed FasL and the majority of the apoptotic cells in the specimens were leukocytes with very few tumor cells. In the in vitro functional assay, only the Fasl expressing cell line and not the Fasl negative cell line was able to induce apoptosis of the Fas-expressing Jurkat cells. On examining the normal cervical tissues, the authors found that the expression of Fasl was confined to the basal cell layer with loss of expression observed in the suprabasal layers, which made it an immune privileged site. Conversely, there was persistent expression of FasL in the dysplastic layers in cervical dysplasia and squamous cell carcinoma specimens. CONCLUSIONS The findings of the current study support the authors' hypothesis that persistent expression of FasL plays a role in the ability of cervical carcinoma cells to escape from the immune system. Cancer 2006. Published 2006 by the American Cancer Society. [source] Purification and characterization of 66-kDa glycoprotein from human breast carcinomaCANCER SCIENCE, Issue 9 2007Renqing Feng We extracted a 66-kDa glycoprotein (GP-1D8) from breast invasive ductal carcinoma tissues. The monoclonal antibody (mAb) against GP-1D8 was prepared in our laboratory. Western blotting with the purified protein using the mAb demonstrated a single band of 66 kDa. Immunocytochemical and immunohistochemical analysis revealed strong expression of GP-1D8 protein in the cytoplasm of MCF-7 cells and different types of breast carcinoma tissues, but GP-1D8 is absent in normal breast and benign breast tumor tissues. Glycosylation analysis showed GP-1D8 contained methylated salic acid. GP-1D8 was identified using mass-spectrometric techniques and N -terminal sequencing. These data were used to identify the protein through the SWISSPROT protein sequence database and BLAST homology search. These results showed GP-1D8 had some similarity to human albumin precursor. Co-immunoprecipitation assays of lysate from MCF-7 cells and mass spectrometric analysis revealed the interaction of GP-1D8 with ,-tubulin. This is the first time human breast carcinoma tissues and MCF-7 cells have been shown to express a 66-kDa glycoprotein similar to human albumin precursor. These results might be important in the detection of novel potential biomarkers and may provide insight into the molecular mechanisms of tumorigenesis. (Cancer Sci 2007; 98: 1344,1349) [source] Expression of Multidrug Resistance-related Transporters in Human Breast CarcinomaCANCER SCIENCE, Issue 4 2001Atsuko Kanzaki The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP), which confer multidrug resistance in vitro, were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently received doxorubicin-based chemotherapy after surgery, in order to elucidate the roles of these genes in drug resistance in vivo. The mRNA levels were determined using a semi-quantitative reverse-transcription polymerase chain reaction method in breast carcinoma tissues including at least 80% carcinoma cells. The expression level of BCRP gene was low and did not vary markedly in comparison with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were correlated with each other, but the expression of BCRP or LRP gene did not correlate with that of other genes. These four gene expressions were independent of age, TNM categories and the status of progesterone or estrogen receptor. The expression levels of these four genes were not related to the relapse or prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P-glycoprotein (P-gp)/MDRl, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma. [source] | ||||||||||||||||||||||||||||