Array-based DNA methylation profiling for breast cancer subtype discrimination.

Background: Abnormal DNA methylation is well established for breast cancer and contributes to its progression by silencing tumor suppressor genes. DNA methylation profiling platforms might provide an alternative approach to expression microarrays for accurate breast tumor subtyping. We sought to determine whether the distinction of the inflammatory breast cancer (IBC) phenotype from the non-IBC phenotype by transcriptomics could be sustained by methylomics.

Is there a role for mammary stem cells in inflammatory breast carcinoma?: a review of evidence from cell line, animal model, and human tissue sample experiments.

Stem cells are pluripotent cells, with a large replicative potential, which perform normal physiological functions such as tissue renewal and damage repair. However, because of their long lifespan and high replicative potential, stem cells are ideal targets to accumulate multiple mutations. Therefore, they can be regarded as being responsible for the initiation of tumor formation.

Quantitative methylation profiling in tumor and matched morphologically normal tissues from breast cancer patients.

Background: In the present study, we determined the gene hypermethylation profiles of normal tissues adjacent to invasive breast carcinomas and investigated whether these are associated with the gene hypermethylation profiles of the corresponding primary breast tumors.

Methods: A quantitative methylation-specific PCR assay was used to analyze the DNA methylation status of 6 genes (DAPK, TWIST, HIN-1, RASSF1A, RARbeta2 and APC) in 9 normal breast tissue samples from unaffected women and in 56 paired cancerous and normal tissue samples from breast cancer patients.

Results: Normal tissue adjacent to breast cancer displayed statistically significant differences to unrelated normal breast tissues regarding the aberrant methylation of the RASSF1A (P = 0.

Fibrous intimal thickening at implantation adversely affects long-term kidney allograft function.

Background: Kidneys from marginal and older donors are increasingly used to respond to the increasing demand for kidney transplants. This study evaluated the predictive value of intimal hyperplasia, as a marker of vasculopathy, in the renal allograft at the time of transplantation (transplantation) on the subsequent graft function (7 years).

Methods: The intima/media ratio of the arterial walls (I/M) was morphometrically determined by the sectorial elliptic method, in 51 implantation biopsies.

Gene expression profiles associated with the presence of a fibrotic focus and the growth pattern in lymph node-negative breast cancer.

Purpose: A fibrotic focus, the scar-like area found in the center of an invasive breast tumor, is a prognostic parameter associated with an expansive growth pattern, hypoxia, and (lymph)angiogenesis. Little is known about the molecular pathways involved.

Experimental Design: Sixty-five patients were selected of whom microarray data of the tumor and H&E slides for histologic analysis were available.

Increased sentinel lymph node lymphangiogenesis is associated with nonsentinel axillary lymph node involvement in breast cancer patients with a positive sentinel node.

Purpose: Lymph node (LN) lymphangiogenesis has recently been shown to be important in the premetastatic niche of sentinel LNs. To study its role in the further metastatic spread of human breast cancer, we investigated the association of angiogenesis and lymphangiogenesis in sentinel LN metastases with the presence of nonsentinel LN metastases in breast cancer patients with a positive sentinel LN.

Experimental Design: Angiogenesis and lymphangiogenesis--quantified as endothelial cell proliferation fraction (ECP%) and lymphatic ECP fraction (LECP%)--were assessed in sentinel LN metastases of 65 T(1)/T(2) patients with breast cancer using CD34/Ki67 and D2-40/Ki67 immunohistochemical double stains.

Fine needle trucut biopsy in focal liver lesions: a reliable and safe method in identifying the malignant nature of liver lesions.

Background And Study Aims: The correct management of a focal liver lesion, suspected of being malignant, requires tissue for histopathological examination. To this purpose an ultrasonically guided fine needle trucut biopsy technique (FNTCB) can be used, to allow obtaining large tissue samples. The aim of the study is to see that FNTCB is a reliable method in identifying the malignant or benign character of a focal liver lesion.

Epilepsy and migraine in a patient with Urbach-Wiethe disease.

We report the clinical, neuroradiological, and molecular genetic findings in a patient with lipoid proteinosis or Urbach-Wiethe disease. Interestingly, in this patient epilepsy and migraine were the symptoms leading to the diagnosis of the disease, contrary to most patients in whom skin abnormalities are the first recognized symptoms.

Differential expression of hypoxia and (lymph)angiogenesis-related genes at different metastatic sites in breast cancer.

Introduction: Breast cancer can metastasize via lymphatic and hematogenous pathways. Hypoxia and (lymph)angiogenesis are closely related processes that play a pivotal role in the tumor progression and metastasis. The aim of this study was to compare expression of hypoxia and (lymph)angiogenesis-related genes between primary breast tumors and metastases in different tissues.

The host's genetic background determines the extent of angiogenesis induced by schistosome egg antigens.

Schistosomiasis is characterised by periovular granuloma formation within the portal tract and presinusoidal venules. As inflammation wanes, continued attempts to wall off and repair hepatic injury, lead to the development of extensive fibrosis. The codependence of chronic inflammation and angiogenesis is a well-known phenomenon.

