Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.
 ...
PMID:Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. 151 67

The ongoing JANUS project was started in 1973. The serum bank comprises 424,938 serum samples consolidated from 293,692 donors. The specimens are stored at -25 degrees C. From 1 to 13 consecutive samples are available from each donor. Up to October 1993 about 14,000 of the donors had developed some form of cancer. Frozen serum samples collected from a few months to 19 years prior to clinical recognition of their disease are available for research purposes. The principle aim of the JANUS project is to search in the premorbid sera for chemical, biochemical, immunological or other changes that might be indicative of cancer development at early stages. Gas chromatography-mass spectrometry and two-dimensional protein electrophoresis have been used to evaluate the stability of the frozen sera. Some recent findings are: CA-125 may be elevated months prior to the diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumor marker in subgroups of thyroid cancer; low levels of selenium in serum reflects increased risk of thyroid cancer; raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkins disease; prostate-specific antigen may be elevated years prior to clinical diagnosis of prostate cancer; and linoleic acid in serum phospholipids is inversely related to breast cancer risk. The serum bank is, in principle, suitable for environmental studies, e.g., human exposure assessment. The steering committee of the JANUS project is open to suggestions for collaborative research on this topic.
 ...
PMID:Experiences of the Janus Serum Bank in Norway. 763 18

Locally advanced prostate cancer patients comprise those with iatrogenic capsular injury, extracapsular extension resulting in positive surgical margins following radical prostatectomy, and tumors with lymph node metastases, thus representing stage T3,N0,M0 or T1-4,N1-2,M0 disease. Parameters can be combined, as shown below, in a nomogram to predict advanced prostate cancer: if, for example, stage T2c is coupled with a PSA of 16 ng/ml and a high Gleason grade, the patient will have an approximately 70% likelihood of having extracapsular extension; then again, if the Gleason score is known from biopsies and a PSA of 10-20 ng/ml is given, then a stage T2c prostate cancer patient with a Gleason of 7 will have a 39% probability of having positive lymph nodes. The following therapeutic considerations may be used to enhance the chance of eradicating advanced disease through radical prostatectomy: (1) Neoadjuvant hormonal therapy helps downsize the tumor and may eventually reduce the number of positive margins by almost 50%. However, it is a moot point if this will lead to a prolonged survival period. (2) Technical refinements on radical prostatectomy may be achieved through the principle of wide extension excision, a modification of current apical dissection procedures, which involves the use of panoramic magnifying loupes, and an examination of resection margins during surgery using repetitive frozen sections. (3) If positive (not simply 'equivocal' as defined by Epstein) margins are found, radical prostatectomy alone is not curative. Among the various options available is postoperative irradiation with or without adjuvant hormonal therapy. The latter should probably be reserved for patients with extracapsular extension, a high Gleason score or positive lymph nodes. Hormonal therapy may be used continuously or intermittently. The value of adjuvant treatment is currently being tested in phase-III trials. (4) Hormonal therapy may be commenced at the time of biochemical or clinical progression, although it is not clear whether this modality is inferior to adjuvant forms of treatment. Technical expertise in radical prostatectomy accumulated at major institutions can be used to the advantage of patients with locally advanced prostate cancer. In this regard, results of ongoing phase-III trials testing various options including this procedure are eagerly awaited.
 ...
PMID:Enhancing the efficacy of radical prostatectomy in locally advanced prostate cancer. 960 52

