Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of neonatal androgenization on 7,12-dimethylbenz[a]anthracene (DMBA)-induced endometrial carcinogenesis in Sprague-Dawley rats are studied. Testosterone propionate (1.25 mg) was injected subcutaneously into 110 2-day-old rats. At 8 weeks of age, a pellet containing 0.2 or 1mg DMBA was introduced into each uterine horn of both neonatally intact control rat (NR) and neonatally androgenized rat (ASR). All rats were killed at 24 or 48 weeks of age. The results were as follows. Vehicle group: No malignant uterine tumor was observed during both 16- and 40-week observation periods in either 122 horns of NR or 98 of ASR. 0.2 mg DMBA treated group: No malignant uterine tumor was detected in either 80 NR or 72 ASR during a 16-week observation period. Although three malignant uterine tumors were found among 72 NR during a 40-week observation period, no malignant uterine tumor was observed in 30 ASR. 1mg DMBA treated group: Although one malignant uterine tumor of 16 NR was found during a 16-week observation period, no malignant uterine tumor was observed in 20 ASR. Four malignant uterine tumors of 168 NR induced by DMBA were histologically 2 squamous cell carcinomas and two sarcomas. As mentioned above, although four malignant uterine tumors were induced by DMBA in 168 NR, no malignant uterine tumor was found in 122 ASR. These results seem to indicate that neonatal androgenization suppressed the induction of malignant rat uterine tumors by DMBA.
 ...
PMID:[Effects of neonatal androgenization on 7,12-dimethylbenz[a] anthracene-induced rat endometrial carcinogenesis]. 392 Mar 33

CBA male mice treated with 1,2-dimethylhydrazine (DMH) developed high incidence (up to 97%) of pararenal angiosarcomas. Castration that preceded DMH-treatment almost completely inhibited the induction of these tumours while castration that followed DMH-treatment had on influence on their development. Testosterone propionate (TP) was efficient in restoring the incidence of DMH-induced pararenal tumours in castrated males only when given simultaneously with DMH and was totally inefficient when given after the cessation of DMH-administration. Castrated CBA female mice developed 92% of pararenal angiosarcomas when they received combined treatment with DMH and TP; no such tumours appeared in the intact females treated with DMH alone. The incidence of pararenal tumours in males of different strains was as follows: CBA, 97%; (CBA X C57Bl)F1, 36%; C57Bl, 4%; C3H, 35%; BALB/c, 13%; C3HA, 7%.
Carcinogenesis 1985 Mar
PMID:Pararenal angiosarcoma induced in male mice by 1,2-dimethylhydrazine--a model for studying the role of androgens in chemical carcinogenesis. 403 21

The antiandrogen, cyproterone acetate (CPA), applied simultaneously with 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of male and female SENCAR mice initiated with 7,12-dimethylbenz[a]anthracene inhibited the production of papillomas of the skin. Although 125 and 250 micrograms of CPA had no effect on the incidence of papillomas per mouse, 500 micrograms of CPA inhibited papilloma production by 95% and 91% in female mice after 20 and 37 weeks of promotion, respectively. Testosterone propionate only partially blocked the inhibitory effect of CPA. In male mice 500 micrograms and 1 mg of CPA inhibited papilloma production by 77% and 88%, respectively. In the two-stage promotion protocol 500 micrograms of CPA was ineffective as an inhibitor when it was applied with TPA during the 1st stage but inhibited papilloma production by 71% when it was applied with mezerein during the 2nd stage. CPA was also observed to inhibit TPA-stimulated epidermal DNA synthesis and inflammation but had no effect on TPA-induced epidermal ornithine decarboxylase activity.
Carcinogenesis 1984 May
PMID:Effects of the antiandrogen, cyproterone acetate, on the induction of papillomas, DNA synthesis and ornithine decarboxylase activity in mouse skin. 623 44

It is generally accepted that early human prostate cancers reveal higher androgen dependency than do advanced ones. In the present study, we examined whether the animal model of prostate cancer has already lost androgen dependency at the early stages of carcinogenesis. At experimental week 46, androgen deprivation was induced in rats and the incidences of atypical hyperplasia and cancer were examined in the ventral, dorsolateral prostate, coagulating glands, and seminal vesicles. Androgen deprivation significantly lowered the incidence of atypical hyperplasia in all four organs. As for the incidence of cancer, no significant differences were observed in the coagulating glands and seminal vesicles. Regarding atypical hyperplasia, androgen deprivation significantly decreased the proliferative cell nuclear antigen labeling index in the coagulating gland and seminal vesicles. The presence of cancer was also decreased in the coagulating gland but not in the seminal vesicles. With control group specimens, more intense staining of androgen receptor was observed in atypical hyperplasias than in cancers. Compared with the atypical hyperplasias, the cancers revealed low androgen dependency at the early stages of carcinogenesis. The cancers in the seminal vesicles also revealed higher androgen independency than did those in the coagulating gland.
 ...
PMID:Carcinogenesis in accessory sex organs of rats induced by 3,2'-dimethyl-4-aminobiphenyl: response to androgen deprivation. 945 Jun 33

Urological malignancies kill over 16,000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel-Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E-cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer 'escapes' hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen-dependent processes and these too have been implicated in prostate carcinogenesis.
 ...
PMID:The molecular pathology of urological malignancies. 949 53

