Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factors are known to inhibit apoptosis and promote tumour angiogenesis. Previously we have shown that insulin-like growth factor binding protein-4 (IGFBP-4) gene therapy increased apoptosis and decreased mitosis in colon cancer. In this experiment we used HT-29 colon cancer cells to induce subcutaneous cancers in nude mice and administered either the mammalian expression vector with IGFBP-4 insert or vector only around the tumour site. Three weeks after gene transfer, tumours were harvested and expressions of Bax, Bcl-2 and IGF-I receptor in tumours were determined by Western blotting and immunofluorescence. Micro-vessel counting was performed by immunostaining with CD34 and von Willebrand antibodies. Results showed that tumours treated with IGFBP-4 gene had higher expression of Bax, lower expression of Bcl-2 and IGF-I receptor. Bcl-2 was localised to tumour cell cytoplasm while Bax was expressed both in the interstitial area and cytoplasm. IGFBP-4 treatment also decreased micro-vessel count in tumour tissues. Micro-vessels were mainly located in the periphery and interstitial area. This experiment shows that IGFBP-4 gene therapy increases tumour apoptosis via altering the expressions of Bcl-2 and Bax and decreasing the angiogenesis in colorectal cancer.
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PMID:Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer. 1733 27

Solitary fibrous tumours (SFT) are rare neoplasms, with an uncommon laryngeal involvement. Only five cases of laryngeal localization have been described in literature. The following is a case of a 75-year-old man with a supraglottic neoplasm of the larynx; after the biopsy immunohistochemical study demonstrated a strong positivity for vimentin, CD34 and Bcl-2. The neoplasm was consequently classified as a SFT. CO(2) laser surgery of the supraglottic larynx, with a wide excision of the neoplasm, was performed. Twenty-four months on, the patient is alive, well and free of disease. Surgical resection is the treatment of choice for laryngeal SFT, but tumour-free resection margins must be achieved to prevent the possibility of local recurrence. Endoscopic resection by means of the CO(2) laser must be accurately planned with MRI or CT imaging to confirm of this kind of surgery.
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PMID:Laryngeal solitary fibrous tumour. 1733 42

A solitary fibrous tumor (SFT) is an unusual spindle cell neoplasm that usually occurs in the pleura but has recently been described in diverse extrapleural sites. Urogenital localization is rare, and only 19 cases of SFT of the kidney have been described. We report a case of a large SFT clinically thought to be renal cell carcinoma arising in the kidney of a 70-year-old man. The tumor was well circumscribed and composed of a mixture of spindle cells and dense collagenous bands, with areas of necrosis or cystic changes noted macroscopically and microscopically. Immunohistochemical studies revealed reactivity for CD34, CD99, and Bcl-2 protein, with no staining for keratin, S-100 protein, or muscle markers, confirming the diagnosis of SFT. This tumor is benign in up to 90% of cases. The immunohistochemical study is the key to diagnosis.
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PMID:Solitary fibrous tumor of the kidney: a case report and review of the literature. 1739 71

The work is devoted to consequent expression of different cell types' protein markers such as vimentin, desmin, cytokeratins 7, 18, 19, stem cell markers CD34 and Bcl-2 at early stages of human prenatal development. Desmin was revealed in sinusoidal liver cells on 3.5-12 weeks of gestation, in mesenchymal cells of ventral mesentery and hepatoblasts on the 4-7 accordingly. During hepatic period of blood formation such desmin positive sinusoidal cells were found to be located close to blood cells. So called "cholangio-" cytokeratins 7 and 19 showed different expression, the first one was found only in cholangiocytes, while cytokeratin 19 existed in hepatoblasts as well until week 15-16 of prenatal development. Mesenchymal cells of ventral mesentery are positive for cytokeratins 18 and 19 even brighter than hepatoblasts in the 4-7 weeks of gestation. Bcl-2 expression was seen in the same periods in most sinusoidal and mesenchymal cells of ventral mesentery. CD34 positive cells are strongly depicted in liver sinusoids from 4th until 9th weeks of gestation, but probably they are not a source of hepatocytes' development in embryonic ontogenesis. Ventral mesentery mesenchyme was negative for this very marker. These results let us suppose that hepatocytes and cholangiocytes may develop from quite different embryonic sources: cholangyocytes grow exceptionally from duodenum epithelial cells, while there is a strong possibility that hepatoblasts formation occurs with participation of mesenchymal cells.
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PMID:[Cell sources of liver development]. 1743 98

