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)

The presence of periacinar and pericellular basement membranes (BMs) has been reported recently in common prostatic adenocarcinomas. In this study we extended our investigations of BMs on lymph node and hematogenous metastases, primary prostatic cancer with unusual histologic features, and posttreatment tumors. In contrast to prostatic malignancies that derive from the transitional epithelium (squamous cell carcinoma, prostatic transitional cell carcinoma) and prostatic involvement by bladder cancer, inconspicuous stromal changes and distinct BM formations at the site of tumor invasion were observed in carcinomas deriving from the secretory epithelium (papillary ductal carcinoma) and from the basal cell (basal cell carcinoma). Even highly malignant anaplastic and small cell carcinomas, as well as irradiated and/or hormonally treated tumors, showed distinct BM formations in contact with the stroma. The same observations could be made in lymphatic and hematogenous metastases of different anatomic sites. These findings indicate that prostatic malignancies may retain BMs even in high-grade lesions, metastases, posttreatment tumors, and variants of prostatic adenocarcinoma.
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PMID:Distribution of basement membranes in primary and metastatic carcinomas of the prostate. 164 38

In the past, several authors described an association of cutaneous malignant melanoma (MM) with other neoplasms. As their results were not conclusive, we designed this study with the aim to determine whether the frequency and spectrum of coexisting neoplasms in patients with cutaneous MM are either a significant or a random event. Therefore, the histories of 623 patients with primary MM from our clinic have been evaluated by a direct questionnaire. Diagnosis of MM has been established by histologic examination after excisional biopsy. The male/female (M/F) ratio was 240/383, the mean age 52.5 years (range 14-93). The distribution of risk groups yielded 277 patients (M/F = 90/187) for low risk (Breslow < 0.75 mm trunk, < 1.50 mm extremities), 245 patients (M/F = 105/140) for intermediate risk (Breslow 0.76-3.00 and 1.51-5.00 mm, respectively). 101 patients (M/F = 45/56) for high risk (Breslow > 3.00 and > 5.00 mm, respectively). 64 patients (10.3%) had associated primary carcinomas including 7 patients with 2 primary carcinomas compared to a control group (n = 313) with 12 carcinomas (3.8%). 50% of the carcinomas were diagnosed before the diagnosis of melanoma. The M/F ratio of this group was 25/39, the mean age at diagnosis of MM 62.7 years (range 28-91), the mean age at diagnosis of carcinoma 55.6 years (range 29-90). In the female group, breast cancer predominated (18/39), followed by uterus (7/39) and basal cell carcinoma (7/39); in the male group, basal cell carcinoma (10/25) was followed by prostate cancer (6/25).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cutaneous malignant melanomas with other coexisting neoplasms: a true association? 843 11

It has long been suggested that subjects diagnosed with cutaneous malignant melanoma (CMM) have an excess rate of subsequent neoplasms. To provide further quantitative information on the issue, we have considered 1,780 histologically confirmed CMM diagnosed between 1974 and 1994 by the Cancer Registries of the French-speaking Swiss Cantons of Vaud and Neuchatel (760,000 inhabitants) and followed up to the end of 1994 for the occurrence of a second primary. A total of 194 neoplasms was observed vs. 111.7 expected, corresponding to a standardized incidence ratio (SIR) of 1.7 [95% confidence interval (CI) 1.5-2.0]. When skin cancers were excluded, 87 subsequent neoplasms were observed vs. 84.9 expected (SIR 1.0). Significant excess rates were observed for basal cell (SIR 4.4), squamous cell (SIR 3.1) and melanoma (SIR 4.7) of the skin, as well as for prostatic cancer (SIR 2.1). The increased rates of subsequent skin cancer were somewhat larger in males, whereas all the SIRs were systematically greater below age 60. The SIRs of subsequent skin cancer remained above unity for 5 years or longer since diagnosis of CMM, in the absence of a clear pattern in trend with time since diagnosis. The cumulative incidence following CMM was 3% for CMM, 4% for squamous cell and 14% for basal cell carcinoma 20 years after diagnosis of CMM. Our results confirm that patients diagnosed with CMM have excess risks of subsequent melanoma and non-melanomatous skin neoplasms which justify focused prevention and surveillance of skin lesions in these patients. Subjects with CMM do not have any appreciable overall excess of non-skin neoplasms, even after long-term follow-up.
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PMID:Incidence of invasive cancers following cutaneous malignant melanoma. 931 93

