Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urothelial carcinoma in situ (CIS) is a high-grade neoplasm and an indicator of recurrence and progression that requires specific treatment. The distinction of CIS from flat non-neoplastic urothelium, in particular dysplasia, on the basis of histologic features is often difficult, and this study aims to validate cytokeratin 20 (CK20) and Ki-67 as discriminatory markers for this purpose. Immunostaining of these markers was applied to 26 cases of CIS, 14 atypia of unknown significance, 4 dysplasia, 6 normal, and 9 hyperplastic urothelium. CIS showed CK20 staining of deep urothelial cells in 23/26 CIS compared with restricted staining in surface cells in all non-neoplastic lesions. CIS had significantly increased Ki-67 index with a mean of 53.37% compared with that of non-neoplastic urothelium, which was <10% (P<0.0001). The proliferating cells were distributed randomly in CIS, whereas in non-neoplastic urothelium, staining was confined to the basal layer. Among the cases of atypia, 3/14 displayed deep staining for CK20 and 6/14 had elevated Ki-67 counts. In dysplasia similar findings were present in 1/4 and 2/4 cases, respectively. These findings suggest that CK20 and Ki-67 are objective markers to distinguish CIS from non-neoplastic urothelium. In cases of "atypia of unknown significance" and "dysplasia," positivity for both markers should raise the possibility of CIS or preneoplastic change and identify those cases for follow-up.
Appl Immunohistochem Mol Morphol 2006 Sep
PMID:Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium. 1693 15

Longstanding ulcerative colitis (UC) is associated with a high risk of developing UC-related colonic adenocarcinoma (UCC). These carcinomas originate from nonadenomatous dysplastic regions referred to as dysplasia associated lesion or mass (DALM). We evaluated chromosomal and microsatellite instability (MSI) in 21 DALM/UCCs. Chromosomal instability was determined by high-resolution array comparative genomic hybridization with a 3500-element BAC-PAC array. MSI was assessed with markers BAT25 and BAT26 and by immunohistochemical analysis of mismatch repair genes. Comparative genomic hybridization revealed frequent losses of array clones (>20% of tumors) at chromosome arms 4p, 5q, and 18q, frequent gains of array clones (>20% of tumors) were found at 1q, 5p, 6p, 7p, 7q, 8p, 8q, 11p, 11q, 12q, 14q, 17q, 19q, 20p, and 20q. The pattern of alterations is dominated by gains on 5p and 20q with loss of 4p, all of which were already present in a patient with carcinoma in situ. Immunohistochemical analysis of mismatch repair genes MLH1, PMS2, MSH2, and MSH6 showed negative immunostaining in 1 neoplasm (5%). MSI of BAT25 and BAT26 was seen in 3 tumors (14%) including the neoplasm with aberrant immunostaining. In conclusion, we constructed a genomic profile of DALM/UCC including several novel genetic alterations. Further, we found a low percentage of MSI. Thus, DALM/UCCs display profound chromosomal instability, but this is not associated with concurrent MSI.
Diagn Mol Pathol 2006 Dec
PMID:Chromosomal and microsatellite instability of adenocarcinomas and dysplastic lesions (DALM) in ulcerative colitis. 1712 49

The amino-imino tautomerization of the 4-aminopyrimidine (4APM)/acetic acid (AcOH) system through dual hydrogen bonding in n-hexane at room temperature was investigated using UV absorption and fluorescence spectroscopies, fluorescence time-profile measurements, and molecular orbital calculations, with those of the imino-model compound of 3-methyl-4(1H)-pyrimidinimine (3M4PMI). From the experimental results, it was confirmed that the imino-tautomer was formed in the first excited singlet state (S1) state through the double-proton transfer of the dual hydrogen-bonded complex of 4APM with AcOH. The fluorescences of the free 4APM monomer (band maximum at 353nm), imino-tautomer (at 414nm), and 3M4PMI monomer (at 437nm) exhibit the single-exponential decays of 98, 73, and 19ps time constants, respectively. The shorter decay time of the imino-tautomer fluorescence compared with the free monomer one is suggestive of the low activation energy process in the S1 state. From the result of the shortest decay time of the 3M4PMI fluorescence, it can be deduced that 3M4PMI has a non-planar structure in the S1 state. The theoretical calculations on the S0 and S1 state double-proton transfer for the 4APM/AcOH dual hydrogen-bonded system were performed with the use of formic acid (FoOH) in place of AcOH for the sake of simplicity. Only one peak of transition state was resolved in the S0 and S1 states. The energy barrier for the S1 state double-proton transfer of the 4APM/FoOH complex-->3H-4(1H)-pyrimidinimine/FoOH tautomer was estimated to be approximately 2kJmol(-1) using the CIS/6-31G(d) methods. On the other hand, the energy barrier for the S0 state reverse proton transfer of the 3H-4(1H)-pyrimidinimine/FoOH tautomer-->4APM/FoOH complex was estimated to be almost zero kJmol(-1) at B3LYP/6-31G(d) level.
Spectrochim Acta A Mol Biomol Spectrosc 2008 Feb
PMID:Amino-imino tautomerization reaction of the 4-aminopyrimidine/acetic acid system. 1754 20

