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

The homeodomain-containing transcription factor NKX3.1 is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. Loss of NKX3.1 protein expression is common in human prostate carcinomas and prostatic intraepithelial neoplasia (PIN) lesions and correlates with tumor progression. Disruption of the murine Nkx3.1 gene results in defects in prostate branching morphogenesis, secretions, and growth. To more closely mimic the pattern of NKX3.1 loss that occurs in human prostate tumors, we have used Cre- and loxP-mediated recombination to delete the Nkx3.1 gene in the prostates of adult transgenic mice. Conditional deletion of one or both alleles of Nkx3.1 leads to the development of preinvasive lesions that resemble PIN. The pattern of expression of several biomarkers (Ki-67, E-cadherin, and high-molecular-weight cytokeratins) in these PIN lesions resembled that observed in human cases of PIN. Furthermore, PIN foci in mice with conditional deletion of a single Nkx3.1 allele lose expression of the wild-type allele. Our results support the role of NKX3.1 as a prostate tumor suppressor and indicate a role for this gene in tumor initiation.
Mol Cell Biol 2002 Mar
PMID:Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia. 1183 15

Ki-67 nuclear antigen is present in proliferating cells. MIB-1 antibody, raised to the recombinant part of the Ki-67 antigen, is a widely used biologic marker to assess cell proliferation. Ki-67 expression is normally observed in parabasal and basal cells in the cervix. With increasing severity of dysplasia, MIB-1 labeling is seen in cells of the superficial layers of cervical epithelium, which are exfoliated. The purpose of this study was to determine the sensitivity and specificity of presence of MIB-1-positive cells in Papanicolaou tests for predicting cervical neoplasia, condyloma, or both, on follow up. Using microwave antigen retrieval method, 49 air-dried cervical smears in two-smear cases were evaluated with immunostaining with MIB-1 monoclonal antibody. Presence of MIB-1 positivity was arbitrarily set at > or = 4 MIB-1 immunoreactive cells in each smear. The degree of positive staining was correlated with the cytologic diagnoses, subsequent colposcopy-directed biopsies, endocervical curettage, and/or cytologic follow ups. Follow-up findings correlated with cytology in 33 cases (67%), with MIB-1 positivity in 35 cases (71%). Three cases with positive follow ups were missed by cytology but detected by MIB-1 staining, and three cases were missed by MIB-1 but detected by cytology. Both cytology and MIB-1 staining failed to detect a subsequent cervical lesion in two cases, and in six cases each, an abnormal finding was not substantiated on follow ups. MIB-1 immunostaining is a powerful technique for evaluating gynecologic smears and is as equally sensitive and specific as cervical cytology. It is able to identify cervical disease overlooked by cytologic screening; therefore, it may serve as an adjunct and complimentary tool to cervical cytology.
Appl Immunohistochem Mol Morphol 2002 Mar
PMID:MIB-1 expression in cervical Papanicolaou tests correlates with dysplasia in subsequent cervical biopsies. 1189 30

The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. 11C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of 11C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased 11C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal 11C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased 11C-methionine uptake, the extent and degree of which exceeded 18F-FDG uptake, and the 11C-methionine uptake correlated with the proliferation index (r=0.67). The mean (+/-SD) uptake ratios of glioma to normal brain on FDG and 11C-methionine PET were 0.92+/-0.34 and 2.54+/-1.25, respectively. All metastatic tumors except one showed intense 11C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, 11C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo- or isometabolism on FDG PET can be detected and differentiated with high sensitivity and good contrast using 11C-methionine PET. 11C-methionine PET can provide additional information when used in combination with FDG PET in the evaluation of these patients.
Eur J Nucl Med Mol Imaging 2002 Feb
PMID:Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET. 1192 79

CD56+ NK/T cell lymphoma (NKTL) frequently involves skin and subcutaneous tissue. The characteristics of primary cutaneous nasal-type CD56+ NKTLs and secondary cutaneous involvement of nasal CD56+ NKTLs have not been clearly separated. This retrospective study analyzed 15 cases of NKTL (10 primary CD56+ NKTLs and 5 secondary CD56+ NKTLs) for their clinicopathologic and immunophenotypic characteristics using CD3, CD4, CD20, CD45RO, CD56, TIA-1, CD30, and Ki-67 antigens. In situ hybridization for Epstein-Barr virus RNA (EBERISH) and PCR for T cell receptor (TCR) gamma gene rearrangement were also performed. Clinically, NKTL-P was seen with equal frequency among male (five cases) and female (five cases) patients and presented with subcutaneous nodules without epidermal changes (nine cases), whereas all cases of NKTL-S occurred in male patients and presented with nodules or plaques with distinct epidermal changes (five cases). Microscopically, initial NKTL-P lesions had the panniculitic patterns of small to medium-sized cells (nine cases). NKTL-S lesions were extensive in both subcutis and dermis, with larger and more pleomorphic tumor cells (four cases) that also showed signs epidermotropism (five cases). In initial biopsies of CD56+ NKTL-P, a minority of tumor cells showed signals for EBERISH and in biopsies of CD56+ NKTL-S, virtually every tumor cell showed signals. While all five patients with secondary CD56+ NKTL died of disease with widespread systemic involvement within 16 months after onset of skin lesions, 7 out of the 10 primary CD56+ NKTL patients survived more than 20 months after onset of skin lesions, with slow progression and episodic recurrences. The primary and secondary cutaneous CD56+ NKTLs showed considerable clinicopathologic differences, suggesting differences in pathogenesis.
Appl Immunohistochem Mol Morphol 2002 Jun
PMID:Comparison of primary and secondary cutaneous CD56+ NK/T cell lymphomas. 1205 36

