Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the case of an 82-year-old male patient with a > 8-year history of prostate cancer (PrCa), who developed breast adenocarcinoma (BrCa) (Ki-67+ and negative for ER, PR, PSA and HER2/neu) after prolonged (approximately 7-year) anti-androgen (flutamide) monotherapy for locally advanced PrCa. Biochemical and molecular analyses showed hyperestrogenemia (serum estradiol = 266 pg/ml, with normal range < 74 pg/ml), germline BRCA-1 mutation (T to C at nucleotide 3232, in exon 11, causing Glu to Gly change at codon 1038) and chromosome 9 inversion (karyotype of 46,XY with inv(9) (p11q21)). Following bilateral mastectomy without adjuvant systemic therapy, the patient has been disease-free (from both BrCa and PrCa) for > 3 years. In contrast to LHRH-based hormonal therapies for PrCa, anti-androgen monotherapy causes hyper-estrogenemia due to the suppressed negative feedback loop of androgens on LHRH and LH production, stimulation of testicular androgen production and their intracrine transformation to estrogens in peripheral target tissues. In this case report, the hyperestrogenemia may have further increased the BrCa risk in a patient with other risk factors (BRCA-1 mutation and chromosome 9 inversion, which has been previously shown to impinge upon testicular function and intracrine balance of androgens vs. estrogens). This case report illustrates that PrCa patients receiving anti-androgen monotherapy may be at risk of BrCa, in the event of the concomitant presence of other genetically-determined predisposing factors, and indicates the importance of exercising caution against indiscriminate and prolonged use of anti-androgen monotherapy in patients with risk factors for male BrCa.
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PMID:Male breast adenocarcinoma in a prostate cancer patient following prolonged anti-androgen monotherapy. 1515 26

Various hormones and growth factors have been implicated in progression of prostate cancer, but their role and the underlying molecular mechanism(s) involved remain poorly understood. In this study, we investigated the role of human growth hormone (GH) and its receptor (GHR) in human prostate cancer. We first demonstrated mRNA expression of GHR and of its exon 9-truncated isoform (GHR(tr)) in benign prostate hyperplasia (BPH) and prostate adenocarcinoma patient tissues, as well as in LNCaP, PC3 and DU145 human prostate cancer cell lines. GHR mRNA levels were 80% higher and GHR(tr) only 25% higher, in the carcinoma tissues than in BPH. Both isoforms were also expressed in LNCaP and PC3 cell lines and somewhat less so in DU145 cells. The LNCaP cell GHR protein was further characterized, on the basis of its M(r) of 120kDa, its binding to two different GHR monoclonal antibodies, its high affinity and purely somatogenic binding to (125)I-hGH and its ability to secrete GH binding protein, all characteristic of a functional GHR. Furthermore, GH induced rapid, time- and dose-dependent signaling events in LNCaP cells, including phosphorylation of JAK2 tyrosine kinase, of GHR itself and of STAT5A (JAK2-STAT5A pathway), of p42/p44 MAPK and of Akt/PKB. No effect of GH (72h) could be shown on basal or androgen-induced LNCaP cell proliferation nor on PSA secretion. Interestingly, however, GH caused a rapid (2-12h) though transient striking increase in immunoreactive androgen receptor (AR) levels (< or =5-fold), followed by a slower (24-48h) reduction (< or = 80%), with only modest parallel changes in serine-phosphorylated AR. In conclusion, the GH-induced activation of signaling pathways, its effects on AR protein in LNCaP cells and the isoform-specific regulation of GHR in prostate cancer patient tissues, suggest that GH, most likely in concert with other hormones and growth factors, may play an important role in progression of human prostate cancer.
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PMID:Growth hormone (GH) receptors in prostate cancer: gene expression in human tissues and cell lines and characterization, GH signaling and androgen receptor regulation in LNCaP cells. 1519 5

In a previous study we demonstrated that repeated duplications of the tissue kallikrein gene (Klk1) had resulted in 24 paralogs in mouse. Here we demonstrate a different evolution of rat glandular kallikrein genes. Repeated duplications of an approximately 30-kb region, encompassing Klk1, Klk15, and Klk2-ps, resulted in 10 copies of each gene, but only the Klk1 paralogs are functional. The number of genes varies also between nonrodent mammals, e.g., there are probably no paralogs to KLK1 in cow and pig, whereas horse could have up to 5. In the dog, the gene encoding the prostatic arginine esterase was identified as an ortholog to the progenitor of the PSA and hK2 genes, and it carries the same conserved androgen-responsive elements directing prostate transcription as these genes. This is highly interesting with respect to animal models of benign prostate hyperplasia and prostate adenocarcinoma--diseases that have been described only in humans and dogs.
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PMID:Taxon-specific evolution of glandular kallikrein genes and identification of a progenitor of prostate-specific antigen. 1520 12

