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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For therapeutic decisions it is essential to have an evaluation of the tumor volume and the grade of dedifferentiation. Measurement of PSA gives a good additional guide to the tumor volume and to dissemination of the disease. Investigation of the DNA ploidy values can offer further important information on the aggressiveness of the tumor and be helpful for our understanding of the process of tumor propagation. However, DNA studies can still not be regarded as being standard in the clinical work-up of these patients. They are optional but they have a definite place in the research on prostatic cancer. The various methods to study tumor growth by analysis of the S phase fraction are interesting new contributions but still belong to the research laboratories. When we consider prognostic indicators we have to take into account the biologic character of carcinogenesis. Modern research has shown that the development and the progression of cancer is not an instantaneous and solitary reaction. It is a series of events and a net-work reaction between growth-regulating factors, stimulating and inhibiting, a step-wise alteration of the genome. We must recognize that what we are observing is the condition at the present time, and, of course, the observation must be evaluated together with the whole clinical scenario, the man's age, his general condition etc. But still the series of diagnostic procedures presented here will give a rather solid ground for both our therapeutic decisions and for evaluation of the results of treatment.
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PMID:Prognostic indicators in prostatic cancer. 150 80

Male rats were fed, from weaning onwards, either 2, 12.5 or 25% sunflower seed oil (polyunsaturated fatty acids, PSA) or lard (saturated fatty acids, SFA) and from the age of 15 weeks subgroups were given N-nitrosodimethylamine (NDMA) for 30 weeks. Blood levels of lipids were assayed and during the study exhaled ethane was measured as an index of in vivo lipid peroxidation (LPO). At the age of 50 weeks, rats were killed and livers were analysed for tumours. PSA diets decreased plasma cholesterol and triglyceride concentrations vs. respective SFA diet; NDMA administration did not affect plasma cholesterol but enhanced triglyceride concentration. NDMA markedly enhanced LPO. An increase in dietary fat content from 2 to 25% enhanced ethane exhalation, more in rats fed PSA than the SFA diet. In the 25% PSA group, indomethacin in the diet strongly inhibited LPO. Prevalence of liver haemangiosarcomas increased from 42% to 80% (p less than 0.05) in NDMA-treated animals when PSA increased from 2 to 25%; in the group having a 25% PSA diet containing indomethacin, the NDMA-induced tumour incidence was reduced to 64%. In NDMA-treated rats fed SFA diets the prevalence of haemangiosarcoma increased from 43% (2% fat) to 67% (25% fat). The data show that NDMA modifies plasma lipids and increases LPO. The quantity and saturation degree of fats altered the frequency of chemically-induced tumours and modified LPO. As an index of free radical reactions, LPO may have an important role in carcinogenesis. Dietary fat thus appears to promote carcinogenesis through mechanisms that involve LPO.
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PMID:Quantity and saturation degree of dietary fats as modulators of oxidative stress and chemically-induced liver tumours in rats. 221 Aug 84

