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)

In this article, the pathologic findings of carcinoma of the prostate were reviewed. Criteria were discussed for the pathologic diagnosis of prostatic carcinoma (PC), premalignant lesions, lesions that simulate PC, immunopathologic findings, special types of PC, effects of therapy on the prostate, and recent efforts to improve diagnostic and prognostic capabilities. The possible role of the study of nucleolar organizing regions was reported. A new method for demonstrating chromosomes in formaldehyde-fixed paraffin-embedded tissue was mentioned. The need for research in all aspects of the pathology of prostatic cancer was emphasized.
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PMID:A pathologist's view of prostatic carcinoma. 767 44

In 1994, the International Agency for Research on Cancer (IARC) classified wood duct as a human carcinogen, based on very strong evidence of a carcinogenic risk of sino-nasal cancer. Excesses of other cancers, including lung and stomach, have been reported among persons employed in wood industries or occupationally exposed to wood dust, but not as consistently. We investigated such possible associations using the mortality experience of 362,823 men enrolled in the American Cancer Society's Cancer Prevention Study-II in 1982 and followed up for 6 years. Within this group, 45,399 men (12.5%) reported either employment in a wood-related occupation or exposure to wood dust or both. Among woodworkers, a small but significant excess risk was found for all cases of death (RR 1.17 (95% CI 1.11-1.24)) and for total malignancies (RR 1.17 (1.05-1.30)). Among men who reported exposure to wood dust, there was an elevated risk of total mortality (Rr 1.07 (1.03-1.11)), total malignancies (RR 1.08 (1.01-1.15)), and lung cancer (RR 1.17 (1.04-1.31)). Among woodworkers, a significant trend (P = 0.02) of increasing risk of lung cancer with increasing duration of exposure was observed. An unexpected, significantly increased mortality from prostate cancer was observed in both wood-employed and wood-exposed, and a twofold increased risk of fatal brain cancer was seen among the former. Lung cancer mortality was especially high among woodworkers who also reported exposure to asbestos or formaldehyde, and it appears that exposure to these known carcinogens may partly explain the observed increased risks. Excess sino-nasal cancer was not observed, but the number of cases was small.
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PMID:Cancer mortality and wood dust exposure among participants in the American Cancer Society Cancer Prevention Study-II (CPS-II). 969 91

Cytoplasmic clarity is a histological feature of normal prostatic secretory cells, but in this study, tissue fixation in strong (>2.5%) glutaraldehyde dramatically altered cytological staining. Secretory cytoplasm appeared red and granular on routine stains because of myriad intensely staining eosinophilic granules (PSG). Immunostaining for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) showed their exclusive localization to the PSG. Electron microscopy confirmed these findings and also showed that after fixation in many agents, including formaldehyde, PSG appeared empty, accounting for the artefactual "clear cell" appearance on light microscopy. PSG were most densely concentrated apically in a bud-shaped luminal compartment in which cytokeratin was selectively absent. Normal exocrine secretion was visualized as detachment of apocrine buds or their in situ disintegration. Distinctively in dysplasia and almost all carcinomas, PSG were rare to absent, and proteases were free in the cytoplasm, often concentrated beneath the apical membrane. The apocrine compartment was absent, with no observed secretory mechanism. Tumor cells had dark amphiphilic cytoplasm after all fixatives. This provided a reliable method of distinguishing malignant from benign glands in tissues fixed in strong glutaraldehyde. Clear cell carcinomas, whose cytoplasm mimicked routinely fixed normal secretory cells, surprisingly had almost no PSG. Instead, their "granules" were lipid-filled vacuoles reflecting a secretory pathway not seen in normal cells, dysplasia, or the common "dark cell" carcinomas. These observations may define two distinctive biological pathways of prostate cancer evolution and may facilitate diagnostic decisions on needle biopsy samples.
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PMID:Characterization of cytoplasmic secretory granules (PSG), in prostatic epithelium and their transformation-induced loss in dysplasia and adenocarcinoma. 1123 Jul 17

