The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.

Identification of human brain tumour initiating cells

Preeclampsia is a relatively common pregnancy disorder that originates in the placenta and causes variable maternal and fetal problems. In the worst cases, it may threaten the survival of both mother and baby. We summarize recent work on the causes of preeclampsia, which reveals a new mode of maternal immune recognition of the fetus, relevant to the condition. The circulating factors derived from the placenta, which contributes to the clinical syndrome, are now better understood. This brief review on preeclampsia does not cover all aspects of this intriguing condition but focuses on some new and interesting findings.

https://science.sciencemag.org/content/sci/308/5728/1592.full.pdf

Latest advances in understanding preeclampsia.

Sponsors asked the IOM's Food and Nutrition Board and the Division of Behavioral and Social Sciences and Education Board on Children, Youth, and Families to review and update the IOM (1990) recommendations for weight gain during pregnancy and recommend ways to encourage their adoption through consumer education, strategies to assist practitioners, and public health strategies.The committee was asked to address the following tasks: 1. Review evidence on the relationship between weight gain patterns before, during, and after pregnancy and maternal and child health outcomes, with particular attention to the prevalence of maternal obesity racial/ethnic and age differences, components of GWG, and implications of weight during pregnancy on postpartum weight retention, maternal and child obesity, and later child health. 2. Within a life-stage framework consider factors in relation to GWG that are associated with maternal health outcomes such as lactation performance, postpartum weight retention, cardiovascular disease, metabolic processes including glucose and insulin-related issues, and risk of other chronic diseases; for infants and children, in addition to low birth weight, consider early developmental impacts and obesity-related consequences (e.g., mental health, diabetes). 3. Recommend revisions to the existing guidelines, where necessary, including the need for specific pregnancy weight guidelines for underweight, normal weight, and overweight and obese women and adolescents and women carrying twins or higher-order multiples. 4. Consider a range of approaches to promote appropriate weight gain, including: individual (behavior), psychosocial, community, health care, and health systems; timing and components of interventions; and ways to enhance awareness and adoption of the guidelines, including interdisciplinary approaches, consumer education to men and women, strategies to assist practitioners to use the guidelines, and public health strategies. 5. Identify gaps in knowledge and recommend research priorities.

/pdf/weight-gain-during-pregnancy-reexamining-the-guidelines-54naat6auf.pdf

Weight Gain During Pregnancy: Reexamining the Guidelines

A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell death has been characterized as apoptosis in many of these systems. It is increasingly being

Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells

MicroRNAs (miRNAs) are short endogenous RNAs known to post-transcriptionally repress gene expression in animals and plants. A microarray profiling survey revealed the expression patterns of 175 human miRNAs across 24 different human organs. Our results show that proximal pairs of miRNAs are generally coexpressed. In addition, an abrupt transition in the correlation between pairs of expressed miRNAs occurs at a distance of 50 kb, implying that miRNAs separated by <50 kb typically derive from a common transcript. Some microRNAs are within the introns of host genes. Intronic miRNAs are usually coordinately expressed with their host gene mRNA, implying that they also generally derive from a common transcript, and that in situ analyses of host gene expression can be used to probe the spatial and temporal localization of intronic miRNAs.

/pdf/microarray-profiling-of-micrornas-reveals-frequent-1y169f6thc.pdf

Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes

Preface.- Examination of the placenta.- Macroscopic features of the delivered placenta.- Microscopic survey.- Placental types.- Early development of the human placenta.- Basic structure of the villous trees.- Architecture of normal villous trees.- Characterization of the developmental stages.- Nonvillous parts and trophoblast invasion.- Involution of implantation site - retained placenta.- Anatomy and pathology of the placental membranes.- Anatomy and pathology of the umbilical cord and major fetal vessels.- Placental shape aberrations.- Histopathologic approach to villous alterations.- Classification of villous maldevelopment.- Erythroblastosis fetalis and hydrops fetalis.- Transplacental hemorrhage, cell transfer, trauma.- Fetal storage disorders.- Maternal diseases complicating pregnancy - diabetes - tumors - pre-eclampsia - lupus anticoagulant.- Infectious diseases.- Abortion, Placentas of trisomies, and immunological considerations of recurrent reproductive failure.- Molar pregnancies.- Trophoblastic neoplams.- Benign tumors, chorangiosis.- Multiple pregnancies.- Legal considerations.- Glossary.- Normative values and tables.- Index.

Pathology of the human placenta

Maternal uteroplacental blood flow increases during pregnancy. Altered uteroplacental blood flow is a core predictor of abnormal pregnancy. Normally, the uteroplacental arteries are invaded by endovascular trophoblast and remodeled into dilated, inelastic tubes without maternal vasomotor control. Disturbed remodeling is associated with maintenance of high uteroplacental vascular resistance and intrauterine growth restriction (IUGR) and preeclampsia. Herein, we review routes, mechanisms, and control of endovascular trophoblast invasion. The reviewed data suggest that endovascular trophoblast invasion involves a side route of interstitial invasion. Failure of vascular invasion is preceded by impaired interstitial trophoblast invasion. Extravillous trophoblast synthesis of nitric oxide is discussed in relation to arterial dilation that paves the way for endovascular trophoblast. Moreover, molecular mimicry of invading trophoblast-expressing endothelial adhesion molecules is discussed in relation to replacement of endothelium by trophoblast. Also, maternal uterine endothelial cells actively prepare endovascular invasion by expression of selectins that enable trophoblast to adhere to maternal endothelium. Finally, the mother can prevent endovascular invasion by activated macrophage-induced apoptosis of trophoblast. These data are partially controversial because of methodological restrictions associated with limitations of human tissue investigations and animal studies. Animal models require special care when extrapolating data to the human due to extreme species variations regarding trophoblast invasion. Basal plates of delivered placentas or curettage specimens have been used to describe failure of trophoblast invasion associated with IUGR and preeclampsia; however, they are unsuitable for these kinds of studies, since they do not include the area of pathogenic events, i.e., the placental bed.

https://bioone.org/journals/Biology-of-Reproduction/volume-69/issue-1/biolreprod.102.014977/Endovascular-Trophoblast-Invasion--Implications-for-the-Pathogenesis-of-Intrauterine/10.1095/biolreprod.102.014977.pdf

Peter Kaufmann

Papers

Pathology of the human placenta

Endovascular Trophoblast Invasion: Implications for the Pathogenesis of Intrauterine Growth Retardation and Preeclampsia

Development of the placental villous tree and its consequences for fetal growth

Oxygen and placental villous development: origins of fetal hypoxia.

Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy.