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At least 397 records · Page 22Linked to original sources
PubMed2006

Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases.

A major cause of treatment failure for prostate cancer is the development of androgen-independent metastatic disease. Id protein family, a group of basic helix-loop-helix transcription factors, has been shown to be involved in carcinogenesis and a prognostic marker in several types of human cancers. In this study, we examined the expressions of four Id proteins, Id-1, -2, -3 and -4, in 125 clinical prostate cancer specimens as well as 40 nodular hyperplasia specimens by immunohistochemistry. The expressions of Id proteins were correlated with Gleason grading and metastatic progress of the tumors. We found that Id proteins were dysregulated in prostate cancer. Id-1 and -2 expressions were elevated while Id-3 and -4 expressions were reduced in prostate cancers compared to nodular hyperplasia. Cytoplasmic staining of Id-1 (P=0.013) and nuclear staining of Id-2 (P=0.001) and Id-4 (P<0.001) were positively correlated with Gleason score. The results indicate that these Id proteins may play a positive role in the development of prostate cancer. In contrast, Id-3 might have an inverse relationship with prostate neoplastic transformation (P=0.002) and cancer progression (P=0.022). We found that Id-4 nuclear overexpression in the primary prostate cancers significantly increased the risks to the development of metastasis in the patients (odds ratio=3.215, 95% confidence interval=1.150-8.987, P=0.026). Our results suggest that in prostate cancer patients, differential Id proteins expressions may be a useful marker for poor prognosis, and Id-4 may be a potential prognostic marker for distant metastasis.

Aged↗
PubMed2006

Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis.

Many endometrial adenocarcinomas, particularly those of endometrioid type, express estrogen receptors (ERs), progesterone receptors (PRs), and vimentin. This typical immunophenotype is frequently considered a standard against which others are compared when immunohistochemistry is used for differential diagnosis. We tested large numbers of endometrial cancers, enriched for high-grade tumors, to determine whether this reported immunophenotype was valid and whether expression differences between types of endometrial carcinoma could be exploited for diagnostic purposes. Immunohistochemical stains were performed on the following types of endometrial cancers using established methodology: International Federation of Gynecology and Obstetrics (FIGO) grades 1 and 2 endometrioid-42; FIGO grade 3 endometrioid-40; serous-24; clear cell-11; carcinosarcoma-9. In total, 92% of serous carcinomas expressed p16 strongly compared to weak-to-moderate expression of p16 in 7-67% of other tumors (FIGO grades 1 and 2 carcinoma and carcinosarcoma, respectively). A total of 84% of FIGO grades 1 and 2 carcinomas expressed ER compared to 9-54% of other tumors (clear cell and serous carcinomas respectively); 83% of FIGO grades 1 and 2 expressed PR compared to 11-54% of other carcinomas (carcinosarcoma and serous carcinoma, respectively). Most carcinomas were negative for monoclonal carcinoembryonic antigen (mCEA), and those that were positive showed mostly only focal membrane expression. Vimentin was expressed in nearly every tumor. Most tumors were diffusely vimentin positive, but a large range of expression patterns, from focal to diffuse and from weak to strong, was noted. Only 70% of FIGO grades 1 and 2 endometrioid carcinomas and 26% of grade 3 endometrioid carcinomas possessed the reportedly characteristic endometrial cancer immunophenotype p16 (-), ER (+), PR (+), mCEA (-), and vimentin (+). Endometrial cancers demonstrate substantial immunophenotypic diversity that remained apparent even within groups of similar histologic subtype and grade. ER, PR, and p16 expression was more illustrative of tumor type and degree of differentiation than they were of endometrial origin. In contrast, the vimentin-positive/CEA-negative phenotype remained the most constant among all endometrial cancers.

Adenocarcinoma, Clear Cell↗
PubMed2006

Expression of p14ARF, p15INK4b, p16INK4a, and DCR2 increases during prostate cancer progression.

