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  • 1
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; SURVIVAL ; tumor ; carcinoma ; CELL ; PATHWAYS ; CLASSIFICATION ; DIAGNOSIS ; GENE ; GENE-EXPRESSION ; RNA ; SAMPLE ; SAMPLES ; TUMORS ; PATIENT ; NF-KAPPA-B ; INDEX ; DOWN-REGULATION ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; PROGRESSION ; gene expression ; DESIGN ; AGE ; METASTASIS ; PHENOTYPE ; CANCER-PATIENTS ; CARCINOMAS ; experimental design ; BEHAVIOR ; CANCER PATIENTS ; ESTROGEN-RECEPTOR ; ONCOLOGY ; RE ; GRADE ; ESTROGEN ; analysis ; SUBTYPES ; CHIP ; SIGNATURE ; USA ; cancer research ; VARIABLES ; MOTILITY ; NOV ; aggressiveness ; PROFILE ; response ; CELL MOTILITY ; expression profile ; neoplasm ; POOR SURVIVAL ; HISTOLOGIC GRADE ; SIGNATURES
    Abstract: Purpose: We hypothesize that a gene expression profile characteristic for inflammatory breast cancer (IBC), an aggressive form of breast cancer associated with rapid cancer dissemination and poor survival, might be related to tumor aggressiveness in non-IBC (nIBC). Experimental Design: RNA from 17 IBC samples and 40 nIBC samples was hybridized onto Affymetrix chips. A gene signature predictive of IBC was identified and applied onto 1,157 nIBC samples with survival data of 881 nIBC samples. Samples were classified as IBC-like or nIBC-like. The IBC signature classification was compared with the classifications according to other prognostically relevant gene signatures and clinicopathologic variables. In addition, relapse-free survival (RFS) was compared by the Kaplan-Meyer method. Results: Classification according to the IBC signature is significantly (P 〈 0.05) associated with the cell-of-origin subtypes, the wound healing response, the invasive gene signature, the genomic grade index, the fibroblastic neoplasm signature, and the 70-gene prognostic signature. Significant associations (P 〈 0.01) were found between the IBC signature and tumor grade, estrogen receptor status, ErbB2 status, and patient age at diagnosis. Patients with an IBC-like phenotype show a significantly shorter RFS interval (P 〈 0.05). Oncomine analysis identified cell motility as an important concept linked with the IBC signature. Conclusions:We show that nIBC carcinomas having an IBC-like phenotype have a reduced RFS interval. This suggests that IBC and nIBC show comparable phenotypic traits, for example augmented cell motility, with respect to aggressive tumor cell behavior. This observation lends credit to the use of IBC to study aggressive tumor cell behavior
    Type of Publication: Journal article published
    PubMed ID: 19010862
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  • 2
    ISSN: 1432-1084
    Keywords: Key words: Desmoid ; Aggressive fibromatosis ; Soft tissue tumor ; MR imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The objective of this study was to evaluate the appearance and the natural evolution of desmoid tumors on MR imaging, given histologic correlation. The MR images of 30 desmoids (20 primary and 10 recurrent) in 26 patients were scored for a multiplicity of morphological parameters, signal intensity (SI) on different pulse sequences, and behavior after contrast administration. Natural evolution was evaluated in 2 primary and 3 recurrent lesions, and correlated with evolution on histologic specimens. Desmoid tumors are mostly found in muscles of shoulder and hip girdle and are often fusiform with partially ill-defined margins. Rare subcutaneous desmoids have a more stellar morphology. Variable amounts of low-SI areas are present on all sequences. On T1-weighted images (T1-WI), most lesions are near homogeneous and isointense to muscle, whereas on T2-WI they are more heterogeneous with an overall SI equal to or slightly lower than fat. Histologic correlation reveals that SI on T2-WI cannot be explained solely by cellularity. After initial growth, spontaneous evolution of desmoids is characterized by shrinking and an increase in low-SI areas on T2-WI. While distal lesions shrink, the more recent lesions in asynchronous multicentric desmoids have a tendency to develop proximally in the same limb, and should not be confused with recurrences. Fast growth, extracompartmental spread, and bone involvement are often seen in recurrences. Follow-up MR imaging of desmoids indicates natural regression of desmoids and more aggressive behavior of recurrences, which may justify a more conservative therapeutic approach.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 435 (1999), S. 1-7 
    ISSN: 1432-2307
