Expression analysis of mRNA in formalin-fixed, paraffin-embedded archival tissues by mRNA in situ hybridization.

Gene expression in diseased tissues can indicate the contribution to a disease process and potentially guide therapeutic decision-making. Archival tissues with associated clinical outcome may be useful to discover or validate the role of a candidate gene in a disease process or the response to therapy. Such archival tissues are commonly formalin-fixed and paraffin-embedded, restricting the methods available for gene expression analysis.

MRI of adenomyosis: changes with uterine artery embolization.

Objective: Our objective was to describe the MRI features of patients with pure or dominant adenomyosis treated with uterine artery embolization (UAE) and to correlate imaging features with symptoms.

Subjects And Methods: Nineteen patients with symptomatic pure or dominant adenomyosis on MRI were referred for UAE. All 19 patients had repeat MRI 4 months after UAE.

Role of SCC-S2 in experimental metastasis and modulation of VEGFR-2, MMP-1, and MMP-9 expression.

SCC-S2/GG2-1/NDED (approved gene symbol TNFAIP8) is a transcription factor NF-kappaB-inducible, antiapoptotic, and oncogenic molecule. In this study, we examined the role of SCC-S2 in invasion and experimental metastasis. We demonstrate that expression of SCC-S2 cDNA in MDA-MB 435 human breast cancer cells is associated with enhanced invasion in vitro and increased frequency of pulmonary colonization of tumor cells in athymic mice.

In vivo magnetic resonance volumetric and spectroscopic analysis of mouse prostate cancer models.

Background: Mouse prostate cancer modeling presents unique obstacles to the study of spontaneous tumor initiation and progression due to the anatomical location of the tissue.

Results: High resolution (130 microm(x) x 130 microm(y) x 300 microm(z)), three-dimensional MRI allowed for the visualization, segmentation, and volumetric measurement of the prostate from normal and genetically engineered animals, in vivo. Additionally, MRS performed on the prostate epithelia of probasin-ErbB-2Delta x Pten(+/-) mice identified changes in the relative concentrations of the metabolites choline and citrate, which was not observed in TRAMP mice.

Expression of a fibroblast growth factor-binding protein during the development of adenocarcinoma of the pancreas and colon.

The activity of growth factors is crucial for tumor progression. We previously characterized a secreted fibroblast growth factor-binding protein (FGF-BP1) as a chaperone molecule, which enhances the biological functions of FGFs by releasing FGFs from the extracellular matrix. Here, we characterize the frequency and pattern of FGF-BP1 expression during the malignant progression of pancreas and colorectal carcinoma.

Therapeutic drug monitoring of antithyroid drugs in pregnancy: the knowledge gaps.

Despite being a common condition in pregnancy, and despite propylthiouracil (PTU) being perceived as safer than methimazole, there are virtually no epidemiological controlled studies on malformation rate an neurobehavioral outcomes with the former. This knowledge gap must be filled to ensure fetal safety.

Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals.

During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid hormone concentrations. Accurate assessment of thyroid function during pregnancy is critical, for both the initiation of thyroid hormone therapy, and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits.

The role of bevacizumab as first-line therapy for colon cancer.

The addition of oxaliplatin and irinotecan to the armamentarium for the treatment of colorectal cancer (CRC) has resulted in significant improvements in response rates and survival. Targeted therapies directed at the epidermal growth factor pathway and the vascular endothelial growth factor pathway are beginning to play a role in the treatment of CRC. Bevacizumab is a monoclonal antibody that has been evaluated in randomized studies.

Adaptor proteins and ubiquinators in TGF-beta signaling.

The emergence of research analyzing the TGF-beta signaling pathway and its role in stem cell plasticity and differentiation has been a source of new insights into multiple cancers. TGF-beta signaling mediator Smads are tightly dependent on modulation by adaptor proteins, such as ELF, SARA, filamin, and crkl as well as ubiquitinators, such as PRAJA and SMURFs. Despite widespread inactivation of the TGF-beta pathway in gastrointestinal tumors, only a fraction of sporadic tumors exhibit inactivating mutations in early tumor formation, which suggests a role for the modulation of TGF-beta signals by stem/progenitor cell proteins, such as ELF and PRAJA.

Contrast-enhanced in vivo imaging of breast and prostate cancer cells by MRI.

The development of effective cancer therapies has been hampered, in part, by the inability to noninvasively follow tumor progression from the initial cancerous lesion through to metastasis. We have previously shown that superparamagnetic iron oxide particles can be used as magnetic resonance imaging contrast agents to label embryonic, mesenchymal and hematopoietic stem cells in vivo. Improving the capacity to non-invasively image cancer progression is an appealing method that could be useful for assessing the efficacy of anticancer therapies.

New perspectives in hemophilia treatment.

A variety of factor concentrates are currently available for replacement therapy for patients with hemophilia. These differ by several parameters, including source (pooled from pooled blood vs recombinant), purity, pathogen inactivation, and by the presence or absence of extraneous proteins such as albumin. The choice of replacement product reflects both safety issues of pathogen transmission or inhibitor development, and personal preferences of the patient and the physician.

Critical interactions between TGF-beta signaling/ELF, and E-cadherin/beta-catenin mediated tumor suppression.