Prostate carcinoma is a hormonally driven age-related neoplasm. Cellular senescence is an age-related process where cells remain metabolically active but in a growth-arrested state at the G1 phase. p14(ARF), p15(INK4b), and p16(INK4a), which are known to regulate G1 cell cycle arrest, and the tumor necrosis factor receptor superfamily member decoy receptor 2 (DCR2), have been recently identified as senescence markers. The purpose of this study was to characterize and compare the expression of p14(ARF), p15(INK4b), p16(INK4a), and DCR2 in tissue microarrays containing cases of normal prostate, nodular hyperplasia, prostate intraepithelial neoplasia (PIN), and malignant prostate cancer tissue. We performed immunohistochemical staining for p14(ARF), p15(INK4b), p16(INK4a), and DCR2 in tissue microarray blocks containing 41 cores of normal prostate, 65 cores of nodular hyperplasia, 21 cores of PIN, 69 cores of low-grade prostate carcinoma, and 42 cores of high-grade prostate carcinoma, derived from 80 cases of prostatectomy with adenocarcinomas. We detected positive staining of p16(INK4a) in 19% of the PIN, 25% of the low-grade carcinoma, and 43% of the high-grade carcinoma specimens but none in the normal prostate and nodular hyperplasia specimens. Expression of p14(ARF) revealed very high levels of expression in normal tissues (83%), nodular hyperplasia (88%), PIN (89%), and cancer cells (100%). P15(INK4b) and DCR2 were found positive in 81 and 33% normal, 46 and 10% nodular hyperplasia, 74 and 36% PIN tissues, 87 and 89% low-grade carcinomas, and 100 and 93% high-grade carcinomas. There is an increased protein expression of senescence-associated molecular markers, indicating that cellular senescence might play a role in prostate carcinoma. Because p16(INK4a)-positive cells were detected only in premalignant lesions and carcinomas but not in normal or benign tissues, p16(INK4a) may aid in the diagnosis of PIN and prostate cancer in difficult cases.

Adenocarcinoma↗
PubMed2006

Immunohistochemical expression of heparan sulfate correlates with stromal cell proliferation in breast phyllodes tumors.

Phyllodes tumors are fibroepithelial neoplasms typified by stromal proliferation. We have previously shown the role of pathologic parameters and the prognostic significance of p53 and CD117 protein expression in these tumors. In this study, we evaluated the expression of heparan sulfate, which has been implicated in many biological processes such as cell adhesion, embryogenesis, and tumorigenesis (including malignant transformation of mammary cells) in 232 breast phyllodes tumors. We used a monoclonal antibody, 10E4, to examine the localization of heparan sulfate in phyllodes tumors by immunohistochemistry. The immunoreactivity of both epithelial and stromal components was examined and analyzed with pathological parameters and other immunohistochemical markers, including p53, MIB1, bcl2, and CD117. Stromal 10E4 expression was significantly associated with tumor grade, stromal p53, and MIB1 expression in proliferating cells, suggesting that heparan sulfate may participate in malignant tumor growth.

Antibodies, Antinuclear↗
PubMed2006

EGFR is phosphorylated at Ty845 in hepatocellular carcinoma.

Epidermal growth factor receptor (EGFR) is overexpressed in a significant proportion of hepatocellular carcinomas. Recent studies of EGFR inhibitors to treat hepatocellular carcinoma have been encouraging and better understanding of EGFR signaling may lead to more effective strategies for inhibiting this key pathway. The EGFR can be phosphorylated at different tyrosine sites, leading to subsequent activation of different pathways. Cell line and animal studies have shown that MAPK and STAT-3 are important mediators of the EGFR signal in liver cells. However, little is known about EGFR phosphorylation and subsequent signaling in primary hepatocellular carcinoma. We investigated the site of EGFR phosphorylation by Western blot in 18 hepatocellular carcinomas. Fourteen of 18 hepatocellular carcinomas had detectable EGFR by Western blotting and 13 of 14 showed phosphorylation at tyrosine 845. In contrast, no EGFR phosphorylation was detected at tyrosine 998, tyrosine 1045, or tyrosine 1068, which signal through other pathways including STAT-3 and MAPK. These findings were further explored by examination of EGFR expression and signaling pathway activation in tissue arrays comprised of 73 hepatocellular carcinomas using antibodies that recognize phosphorylated (or activated) proteins. Tissue array studies also found no correlation between EGFR expression (29% of cases) and STAT-3 nuclear positivity (16%), AKT (4%), MAPK (3%), or STAT-5 (3%) positivity, all P>0.05. EGFR expression was correlated with hepatitis B infection, but not with tumor size, nuclear grade, or proliferative rate. We conclude that EGFR is phosphorylated at tyrosine 845 in most hepatocellular carcinomas and that EGFR expression by immunohistochemistry does not correlate well with STAT-3, STAT-5, MAPK, or AKT immunostaining.

Adolescent↗
PubMed2006

Immunohistochemical staining of hMLH1 and hMSH2 reflects microsatellite instability status in ovarian carcinoma.

Microsatellite instability is due to defects in the family of DNA repair genes, primarily hMLH1 and hMSH2, which can be detected by immunohistochemical staining. However, it is unclear whether immunohistochemical staining can accurately predict microsatellite instability status. We sought here to evaluate the sensitivity, specificity, and predictive values of immunostaining for the expression of the DNA mismatch-repair genes hMLH1 or hMSH2 in predicting microsatellite instability in ovarian carcinoma. Tissue microarrays with specimens from 322 women with primary ovarian carcinoma were stained with antibodies to hMLH1 and hMSH2; cases in which either hMLH1 or hMSH2 were negative were analyzed for microsatellite instability with the five-marker panel recommended by the National Cancer Institute (BAT26, BAT25, D5S346, D2S123, and D17S250). Microsatellite instability was also analyzed in another 19 cases selected at random in which both hMLH1 and hMSH2 were positive. Tumors with instability at two or more of the five NCI markers were considered to have a high level of microsatellite instability; tumors showing instability at only one marker were considered microsatellite instability-low; and tumors in which no markers exhibited microsatellite instability were considered microsatellite stable. We found that negative staining for hMLH1 protein (five cases) or hMSH2 protein (two cases) was associated with high level of microsatellite instability. The sensitivity and specificity of immunohistochemical staining for hMLH1 were 62 and 100% and those of hMSH2 alone were 25 and 100%. Combining loss of expression of both hMLH1 and hMSH2 led to sensitivity, specificity, and positive and negative predictive values of 87, 100, 100, and 95%. These results suggest that use of a two-molecule panel (hMLH1 and hMSH2) can accurately determine the microsatellite instability status of patients with ovarian cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Steroid receptor coactivator AIB1 in endometrial carcinoma, hyperplasia and normal endometrium: Correlation with clinicopathologic parameters and biomarkers.

Members of the p160 steroid receptor cofactor family, including AIB1 (Amplified in Breast Cancer 1) (also known as SRC-3/RAC3/ACTR/pCIP/TRAM-1), are of interest in endometrial carcinoma as they affect the function of estrogen (ER) and progesterone receptors (PR). Since it is feasible that alterations in the expression levels of coregulators can either augment ER activity or reduce the ability of PR to oppose ER action in endometrial cancers, our primary aim was to analyze expression of the AIB1 protein in endometrial carcinoma, carcinoma-associated complex atypical hyperplasia, and carcinoma-associated normal endometrium using immunohistochemistry and tissue microarrays. Expression of AIB1 was compared with other biomarkers and clinicopathologic parameters. We also tested AIB1 expression in non-carcinoma associated hyperplastic, normal secretory and proliferative endometrium to determine baseline AIB1 levels. In endometrial carcinoma, there is a higher expression of AIB1 compared to carcinoma-associated complex atypical hyperplasia (0.007) or carcinoma-associated normal endometrium (<0.001). AIB1 expression correlates with older age (P = 0.003), peri- or postmenopausal status (P = 0.002) and a higher grade of carcinomas (P = 0.04). There were no differences in the expression of additional steroid hormone receptor co-activators (SRC-1 and p300/CBP) and the co-repressor SMRT between histologic categories. AIB1 expression correlated with ER (r = 0.30, P = 0.006). The strongest correlation was between ER and PR-B isoform nuclear expression (r = 0.52, P < 0.0001). AIB1 levels were higher in non-carcinoma associated normal and hyperplastic endometrium compared to carcinoma-associated complex atypical hyperplasia and carcinoma-associated normal endometrium, and were the highest in normal secretory endometrium. In conclusion, high AIB1 expression in endometrial carcinoma is associated with parameters of poor prognosis. We propose that when AIB1 is overexpressed in endometrial carcinoma, ER action is augmented, leading to endometrial hyperplasia and progression to malignancy. Future studies correlating expression with response to hormonal therapy may be beneficial.

Adenocarcinoma↗
PubMed2006

Increased expression of hypoxia-inducible factor 1alpha in type I and type II endometrial carcinomas.

Hypoxia-inducible factor 1alpha (HIF-1alpha) is a nuclear protein that is upregulated in many tumors and triggers biologic events intimately associated with aggressive tumor behavior. The aim of this study was to analyze the expression of HIF-1alpha, vascular endothelial growth factor (VEGF), Ki-67 and p53 in type I and type II endometrial adenocarcinoma. In total, 149 patients diagnosed with endometrial adenocarcinoma in our institute from 1995 to 2001 were included in this study, of which 108 were type I and 41 were type II endometrial adenocarcinoma. Patient demographics, clinical and pathological data were reviewed. Tissue microarrays were prepared from the paraffin blocks and immunohistochemistry was performed for antibodies against HIF-1alpha, VEGF, Ki-67 and p53. High expression of HIF-1alpha, VEGF, Ki-67 and p53 were significantly more frequent in type II than type I endometrial adenocarcinoma (P<0.001). HIF-1alpha expression was highly correlated with VEGF expression in the tumor cells (P=0.001). In type I endometrial adenocarcinoma, high expression of HIF-1alpha showed a significant correlation with higher grade of the tumor, depth of myometrial invasion, adnexal invasion and clinical stage. A similar correlation was not observed in type II endometrial adenocarcinoma. Surgical stage was the only independent prognostic marker for survival. In conclusion, high expression of HIF-1alpha is more frequent in type II than in type I endometrial adenocarcinoma. In type I endometrial adenocarcinoma, HIF-1alpha expression correlates with morphologic features of aggressiveness. In type II endometrial adenocarcinoma, there is no correlation between HIF-1alpha expression and these features. Thus, HIF-1alpha may play an important role in endometrial adenocarcinoma progression, particularly in type I endometrial adenocarcinoma. Additional investigations of HIF-1alpha as a biomarker of aggressive potential and as a novel target for therapeutics in endometrial adenocarcinoma are warranted.

Adenocarcinoma↗
PubMed2006

Increased expression of stem cell markers in malignant melanoma.

The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P=0.005), CD133 (P=0.003), and nestin (P=0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P=0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P=0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.

AC133 Antigen↗
PubMed2005

Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study.

Several reports suggest that the canonical nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappaB transcription factors in prostate cancer tissues. To clarify the status of NF-kappaB subunits, we analysed the expression and subcellular localisation of RelA, RelB, c-Rel, p50, and p52 on tissue array sections containing respectively 344, 346, 369, 343, and 344 cores from 75 patients. The subcellular localisation of NF-kappaB factors was tested against relevant clinical parameters (preoperative prostate-specific antigen, pathological stage, and postoperative Gleason grade). With the exception of c-Rel, each subunit was detected in the nucleus of cancer cells: significant nuclear expression of RelB, RelA, p52, and p50 was seen in 26.6, 15.6, 10.7, and 10.5% of cores, respectively. Surprisingly, cores expressing both nuclear RelA and p50 canonical pathway proteins were less frequently observed than cores expressing other subunit combinations such as RelB-p52 and RelA-RelB. In addition, the nuclear localisation of RelB correlated with patient's Gleason scores (Spearman correlation: 0.167; P=0.018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease.

Adenocarcinoma↗
PubMed2006

Nuclear ING2 expression is reduced in human cutaneous melanomas.

Cutaneous malignant melanoma is a severe and sometimes life-threatening cancer. The molecular mechanism of melanomagenesis is incompletely understood. Deregulation of apoptosis is probably one of the key factors contributing to the progression of melanoma. The inhibitor of growth (ING) family proteins are candidate tumour suppressors which play important roles in apoptosis. Downregulated expression of ING proteins have been reported in several tumour types, including the loss of nuclear expression of p33ING1b in melanoma. As ING2 exhibits 58.9% homology with p33ING1b, we hypothesized that the aberrant expression of ING2 may be involved in melanomagenesis. Here, we used tissue microarray technology and immunohistochemistry to examine ING2 expression in human nevi and melanoma biopsies. Our data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (P < 0.05). Our data also revealed that nuclear ING2 expression was not associated with patient's gender, age or tumour thickness, ulceration, American Joint Committee on Cancer (AJCC) stage, tumour subtype, location and 5-year survival (P > 0.05). Taken together, our results suggest that nuclear ING2 expression is significantly reduced in human melanomas and that reduced ING2 may be an important molecular event in the initiation of melanoma development.

Adult↗
PubMed2005

Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1.

Although cyclin G1 has been implicated in certain p53-related biological phenomena, other aspects of its function remain unclear. Here we report hitherto unknown mechanism by which cyclin G1 increases radiation sensitivity by regulating the level of cyclin B1. Overexpression of cyclin G1 was observable in lung carcinoma tissues. Irradiation of human lung cells with cyclin G1 overexpression resulted in increased cell death and gamma-H2AX foci suggesting that cyclin G1 rendered the cells more susceptible to DNA damage. Enhanced radiosensitivity by cyclin G1 was correlated with increased cyclin B1, CDC2/cyclin B1 complex, and MPM2. Cell cycle synchronization clearly showed coexpression of cyclin G1 and cyclin B1 in G2/M phase. Depletion of cyclin G1 by interference RNA revealed that cyclin G1 regulated transcription of cyclin B1 in a p53-independent manner, and confirmed that the increased mitotic cells and cell death by cyclin G1 were dependent upon cyclin B1. Therefore, our data suggest that cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1.

Adenocarcinoma, Papillary↗
PubMed2006

Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer.

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.

Acid Anhydride Hydrolases↗
PubMed2006

Simple and versatile methods for the fabrication of arrays of live mammalian cells.

Single-step methods for the generation of patterned surfaces on hydrogels are presented. Poly(vinyl alcohol) films covalently bonded on glass cover slips and commercially available hydrogel-coated polystyrene plates were used as cell-repellent surfaces. Cell-adhesive domains were created by spotting dilute solutions of sodium hypochlorite onto the surfaces. Alternatively, domains supporting cell attachment were created by exposure to UV light from a xenon excimer lamp, employing a contact mask. Rat skeletal myoblast cells, HEK 293 human embryonic kidney cells and Caco-2 colon carcinoma cells adhered and spread exclusively on modified areas. The surfaces are durable for weeks under cell culture conditions and re-usable after removal of the cells by trypsin treatment. Arrays of adhesive spots seeded with cells at a low density permitted dynamic monitoring of cell proliferation. Selected colonies can be harvested from the surfaces by means of local trypsination. Thus, these techniques may provide useful tools for the isolation of clonal cell populations. Additionally, we demonstrate the possibility of surface-mediated gene delivery from the micro patterns. We show that DNA, complexed with a lipid reagent, can be adsorbed on modified poly(vinyl alcohol) coatings, resulting in spatially controlled adhesion and reverse transfection of HEK 293 cells.

Animals↗
PubMed2002

Activation of polycyclic aromatic hydrocarbon trans-dihydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung carcinoma (A549) cells.

