Standard setting anchor statements: a double cross-over trial of two different methods.

This article was migrated. The article was marked as recommended. We challenge the philosophical acceptability of the Angoff method, and propose an alternative method of standard setting based on how important it is for candidates to know the material each test item assesses, and how difficult it is for a subgroup of candidates to answer each item.

OncoSim and OncoWiki: an authentic learning approach to teaching cancer genomics.

Background: Personalised medicine is rapidly changing the clinical environment, especially in regard to the management of cancer. However, for the large part, methods used to educate undergraduate students as future biomedical scientists and medical doctors have not reflected these changes. In order to make effective use of advances in cancer genomic knowledge, there is a need to expose students to the challenges of genomic medicine and to do so in a manner that makes this complex information accessible.

Single Transcription Factor Conversion of Human Blood Fate to NPCs with CNS and PNS Developmental Capacity.

The clinical applicability of direct cell fate conversion depends on obtaining tissue from patients that is easy to harvest, store, and manipulate for reprogramming. Here, we generate induced neural progenitor cells (iNPCs) from neonatal and adult peripheral blood using single-factor OCT4 reprogramming. Unlike fibroblasts that share molecular hallmarks of neural crest, OCT4 reprogramming of blood was facilitated by SMAD+GSK-3 inhibition to overcome restrictions on neural fate conversion.

The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis.

Glioblastoma multiforme (GBM) is an aggressive form of glial brain tumors, associated with angiogenesis, thrombosis, and upregulation of tissue factor (TF), the key cellular trigger of coagulation and signaling. Since TF is upregulated by oncogenic mutations occurring in different subsets of human brain tumors we investigated whether TF contributes to tumourigenesis driven by oncogenic activation of EGFR (EGFRvIII) and RAS pathways in the brain. Here we show that TF expression correlates with poor prognosis in glioma, but not in GBM.

Tissue factor expression provokes escape from tumor dormancy and leads to genomic alterations.

The coagulation system links immediate (hemostatic) and late (inflammatory, angiogenic) tissue responses to injury, a continuum that often is subverted in cancer. Here we provide evidence that tumor dormancy is influenced by tissue factor (TF), the cancer cell-associated initiator of the coagulation system and a signaling receptor. Thus, indolent human glioma cells deficient for TF remain viable but permanently dormant at the injection site for nearly a year, whereas the expression of TF leads to a step-wise transition to latent and overt tumor growth phases, a process that is preceded by recruitment of vascular (CD105(+)) and myeloid (CD11b(+) and F4/80(+)) cells.

Cancer cells induced to express mesenchymal phenotype release exosome-like extracellular vesicles carrying tissue factor.

Aggressive epithelial cancer cells frequently adopt mesenchymal characteristics and exhibit aberrant interactions with their surroundings, including the vasculature. Whether the release/uptake of extracellular vesicles (EVs) plays a role during these processes has not been studied. EVs are heterogeneous membrane structures that originate either at the surface (microparticles), or within (exosomes) activated or transformed cells, and are involved in intercellular trafficking of bioactive molecules.

Genetic pathways linking hemostasis and cancer.

Oncogenic events impact interactions of cancer cells with their surroundings. Amongst the most consequential, in this regard, is the influence on angiogenesis, inflammation and hemostasis. Indeed, mutant oncogenes (EGFR, HER2, RAS, MET, PML-RARα) are known to alter the expression of angiogenic and pro-inflammatory factors, as well as change the cancer cell coagulome, including the levels of tissue factor (TF) and other mediators (PAI-1, COX2).

Metronomic oral topotecan prolongs survival and reduces liver metastasis in improved preclinical orthotopic and adjuvant therapy colon cancer models.

Objective: Advanced and recurrent diseases are the major causes of death in colon cancer. No standard preclinical model addresses advanced disease and spontaneous metastasis after orthotopic tumour growth. In this study, the authors report the establishment of such standardised orthotopic mouse models of colon cancer and their use in evaluating metronomic topotecan alone or in combination with standard chemotherapy.

