Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocytoid B cells (MBCs) are a subset of B cells that may be recognized in several reactive and tumoral lymph node conditions, including toxoplasmic lymphadenitis, infectious mononucleosis, and Hodgkin's lymphoma. Although this is a commonly observed cell population, which has even given its name to a type of lymphoma, MBC lymphoma, scarcely any information is available about the function and characteristics of this cell type. A relationship with marginal zone (MZ) B lymphocytes has been claimed for MBCs, but this has not yet been fully proven. Indeed, specific markers for MBCs are still lacking, which has made it difficult to analyze their relationship with other B cell subpopulations and confirm the existence of tumors deriving from this B cell subset. We used a panel of cell cycle markers to explore the characteristics of MBCs and their relationship with MZ B cells, nodal MZ lymphoma, and splenic MZ lymphoma. We therefore compared the phenotypic profile of MBCs in different conditions with normal MZ B cells within the spleen and mesenteric lymph nodes, with a group of seven cases of nodal MZ/MBC lymphoma and another group of five cases of splenic MZ lymphoma. MBCs were mainly in the G(0) to G(1) phases, as deduced from the presence of a proportion of between 10 and 35% Ki67-positive cells, whereas very low expression was observed with cyclin A and cyclin B staining. Nests of MBCs were clearly labeled by the expression of p21(WAF1), a cyclin-dependent kinase inhibitor (CKI), rarely detectable in benign lymphocytes, and by cyclin E. Basically all MBCs were bcl-2-negative, and high cyclin D2 and cyclin D3 were also detected in these cells, at proportions and intensities above expected levels, when the percentage of proliferating cells was taken into account. p27(KIP1) expression was characterized by homogeneous reactivity, higher than that observed in other B cell populations with a relatively high-growth fraction. Immunoglobulin staining showed undetectable light and heavy chains. However, splenic MZ cells, nodal MZ lymphoma, and splenic MZ lymphoma showed a distinct expression of IgM and bcl-2, with high p27 (KIP1) nuclear expression and undetectable or low levels of cyclin A, B, E, or D, or p21(WAF1) expression. The data from this study show an unexpected immunophenotype in MBCs, different from the one observed in splenic and lymph node MZ B cells. This suggests that either MBCs are a unique B cell population from a distinct cell lineage, or if related to MZ cells, they would represent a definite differentiation stage characterized by a distinctive immunophenotype. They also show so-called MZ/MBC lymphoma to be more closely related to lymph node and splenic MZ B cells, as they do not share the most distinctive features of MBCs.
 ...
PMID:Unique phenotypic profile of monocytoid B cells: differences in comparison with the phenotypic profile observed in marginal zone B cells and so-called monocytoid B cell lymphoma. 1129 May 54

In the rat mammary carcinogenesis model, premalignant lesions known as intraductal proliferations (IDPs) are detectable within a few weeks after carcinogen treatment. These early transformed colonies are the precursors for the eventual formation of carcinomas. Our past research indicated that methylselenocysteine added to the diet of rats reduced the development of IDPs of all sizes (the size of each IDP was estimated operationally by the number of 5-micron serial sections showing the same pathology). The appearance of an IDP lesion represents a balance between cell proliferation and cell death. The modulation of these two cellular events by methylselenocysteine was investigated. The abdominal-inguinal mammary gland was excised 6 weeks after MNU administration. Proliferation and apoptosis were evaluated by BrdU labeling and the TUNEL assay, respectively. The expression levels of several cell cycle and apoptosis regulatory proteins, including cyclin D1, cyclin A, p27, p16, bcl-2, box and bak, were also assessed. All of the above endpoints were quantified by immunohistochemistry in paraffin-embedded sections. The results showed that the magnitude of the response to methylselenocysteine intervention seemed to depend on the size of the IDP lesion. For the purpose of this study, the small and large lesions were classified as those containing < or = 30 or > 30 serial sections, respectively. With the small lesions, methylselenocysteine significantly inhibited BrdU labeling and the expression of cyclin D1 and cyclin A, but increased the expression of p27. Interesting, only p27 was upregulated in the larger IDP lesions, while BrdU labeling and the cyclins were not affected. It is possible that the transformed phenotype becomes less sensitive to selenium-mediated arrest of proliferation once it progresses to a more advanced pathological stage. In contrast, methylselenocysteine stimulated apoptosis (TUNEL assay) by 3 to 4 fold, and this increase was evident in both the small and large IDP lesions. Consistent with the induction of apoptosis, a reduced expression of bcl-2 was also observed in the methylselenocysteine group. In summary, our data suggest that exposure to methylselenocysteine blocks clonal expansion of premalignant lesions at an early stage. This is achieved by simultaneously modulating certain molecular pathways that are responsible for inhibiting cell proliferation and enhancing apoptosis.
 ...
PMID:Methylselenocysteine modulates proliferation and apoptosis biomarkers in premalignant lesions of the rat mammary gland. 1139 76