We have initiated regular molecular monitoring based on nested RT-PCR detection of circulating tumor cells for monitoring recipients of organs from cancer-affected donors in Italy (in the context of a "Donation Safety and Donated Organ Quality" project organized by the Centro Nazionale Trapianti). Five patients are being monitored. For two patients who each received a kidney from a single donor with prostate adenocarcinoma, RT-PCR was performed using PSA mRNA. For three recipients of organs (two livers and one kidney) from donors with renal cell carcinoma, RT-PCR was performed using cytokeratine 18 and 19 mRNA. Blood samples from five healthy subjects were used as negative controls. After a median monitoring time of 26 months (range 8 to 32), none of the regular 3-month assays has tested positive. This pilot study suggests that detection of circulating tumor cells by nested RT-PCR may provide a feasible molecular monitoring, which might assist decision making regarding other forms of clinical surveillance.
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PMID:Molecular monitoring of organ recipients from cancer-affected donors by detection of circulating tumor cells. 1525 28

The purpose of this review is to discuss the epidemiologic literature on the association of sex steroid hormones and components of their signaling and metabolic pathways with prostate cancer and to describe data evaluating racial variation in sex steroid hormone pathways as a possible explanation for the notably higher risk of prostate cancer in African-American men compared to white or Asian men. Although sex steroid hormones likely contribute to the growth and progression of prostate cancer, associations between hormones and prostate cancer risk across the range of normal levels have been difficult to reliably demonstrate epidemiologically. Methodologic issues no doubt have made the detection of these associations difficult. Of particular importance are (1) the inadequacy of measuring circulating hormones in middle age as a surrogate for the exposure in the target cells in the prostate at the relevant time in life and (2) the current inability to integrate across components of the sex steroid hormone signaling pathway to fully capture target cell androgenic and estrogenic stimulation. Although the approach of evaluating polymorphisms in genes involved in sex steroid hormone signaling or metabolism as a way to minimize some of the issues in the direct measurement of hormones is logical, the findings among these studies are somewhat difficult to reconcile as well. The problems of the changing case mix due to screening for elevated PSA, small sample sizes increasing the likelihood of false negative and false positive results, the controls and their allele frequencies not being representative of the population at risk, and lack of knowledge of the functional consequence of a polymorphism in relation to other polymorphisms in that gene or without consideration of other genes involved in the same pathway may be contributory. The primary result of the Prostate Cancer Prevention Trial confirms that intraprostatic dihydrotestosterone levels in the normal range indeed do contribute to the growth of prostate adenocarcinoma. However, the secondary result of higher-grade disease in cases in the finasteride arm coupled with clinical studies showing higher grade disease in non-metastatic cases with lower serum androgens, if not a pathological artifact or detection bias in the finasteride arm, possibly suggests a complex relationship between androgens and the growth versus differentiation of a prostate tumor. Finally, racial variation in components of the sex steroid hormone pathway do appear to exist, but whether the extent of the variation is adequately great such that it accounts for some of the substantial differences in prostate cancer incidence among blacks, whites, and Asians is unclear.
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PMID:The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer. 1566 87

Preclinical studies of prostate cancer (CaP) have employed a genetically engineered mouse model, since there is no naturally occurring CaP in rodents. We have previously reported a new knock-in mouse adenocarcinoma prostate (KIMAP) model. In this study, we demonstrate that the new model possesses a tumor architecture of heterogeneity and multifocality similar to that of human CaP, by utilizing a new compound scoring system to compare with the PSP94 (approved gene symbol Msmb) gene-directed transgenic mouse CaP model (TGMAP). KIMAP mice showed a balanced distribution of tumor extent, which penetrated the prostate gland. Comparative studies on cDNA microarrays demonstrated that KIMAP tumors were upregulated with higher contents of immunoresponse genes, whereas PSP-TGMAP tumors had neuroendocrine (NE) differentiation. The majority of KIMAP mice did not progress to NE CaP, which was observed only at a very late stage and a low frequency. Several tumor marker genes characteristic of human CaP were uniquely identified in KIMAP tumors, including hepsin, maspin, Nkx3.1, CD10 and PSP94 (similar to PSA), etc. The differences between these two CaP models are attributed to the introduction of a single endogenous knock-in mutation. Due to the similarities between human CaP tumors and the PSP-KIMAP tumors, this preclinical model may supplement the current transgenic models to study CaP more accurately.
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PMID:A novel knock-in prostate cancer model demonstrates biology similar to that of human prostate cancer and suitable for preclinical studies. 1572 31

