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

Estrogens exert a key biological role in mammary gland epithelial cells and promote breast carcinogenesis and tumor progression. We recently identified a new large set of estrogen responsive genes from breast cancer (BC) cells by DNA microarray analysis of the gene expression profiles induced by 17beta-estradiol in ZR-75.1 and MCF-7 cells. The purpose of the present study was to test whether the expression pattern of hormone regulated genes from this set identifies estrogen receptor (ERalpha) positive, hormone responsive BC cells. To this aim, we carried out in silico metanalysis of ERalpha positive and ERalpha negative human BC cell line transcriptomes, focusing on two sets of 171 and 218 estrogen responsive genes, respectively. Results show that estrogen dependent gene activity in hormone responsive BC cells is significantly different from that of non-responsive cells and, alone, allows to discriminate these two cellular phenotypes. Indeed, we have identified 61 genes whose expression profile specifically marks ERalpha positive BC cells, suggesting that this gene set may be exploited for phenotypic characterization of breast tumors. This possibility was tested with data obtained by gene expression profiling of BC surgical samples, where the ERalpha positive phenotypes were highlighted by the expression profile of a subset of 27 such hormone responsive genes and four additional BC marker genes, not including ERs. These results provide direct evidence that the expression pattern of a limited number of estrogen responsive genes can be exploited to assess the estrogen signaling status of BC cells both in vitro and ex-vivo.
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PMID:Molecular identification of ERalpha-positive breast cancer cells by the expression profile of an intrinsic set of estrogen regulated genes. 1525 72

Interleukin-6 is a pleiotropic cytokine which plays a crucial role in immune physiology and is tightly controlled by hormonal feedback mechanisms. After menopause or andropause, loss of the normally inhibiting sex steroids (estrogen, testosterone) results in elevated IL6 levels that are further progressively increasing with age. Interestingly, excessive IL6 production promotes tumorigenesis (breast, prostate, lung, colon, ovarian), and accounts for several disease-associated pathologies and phenotypical changes of advanced age, such as osteoporosis, rheumatoid arthritis, multiple myeloma, neurodegenerative diseases and frailty. In this respect, pharmacological modulation of IL6 gene expression levels may have therapeutical benefit in preventing cancer progression, ageing discomforts and restoring immune homeostasis. Although "plant extracts" are used in folk medicine within living memory, it is only since the 20th century that numerous scientific investigations have been performed to discover potential health-protective food compounds or "nutraceuticals" which might prevent cancer and ageing diseases. About 2000 years ago, Hippocrates already highlighted "Let food be your medicine and medicine be your food". Various nutrients in the diet play a crucial role in maintaining an "optimal" immune response, such that deficient or excessive intakes can have negative consequences on the organism's immune status and susceptibility to a variety of pathologies. Over the last few decades, various immune-modulating nutrients have been identified, which interfere with IL6 gene expression. Currently, a broad range of phyto-pharmaceuticals with a claimed hormonal activity, called "phyto-estrogens", is recommended for prevention of various diseases related to a disturbed hormonal balance (i.e. menopausal ailments and/or prostate/breast cancer). In this respect, there is a renewed interest in soy isoflavones (genistein, daidzein, biochanin) as potential superior alternatives to the synthetic selective estrogen receptor modulators (SERMs), which are currently applied in hormone replacement therapy (HRT). As phyto-chemicals integrate hormonal ligand activities and interference with signaling cascades, therapeutic use may not be restricted to hormonal ailments only, but may have applications in cancer chemoprevention and/or NF-kappaB-related inflammatory disorders as well.
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PMID:Soy isoflavone phyto-pharmaceuticals in interleukin-6 affections. Multi-purpose nutraceuticals at the crossroad of hormone replacement, anti-cancer and anti-inflammatory therapy. 1531 15

The modulation of Bmi-1 is observed in several tumor tissues, and its heightened protein level is suspected to be involved in tumorigenesis by acting as a transcriptional repressor in the INK4a/ARF locus. To elucidate the modulation of Bmi-1 in invasive ductal breast cancers, we examined its transcript and protein levels. The bmi-1 mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) showed that it was significantly up-regulated in 28 specimens out of 33 breast carcinoma tissues compared with those of non-neoplastic tissues just adjusted to tested specimens. Immunohistochemical staining for Bmi-1 also showed that 44 specimens out of 71 breast carcinoma tissues (62%) had strong positive signals with a more intense staining pattern in the invading fronts than in the central portions of primary invasive breast cancers. Univariate and multivariate analyses showed that a high level of Bmi-1 expression was significantly correlated with axillary lymph node metastases and positive estrogen receptor status. These findings suggested that Bmi-1 might be involved in the tumor progression and metastasis of invasive ductal breast cancer.
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PMID:Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. 1545 93