Androgen signaling is crucial for the growth and development, as well as for tumorigenesis of the prostate. However, many of the prostate epithelial cell lines developed previously, either normal or tumorigenic, do not express androgen receptor (AR) or respond to androgen. In order to advance our understanding on how androgen signaling regulates the growth and the differentiation status, and affects tumorigenicity of the epithelial cell, we performed experiments on HPr-1, a prostate cell line recently immortalized from normal human prostate epithelial cells. In the present study, AR was stably transfected into HPr-1 cells by replication-defective retrovirus. Treatment of HPr-1AR cells with androgen resulted in cell differentiation and growth retardation accompanied with up-regulation of cytokeratins K8 and K18, prostate specific antigen, p21 and p27, and down-regulation of c-myc, bcl-2 and telomerase activity. Our results suggest that androgen promotes the process of differentiation in a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line which may reflect the normal effects of androgen on prostate cells.
 ...
PMID:Androgen induces differentiation of a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line. 1143 Nov 62

There is increasing evidence that there are different progression routes leading to invasive breast cancer, depending on histology and differentiation grade. The aim of this study was to determine alterations in the expression of proteins involved in proliferation and apoptosis in non-invasive and invasive ductal breast lesions. Immunohistochemistry was performed on 106 usual ductal hyperplasias (UDH), 61 DCIS lesions and 53 invasive ductal breast carcinomas. Increased proliferation (Ki67), overexpression of cyclin D1, HER-2/neu, p21 and p53, and decreased expression of bcl-2 and p27 could already be found in UDH. Significant differences between UDH and DCIS lesions were found for only one protein when UDH was compared with well-differentiated DCIS (p27), for three proteins when compared with intermediately differentiated DCIS (p21, cyclin D1, Ki-67), and for all proteins when compared with poorly-differentiated DCIS. Comparing DCIS with invasive lesions of same differentiation grade, proliferation was elevated in the invasive lesions. Altered expression of the other proteins was in general only slightly increased in the invasive lesion compared with DCIS. The number of proteins with altered expression per lesion was highest in poorly-differentiated lesions and was comparable between DCIS and invasive cancer of the same differentiation grade. In conclusion, the biggest changes in expression of these proliferation and apoptosis related proteins appear to occur during the transition from hyperplasia to DCIS; they probably play a minor role in the transition from DCIS to invasive breast lesion of same differentiation grade. Well-differentiated in situ and invasive breast lesions share many of the aberrations in expression of these proteins, as do poorly-differentiated in situ and invasive lesions. However, there are many differences between the well and poorly-differentiated lesions. This further supports the existence of different progression routes leading to breast cancer.
 ...
PMID:Similarity in expression of cell cycle proteins between in situ and invasive ductal breast lesions of same differentiation grade. 1143 65

