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

Interactions of metastatic cancer cells with vasculatory endothelium are critical during early stages of cancer metastasis. Understanding the molecular underpinnings of these interactions is essential for the development of new efficacious cancer therapies. Here we demonstrate that cancer-associated carbohydrate T antigen plays a leading role in docking breast and prostate cancer cells onto endothelium by specifically interacting with endothelium-expressed beta-galactoside-binding protein, galectin-3. Importantly, T antigen-bearing glycoproteins are also capable of mobilizing galectin-3 to the surface of endothelial cells, thus priming them for harboring metastatic cancer cells. The T antigen-mediated, tumor-endothelial cell interactions could be efficiently disrupted using synthetic compounds either mimicking or masking this carbohydrate structure. High efficiency of T antigen-mimicking and T antigen-masking inhibitors of tumor cell adhesion warrants their further development into antiadhesive cancer therapeutics.
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PMID:The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. 1140 62

Farmers may experience exposure to several hazardous substances, and cancer risk in this occupational group is considered an important public health issue. In order to examine the association between cancer and farming among male agricultural workers, a hospital-based case-control study was conducted in five Italian rural areas. The cancer sites selected for the study were: lip, oral cavity and oropharynx, oesophagus, stomach, colon, rectum, lung, skin melanoma, skin non-melanoma, prostate, bladder, kidney, and non-Hodgkin's lymphoma. In all, 1525 newly diagnosed cases, aged 20-75 years, were ascertained in hospital records, covering the period between March 1990 and September 1992, and for 1279 of them, a detailed exposure information was collected by a standard questionnaire. Data analyses were performed comparing each cancer site to a control group, including a subset of the other cancer sites in the study. Unconditional logistic regression models were used in the statistical analyses. Increased risks of cancer associated with agricultural work were found for stomach (OR = 1.4, 95%CI:0.9-2.0), rectum (OR = 1.5, 95%CI:0.8-2.7), larynx (OR = 1.4, 95%CI:0.8-2.5), and prostate (OR = 1.4, 95%CI:1.0-2.1). The excess of prostate cancer was specifically related to application of pesticides (OR = 1.7, 95%CI:1.2-2.6).
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PMID:Cancer risk among male farmers: a multi-site case-control study. 1188 17

SOX transcription factors with high-mobility-group DNA-binding domain (HMG box) play key roles in embryogenesis. Some members of the SOX family are negative regulators of the WNT-beta-catenin-TCF signaling pathway. We have previously cloned and characterized human SOX17, constituting a subfamily with SOX7 and SOX18. Another group mapped SOX7 gene to human chromosome 8p22, and reported almost ubiquitous expression of 5.0-kb SOX7 mRNA in human normal tissues. Here, expression of SOX7 mRNA was investigated by using SOX7 specific probe, which hybridized to 3.8-kb human SOX7 mRNA, but not to 5.0-kb mRNA. SOX7 mRNA was relatively highly expressed in adult lung, trachea, lymph node, placenta, fetal lung, and heart. In adult heart, SOX7 mRNA was more highly expressed in ventricules, inter-ventricular septum and apex than in atriums. SOX7 mRNA was significantly up-regulated in pancreatic cancer cell lines BxPC-3, PSN-1, Hs766T, and in 4 cases out of 8 cases of primary gastric cancer. SOX7 mRNA was relatively highly expressed in a gastric cancer cell line MKN45, esophageal cancer cell lines TE2, TE3, TE4, TE5, TE7, TE8, TE11, TE12, and TE13. On the other hand, SOX7 mRNA was significantly down-regulated in 7 out of 18 cases of primary colorectal tumors, in 4 out of 9 cases of primary breast cancer, in 4 out of 14 cases of primary kidney tumors, and also in some cases of primary lung and prostate cancer. SOX7 gene might be one of cancer-associated genes on human chromosome 8p22.
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PMID:Expression of human SOX7 in normal tissues and tumors. 1189 28

