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)

The Akt pathway is one of the most common molecular alterations in various human malignancies. However, its involvement in nasopharyngeal carcinoma (NPC) tumorigenesis has not been well established. In this study, the status of Akt activation and expression of its upstream and downstream molecules was investigated in 64 NPC and 38 non-malignant nasopharyngeal tissues by immunohistochemistry. The hotspot mutations of PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), were also determined in 25 of these NPC tissues. No hotspot mutations were found in any of the samples tested. Akt was activated in 27 (42.2%) and 23 (35.9%) NPCs, as indicated by p-Akt (Thr308) and p-Akt (Ser473) immunoreactivity, respectively. PTEN loss did not correlate statistically with activated Akt. However, a positive correlation was observed between activated Akt and phospho-epidermal growth factor receptor (p-EGFR), suggesting that the EGFR signaling might be one of the upstream regulators of the Akt pathway. The phosphorylation of forkhead (FKHR) and Bcl-2 associated death domain (BAD), but not mammalian target of rapamycin and glycogen synthase kinase-3beta, was significantly correlated with Akt activation. This implies that Akt promotes cell proliferation (as estimated by Ki-67) and survival, at least, through the inactivation of FKHR and BAD in NPC. Our data revealed that the EGFR/PI3K/Akt signaling pathway is important in NPC pathogenesis and that PIK3CA hotspot mutations are rare in NPC.
 ...
PMID:Overexpression of phospho-Akt correlates with phosphorylation of EGF receptor, FKHR and BAD in nasopharyngeal carcinoma. 1820 77

The aims of the present work were to evaluate the prognostic significance of the micropapillary pattern of lung adenocarcinoma and determine whether there are differences in the behavior of this type of tumor according to its immunohistochemical profile. A series of 191 consecutively resected pulmonary adenocarcinomas were divided into those with (n = 62) and those without (n = 129) micropapillary components. The disease was stage I in 38 and 54 patients, respectively. The 5-year survival rates of patients with and without micropapillary components were 54% and 77%, respectively (log rank P = .03). In multivariate survival analysis, the micropapillary component proved to be an independent prognostic factor (hazard ratio, 3.2). Five autopsy cases were used to investigate the immunohistochemical profile. The percentages of cases positive for various markers were 56.7 for p53, 94 for Ki67, 85.1 for c-myc, 2.9 for Bcl-2, 35.8 for epidermal growth factor receptor, 43.3 for cyclin D1, and 46.3 for Bax. The prognostic value was evaluated according to the expression of the different markers in micropapillary carcinomas in stage I. In univariate analysis, only cyclin D1 expression and Bax expression were associated with significantly worse survival (log rank P = .03 and P = .02, respectively). We conclude that it is important to recognize the micropapillary growth pattern in lung adenocarcinoma. Moreover, cyclin D1 and Bax seem to be markers of a poor prognosis.
 ...
PMID:Micropapillary lung adenocarcinoma: a distinctive histologic subtype with prognostic significance. Case series. 1826 22

Progress in the systemic therapy of thymic malignancies has been hampered in the past by the rarity of this disease entity and the lack of a global collaborative effort in conducting phase II studies. Cisplatin-based therapy has been considered the standard of care, though data typically has been derived from a retrospective case-series approach. However, the arrival of novel cytotoxic agents and molecularly targeted agents into the clinic has helped provide the impetus for improved methodology in thymic malignancy research with an emphasis on more prospective phase II studies. This review discusses the results of traditional cytotoxic agents, novel cytotoxic agents, biologic therapy and the initial evaluation of molecularly targeted therapeutics, such as epidermal growth factor receptor inhibitors, for the treatment of thymic malignancies. In addition, potential novel targets such as VEGF, Bcl-2 and c-KIT are assessed.
 ...
PMID:Systemic therapeutic options in thymic malignancies: a glimmer of hope. 1847 5