Lipomatous hemangiopericytoma is a rare mesenchymal tumor showing areas of lipid-containing cells admixed with a spindle-cell component. Like other hemangiopericytomas, it shows a similar vascular pattern to solitary fibrous tumor and, partly for this reason, it and other hemangiopericytomas have been subsumed into solitary fibrous tumor. The present study provides a comprehensive documentation of a single case of pulmonary lipomatous hemangiopericytoma of the lung, the first to be described at this site, and compares it with solitary fibrous tumor, in terms of clinical, histological, immunohistochemical, ultrastructural, and cytogenetic findings. Apart from the lipid-laden-cell component, pulmonary lipomatous hemangiopericytoma and solitary fibrous tumor were similar histologically. Bcl-2 was positive in both. CD34 was minimally expressed in pulmonary lipomatous hemangiopericytoma, which possessed some non-descriptive intercellular junctions, a feature shared by solitary fibrous tumor, which was CD34 positive. However, one of the latter was rich in gap junctions, a feature consistent with strong connexin (Cx) 43 staining and the existence, hitherto unappreciated, of a CD34/Cx43-positive tumor cell network. In pulmonary lipomatous hemangiopericytoma, chromosomal deletions of 43-44, X, -Y were found. In solitary fibrous tumor, 46, XY, del(13)(q?) abnormalities and abnormalities involving chromosome 10 were frequently observed. These similarities and differences are discussed in the context of the currently favored diagnostic fusion of hemangiopericytoma and solitary fibrous tumor.
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PMID:Pulmonary lipomatous hemangiopericytoma: report of a rare tumor and comparison with solitary fibrous tumor. 1745 98

One of the least commonly encountered spindle cell tumors seen on prostatic needle biopsy or transurethral resection (TUR) of the prostate is solitary fibrous tumor (SFT). We studied 13 cases of SFTs identified on either prostate needle biopsy (n=9) or TUR of the prostate (n=4). Mean patient age at diagnosis was 63 years (range: 46 to 75 y; median: 65 y). Twelve men presented with urinary tract symptoms and 1 patient was biopsied during work-up of bone metastases. Ten cases were SFTs originating in the prostate, 2 cases arose between the prostate and rectum extending into the prostate (n=2), and 1 case was a pelvic mass without infiltration of the prostate. In 9 cases, a complete tumor resection was attempted by cystoprostatectomy (n=2), radical prostatectomy (n=4), pelvic exenteration (n=2), or pelvic tumor resection (n=1). Enucleation (n=1) and TUR (n=1) were performed in 2 other cases. Tumor sizes ranged from 8.5 to 15 cm in 7 radically resected cases. Mitotic rates were 3 to 5 per 10 high power fields in 5 cases, with the remaining cases having either rare (n=4) or no mitoses (n=4). Seven cases demonstrated areas of necrosis. Based on a combination of increased cellularity, mitotic activity, necrosis, nuclear pleomorphism, and infiltrativeness, 4 prostatic SFTs were malignant, 4 were benign, and 2 were borderline. Of the 3 non-prostatic SFTs, 1 was malignant and 2 were borderline. All tumors but 1 were immunoreactive for CD34 (n=12). Material for additional immunohistochemistry was available for the majority of cases with positive stains for Bcl-2 (11/11), CD99 (7/10), beta-catenin (5/10), and c-kit (0/11). Three SFTs demonstrated >or=10% p53 immunoreactivity including 1 tumor with 50% positivity; and 3 cases had Ki-67 rates of >or=20%. Although all SFTs were initially clinically considered to be of prostatic origin, some of the cases arose in the pelvis with secondary involvement of the prostate. Approximately 50% of prostatic SFTs were malignant. Even in the prostatic and nonprostatic SFTs with no overt malignant features, sometimes it was necessary to remove the prostate and in some instances the adjacent organs because of the large size of the tumors. SFTs must be differentiated from other spindle cell neoplasms of the prostate especially from gastrointestinal stromal tumors that may arise from the rectal wall with invasion of the prostate or from the region between the rectum and the prostate.
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PMID:Solitary fibrous tumor on needle biopsy and transurethral resection of the prostate: a clinicopathologic study of 13 cases. 1752 73