Basic fibroblast growth factor (bFGF) is a potent tumor angiogenesis factor which lacks an amino-terminal signal sequence and does not normally circulate in serum from normal subjects. Naturally-occurring autoantibodies which mimicked basic fibroblast growth factor were described in serum from patients with multiple endocrine neoplasia type 1 prolactinoma or sporadic growth-hormone-secreting adenoma associated with increased bFGF. Since bFGF was increased in serum from a variety of cancers, we used endothelial cell proliferation assay(s) to test for bioactivity in the IgG fraction of serum from 56 patients with cancer-associated hypercalcemia, and normal or control subjects. We now report increased IgG-like endothelial cell activity in serum from a hyper prolactinemic subset (4/19 breast cancer; 1/14 renal cancer; 0/23 lung cancer) of cancer-associated hypercalcemic subjects. Highest activity was found in serum from three breast cancer patients who suffered spinal cord compression/metastases. The activity had properties of antiidiotype bFGF antibodies including reaction with anti-human IgG antibodies, and complete neutralization by rabbit antibodies to intact bFGF. The activity in endothelial cells persisted after storage at 0-4 C for 5 yrs; and [prepared by SDS-PAGE and immunoblotting with anti-human IgG] had apparent mol wt corresponding to the heavy chains of IgG. Serum IgG-like activity from 5 of 5 breast cancer patients and 2 of 2 prostate cancer subjects tested [prepared by anti-bFGF antibody, protein-A immunoaffinity, and hydroxyapatite (HA) chromatography] yielded peak HA-adsorbed activity that eluted with 0.4 M sodium phosphate, and was neutralized 70% by antibodies to intact bFGF. Cancer sera mean peak specific activity (12.0 ng-eq bFGF/ug protein) (n = 7) significantly exceeded (P < 0.001) normal sera mean peak specific activity (0.46 ng-eq bFGF/ug protein) (n = 6) in the 0.4 M sodium phosphate eluate fraction from hydroxyapatite columns. These results imply that long-lasting, bioactive FGF-like autoantibodies may arise spontaneously (and contribute to pathophysiology) in subsets of cancer patients with osseous metastases.
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PMID:Increased fibroblast growth factor-like autoantibodies in serum from a subset of patients with cancer-associated hypercalcemia. 1238 79

International research through epidemiological techniques has provided information on risk factors and preventive approaches in chronic disease. Causation complementing this base of knowledge with laboratory research on associated markers for each disease has outlined the possible mechanisms whereby risk factors and preventive conditions operate. Furthermore, laboratory research in animal models and cell cultures has expanded the appropriate elements associated with each condition. Individuals in the Mediterranean area present with a lower risk of several important chronic diseases, including coronary heart disease and a number of types of cancer associated with nutritional traditions, such as breast, colon, and prostate cancer. Vegetables and fruits in general and cooked tomatoes, together with olive oil, appear to be the nutritional traditions that account for this lower risk. These results lead to public health recommendations to consume more vegetables and, especially, cooked tomatoes with olive oil.
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PMID:Lycopene and tomato products in health promotion. 1242 36

Mutations in the androgen receptor (AR) are associated with a variety of diseases including androgen insensitivity syndrome and prostate cancer, but the way in which these mutations cause disease is poorly understood. We present a method for distinguishing likely disease-causing mutations from mutations that are merely associated with disease but have no causal role. Our method uses a measure of nucleotide conservation, and we find that conservation often correlates with severity of the clinical phenotype. Further, by only including mutations whose pathogenicity has been proven experimentally, this correlation is enhanced in the case of prostate cancer-associated mutations. Our method provides a means for assessing the significance of single nucleotide polymorphisms (SNPs) and cancer-associated mutations.
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PMID:A functional analysis of disease-associated mutations in the androgen receptor gene. 1268 77

BPSA and proPSA are distinct molecular forms of free PSA in serum. BPSA is a form of free PSA that is associated with BPH. The inactive precursor of PSA, proPSA, is associated with prostate tumors. ProPSA is comprised of native proPSA as well as truncated proPSA forms, [-2]pPSA and [-4]pPSA, which have been shown to be more cancer-associated than native proPSA. We have developed highly specific and sensitive research immunoassays for BPSA, and the different forms of proPSA. Free PSA in prostate cancer serum contains a median of 28% BPSA and 32% proPSA, though each form of PSA can range from 0 to more than 50% in individual samples. Early studies revealed that proPSA significantly increases the specificity for prostate cancer, especially in the 2-4 ng/ml PSA range. It is estimated that 20-30% of men with PSA values from 2-4 ng/ml have prostate cancer. In the 2.5-4 ng/ml PSA range proPSA gave a receiver operating characteristic-area under the curve (ROC-AUC) of 0.636 compared with free PSA (0.506) and complex PSA (0.509). At 90% sensitivity the specificity for proPSA was 25% compared to 10% for %FPSA and cPSA (P = < 0.001). ProPSA was superior to %FPSA and complexed PSA in the 4-10 ng/ml PSA range (AUC = 0.689, 0.637 and 0.538, respectively). ProPSA represents a more cancer-specific form of PSA that better discriminates prostate cancer from BPH.
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PMID:Pro PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer. 1286 59

