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Nathan Goodyear

Full article: Local recurrence of brain metastasis reduced by intra-operative hyperther... - 0 views

www.tandfonline.com/...02656736.2018.1488004

hyperthermia metastasis recurrence brain cancer local recurrence

shared by Nathan Goodyear on 26 Apr 21 - No Cached
  • Nathan Goodyear on 26 Apr 21
     
    Hyperthermia reduces recurrence risk by 55% of metastatic brain cancer after surgery over conventional therapies.
Nathan Goodyear

Surgically induced accelerated local and distant tumor growth is significantly attenuat... - 0 views

pubmed.ncbi.nlm.nih.gov/15734421

cancer metastasis surgery

shared by Nathan Goodyear on 13 Aug 20 - No Cached
  • Nathan Goodyear on 13 Aug 20
     
    Cox II inhibition helps to slow surgical induced metastatic and local recurrence of cancer. Surgery does cause metastasis and local recurrence and cox II inhibition stops spread.
Nathan Goodyear

Preoperative hyperthermia combined with chemotherapy and radiotherapy for patients with... - 0 views

pubmed.ncbi.nlm.nih.gov/1293242

local recurrence cancer surgery hyperthermia

shared by Nathan Goodyear on 25 Apr 21 - No Cached
  • Nathan Goodyear on 25 Apr 21
     
    Hyperthermia + chemotherapy and radiation reduce local recurrence from surgery.
Nathan Goodyear

Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunolog... - 0 views

edrv.endojournals.org/...44.full

natural killer cells pregnancy loss recurrent immune system miscarriage NK

shared by Nathan Goodyear on 15 Apr 12 - No Cached
  • NK cells have been the cells most extensively studied, primarily because they constitute the predominant leukocyte population present in the endometrium at the time of implantation and in early pregnancy
  • parental chromosomal abnormalities, uterine anatomic anomalies, endometrial infections, endocrine etiologies (luteal phase defect, thyroid dysfunction, uncontrolled diabetes mellitus), antiphospholipid syndrome, inherited thrombophilias, and alloimmune causes
  • estrogen
  • ...28 more annotations...
  • progesterone
  • prolactin
  • In summary, in vivo animal experiments have shown an inhibitory role of estrogen on peripheral NK cell lytic activity, which is partly due to suppression of NK cell output by the bone marrow and partly due to suppression of individual NK cell cytotoxicity. However, in vitro studies so far have failed to show conclusively a direct effect of estrogen on NK cells.
  • At the progesterone concentrations believed to be present in the uterus [up to 10−5 m at the maternal-fetal interface (35)], studies consistently show inhibition of lymphocyte proliferation (33) and inhibition of NK cytolytic activity in vitro
  • The exact role of prolactin in NK cell regulation is unknown.
  • The overall effects of estrogen on NK cells are likely multifactorial, therefore, and depend on the type of cell affected as well as the kind of ER expressed by that cell.
  • It is known that progesterone can directly affect T cell differentiation in vitro, suppressing development of the Th1 pathway and enhancing differentiation along the Th2 pathway (44)
  • Th1 cells predominantly produce interferon-γ (IFN-γ), IL-2, and TNF-β and are involved in cell-mediated immunity. Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and stimulate humoral immunity
  • Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
  • A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
  • NK cell function is mainly regulated by IL-2 and IFN-γ
  • IL-2 causes both NK cell proliferation and enhanced cytotoxicity. IFN-γ augments NK cytolytic activity, but does not cause NK proliferation. The two cytokines act synergistically to augment NK cytotoxicity (6).
  • The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
  • there is a significant increase in the number of uNK cells throughout the secretory phase, which peaks in early pregnancy when uNK cells comprise about 75% of uterine leukocytes (62)
  • Second, uNK cell phenotype changes during the normal menstrual cycle and early pregnancy (68)
  • general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
  • The mechanism of such a progesterone-induced local immunosuppression is unclear.
  • progesterone plays an important role in proliferation and differentiation of uNK cells (32).
  • Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
  • The mechanism of this increase in uNK cell numbers has been addressed in both human and mouse models, and is likely the result of: 1) recruitment of peripheral NK cells to the uterus, and 2) proliferation of existing uNK cells
  • prolactin system plays an important role in implantation and the maintenance of pregnancy
  • the exact pathways of hormonal regulation of NK cells remain to be delineated.
  • The exact function of uNK cells has not yet been unequivocally determined
  • uNK cells express a different cytokine profile, compared with resting peripheral NK cells. mRNAs for granulocyte CSF, M-CSF, GM-CSF, TNF-α, IFN-γ, TGF-β, and leukemia inhibitory factor (LIF) have been found in decidual CD56+ cells
  • Their increased numbers in early pregnancy, their hormonal dependence, and their close proximity to the infiltrating trophoblast all suggest that they play an important role in the regulation of the maternal immune response to the fetal allograft and the control of trophoblast growth and invasion during human pregnancy
  • role of uNK cell-derived cytokines on trophoblast growth and differentiation (114, 115, 116, 117).
  • Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
  • RPL is associated with Th1 immunity, for which NK cells are partly responsible.
  • Nathan Goodyear on 15 Apr 12
     
    dysregulated immune system plays role in recurrent miscarriage.  Specifically, this article discusses natural killer cells (NK).
Nathan Goodyear

Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosi... - 0 views

pubmed.ncbi.nlm.nih.gov/15741161

metastasis local recurrence surgery

shared by Nathan Goodyear on 13 Aug 20 - No Cached
  • Nathan Goodyear on 13 Aug 20
     
    Again, surgical upregulation of PI3k stimulates local recurrence via anti-apoptosis and induction of chemoresistance.
Nathan Goodyear

Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia for pain relief... - 0 views

pubmed.ncbi.nlm.nih.gov/16423749

hyperthermia pain

shared by Nathan Goodyear on 25 Jan 21 - No Cached
  • Nathan Goodyear on 25 Jan 21
     
    Radiotherapy hyperthermia found to reduce pain in colorectal cancer recurrence. This was regional/local hyperthermia.
Nathan Goodyear

Tumor regionalization after surgery: Roles of the tumor microenvironment and neutrophil... - 0 views

www.nature.com/...s12276-022-00784-2

TME NETosis metastasis surgery cancer tumor microenvironment

shared by Nathan Goodyear on 20 Apr 23 - No Cached
  • tumor surgery must be carefully considered because the risk of metastasis could be increased by the surgical procedure.
  • NETosis, which is the process of forming neutrophil extracellular traps (NETs)
  • surgery-induced metastasis
  • ...61 more annotations...
  • surgery per se can promote cancer metastasis through a series of local and systemic events
  • surgery results in a serious wound that disrupts the structural barrier preventing the outspreading of cancer cells, change the properties of the cancer cells and stromal cells remaining in the tumor microenvironment, or impairs the host defense systems against cancers
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Key point; add to presentation on surgery and metastasis
  • After the primary tumor is surgically removed, the metastases can start to grow vigorously via neoangiogenesis because the circulating inhibitors disappear
  • infection and inflammation during the postoperative period have been reported to increase the risk of cancer recurrence in patients
  • Surgeons have long suspected that surgery, even if it is a necessary step in cancer treatment, facilitates cancer metastasis
  • Surgery-induced cancer metastasis has been well established in animal models
  • tumor cell dissemination, tumor-favoring immune responses, and neoangiogenesis
  • the surgical resection of primary tumors is beneficial is controversial
  • CTCs abruptly increase just after surgery
  • Even externally palpitating tumors for diagnosis could increase the numbers of CTCs in skin cancer and breast cancer
  • excessive glucocorticoids negatively modulate immune functions
  • immune surveillance against tumors is considered to be impaired by surgical stress
  • In addition to glucocorticoids, during stimulation of the HPA axis, the catecholamine hormones epinephrine and norepinephrine are released from the adrenal medulla
  • NK cell suppression may be attributed to increased levels of catecholamines as well as glucocorticoids
  • In mice bearing a primary tumor, it was observed that the removal of the primary tumor facilitated the growth of highly vascularized metastases
  • primary tumors may secrete angiogenic inhibitors as well as angiogenic activators
  • second phase of tumor recurrence and metastasis, which are newly acquired events, rather than just outcomes of incomplete treatment.
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Another key point
  • double-edged sword
  • HIF-1 in neutrophils plays a critical role in NETosis and bacteria-killing activity
  • neutrophils play various roles in the initiation and progression of cancer
  • NETosis
  • many inflammatory and neoplastic diseases
  • formation of neutrophil extracellular traps (NETs), which are large extracellular complexes composed of chromatin and cytoplasmic/granular proteins1
  • NETosis has been highlighted as an inflammatory event that promotes cancer metastasis
  • Once activated, neutrophils produce intracellular precursors by using DNA, histones, and granular and cytoplasmic proteins and then spread the mature form of NETs out around themselves
  • A series of these events is called NETosis.
  • neutrophil elastase, myeloperoxidase, cathepsin G, proteinase 3, lactoferrin, gelatinase, lysozyme C, calprotectin, neutrophil defensins, and cathelicidins
  • innate immune response against infection
  • Neutrophils are the most abundant type of granulocytes, comprising 40–70% of all white blood cells
  • two types of NEToses, suicidal (or lytic) NETosis and vital NETosis
  • Suicidal NETosis mainly depends on the production of reactive oxygen species (ROS)
  • Since neutrophils die during this process, it is called suicidal NETosis.
  • vital NETosis
  • vital NETosis occurs independently of ROS production
  • Vital NETosis can be induced by Gram-negative bacteria. LPS
  • NETs are present in a variety of cancers, such as lung cancer, colon cancer, ovarian cancer, and leukemia
  • neutrophils actively undergo NETosis in the tumor microenvironment
  • Hypoxia
  • NETosis plays a pivotal role in noninfectious autoimmune diseases,
  • cytokines
  • tumor-derived proteases
  • tumor exosomes
  • NETosis generally actively progresses in the tumor microenvironment.
  • the proliferative cytokines TGFβ and IL-10 and the angiogenic factor VEGF are representative of neutrophil-derived tissue repair proteins.
  • NETosis is a defense system to protect the body from invading pathogens
  • when neutrophils are excessively stimulated, they produce excess NETs, thereby leading to pathological consequences
  • plasma levels of NETosis markers are elevated after major surgeries
  • local invasion, intravasation into the blood or lymphatic vessels, escape from the immune system, anchoring to capillaries in target organs, extravasation into the organs, transformation from dormant cells to proliferating cells, colonization to micrometastases, and growth to macrometastases
  • NETs promote metastasis at multiple steps
  • NETs loosen the ECM and capillary wall to promote the intravasation of cancer cells
  • NETs and platelets wrap CTCs, which protects them from attack by immune cells and shearing force by blood flow
  • NETs promote the local invasion of cancer cells by degrading the extracellular matrix (ECM)
  • neutrophil elastase, matrix metalloproteinase 9, and cathepsin G
  • NETs also promote the intravasation of cancer cells
  • millions of tumor cells are released into the circulation every day,
  • NETs can wrap up CTCs with platelets
  • β1-integrin plays an important role in the interaction between CTCs and NETs
  • NET-platelet-CTC aggregates.
  • After metastasizing to distant tissues, tumor cells are often found to remain dormant for a period of time and unexpectedly regrow late
  • NETs are believed to participate in the reactivation of dormant cancer cells in metastatic regions
  • NET-associated proteases NE and MMP-9 were found to be responsible for the reactivation of dormant cancer cells
  • Nathan Goodyear on 20 Apr 23
     