The ability of primary tumours to metastasize accounts for the majority of cancer deaths. The emergence of circulating carcinoma cells in the peripheral blood is supposed to be an indicator for cancer cell spread. We have focused on this phenomenon in order to develop a sensitive technique for enriching epithelial derived cells on the basis of a two-layer density gradient and subsequent immune magnetic cell sorting. Epithelial cells are possess a cytoskeleton containing an assembly of intermediate filaments. During carcinogenesis these filaments do not undergo modifications of antibody binding epitopes such as occur in the protein domains of surface markers. We have developed a two-layer density gradient in which the epithelial cells form a single density band. This was demonstrated by recovery experiments using [3H]thymidine-labelled epithelial cells which showed epithelial cells were enriched within this first step by a factor of 20. In a second step the MACS system was applied. Cells were stained with a performed FITC-conjugated mouse anti-human cytokeratin antibody bound to a rat anti-mouse antibody coupled to superparamagnetic particles (immune paramagnetic separation complex; IPSC) and subjected to high gradient magnetic fields. The two-step procedure was confirmed by dispersing 50 epithelial cells in 5 x 10(5), 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9) peripheral blood leucocytes. Specific binding of the preformed IPSC was demonstrated by flow cytometry, confocal laser, fluorescent and electron microscopy. The specificity of the method was further proved by dual staining with IPSC and anti-human PSA antibody of epithelial prostatic cells separated from peripheral blood in vitro. By means of this double-step separation method it was possible to isolate up to 15-20 cells out of 50 epithelial cells originally suspended into 5 x 10(7) to 5 x 10(9) human peripheral blood leucocytes. This represented an enrichment factor between 20,000 and 200,000, depending on the initial cell number. The immunologically captured epithelial cells can be used for further cytogenetic investigations such as in situ hybridization (ISH) and/or polymerase chain reaction (PCR) to detect cancer cell specific gene aberrations. This sensitive combined buoyant density immune magnetic cell separation technique is capable of detecting free carcinoma cells in the peripheral blood.
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PMID:An immunological enrichment method for epithelial cells from peripheral blood. 760 48

The involvement of vitamin D in prostate carcinogenesis was investigated using the human prostatic LNCaP cells. Incubation of the LNCaP with 100 nM 1 alpha,25-dihydroxyvitamin D3 for 2 days resulted in a 30-40% suppression of cell growth, which was accompanied by a greater than 70% down-regulated expression of the proliferating cell nuclear antigen (PCNA). The intracellular and secreted forms of PSA showed a 2-fold increase following a 48 h culture in the presence of vitamin D3. The vitamin D3-elicited PSA increases were preceded by an induction of androgen receptor (AR) expression, as measured by Western blot analysis and by binding assays using [3H]R1881 as the ligand. These results are consistent with the hypothesis that the growth inhibitory effects of vitamin D3 is partially mediated through its ability to modulate PCNA expression. Moreover, vitamin D3 may effect increases in PSA expression indirectly by up-regulating androgen receptors.
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PMID:Regulation of growth, PSA/PAP and androgen receptor expression by 1 alpha,25-dihydroxyvitamin D3 in the androgen-dependent LNCaP cells. 866 Mar 60

Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotrophic growth factor in carcinogenesis and regulars multiple cell functions. We wanted to evaluate the diagnostic meaning of TGF-beta 1 plasma levels in patients with a biopsy proven prostate cancer. The TGF-beta 1 blood level was analysed in 394 patients. In 242 patients (group I) the blood was taken before any prostate manipulation and biopsy. The TGF-beta 1 plasma concentrations were almost similar in the group of patients with a prostate cancer (n = 157) and patients with a benign prostate hyperplasia (n = 85; 14,258 pg/ml versus 14,658 pg/ml, SD 10,516 pg/ml). In 152 patients the blood was taken 6-12 months after radical prostatectomy (group II). There was no significant difference between the patients with a PSA-progress and without PSA-progress after. Our results suggest that TGF-beta 1 plasma levels can not be used to distinguish between patients with prostate cancer and benign prostate hyperplasia.
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PMID:[Plasma TGF-beta1 concentrations in patients with prostate carcinoma or benign prostatic hyperplasia]. 956 35

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC-E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.
Carcinogenesis 1998 Apr
PMID:Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma. 960 Mar 41

Although adenocarcinoma of the prostate is recently becoming one of most common malignancies in Japanese men, it still poses many questions regarding its etiology, pathology, pathogenesis and clinical management. Many reports have been made on oncogene and tumor suppressor gene, however, frequent genetic alterations have not been identified during prostate cancer development. Loss of heterozygosity (LOH) on 8p might be an important event in the early stage of prostatic carcinogenesis, whereas alteration in 17p is now considered a late event. Numerous reports about the androgen receptor (AR) gene have revealed that mutations in the coding region of AR possibly results in an acquired resistance to androgen blockade therapy and anti-androgen withdrawal syndrome. It has been also shown that shorter CAG repeats of AR gene are associated with a higher risk of prostate cancer. Regarding molecular diagnosis, prostate-specific membrane antigen (PSM) appears to be a new molecule with many potentially valuable applications. PSM-reverse transcriptase-polymerase chain reaction (RT-PCR) is probably more sensitive and specific than PSA-RT-PCR to predict micrometastatic disease. Gene therapy based on the above molecular aspect is currently under investigation but not generally used yet.
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PMID:[Molecular biological aspect]. 961 16

Publications (up to the year 1997) on the interactions of "prostatic" kallikreins (prostatic specific antigen-PSA, etc.), sex hormones, insulin-like growth factors (IGF) and proteins binding them (IGFBP) in physiological processes (ageing, menstrual cycle, pregnancy) and oncogenesis (prostatic and mammary cancer) are reviewed. The concentrations of PSA, IGF, and IGFBP in organs and liquid media of men and women are presented. A concept of similarity in the mechanisms of interactions of sex hormones (dihydrotestosterone in men and progesterone in women), PSA, IGFBP, and IGF during activation of anabolic and proliferative processes in health and carcinogenesis is presented as a scheme. The diagnostic and prognostic value of PSA as a cancer marker should not be confined to male tumors (prostatic cancer and benign prostatic hyperplasia). Our data permits us to regard PSA as an oncofetal marker for men and women, indicating normal and neoplastic proliferative processes in the prostatic, mammary, salivary, and other glands and in the lungs and endometrium. Diagnostic and prognostic significance of PSA in breast cancer is shown. The traditional name "PSA" does not reflect its physiological and pathogenetic role as a member of the kallikrein family with chymotrypsin-like activity. PSA is not absolutely specific towards the producer organ and sex. Its relative specificity for the prostate is undoubted, because the content of PSA in prostatic tissue and seminal plasma is 10(6)-10(8) times higher than in the serum and other organs of men and women. Therefore, although the terms "prostatic, "specific", and "antigen" now became trivial and it is difficult to refuse from them, they can be used only in quotation marks.
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PMID:["Prostatic" kallikreins, sex hormones and insulin-like growth factors: complex of male and female regulatory elements in health and carcinogenesis]. 1022 33

Early prostatic carcinoma is a slowly progressing, localized malignant tumor which has been recently discovered with increased frequency due to the use of improved diagnostic methods. The combination of digital rectal examination, serum PSA level and transrectal ultrasound is currently the best available diagnostic tool, although other putative diagnostic markers and techniques are being investigated. Core needle biopsy may follow if there is suspicion of malignancy and in doubtful cases the most useful antibody for the immunohistochemical diagnosis of early, low grade prostatic carcinoma is clone 34 beta E12. Cytogenetic techniques and molecular biological methods are increasingly being used for further investigating localized prostate carcinomas in order to identify early molecular targets and alterations, which may lead to progression. Chromosome abnormalities, cell to cell and cell to matrix interactions, changes in the status of steroid hormone receptors, oncogenes and tumor suppressor genes, as well as other, as yet unclear, events may be of importance in prostate carcinogenesis and the progression of early malignant tumors to aggressive phenotypes. A variety of putative prognostic markers, apart from serum PSA levels, histological grade and tumor volume, such as neuroendocrine differentiation, angiogenesis, cell proliferation labeling index and ploidy analysis may prove useful in evaluating tumor progression in early prostatic carcinomas. The final and most important goal of all investigations related to early prostate cancer is to contribute to the best therapeutic management of the individual patient.
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PMID:Recent advances in early prostatic cancer. 1047 53

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, a decade after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum PSA concentration or its derivatives and cannot be detected by ultrasonography. Most studies suggest that most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.
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PMID:Prostatic intraepithelial neoplasia is a risk factor for cancer. 1063 20


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