Contesting the cruel treatment of abortion-seeking women

NOTICE: this is the author’s version of a work that was accepted for publication in Reproductive Health Matters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in REPRODUCTIVE HEALTH MATTERS, [VOL 22, ISSUE 44, (2014)] DOI: 10.1016/S0968-8080(14)44818-

ORGAN SPECIFIC VASCULAR RESPONSE TO FIBROSIS AFFECTS BREAST CANCER METASTATIC ORGANOTROPISM

The solid tumor microenvironment, pre-metastatic niche, and fibrotic environment are known to have significant biochemical and biomechanical similarities to the fibrotic environment. All have significantly increased levels of factors such as TGFβ, HIF1α, TNFα, PDGF, VEGF, FGF, interleukins and other growth factors that are known to be pro-tumorigenic. Clinical and basic science research has shown that fibrosis presents an environment that favors tumor growth, such as hepatocellular carcinoma being commonly preceded by liver cirrhosis, or bleomycin induced lung fibrosis enhancing pulmonary metastasis in mouse models of breast cancer. In addition to the evidence indicating that fibrosis enhances primary tumor growth and metastasis it is also well characterized that primary tumor metastasis has specific organotropism, for example breast cancer commonly spreads to the lungs, brain, bone, liver and lymph nodes. However, whether non-organtropic fibrosis can redirect metastasis to the damaged organ has not been investigated. To elucidate the fibrotic effect on tumor organotropism we induced fibrosis in the organotropic lungs and in the non-organotropic kidney of two mouse models of breast cancer, the 4T1 murine cancer cell line model and the genetic MMTV-Pymt model, both of which are known to metastasize. Using histopathology, microarrays, gene expression by polymerase chain reaction, ELISA, chemokine array, and in vitro experiments we demonstrate that despite the pro-tumorigenic environment, kidney fibrosis does not redirect metastasis to the non-organotropic damaged organ. However, mice with kidney fibrosis had increased metastasis to their lungs. Furthermore, we found that kidney fibrosis increases the circulating levels of the pro-angiogenic factor Angiopoietin 2 that increased vascular permeability of the lungs, but not the kidneys. In fact, while fibrotic lungs showed decreased expression of endothelial tight gap junction protein Claudin-5, the fibrotic kidneys had an elevated expression of Claudin-5. Our findings suggest that despite the similarities between fibrosis, the tumor microenvironment and the pre-metastatic niche, that while it can enhance tropic metastatic disease, it cannot redirect organotropism indicating that other factors must be involved in directing organotropism. Here we report that tumor organotropism may be a result of organ specific vascular responses to excess circulating factors and increased fibrotic factors. These findings indicate that organotropism is directly related to and as a result of organ specific vascular alterations

On the horns of a dilemma

Illegality, as a concept, covers a multitude of sins and the differences that arise and the decisions of the courts are based on the principle of public policy. Under this heading it is the author's intention to examine the resulting trust, through the transfer of property in furtherance of a fraud, and illegality

“Why Wouldn’t I Use It?”: Purdue Pharmaceutical’s Push of Pills

Throughout the early 1940’s to mid 1960’s, the popular habit of smoking cigarettes was not only condoned, but advertised by doctors and lawmakers. With the support of medical professionals and non-restrictive advertisement laws, the widespread use of this deadly product exploded. The ‘Big Tobacco’ industry and the federal government made enormous amounts in profit and tax revenue. Numerous similarities can be found between the advertising of cigarettes and the prescription opioid, OxyContin. ‘Big Tobacco’ and the producer of OxyContin, Purdue Pharma (Hoffman and Williams Walsh), employed incredibly similar tactics to encourage the public to use their lethal products. By controlling the narrative about the potential dangers, and the addictive properties through their use of advertisements, both “Big Tobacco” and Purdue Pharmaceuticals accomplished their goals of inspiring the “why wouldn’t I use it” question in the consumers’ minds