H T Idriss 1, J H Naismith
Affiliations expand
PMID: 10891884
DOI: 10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H
Abstract
Tumour Necrosis Factor alpha (TNF alpha), is an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signalling events within cells, leading to necrosis or apoptosis.
Microsc Res Tech
. 2000 Aug 1;50(3):184-95.doi: 10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H.
https://pubmed.ncbi.nlm.nih.gov/10891884/
Front Immunol. 2018; 9: 1170.
Published online 2018 May 28. doi: 10.3389/fimmu.2018.01170
PMCID: PMC5985372
PMID: 29892300
TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors
Yuqiao Sheng,1 Feng Li,2 and Zhihai Qin1,*
Tumor necrosis factor (TNF) is widely accepted as a tumor-suppressive cytokine via its ubiquitous receptor TNF receptor 1 (TNFR1). The other receptor, TNFR2, is not only expressed on some tumor cells but also on suppressive immune cells, including regulatory T cells and myeloid-derived suppressor cells. In contrast to TNFR1, TNFR2 diverts the tumor-inhibiting TNF into a tumor-advocating factor. TNFR2 directly promotes the proliferation of some kinds of tumor cells. Also activating immunosuppressive cells, it supports immune escape and tumor development. Hence, TNFR2 may represent a potential target of cancer therapy. Here, we focus on expression and role of TNFR2 in the tumor microenvironment. We summarize the recent progress in understanding how TNFR2-dependent mechanisms promote carcinogenesis and tumor growth and discuss the potential value of TNFR2 in cancer treatment.
Keywords: tumor necrosis factor, TNF receptor 2, tumor, myeloid-derived suppressor cells, regulatory T cells, macrophages
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372/
Cell Stress. 2020 Jan; 4(1): 1–8.
Published online 2019 Dec 19. doi: 10.15698/cst2020.01.208
Necroptosis, tumor necrosis and tumorigenesis
Zheng-gang Liu1,* and Delong Jiao1
Necroptosis, known as programmed necrosis, is a form of caspase-independent, finely regulated cell death with necrotic morphology. Tumor necrosis, foci of necrotic cell death, occurs in advanced solid tumors and is often associated with poor prognosis of cancer patients. While it is well documented that apoptosis plays a key role in tumor regression and the inactivation of apoptosis is pivotal to tumor development, the role of necroptosis in tumorigenesis is still not fully understood as recent studies have reported both tumor-promoting and tumor-suppressing effects of necroptosis. In this short review, we will discuss some recent studies about the role of necroptosis in tumorigenesis and speculate the implications of these findings in future research and potential novel cancer therapy targeting necroptosis.
Keywords: necroptosis, tumor necroptosis, tumorigenesis, tumor metastasis, inflammation, immunosuppression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946014/
Volume 2018 |Article ID 3537471 | https://doi.org/10.1155/2018/3537471
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Regulation of Tumor Progression by Programmed Necrosis
Su Yeon Lee,1 Min Kyung Ju,1 Hyun Min Jeon,1 Eui Kyong Jeong,1 Yig Ji Lee,1 Cho Hee Kim,1,2 Hye Gyeong Park,3 Song Iy Han,4 and Ho Sung Kang1
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Academic Editor: Rodrigo Franco
Received30 Aug 2017
Accepted28 Nov 2017
Published31 Jan 2018
Abstract
Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness.
https://www.hindawi.com/journals/omcl/2018/3537471/
Tumor necrosis factor (TNF, cachexin, or cachectin; often called tumor necrosis factor alpha or TNF-α) is a cytokine – a small protein used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain.
TNF signaling occurs through two receptors: TNFR1 and TNFR2.[5][6] TNFR1 is constituitively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells.[5][6] TNF1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation.[5][6] Suppression of TNFR1 signaling has been important for treatment of autoimmune disease,[7] whereas TNFR2 signaling promotes wound healing.[6]
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
Published: 06 February 2015
The role of CD95 and CD95 ligand in cancer
M E Peter,
A Hadji,
A E Murmann,
S Brockway,
W Putzbach,
A Pattanayak &
P Ceppi
Cell Death & Differentiation volume 22, pages 549–559 (2015)
A Corrigendum to this article was published on 07 April 2015
Abstract
CD95 (Fas/APO-1) and its ligand, CD95L, have long been viewed as a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. In addition, these molecules are important in the immune elimination of virus-infected cells and cancer cells. CD95L was, therefore, considered to be useful for cancer therapy. However, major side effects have precluded its systemic use. During the last 10 years, it has been recognized that CD95 and CD95L have multiple cancer-relevant nonapoptotic and tumor-promoting activities. CD95 and CD95L were discovered to be critical survival factors for cancer cells, and were found to protect and promote cancer stem cells. We now discuss five different ways in which inhibiting or eliminating CD95L, rather than augmenting, may be beneficial for cancer therapy alone or in combination with standard chemotherapy or immune therapy.
https://www.nature.com/articles/cdd20153
The Janus Face of Death Receptor Signaling during Tumor Immunoediting
Eimear O’ Reilly, Andrea Tirincsi, Susan E. Logue and Eva Szegezdi*
Apoptosis Research Center, School of Natural Sciences, National University of Ireland, Galway, Ireland
Cancer immune surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognized by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumor cells by expressing death ligand cytokines of the tumor necrosis factor ligand family. However, some tumor cells can escape immune elimination and progress. Acquisition of resistance to the death ligand-induced apoptotic pathway can be obtained through cleavage of effector cell expressed death ligands into a poorly active form, mutations or silencing of the death receptors, or overexpression of decoy receptors and pro-survival proteins. Although the immune system is highly effective in the elimination of malignantly transformed cells, abnormal/dysfunctional death ligand signaling curbs its cytotoxicity. Moreover, DRs can also transmit pro-survival and pro-migratory signals. Consequently, dysfunctional death receptor-mediated apoptosis/necroptosis signaling does not only give a passive resistance against cell death but actively drives tumor cell motility, invasion, and contributes to consequent metastasis. This dual contribution of the death receptor signaling in both the early, elimination phase, and then in the late, escape phase of the tumor immunoediting process is discussed in this review. Death receptor agonists still hold potential for cancer therapy since they can execute the tumor-eliminating immune effector function even in the absence of activation of the immune system against the tumor. The opportunities and challenges of developing death receptor agonists into effective cancer therapeutics are also discussed.
https://www.frontiersin.org/articles/10.3389/fimmu.2016.00446/full
Suppression of TNFR1 signaling has been important for treatment of autoimmune disease,[7] whereas TNFR2 signaling promotes wound healing.[6]
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
TNF-α) is a cytokine – a small protein used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain.
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
The primary role of TNF is in the regulation of immune cells. TNF, as an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis, viral replication, and respond to sepsis via IL-1 and IL-6-producing cells.
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
Note. Do not use TNF or genmod in operation covid - mssg to USA/amcan/etc..
Under the name tasonermin, TNF is used as an immunostimulant drug in the treatment of certain cancers. Drugs that counter the action of TNF are used in the treatment of various inflammatory diseases, for instance rheumatoid arthritis.
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
Certain cancers can cause overproduction of TNF. TNF parallels parathyroid hormone both in causing secondary hypercalcemia and in the cancers with which excessive production is associated.
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
JAMA Oncology Patient Page
June 2018
Tumor Lysis Syndrome
Arjun Gupta, MD; Joseph A. Moore, MD
Article Information
JAMA Oncol. 2018;4(6):895. doi:10.1001/jamaoncol.2018.0613
When cancer cells break down quickly in the body, levels of uric acid, potassium, and phosphorus rise faster than the kidneys can remove them
Excess phosphorus can “sop up” calcium, leading to low levels of calcium in the blood. (c
https://jamanetwork.com/journals/jamaoncology/fullarticle/2680750
Transformation of amorphous calcium phosphate to bone-like apatite
Antiope Lotsari,
Anand K. Rajasekharan,
Mats Halvarsson &
Martin Andersson
Nature Communications volume 9, Article number: 4170 (2018)
Mineralisation of calcium phosphates in bone has been proposed to proceed via an initial amorphous precursor phase which transforms into nanocrystalline, carbonated hydroxyapatite. While calcium phosphates have been under intense investigation, the exact steps during the crystallisation of spherical amorphous particles to platelet-like bone apatite are unclear. Herein, we demonstrate a detailed transformation mechanism of amorphous calcium phosphate spherical particles to apatite platelet-like crystals, within the confined nanodomains of a bone-inspired nanocomposite. The transformation is initiated under the presence of humidity, where nanocrystalline areas are formed and crystallisation advances via migration of nanometre sized clusters by forming steps at the growth front. We propose that such transformation is a possible crystallisation mechanism and is characteristic of calcium phosphates from a thermodynamic perspective and might be unrelated to the environment. Our observations provide insight into a crucial but unclear stage in bone mineralisation, the origins of the nanostructured, platelet-like bone apatite crystals.
https://www.nature.com/articles/s41467-018-06570-x
Calcium phosphate is a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. Calcium phosphates are white solids of nutritious value[1] and are found in many living organisms, e.g., bone mineral and tooth enamel.[2] In milk, it exists in a colloidal form in micelles bound to casein protein with magnesium, zinc, and citrate–collectively referred to as colloidal calcium phosphate (CCP).[3] Various calcium phosphate minerals are used in the production of phosphoric acid and fertilizers. Overuse of certain forms of calcium phosphate can lead to nutrient-containing surface runoff and subsequent adverse effects upon receiving waters such as algal blooms and eutrophication.
