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Nathan Goodyear

Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic... - 0 views

pubmed.ncbi.nlm.nih.gov/24239723

metabolic endotoxemia NF-kappaB vitamin C inflammation NFKB

shared by Nathan Goodyear on 09 Oct 21 - No Cached
  • Nathan Goodyear on 09 Oct 21
     
    Vitamin C inhibits metabolic endotoxemia NFKB inflammatory signaling.
Nathan Goodyear

Medroxyprogesterone Acetate Induces Cell Proliferation through Up-Regulation ... - 0 views

endo.endojournals.org/...4917.long

medroxyprogesterone acetate progestin progestins breast cancer prover NF-kapppB

shared by Nathan Goodyear on 20 Nov 12 - No Cached
  • Nathan Goodyear on 20 Nov 12
     
    medroxyprogesterone acetate, synthetic progestin, shown to increase inflammation signaling in human breast cancer cells.  This is a proposed mechamism by which growth stimulation occurs with prover and breast cancer.  
Nathan Goodyear

Renin-angiotensin system and cancer: A review - 0 views

www.oatext.com/system-and-cancer-A-review.php

renin angiotensin system cancer

shared by Nathan Goodyear on 10 Sep 18 - No Cached
  • crucial role of the RAS in the development and maintenance of cancer
  • kidneys, which produce renin in response to decreased arterial pressure, reduced sodium in the distal tubule, or sympathetic nervous system activity via the β-adrenergic receptors
  • Renin is secreted from the juxtaglomerular cells into the bloodstream where it encounters angiotensinogen (AGN), normally produced by the liver
  • ...22 more annotations...
  • Renin catalyses the conversion of AGN to angiotensin I (ATI), which is quickly cleaved by angiotensin converting enzyme (ACE) to form angiotensin II (ATII)
  • ATII triggers the release of aldosterone from the adrenal glands, which stimulates reabsorption of sodium and water and thereby increases blood volume and blood pressure
  • ATII also acts on smooth muscle to cause vasoconstriction of the arterioles
  • ATII promotes the release of antidiuretic hormone from the posterior pituitary gland, which results in water retention and triggers the thirst reflex
  • ability of non-CSCs to ‘de-differentiate’ into CSCs due to epigenetic or environmental factors, which further increases the complexity of tumour biology and treatment
  • efficacy of RAS modulators on cancer in both cancer models and cancer patients
  • A localised (‘paracrine’) RAS mechanism has been identified in many types of cancers, and interruption of the control of the RAS is thought to be the basis for its role in cancer
  • Components of the RAS are expressed by these CSCs, supporting the hypothesis of the presence of a ‘paracrine RAS’ in regulating these CSCs
  • Renin is an enzyme normally released by the kidneys in response to falling arterial pressure
  • a study of GBM demonstrating overexpression of PRR coupled with the observation that inhibition of renin reduces cellular proliferation and promotes apoptosis
  • PRR has been found to be vital for normal Wnt signalling
  • A major focus of PRR research is its relationship with Wnt signalling
  • suggest a crucial role for PRR activation on the proliferation of CSCs, possibly via Wnt/β-catenin signalling, leading to carcinogenesis.
  • Angiotensin converting enzyme (ACE), also known as CD143, is the endothelial-bound peptidase which physiologically converts ATI to ATII
  • ACE is crucial in the regulation of blood pressure, angiogenesis and inflammation
  • results suggest that an overactive ACE promotes cancer growth and progression, and an inhibited or low-activity ACE may have cancer-protective effects
  • When bound to ATII or ATIII it causes vasoconstriction by stimulating the release of vasopressin, reabsorption of water and sodium by promoting secretion of aldosterone and insulin, fibrosis, cellular growth and migration, pro-inflammation, glucose release from the liver, increased plasma triglyceride concentration, and reduced gluconeogenesis
  • ATIIR1 is a G-protein-coupled receptor, with downstream signalling involved in vasodilation, hypertrophy and NF-κB activation leading to TNF-α and PAI-1 expression
  • ATIIR1 has well-documented links with cancer, with one study demonstrating its overexpression in ~20% of breast cancer patients
  • the effect of RAS dysregulation has been associated with increased VEGF expression and angiogenesis in cancers
  • In ovarian and cervical cancer, ATIIR1 overexpression has been shown to be an indicator of tumour invasiveness
  • administration of ATIIR1 blockers (ARBs) have been associated with reduced tumour size, reduction in tumour vascularisation, lower occurrence of metastases, and lower VEGF levels
  • Nathan Goodyear on 10 Sep 18
     