Transforming growth factor beta (TGF-beta)1 is thought to be involved in breast carcinogenesis. TGF-beta1 acts in an antiproliferative manner in the early stages of breast carcinogenesis, but promotes tumor progression and metastases in the advanced stages of the disease. No data have been published on serum TGF-beta1 in breast cancer. We investigated TGF-beta1 serum levels in patients with breast cancer (n=135), ductal carcinoma in situ (DCIS) I to III (n=67) or fibroadenoma (n=35), and in healthy women (n=40) to determine its value as a differentiation marker between malignant, pre-invasive and benign diseases and as a predictive marker for metastatic spread. Median (range) TGF-beta1 serum levels in patients with breast cancer, DCIS I-III or benign breast lesions and in healthy women were 48.8 (18-82.4) pg/mL, 45.3 (26.9-58.3) pg/mL, 47.2 (17.2-80.5) pg/mL and 51.6 (30.9-65.1) pg/mL, respectively (p=0.2). In breast cancer patients TGF-beta1 serum levels showed no statistically significant correlation with tumor stage, lymph node involvement, histological grade, estrogen receptor status and progesterone receptor status. Our data fail to indicate any correlation between serum TGF-beta1 levels and clinicopathological parameters of breast diseases. Serum TGF-beta1 levels do not provide clinical information in addition to established tumor markers.
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PMID:Transforming growth factor beta 1 serum levels in patients with preinvasive and invasive lesions of the breast. 1550 26

Human breast epithelium and the stroma are separated by a layer of myoepithelial (ME) cells and basement membrane, whose disruption is a prerequisite for tumor invasion. The dissolution of the basement membrane is traditionally attributed primarily to an over-production of proteolytic enzymes by the tumor or the surrounding stromal cells. The results from matrix metalloproteinase inhibitor clinical trials, however, suggest that this "protease-centered" hypothesis is inadequate to completely reflect the molecular mechanisms of tumor invasion. The causes and signs of ME cell layer disruption are currently under-explored. Our studies revealed that a subset of pre- and micro-invasive tumors contained focal disruptions in the ME cell layers. These disruptions were associated with immunohistochemical and genetic alterations in the overlying tumor cells, including the loss of estrogen receptor expression, a higher frequency of loss of heterozygosity, and a higher expression of cell cycle, angiogenesis, and invasion-related genes. Focal ME layer disruptions were also associated with a higher rate of epithelial proliferation and leukocyte infiltration. We propose the novel hypothesis that a localized death of ME cells and immunoreactions that accompany an external environmental insult or internal genetic alterations are triggering factors for ME layer disruptions, basement membrane degradation, and subsequent tumor progression and invasion.
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PMID:The significance of focal myoepithelial cell layer disruptions in human breast tumor invasion: a paradigm shift from the "protease-centered" hypothesis. 1553 Aug 47

The estrogen receptor plays an important role in the development of hormone-dependent breast cancer. Experimental and clinical studies showed that hypoxia was involved in tumor progression and in the resistance to anticancer agents. The scope of this review is to summarize recent observations on these two signaling pathways and to show their importance and possible interaction in the development of hormone-dependent breast cancer.
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PMID:[Hypoxia, HIF1alpha and estrogen receptor]. 1554 93

The matrix metalloproteinases (MMPs) have been shown to play important roles in cancer progression. In this study we examined whether common genetic variants in two key MMPs are associated with phenotypic features of breast cancers and patient outcome. A single nucleotide polymorphism in the promoter region of MMP-2 (-1306 C-->T) abolishes Sp1 binding and is associated with lower transcriptional activity, while another in the promoter region of MMP-9 (-1562 C-->T) increases the transcription of this gene. MMP-2 TT homozygous patients had smaller tumors (p=0.006) and contained lower concentrations of estrogen receptor (ER; p=0.002) compared to patients with the MMP-2 CC or CT genotype. Homozygosity for the MMP-2 -1306 T allele was associated with markedly different patient survival depending upon tumor ER status. For patients with ER negative tumors, the MMP-2 TT genotype was associated with poor survival (2/8 patients alive at end of study, 25%) compared to the CC or CT genotypes (59/70, 84%; p < 0.001). For patients with ER positive tumors, the MMP-2 TT genotype was associated with a trend for very good survival (10/10, 100%) compared to the CC or CT genotypes (130/157, 83%; p=0.16). The MMP-9 -1562 T allele was associated with features of good prognosis including non-ductal type histology, positive ER status and the absence of TP53 mutation. Patients with MMP-9 -1562 CT or TT genotypes showed marginally better prognosis compared to CC homozygotes (p=0.06). These findings suggest that breast cancer phenotype and outcome can be influenced by common functional polymorphisms in MMP genes.
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PMID:Genetic polymorphisms in the MMP-2 and MMP-9 genes and breast cancer phenotype. 1560 21