Polycyclic aromatic hydrocarbons (PAH) are environmental pollutants and suspected human lung carcinogens. In patients with non-small cell lung carcinoma, differential display shows that aldo-keto reductase (AKR1C) transcripts are dramatically overexpressed. However, whether AKR1C isoforms contribute to the carcinogenic process and oxidize potent PAH trans-dihydrodiols (proximate carcinogens) to reactive and redox active o-quinones is unknown; nor is it known whether these reactions occur in human lungs. We now show that four homogeneous human recombinant aldo-keto reductases (AKR1C1-AKR1C4) are regioselective and oxidize only the relevant non-K region trans-dihydrodiols. However, these enzymes are not stereo-selective, since they oxidized 100% of these racemic substrates. The highest utilization ratios (V(max)/K(m)) were observed for some of the most potent proximate carcinogens known (e.g. 7,12-dimethylbenz[a]anthracene-3,4-diol (DMBA-3,4-diol) and benzo[g]chrysene-11,12-diol). In vitro, DMBA-3,4-diol was oxidized by AKR1C4 to the highly reactive 7,12-dimethylbenz[a]anthracene-3,4-dione (DMBA-3,4-dione), which was trapped in situ as its mono- and bis-thioether conjugates, which arise from the sequential 1,6- and 1,4-Michael addition of thiol nucleophiles. Human multiple tissue expression array analysis showed that AKR1C isoform transcripts were highly expressed in the human lung carcinoma cell line A549. Isoform-specific reverse transcriptase-PCR showed that AKR1C1, AKR1C2, and AKR1C3 transcripts were all expressed. Western blot analysis and functional assays confirmed high expression of AKR1C protein and enzyme activity in these lung cells. A549 cell lysates were found to convert DMBA-3,4-diol to the corresponding o-quinone. In trapping experiments, LC/MS analysis identified peaks in the cell lysates that corresponded to the synthetically prepared mono- and bis-thioether conjugates of DMBA-3,4-dione. This quinone is one of the most electrophilic and redox-active o-quinones produced by AKRs. Its unique ability to form bis-thioether conjugates parallels the formation of bis- and tris-glutathionyl conjugates of hydroquinone, which display end organ toxicity. The ability to measure DMBA-3,4-dione formation in A549 cells implicates the AKR pathway in the metabolic activation of PAH in human lung.

20-Hydroxysteroid Dehydrogenases↗
PubMed2003

Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues.

Here we show that an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments can be used for chromosome-wide protein profiling. The approach is based on affinity reagents raised toward bioinformatics-designed protein epitope signature tags corresponding to unique regions of individual gene loci. The genes of human chromosome 21 identified by the genome efforts were investigated, and the success rates for de novo cloning, protein production, and antibody generation were 85, 76, and 56%, respectively. Using human tissue arrays, a systematic profiling of protein expression and subcellular localization was undertaken for the putative gene products. The results suggest that this affinity proteomics strategy can be used to produce a proteome atlas, describing distribution and expression of proteins in normal tissues as well as in common cancers and other forms of diseased tissues.

Antibodies↗
PubMed2006

Proteomics in clinical trials and practice: present uses and future promise.

The study of clinical proteomics is a promising new field that has the potential to have many applications, including the identification of biomarkers and monitoring of disease, especially in the field of oncology. Expression proteomics evaluates the cellular production of proteins encoded by a particular gene and exploits the differential expression and post-translational modifications of proteins between healthy and diseased states. These biomarkers may be applied towards early diagnosis, prognosis, and prediction of response to therapy. Functional proteomics seeks to decipher protein-protein interactions and biochemical pathways involved in disease biology and targeted by newer molecular therapeutics. Advanced spectrometry technologies and new protein array formats have improved these analyses and are now being applied prospectively in clinical trials. Further advancement of proteomics technology could usher in an era of personalized molecular medicine, where diseases are diagnosed at earlier stages and where therapies are more effective because they are tailored to the protein expression of a patient's malignancy.

Clinical Trials as Topic↗