    Great review on RAS in cancer.
Nathan Goodyear

Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on g... - 0 views

www.ncbi.nlm.nih.gov/...PMC4741919

adenoid cystic carcinoma

shared by Nathan Goodyear on 03 Oct 18 - No Cached
  • Cisplatin and 5-FU or CAP (cisplatin, doxorubicin, and cyclophosphamide) regimens can be used for combination chemotherapy
  • patients with advanced salivary gland malignancy treated with the CAP regimen achieved partial response (PR) or stable disease (SD) rates of 67% (8 out of 12 patients)
  • Agents commonly given as monotherapy for treating ACC are cisplatin, mitoxantrone, epirubicin, vinorelbine, paclitaxel, and gemcitabine. However, few of these agents have shown efficacy
  • ...23 more annotations...
  • single agent mitoxantrone or vinorelbine were recommended as reasonable choices
  • ACC is subdivided into 3 histological groups based on solid components of the tumor including cribriform, tubular, and solid
  • Cribriform and tubular ACCs usually exhibit a more indolent course, whereas the solid subtype is associated with worse prognosis
  • ACC consists of two different cell types: inner luminal epithelial cells and outer myoepithelial cells
  • epithelial cells express c-kit, cox-2 and Bcl-2
  • myoepithelial cells express EGFR and MYB
  • a balanced translocation of the v-myb avian myeloblastosis viral oncogene homolog-nuclear factor I/B (MYB-NFIB) is considered to be a signature molecular event of ACC oncogenesis
  • As a transcription factor, MYB is known to modulate multiple genetic downstream targets involved in oncogenesis, such as cox-2, c-kit, Bcl-2 and BclX
  • Various signaling cascades are essential for cancer cells to survive and grow. The PI3K/Akt/mTOR pathway is one of them
  • This pathway regulates cell survival and growth and is upregulated in many cancers
  • Mutations in genes associated with DNA repair are frequently found in familial cancer syndromes, such as hereditary breast-ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC, also called Lynch syndrome) and Li-Fraumeni syndrome [30, 31]. These mutations were also reported in non-hereditary cancers
  • 70% of ACC samples (58 of 84) were found to have genetic alterations in the MYB/MYC pathway, indicating that changes in this pathway are crucial in ACC pathogenesis
  • The second most frequently mutated pathway was involved in chromatin remodeling (epigenetic modification), a pathway that includes multiple histone related proteins, and was altered in 44% of samples
  • C-kit
  • VEGF, iNOS and NF-κB were noted to be highly expressed in ACC cells as compared to normal salivary gland cells
  • members of the SOX family, such as SOX 4 and SOX10, are overexpressed in ACC
  • FABP7 (Fatty acid binding protein 7) and AQP1 (Aquaporin 1) tend to be overexpressed in ACC cell lines
  • considerable variability in HER2 overexpression ranging from 0–58% in patients with ACC
  • the study with cetuximab and concurrent chemoradiation or chemotherapy showed the highest ORR (total 43%, 9.5% CR and 33% PR), but this regimen was only given to the EGFR positive patients
  • Cancer immunotherapy can be classified into 3 major groups. Active immunization using anti-tumor vaccines to induce and recruit T cells, passive immunization based on monoclonal antibodies, and adoptive cell transfer to expand tumor-reactive autologous T cells ex vivo and then reintroduce these cells into the same individual
  • LAK cells showed cytotoxicity against ACC cells
  • cytokine-induced cell apoptosis and the cytotoxic effect of the LAK cells contributed to tumor regression
  • molecular finding of the MYB-NFIB fusion gene has the greatest potential to target what appears to be a fundamental event in disease pathogenesis
  • Nathan Goodyear on 03 Oct 18
     