The reputation of garlic (Allium sativum) as an effective remedy for tumours extends back to the Egyptian Codex Ebers of 1550 b.c. Several garlic compounds including allicin and its corresponding sulfide inhibit the proliferation and induce apoptosis of several human non-leukaemia malignant cells including breast, bladder, colorectal, hepatic, prostate cancer, lymphoma and skin tumour cell lines. Ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide) is a garlic-derived compound produced most efficiently from pure allicin and has the advantage of a greater chemical stability than allicin. Several clinical trials and in vitro studies of ajoene have demonstrated its best-known anti-thrombosis, anti-microbial and cholesterol lowering activities. Recently, topic application of ajoene has produced significant clinical response in patients with skin basal cell carcinoma. Ajoene was shown to inhibit proliferation and induce apoptosis of several human leukaemia CD34-negative cells including HL-60, U937, HEL and OCIM-1. Also, ajoene induces 30% apoptosis in myeloblasts from chronic myeloid leukaemia patient in blast crisis. More significantly, ajoene profoundly enhanced the apoptotic effect of the two chemotherapeutic drugs: cytarabine and fludarabine in human CD34-positive resistant myeloid leukaemia cells through enhancing their bcl-2 inhibitory and caspase-3 activation activities. The two key anti-leukaemia biological actions of ajoene were the inhibition of proliferation and the induction of apoptosis. Studies have shown the anti-proliferation activity of ajoene to be associated with a block in the G2/M phase of cell cycle in human myeloid leukaemia cells. The apoptosis inducing activity of ajoene is via the mitochondria-dependent caspase cascade through a significant reduction of the anti-apoptotic bcl-2 that results in release of cytochrome c and the activation of caspase-3. Since acute myeloid leukaemia (AML) is a heterogeneous malignant disease in which disease progression at the level of CD34-positive cells has a major impact on resistance to chemotherapy and relapse and the inability to undergo apoptosis is a crucial mechanism of multi-drug resistance in AML patients. The recent findings of the potent enhancing activity of ajoene on chemotherapy-induced apoptosis in CD34-positive resistant human myeloid leukaemia cells suggest a novel promising role for the treatment of refractory and/or relapsed AML patients as well as elderly AML patients. Further studies are warranted to evaluate similar enhancing effect for ajoene in blast cells from AML patients in primary cultures before its introduction in pilot clinical study.
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PMID:Ajoene (natural garlic compound): a new anti-leukaemia agent for AML therapy. 1515 86

Sonic hedgehog (SHH), Desert hedgehog (DHH) and Indian hedgehog (IHH) bind to Patched family receptors (PTCH1 and PTCH2) to transduce signals to GLI1, GLI2 and GLI3. GLI family transcription factors then activate transcription of Hedgehog target genes, such as FOXE1 and FOXM1 encoding Forkhead-box transcription factors. Hedgehog signaling pathway plays a pivotal role in a variety of human tumors, such as gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, prostate cancer, basal cell carcinoma and brain tumors. Rat orthologs for human DHH and IHH remain to be identified. Here, we identified and characterized rat Dhh and Ihh genes by using bioinformatics. Rat Dhh complete coding sequence (CDS) was determined by assembling nucleotide positions 426397-426963, 429715-429976 and 430244-430898 of the AC114446.3 genome sequence. Rat Ihh complete CDS was determined by assembling nucleotide positions 63433-64033, 66432-66693 and 68242-69169 of AC095777.6 genome sequence. Rat Dhh mRNA was expressed in prostate, duodenum and dorsal root ganglia, while rat Ihh mRNA was expressed in cartilage. Rat Dhh showed 99.7% total-amino-acid identity with mouse Dhh, and 96.5% total-amino-acid identity with human DHH. Rat Ihh and human IHH were shorter than mouse Ihh by 38 amino acids. Rat Ihh showed 97.6% total-amino-acid identity with mouse Ihh and 94.4% total-amino-acid identity with human IHH. Hedgehog family proteins consist of signal peptide, Hedgehog ligand peptide and C-terminal peptide. Hedgehog ligand peptides derived from mammalian Hedgehog family proteins were conserved well, while C-terminal peptides were relatively divergent. The HPLGMXXXXS motif in the C-terminus was conserved in Shh orthologs and Ihh orthologs, but not in Dhh orthologs.
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PMID:Identification and characterization of rat Desert hedgehog and Indian hedgehog genes in silico. 1564 42

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
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PMID:Noncalcemic actions of vitamin D receptor ligands. 1579 98

Quantum dots are semiconductor nanocrystals with physical dimensions smaller than the exciton Bohr radius. As their fluorescence emissions are size-tunable, we can acquire any spectrum from ultraviolet (UV) to near-infrared by changing the particles' radiuses. The large Stokes shifts of quantum dots can be used to further improve detection sensitivity. The luminescence intensity is high and stable. Single quantum dots have longer excited state lifetimes, and they appear 10-20 times brighter than organic fluorescent dyes. And they have good biocompatibility because quantum dots with appropriate shells don't interfere with physiological processes, such as growth, development, signaling and motility. With the development of optical labeling and imaging technology, many present conventional biomedical methods have limitations in microcosmic direct real-time researches of bio-molecular interactions and early diagnosis of malignant tumors. The invention of quantum dots and their biomedical applications make them as good markers for tumor cell tracing and targeting in cancer research, such as prostate cancer, mammary cancer, cervical cancer, basal cell carcinoma, liver cancer, and melanoma. The current research is focused on tumor markers imaging and molecular interaction based on tangible carriers such as cells and tissues. The next research orientation would be to tap the potential of this highly sensitive technology to image tumor biomarkers in serum and other body fluids, so as to increase the early diagnosis rate of malignant tumors.
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PMID:[Quantum dots and their applications in cancer research]. 1668 92