WWOX is a cancer gene, spanning the common chromosomal fragile site 16D. Genomic and expression aberrations affecting this gene and locus are common in various neoplasias including breast cancer. The aim of the present study was to evaluate the relationship between WWOX expression at the protein level with respect to clinico-pathological characteristics. We performed immunohistochemical analyses on breast specific tissue microarrays representing, human normal breast epithelium (n = 16), ductal carcinoma in situ (n = 15) and invasive breast cancer cases (n = 203). Staining intensity measurements were objectively determined utilizing an image analysis system. Western blot analyses were also performed on an independent set of 23 invasive breast carcinomas. All normal breast epithelial samples express WWOX protein abundantly while 34% (69/203 cases) of invasive breast carcinomas were 'completely negative' for WWOX expression and an additional 26% (52/203) of cases expressed WWOX very weakly. For DCIS samples five out of 15 (33%) were negative or weak for WWOX staining. Interestingly, we found a statistically significant correlation between WWOX expression and estrogen receptor (ER) status, 27% of ER+ breast carcinomas were completely negative for WWOX expression versus 46% for ER-cases (p = 0.0054). Furthermore, when negative plus weakly WWOX stained cases were considered the difference became more significant with 51% of ER+ cases and 73% for the ER-group, with a p = 0.003. These data indicate that loss of WWOX expression is a common event in breast cancer. It is unclear at this point whether loss of WWOX expression is a consequence of tumor progression or represents a subclass of breast carcinomas. The strong association of WWOX expression with ER status reinforces the suggested role of this protein as an enzyme involved in sex steroid metabolism.
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PMID:Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status. 1569 50

The genetic changes underlying in the development and progression of familial breast cancer are poorly understood. To identify a somatic genetic signature of tumor progression for each familial group, BRCA1, BRCA2, and non-BRCA1/BRCA2 (BRCAX) tumors, by high-resolution comparative genomic hybridization, we have analyzed 77 tumors previously characterized for BRCA1 and BRCA2 germ line mutations. Based on a combination of the somatic genetic changes observed at the six most different chromosomal regions and the status of the estrogen receptor, we developed using random forests a molecular classifier, which assigns to a given tumor a probability to belong either to the BRCA1 or to the BRCA2 class. Because 76.5% (26 of 34) of the BRCAX cases were classified with our predictor to the BRCA1 class with a probability of >50%, we analyzed the BRCA1 promoter region for aberrant methylation in all the BRCAX cases. We found that 15 of the 34 BRCAX analyzed tumors had hypermethylation of the BRCA1 gene. When we considered the predictor, we observed that all the cases with this epigenetic event were assigned to the BRCA1 class with a probability of >50%. Interestingly, 84.6% of the cases (11 of 13) assigned to the BRCA1 class with a probability >80% had an aberrant methylation of the BRCA1 promoter. This fact suggests that somatic BRCA1 inactivation could modify the profile of tumor progression in most of the BRCAX cases.
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PMID:A predictor based on the somatic genomic changes of the BRCA1/BRCA2 breast cancer tumors identifies the non-BRCA1/BRCA2 tumors with BRCA1 promoter hypermethylation. 1570 82

The management of breast cancer in elderly women is controversial. Breast cancer in this age group tends to be biologically less aggressive and is highly responsive to hormonal intervention. The risk of dying of other causes often exceeds the risk of cancer recurrence. For these reasons, older patients tend to be treated less aggressively. One large study of elderly women with breast cancer found that half of the patients were undertreated. Four patients (mean age 72 years, range 61-95 years) underwent a unilateral total mastectomy for cancer under local anesthesia using the tumescent technique of infiltrating dilute lidocaine with epinephrine (25 ml of 1% lidocaine [250 mg] and 1 ml of 1:1000 epinephrine [1 mg] to 1 L of Ringers lactate) via an infusion pump. Three of the patients had estrogen receptor (ER)-negative tumors and one patient had tumor progression despite switching from tamoxifen to anastrozole. All four patients were class IV as defined by the American Society of Anesthesiology (ASA). There was no morbidity related to the surgery in the form of hematoma, wound infection, or skin flap necrosis. The patients were discharged 1-4 days after surgery. The anesthesia was adequate in all four cases and there was no deviation from the described technique. The mean operative time was 35 minutes (range 24-46 minutes). The tumescent technique is a safe, effective method for performing a total mastectomy in patients who would not be considered candidates for general anesthesia.
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PMID:Total mastectomy under local anesthesia: the tumescent technique. 1573 Apr 54


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