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)

Chemosensitivity is affected by molecular biological factors, including factors related to the induction of apoptosis and the activity of proliferation. We analyzed immunohistochemically the expression of p53, Bcl-2, and Ki-67 in various types of cancers and assessed the correlation between this expression and chemosensitivity. Moreover, we investigated whether the expression of these factors could be a useful predictor for the clinical response to chemotherapy. Study subjects comprised 63 preoperative patients with untreated malignant tumors (9 with esophageal cancer, 12 with stomach cancer, 12 with colon cancer, 16 with liver cancer, and 14 with breast cancer). Immunohistochemical staining (the labeled streptavidin biotin technique: LSAB method) was used to assess expression of p53 protein, Bcl-2 protein, and Ki-67. A chemosensitivity test was carried out with the histoculture drug response assay method using four drugs: mitomycin C, 5-fluorouracil, doxorubicin hydrochloride (ADM), and cisplatin (CDDP). Immunohistochemical studies for p53 were found to be useful for predicting chemosensitivity.
Methods Mol Med 2005
PMID:Immunohistochemistry of p53, Bcl-2, and Ki-67 as predictors of chemosensitivity. 1590 38

The objective of this study was to examine the incidence of apoptosis in placentas of intrauterine growth restriction (IUGR) without maternal disease. We focused on cases of IUGR with both unknown causes and no maternal complications. In addition, apoptosis of IUGR placentas was correlated with the expression of proteins involved in apoptosis and cell turnover. The term placentas were obtained from 16 normal and 10 IUGR pregnancies without maternal symptoms. We analyzed the localization of apoptosis and counted >2000 nuclei by TUNEL assay and transmission electron microscopy in placentas from normal and IUGR cases. We found the incidence of apoptosis to be significantly higher in placentas with IUGR (2.98%) than in normal placentas (1.46%) by TUNEL assay (p=0.03). In addition, immunohistochemical analysis was performed to examine the expression of proteins related to apoptosis and general cell turnover, including the active form of caspase-3, Bax, p53, and Ki-67. Expression of the active form of caspase-3 was significantly higher in IUGR than in a normal pregnancy (p=0.03). These results suggest that enhanced execution of apoptosis through caspase-3 may play a role in IUGR without maternal symptoms.
Int J Mol Med 2005 Jul
PMID:Frequent apoptosis in placental villi from pregnancies complicated with intrauterine growth restriction and without maternal symptoms. 1594 81

Barrett's esophagus is a premalignant condition associated with gastroesophageal reflux disease, and consists of mucosa with a metaplastic columnar epithelium (specialized columnar epithelium). In this study, we examined the expression of mucin and the Ki-67 labeling index (LI) in 15 cases of esophageal Barrett's adenocarcinoma, and clarified the significance of incomplete intestinal metaplasia of Barrett's mucosa as a premalignant lesion. Gastric mucin (MUC5AC, HGM, and/or MUC6) was detected in 93.3% of the adenocarcinomas, while MUC2 and CD10 (markers of intestinal phenotypes) were detected in 73.3% and 46.2%, respectively. The Ki-67 LI was 34.1% in Barrett's adenocarcinoma. In all cases, gastric mucin was found in the non-neoplastic Barrett's mucosa around the adenocarcinoma. MUC2 was detected in 86.7% of proximal non-neoplastic mucosa and 100% of distal non-neoplastic mucosa, while CD10 was found in 20.0% of proximal non-neoplastic mucosa and 40.0% of distal non-neoplastic mucosa of Barrett's adenocarcinoma. In conclusion, Barrett's esophageal mucosa with intestinal metaplasia and a high Ki-67 LI is suggested to be more important as a premalignant lesion, and predominantly found in the proximal rather than distal region of Barrett's esophagus.
Int J Mol Med 2005 Sep
PMID:Mucin expression and proliferating cell index of esophageal Barrett's adenocarcinoma. 1607 42

The p63 gene, a homolog of the tumor suppressor gene TP53, maps to chromosome 3q27-28, a region frequently displaying genomic amplification in squamous cell carcinomas. p63 is expressed in a variety of epithelial tissues and has been reported to be critical for the normal development of stratified epithelia, including skin epidermis. In a previous study, the authors reported the expression of p63 in occasional cells in the germinal center of lymph nodes and also observed p63 expression in B-cell lymphomas, among other tumor types surveyed in that analysis. The present study was conducted to further analyze the potential clinical significance of identifying p63 expression, assessing a larger cohort of well-characterized patients with diffuse large B-cell lymphoma (DLBCL) (n = 172 cases) and a panel of established lymphoma cell lines. p63 expression at the microanatomic detail was examined by immunohistochemistry using a monoclonal antibody (clone 4A4), while distinction of p63 isoforms was analyzed by Western blotting and reverse transcription-polymerase chain reaction using isoform-specific primers. The authors found that a subset of DLBCL (32% of cases) expressed p63 in the nuclei of neoplastic lymphocytes. Examination of the different p63 isoforms revealed that the DeltaNp63 species was expressed by only one cell line, while the other p63 isoforms were found in most cell lines analyzed. The authors also observed that p63 expression correlated with high proliferative index, as assessed by Ki-67 immunostaining. Even though in univariate analysis p63 expression did not correlate with overall survival, the association of p63 with increased proliferative index suggests its involvement in DLBCL tumor progression.
Appl Immunohistochem Mol Morphol 2005 Sep
PMID:Expression of p63 in diffuse large B-cell lymphoma. 1608 48

Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer and the prognosis is usually very poor. The biologic pathways involved in its oncogenesis are unknown. beta-catenin, a key target in the Wnt-signaling pathway, is recognized to play an important role in the carcinogenesis in conventional colorectal carcinoma. This study explores the involvement of Wnt-signaling molecules beta-catenin and cyclin D1, cell cycle regulators cyclin D3, proliferative index Ki-67, apoptotic index, and angiogenic indicator CD31 in 20 colorectal SRCC paraffin-embedded specimens. Results showed that there were 2 specimens with nuclear beta-catenin and higher expression of cyclin D1 than the remaining 18 specimens. Surprisingly, those 2 patients had a much shorter survival of 6 months than the remaining 15 patients, who had around 24 months. Moreover, all colorectal SRCC specimens had an overexpression of cyclin D1, cyclin D3, and Ki-67, as well as much more angiogenesis and apoptosis than adjacent normal epithelial tissues. The authors make the preliminary comment that nuclear beta-catenin is a rare phenomenon in colorectal SRCC, but the involvement of it may indicate a worse prognosis with shorter survival than colorectal SRCC without nuclear beta-catenin expression. Besides, overexpression of cyclin D1, cyclin D3, Ki-67, and increased angiogenesis and apoptosis may play a vital role in promoting colorectal SRCC development.
Appl Immunohistochem Mol Morphol 2005 Sep
PMID:Nuclear beta-catenin expression is rare and its potential association with short survival in colorectal signet-ring cell carcinoma. 1608 50

A recently introduced histologic fixative (Universal Molecular Fixative [UMFIX]) has been shown to preserve macromolecules in tissue at ambient temperature. When UMFIX-exposed tissues are processed by a formalin-free, microwave-assisted rapid processing system, the resulting paraffin blocks retain good histomorphology and intact nucleic acids suitable for expression microarray analysis. Because UMFIX may be used as an alternative to formalin, the authors set out to study the effect of this new fixation and processing system on immunohistochemistry (IHC) by analyzing a range of human neoplastic and non-neoplastic specimens. Parallel slices from surgically removed specimens were fixed in formalin and UMFIX and processed in a rapid microwave-assisted tissue processor. IHC was performed following routine procedures. The staining for those antibodies that normally required antigen retrieval was carried out with and without that step. The intensity and pattern of reactions were compared in 144 tissue samples fixed by the two methods using 70 monoclonal and polyclonal antibodies. The intensity of IHC reactions for most cytoplasmic antigens was generally equal or stronger in UMFIX tissues. This was particularly true with intermediate filaments and HercepTest, where the antigen retrieval step became unnecessary. Conversely, there was a decrease in the intensity of reactions for HepPar1, bcl-2, and three nuclear antigens (Ki-67, TTF-1, and estrogen receptor). Increasing their exposure times optimized the sensitivity of the latter four antibodies. The study shows that IHC staining results of tissues fixed in UMFIX and processed by the microwave-assisted system are comparable to those obtained on formalin-fixed, similarly processed specimens. There is an enhancement of the sensitivity of few antibodies in UMFIX-exposed tissue, rendering antigen retrieval unnecessary. This increased sensitivity may be due to the effect of eliminating formalin from fixation and processing or the microwave energy.
Appl Immunohistochem Mol Morphol 2005 Sep
PMID:Immunohistochemistry of tissue prepared by a molecular-friendly fixation and processing system. 1608 56

New therapeutic strategies are required to overcome the limitations of conventional breast cancer treatment. Suicide gene therapy offers a potential approach to this type of tumour, since systems based on the use of prodrugs may present some drawbacks related to toxicity, drug release and bioavailability. The gef gene has cell-killing functions in Escherichia coli and does not depend on the use of a prodrug for its action, making it an attractive target for suicide gene therapy. We created a gef-overexpressing human breast cancer cell line (MCF-7TG) by transfecting the gef gene under the control of a pMAMneo promotor. Dexamethasone-induction of gef gene expression in MCF-7TG cells produced a significant decrease in Ki-67 expression, which is a known proliferation marker. In addition, annexin-V-FITC and propidium iodide assays showed the presence of apoptotic cell death, which was confirmed by scanning electron microscopy. The most significant finding was the presence of "craters" in the cell membrane, as previously described in other apoptotic breast cancer cells. These results demonstrate the ability of the gef gene to down regulate Ki-67 expression and induce apoptosis in a breast cancer cell line, suggesting its potential application as a new gene therapy strategy for this type of tumor.
Cell Mol Biol (Noisy-le-grand) 2005 Sep 02
PMID:Modulation of Ki-67 expression and morphological changes induced by gef gene in MCF-7 human breast cancer cells. 1617 67