Nuclear factor-kappaB signature of inflammatory breast cancer by cDNA microarray validated by quantitative real-time reverse transcription-PCR, immunohistochemistry, and nuclear factor-kappaB DNA-binding.

Purpose: Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer with high metastatic potential. In a previous study, we showed that IBC is a different form of breast cancer compared with non-IBC by cDNA microarray analysis. A list of 756 genes with significant expression differences between IBC and non-IBC was identified.

LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for schistosome egg-induced hepatic granuloma formation.

Schistosomes, major parasitic helminths, express numerous glycoconjugates that provoke humoral and cellular immune responses in the infected human host. The main pathology in schistosomiasis is due to the formation of granulomas around tissue-trapped eggs and the resulting organ damage. By using a mouse model of induction of granulomas by hepatic implantation of antigen-coated beads, it has been determined that the glycan part of schistosomal soluble egg antigens (SEA) initiates granulomogenesis.

Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric study.

Purpose: At the time of diagnosis, metastatic dissemination of tumor cells via the lymphatic system has occurred in nearly all patients with inflammatory breast cancer (IBC). The objective of this study was twofold: (a) to determine which is the most suitable marker of lymph vessels in primary breast tumors and (b) to compare histomorphometric lymph vessel variables in IBC and non-IBC.

Experimental Design: Serial sections of 10 IBCs and 10 non-IBCs were immunostained for D2-40, LYVE-1, podoplanin, and PROX-1.

Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling.

Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer with high metastatic potential. Most patients have lymph node involvement at the time of diagnosis and 1/3 of the patients have distant metastases. In a previous study, we demonstrated that IBC is a distinct form of breast cancer in comparison with non-IBC.

Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer.

Purpose: Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer (LABC). The IBC phenotype is characterized by an infiltrative growth pattern, increased (lymph)angiogenesis and the propensity to invade dermal lymphatics. In pancreatic cancer, interactions between caveolin-1 and RhoC GTPase, a key molecule in causing the IBC phenotype, regulate tumour cell motility and invasion.

Combined Pap and HPV testing in primary screening for cervical abnormalities: should HPV detection be delayed until age 35?

In 2003, the United States Food and Drug Administration has approved the Hybrid Capture 2 assay for use with a Pap test to adjunctively screen women of 30 years and older for the presence of high-risk human papillomavirus (HR-HPV) infection. Although the predictive power of a negative test is strong, the number of false-positives may still be high. We investigated HPV prevalence in relation to age in a group of 2293 women, aged between 20 and 50, with normal cytology.

Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada.

Purpose: We conducted a phase III trial to determine whether first-line treatment with raltitrexed, a thymidine synthase inhibitor, and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma (MPM).

Patients And Methods: Eligible patients with histologically proven advanced MPM, not pretreated with chemotherapy, WHO performance status (PS) 0 to 2, and adequate hematological, renal, and hepatic function were randomly assigned to receive cisplatin 80 mg/m2 IV on day 1, alone (arm A) or combined with raltitrexed 3 mg/m2 (arm B). In patients with measurable disease, response was monitored using the Response Evaluation Criteria in Solid Tumors criteria.

Distinct molecular signature of inflammatory breast cancer by cDNA microarray analysis.

Inflammatory breast cancer (IBC) is a clinically distinct and aggressive form of locally advanced breast cancer with largely unknown genetic determinants. Overexpression of the RhoC GTPase and of HER2, and decreased ER-expression are involved in IBC. Multimodality treatment has increased survival but prognosis is still poor.

Immunocytochemistry in liquid-based cervical cytology: analysis of clinical use following a cross-sectional study.

Cytological screening for cervical cancer is hampered by imperfect sensitivity and low inter-observer reproducibility. Human papillomavirus (HPV) testing lacks specificity as a primary screening method. Studies indicate that immunocytochemical detection of alterations caused by HPV in the host cells can optimise screening.

Multivariate prognostic evaluation of the mitotic activity index and fibrotic focus in node-negative invasive breast cancers.

We validated with univariate and multivariate (Cox) analysis, the prognostic value of the mitotic activity index (MAI), the fibrotic focus (FF) and other prognosticators in 448 patients with lymph node-negative (LN-) invasive breast cancer <55 years without adjuvant systemic treatment (72.5 months median follow-up, range 4-119). Of these patients, 24.

Increased angiogenesis and lymphangiogenesis in inflammatory versus noninflammatory breast cancer by real-time reverse transcriptase-PCR gene expression quantification.

Purpose: Inflammatory breast cancer is a distinct and aggressive form of locally advanced breast cancer with unique clinical and pathological features. Recently, histologic evidence of intense angiogenesis was found in inflammatory breast cancer specimens. The aim of this study was to confirm the angiogenic phenotype of inflammatory breast cancer and to investigate its potential to induce lymphangiogenesis.

Juvenile rhesus monkeys have more colonic granulomas than adults after primary infection with Schistosoma mansoni.

Adults and children have differences in their susceptibility to schistosomiasis. Whether this age-dependent innate susceptibility influences parasite-caused granulomogenesis is difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni.