Can dietary factors influence prostatic disease?
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Antioxidants↗
Biomedical subjects
K Griffiths
Publications and source records attributed to K Griffiths.
Certain aspects of molecular endocrinology that relate to the influence of dietary factors on the pathogenesis of prostate cancer.
Isoflavonoids, flavonoids and lignans are natural oestrogenic compounds derived from soya, tea, fruits and vegetables and they have been proposed as chemopreventive agents in Asian men, in whom the incidence of prostate cancer is much lower than in men from the West. In addition to their weak oestrogenic activity, oestrogen antagonistic activity has also been described for some of these compounds. Furthermore, the lignan, enterolactone and the soya-derived isoflavone genistein are inhibitors of several steroid metabolising enzymes, such as aromatase, 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase. Genistein is a potent inhibitor of tyrosine kinases and along with flavonoids such as kaempferol and apigenin is also an inhibitor of topoisomerases I and II, enzymes which are crucial to cellular proliferation. Genistein is also an inhibitor of angiogenesis and many experimental in vivo and in vitro models, including those for prostate cancer, are growth inhibited by isoflavonoids, flavonoids and lignans. It is estimated that the traditionally eating Japanese male consumes approximately 20 mg of isoflavones per day, whereas for Western men, the daily consumption would be less than 1 mg/day. This is reflected in a high mean plasma concentration of genistein (180 ng/ml, n = 72) in Japanese men, compared to a level of <10 ng/ml for Western males.
Animals↗
Diet and its preventive role in prostatic disease.
Asian men have much lower incidences of prostate cancer and possibly of benign prostatic hyperplasia (BPH) than their Western counterparts. Vegetarian men also have a lower incidence of prostate cancer than omnivorous males. Both Asian and vegetarian men consume low-fat, high-fibre diets which provide a rich supply of weak dietary oestrogens. These plant or phyto-oestrogens have been proposed as chemopreventive agents, particularly for Asian men and to a lesser extent, for vegetarian men also. The three principal classes of phyto-oestrogens are the isoflavonoids, flavonoids and lignans. Many foods of plant origin contain varying amounts of these compounds and hundreds of plants manifest some degree of oestrogenic activity. Soya, a dietary staple in many parts of Asia, is a major source of the isoflavonoids, daidzein and genistein. Flavonoids are present in high concentration in many fruits, vegetables and crop species. In particular, apigenin and kaempferol are regarded as major flavonoids because of their common occurrence in plants, and their significant concentrations when present. Apples, onions and tea-leaves are excellent sources of flavonoids. Plant lignans are present in many cereals, grains, fruits and vegetables, and give rise to the mammalian lignans, enterodiol and enterolactone; however, the richest source is linseed (flaxseed) and other oilseeds. In addition to their oestrogenic activity, many of these plant compounds can interfere with steroid metabolism and bioavailability, and also inhibit enzymes, such as tyrosine kinase and topoisomerase, which are crucial to cellular proliferation.
Animals↗
Injury prevention takes root. EMS evolves to assume expanded mission.
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Accidents, Traffic↗
Phytoestrogens and diseases of the prostate gland.
Both benign hyperplasia (BPH) and cancer of the prostate are manifest in men beyond the age of 50. Approximately 50% of men greater than 50 years of age will suffer from the symptoms associated with BPH, especially from bladder outlet obstruction. With the ever-increasing proportion of the population over 65 years of age worldwide, BPH is becoming an important medical problem as the world moves into the next millennium. Cancer of the prostate is the second most commonly diagnosed cancer after skin cancer in the male population of the United States, and the second most common cause of death from cancer after that of the lung. Overall, around the world the incidence of carcinoma of the prostate is increasing annually by 2-3%. Both race and geographical location have a profound influence of the prevalence of prostate cancer worldwide. Black men in the USA have the highest incidence, while the incidence is much lower in Asian men from China, Japan and Thailand. Although the prostate gland is androgen-dependent, it is now recognized that the biological actions of endocrine-related factors, such as androgens, oestrogens, glucocorticoids and certain dietary and environmental factors, are mediated within the gland by various growth regulatory factors. The growth regulatory factors such as epidermal growth factor (EGF), keratinocyte growth factors (KGF), fibroblast growth factors (FGFs) and insulin-like growth factors II and I are mitogenic and directly stimulate cell proliferation under the modulating influence of steroid hormones. Steroids are therefore essential but not directly responsible for cell proliferation. Certain plant compounds such as isoflavonoids, flavonoids and lignans have been proposed as cancer protective compounds in populations with low incidences of prostate diseases. In particular, soya contains the isoflavone genistein, a compound with many properties which could influence both endocrine and growth factor signalling pathways.
Estrogens, Non-Steroidal↗
Possible relationship between dietary factors and pathogenesis of prostate cancer.
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Animals↗
Progesterone resistance in women who have had breast cancer.
OBJECTIVE: To investigate whether certain physiological responses to luteal progesterone are normal in women previously treated for breast cancer. DESIGN: Salivary progesterone concentrations, basal body temperatures, and breast blood flow changes (surface temperature method) were all recorded daily for one natural menstrual cycle. SETTING: Participants in the study made saliva collections and temperature measurements at home under semi-standardised conditions with supervisory visits by a project nurse. PARTICIPANTS: Twenty-five controls were compared with 30 women with previous breast cancer; all but three participants were parous and the average ages were 39 years (range 28-48) and 40 years (range 29-46), respectively. On average the women with previous breast cancer had had surgery 2.4 years previously; the operation was usually mastectomy, leaving the contralateral breast for study. RESULTS: Follicular phase (day 1-14) oral temperature averages were statistically indistinguishable between women in the control group and those with previous breast cancer. Luteal progesterone profiles were considered in the normal range for the controls and patients. However, the women with previous breast cancer, on average, exhibited a significantly smaller rise in the luteal phase basal body temperature. Follicular phase breast surface temperature was significantly higher in the breast cancer group (+0.30 degree C). This group showed a highly significant reduction of the luteal heat cycle in their breasts. CONCLUSIONS: Two progesterone-mediated physiological mechanisms have been found to be significantly less responsive in women with previous breast cancer than controls. The literature has been reviewed. Progesterone resistance could be a clinical entity and could be important in carcinogenesis.
Adult↗
Angiogenic factors expressed by human prostatic cell lines: effect on endothelial cell growth in vitro.
BACKGROUND: Antiangiogenic therapy for prostatic cancer should offer additional ways of combating tumor progression. Knowledge of the possible angiogenic factors expressed by prostate cancer cell lines would therefore assist in the design and testing of such potential treatments. METHODS: Changes in the proliferation and morphology of several endothelial cell lines (BAEC, HUVEC, and BACE) in response to either coculturing with human prostatic cell lines or culturing with conditioned medium derived from these lines were assessed. RESULTS: Proliferation of BAEC cells was significantly stimulated by conditioned media from DU145, LNCaP, and DuPro-1, and also by coculture with LNCaP and DuPro-1. Growth of HUVEC cells was significantly increased with conditioned media from LNCaP, Ten12, and PC3, and by coculture with DU145 and DuPro-1. FGF2 supplementation is required for BACE growth in vitro, and only conditioned medium from Ten12 cells, which produce the highest levels of this growth factor, significantly increased cell numbers. BACE growth, however, was stimulated in coculture experiments with DU145, DuPro-1, PC3, and LNCaP. Morphological changes were only observed in the BAEC and BACE cells when cultured with conditioned media. CONCLUSIONS: Prostatic carcinoma cell lines express a variety of angiogenic substances, including FGF2, which can stimulate endothelial cell proliferation in vitro, but this response may be modified by the prostatic-cell expression of other factors such as TGF alpha and TGF beta.
Adrenal Cortex↗
Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom.
BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.
4-Butyrolactone↗
Measurement and metabolism of isoflavonoids and lignans in the human male.
Asian men, who consume a low fat/high fibre soya-based diet, have very much lower incidence of prostate cancer than men from North America and Europe. The soya bean is a rich source of the isoflavonic phyto-oestrogens, daidzein, genistein and equol, compounds which may be cancer-protective in Asian populations. The lignans, enterolactone and enterodiol, plant oestrogens derived from cereals and vegetables, may act in a similar manner in vegetarian men. We report here on the measurement of isoflavonoids and lignans, by gas chromatography-mass spectrometry, in prostatic fluid of men from Asia and Europe and also on the metabolism of these compounds in Western men following dietary supplementation.
Adult↗
Comparative studies of the mitogenic effects of epidermal growth factor and transforming growth factor-alpha and the expression of various growth factors in neoplastic and non-neoplastic prostatic cell lines.