Ultraviolet radiation exposure increases basal cell carcinoma (BCC) risk, but may be protective against prostate cancer. We attempted to identify exposure patterns that confer reduced prostate cancer risk without increasing that of BCC. We used a questionnaire to assess exposure in 528 prostate cancer patients and 442 men with basal cell carcinoma, using 365 benign prostatic hypertrophy patients as controls. Skin type 1 (odds ratio (OR)=0.47, 95% CI=0.26-0.86), childhood sunburning (OR=0.38, 95% CI=0.26-0.57), occasional/frequent sunbathing (OR=0.21, 95% CI=0.14-0.31), lifetime weekday (OR=0.85, 95% CI=0.80-0.91) and weekend exposure (OR=0.79, 95% CI=0.73-0.86) were associated with reduced prostate cancer risk. Skin type 1 (OR=4.00, 95% CI=2.16-7.41), childhood sunburning (OR=1.91, 95% CI=1.36-2.68), regular foreign holidays (OR=6.91, 95% CI=5.00-9.55) and weekend (OR=1.17, 95% CI=1.08-1.27) but not weekday exposure were linked with increased BCC risk. Combinations of one or two parameters were associated with a progressive decrease in the ORs for prostate cancer risk (OR=0.54-0.25) with correspondingly increased BCC risk (OR=1.60-2.54). Our data do not define exposure patterns that reduce prostate cancer risk without increasing BCC risk.
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PMID:A comparison of sunlight exposure in men with prostate cancer and basal cell carcinoma. 1726 85

Basal cell carcinoma (BCC) is characterized by slow growth, virtual absence of metastases, and strong stroma-dependency. Cancer-associated fibroblasts (CAFs) in the tumor stroma influence tumor growth, invasion, and metastasis. To comprehensively characterize CAFs of BCC in their in situ cancer environment, laser capture microdissection, linear gene amplification, microarray analysis, and quantitative real-time PCR (qRT-PCR) were combined. Pair-wise comparison of gene expression of microdissected CAFs and corresponding normal perifollicular fibroblasts identified 65 genes that were significantly upregulated in at least two of three different patients. Among the annotated genes, as many as 13 genes encoded secreted proteins, of which six were previously implicated as CAF-associated proteins in various tumor types. Four of the seven novel CAF genes--matrix Gla-protein, secreted frizzled-related protein 2, angiopoietin-related protein-2, and platelet-derived growth factor receptor-like protein--were selected for further analyses by qRT-PCR and were found to be frequently upregulated in CAFs of three independent BCC tissues. Analyses of CAFs from squamous cell cancer, prostate cancer, and colon cancer did not indicate that these genes were upregulated in these cancers. This study thus validates a novel approach for comprehensive characterization CAFs in their in situ environment of BCC. The results suggest a specific expression profile of CAFs in BCC possibly accounting for disease-specific pathological roles.
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PMID:In situ identification of genes regulated specifically in fibroblasts of human basal cell carcinoma. 1727 63

Sonic hedgehog (Shh) is the most widely characterized of the three vertebrate Hedgehog homologs, and is essential for proper embryonic development. Shh binds to its receptor, Patched (Ptch1), resulting in the de-repression of Smoothened (Smo). This leads to the activation of Gli2, which regulates the transcription of target genes that include Gli1 and Ptch1. Several synthetic and naturally occurring small-molecule modulators of Smo have been discovered. Shh-signaling antagonists that bind to Smo include cyclopamine, SANT1, and Cur-61414. Shh signaling agonists that bind to Smo include the synthetic small molecules purmorphamine and SAG. Small molecules that inhibit Shh signaling downstream of Smo, GANT58 and GANT61 have also been reported. Robotnikinin inhibits the Shh pathway by directly targeting Shh. Although progress has been made in understanding and modulating Shh signaling, fundamental aspects of Shh signal transduction remain obscure, including the mechanism(s) whereby Ptch1 regulates Smo activity. Small-molecule modulators of Shh signaling provide a means to regulate the activity of a pathway implicated in medulloblastoma, basal cell carcinoma (BCC), pancreatic cancer, prostate cancer and developmental disorders. Several Shh inhibitors have not succeeded in the clinic for unknown reasons, but clinical trials in BCC and pancreatic cancer with the promising Smo antagonists GDC-0449 and IPI-926 are currently underway.
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PMID:Small-molecule modulators of the Sonic Hedgehog signaling pathway. 2002 66


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