Prolonged formalin fixation is known to reduce the immunohistochemical reactivity of many paraffin section antibodies. Before the common use of heat induced epitope retrieval methods, vimentin reactivity was proposed as a marker of antigen preservation. To evaluate the effect of formalin fixation on breast tumor markers, multitumor blocks of tissue fixed in formalin for varying time intervals from 33 different infiltrating breast carcinomas were analyzed for the expression of estrogen receptor (ER), progesterone receptor (PR), c-erb-B2, Ki-67, p27, and vimentin. The mean/median length of the longest fixation time per specimen was 53/42 days (range 7 days-154 days). Formalin fixation did not significantly reduce immunoreactivity for Ki-67, p27, or vimentin, even in tissue fixed for 154 days. Of 23 ER-positive cases, a significant reduction in immunoreactivity (2 grades or more) was identified in three samples, occurring at 57 to 64 days. For 21 PR-positive cases, only one showed a significant reduction (from 3+ to 1+) at 120 days. Of nine c-erb-B2 positive (2 + or 3+) cases, four became negative (1+ or 0) at 20, 42, 49, and 99 days. The immunoreactivity of some breast prognostic markers is reduced by formalin over-fixation, but only after extensive fixation that may not be clinically relevant. The loss of antigen preservation is not accompanied by a loss of vimentin immunoreactivity, making vimentin a suboptimal marker for ER, PR, or c-erb-B2 preservation.
Appl Immunohistochem Mol Morphol 2002 Jun
PMID:Effect of prolonged formalin fixation on the immunohistochemical reactivity of breast markers. 1205 39

Immunohistochemistry is part of the routine diagnosis of the neuroendocrine tumors. In our study, we included 52 paragangliomas with various localizations by routine histology and immunohistochemistry. In order to increase the diagnostic specificity, a complex immunohistochemistry panel has been performed consisting of Bcl-2, Ki-67, Bax and Pituitary Adenylate Cyclase-Activating Peptide (PACAP), somatostatin, VIP and Calcitonin Gene Related Peptide (CGRP). After heat induced antigen retrieval, the immunostaining was performed by StreptABC using DAB as a chromogen. We were the first to demonstrate the presence of Bax and PACAP in paragangliomas. Some of the used markers are of prognostic value. The relationship between Bcl-2 and Bax is decisive in generating the final response to the input apoptotic signals. The Ki-67 antigen staining has gained wide acceptance in prognostic evaluation of other tumor types. We noted a small number of Ki-67 positive cases, which signifies a low mitotic activity of these tumors and a relatively high number of Bax positivities (32.9%) and the much lower number of Bcl-2 positivities (11.39%), and could explain the benign behaviour of paragangliomas.
J Cell Mol Med
PMID:Immunohistochemical features of paragangliomas. 1206 90

Overexpression of cyclin D2 was studied in 10 human squamous cell carcinoma lines, to establish whether this gene plays a role in tumor progression. We found that those cell lines that overexpressed cyclin D2 (CCND2) had the most invasive in vivo behavior. The invasive ability of the cell lines was determined by evaluating the penetration of carcinoma cells into the tracheal wall in an in vivo assay with de-epithelialized tracheas transplanted into the subcutaneous tissue of nude mice. From five cell lines that exhibited low invasive ability, we selected two that had very little CCND2 expression (SCC9 and SCC15), to evaluate whether CCND2 gene transfer would increase the invasive behavior. After confirming the successful transfer of CCND2 by Northern, Western, and kinase-activity assays, we assessed the in vivo invasive behavior of the CCND2-transfected cells and their respective vector alone-transfected controls. The cell lines containing the transferred CCND2 gene had a significantly higher invasive ability than respective controls. This was accompanied by a moderate increase in gelatinase activity. In addition, the in vitro proliferative abilities, under normal culture conditions, of the parental CCND2-transfected and vector alone-transfected cells were found to be similar, as was the in vivo labeling index of Ki-67 in the tracheal transplants. These results indicated that the overexpression of CCND2 in squamous cell carcinoma lines modulates cell proliferation after induced quiescence and also has a powerful enhancing effect on in vivo aggressive growth behavior.
Mol Carcinog 2002 Jul
PMID:Overexpression of cyclin D2 is associated with increased in vivo invasiveness of human squamous carcinoma cells. 1211 7

This study examined the clinicopathological significance of minichromosome maintenance-2 (MCM2) expression in 38 human malignant fibrous histiocytomas (MFHs) and 36 benign fibrohistiocytic tumors (BFHTs) immunohistochemically, and in 9 human sarcoma or carcinoma cell lines, as well as 7 surgical specimens by Western blotting. MCM2 was detected in all the cell lines and surgical specimens as a single band at 120 kDa, while P53 expression was variable. Nuclear expression of MCM2 was noted in tumor but not mitotic cells of all the MFHs and 26 (72.2%) of the BFHTs, the labeling indices (LIs) being 62.0% in the 28 ordinary types, 38.5% in the 10 myxoid types, and 11.2% in the BFHTs with significant difference. Moreover, the LI was significantly higher for MCM2 than that for Ki-67 in the MFHs of both types (p<0.05). No correlation was noted between the MCM2-LI and P53 expression or apoptotic indices, which were significantly higher in the MFHs than BFHTs (p<0.01). These results indicate that MCM2 would correlate with cell proliferation rather than apoptosis in MFHs, and the expression is ubiquitous in proliferating cells, regardless of the expression of P53. Thus, MCM2 might be a reliable marker of proliferating cells in human MFH.
Int J Mol Med 2002 Aug
PMID:Expression of minichromosome maintenance-2 in human malignant fibrous histiocytomas: Correlations with Ki-67 and P53 expression, and apoptosis. 1211 52

The aim of this study was to evaluate the possible correlation between preoperative FDG-PET results in human breast cancer and the prognostic markers Ki-67, c- erb B2, p53, oestrogen/progesterone receptor status, axillary lymph node status, tumour size and tumour grading. Seventy-five female patients with breast cancer were included in this prospective study. Patient selection was independent of tumour size and the suspected clinical stage of disease. A high-resolution full-ring scanner (Siemens ECAT HR+) was used for PET imaging. The FDG uptake of breast tumours was calculated as the tumour to background ratio (TBR). In resected cancer tissue specimens, the proliferative fraction was evaluated by Ki-67 immunostaining. Additionally, immunostaining of the prognostic markers c-erb B2, p53, and progesterone and oestrogen receptors was performed. Haematoxylin and eosin-stained sections were used for tumour grading. Correlations between FDG uptake and prognostic markers were assumed to be significant at P<0.05 using the Mann-Whitney U test. In ductal breast cancer, mean TBR was 17.3 (median 7.7, range 1.6-122.7), while in lobular cancer it was 6.5 (median 3.7, range 1.4-22.7). Mean proliferative fraction (% Ki-67 positive tumour cells) was 15%+/-13.8% (median 10%, range 0%-60%). Twenty-three carcinomas showed <5% Ki-67 positive tumour cells. Statistical analysis indicated a positive correlation between FDG uptake and proliferative index in ductal breast cancer ( P<0.0001, r=0.63). By contrast, there was no correlation between FDG uptake and c- erb B2 ( P=0.79), p53 ( P=0.92), tumour grading ( P=0.09), oestrogen receptor status ( P=0.41), progesterone receptor status ( P=0.34), axillary lymph node status ( P=0.90) and tumour size ( P=0.3). It is concluded that FDG uptake is significantly higher in ductal breast cancer than in lobular cancer ( P<0.05). FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining ( P<0.05). A significant correlation with the other prognostic markers, however, could not be demonstrated.
Eur J Nucl Med Mol Imaging 2002 Oct
PMID:FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. 1227 13

Amino acid transport system A is expressed strongly in neoplastic cells. [ N-methyl-(11)C]alpha-Methylaminoisobutyric acid ((11)C-MeAIB) is a recently developed tracer for PET studies on system A amino acid transport. (11)C-MeAIB is a metabolically stable amino acid analogue which is transported from plasma into the tissue by system A. This study evaluated the kinetics of (11)C-MeAIB uptake from plasma into tumour tissue and normal tissues in 13 patients with untreated head and neck cancer. (11)C-MeAIB uptake in tumour was compared with histological grade and proliferative activity. Tracer uptake was quantitated by calculating the standardised uptake values (SUVs) and the kinetic influx constants ( K(i)) using graphical analysis. All tumours accumulated (11)C-MeAIB and were visualised clearly. In the graphical analysis, linear plots were achieved; the mean K(i) value of tumour was 0.056+/-0.026 min(-1), and the mean SUV was 6.1+/-2.7. A close correlation between graphically obtained K(i) and semi-quantitative SUV in tumours was found ( r=0.887, P=0.00005). We could not demonstrate a correlation between the uptake of (11)C-MeAIB and the grade of malignancy or the proliferative index, as assessed using Ki-67 immunohistochemical assay. Head and neck cancer can be effectively imaged with (11)C-MeAIB PET. (11)C-MeAIB showed active and rapid transport into tumour tissue and salivary glands. Further studies on the applicability of (11)C-MeAIB PET for radiation treatment planning in the head and neck region and the regulation of system A amino acid transport under different metabolic states are warranted.
Eur J Nucl Med Mol Imaging 2003 Jan
PMID:Uptake of [N-methyl-11C]alpha-methylaminoisobutyric acid in untreated head and neck cancer studied by PET. 1248 12


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