BACKGROUND: The role of growth factors in prostate cell growth has been investigated as these peptides may be involved in the autonomous growth of hormone-independent prostate cancer. METHODS: Responses of neoplastic (PC-3 and CPA) and non-neoplastic (CAPE) prostatic cell lines to epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) were determined using clonogenic and growth curve analysis. The constitutive expression of EGF, TGF-alpha, and TGF-beta 1-3 mRNA was examined using Northern blotting and EGF and TGF-alpha protein levels were determined immunohistochemically. RESULTS: Growth curve and clonogenic analysis indicated that EGF and TGF-alpha were mitogenic in each cell line. The magnitude of the clonogenic response varied between the cell lines, with CPA cells showing the greatest growth increases. CPA cells also displayed the highest levels of EGF and TGF-alpha mRNA and protein. TGF-beta 1 mRNA was detected in the order of magnitude, PC-3 > CPA > CAPE. Furthermore, PC-3 and CPA cells expressed TGF-beta 3 and TGF-beta 2 transcripts respectively. In each cell line, the expression of any growth factor mRNA was not affected by exogenous EGF. CONCLUSIONS: The growth responses of the cell lines to EGF and TGF-alpha did not correlate with their constitutive levels of EGF and TGF-alpha mRNA and protein, thus whilst growth factors may be important in malignant cell growth, other pathways may also be involved in the autocrine regulation of cell proliferation.
Animals↗
Response of cell growth and retinoic acid receptor expression to retinoic acid in neoplastic and non-neoplastic prostate cell lines.
BACKGROUND: Retinoic acid (RA) is recognized as an inhibitor of tumorigenesis, but conversely, has also been shown to act as a tumor enhancer, therefore its role in prostate tumor cell growth was investigated. METHODS: The response of two human prostate tumor cell lines (PC-3 and DU-145), and cell lines derived from a well-differentiated canine prostate adenocarcinoma (CPA) and normal canine prostate epithelium (CAPE) to all-trans RA was determined using growth curve analysis. Additionally, the constitutive expression and RA-challenged expression of retinoic acid receptors (RARs) -alpha, -beta, and -gamma mRNA was examined using Northern blotting techniques. RESULTS: In response to all-trans RA, the PC-3 and DU-145 cell lines showed considerable growth promotion, while CAPE and CPA cell growth was dramatically inhibited. Each cell line expressed RAR alpha and RAR gamma, with either negligible or no RAR beta transcripts being detected. RAR alpha and -gamma mRNAs detected in the four cell lines were variably regulated in response to RA, and no distinct patterns of RAR regulation that could be related to cell growth responses were observed. CONCLUSIONS: The data indicates that no simple association exists between the expression or regulation of RAR subtype mRNAs and the divergent growth responses to RA displayed by the prostate cell lines.
Adenocarcinoma↗
A randomized controlled trial of penicillin vs clindamycin for the treatment of aspiration pneumonia in children.
OBJECTIVE: To compare the effectiveness of intravenous penicillin vs clindamycin for the treatment of aspiration pneumonia. DESIGN: A double-blind, randomized controlled trial. SETTING: A tertiary care pediatric hospital. PATIENTS: We enrolled 42 children, aged 6 months to 18 years, who were admitted to the hospital for the treatment of aspiration pneumonia. All of the children had underlying conditions that predispose to aspiration. INTERVENTION: The patients were randomly assigned to receive intravenous penicillin G sodium, 250,000 U/kg every 24 hours, or intravenous clindamycin phosphate, 30 mg/kg every 24 hours. MAIN OUTCOME MEASURE: The primary outcome measure was "time to ready for discharge" from the hospital. RESULTS: In an effectiveness (intention to treat) analysis, the median time (interquartile range) to ready for discharge from the hospital was 4.9 days (range, 2.8-6.5 days) in the penicillin-treated group and 3.4 days (range, 2.3-6.8 days) in the clindamycin-treated group (P = .66). Results were not markedly altered when adjusted for the age difference of the groups or in the efficacy analysis (after the exclusion of 9 patients who withdrew from the trial). Rates for readmission to the hospital were similar in the 2 groups. CONCLUSION: Penicillin and clindamycin seem to be equally effective for the treatment of aspiration pneumonia in children hospitalized for this illness.
Adolescent↗
CI solvent yellow 14 shows activity in the bone marrow micronucleus assay in both the rat and mouse.
CI Solvent Yellow 14 has been reported to be carcinogenic in the rat, inducing neoplastic liver nodules, but non-carcinogenic in the mouse. The present experiments have extended previously reported investigations on the activity of CI Solvent Yellow 14 in in vivo genotoxicity assays. CI Solvent Yellow 14 has been examined for genotoxicity in vivo in the bone marrow micronucleus assay in both the rat and the mouse, and in the rat liver unscheduled DNA synthesis (DNA repair) assay, to limit doses of 5000 and 2000 mg/kg respectively, by oral gavage. CI Solvent Yellow 14 showed evidence of clastogenic activity in both the rat and mouse bone marrow (clear effect in the rat; weak effect in the mouse), but no evidence of DNA repair in the rat liver. In view of the latter finding, the contribution, if any, of the genotoxicity expressed by the micronucleus assay to the formation of liver nodules on chronic administration of the compound, is unclear.
Animals↗
Androgens, androgen receptors, antiandrogens and the treatment of prostate cancer.
Androgens play a major role in promoting the growth of the prostate gland. The DHT-androgen receptor complex, by association with the androgen response elements, specifically promotes this androgenic effect on the genome. Also recognized now, however, is that there is a close relationship between this androgen-mediated signalling pathway and those promoted by peptide growth factors, the crosstalk between the pathways being pivotal to growth regulatory control. This is discussed together with the perceived clinical potential of tyrosine kinase inhibitors for the treatment of prostate cancer, when the intracellular signalling, induced by the growth stimulatory factors, can be repressed.
Androgen Antagonists↗
A quantitative review of cognitive deficits in depression and Alzheimer-type dementia.
Meta-analysis was used to examine the performance of depressed and Alzheimer-type dementia (DAT) patients on standard and experimental clinical tests of cognitive function. Deficits were found for depression on almost every psychological test. Relative to nondepressed controls, the average deficit was 0.63 of a standard deviation, but the magnitude of the effect varied with the type of test. DAT patients performed worse than depressed patients, with an average effect size of 1.21 standard deviations, but the size of the effect depended on the clinical test. Effect sizes for the comparison between depressives and controls were significantly affected by age, treatment setting, ECT use, severity of depression, and the source of diagnostic criteria, but not by the type of depression. Effect sizes in the comparison of depressives to DAT patients were influenced by age, the severity of depression, and ECT. Depressives performed proportionately worse than controls on tasks with pleasant or neutral, compared with unpleasant content, on speeded compared with nonspeeded tasks, and on vigilance tasks. However, there were no differences in the magnitude of effect size for tests using recall compared with recognition, using categorical compared with noncategorical word lists, on story compared with word comprehension, and using verbal compared with visual material. Relative to DAT patients, depressives performed no better on recall compared to recognition tasks, or verbal compared to visual material. The findings of the review are not consistent with the hypothesis that depression is associated with deficits in effortful processing. A model of psychological deficit in depression as a deficit in speed or attention has more promise.
Aged↗
Low incidence of androgen receptor gene mutations in human prostatic tumors using single strand conformation polymorphism analysis.
It is possible that structural changes of the androgen receptor (AR) contribute to the insensitivity of prostatic carcinomas to endocrine therapy. We have isolated DNA from 58 human prostate tumor specimens (31 carcinomas pretreatment, 13 carcinomas after relapse to hormonal therapy, and 14 benign prostatic hyperplasia), three established human prostate carcinoma cell lines and two transplantable human prostatic carcinoma xenografts. Twelve pairs of oligonucleotide primers were used to amplify the majority of the coding region of the AR gene and the products screened for mutations using single-strand conformation polymorphism (SSCP) techniques. In one tumor sample a cytosine to guanine transition in exon F which leads to substitution of glutamic acid for the wild type glutamine at position 798 of the ligand binding domain was detected. The same mutation was also found in the patient's genomic DNA and as been described in a patient with partial androgen insensitivity syndrome. Intronic mutations were detected in two of the benign prostatic hyperplasia samples, and a silent mutation at nucleotide 995 was found to be present in eight poorly differentiated carcinomas, one BPH specimen, as well as in the cell line DU145 (18% of the samples studied). In agreement with most of the literature, these studies indicate that AR mutations are rare both prior to therapy and even in androgen relapsed tumors.
Humans↗
The luteal heat cycle of the breast in disease.
Wearing a special thermometric brassiere, selected women self-measured their breast surface temperature. These measurements were made during one hour each evening at home for one menstrual cycle under standard conditions of overclothing and room temperature. To stage their cycle they also collected daily samples of saliva in their freezer for immuno-assay of progesterone concentration in the laboratory. A total of 82 women participated, most having young families. This total included four groups, a control group (N = 25) and three 'disease' groups, namely: family history of breast cancer (14); benign breast disease (12); and a 'cancer-associated' group (31) who had had previous cancer surgery. A significant breast temperature rhythm with a period at or about 28 days was found not only in the controls but also in the three groups of breasts designated 'disease'. Nevertheless, consistent rhythm abnormalities were found in all the disease groups. Most evident was a hyperthermia throughout the cycle, a reduction in the rhythm amplitude, and a tendency for the breast temperature rhythm to be manifest 1-2 days earlier in the menstrual cycle.
Adult↗