Recent data indicate that the clinical anthracycline anti-tumor drugs, doxorubicin (DOX), daunorubicin (DAU), and epidoxorubicin (EPI), catalyze the production of formaldehyde through induction of oxidative stress and bind the formaldehyde to form a metabolite which covalently bonds to DNA. Based upon this discovery, anthracycline-formaldehyde conjugates were synthesized and evaluated in three metastatic prostate cancer cell lines, LNCaP, PC-3, and DU-145. The doxorubicin-formaldehyde conjugate, Doxoform (DOXF), inhibits the growth of PC-3 and DU-145 cells 50- and 80-fold better, respectively, than the corresponding clinical drug, DOX. Daunorubicin- and epidoxorubicin-formaldehyde conjugates, Daunoform and Epidoxoform (DAUF and EPIF), inhibit the growth about 6 to 10-fold better than the clinical drugs, DAU and EPI. In addition, DAUF, DOXF, and EPIF are 2- to 20-fold more toxic to the doxorubicin-sensitive metastatic prostate cancer cell line, LNCaP. Fluorescence microscopy indicates that the nucleus is the major target for all six drugs. Flow cytometry together with fluorescence microscopy shows that DOXF and EPIF are taken up more rapidly and more abundantly and are retained in the nucleus longer than DOX and EPI, respectively, especially in DU-145 cells. The enhanced toxicity of the anthracycline-formaldehyde conjugates is attributed to their increased nuclear uptake and retention and suggests that DOXF, DAUF, and EPIF are prodrugs to the active metabolites of the clinical drugs DOX, DAU, and EPI.
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PMID:Growth inhibition, nuclear uptake, and retention of anthracycline-formaldehyde conjugates in prostate cancer cells relative to clinical anthracyclines. 1036 76

We have used selected ion flow tube mass spectrometry (SIFT-MS) to determine the concentration of formaldehyde in the headspace of urine from patients suffering from bladder and prostate cancer and from several healthy subjects as controls. We address the potential problems associated with the use of ion chemistry to quantify formaldehyde in the presence of the relatively large number densities of water molecules and show that formaldehyde can be quantified in urine headspace using analysis by SIFT-MS. These studies show that formaldehyde is clearly elevated in the headspace of the urine from the cancer patients as compared with urine from the healthy controls. Thus, with further improvements in the methodology and the sensitivity of our SIFT-MS technique, formaldehyde quantification in urine headspace using this new analytical method could be a valuable non-invasive indicator of the presence of early-stage tumours in the body.
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PMID:Analysis of formaldehyde in the headspace of urine from bladder and prostate cancer patients using selected ion flow tube mass spectrometry. 1040 24

Recent and new results which support a drug-DNA covalent bonding mechanism for cell toxicity of the clinical antitumor drugs, daunorubicin, doxorubicin, and epidoxorubicin, are summarized. The mechanism involves the iron complex of the drugs inducing oxidative stress to yield formaldehyde, which then mediates covalent attachment to G-bases of DNA. At NGC sites the combination of covalent and non-covalent drug interactions serve to virtually crosslink the DNA. Structural data for virtual crosslinks are compared as a function of drug structure. Elucidation of the mechanism led to the synthesis and evaluation of drug formaldehyde conjugates, Daunoform, Doxoform, and Epidoxoform, as improved chemotherapeutics. Drug uptake, nuclear targeting, drug release, and cytotoxicity of the clinical drugs by sensitive and resistant breast and prostate cancer cells are contrasted with those of the corresponding formaldehyde conjugates. Conjugates are taken up better, retained longer, and are more toxic to a wide variety of tumor cells. The kinetics of drug release from Doxoform and Epidoxoform treated MCF-7/Adr cells are biexponential and correlate with the biexponential kinetics of drug release from extracellular DNA. The results of the lead conjugate, Epidoxoform, in the National Cancer Institute 60 human tumor cell screen are presented and discussed in terms of some resistance mechanisms. Epidoxoform shows increased toxicity to all panels relative to doxorubicin and epidoxorubicin, and this enhanced toxicity is especially evident with the more resistant cell lines.
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PMID:Nuclear targeting and retention of anthracycline antitumor drugs in sensitive and resistant tumor cells. 1117 89