We performed a decision analysis to evaluate the usefulness of pretreatment prediction of clinically significant or insignificant tumor in patients with prostate-specific antigen (PSA)-detected stage T1c prostate cancer nonpalpable on rectal examination. Analysis was done for otherwise healthy subjects with 20 years of life expectancy. The prevalence of insignificant tumor among those with T1c prostate cancer was initially assumed to be 0.2. Quality-adjusted life expectancy was calculated and compared between 2 strategies; one with prediction-based selection of either radical prostatectomy or watchful waiting and the other with unselective assignment of one of the treatments. The selection strategy was superior when the sensitivity and specificity for detecting clinically significant tumor were 0.92 and 0.73, respectively, as reported by Epstein et al. (1994) using criteria of PSA density and Gleason score in a needle biopsy specimen. Sensitivity analysis revealed that the prediction-based selection strategy is preferred, with sensitivity and specificity constant, when the prevalence of insignificant tumor exceeds 0.16. On the other hand, when the prevalence of insignificant tumor is kept constant at 0.2, sensitivity should be 0.85 or higher for the prediction strategy to be preferred. As the prevalence of insignificant tumor among those with T1c prostate cancer increased, the prediction-based selection strategy is preferred with lower values of sensitivity and specificity for detecting significant tumor. These results suggest that a selective treatment strategy of either radical or conservative treatment based on pretreatment prediction for significant tumor is a beneficial alternative to radical prostatectomy unselectively assigned to all patients at the T1c stage, if a reasonable accuracy in prediction is attained.
 ...
PMID:Decision analysis for treatment of early stage prostate cancer. 970 67

Compared to pseudocyst formation after prior pancreatitis, true cysts of the pancreas are rare. Pancreatic cysts with irregular wall components or a mucinous content raise the suspicion for the presence of a cystic neoplasm, and surgical resection is recommended. A case of a patient with a history of prostate cancer is described in whom a cyst of the pancreatic tail was discovered incidentally. Based on the radiographic features, which did not support the presence of a serous cystadenoma, a spleen-preserving distal pancreatectomy was performed. Histologic features were characteristic for a lymphoepithelial cyst (LEC) of the pancreas, lined with thinned squamous epithelium surrounded by benign lymphoid tissue. Since LECs of the parotid gland, which are associated with acquired human immunodeficiency, are frequently related to Epstein-Barr virus (EBV) infection, EBV in situ hybridization was performed and did not reveal evidence for EBV. Twenty-eight instances of pancreatic LECs have been reported, primarily affecting adult males, without evidence of increased numbers of EBV-positive cells. The pathogenesis, differential diagnosis, and clinical implications of lymphoepithelial pancreatic cysts are discussed.
 ...
PMID:Lymphoepithelial cyst of the pancreas. No evidence for Epstein-Barr virus-related pathogenesis. 1045 24

The polypeptide component of telomerase (TERT) is an attractive candidate for a broadly expressed tumor rejection antigen because telomerase is silent in normal tissues but is reactivated in more than 85% of cancers. Here we show that immunization against TERT induces immunity against tumors of unrelated origin. Immunization of mice with TERT RNA-transfected dendritic cells (DC) stimulated cytotoxic T lymphocytes (CTL), which lysed melanoma and thymoma tumor cells and inhibited the growth of three unrelated tumors in mice of distinct genetic backgrounds. TERT RNA-transfected human DC stimulated TERT-specific CTL in vitro that lysed human tumor cells, including Epstein Barr virus (EBV)-transformed B cells as well as autologous tumor targets from patients with renal and prostate cancer. Tumor RNA-transfected DC were used as surrogate targets in the CTL assays, obviating the difficulties in obtaining tumor cells from cancer patients. In one instance, where a tumor cell line was successfully established in culture from a patient with renal cancer, the patient's tumor cells were efficiently lysed by the CTL. Immunization with tumor RNA was generally more effective than immunization with TERT RNA, suggesting that an optimal immunization protocol may have to include TERT as well as additional tumor antigens.
 ...
PMID:Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. 1097 7

Employing a technology called differential immunization for antigen and antibody discovery (DIAAD), we aimed to generate monoclonal antibodies (mAbs) specific to human multiple myeloma (MM) cells. The fundamental principles of DIAAD rely on the induction of high zone tolerance to the "wild type" (normal) antigen. followed by immunization with the modified (diseased) antigen. Because chronic myelogenic leukemia (CML) cells are derived from a lineage closely related to MM, we immunized mice by contrasting a pool of MM cells with CML cells. Monoclonal antibody VAC69 reacted exclusively with MM cells, identifying a membrane molecule composed of a single-chain glycoprotein with a molecular weight of 78-120 kd. This antigen exhibited narrow tissue specificity and was not found on human cancers such as prostate, breast, or cervical carcinoma; leukemia; or lymphoma, nor was it seen on normal human peripheral lymphocytes or on Epstein-Barr virus-transformed B-cell lines. By immunohistochemistry, mAb VAC69 showed no binding to antigens expressed on normal human ovary, breast, prostate, lung or colon tissue, nor did it bind to human breast or prostate cancer. Conversely, mAb VAC69 bound strongly to human MM, although showing only slight binding to histiocytes or inflamed cells in human lymph nodes and human tumors of the colon, lung, and ovary. Monoclonal antibody VAC69 also triggered cancer-specific cytotoxicity in vitro (in the presence of complement) as well as in vivo using a sever combined immunodeficiency model transplanted with human MM. Further studies showed the ability of mAb VAC69 to be specifically internalized by human MM cells, indicating its potential use for therapeutic intervention in MM by delivering drugs into cancer cells.
 ...
PMID:Monoclonal antibody identifies a distinctive epitope expressed by human multiple myeloma cells. 1156 35