G-CSF supplementation with chemotherapy can promote revascularization and subsequent tumor regrowth: prevention by a CXCR4 antagonist.

Recombinant granulocyte colony-stimulating factor (G-CSF) is used to accelerate recovery from chemotherapy-induced myelosuppression. G-CSF has been recently shown to stimulate angiogenesis mediated by several types of bone marrow-derived cell populations. To investigate whether G-CSF may alter tumor response to therapy, we studied Lewis lung and EMT/6 breast carcinomas in mice treated with paclitaxel (PTX) chemotherapy in combination with G-CSF.

Modulation of the oncogene-dependent tissue factor expression by kinase suppressor of ras 1.

Introduction: Tissue factor (TF) is the key trigger of the coagulation cascade and the membrane signalling receptor for coagulation protease, factor VIIa. In cancer, TF has been implicated in tumor cell survival, growth, and angiogenesis, and is upregulated as a result of oncogenic transformation.

Materials And Methods: We assayed TF expression and tumourigenicity in mice in the case of human cancer cell lines expressing oncogenic receptor tyrosine kinases.

Role of the tissue factor pathway in the biology of tumor initiating cells.

Oncogenic transformation and aberrant cellular differentiation are regarded as key processes leading to malignancy. They produce heterogenous cellular populations including subsets of tumour initiating cells (TICs), also known as cancer stem cells (CSCs). Intracellular events involved in these changes profoundly impact the extracellular and systemic constituents of cancer progression, including those dependent on the vascular system.

Tissue factor and cancer stem cells: is there a linkage?

A common feature in the progression of multiple human malignancies is the protracted deregulation of the coagulation system, often referred to as cancer coagulopathy. Indeed, cancer cells and their vascular stroma often exhibit procoagulant properties, of which deregulation of tissue factor (TF) expression is a notable, although not the sole example. These changes can be traced to oncogenic influences affecting epidermal growth factor receptor (EGFR), EGFRvIII, K-ras, p53, PTEN, and probably many other proto-oncogenes and tumor suppressors in tumor parenchyma.

Tissue factor in tumour progression.

The linkage between activation of the coagulation system and cancer is well established, as is deregulation of tissue factor (TF) by cancer cells, their vascular stroma and cancer-associated inflammatory cells. TF is no longer perceived as an 'alternative' coagulation factor, but rather as a central trigger of the coagulation cascade and an important cell-associated signalling receptor activated by factor VIIa, and interacting with several other regulatory entities, most notably protease-activated receptors (PAR-1 and PAR-2). Preclinical studies revealed the role of oncogenic transformation and tumour micro-environment as TF regulators in cancer, along with the impact of this receptor on gene expression, tumour growth, metastasis, angiogenesis and, possibly, formation of the cancer stem cell niche.

Tissue factor and cancer.

Tissue factor (TF), the key regulator of haemostasis and angiogenesis, is also involved in the pathology of several diseases, including cardiovascular, inflammatory and neoplastic conditions. In the latter, TF is upregulated by cancer cells, as well as by certain host cells, and it is the interactions between these distinct pools of TF-expressing cells that likely influence tumour progression in several ways. Furthermore, the release of TF microparticles into the circulation is thought to contribute to the systemic coagulopathies commonly observed in cancer patients.

Tissue factor regulation by epidermal growth factor receptor and epithelial-to-mesenchymal transitions: effect on tumor initiation and angiogenesis.

ErbB oncogenes drive the progression of several human cancers. Our study shows that in human carcinoma (A431) and glioma (U373) cells, the oncogenic forms of epidermal growth factor receptor (EGFR; including EGFRvIII) trigger the up-regulation of tissue factor (TF), the transmembrane protein responsible for initiating blood coagulation and signaling through interaction with coagulation factor VIIa. We show that A431 cancer cells in culture exhibit a uniform TF expression profile; however, these same cells in vivo exhibit a heterogeneous TF expression and show signs of E-cadherin inactivation, which is coupled with multilineage (epithelial and mesenchymal) differentiation.

Vascular determinants of cancer stem cell dormancy--do age and coagulation system play a role?