A rapid and highly sensitive method for the detection of formaldehyde utilizing selected ion flow tube-chemical ionization mass spectrometry is reported. Formaldehyde in aqueous biological samples is preconcentrated by distillation and directly analyzed using gas-phase thermal energy proton transfer from H30+; this procedure can be performed in 30 min. The method detection limit for formaldehyde based on seven replicate measurements of reference water samples (2.5 mL) is 80 nM at the 99% confidence level. Detection is linear up to 130 microM. This technique allows the first measurement of natural formaldehyde levels in human cancer cells in vitro. Elevated levels of formaldehyde relative to the reference water are observed for doxorubicin-sensitive cells (MCF-7 breast cancer, K562 leukemia, HeLa S3 cervical cancer) with estimated intracellular formaldehyde concentrations ranging from 1.5 to 4.0 microM, whereas formaldehyde in doxorubicin-resistant MCF-7/Adr breast cancer cells is essentially at reference level. This trend is inverted for prostate cancer cells LNCaP (sensitive) and DU-145 (resistant). Correlation of natural formaldehyde level with doxorubicin cytotoxicity is a function of the expression of enzymes that neutralize oxidative stress and the drug efflux pump, P-170 glycoprotein.
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PMID:Formaldehyde in human cancer cells: detection by preconcentration-chemical ionization mass spectrometry. 1146 45

The aim of this study was the immunohistochemical evaluation of p53 protein expression in localized prostate cancer (Pca) following radical prostatectomy and analysis of its relationship to chosen anatomo-clinical and morphological parameters of the tumours. The present investigation included material from 28 randomly selected patients undergoing radical prostatectomy. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the anti-human p53 protein monoclonal antibody. The immunolocalization of p53 protein was performed using the Labelled Streptavidyn Biotin (LSAB) method. The p53 protein expression was semiquantitatively assessed in neoplastic cells and the reaction present in more then 25% of tumour cells was accepted as the threshold of positivity. No correlation was found between p53 protein expression and Gleason score, pT stage, lymph node metastases, seminal vesicles invasion, positive or negative surgical resection margins, age of patients. However, p53 protein expression and capsular penetration was found statistically significantly correlated.
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PMID:Study of p53 protein expression in prostate cancer. 1182 Jun 5

Prostate cancer (Pca) is the most prevalent cancer diagnosed and the second leading cause of cancer-related deaths among men in the Poland. The present study was designed to analyse the relationship between expression of Bcl-2 protein in prostate cancer (PCa) following radical prostatectomy to chosen anatomoclinical and morfological parameters of the tumours. Tumours from 28 patients were assessed by immunohistochemistry. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the anti-human Bcl-2 antibody (Dako/Clon124). The immunolocalization of Bcl-2 was performed using the Labelled Streptavidin Biotin (LSAB) method. No correlation was found between Bcl-2 protein expression and pT stage, lymph node metastases, Gleason score, seminal vesicles invasion, positive or negative resection margins as well as capsular penetration and preoperative PSA serum level.
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PMID:Bcl-2 immunohistochemical detection in prostate cancer. 1253 68

The synthesis and preliminary evaluation of a doxorubicin-formaldehyde conjugate tethered to the nonsteroidal antiandrogen, cyanonilutamide (RU 56279), for the treatment of prostate cancer are reported. The relative ability of the targeting group to bind to the human androgen receptor was studied as a function of tether. The tether served to attach the antiandrogen to the doxorubicin-formaldehyde conjugate via an N-Mannich base of a salicylamide derivative. The salicylamide was selected to serve as a trigger release mechanism to separate the doxorubicin-formaldehyde conjugate from the targeting group after it has bound to the androgen receptor. The remaining part of the tether consisted of a linear group that spanned from the 5-position of the salicylamide to the 3'-position of cyanonilutamide. The structures explored for the linear region of the tether were derivatives of di(ethylene glycol), tri(ethylene glycol), N,N'-disubstituted-piperazine, and 2-butyne-1,4-diol. Relative binding affinity of the tethers bound to the targeting group for human androgen receptor were measured using a (3)H-Mibolerone competition assay and varied from 18% of nilutamide binding for the butynediol-based linear region to less than 1% for one of the piperazine derivatives. The complete targeted drug with the butynediol-based linear region has a relative binding affinity of 10%. This relative binding affinity is encouraging in light of the cocrystal structure of human androgen receptor ligand binding domain bound to the steroid Metribolone which predicts very limited space for a tether connecting the antiandrogen on the inside to the cytotoxin on the outside.
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PMID:Rational design and synthesis of androgen receptor-targeted nonsteroidal anti-androgen ligands for the tumor-specific delivery of a doxorubicin-formaldehyde conjugate. 1461 28


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