Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

"Incidental" cancer refers to predominantly well differentiated cancer that arises in the transition zone and is found by chance in TURP chips. These tumours are frequently small and may be completely resected by TURP, although a significant number have an additional tumour that is unreachable with a resectoscope. These tumours often co-exist with benign prostatic hyperplasia. Putative precursors of incidental carcinoma include high grade PIN and AAH, and these lesions are frequently found in the transition zone in prostatectomies for cancer. The single most significant question in treating incidental adenocarcinoma is how to separate tumours that will progress from those that will not progress during the expected lifetime of the patient. The 1992 revision of the TNM staging system separated non-aggressive (T1a) and aggressive (T1b) incidental cancer according to the number of foci of cancer, using more than three foci as the cutpoint to identify more aggressive cancer. However, 8-37% of patients with T1 a cancer will develop cancer progression within 10 years if untreated, with the risk of progression increasing with additional years of follow-up. Important prognostic factors include the patient's age, tumour location (peripheral zone v. transition zone), tumour grade, tumour volume, serum PSA concentrations and morphometric factors such as nuclear roundness. Studies directed at early detection allow discovery of increasingly smaller cancers.
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PMID:The pathology of incidental carcinoma. 762 75

Transrectal fine-needle aspiration biopsy (FNAB) of the prostate under digital control is a cheap and rapid method for diagnostic evaluation of palpable and non-palpable nodules, yielding high sensitivity (ca. 95%) and a low complication rate (< 1%). Its specificity amounts to > 97%. The scarcity of urologists trained in the FNAB method and of pathologists experienced in cytology of the prostate limit the clinical application so far. Besides various forms of prostatitis, five different types of cancer can cytologically be differentiated. While PIN I cannot be cytologically identified, PIN II/III lesions may lead to false-positive diagnoses. Cytologic grading of adenocarcinomas of the prostate is of statistically proven prognostic validity and strictly correlated with its histologic counterpart. Preoperative, radiologically controlled FNAB of pelvic and paraortal lymph nodes has sensitivity of ca.86% and specificity of 100%. It thus helps to avoid unnecessary prostatectomies if nodal tumor spread has preoperatively been proven. Diagnostic DNA cytometry is able to identify those prostatic cancer patients who do not reveal significantly increased risk of tumor progression or decreased survival probability, even without therapy (constantly and representatively diploid and tetraploid patterns). Patients with DNA tetraplid histograms may show deteriation of prognosis under hormonal therapy. DNA-aneuploid prostatic cancers should not be subjected to a "wait and see" strategy; they do not respond to hormonal therapy.
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PMID:[Cytopathology of the prostate]. 954 42

We have previously identified (M. Wang et al., Oncol. Res., in press, 1998) an enhancer element [human tissue inhibitor of metalloproteinase-1 enhancer-1 (HTE)] for the human tissue inhibitor of metalloproteinase-1 promoter that binds a novel zinc finger, cysteine-rich transcription factor (CRTF). In this study, we have used electrophoretic mobility shift assays to examine the relative level of expression of CRTF, jun/fos, and IFN-gamma responsive signal transducer activators of transcription (STATs) that bind specific HTE, activator protein, and IFN-gamma (Fcy and interferon regulatory factor) response motifs in tumor lines and human prostate tissue [i.e., normal (n = 3); benign prostatic hyperplasia (BPH; n = 12); high grade prostate intraepithelial neoplasia (PIN; n = 10); and prostate cancer adenocarcinoma (PCA; n = 61) plus seminal vesicle (n = 10) tissues]. The data showed that CRTF was overexpressed in PCA (Gleason's score, 10>8>6>5>4) compared with BPH, PIN, seminal vesicle, and normal tissues. To a much lesser degree, jun/fos and STAT 1 were also elevated in PCA compared to BPH, PIN, and normal tissues. In addition, blinded studies showed that CRTF and jun/fos were present at low levels in organ-confined specimens but at significantly elevated levels (P < 0.001) in samples exhibiting capsular penetration and localized spread, which indicated that CRTF and perhaps jun/fos were markers for cancer progression.
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PMID:Specific transcription factors prognostic for prostate cancer progression. 974 34

Galectin-1, a member of the beta-galactoside-binding galectin family, is a pleiotropic dimeric protein participating in a variety of normal and pathological processes, including cancer progression. Modulation of the interactions with the basement membrane glycoprotein laminin and induction of apoptosis in activated T lymphocytes are well-known functions of this galectin. In this study, the expression of galectin-1 was examined in 148 human primary prostate carcinoma samples. Immunohistochemical staining of paraffin sections of prostate tissues revealed that galectin-1 was not detected in normal, PIN (prostatic intraepithelial neoplasia) or carcinoma cells, but accumulated in the stroma and associated fibroblasts. Galectin-1 expression was significantly increased in the tumour-associated stroma compared with the non-neoplastic gland-associated stroma in 21.3% of the cases (Mantel-Haenszel test, p=0.001; Wilcoxon signed rank test, p<0.0001). Increased galectin-1 expression in the cancer-associated stroma compared to the normal gland-associated stroma (p=0.03) was identified by multivariate analysis as a strong independent predictor of prostate-specific antigen (PSA) recurrence, just after the pathological stage (p<0.0001). The association between accumulation of galectin-1 in the stroma of the malignant tissue and aggressiveness of the tumour adds weight to the body of evidence that identifies a role for galectin-1 in the acquisition of the invasive phenotype. In addition to modulating cancer cell interactions with laminin, galectin-1 accumulated around the cancer cells may act as an immunological shield by inducing activated T-cell apoptosis. This exciting hypothesis warrants further investigation.
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PMID:Increased expression of galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients. 1116 19