    good review of adenoid cystic carcinoma
Nathan Goodyear

Oncotarget | Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in... - 0 views

www.oncotarget.com/index.php

Niclosamide cancer ovarian cancer

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • Ovarian cancer is the most lethal gynecologic malignancy in the world
  • paclitaxel represents a breakthrough in the treatment of ovarian cancer, the overall 5-year survival rate of patients with stage III disease is still approximately 40%
  • Targeting cancer stem cells is an emerging concept in cancer therapy
  • ...8 more annotations...
  • Ovarian cancer stem cells play an important role in chemoresistance and cancer recurrence
  • Furthermore, recent studies indicate that niclosamide exhibits anticancer effects against various human cancer cells by acting on multiple cell signaling pathways and inducing mitochondrial uncoupling [16–21]
  • This toxicity evaluation showed that oral nano-NI had no toxic effect on either group of mice in terms of weight, plasma albumin levels, and blood cell counts, and revealed no adverse effects on vital organ function in the rodents, which suggests that nano-NI is safe for animals
  • The nano-NI demonstrated significantly higher inhibitory effects on sphere formation than the original niclosamide did
  • the nano-NI formulation decreased the metabolic activity of ovarian cancer cells and caused a metabolic shift from oxidative phosphorylation to glycolysis
  • has low systemic bioavailability (~10%) when administered orally, which is beneficial for treating local parasitic infections of the intestines while minimizing systemic exposure
  • niclosamide inhibits tumor cell growth by interrupting multiple pathways (Wnt, Notch, STAT3, NF-κB, and mTORc1) and the generation of reactive oxygen species in several cancer cells
  • The current standard therapy for ovarian cancer includes taxanes and platinum-based chemotherapy after cytoreductive surgery. Among treated patients, nearly 70 to 80% will experience disease recurrence
  • Nathan Goodyear on 16 Apr 18
     
    nano-Niclosamide more effective than traditional Niclosamide in in vitro and in vivo ovarian cancer.
Nathan Goodyear

Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-indu... - 0 views

www.ncbi.nlm.nih.gov/...PMC5525354

omega 3 omega-3 microglia TBI traumatic brain injury brain inflammation

shared by Nathan Goodyear on 01 Aug 17 - No Cached
  • Nathan Goodyear on 01 Aug 17
     
    Omega 3 supplementation found to blunt microglial TBI inflammation. 
Nathan Goodyear

Cancers | Free Full-Text | A Second WNT for Old Drugs: Drug Repositioning against WNT-D... - 0 views

www.mdpi.com/htm

cancer Niclosamide ivermectin Wnt

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • To date nearly half of known human tumors show a dysregulation of the WNT signaling pathway
  • It should be also noted that the WNT pathway is not exclusively employed during development or overactivated in cancer. In adults many healthy tissues rely on it for renewal and homeostasis maintenance, most notably the intestine, haematopoietic system, hair, bones and skin. Therefore one might expect adverse reactions in all these organ systems, which has indeed been observed for many WNT-targeting compounds upon attempts to push them into the clinics
  • The intestine seems to be the most vulnerable in this regard
  • ...8 more annotations...
  • Ivermectin inhibits proliferation of human colon cancer and lung cancer cells both in vitro and in vivo
  • The anti-proliferative action, affecting both the bulk tumor cells and CSCs, was linked in this study to inhibition of WNT signaling
  • the anti-WNT IC50 of ivermectin is 5–10 times (~1–2 µM vs. 10 µM) lower than that of its toxic effect against chloride channels
  • oral bioavailability of the drug, as for other antiparasitic drugs discussed in this section, is very low
  • Toxicity studies in vivo have also demonstrated a wide therapeutic index for ivermectin
  • Its anti-proliferative activity has been demonstrated in a wide array of cancer cell lines representative of WNT-dependent cancers: non-small lung carcinoma [96], multiple myeloma [97], hepatoma [98], adrenocortical carcinoma [99], ovarian cancer [100] and glioblastoma
  • Niclosamide inhibits the canonical WNT pathway
  • In addition to inhibiting the canonical WNT pathway, niclosamide may mediate its anticancer activities through several other signaling pathways such as NOTCH [107], MTOR [108], NF-κB [97] and STAT3 [96]
  • Nathan Goodyear on 16 Apr 18
     
    review article highlights older medications that have anti-Wnt pathway effects in cancer.  Roughly, 50% of cancer involve upregulated Wnt pathway activity. Other drugs of note: metformin
Nathan Goodyear