The DNA-damage-signaling pathway has been implicated in all human cancers. However, the genetic defects and the mechanisms of this pathway in prostate carcinogenesis remain poorly understood. In this study, we analyzed CHEK2, the upstream regulator of p53 in the DNA-damage-signaling pathway, in several groups of patients with prostate cancer. A total of 28 (4.8%) germline CHEK2 mutations (16 of which were unique) were found among 578 patients. Additional screening for CHEK2 mutations in 149 families with familial prostate cancer revealed 11 mutations (5 unique) in nine families. These mutations included two frameshift and three missense mutations. Importantly, 16 of 18 unique CHEK2 mutations identified in both sporadic and familial cases were not detected among 423 unaffected men, suggesting a pathological effect of CHEK2 mutations in prostate cancer development. Analyses of the two frameshift mutations in Epstein Barr virus-transformed cell lines, using reverse-transcriptase polymerase chain reaction and western blot analysis, revealed abnormal splicing for one mutation and dramatic reduction of CHEK2 protein levels in both cases. Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer.
 ...
PMID:Mutations in CHEK2 associated with prostate cancer risk. 1253 88

To accomplish efficient nonviral gene therapy against prostate cancer (PC), Epstein-Barr virus (EBV)-based plasmid vectors containing EBNA1 gene and oriP were employed and combined with a cationic polymer or cationic lipid. When EBV-plasmid/poly-amidoamine dendrimer complex was injected into PC-3-derived tumors established in severe combined immunodeficiency mice, a considerable expression of marker gene was obtained in the tumors, and the expression level was more than eight-fold higher than that achieved by conventional plasmid vector/dendrimer. Since most PC cells express the apoptotic signal molecule Fas (Apo-1/CD95) on their surface, Fas ligand (FasL) gene was transferred into PC cells to kill the tumor cells. In vitro transfection with pGEG.FasL (an EBV-plasmid with the FasL gene) significantly reduced the viability of PC cells, which subsequently underwent apoptosis. Intratumoral injections of pGEG.FasL into PC induced significant growth suppression of the xenograft tumors, in which typical characteristics of apoptosis were demonstrated by TUNEL staining and electron microscopic observations. When pGEG.FasL transfer was accompanied by systemic administrations of cisplatin, the tumors were inhibited even more remarkably, leading to prolonged survival of the animals. FasL gene transfection by means of EBV-based plasmid/cationic macromolecule complexes may provide a practical therapeutic strategy against PC.
 ...
PMID:Nonviral genetic transfer of Fas ligand induced significant growth suppression and apoptotic tumor cell death in prostate cancer in vivo. 1260 98

Expectant treatment with curative intent for treatment of low-risk prostate cancer faces 3 challenges in the PSA era: (1) appropriate patient selection, (2) adequate surveillance strategies, and (3) identification of triggers for definitive intervention when cure is still possible. Men 65 years or older with T1c disease, prostate-specific antigen density <0.15 ng/ml/cm3, and favorable biopsy characteristics per the Epstein criteria currently appear to be the safest candidates for expectant treatment. Changes in biopsy characteristics are the most objective trigger for definitive therapy currently in use. Outcomes data are still required to determine the safety of expectant treatment for localized disease.
 ...
PMID:Expectant treatment with curative intent in the prostate-specific antigen era: triggers for definitive therapy. 1641 95


1 2 3 4 Next >>