We recently demonstrated the existence of specific patterns of somatic mitochondrial DNA (mtDNA) mutations in several cancers. Here we sought to identify the presence of mtDNA mutations in prostate cancer and their paired PIN lesions. The D-loop region, 16S rRNA, and the NADH subunits of complex I were sequenced to identify mtDNA mutations in 16 matched PIN lesions and primary prostate cancers. Twenty mtDNA mutations were detected in the tumor tissue of three patients. Identical mutations were also identified in the PIN lesion from one patient. This patient with multiple point mutations also harbored a high frequency of microsatellite instability (MSI-H) in nuclear mononucleotide repeat markers. Remarkably, identical mutations were also detected in all (3/3) matched urine and plasma samples obtained from these patients. Although mitochondrial mutations are less common in prostate adenocarcinoma, they occur early in cancer progression and they can be detected in bodily fluids of early stage disease patients. The identification of MtDNA mutations may complement other early detection approaches for prostate cancer.
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PMID:Mitochondrial mutations in early stage prostate cancer and bodily fluids. 1152 8

A search for novel and biologically relevant androgen-regulated genes and processes in the human prostate led to the intriguing observation that androgens provoke a remarkable and coordinated increase in the expression of several genes involved in triglyceride and cholesterol synthesis in various prostatic adenocarcinoma cell lines. This coordinated activation was shown to be the result of a novel and indirect pathway in which androgens cause activation of a secondary transcription regulator, Sterol Regulatory Element Binding Protein (SREBP), a pivotal factor in the control of intracellular lipid homeostasis. The biological relevance of increased lipogenesis in the biology of prostate cancer is underlined by recent immunocytochemical investigations on needle biopsies showing an increase in the expression of Fatty Acid Synthase (FAS) in 94% of the tumor-lesions examined. This increase is already evident in the earliest recognizable lesions (Prostatic Intra-epithelial Neoplasia; PIN) and is more pronounced in tumors with a higher Gleason score, suggesting that increased FAS expression may serve both as an early tumor marker and as a marker of tumor progression. As in tumor cell-lines, increased FAS expression in prostate tumors seems to be only part of a more general and coordinated activation of lipogenic pathways. Further studies revealed that lipogenesis in prostate tumor cells can be enhanced not only by androgens but also by growth factors and by tumor-associated disturbances in signal transduction pathways. EGF, for instance, is also able to activate lipogenesis via the SREBP pathway and activation of the P13 kinase system by inactivation of PTEN (a phenomenon observed in some 50% of the prostate cancers) also causes increased lipogenesis. The early and nearly universal activation of lipogenesis in prostate cancers (and also in various other tumors) suggests that this may be a fundamental event in the development of the tumoral phenotype, an element that certainly merits further investigation. In addition, there are serious indications that interference with enhanced lipogenic activity in tumor cells may cause tumor cell death and delayed tumor development, suggesting that increased lipogenic activity in tumor cells may open a novel avenue for therapeutic intervention.
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PMID:[Androgens and increased lipogenesis in prostate cancer. Cell biologic and clinical perspectives]. 1223 42

The cells' ability to proliferate in response to growth factor stimulation is significantly altered during cancer progression. To investigate the mechanisms underlying these alterations in prostate cancer, the role and expression of beta1A integrin and type 1 insulin-like growth factor receptor (IGF-IR), known to contribute to cell proliferation and transformation, were analyzed. Using small interfering RNA oligonucleotides to down-regulate beta1A, we show that beta1A expression is required for IGF-IR-mediated prostate cancer cell proliferation and anchorage-independent growth. In vivo, using age-matched transgenic adenocarcinoma of mouse prostate (TRAMP) mice at different stages of prostate cancer [prostatic intraepithelial neoplasia, PIN; well-differentiated adenocarcinoma, WD; and poorly differentiated adenocarcinoma, PD], the expression of beta1A and of IGF-IR was studied. beta1A and IGF-IR expression levels were concurrently up-regulated in high PIN and WD, whereas their expression did not correlate in late-stage PD. In contrast to the up-regulated expression of beta1A, the levels of beta1C, a beta1 cytoplasmic variant that inhibits cell proliferation, were down-regulated in all stages of prostate cancer. A similar expression pattern was observed for a beta1C downstream effector, Grb2-associated binder-1 (Gab1) which is known to inhibit IGF-IR phosphorylation. To analyze in vitro the mechanistic implications of beta1A, beta1C, and Gab1 deregulation in prostate cancer, we investigated whether expression of either beta1 variant in beta1-null cells affected IGF-IR localization. We found that IGF-IR and beta1A were colocalized in highly specialized integrin signaling compartments, designated focal contacts. However, in the presence of beta1C, IGF-IR remained diffuse on the cell surface and did not localize to focal contacts. The findings that beta1 integrins and IGF-IR are concurrently deregulated and that expression of beta1 integrins is necessary to achieve appropriate IGF-IR intracellular distribution point to the important role that the cross-talk between these receptors may have during prostate cancer progression and will be helpful in formulating new therapeutic strategies.
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PMID:beta1A integrin expression is required for type 1 insulin-like growth factor receptor mitogenic and transforming activities and localization to focal contacts. 1606 50