    Keywords: Key words Mesothelioma ; SV40 ; Telomerase ; Immortalisation ; Tyramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  DNA-like sequences of the p53 and pRB-inactivating simian virus 40 large T-antigen (SV40 LTag) have recently been found in mesotheliomas in the United States and several European countries. Nuclear expression of SV40 LTag, possibly in concert with detectable telomerase activity, could be responsible for immortalisation of (pre)malignant clones, as suggested by the mesothelioma-specific latency period. Depending on the antibody used, different results have been observed regarding the subcellular expression of SV40 LTag in mesotheliomas with SV40 LTag-like DNA sequences. In this study, we screened 28 Belgian mesothelioma tumour samples for the presence of SV40 LTag-like DNA and its gene product by polymerase chain reaction amplification, using the SV.for3/SV.rev primer set, and by tyramine-amplified immunohistochemistry, using the pAb419 and the pAb101 SV40 LTag antibodies. Amplicons were found in 13 of the 28 (46%) mesotheliomas. Cytoplasmic, but no nuclear, staining was found in 10 of these 13 cases. Although our study confirms the presence of SV40 LTag-like DNA sequences in Belgian mesotheliomas, we did not detect nuclear expression of the viral oncoprotein, which makes a pathogenic role of SV40 LTag in mesothelioma carcinogenesis questionable.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2307
    Keywords: Key words Carcinosarcoma ; Sarcomatoid carcinoma ; Urothelial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A case of a man with biphasic sarcomatoid carcinoma of the right kidney with chondrosarcomatous foci and with invasion of the pelvic mucosa and submucosa into the peripelvic adipose tissue is presented. In situ carcinoma of the urothelium of the right renal pelvis and proximal ureter was also noted. Comments on the nomenclature of malignant tumours with apparently mixed carcinomatous and sarcomatous phenotypes and a hypothesis on the histogenesis of these tumours are presented. Cytokeratin and p53 protein expression patterns, and the results of angiogenesis quantification are consistent with an epithelial-to-mesenchymal conversion induced by the stroma.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 437 (2000), S. 1-16 
    ISSN: 1432-2307
    Keywords: Key words Telomeres ; Telomerase ; Cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the mid 1990s, the hypothesis emerged that the upregulation or re-expression of a telomere- synthesising ribonucleoprotein, called telomerase, is a critical event responsible for continuous tumour cell growth. In contrast to normal cells, in which gradual mitosis-related erosion of telomeres eventually limits replicative life span, tumour cells have telomerase and show no loss of these chromosomal ends. These data suggest that telomere stabilisation may be required for cells to escape replicative senescence and to proliferate indefinitely. Because of the close association between telomerase and malignancy, both pathologists and clinicians expect this molecule to be a useful malignancy-marker and a new therapeutic target. This review focuses on the components of the human telomere and of the human telomerase enzyme. A synopsis of reports studying the clinical–diagnostic value of telomere length measurements, of telomerase activity analyses and of the in situ telomerase detection is given. Finally, a summary of recent experimental work that sheds new light on the biological role of this fascinating molecule is presented.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2161
    Keywords: Key words Clear cell sarcoma ; Malignant melanoma of soft parts ; MRI ; Magnetic resonance ; Neoplasm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). Design and patients. MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. Results. On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. Conclusions. Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Fifteen to 20% of type 1 diabetic patients exhibit parietal cell antibodies (PCA), which are associated with autoimmune gastritis, hypochlorhydria, iron deficiency and pernicious anaemia.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To examine whether Helicobacter pylori infection could explain the high prevalence of PCA and autoimmune gastropathy in diabetes. If so, H. pylori eradication could prevent autoimmune gastritis.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:In 229 type 1 diabetics (M/F: 135/94; age: 41 ± 12 years) PCA were measured. H. pylori infection was assessed by serology, urea breath test in all and by histology (updated Sydney system) in 88 subjects. Pentagastrin tests were performed in 42 patients.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Sixty-nine patients were PCA-positive. H. pylori infection was present in 72 patients and was negatively associated with HLA-DQA1*0103-B1*0603 (OR=0.12, P=0.015) and positively with DQA1*0501-B1*0201 (OR=1.9, P=0.032). PCA-positivity was linked to HLA-DQA1*0501-B1*0301 (OR=3.9, P=0.017). A link between H. pylori and PCA was observed when PCA-positivity was defined as a titre ≥ 1/20 (OR=2.0, P=0.03), but not if ≥ 1/40 was the cut-off point. PCA-positivity, but not H. pylori infection, was associated with iron deficiency anaemia (OR=2.7, P=0.008), pernicious anaemia (OR= 33.5, P 〈 0.0001), hypochlorhydria (OR=12.1, P=0.0008) and autoimmune gastritis (OR=12.5, P 〈 0.0001).