Cure Alveolar Soft Part Sarcoma International (iCureASPS)

An interesting and intense read on the bodies reaction to either initial induced tumor necrosis and or secondary immune response , of the “removal “ of the necrotic material .

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630647/

Abstract

When apoptotic cells are not cleared in an efficient and timely manner, they progress to secondary necrosis and lose their membrane integrity. This results in a leakage of immunostimulatory, danger associated molecular patterns (DAMPs), similar to accidental (or primary) necrosis. However, primary necrosis is a sudden event with an inadvertent release of almost unmodified DAMPs. Secondary necrotic cells, in contrast, have gone through various modifications during the process of apoptosis. Recent research revealed that the molecules released from the cytoplasm or exposed on the cell surface differ between primary necrosis, secondary necrosis, and regulated necrosis such as necroptosis. This review gives an overview of these differences and focusses their effects on the immune response. The implications to human physiology and diseases are manifold and will be discussed in the context of cancer, neurodegenerative disorders and autoimmunity.

Keywords: Primary necrosis, Apoptosis, Secondary necrosis, Efferocytosis, Inflammation, Cancer immunotherapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630647/

Abstract

Cells can respond to stress in various ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Whether cells mount a protective or destructive stress response depends to a large extent on the nature and duration of the stress as well as the cell type. Also, there is often the interplay between these responses that ultimately determines the fate of the stressed cell. The mechanism by which a cell dies (i.e., apoptosis, necrosis, pyroptosis, or autophagic cell death) depends on various exogenous factors as well as the cell's ability to handle the stress to which it is exposed. The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson's disease, myocardial infarction, and cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825543/

The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis



Abstract

Apoptosis can be induced in response to hypoxia. The severity of hypoxia determines whether cells become apoptotic or adapt to hypoxia and survive. A hypoxic environment devoid of nutrients prevents the cell undergoing energy dependent apoptosis and cells become necrotic. Apoptosis regulatory proteins are delicately balanced. In solid tumours, hypoxia is a common phenomenon. Cells adapt to this environmental stress, so that after repeated periods of hypoxia, selection for resistance to hypoxia induced apoptosis occurs. These resistant tumours probably have a more aggressive phenotype and may have decreased responsiveness to treatment. The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. However, during hypoxia, antiapoptotic proteins, such as IAP-2, can be induced, whereas the proapoptotic protein Bax can be downregulated. During hypoxia, an intricate balance exists between factors that induce or counteract apoptosis, or even stimulate proliferation. Understanding the regulation of apoptosis during hypoxia and the mechanisms of resistance to apoptosis might lead to more specific treatments for solid tumours.

Keywords: hypoxia, apoptosis,* hypoxia inducible factor 1, tumour

https://www.ncbi.nlm.nih.gov/pmc/articl ... 68000title

Therapeutic Vulnerability of an In Vivo Model of Alveolar Soft Part Sarcoma (ASPS) to Anti -Angiogenic Therapy

Abstract

In vivo growth of Alveolar Soft Part Sarcoma (ASPS) was achieved using subcutaneous xenografts in sex matched NOD.SCID\NCr mice. One tumor, currently at passage 6, has been maintained in vivo for 32 months and has maintained characteristics consistent with those of the original ASPS tumor including (1) tumor histology and staining with Periodic Acid Schiff/Diastase (2) the presence of the ASPL-TFE3 type 1 fusion transcript (3) nuclear staining with antibodies to the ASPL-TFE3 type 1 fusion protein, (4) maintenance of the t(X;17)(p11;q25) translocation characteristic of ASPS, (5) stable expression of signature ASPS gene transcripts and finally, the development and maintenance of a functional vascular network, a hallmark of ASPS. The ASPS xenograft tumor vasculature encompassing nests of ASPS cells is highly reactive to antibodies against the endothelial antigen CD34 and is readily accessible to intravenously administered FITC-dextran. The therapeutic vulnerability of this tumor model to anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF) and hypoxiainducible factor-1 alpha (HIF-1 α), was examined utilizing bevacizumab and topotecan alone and in combination. Together, the two drugs produced a 70% growth delay accompanied by a 0.7 net log cell kill which was superior to the antitumor effect produced by either drug alone. In summary, the current study describes a pre-clinical in vivo model for ASPS which will facilitate investigation into the biology of this slow growing soft tissue sarcoma and demonstrates the feasibility of employing an anti-angiogenic approach in the treatment of ASPS.




*https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784654/