The thyroid gland is an endocrine organ composed of stable cells. It is well known that regenerative capacity of the thyroid tissue is minimal. Various degrees of morphologic alterations do occur in chronic lymphocytic thyroiditis (CLT), including Hashimoto's thyroiditis. Eighty-five CLT cases were analyzed for these morphologic alterations. Small, irregular, atrophic or hyperplastic thyroid follicles were seen adjacent to the lymphocytic infiltration. There was nuclear enlargement, loss of nuclear polarity in thyrocytes and intrafollicular thyrocyte proliferation in these follicles. We thought that the morphologic alterations in involved follicles could be due to regenerative hyperplasia with increased proliferative activity and basement membrane abnormalities. To examine this hypothesis we investigated Ki-67 and laminin immunoreactivity in the involved follicles adjacent to lymphocytic infiltration areas. The uninvolved follicles were used as controls. Immunopositivity of Ki-67 in involved follicles was significantly higher than that in uninvolved follicles (2.97% +/- 2.16 versus 0.83% +/- 1.63, P < 0.001). Laminin immunostaining indicated the destruction or irregular distribution of basement membrane in involved follicles. We conclude that the increased cell proliferation activity and basement membrane abnormalities in the follicles with morphologic changes adjacent to CLT occur in conjunction with regenerative hyperplasia.
Appl Immunohistochem Mol Morphol 2005 Dec
PMID:Regenerative hyperplasia of follicular epithelium in chronic lymphocytic thyroiditis. 1628 Jun 65

The phenomenon of adult neurogenesis (AN), that is, the generation of functional neurons from neural stem cells in the dentate gyrus of the hippocampus, has attracted remarkable attention, especially as it was shown that this process is also active in the human brain. Based on animal studies, it has been suggested that reduced AN is implicated in the etiopathology of psychiatric disorders, and that stimulation of AN contributes to the mechanism of action of antidepressant therapies. As data from human post-mortem brain are still lacking, we investigated whether the first step of AN, that is, the level of neural stem cell proliferation (NSP; as quantified by Ki-67 immunohistochemistry), is altered in tissue from the Stanley Foundation Neuropathology Consortium comprising brain specimens from patients with bipolar affective disorder, major depression, schizophrenia as well as control subjects (n=15 in each group). The hypothesis was that stem cell proliferation is reduced in affective disorders, and that antidepressant treatment increases NSP. Neither age, brain weight or pH, brain hemisphere investigated nor duration of storage had an effect on NSP. Only in bipolar disorder, post-mortem interval was a significant intervening variable. In disease, onset of the disorder and its duration likewise did not affect NSP. Also, cumulative lifetime dose of fluphenazine was not correlated with NSP, and presence of antidepressant treatment did not result in an increase of NSP. Concerning the different diagnostic entities, reduced amounts of newly formed cells were found in schizophrenia, but not in major depression. Our findings suggest that reduced NSP may contribute to the pathogenesis of schizophrenia, whereas the rate of NSP does not seem to be critical to the etiopathology of affective disorders, nor is it modified by antidepressant drug treatment.
Mol Psychiatry 2006 May
PMID:Neural stem cell proliferation is decreased in schizophrenia, but not in depression. 1641 15

Vascular endothelial growth factor (VEGF) expression pattern and blood vessel remodelling were evaluated during the transition from the preovulatory follicle to the corpus luteum (CL). To this end, prepubertal gilts were treated with equine chorionic gonadotrophin (eCG) to collect preovulatory follicles (60 h after eCG) and with human chorionic gonadotrophin (hCG) to obtain periovulatory follicles 18 h and 36 h later. The VEGF mRNA content was analysed by in situ hybridization, while protein localization in follicular fluid (FF) and in granulosa and theca compartments was evaluated by ELISA, immunohistochemistry or western blot. Blood vessel architecture and vascular area (VA) were investigated using immunohistochemistry for von Willenbrand Factor, a specific endothelial marker. Vascular remodelling was finally tested using Ki-67 immunocytochemistry as a proliferation marker, or alpha-smooth muscle actin (alpha-SMA) as a specific mural cell marker. eCG-treated follicles showed high VEGF levels and two concentric blood vessel networks composed of proliferating endothelial cells without any association with mural components. hCG injection inhibited VEGF synthesis in the granulosa compartment and, as a consequence, the protein fell within the FF. In parallel, endothelial cell proliferation stopped and the VA decreased. Close to ovulation, VEGF production restarted in both follicular compartments and VEGF mRNA content significantly increased in the theca layer. Changes in follicular VEGF secretion were observed; the protein disappeared from FF and was observed in the extracellular matrix. An active angiogenesis characterized the follicle; endothelial cell proliferation was associated with a recruitment of alpha-SMA-positive mural cells. The data presented in this work showed that, in the phases preceding ovulation, a complete vascular remodelling occurs, characterized by both an evident neovascularization and the appearance of blood vessels presenting smooth musculature which could be involved in CL formation after ovulation.
J Mol Endocrinol 2006 Feb
PMID:Spatio-temporal analysis of vascular endothelial growth factor expression and blood vessel remodelling in pig ovarian follicles during the periovulatory period. 1646 31


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