The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect.

Human exposure to bisphenol A (BPA).

One of the main engines that drives cellular transformation is the loss of proper control of the mammalian cell cycle. The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) promotes cell cycle arrest in response to many stimuli. It is well positioned to function as both a sensor and an effector of multiple anti-proliferative signals. This Review focuses on recent advances in our understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.

p21 in cancer: intricate networks and multiple activities

In 1991, a group of 21 scientists gathered at the Wingspread Conference Center to discuss evidence of developmental alterations observed in wildlife populations after chemical exposures. There, the term "endocrine disruptor" was agreed upon to describe a class of chemicals including those that act as agonists and antagonists of the estrogen receptors (ERs), androgen receptor, thyroid hormone receptor, and others. This definition has since evolved, and the field has grown to encompass hundreds of chemicals. Despite significant advances in the study of endocrine disruptors, several controversies have sprung up and continue, including the debate over the existence of nonmonotonic dose response curves, the mechanisms of low-dose effects, and the importance of considering critical periods of exposure in experimental design. One chemical found ubiquitously in our environment, bisphenol-A (BPA), has received a tremendous amount of attention from research scientists, government panels, and the popular press. In this review, we have covered the above-mentioned controversies plus six additional issues that have divided scientists in the field of BPA research, namely: 1) mechanisms of BPA action; 2) levels of human exposure; 3) routes of human exposure; 4) pharmacokinetic models of BPA metabolism; 5) effects of BPA on exposed animals; and 6) links between BPA and cancer. Understanding these topics is essential for educating the public and medical professionals about potential risks associated with developmental exposure to BPA and other endocrine disruptors, the design of rigorously researched programs using both epidemiological and animal studies, and ultimately the development of a sound public health policy.

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Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption

BackgroundBisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to whic...

/pdf/urinary-circulating-and-tissue-biomonitoring-studies-3sv3m05feu.pdf

Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A.

Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester.

Osteoporosis is a multifactorial trait with low bone mineral density (BMD). We report results of an association study between BMD and nine candidate genes (TGFB1, TGFBR2, SMAD2, SMAD3, SMAD4, IFNB1, IFNAR1, FOS and LRP5), as well as of a case-control study of osteoporosis. Samples for the former association study included 481 general Japanese women. Among the nine candidate genes examined, only LRP5 showed a significant association with BMD. We identified a strong linkage disequilibrium (LD) block within LRP5. Of five LPR5 single nucleotide polymorphisms (SNPs) that are located in the LD block, three gave relatively significant results: Women with the C/C genotype at the c.2220C>T SNP site had higher adjusted BMD (AdjBMD) value compared to those with C/T and T/T (p=0.022); and likewise, G/G at IVS17–30G>A and C/C women at c.3989C>T showed higher AdjBMD than those with G/A or A/A (p=0.039) and with C/T or T/T (p=0.053), respectively. The case-control study in another series of samples consisting of 126 osteoporotic patients and 131 normal controls also gave a significant difference in allele frequency at c.2220C>T (ϰ2=6.737, p=0.009). These results suggest that LRP5 is a BMD determinant and also contributes to a risk of osteoporosis.

/pdf/lrp5-low-density-lipoprotein-receptor-related-protein-5-is-a-36qd0vfidp.pdf

LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density.

Bacterial vaginosis (BV), the etiology of which is still uncertain, increases the risk of preterm birth. Recent PCR-based studies suggested that BV is associated with complex vaginal bacterial communities, including many newly recognized bacterial species in non-pregnant women. To examine whether these bacteria are also involved in BV in pregnant Japanese women, vaginal fluid samples were taken from 132 women, classified as normal (n = 98), intermediate (n = 21), or BV (n = 13) using the Nugent gram stain criteria, and studied. DNA extracted from these samples was analyzed for bacterial sequences of any Lactobacillus, four Lactobacillus species, and four BV-related bacteria by PCR with primers for 16S ribosomal DNA including a universal Lactobacillus primer, Lactobacillus species-specific primers for L. crispatus, L. jensenii, L. gasseri, and L. iners, and BV-related bacterium-specific primers for BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium. The prevalences of L. crispatus, L. jensenii, and L. gasseri were significantly higher, while those of BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium were significantly lower in the normal group than in the BV group. Unlike other Lactobacillus species, the prevalence of L. iners did not differ between the three groups and women with L. iners were significantly more likely to have BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium. Linear regression analysis revealed associations of BVAB2 and Megasphaera with Nugent score, and multivariate regression analyses suggested a close relationship between Eggerthella-like bacterium and BV. The BV-related bacteria, including BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium, are common in the vagina of pregnant Japanese women with BV. The presence of L. iners may be correlated with vaginal colonization by these BV-related bacteria.

/pdf/association-between-lactobacillus-species-and-bacterial-2nekc3laxr.pdf

Association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scores in pregnant Japanese women

Estrogen receptor α polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen

https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/57971/1/text.pdf

Itsuko Furuta

Papers

Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester.

LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density.

Association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scores in pregnant Japanese women

Estrogen receptor α polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen

Autophagy in the placenta of women with hypertensive disorders in pregnancy