Proliferative signaling by the IL-2R can occur through two distinct pathways, one mediated by Stat5 and one by the adaptor protein Shc. Although Stat5 induces T cell proliferation by serving as a transcription factor, the mechanism of proliferative signaling by Shc is poorly defined. We examined the roles of two major signaling pathways downstream of Shc, the p44/p42 mitogen-activated protein kinase (extracellular signal-related kinase (Erk)) and phosphatidylinositol 3-kinase (PI3K) pathways, in promitogenic gene induction and proliferation in the IL-2-dependent T cell line CTLL-2. Using IL-2R mutants and specific pharmacologic inhibitors, we found that the PI3K, but not Erk, pathway is required for maximal induction of c-myc, cyclin D2, cyclin D3, cyclin E, and bcl-x(L) by Shc. To test whether the PI3K pathway is sufficient for proliferative signaling, a tamoxifen-regulated form of PI3K (mp110*ER) was expressed in CTLL-2 cells. Activation of the PI3K pathway through mp110*ER failed to up-regulate expression of the c-myc, cyclin D2, cyclin D3, cyclin E, bcl-2, or bcl-x(L) genes or down-regulate expression of p27(Kip1), even when coactivated with the Janus kinases (Jak) or the Raf/Erk pathway. Moreover, mp110*ER induced modest levels of thymidine incorporation without subsequent cell division. Although insufficient for mitogenesis, mp110*ER enhanced Stat5-mediated proliferative signaling through a mechanism independent of Stat5 transcriptional activity. Thus, in addition to serving a necessary, but insufficient role in Shc-mediated promitogenic gene expression, the PI3K pathway contributes to T cell proliferation by potentiating mitogenic signaling by Stat5.
 ...
PMID:Phosphatidylinositol 3-kinase potentiates, but does not trigger, T cell proliferation mediated by the IL-2 receptor. 1150 15

Even in localized stages of non-small cell lung cancer, which are amenable to curative surgery, prognosis has remained disappointing over the last decades. Thus, in these tumor stages, adjuvant therapy strategies are discussed. In the last decade, numerous prognostic factors have been investigated, which might select patients for additional treatment. In this review, the prognostic impact of individual tumor cell dissemination, tumor cell proliferation, apoptosis, several parameters of angiogenesis (microvessel density, VEGF, bFGF, VEGF receptors), p53, bcl-2, ras, p27(Kip1), erbB-2, telomerase as well as the retinoblastoma tumor suppressor gene is analysed. Up to now, none of these factors has gained a sufficient selectivity to serve as an exclusive discriminator for adjuvant therapy. Nevertheless, a combination of several parameters might contribute to characterize patient subgroups with localized non-small cell lung cancer at high risk for distant relapse.
 ...
PMID:Prognostic factors in stage I/II non-small cell lung cancer. 1157 3

For the typical patient who has newly diagnosed prostate cancer, clinically organ-confined disease of moderate grade, and a PSA less than 10 ng/mL, the current role of imaging studies and molecular biomarkers is limited. Bone scans are not necessary for newly diagnosed men with a PSA less than 10 ng/mL in the absence of bone pain. Similarly, abdominal and pelvic CT scanning rarely provides any useful diagnostic or staging information when the PSA is less the 20 ng/mL and is indicated rarely. Endorectal coil MR imaging adds staging information for patients with a PSA between 10 and 20 ng/mL, a Gleason score of 7 or less, and 50% or more positive biopsies on a sextant sampling. Indium 111 capromab pendetide scanning (ProstaScint) is FDA-approved to evaluate newly diagnosed patients at high risk for metastases. These patients have a Gleason score of 7 or greater and a PSA greater than 20 ng/mL, a Gleason score of 8 to 10 regardless of the PSA value, or clinical stage T3 disease and a Gleason score of 6 or greater. RT-PCR testing of blood or bone marrow for prostate-specific or prostate cancer-specific gene expression, or "molecular staging," is a promising technique whose current use is still investigational. Much useful information may be gained by careful study of prostate needle biopsy material. Aside from current Gleason grading and the number or percentage of cores involved with cancer, no molecular biomarker is approved for clinical use. p27, p53, bcl-2, Ki-67 (MIB-1), and the assessment of neovascularity hold promise, but prospective multicenter studies are needed. In the long-term, multiple gene expression profiling of biopsy material using gene chips may revolutionize the care of patients with prostate cancer and those who elect radical prostatectomy.
 ...
PMID:The role of imaging studies and molecular markers for selecting candidates for radical prostatectomy. 1159 Aug 6

Rapamycin, a specific inhibitor of the serine/threonine mTOR kinase, markedly inhibited both cell growth and apoptosis in human B-cell lines. Besides arresting cells in G(1) by increasing p27(kip1), rapamycin tripled the cellular level of the BCL-2 protein. The activity was dose-dependent and specific for the p27(kip1) and BCL-2 proteins. Rapamycin did not affect bcl-2 mRNA although it increased cellular BCL-2 concentration by inhibiting phosphorylation, a mechanism initiating the decay process. To add new insight, we combined rapamycin treatment with treatment by taxol, which, by damaging microtubules, can phosphorylate BCL-2 and activate apoptosis. It was found that the mTOR kinase was activated in cells treated with taxol or with nocodazole although it was inhibited in cells pre-treated with rapamycin. BCL-2 phosphorylation, apoptosis and hyperdiploidy were also inhibited by rapamycin. In contrast, taxol-induced microtubule stabilization or metaphase synchronization were not inhibited by rapamycin. Taken together, these findings indicate that mTOR belongs to the enzymatic cascade that, starting from damaged microtubules, phosphorylates BCL-2. By regulating apoptosis, in addition to the control of a multitude of growth-related pathways, mTOR plays a nodal role in signaling G(1) and G(2)-M events.
 ...
PMID:Damaged microtubules can inactivate BCL-2 by means of the mTOR kinase. 1159 25

Several genetic alterations have been implicated in the development of malignant melanoma, but the expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes and their interactions in melanoma have not been completely clarified. We simultaneously examined the expression of p73, c-erbB-2, ras, p53, Mdm2, p27, DCC, hMLH-1, hMSH-2, bcl-2, Bax and NF-kappaB, by immunocytochemistry, in both primary and metastatic melanoma cell lines derived from melanoma patients. p73 was expressed in 7/8 cell lines, but stronger expressed in the metastatic cells than in the primary melanoma cells. c-erbB-2 was detected in all 8 cell lines and ras in 2/5 metastases. p53 was found in all the cell lines and Mdm2 in 1/8 of the cell lines. In the same patient, the intensity of p27 expression was decreased from the primary to the metastatic tumours. bcl-2 was expressed in all the cell lines. Bax was absent in 5/8 cell lines. In the same patient, Bax was weakly expressed in the primary tumour but lacking in the metastases. The data demonstrate that overexpression of p73, c-erbB-2, p53 and bcl-2, and loss of Mdm2 and Bax may interact and play important roles in the development and aggressiveness of human melanoma.
 ...
PMID:Expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes in primary and metastatic melanoma cells. 1171 83

Chemotherapy does not have a prominent role in the treatment of hepatoma. However, an acyclic retinoid prevented tumor recurrence post-hepatectomy, and tamoxifen (TAM) induced apoptosis in tumor cells. Combination therapy of these agents on proliferation and apoptosis of hepatoma cells has not been explored. HepG2, Hep1B, Hepa1-6 and MH1C1 hepatoma cells were incubated with TAM, 9-cis- and all-trans retinoic acid (CRA, ATRA, respectively) alone or in combination. Proliferation rate was assessed and apoptosis was analyzed by flow cytometry, immunostaining, caspase activity assays and the expression of apoptosis- and/or cell cycle-related molecules. CRA and TAM, but not ATRA monotherapy were moderately effective. Apoptosis was accompanied by upregulation of caspase 3 and 8 activity, and increased p27, bax, caspase 3 expression, while the levels of p21cip/waf and bcl-2 were unchanged or decreased. Combination therapy enhanced apoptosis from a maximum of 60% after monotherapy to more than 90% after 96 h in all cell types. Pro-apoptotic effects were paralleled by inhibition of proliferation. Combination of TAM and CRA, but not ATRA, have an additive to synergistic anti-proliferative and pro-apoptotic effect on HCC cells. This justifies trials for HCC using combinations of these biological response modifiers.
 ...
PMID:Combined in vitro anti-tumoral action of tamoxifen and retinoic acid derivatives in hepatoma cells. 1174 47


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