Binding of GH to its receptor induces rapid phosphorylation of conserved tyrosine motifs that function as recruitment sites for downstream signaling molecules. Using mammalian protein-protein interaction trap (MAPPIT), a mammalian two-hybrid method, we mapped the binding sites in the GH receptor for signal transducer and activator of transcription 5 (STAT5) a and b and for the negative regulators of cytokine signaling cytokine-inducible Src-homology 2 (SH2)-containing protein (CIS) and suppressor of cytokine signaling 2 (SOCS2). Y534, Y566, and Y627 are the major recruitment sites for STAT5. A non-overlapping recruitment pattern is observed for SOCS2 and CIS with positions Y487 and Y595 as major binding sites, ruling out SOCS-mediated inhibition of STAT5 activation by competition for shared binding sites. More detailed analysis revealed that CIS binding to the Y595, but not to the Y487 motif, depends on both its SH2 domain and the C-terminal part of its SOCS box, with a critical role for the CIS Y253 residue. This functional divergence of the two CIS/SOCS2 recruitment sites is also observed upon substitution of the Y+1 residue by leucine, turning the Y487, but not the Y595 motif into a functional STAT5 recruitment site.
Mol Endocrinol 2007 Nov
PMID:Mammalian protein-protein interaction trap (MAPPIT) analysis of STAT5, CIS, and SOCS2 interactions with the growth hormone receptor. 1766 91

Understanding the molecular etiology and heterogeneity of disease has a direct effect on cancer therapeutics. To identify novel molecular changes associated with breast cancer progression, we conducted phosphoproteomics of the MCF10AT model comprising isogenic, ErbB2- and ErbB3-positive, xenograft-derived cell lines that mimic different stages of breast cancer. Using in vitro animal model and clinical breast samples, our study revealed a marked reduction of epidermal growth factor receptor (EGFR) expression with breast cancer progression. Such diminution of EGFR expression was associated with increased resistance to Gefitinib/Iressa in vitro. Fluorescence in situ hybridization showed that loss of EGFR gene copy number was one of the key mechanisms behind the low/null expression of EGFR in clinical breast tumors. Statistical analysis on the immunohistochemistry data of EGFR expression from 93 matched normal and breast tumor samples showed that (a) diminished EGFR expression could be detected as early as in the preneoplastic lesion (ductal carcinoma in situ) and this culminated in invasive carcinomas; (b) EGFR expression levels could distinguish between normal tissue versus carcinoma in situ and invasive carcinoma with high statistical significance (P < 0.001, n = 81). However, no significant correlation of EGFR expression with disease-free survival and overall survival was observed. This is the first time EGFR expression has been tracked meaningfully and developmentally from the normal condition through disease progression using in vitro, xenograft, and matched normal and tumor samples. Thus, our study provides a new insight into the role of EGFR in breast cancer development. Although no value of EGFR expression in prognosis was found, our findings are likely to have implications in the design of clinical trials targeting the EGFR family of proteins in breast cancer.
Mol Cancer Ther 2007 Nov
PMID:Progressive loss of epidermal growth factor receptor in a subpopulation of breast cancers: implications in target-directed therapeutics. 1798 21

The electronic absorption spectra of benzoyl azide and its derivatives: p-methyl, p-methoxy, p-chloro and p-nitrobenzoyl azide were investigated in different solvents. The observed spectra differ basically from the electronic spectra of aryl azides or alkyl azides. Four intense pi-pi* transitions were observed in the accessible UV region of the spectrum of each of the studied compounds. The contribution of charge transfer configurations to the observed transitions is rather weak. Shift of band maximum with solvent polarity is minute. On the other hand, band intensity is highly dependent on the solvent used. The observed transitions are delocalized rather than localized ones as in the case with aryl and alkyl azides. The attachment of the CO group to the azide group in acyl azides has a significant effect on the electronic structure of the molecule. The arrangements as well as energies of the molecular orbitals are different in acyl azides from those in aryl azides. The first electronic transition in phenyl azide is at 276 nm, whereas that of bezoyle azide is at 251 nm. Ab initio molecular orbital calculations using both RHF/6-311G* and B3LYP/6-31+G* levels were carried out on the ground states of the studied compounds. The wave functions of the excited states were calculated using the CIS and the AM1-CI procedures.
Spectrochim Acta A Mol Biomol Spectrosc 2008 Jun
PMID:The electronic absorption spectra of some acyl azides molecular orbital treatment. 1799 49

The excited state (S1) dipole moment of m-AMSA (1), an acridine derivative with antitumor activity, was determined from solvatochromic shifts of the lowest energy absorption band in several organic solvents. The effect of the solute shape and the values of polarizability on the determined change of dipole moment between ground and excited state was discussed. The dipole moments in S0 and S1 state were calculated in gas phase with semiempirical quantum-chemical and DFT and CIS methods and in solvents with SM5.4A solvation model and compared with values obtained experimentally. All the results show that the dipole moment of compound 1 in the excited state is higher than that in the ground state. These methods quite well predict the values of Deltamicro between two states of an investigated compound.
Spectrochim Acta A Mol Biomol Spectrosc 2008 Sep
PMID:An experimental and theoretical study of dipole moments of N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulfonamide. 1803 96

Cervical cancer is characterized by a long period of preclinical dysplasia or carcinoma in situ progressing into invasive cancer. Although Papanicolaou (Pap) smear test has contributed significantly to the early detection of precursor lesions, the cytological screening has inherent problems that produce considerable false negative/positive results. Since the infection of high-risk type of human papillomavirus (HPV) is strongly associated with cervical cancer, we investigated the feasibility of an immunostaining test to detect cells infected by HPV in cervical smear. We produced monoclonal antibodies against HPV16 E7 in mice by repeated injections with the recombinant HPV16 E7. Western blot analysis and immunocytochemical assay demonstrated that the selected monoclonal antibody, mAb (130-9-7), reacts specifically with cultured cervical cancer cell lines infected by HPV16. Specific staining was observable with the HPV16-positive smear specimens obtained from the cervical cancer patients, whereas no staining was detected with the HPV-negative smear specimens. To achieve the desired sensitivity, specificity and reproducibility, we modified and optimized the conventional immunocytochemical procedure for cervical smear specimens. Our results suggest that this immunostaining method for detecting high-risk HPV in cervical smear may be used as a strategy to distinguish a high-risk group, especially those patients with low grade cytological abnormality.
Exp Mol Med 2007 Oct 31
PMID:Immunocytochemical detection of HPV16 E7 in cervical smear. 1805 38

Diets high in fat seem to correspond with an increased risk of certain forms of cancer, including bladder BlCa. This preliminary study examined the expression and enzyme activity profile of the polyunsaturated fatty acid metabolizing enzyme 15-Lipoxygenase-1 (15-LO-1) in human tissues from normal bladder and bladder tumors (stages CIS-T3/T4). Human tissue samples from normal (donor) bladder and bladder tumors (stages CIS-T3/T4; non-Bacillus Calmette-Guerin-treated) were grossly microdissected and analyzed for 15-LO-1 protein expression [immunohistochemistry (IHC)/Western blot], mRNA expression (quantitative real-time polymerase chain reaction) and enzyme activity profiles. Our results demonstrated that 15-LO-1 expression (protein/mRNA) and enzyme activity varied with BlCa progression. Specifically, IHC analyses of 15-LO-1 protein levels revealed decreased expression with increased bladder tumor stage. In particular, a statistically significant decrease in 15-LO-1 expression in stage T3/T4 bladder tumors compared with normal tissues (P<0.001) was observed. In agreement with IHC results, Western blot, quantitative real-time polymerase chain reaction, and enzymatic activity analyses demonstrated increased 15-LO-1 protein, mRNA, and enzyme activity, respectively, in normal human bladder tissues in comparison with stage T3/T4 human bladder tumors. Our finding of variable 15-LO-1 expression and enzyme activity in bladder tissues suggests a role for 15-LO-1 in bladder carcinogenesis.
Appl Immunohistochem Mol Morphol 2008 Mar
PMID:Polyunsaturated fatty acid metabolizing 15-Lipoxygenase-1 (15-LO-1) expression in normal and tumorigenic human bladder tissues. 1822 26

1,5-Dihydrodiimidazo[4,5-b:4'5'e]pyrazine, 1H-imidazo[4,5-b]pyrazine, and 1H-imidazole were considered as possible products of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) photodecomposition. Since we took as a reference the product obtained after CL-20 irradiation in methanol solution, the nature of intermolecular bonds between heterocycles under study and methanol molecules was analyzed in detail. Existing hydrogen bonds were found to be quite strong, so dependence of calculations results on an influence of solvent was taken into account using both the polarizable continuum model (PCM) and the supermolecular approach. Electronic spectra of 1,5-dihydrodiimidazo[4,5-b:4'5'e]pyrazine, 1H-imidazo[4,5-b]pyrazine and 1H-imidazole were simulated using time dependent density functional theory (TD-DFT) and single-excitation configuration interaction (CIS) method. We observed that TD-DFT excitation energies are lower if compared to corresponding values obtained by the CIS method. Results of calculations with PCM and the supermolecular approach are very close. It was found that differences between calculated gas phase excitation energies and those values obtained by applying solvent models increases when the number of conjugated bonds in a molecule increases. Oscillator strengths of UV bands of the considered molecules are higher in the gas phase than in modeled methanol solutions. We found that the predicted spectrum of 1H-imidazole is in close agreement with the experimental UV spectrum of the CL-20 photolysis product.
Spectrochim Acta A Mol Biomol Spectrosc 2008 Nov 01
PMID:CL-20 photodecomposition: ab initio foundations for identification of products. 1826 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>