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:The HLA-bound susceptibility of H. pylori and PCA differed. PCA-positivity but not ongoing H. pylori infection is associated with autoimmune gastritis. Low titres of PCA might reflect H. pylori infection rather than autoimmune gastropathy.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Cyclooxygenase (COX)-2 expression and tumour-induced angiogenesis appear to be increased in squamous cell carcinoma (SCC) of the skin. In other cancers, COX-2 is a pro-angiogenic factor. The association between angiogenesis and COX-2 has not been studied in skin cancer.Objectives  To assess the onset of increased COX-2 expression and angiogenesis in the multistage carcinogenesis of SCC as well as the correlation between those two parameters.Patients/methods  We performed a retrospective paired immunohistochemical analysis of normal skin, actinic keratosis (AK), Bowen's disease (BD) and SCC among 35 individuals. Specimens were considered COX-2 immunopositive when 5% or more of the tumour cells showed clear evidence of immunostaining. To quantify active angiogenesis, we used a Ki-67–CD34 double-labelling immunohistochemical stain and calculated the fraction of proliferating endothelial cells. The Chalkley method was used to determine the microvessel density. To detect hypoxia, a carboanhydrase IX immunostain was used.Results  Compared with normal epidermis (0%), AK (31%), BD (22%) and SCC (40%) were significantly more likely to be COX-2 immunopositive (P 〈 0·01). The fraction of proliferating endothelial cells and the Chalkley scores paralleled multistage carcinogenesis (P 〈 0·05 between different stages). COX-2 immunopositivity was fairly correlated with hypoxia and higher proliferating endothelial cell fractions but not with Chalkley counts.Conclusions  Induction of COX-2 expression and angiogenesis are both early events in the development of SCC. In addition to ultraviolet light, hypoxia and COX-2 may be involved in skin tumour angiogenesis.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract To further investigate the factors involved in the modulation of the schistosomal granuloma, mice were primed with immunogenic carbohydrates which were common to soluble egg antigen (SEA) and adult worm antigen. Mice sensitized with LewisX trisaccharide or lacto-N-fucopentaose-III (LNFP-III) displayed an increased cellular response towards SEA-coupled beads implanted in the liver by mesenteric injection, resulting in the formation of larger periparticular granulomas. When animals were sensitized with bovine serum albumin or a structurally related carbohydrate, an accelerated response was not seen. Since LNFP-III is built up of LewisX molecules, and LewisX carbohydrates are common to SEA and worm antigens such as the gut-secreted antigens CCA and CAA (two antigens that could prime egg-antigen-induced granuloma formation), this may explain why adult, live Schistosoma mansoni worms positively modulate egg-antigen-induced hepatic granuloma formation in the murine host. These observations provide new insights into the role of carbohydrates in parasite-host immunity and may yield important implications for choosing worm-derived antigens for the development of anti-schistosome vaccines.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adult Schistosoma mansoni worms can positively modulate soluble egg antigen (SEA)-induced granulomas formed around SEA-coupled beads implanted in the liver. In this study, our aim was to further unravel the immunopathological characteristics of S. mansoni-worm-derived antigens in vivo. (a) Adult worm antigen (AWA)-coupled Sepharose beads, implanted into the liver, induced granulomas, containing numerous eosinophilic granulocytes and elicited marked periparticular fibrosis (composed of interstitial matrix proteins and basement membrane components). (b) Quantitative morphological analysis demonstrated that in naive mice, AWA-induced hepatic granuloma formation peaked in volume 16 days after injection of the beads. An accelerated response against AWA-coupled particles (peak volume at 8 days) was observed in mice carrying a single-sex, male S. mansoni infection. (c) When the granuloma volume induced by SEA-coupled beads in unisexually S. mansoni infected mice was compared to granulomas induced by beads laden with both SEA and AWA in unsensitized mice, no significant differences in granuloma volume were seen, indicating the existence of in vivo egg/worm antigen cross-sensitization. (d) Naive mice, sensitized with the worm antigens circulating anodic antigen (CAA) or circulating cathodic antigen (CCA), mounted a strongly accelerated response towards SEA-coupled beads implanted in the liver. We infer that, in vivo, worm antigens cross-sensitize with egg antigens and have both granulomogenic and fibrogenic characteristics. The S. mansoni soluble worm antigens CCA and CAA prime hepatic egg-antigen-induced granuloma formation possibly through the presence of immunogenic carbohydrates. These mechanisms lead to an accelerated response against SEA.
    Type of Medium: Electronic Resource
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