The inability of tumour-initiating cancer stem cells (CSCs) to bring about a net increase in tumour mass could be described as a source of tumour dormancy. While CSCs may be intrinsically capable of driving malignant growth, to do so they require compatible surroundings of supportive cells, growth factors, adhesion molecules and energy sources (e.g.

Contribution of host-derived tissue factor to tumor neovascularization.

Objective: The role of host-derived tissue factor (TF) in tumor growth, angiogenesis, and metastasis has hitherto been unclear and was investigated in this study.

Methods And Results: We compared tumor growth, vascularity, and responses to cyclophosphamide (CTX) of tumors in wild-type (wt) mice, or in animals with TF levels reduced by 99% (low-TF mice). Global growth rate of 3 different types of transplantable tumors (LLC, B16F1, and ES teratoma) or metastasis were unchanged in low-TF mice.

Tissue factor in cancer.

Purpose Of Review: Tissue factor is increasingly viewed as an integral part of the vicious circle that links the vascular system with cancer progression at multiple systemic, cellular and molecular levels.

Recent Findings: The emerging tenet in this area is that oncogenic events/pathways driving the malignant process also stimulate the expression of tissue factor by cancer cells and promote the release of tissue factor-containing microvesicles into the circulation. The combined effects of these changes likely contribute to cancer coagulopathy, cessation of tumour dormancy, aggressive growth, angiogenesis and metastasis, notably through a combination of procoagulant and signalling effects set in motion by tissue factor.

Diverse roles of tissue factor-expressing cell subsets in tumor progression.

Oncogenic upregulation of tissue factor (TF) and release of TF-containing microvesicles play an important role in cancer-related coagulopathy (Trousseau's syndrome), angiogenesis, and disease progression. In addition, certain types of host cells (stromal cells, inflammatory cells, activated endothelium) may also express TF. Although the relative contribution of host-related versus tumor-related TF to tumor progression is not known, our recent studies indicate that the role of both sources of TF in tumor formation is complex and context-dependent.

The role of tumor-and host-related tissue factor pools in oncogene-driven tumor progression.

Oncogenic events play an important role in cancer-related coagulopathy (Trousseau syndrome), angiogenesis and disease progression. This can, in part, be attributed to the up-regulation of tissue factor (TF) and release of TF-containing microvesicles into the pericellular milieu and the circulation. In addition, certain types of host cells (stromal cells, inflammatory cells, activated endothelium) may also express TF.

Atherosclerosis and vascular aging as modifiers of tumor progression, angiogenesis, and responsiveness to therapy.

It is rarely considered that age-related common vascular co-morbidities may affect therapeutic outcomes of antiangiogenic therapy in cancer. Indeed, the accepted model of human disease consists of 4- to 8-week-old (young) tumor-bearing, but otherwise healthy, experimental mice, yet human cancers are diagnosed and treated in later decades of life when atherosclerosis and vascular diseases are highly prevalent. Here we present evidence that tumor growth and angiogenesis are profoundly altered in mice affected by natural aging and with genetically induced atherosclerosis (in ApoE(-/-) mice).

Tissue factor in cancer and angiogenesis: the molecular link between genetic tumor progression, tumor neovascularization, and cancer coagulopathy.

Tissue factor (TF), the primary cellular initiator of blood coagulation, is also involved in cancer-related processes such as hypercoagulability (Trousseau syndrome), tumor growth, angiogenesis, and metastasis. Indeed, elevated TF expression by cancer cells and their associated endothelial cells has been reported frequently. Oncogenic events in cancer cells (e.

Regulation of tissue factor and angiogenesis-related genes by changes in cell shape.

During development, tissue injury, and cancer, epithelial cells engage in communication with the vascular system by using several molecular mediators acting directly or through changes in the haemostatic system.The latter category is epitomised by the procoagulant cellular receptor known as tissue factor (TF). Here, we show that when cellular architecture is altered by a shift in culture conditions from monolayer to three-dimensional multicellular spheroids, expression of multiple angiogenesis effectors (VEGF, TSP-1, TSP-2, Ang-1, and TF) is profoundly altered.