Di- and polyphosphates[edit]
These materials contain Ca2+ combined with the polyphosphates, such as P2O74− and triphosphate [P3O10]5−:
Dicalcium diphosphate (CAS#7790-76-3]: Ca2P2O7
Calcium triphosphate (CAS# 26158-70-3): Ca5(P3O10)2
Hydroxy- and oxo-phosphates[edit]
These materials contain other anions in addition to phosphate:
Hydroxyapatite Ca5(PO4)3(OH)
Apatite Ca10(PO4)6(OH, F, Cl, Br)2
Tetracalcium phosphate (CAS#1306-01-0): Ca4(PO4)2O
https://en.wikipedia.org/wiki/Calcium_phosphate
Biomatter. 2012 Apr 1; 2(2): 53–70.
doi: 10.4161/biom.21340
PMCID: PMC3549858
PMID: 23507803
Calcium orthophosphates and human beings
A historical perspective from the 1770s until 1940
Sergey V. Dorozhkin*
The historical development of a scientific knowledge on calcium orthophosphates from the 1770s until 1940 is described. Many forgotten and poorly known historical facts and approaches have been extracted from old publications and then they have been analyzed, systematized and reconsidered from the modern point of view. The chosen time scale starts with the earliest available studies of 1770s (to the best of my findings, calcium orthophosphates had been unknown before), passes through the entire 19th century and finishes in 1940, because since then the amount of publications on calcium orthophosphates rapidly increases and the subject becomes too broad. Furthermore, since publications of the second half of the 20th century are easily accessible, a substantial amount of them have already been reviewed by other researchers. The reported historical findings clearly demonstrate that the substantial amount of the scientific facts and experimental approaches have been known for very many decades and, in fact, the considerable quantity of relatively recent investigations on calcium orthophosphates is just either a further development of the earlier studies or a rediscovery of the already forgotten knowledge.
Keywords: apatite, calc phosphate, calcium orthophosphate, history, lime phosphate
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549858/
In 1968, Gale A Granger from the University of California, Irvine, reported a cytotoxic factor produced by lymphocytes and named it lymphotoxin (LT).[18] Credit for this discovery is shared by Nancy H. Ruddle from Yale University, who reported the same activity in a series of back-to-back articles published in the same month.[19] Subsequently, in 1975 Lloyd J. Old from Memorial Sloan-Kettering Cancer Center, New York, reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF).[20]
Both factors were described based on their ability to kill mouse fibrosarcoma L-929 cells. These concepts were extended to systemic disease in 1981, when Ian A. Clark, from the Australian National University, in collaboration with Elizabeth Carswell in Old's group, working with pre-sequencing era data, reasoned that excessive production of TNF causes malaria disease and endotoxin poisoning.[21][22]
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
Fibrosarcoma (fibroblastic sarcoma) is a malignant mesenchymal tumour derived from fibrous connective tissue and characterized by the presence of immature proliferating fibroblasts or undifferentiated anaplastic spindle cells in a storiform pattern. In humans it is usually found in males aged 30 to 40.[citation needed] It originates in fibrous tissues of the bone and invades long or flat bones such as the femur, tibia, and mandible. It also involves the periosteum and overlying muscle.
https://en.wikipedia.org/wiki/Fibrosarcoma
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
The cDNAs encoding LT and TNF were cloned in 1984[23] and were revealed to be similar. The binding of TNF to its receptor and its displacement by LT confirmed the functional homologybetween the two factors. The sequential and functional homology of TNF and LT led to the renaming of TNF as TNFα and LT as TNFβ. In 1985, Bruce A. Beutler and Anthony Cerami discovered that cachectin (a hormone which induces cachexia) was actually TNF.[24] They then identified TNF as a mediator of lethal endotoxin poisoning.[25] Kevin J. Tracey and Cerami discovered the key mediator role of TNF in lethal septic shock, and identified the therapeutic effects of monoclonal anti-TNF antibodies.[26][27]
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
Research in the Laboratory of Mark Mattson has shown that TNF can prevent the death/apoptosis of neurons by a mechanism involving activation of the transcription factor NF-κB which induces the expression of antioxidant enzymes and Bcl-2.[28][29]
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
- Activation of NF-κB: TRADD recruits TRAF2 and RIP. TRAF2 in turn recruits the multicomponent protein kinase IKK, enabling the serine-threonine kinaseRIP to activate it. An inhibitory protein, IκBα, that normally binds to NF-κB and inhibits its translocation, is phosphorylated by IKK and subsequently degraded, releasing NF-κB. NF-κB is a heterodimeric transcription factor that translocates to the nucleus and mediates the transcription of a vast array of proteins involved in cell survival and proliferation, inflammatory response, and anti-apoptotic factors.
https://en.wikipedia.org/wiki/Tumor_necrosis_factor
NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.[1][2][3][5][6] NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.[7][8][9][10][11][12]
https://en.wikipedia.org/wiki/NF-κB
Note 3. Biofilm, plaque, tartar, calculus, calcification/mineralization, liequefacation/liquificaton/etc.
Note 4. USA NAC DOM Volatile org chemicals, infiltration/irritation, inflammation, inflammatory response cascade/cycling/layers/etc., wound healing/healing, granulation, keloid scarring/scarring/subst matrix/time variance/etc., biofilm deposition, plaquening (embeddement hairing), signal interference, mineralization, etc..
Note 5. Delta.
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