Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biologic properties of breast cancer in men that might reflect alterations in pathogenesis from the disease in women were examined. We studied 22 tumors from males, 18 invasive carcinomas, three of which were papillary, and three in situ tumors of which one was papillary, and one papilloma. Our data support the previously reported high incidence of papillary carcinoma in men. Estrogen receptor status and the expression of cancer-associated antigens recognized by antibodies DF3, B73.2, SP-1, and c-erbB-2 were compared to matched tumors from females. Immunocytochemistry was performed on formalin-fixed, paraffin-embedded sections using standard avidin-biotin techniques; anti-PSA was used to exclude the possibility of metatastic prostate cancer, and 12 cases of gynecomastia were included as nonmalignant controls. The incidence of estrogen receptor positivity was higher in tumors from males (73%) than from females (54%), as has been reported previously. The range of expression of all breast cancer antigens tested in male tumors was similar to that observed in females, but some interesting differences were noted. With the exception of the anti-mucin DF3, all the antibodies reacted only with neoplastic tissues. Expression of the oncoprotein c-erbB-2 was lower (17%) in males than in females (33%), despite the preponderance in men of the large-cell type carcinomas that have been associated with c-erbB-2 expression. Unexpectedly, the pregnancy-associated hormone detected by SP-1 was expressed in 33% of tumors from males and, in contrast to females, was found in less differentiated tumors.
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PMID:Immunocytochemical characterization of male breast cancer. 136 97

One hundred and twenty-four localized prostate cancer patients operated on at Johns Hopkins Hospital (JHH) since 1975 were identified. The sample was optimized for evaluation of prostate cancer progression. Based upon accurate clinical histories, these radical prostatectomy patients included 50 progressors and 74 non-progressors using appearance of serum PSA as an indication of recurrence (mean follow-up = 8.6 +/- 1.8 years, range 7-15 years). All patients included in the study had no involvement of their seminal vesicles or lymph nodes at the time of prostatectomy. Average time to progression was 3.6 +/- 2 years, range of 1-8 years. Using paraffin-embedded specimens, several five micron sections were cut and placed on Probe-On slides; one slide was H&E-stained and the other was Feulgen-stained. The H&E and Feulgen-stained slides were screened and "dotted" by pathologists at JHH and CytoDynostics, Inc. A CAS-200 Image analysis system (Cell Image Systems, Elmhurst, IL) equipped with a Cell Measurement Program version 1.2 beta, was used to capture the Feulgen-stained images and to perform the calculations. From the "dotted" areas, 150 cancer cells were selected for measurement of DNA content and 27 nuclear morphometric shape and size factors, including 21 Markovian chromatin texture variables. Additional sections were used for immunochemistry staining with an alkaline phosphatase streptavidin-biotin complex stain to detect and quantitate cancer cells binding monoclonal antibodies directed against proliferating cell nuclear antigen (PCNA) and HER-2/neu antigen. All data were entered into a statistical program (STATA) for further analysis and univariate and multivariate statistical analysis was performed using logistic regression and its stepwise variant. The biomarkers of greatest utility to detect progressors when analyzed univariately included post-operative Gleason score (p = < 0.0001), HER-2/neu antigenicity (p = 0.0147), CAS-200 DNA ploidy (p = 0.008), and twelve Markovian nuclear texture and shape features (p = < 0.0001), whereas PCNA (p = 0.160) failed. The optimal set of nuclear morphometry progression tumor features were selected using backward stepwise logistic regression estimate analysis which drops variables due to collinearity. Although post-operative Gleason score is a strong univariate predictor of progression, DNA ploidy and HER-2/neu contributed significantly to further stratification of higher risk groups within the low Gleason score subpopulation. The best Markovian features combined with post-operative Gleason score generated sensitivity = 90%, specificity = 96%, positive predictive value = 94%, negative predictive value = 93% and the area under the receiver operator curve was 0.975.
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PMID:Quantitative nuclear morphometry, Markovian texture descriptors, and DNA content captured on a CAS-200 Image analysis system, combined with PCNA and HER-2/neu immunohistochemistry for prediction of prostate cancer progression. 752 56