Frontiers | Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of... - 0 views

journal.frontiersin.org/...full

LPS lipopolysaccharides Alzheimer's disease brain inflammation

shared by Nathan Goodyear on 23 Sep 17 - No Cached
  • lipopolysaccharides (LPS), either alone or in combination, have indicated that when compared, bacterial LPSs exhibit the strongest induction of pro-inflammatory signaling in human neuronal–glial cells in primary coculture of any single inducer, and different LPS extracts from different gastrointestinal (GI)-tract resident Gram-negative bacteria appeared to have different pro-inflammatory potential
  • powerful inducer of the NF-κB
  • In both neocortex and hippocampus, LPS has been detected to range from a ~7- to ~21-fold increase abundance in AD brain
  • ...15 more annotations...
  • Major Gram-negative bacilli of the human GI-tract, such as the abundant B. fragilis and Escherichia coli (E. coli), are capable of discharging a remarkably complex assortment of pro-inflammatory neurotoxins
  • (i) bacterial amyloids (10, 21); (ii) endotoxins and exotoxins (5, 12); (iii) LPS (12, 18); and (iv) small non-coding RNAs (sncRNAs)
  • integral components of the outer leaflet of the outer membrane of Gram-negative bacteria, LPS
  • LPS, the major molecular component of the outer membrane of Gram-negative bacteria normally serves as a physical barrier providing the bacteria protection from its surroundings
  • LPS is also recognized by the immune system as a marker for the detection of bacterial pathogen invasion and responsible for the development of inflammatory response is perhaps the most potent stimulator and trigger of inflammation known
  • AD-affected brains have remarkably large loads of bacterial-derived toxins compared to controls. The transfer of noxious, pro-inflammatory molecules from the GI-tract microbiome to the CNS may be increasingly important during the course of aging when both the GI-tract and blood–brain barriers become significantly more permeable
  • first evidence of a perinuclear association of LPS with AD brain cell nuclei
  • LPS-mediated stimulation of chronic inflammation, beta-amyloid accumulation, and episodic memory decline in murine models of AD (39, 40) and a biophysical association of LPS with amyloid deposits and blood vessels in human AD patients
  • Strong adherence of LPS to the nuclear periphery has recently been shown to inhibit nuclear maturation and function that may impair or block export of mRNA signals from brain cell nuclei, a highly active organelle with extremely high rates of transcription, mRNA processing, and export into the cytoplasm
  • LPS may be further injurious to the nuclear membrane just as LPS contributes to cerebrovascular endothelial cell membrane injury
  • high intake of dietary fiber is a strong inhibitor of B. fragilis abundance and proliferation in the intact human GI-tract and as such is a potent inhibitor of the neurotoxic B. fragilis-derived amyloids, LPS, enterotoxins, and sncRNAs.
  • GI-tract microbiome-derived LPS may be an important initiator and/or significant contributor to inflammatory degeneration in the AD CNS
  • LPS has been recently localized to the same anatomical regions involved in AD-type neuropathology
  • a known pro-inflammatory transcription factor complex that triggers the expression of pathogenic pathways involved in neurodegenerative inflammation
  • pro-inflammatory amyloids, endo- and exotoxins, LPSs, and sncRNAs but also serve as potent sources of membrane-disrupting agents
  • Nathan Goodyear on 23 Sep 17
     
    LPS links gut to inflammation in Alzheimer's disease
Nathan Goodyear

Resveratrol Inhibits the Epithelial-Mesenchymal Transition of Pancreatic Canc... - 0 views

www.eurekaselect.com/...article

resveratrol epithelial to mesenchymal transition EMT PI3K_Akt_mTOR

shared by Nathan Goodyear on 08 Mar 21 - No Cached
  • Nathan Goodyear on 08 Mar 21
     