The effects of the multikinase inhibitor sorafenib (BAY 43-9006), an agent shown previously to induce apoptosis in human leukemia cells through inhibition of myeloid cell leukemia-1 (Mcl-1) translation, have been examined in Bcr/Abl(+) leukemia cells resistant to imatinib mesylate (IM). When administered at pharmacologically relevant concentrations (10-15 microM), sorafenib potently induced apoptosis in imatinib mesylate-resistant cells expressing high levels of Bcr/Abl, cells exhibiting a Bcr/Abl-independent, Lyn-dependent form of resistance, and CD34(+) cells obtained from imatinib-resistant patients. In addition, Ba/F3 cells expressing mutations rendering them resistant to IM (e.g., E255K, M351T) or to IM, dasatinib, and nilotinib (T315I) remained fully sensitive to sorafenib. Induction of apoptosis by sorafenib was associated with rapid and pronounced down-regulation of Mcl-1 and diminished signal transducer and activator of transcription (STAT) 5 phosphorylation and reporter activity but only very modest and delayed inactivation of the Bcr/Abl downstream target Crkl. Moreover, transfection with a constitutively active STAT5 construct partially but significantly protected cells from sorafenib lethality. Ba/F3 cells expressing Bcr/Abl mutations were as sensitive to sorafenib-induced Mcl-1 down-regulation and dephosphorylation of STAT5 and eukaryotic initiation factor 4E as wild-type cells. Finally, stable knockdown of Bcl-2-interacting mediator of cell death (Bim) with short hairpin RNA in K562 cells significantly diminished sorafenib lethality, arguing strongly for a functional role of this proapoptotic Bcl-2 family member in the lethality of this agent. Together, these findings suggest that sorafenib effectively induces apoptosis in highly imatinib-resistant chronic myelogenous leukemia cells, most likely by inhibiting or down-regulating targets (i.e., STAT5 and Mcl-1) downstream or independent of Bcr/Abl.
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PMID:The multikinase inhibitor sorafenib induces apoptosis in highly imatinib mesylate-resistant bcr/abl+ human leukemia cells in association with signal transducer and activator of transcription 5 inhibition and myeloid cell leukemia-1 down-regulation. 1759 28

The purpose of this work was to study clinical and biological characteristics of solitary fibrous tumor (SFT) of the pleura. We reviewed the clinicopathological and immunohistochemical features of 12 patients who underwent surgical resection for SFT. Ten cases were histologically defined as benign; two were found to be malignant. CD34 negativity and strong expression of p53 could be observed in a patient with fatal outcome. Ki-67 expression was increased in malignant cases, as compared with benign. We also found that Bcl-2 expression inversely correlated with a tumor diameter. As the development of malignant SFT might be associated with these molecular statuses, immunohistochemical staining should be performed in all cases to identify the biological characteristics of the tumor.
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PMID:Solitary fibrous tumors of the pleura: clinicopathological and immunohistochemical examination. 1766 89

In view of obscure clinical and biological significance of leukemic cells heterogeneity, we studied the efficacy of apoptosis, proliferation, and expression levels of the Bcl-2, MDR1, LRP, and BCRP genes in sorted CD34+ and CD34- subpopulations of childhood AML leukemic samples. In five out of nine cases, CD34+ cells were less sensitive to spontaneous apoptosis and had from 1.2- to 5.0-fold higher expression levels of Bcl-2 (eight of ten) and from 1.5- to 28.7-fold higher expression levels of MDR1 (eight of ten). The expression levels of the LRP gene were from 1.1- to 1.8-fold higher in CD34+ subpopulations (five of ten cases), and the expression levels of the BCRP gene were from 1.1- to 22.4-fold higher in CD34+ leukemic cells (six of ten). In all M4 cases, the expression levels of LRP were higher in the CD34- subpopulation. Significant differences in the patterns of genes expression between patients do not allow us to conclude that the CD34+ fractions have more resistant phenotype than the CD34- subpopulations. Nevertheless, distinctions between CD34+ and CD34- cells may lead to different chemosensitivities between leukemic subpopulations in vivo and may determine the alteration of the leukemic immunophenotype during treatment and in relapse.
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PMID:CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34- cells in childhood AML. 1862

Numerous papers have reported that mesenchymal stem cells (MSCs) can be isolated from various sources such as bone marrow, adipose tissue and others. Nonetheless it is an open question whether MSCs isolated from different sources represent a single cell lineage or if cells residing in different organs are separate members of a family of MSCs. Subendothelial tissue of the umbilical cord vein has been shown to be a promising source of MSCs. The aim of this study was to isolate and characterize cells derived from the subendothelial layer of umbilical cord veins as regards their clonogenicity and differentiation potential. The results from these experiments show that cells isolated from the umbilical cord vein displayed fibroblast-like morphology and grew into colonies. Immunophenotyping by flow cytometry revealed that the isolated cells were negative for the hematopoietic line markers HLA-DR and CD34 but were positive for CD29, CD90 and CD73. The isolated cells were also positive for survivin, Bcl-2, vimentin and endoglin, as confirmed by RT-PCR and immunofluorescence. These cells can be induced to differentiate into osteogenic and adipogenic cells, but a new finding is that these cells can be induced to differentiate into endothelial cells expressing CD31, vWF and KDR-2, and also form vessel-like structures in Matrigel. The differentiated cells stopped expressing survivin, thus showing a diminished proliferative potential. It can be assumed that the subendothelial layer of the umbilical cord vein contains a population of cells with the overall characteristics of MSCs, with the additional capability to transform into endothelial cells.
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PMID:Characterization of mesenchymal stem cells isolated from the human umbilical cord. 1839 23


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