Prostate cancer offers a wide range of growth patterns depicted in the classical Gleason diagram. For each Gleason pattern exist a number of benign and malignant mimickers that can simulate prostatic adenocarcinoma. In the present review, the use of immunohistochemical markers is discussed with emphasis to a pattern-based approach to differential diagnosis in prostate pathology. Basal cell markers (34betaE12 and P63) are very useful to analyze histo-architectural features of small and large glandular lesions. AMACR (P504 s) is helpful not only in identifying small amount of cancer in needle biopsies but also in the diagnosis of high grade prostatic intra epithelial neoplasia (HGPIN). A number of lesions which may be confused with small acinar adenocarcinoma (Cowper's gland, nephrogenic metaplasia, mesonephric glands) and poorly differentiated prostate cancer (urothelial neoplasia, mucinous colon cancer and other metastatic lesions) lacks convincing PSA immunoreactivity. Basal cell markers and the nuclear androgen receptors are important markers to differentiate Gleason grade 5 A und 5 B patterns from prostatic involvement by transitional cell carcinoma. Finally, a selected panel of markers is useful to classify prostatic stromal lesions. In each case, immunohistochemical findings should be interpreted in context with the various patterns on routine microscopy.
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PMID:[Differential diagnosis of prostate cancer: impact of pattern analysis and immunohistochemistry]. 1620 99

We report a case in a 70-year-old patient indicated to have a metastatic lesion from a chest X-ray taken during a medical examination. His blood prostatic specific antigen level was very high at 100 ng/ml (normal, less than 4.0 ng/ml). Palpation of the prostate disclosed enlargement to hen's egg size with an irregular surface and indurations bilaterally. Transrectal sextant needle biopsy of the prostate was performed, revealing moderately differentiated adenocarcinoma. Computed tomography (CT) scan and bone scintigraphy showed intrapelvic lymphnode adenopathy and metastasis to the right pubic bone. Under a diagnosis of stage D2 prostate cancer, we initiated endocrine therapy (luteinizing hormone-releasing hormone analogue depot every 4 weeks and bicalutamide). Androgen blockage was very effective and after 6 months, the PSA level had decreased markedly to below 0.2 ng/ml. Sixteen months later, pulmonary metastasis completely disappeared. He is currently free from recurrence and progressing well.
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PMID:[A case of prostatic cancer discovered from lung metastatic lesions]. 1654 71

Constitutive activation of the kinase cascade involving RAS, RAF, MEK and ERK is common to human cancers, and mutations of KRAS and BRAF are mutually exclusive and serve as alternatives to activate the RAS/RAF/ERK signaling pathway. RAS mutations are known to occur in prostate adenocarcinomas, but little is known about BRAF mutations in these tumors. In the present study, BRAF and KRAS mutations were characterized in 206 prostate adenocarcinomas by enhanced PCR-RFLP and direct sequencing. The identified KRAS and BRAF mutations were then analyzed with respect to preoperative serum PSA levels, Gleason scores and tumor stages. Mutations in codon 600 of BRAF were identified in 21 (10.2%) of 206 prostate adenocarcinomas. KRAS mutations in codons 12 or 13 were found in 15 (7.3%) of 206 prostate adenocarcinomas. However, no tumor specimen contained both BRAF and KRAS mutations. Prostate adenocarcinomas with a BRAF mutation tended to show higher preoperative serum PSA levels, Gleason scores and tumor stages than prostate adenocarcinomas with a KRAS mutation. The results obtained show that BRAF mutations are as uncommon as KRAS mutations in prostate adenocarcinoma. Although BRAF and KRAS are members of the same RAS/ERK signaling pathway, prostate adenocarcinomas with a BRAF mutation showed clinicopathologic features that differed from those of prostate adenocarcinoma with a KRAS mutation.
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PMID:BRAF and KRAS mutations in prostatic adenocarcinoma. 1672 85

Small cell carcinoma of the prostate (SCPC) is morphologically similar to small cell carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenocarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).
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PMID:Small cell carcinoma of the prostate: an immunohistochemical study. 1672 47


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