Extensive scientific literature data point to reciprocal interactions between prostate stromal cells and prostate cancer cells that likely regulate tumor progression. To investigate whether these intratumoral-reactive stromal cells in human prostate cancer are predictive of survival, tumor stroma volume and specific stroma markers were quantitated by using tissue microarrays (index tumors of 847 patients), and the results were analyzed relative to the recurrence-free survival data set for these patients. Tumor tissue was evaluated with Masson's trichrome stains and by immunohistochemistry with antibody probes to smooth muscle alpha-actin, desmin, vimentin, pro-collagen type I, and calponin. The relative volume of intratumor stroma (5% stroma, grade 0; 5-15%, grade 1; 15-50%, grade 2; >50%, grade 3) and the expression index of stromal marker (staining intensity grade x percentage of positive cells per field) were quantitated and analyzed. Interpretable data were obtained from 545 patients. Statistical analysis of the survival data set showed that the volume of reactive stroma in the tumor was a significant predictor of disease-free survival. Stroma volume was most optimal as an independent predictor in tumors containing stroma, defined as Gleason 7 and lower grades. Of interest, tumors with either little to no stroma or tumors with abundant stroma each showed reduced recurrence-free survival. For specific stromal markers, reduced desmin and smooth muscle alpha-actin were hallmarks of cancer-associated reactive stroma relative to normal fibromuscular stroma. Quantitative analysis of desmin and smooth muscle alpha-actin expression showed both to be significant and independent predictors of recurrence-free survival. This is the first study to demonstrate that nonepithelial-reactive stroma elements in prostate cancer tumors can be used as prognostic indicators. These data also add to the concept that tumors are not purely epithelial and the tumor-reactive stroma must be considered an important biological component of the cancer.
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PMID:Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. 1458 50

The appropriate management of elderly patients diagnosed with prostate cancer remains controversial. In order to provide guidelines as to when aggressive local treatment may be indicated, we provide estimates of the long-term probability of death from prostate cancer and other competing causes in patients of 70 years of age or older, who underwent radical surgery in the form of radical perineal prostatectomy for clinically non-metastatic disease. In this study, a total of 484 patients with an age of 70 or above who underwent radical perineal prostatectomy between 1970 and 2000 comprised a retrospective cohort of patients with clinically organ confined prostate cancer. Of these patients, 461 patients (95.3%) had a minimum follow-up of half a year and were included in the analysis. The median age was 73 years (range 70-81 years) and the median follow-up was 5.4 years. Overall 115 men died during the follow-up period with 49.6% of deaths attributable to prostate cancer. The median time to cancer-associated death was 17.5 years and the median time to death of any cause 11.6 years. When the likelihood of death from prostate cancer as a function of Gleason score was estimated, the 10-year cancer-associated death rates of patients with Gleason scores of 2-6, 7 and 8-10, were 15.2, 25.2 and 40.2%, respectively. In the subset of patient with margin positive disease the estimated likelihood of a cancer-associated death was 45.3% after 10 years. While the median time to cancer-associated death for margin positive patients with a Gleason score of 2-6 was not reached, patients with a Gleason score of 7 and 8-10 experienced median cancer-associated survival times of 9.6 and 7.6 years, respectively. In conclusion, Gleason score is a strong predictor of the likelihood of prostate cancer related death in elderly patients. Patients with a given Gleason score and a projected life expectancy of at least 10 years may be at similar risk of dying of prostate cancer as younger patients.
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PMID:When to diagnose and how to treat prostate cancer in the "not too fit" elderly. 1460 75

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.
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PMID:Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy. 1504 96


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