We made an effort to identify a reliable source for obtaining large quantities of both free (PSA) and PSA-ACT complex for the preparation of the calibrator for the PSA assay. Using size exclusion chromatography, we found both free PSA and PSA-ACT complex in the conditioned cell medium of the LNCaP cell line, which was derived from a human metastatic adenocarcinoma of the prostate. An assay specific for PSA-ACT reacted only with the PSA-ACT complex from cells grown in serum-free medium, and not with the complex from the cell medium grown in 10% calf serum. We also found both free PSA and PSA-ACT complex in 15% of cytosols prepared from breast tumor tissues; the cytosol PSA concentrations ranged from 0.1 to 110 ng/ml. No correlation was found between cytosol PSA and concentrations of estrogen receptor, progestin receptor, epidermal growth factor receptor, cathepsin D, or the ectodomain of c-erbB-2 protein. Based on chromatographic characterizations and the slope of their dose-response curves, it appears that both free PSA and PSA-ACT complex found in the cytosols are similar to PSA complex from the cell medium and the serum of prostate cancer patients. Ectopic PSA was also detected in pooled sera from patients with breast, ovarian, pancreatic, and colon carcinoma. The PSA concentrations in these serum pools increased with the level of their dominant tumor marker. In any event, the LNCaP cell medium appears to be a reliable source for obtaining both free and ACT-complexed PSA of human tumor origin for the preparation of PSA assay calibrators.
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PMID:PSA immunoreactivity detected in LNCaP cell medium, breast tumor cytosol, and female serum. 756 42

Pre- and post-treatment specimens from 47 patients with hormone resistant prostatic carcinoma were compared with each other regarding histological grade and immunoreactivity for p53 protein, neuron specific enolase and c-erbB-2 protein. Significantly more specimens expressed a high malignancy grade when the tumour had become hormone resistant than at the time of initial diagnosis (Gleason P: < 0.0001, WHO P:0.0003). p53 protein immunoreactivity increased significantly with disease progression (P:0.006), while tissue PSA immunoreactivity was reduced in post-treatment specimens (P:0.011). p53 protein expression did not correlate with histological grade or PSA expression and seems to be an independent parameter which participates late in the neoplastic transformation. Thirty-two percent of the tumours were neuron specific enolase positive, but this parameter did not correlate with development of hormone resistance. c-erbB-2 protein reactivity was not recognised.
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PMID:Hormone resistant prostatic adenocarcinoma. An evaluation of prognostic factors in pre- and post-treatment specimens. 768 48

Chemoprevention is the administration of agents to prevent induction and inhibit or delay progression of cancers. For prostate, as for other cancer targets, successful chemopreventive strategies require well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer for evaluating chemopreventive efficacy. Agent requirements are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the observed chemopreventive activity. On this basis, promising chemopreventive drugs in prostate include retinoids, antiandrogens, antiestrogens, steroid aromatase inhibitors, 5alpha-reductase inhibitors, vitamins D and E, selenium, lycopene, and 2-difluoromethylornithine. Phase II trials are critical for evaluating chemopreventive efficacy. Cohorts in these trials should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen as endpoints. Many cohorts proposed for phase II trials are patients with previous cancers or premalignant lesions. For such patients, trials should be conducted within the context of standard treatment. Two cohorts currently used in phase II prostate cancer chemoprevention trials are patients with PIN and patients scheduled for prostate cancer surgery. Biomarkers should fit expected biological mechanisms, be assayed reliably and quantitatively, measured easily, and correlate to decreased cancer incidence. Protocols for adequately sampling tissue are essential. Changes in PIN provide prostate biomarkers with the ability to be quantified and a high correlation to cancer. PIN measurements include nuclear polymorphism, nucleolar size and number of nucleoli/nuclei, and DNA ploidy. Other potentially useful biomarkers are associated with cellular proliferation kinetics (e.g. PCNA and apoptosis), differentiation (e.g. blood group antigens, vimentin), genetic damage (e.g. LOH on chromosome 8), signal transduction (e.g. TGFalpha, TGFbeta, IGF-I, c-erbB-2 expression), angiogenesis, and biochemical changes (e.g. PSA levels).
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PMID:Chemoprevention of prostate cancer: concepts and strategies. 1032 87

