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Sarah Keating

Bio: Sarah Keating is an academic researcher from University of Toronto. The author has contributed to research in topics: Intrauterine growth restriction & Pregnancy. The author has an hindex of 30, co-authored 86 publications receiving 3533 citations. Previous affiliations of Sarah Keating include Mount Sinai Hospital & Mount Sinai Hospital, Toronto.


Papers
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Journal ArticleDOI
TL;DR: The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria for placental lesions, which will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.
Abstract: Context.—The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories. Objective.—To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community. Data Sources.—Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible. Conclusions.—The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous m...

955 citations

Journal ArticleDOI
TL;DR: STRA6 mutations define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the "STRA" group.
Abstract: We observed two unrelated consanguineous families with malformation syndromes sharing anophthalmia and distinct eyebrows as common signs, but differing for alveolar capillary dysplasia or complex congenital heart defect in one and diaphragmatic hernia in the other family. Homozygosity mapping revealed linkage to a common locus on chromosome 15, and pathogenic homozygous mutations were identified in STRA6, a member of a large group of "stimulated by retinoic acid" genes encoding novel transmembrane proteins, transcription factors, and secreted signaling molecules or proteins of largely unknown function. Subsequently, homozygous STRA6 mutations were also demonstrated in 3 of 13 patients chosen on the basis of significant phenotypic overlap to the original cases. While a homozygous deletion generating a premature stop codon (p.G50AfsX22) led to absence of the immunoreactive protein in patient's fibroblast culture, structural analysis of three missense mutations (P90L, P293L, and T321P) suggested significant effects on the geometry of the loops connecting the transmembrane helices of STRA6. Two further variations in the C-terminus (T644M and R655C) alter specific functional sites, an SH2-binding motif and a phosphorylation site, respectively. STRA6 mutations thus define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the "STRA" group.

327 citations

Journal ArticleDOI
01 Apr 2005-Placenta
TL;DR: This workshop reviewed the results of a recent initiative by the Perinatal Section of the Society for Pediatric Pathology to systematize and validate diagnostic schema for the description of lesions related to three important pathologic processes: amniotic fluid infection, maternal vascular underperfusion, and fetal vascular obstruction.

260 citations

Journal ArticleDOI
TL;DR: It is demonstrated that placenta does maintain differential methylation at the imprinting control regions H19 DMR and KvDMR, and it is shown that the IGF2 DMR2, also paternally methylated in most human tissues, exhibits hypomethylation in placentae.

161 citations

Journal ArticleDOI
TL;DR: Two undifferentiated (embryonal) sarcomas of liver were studied ultrastructurally and immunohistochemically and confirm the mesenchymal nature of this uncommon childhood neoplasm and support the suggestion that the cytoplasmic hyaline globules represent a degenerative phenomenon.

148 citations


Cited by
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Journal ArticleDOI
TL;DR: Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components and have a role in creating extracellular matrix structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy.
Abstract: Cancer is associated with fibroblasts at all stages of disease progression. This Review discusses the pleiotropic actions of cancer-associated fibroblasts (CAFs) on tumour cells and postulates that they are likely to be a heterogeneous and plastic population of cells in the tumour microenvironment. Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.

2,597 citations

Journal ArticleDOI
TL;DR: This delicate balance between tumor-associated macrophages and neoplastic cells may be considered to have a symbiotic relationship and the prospects for its therapeutic manipulation are described.

1,028 citations

Journal ArticleDOI
TL;DR: The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria for placental lesions, which will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.
Abstract: Context.—The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories. Objective.—To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community. Data Sources.—Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible. Conclusions.—The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous m...

955 citations

Journal ArticleDOI
TL;DR: The development and functional characterization of genetically modified mice that lack or overexpress genes that are involved in repair, combined with gene-expression analysis in wounds and tumours, have highlighted remarkable similarities between wound repair and cancer.
Abstract: What is the relationship between the wound-healing process and the development of cancer? Malignant tumours often develop at sites of chronic injury, and tissue injury has an important role in the pathogenesis of malignant disease, with chronic inflammation being the most important risk factor. The development and functional characterization of genetically modified mice that lack or overexpress genes that are involved in repair, combined with gene-expression analysis in wounds and tumours, have highlighted remarkable similarities between wound repair and cancer. However, a few crucial differences were also observed, which could account for the altered metabolism, impaired differentiation capacity and invasive growth of malignant tumours.

844 citations

Journal ArticleDOI
TL;DR: The current evidence for the role of abnormal placentation and therole of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia is discussed.
Abstract: Hypertensive disorders of pregnancy-chronic hypertension, gestational hypertension, and preeclampsia-are uniquely challenging as the pathology and its therapeutic management simultaneously affect mother and fetus, sometimes putting their well-being at odds with each other. Preeclampsia, in particular, is one of the most feared complications of pregnancy. Often presenting as new-onset hypertension and proteinuria during the third trimester, preeclampsia can progress rapidly to serious complications, including death of both mother and fetus. While the cause of preeclampsia is still debated, clinical and pathological studies suggest that the placenta is central to the pathogenesis of this syndrome. In this review, we will discuss the current evidence for the role of abnormal placentation and the role of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia. We will discuss angiogenic biomarker assays for disease-risk stratification and for the development of therapeutic strategies targeting the angiogenic pathway. Finally, we will review the substantial long-term cardiovascular and metabolic risks to mothers and children associated with gestational hypertensive disorders, in particular, preterm preeclampsia, and the need for an increased focus on interventional studies during the asymptomatic phase to delay the onset of cardiovascular disease in women.

829 citations