Inactivation of the transforming growth factor-beta (TGF-beta) pathway occurs often in malignancies of the gastrointestinal (GI) system. However, only a fraction of sporadic GI tumors exhibit inactivating mutations in early stages of cancer formation, suggesting that other mechanisms play a critical role in the inactivation of this pathway. Here, we show a wide range of GI tumors, including those of the stomach, liver and colon in elf+/- and elf+/- / Smad4+/- mutant mice.

DM peptide-editing function leads to immunodominance in CD4 T cell responses in vivo.

DM functions as a peptide editor for MHC class II-bound peptides. We examined the hypothesis that DM peptide editing plays a key role in focusing the in vivo CD4 T cell responses against complex pathogens and protein Ags to only one, or at most a few, immunodominant peptides. Most CD4 T cells elicited in the wild-type BALB/c (H-2d) mice infected with Leishmania major predominantly recognize a single epitope 158-173 within Leishmania homologue of activated receptor for c-kinase (LACK), as is the case when these mice are immunized with rLACK.

BRCA1 regulates gene expression for orderly mitotic progression.

Germline mutations of the BRCA1 gene confer an increased risk for breast cancer and ovarian cancer. To study the contribution of BRCA1 to sporadic cancers, which often exhibit reduced BRCA1 expression, we tested the effect of knocking down BRCA1 on gene expression in human prostate (DU-145) and breast (MCF-7) cancer cells. DNA microarray and confirmatory RNA analyses revealed that BRCA1 small interfering (si) RNA caused down-regulation of multiple genes implicated in the mitotic spindle checkpoint (eg.

Hereditary angioedema.

Purpose Of Review: Hereditary angioedema is an autosomal-dominant deficiency of C1 inhibitor--a serpin inhibitor of kallikrein, C1r, C1s, factor XII, and plasmin. Quantitative or qualitative deficiency of C1 inhibitor leads to the generation of vasoactive mediators, most likely bradykinin. The clinical syndrome is repeated bouts of nonpruritic, nonpitting edema of the face, larynx, extermities, and intestinal viscera.

Transforming growth factor-beta signaling in stem cells and cancer.

Transforming growth factor-beta (TGF-beta) and TGF-beta-related proteins, such as the bone morphogenetic proteins, have emerged as key regulators of stem cell renewal and differentiation. These proteins have disparate roles in regulating the biology of embryonic stem cells and tumor suppression, and they help define the selection of cell fate and the progression of differentiation along a lineage. Here we illustrate their roles in embryonic stem cells and in the differentiation of neural, hematopoietic, mesenchymal, and gastrointestinal epithelial stem cells.

BRCA1 in hormonal carcinogenesis: basic and clinical research.

The breast and ovarian cancer susceptibility gene-1 (BRCA1) located on chromosome 17q21 encodes a tumor suppressor gene that functions, in part, as a caretaker gene in preserving chromosomal stability. The observation that most BRCA1 mutant breast cancers are hormone receptor negative has led some to question whether hormonal factors contribute to the etiology of BRCA1-mutant breast cancers. Nevertheless, the caretaker function of BRCA1 is a generic one and does not explain why BRCA1 mutations confer a specific risk for tumor types that are hormone-responsive or that hormonal factors contribute to the etiology, including those of the breast, uterus, cervix, and prostate.

Biologic therapy for colon cancer.

Targeted biologic therapy remains a very active and evolving field since the US Food and Drug Administration approved cetuximab, a recombinant, human/mouse chimeric monoclonal antibody against the endothelial growth factor receptor, and bevacizumab, a humanized monoclonal antibody directed against vascular endothelial growth factor, for the treatment of colorectal cancer. Benefits of these reagents in diverse clinic settings combined with different chemotherapeutic agents are being defined. Current research is focused on defining which patients will benefit from these treatments and how best to use them in the clinic.

Inactivation of ELF/TGF-beta signaling in human gastrointestinal cancer.

TGF-beta/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. ELF, a beta-spectrin, plays a key role in the transmission of TGF-beta-mediated transcriptional response through Smads. ELF was originally identified as a key protein involved in endodermal stem/progenitor cells committed to foregut lineage.

The breast cancer susceptibility gene BRCA1 regulates progesterone receptor signaling in mammary epithelial cells.

The progesterone receptor (PR) plays roles in normal mammary development and breast cancer formation, where it may exert both stimulatory and inhibitory actions. Previously, the breast cancer susceptibility gene product BRCA1 was found to interact with and inhibit the transcriptional activity of estrogen receptor-alpha. In this study, we found that exogenous wild-type BRCA1 inhibited the activity of the PR in transient transfection assays utilizing a mouse mammary tumor virus-Luc reporter.

Identification and characterization of a response element in the EGFR promoter that mediates transcriptional repression by 1,25-dihydroxyvitamin D3 in breast cancer cells.

Reduction of epidermal growth factor receptor (EGFR) mRNA and protein by 1,25-dihydroxyvitamin D3 has been documented in MCF7, T47D, and BT549 breast cancer cells. In the present report, functional mapping of the EGFR promoter in BT549 cells has revealed a sequence of DNA between nucleotide positions -536 and -478 that resembles a consensus vitamin D response element (VDRE) and confers a vitamin D response upon both the homologous and a minimal heterologous promoter. In vitro footprinting and gel shift assays demonstrate the presence of an unidentified nuclear factor that is required for strong binding of the vitamin D receptor (VDR) to this putative VDRE.