Young pre-menopausal women with breast carcinomas have an overall worse prognosis than older, post-menopausal women. Because histologic grade is a major predictor of tumor behavior and correlates with biomarker expression, we assessed the immunohistochemical expression of epidermal growth factor receptor (EGFR), p185(erbB-2) and Bcl-2, and nuclear accumulation of p53 in breast carcinomas in pre- and post-menopausal women with equivalent histologic grades. This allowed identification of differences in biomarker expression and prognostic significance in pre- and post-menopausal women independent of histologic grade. We investigated 100 infiltrating ductal carcinomas (IDC) in pre-menopausal women, ages 45 years and younger, and 100 IDC in post-menopausal women, ages 65 years and older. The IDC were selected so that the proportions of high and low/moderate grade carcinomas were equal in the pre- and post-menopausal groups. Prognostic utility of biomarker expression in pre- and post-menopausal groups was determined by product limit and multivariate analysis of survival. There were statistically significant differences in cytoplasmic expression of EGFR and Bcl-2 and nuclear accumulation of p53, but not in the expression of p185(erbB-2), in carcinomas of high vs. low histologic grade. There was no difference in the expression of EGFR, p185(erbB-2) or Bcl-2, or in nuclear accumulation of p53 in these IDC from pre- vs. post-menopausal women. Bcl-2 and the nuclear accumulation of p53 were of prognostic significance in our overall study population; however, when assessing pre- and post-menopausal women separately, Bcl-2 and p53 were of prognostic significance only in pre-menopausal, but not post-menopausal women. In summary expression of EGFR and Bcl-2 and nuclear accumulation of p53 were significantly associated with histologic grade, but not with menopausal status. In addition, there were differences in the prognostic effectiveness of these biomarkers in pre- vs. post-menopausal women.
 ...
PMID:Immunohistochemical detection of EGFR, p185(erbB-2), Bcl-2 and p53 in breast carcinomas in pre-menopausal and post-menopausal women. 1856 71

Inhibitors of the epidermal growth factor receptor (EGFR) have generated considerable hope for cancer treatment, specifically for lung and breast cancers. Therefore, identification of a natural, nontoxic agent(s) as an inhibitor of EGFR is of considerable importance. Delphinidin, an anthocyanidin present in pigmented fruits and vegetables, possesses potent antioxidant and antiproliferative properties. In our study, employing EGFR positive breast cancer AU-565 cells and immortalized MCF-10A cells, we evaluated the effect of delphinidin on EGFR and its downstream signaling pathways. Delphinidin (5-40 microM; 3 hr) treatment of both AU-565 cells and MCF-10A cells inhibited the (i) phosphorylation of EGFR, (ii) activation of PI3K, (iii) phosphorylation of AKT and MAPK. Further, delphinidin treatment of AU-565 cells inhibited EGF-induced autophosphorylation of EGFR, AKT and MAPK, activation of PI3K and cell invasion. We then compared the growth inhibitory effects of delphinidin (5-40 microM; 48 hr), and found that it resulted in a decrease in cell growth of AU-565 and MCF-10A cells but had only minimal effects on normal mammary epithelial 184A1 cells. Treatment of AU-565 cells with delphinidin resulted in (i) induction of apoptosis, (ii) cleavage of PARP protein, (iii) activation of caspase-3 and (iv) downregulation of Bcl-2 with an increase in the expression of Bax. In summary, our study identifies a naturally occurring dietary agent delphinidin as an effective inhibitor of EGFR signaling in breast cancer cells. We suggest that delphinidin could be developed as an agent for the management of EGFR positive human cancers.
 ...
PMID:Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables. 1862 29

The purpose of the present study was to evaluate the effect of transforming-growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry. Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis were measured at sacrifice. RT-PCR and Western Blotting was used to determine the level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure epidermal growth factor receptor (EGFr) expression along the villus-crypt axis. The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells results in a significant inhibition of cell apoptosis in a dose-dependent manner. In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis was strongly correlated with EGFr expression along the villus-crypt axis. In conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX- injury in the rat.
 ...
PMID:Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated with EGF receptor expression along the villus-crypt axis during methotrexate-induced intestinal mucositis in a rat. 1880 16

Honokiol is a naturally occurring neolignan abundant in Magnoliae Cortex and has showed anti-proliferative and pro-apoptotic effects in a wide range of human cancer cells. However, the molecular mechanisms on the anti-proliferative activity in cancer cells have been poorly elucidated. In this study, we evaluated the growth inhibitory activity of honokiol in cultured estrogen receptor (ER)-negative MDA-MB-231 human breast cancer cells. Honokiol exerted anti-proliferative activity with the cell cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death in a concentration-dependent manner. The honokiol-induced cell cycle arrest was well correlated with the suppressive expression of CDK4, cyclin D1, CDK2, cyclin E, c-Myc, and phosphorylated retinoblastoma protein (pRb) at Ser780. Apoptosis caused by honokiol was also concomitant with the cleavage of caspases (caspase-3, -8, and -9) and Bid along with the suppressive expression of Bcl-2, but it was independent on the expression of Bax and p53. In addition, honokiol-treated cells exhibited the cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. In the analysis of signal transduction pathway, honokiol down-regulated the expression and phosphorylation of c-Src, epidermal growth factor receptor (EGFR), and Akt, and consequently led to the inactivation of mTOR and its downstream signal molecules including 4E-binding protein (4E-BP) and p70 S6 kinase. These findings suggest that honokiol-mediated inhibitory activity of cancer cell growth might be related with the cell cycle arrest and induction of apoptosis via modulating signal transduction pathways.
 ...
PMID:Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells. 1913 78

Crocetin, a carotenoid compound derived from saffron, has long been used as a traditional ancient medicine against different human diseases including cancer. The aim of the series of experiments was to systematically determine whether crocetin significantly affects pancreatic cancer growth both in vitro and/or in vivo. For the in vitro studies, first, MIA-PaCa-2 cells were treated with crocetin and in these sets of experiments, a proliferation assay using H(3)-thymidine incorporation and flow cytometric analysis suggested that crocetin inhibited proliferation. Next, cell cycle proteins were investigated. Cdc-2, Cdc-25C, Cyclin-B1, and epidermal growth factor receptor were altered significantly by crocetin. To further confirm the findings of inhibition of proliferation, H(3)-thymidine incorporation in BxPC-3, Capan-1, and ASPC-1 pancreatic cancer cells was also significantly inhibited by crocetin treatment. For the in vivo studies, MIA-PaCa-2 as highly aggressive cells than other pancreatic cancer cells used in this study were injected into the right hind leg of the athymic nude mice and crocetin was given orally after the development of a palpable tumor. The in vivo results showed significant regression in tumor growth with inhibition of proliferation as determined by proliferating cell nuclear antigen and epidermal growth factor receptor expression in the crocetin-treated animals compared with the controls. Both the in vitro pancreatic cancer cells and in vivo athymic nude mice tumor, apoptosis was significantly stimulated as indicated by Bax/Bcl-2 ratio. This study indicates that crocetin has a significant antitumorigenic effect in both in vitro and in vivo on pancreatic cancer.
 ...
PMID:Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. 1920 26

Breast cancer is the most frequent malignant tumor in women and the diagnosis, prognosis and therapeutic strategy are based on the pathologic report. In last years, it was shown that conventional pathologic diagnosis brings few data about prognosis and tells nothing about the response of the tumor to specific therapy. In an effort to improve the molecular characterization of breast cancer, gene profile analysis was performed in a large number of cases. Based on this analysis, there were characterized five molecularly different subclasses: basal-like, luminal type A and B, HER-2, and unclassified. It was shown that prognosis and response to adjuvant therapy is significantly different in these five subtypes. Immunohistochemistry was demonstrated to be a good and acceptable surrogate of the gene analysis. A panel of antibody that includes estrogen receptors (ER), progesterone receptors (PR), Her2 protein, cytokeratin 5 (CK5), epidermal growth factor receptor (EGFR), p53 mutation, and Bcl-2 expression, can discriminate between these five molecular subclasses. In the present review there are presented the main characteristics of the molecular subclasses, the relationships with the conventional pathologic classification, critical problems of the molecular classification and their impact on prognosis and therapy.
 ...
PMID:From conventional pathologic diagnosis to the molecular classification of breast carcinoma: are we ready for the change? 1922 40

Vulvar carcinoma is a rare female genital neoplasia. Radical surgery, which has been the standard treatment approach, is often accompanied by considerable morbidity. To reduce the incidence of complications there has been a movement toward individualised therapy and less radical surgery. Associated with this, new tumour markers that could serve as prognostic indicators would be of considerable value to guide treatment decision. In this review, a brief update of molecular pathological markers of vulvar carcinomas is provided, and their impact as prognostic markers is addressed. p16, p21, p14, p27, cyclin A, cyclin D1, p53, vascular endothelial growth factor (VEGF), transforming growth factor alpha, HER-2 and epidermal growth factor receptor (EGFR) have been found to be important in the pathogenesis and/or progression of vulvar carcinomas. Furthermore, human papillomavirus, p16, p21, p14, p53, VEGF, CD44v3, CD44v6, CD44v4, CD44v9, CD44v10, HER-2, EGFR, matrix metalloproteinase-12, caspase 3, Bcl-2 and nm23-H1 have been correlated to clinical outcome of patients with vulvar carcinomas. However, due to the relative small number of studies reported for each molecular pathological marker, and the relative small number of vulvar carcinomas included and the lack of multivariate analysis in the majority of these studies, no conclusion regarding the prognostic value of these markers can be drawn. Therefore, the investigated markers have not yet earned a place in standard clinical diagnostics or treatment, and further studies are needed to clarify the clinical value of these markers.
 ...
PMID:A review of molecular pathological markers in vulvar carcinoma: lack of application in clinical practice. 1925 52


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