Transcription factor Snail1 is a mediator of cell migration and survival, and expression is elevated in several cancer types. The Snail1 gene is reportedly amplified in prostate cancer (PC), and we investigated Snail1 expression in PC. Immunohistochemical Snail1 staining was determined on a tissue microarray which includes 327 specimens of PC, 30 specimens from patients with benign prostatic hyperplasia (BPH), benign tissue from 30 PC patients and 15 high-grade prostate intraepithelial neoplasia (high-grade PIN) specimens. Clinicopathological and follow-up data were available for all patients. No BPH specimen and only 21% of benign tissue from PC patients showed high expression of Snail1. Only 7% of high-grade PIN patients expressed a high level of Snail1. In contrast, approximately 50% of PC tissue from patients with PC showed marked nuclear immunostaining. Snail1 immunostaining was significantly associated with Gleason score (p<0.05). Snail1 expression was not correlated to T stage, metastasis at time of diagnosis, risk of or time to recurrence. Snail1 expression was significantly increased in PC with a positive correlation to dedifferentiation, but not to cancer progression or prognosis. The presented data indicate that Snail1 expression is upregulated from the early stages of PC.
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PMID:Snail1 is over-expressed in prostate cancer. 1924 92

Tumor suppressors function in a coordinated regulatory network, and their inactivation is a key step in carcinogenesis. The tumor suppressor Par-4 is a novel integral player in the PTEN network. Thus, Par-4 is absent in a high percentage of human prostate carcinomas, and its loss is concomitantly associated with PTEN loss. Genetic ablation of Par-4 induces fully invasive prostate carcinomas in PTEN-heterozygous mice. In contrast, Par-4 deficiency alone, like PTEN heterozygosis, results in lesions that are unable to progress beyond the benign neoplastic stage known as PIN. At this PIN transition, the mutual induction of Par-4 and PTEN is an additional regulatory step in preventing cancer progression. Par-4 deficiency cooperates with PTEN haploinsufficiency in prostate cancer initiation and progression and their simultaneous inactivation, in addition to enhancing Akt activation, sets in motion a unique mechanism involving the synergistic activation of NFkappaB. These results suggest that the concurrent interruption of complementary signaling pathways targeting PI3K/Akt and NFkappaB activation could provide new and effective strategies for cancer therapy.
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PMID:The Par-4/PTEN connection in tumor suppression. 1962 70

The role of estrogen and its receptors in the etiology and progression of prostate cancer ( PC ) is poorly understood. In normal and malignant human prostate, estrogen receptor-a is expressed only in the stroma, whereas estrogen receptor-Beta ( ER-Beta ) is present in both normal stroma and epithelium. Because loss of ER-Beta expression is associated with prostate hyperplasia in ER-Beta null mice, this study determined patterns of ERBeta expression in hyperplastic, PIN ( prostatic intraepithelial neoplasia ) and malignant human prostate and associations with tumor progression. Formalin-fixed, paraffin-embedded blocks were obtained from thirty-five patients who underwent radical prostatectomy and pelvic lymphadenectomy for prostate cancer, 15 core biopsies diagnosed as PIN and 10 TURP ( transurethral prostatic resection ) diagnosed as BPH ( benign prostatic hyperplasia ) were assessed for ER-Beta expression using immunohistochemistry. ER-Beta positivity was defined as 5% of cells demonstrating nuclear immunoreactivity. Nine ( 90% ) of the studied BPH cases showed ER-Beta positive expression where they showed 5% ER-Beta positive cells, while eight ( 53% ) of the studied 15 PIN cases were negative for ER-Beta expression. Twenty-nine ( 82.8% ) of the studied adenocarcinoma cases were negative for ERBeta expression, p<0 .0001. The loss of ER-Beta expression is associated with progression from hyperplastic prostate epithelium to PC. The ER-Beta expression is inversely proportional to PCs stage and grade. From these data we can conclude that estrogen can affect prostatic cancerogenesis and neoplastic progression through an ER-Beta mediated process in human prostate tissue. Our data also identify the need for additional studies to address the potential role of ERBeta in the regulation of prostate epithelial cell proliferation at different stages in the development of PC. Key Words:ER Beta - Prostatic hyperplasia - PIN - Prostatic carcinoma.
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PMID:Expression of estrogen receptor-B ( ER-B ) in bengin and malignant prostatic epithelial cells and its correlation with the clinico-pathological features. 1967 87


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