Dendritic cells play a pivotal role in immune induction. Dendritic cells perform antigen uptake, processing and presentation to T cells only when they are matured and in the functional state. In the development of a vaccine, it is of utmost importance to consider how to make dendritic cells' functions immunologically adequate. In this paper, we report the development of a series of antitumor DNA vaccines with similar structural framework, in which a gene encoding tumor-associated antigenic peptide is ligated upstream to the gene coding secondary lymphoid-tissue chemokine and downstream to the gene encoding the Fc portion of IgG (named chemotactic-antigen DNA vaccine [CADV]). CCR7(+) T, B, natural killer and dendritic cells can be attracted by secondary lymphoid-tissue chemokine, and Fc facilitates antigen uptake via Fc receptors expressed on dendritic cells. In a series of experiments in mice vaccinated by CADV with such tumor-associated antigenic specificities as HPV-16 E7, PSA-PSM-PAP, HER-2/neu, p53 and hTERT, CADV can attract immune cells to the vaccine inoculation site, remarkably inhibit tumor growth and extend survival time in tumor-bearing mice. The antitumor effect is more efficacious than that in mice treated with SLC-Ag or Ag-Fc hybrid gene. Tumor-associated antigenic-specific cytotoxic T lymphocytes can be induced by in vitro experiment in a human system. When combined with measures blocking the negative immune feedback circuits, the therapeutic effect of the vaccine can be further enhanced. Large-scale production of CADV is possible for clinical application.
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PMID:Novel chemotactic-antigen DNA vaccine against cancer. 1840 41

Prostate cancers (PCa) that relapse after androgen deprivation therapies [castration-resistant PCa (CRPC)] express high levels of androgen receptor (AR) and androgen-regulated genes, and evidence from several groups indicates that ErbB family receptor tyrosine kinases [epidermal growth factor (EGF) receptor (EGFR) and ErbB2] may contribute to enhancing this AR activity. We found that activation of these kinases with EGF and heregulin-beta1 rapidly (within 8 hours) decreased expression of endogenous AR and androgen-regulated PSA in LNCaP PCa cells. AR expression was similarly decreased in LAPC4 and C4-2 cells, but not in the CWR22Rv1 PCa cell line. The rapid decrease in AR was not due to increased AR protein degradation and was not blocked by phosphatidylinositol 3-kinase (LY294002) or MEK (UO126) inhibitors. Significantly, AR mRNA levels in LNCaP cells were markedly decreased by EGF and heregulin-beta1, and experiments with actinomycin D to block new mRNA synthesis showed that AR mRNA degradation was increased. AR mRNA levels were still markedly decreased by EGF and heregulin-beta1 in LNCaP cells adapted to growth in androgen-depleted medium, although AR protein levels did not decline due to increased AR protein stability. These findings show that EGFR and ErbB2 can negatively regulate AR mRNA and may provide an approach to suppress AR expression in CRPC.
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PMID:Androgen receptor expression in prostate cancer cells is suppressed by activation of epidermal growth factor receptor and ErbB2. 1949 Dec 61

Prostate cancer is the most prevalent cancer and the second leading cause of cancer death in men. There are various modalities for treatment of prostate cancer. Immunotherapy with several vaccines and antibodies has also been successfully used with positive clinical outcome in prostate cancer patients. The majority of these vaccines are palliative and have been employed when a person is already diagnosed with prostate cancer. The aim of this article is to review various vaccines that have been examined for immunoprophylactic prevention of initiation/development/metastasis of prostate cancer. The Pubmed database and Google Scholar search identified 26 articles on various vaccines that have been investigated for prophylactic prevention of cancer development. These vaccines targeted prostate-specific/restricted antigens (PSA/PSMA/PSCA), oncoproteins (GRP/MUC family, erbB2/HER-2/neu), whole tumor cell antigens, prostate regulating hormones (GnRH/testosterone), and various cytokines and immune modulators. The data indicates that the development of immunoprophylactic vaccines for prostate cancer is an exciting proposition, which can translate into a viable reality for clinical application in humans.
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PMID:Prophylactic vaccines for prevention of prostate cancer. 2220