    Resveratrol inhibits EMT
Nathan Goodyear

Boswellia ovalifoliolata abrogates ROS mediated NF-κB activation, causes apop... - 0 views

pubmed.ncbi.nlm.nih.gov/24908637

triple negative breast cancer Boswellia TNBC chemotherapy

shared by Nathan Goodyear on 30 Apr 21 - No Cached
  • Nathan Goodyear on 30 Apr 21
     
    Boswellia shows chemosensitizing effects with doxorubicin and cisplatin with TNBC.
Nathan Goodyear

Curcumin Potentiates the Antitumor Effects of Bacillus Calmette-Guerin agains... - 0 views

cancerres.aacrjournals.org/...8958

curcumin bladder cancer BCG

shared by Nathan Goodyear on 10 Feb 21 - No Cached
  • Nathan Goodyear on 10 Feb 21
     
    Curcumin augments BCG effects in bladder cancer.
Nathan Goodyear

Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer ... - 0 views

www.ncbi.nlm.nih.gov/...PMC5718030

chloroquine hydroxychloroquine cancer repurposed drugs

shared by Nathan Goodyear on 03 May 21 - No Cached
  • HCQ, doses for long-term use range between 200 and 400 mg per day.
  • Short-term administration of CQ or HCQ rarely causes severe side effects
  • Short-term administration of CQ or HCQ rarely causes severe side effects
  • ...24 more annotations...
  • bone marrow suppression
  • cardiomyopathy
  • irreversible retinal toxicity
  • hypoglycaemia
  • daily doses up to 400 mg of HCQ or 250 mg CQ for several years are considered to carry an acceptable risk for CQ-induced retinopathies, with the exception of individuals of short stature
  • chronic CQ or HCQ therapy be monitored through regular ophthalmic examinations (3–6 month intervals), full blood counts and blood glucose level checks
  • long-term HCQ exposure, skeletal muscle function and tendon reflexes should be monitored for weakness
  • both CQ and HCQ, specific caution is advised in patients suffering from impaired hepatic function (especially when associated with cirrhosis), porphyria, renal disease, epilepsy, psoriasis, glucose-6-phosphate dehydrogenase deficiency and known hypersensitivity to 4-aminoquinoline compounds
  • CQ and HCQ can effectively increase the efficacy of various anti-cancer drugs
  • CQ can prevent the entrapment of protonated chemotherapeutic drugs by buffering the extracellular tumour environment and intracellular acidic spaces
  • This study recommends an adjuvant HCQ dose of 600 mg, twice daily.
  • HCQ addition was shown to produce metabolic stress in the tumours
  • HCQ (400 mg/day)
  • important effects of CQ and HCQ on the tumour microenvironment
  • The main and most studied anti-cancer effect of CQ and HCQ is the inhibition of autophagy
  • the expression levels of TLR9 are higher in hepatocellular carcinoma, oesophageal, lung, breast, gastric and prostate cancer cells as compared with adjacent noncancerous cells, and high expression is often linked with poor prognosis
  • TLR9-mediated activation of the NF-κB signalling pathway and the associated enhanced expression of matrix metalloproteinase-2 (MMP-2), MMP-7 and cyclo-oxygenase 2 mRNA
  • HCQ can activate caspase-3 and modulate the Bcl-2/Bax ratio inducing apoptosis in CLL, B-cell CLL and glioblastoma cells
  • In triple-negative breast cancer, CQ was shown to eliminate cancer stem cells through reduction of the expression of Janus-activated kinase 2 and DNA methyl transferase 1 [106] or through induction of mitochondrial dysfunction, subsequently causing oxidative DNA damage and impaired repair of double-stranded DNA breaks
  • CQ or HCQ would be considered for use in combination with immunomodulation anti-cancer therapies
  • Therapies used in combination with CQ or HCQ include chemotherapeutic drugs, tyrosine kinase inhibitors, various monoclonal antibodies, hormone therapies and radiotherapy
  • Most studies hypothesise that CQ and HCQ could increase the efficacy of other anti-cancer drugs by blocking pro-survival autophagy.
  • daily doses between 400 and 1200 mg for HCQ are safe and well tolerated, but two studies identified 600-mg HCQ daily as the MTD
  • HCQ is often administered twice daily to limit plasma fluctuations and toxicity
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