Epidemiologic studies have suggested that nutrition plays an important role in carcinogenesis and that 30% of cancer morbidity and mortality can potentially be prevented with proper adjustment of diets. Resveratrol, a polyphenol present in red wines and a variety of human foods, has recently been reported to exhibit chemopreventive properties when tested in a mouse skin cancer model system. In this study, we investigated the effects of resveratrol on growth, induction of apoptosis, and modulation of prostate-specific gene expression using cultured prostate cancer cells that mimic the initial (hormone-sensitive) and advanced (hormone-refractory) stages of prostate carcinoma. Androgen-responsive LNCaP and androgen-nonresponsive DU-145, PC-3, and JCA-1 human prostate cancer cells were cultured with different concentrations of resveratrol (2. 5 x 10(-5)-10(-7) M). Cell growth, cell cycle distribution, and apoptosis were determined. Addition of 2.5 x 10(-5) M resveratrol led to a substantial decrease in growth of LNCaP and in PC-3 and DU-145 cells, but only had a modest inhibitory effect on proliferation of JCA-1 cells. Flow cytometric analysis showed resveratrol to partially disrupt G1/S transition in all three androgen-nonresponsive cell lines, but had no effect in the androgen-responsive LNCaP cells. In difference to the androgen-nonresponsive prostate cancer cells however, resveratrol causes a significant percentage of LNCaP cells to undergo apoptosis and significantly lowers both intracellular and secreted prostate-specific antigen (PSA) levels without affecting the expression of the androgen receptor (AR). These results suggest that resveratrol negatively modulates prostate cancer cell growth, by affecting mitogenesis as well as inducing apoptosis, in a prostate cell-type-specific manner. Resveratrol also regulates PSA gene expression by an AR-independent mechanism.
 ...
PMID:Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines. 1032 58

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.
 ...
PMID:Prostatic intraepithelial neoplasia is a risk factor for cancer. 1063 20

Prostate cancer (PCA) is the most prevalent cancer diagnosed and the second leading cause of cancer-related deaths among men in the United States. Descriptive epidemiological data suggest that androgens and environmental exposures play a key role in prostatic carcinogenesis. Since androgen action is intimately associated with proliferation and differentiation, at the time of clinical diagnosis in humans most PCA represent themselves as a mixture of androgen-sensitive and androgen-insensitive cells. Androgen-sensitive cells undergo rapid apoptosis upon androgen withdrawal. On the other hand, the androgen-insensitive cells do not undergo apoptosis upon androgen blocking, but maintain the molecular machinery of apoptosis. Thus, agents capable of inhibiting growth and/or inducing apoptosis in both androgen-sensitive and androgen-insensitive cells will be useful for the management of PCA. In the present study, we show that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent present in green tea, imparts antiproliferative effects against both androgen-sensitive and androgen-insensitive human PCA cells, and this effect is mediated by deregulation in cell cycle and induction of apoptosis. EGCG treatment was found to result in a dose-dependent inhibition of cell growth in both androgen-insensitive DU145 and androgen-sensitive LNCaP cells. In both the cell types, EGCG treatment also resulted in a dose-dependent G(0)/G(1)-phase arrest of the cell cycle as observed by DNA cell-cycle analysis. As evident by DNA ladder assay, confocal microscopy, and flow cytometry, the treatment of both DU145 and LNCaP cells with EGCG resulted in a dose-dependent apoptosis. Western blot analysis revealed that EGCG treatment resulted in (i) a dose-dependent increase of p53 in LNCaP cells (carrying wild-type p53), but not in DU145 cells (carrying mutant p53), and (ii) induction of cyclin kinase inhibitor WAF1/p21 in both cell types. These results suggest that EGCG negatively modulates PCA cell growth, by affecting mitogenesis as well as inducing apoptosis, in cell-type-specific manner which may be mediated by WAF1/p21-caused G(0)/G(1)-phase cell-cycle arrest, irrespective of the androgen association or p53 status of the cells.
 ...
PMID:Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. 1073 47

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely pre-invasive 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 prostate-specific antigen concentration or its derivatives and cannot be detected by ultrasound. Most studies suggest that most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that 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.
 ...
PMID:Prostatic intraepithelial neoplasia. 1208 43

Prostatic intraepithelial neoplasia (PIN) is composed of dysplastic cells with a luminal cell phenotype, expressing the androgen receptor as well as prostate specific antigen. PIN is characterized by progressive abnormalities of phenotype which are intermediate between normal prostatic epithelium (NP) and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of carcinogenesis. High-grade PIN is considered the most likely precursor of prostatic carcinoma (PCa), according to virtually all available evidence. Androgen deprivation decreases the prevalence and extent of PIN and the degree of capillary vascularization (e.g., angiogenesis) in the surrounding stroma via the suppression of vascular endothelial growth factor (VEGF) production. It is likely that PCa might also arise from precursor lesions other than high-grade PIN (low-grade PIN, atypical adenomatous hyperplasia, malignancy-associated foci, and atrophy).
 ...
PMID:Prostatic intraepithelial neoplasia and prostate cancer. 1209 35


1 2 3 4 5 6 Next >>