    Surgery induced metastasis: it is real and steered by NETosis.
Nathan Goodyear

Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer t... - 0 views

www.sciencedirect.com/...S0960977617300103

HER-2 breast cancer cancer herceptin Perjeta

shared by Nathan Goodyear on 06 Aug 18 - No Cached
  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
  • ...15 more annotations...
  • shortened survival and an increased risk of disease recurrence and metastasis
  • Currently, four HER2-directed agents are approved for the treatment of patients with HER2+ breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1)
  • biosimilars
  • trastuzumab may provide greater benefit when administered concurrently with chemotherapy rather than after, and this has become the standard approach
  • concurrent use of anthracyclines (ie, doxorubicin or epirubicin) and trastuzumab is not recommended because of an increased risk for cardiac toxicity
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      avoid herceptin in conjuction with antracyclines i.e. doxorubicin
  • Sequential doxorubicin plus cyclophosphamide followed by concomitant paclitaxel or docetaxel and trastuzumab is recommended for most patients
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      top recommended regimen combination
  • Guidelines also recommend trastuzumab in combination with paclitaxel, docetaxel and carboplatin, or docetaxel and cyclophosphamide, particularly for patients with increased risk for cardiac toxicity or those with small (≤1 cm), node-negative HER2+ tumors
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      good alternative in patients with increased risk of cardiac toxicity.
  • guidelines recommend up to 1 year of adjuvant trastuzumab
  • Neoadjuvant chemotherapy with trastuzumab is associated with higher rates of pathologic complete response (pCR) than chemotherapy alone or in combination with lapatinib
  • the combination of trastuzumab, lapatinib, and chemotherapy is not recommended because it failed to demonstrate noninferiority versus trastuzumab and chemotherapy in the adjuvant setting
  • recommend the combination of trastuzumab, pertuzumab, and chemotherapy as neoadjuvant treatment for patients with locally advanced HER2+ breast cancer and for some patients (node-positive or tumor ≥2 cm) with early-stage disease
  • neoadjuvant chemotherapy in combination with pertuzumab and trastuzumab reduced the risk of progression or death by 31% and recurrence or death by 40% versus trastuzumab alone
  • Concurrent chemotherapy and HER2-directed therapy improves survival outcomes over chemotherapy alon
  • dual inhibition of HER2 with trastuzumab and pertuzumab in combination with paclitaxel reduced the risk of death or progression by approximately 40% compared with concurrent trastuzumab and paclitaxel
  • the combination of trastuzumab, pertuzumab, and taxane chemotherapy is the preferred first-line regimen
  • Nathan Goodyear on 06 Aug 18
     
    HER-2 + breast cancer = appx 15-20% of all breast cancers and is a marker of worse prognosis and an indication for targeted immunotherapy blockade.
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]
  • has low systemic bioavailability (~10%) when administered orally, which is beneficial for treating local parasitic infections of the intestines while minimizing systemic exposure
  • 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
  • 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
  • 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

Mitochondrial Fission Induces Glycolytic Reprogramming in Cancer-Associated Myofibrobla... - 0 views

www.ncbi.nlm.nih.gov/...PMC3478457

warburg effect Cancer cancer associated fibroblasts CAFs reverse warburg effect lactate aerobic glycolysis mitochondria oxidative stress ROS H2O2

shared by Nathan Goodyear on 11 Nov 14 - No Cached
  • L-lactate functions as an onco-metabolite, stimulating mitochondrial biogenesis and OXPHOS in adjacent cancer cells, directly providing energy for tumor growth
  • Oxidative stress in stromal fibroblasts then induces their metabolic conversion into cancer-associated fibroblasts. Such oxidative stress drives the onset of autophagy, mitophagy, and aerobic glycolysis in fibroblasts, resulting in the local production of high-energy mitochondrial fuels (such as L-lactate, ketone bodies, and glutamine). These recycled nutrients are then transferred to cancer cells, where they are efficiently burned via oxidative mitochondrial metabolism (OXPHOS)
  • stromal L-lactate serves as a high-energy mitochondrial “fuel” for cancer cells. We have termed this new model of cancer metabolism “Two-Compartment Tumor Metabolism”, where two opposing metabolic compartments co-exist, side-by-side, with stromal glycolysis fueling OXPHOS in cancer cells
  • ...10 more annotations...
  • Two-Compartment Tumor Metabolism
  • Reverse Warburg Effect”, is that catabolic fibroblasts should promote tumor growth, without any increases in angiogenesis
  • when cancer cells use L-lactate as a mitochondrial fuel source, this metabolic phenotype is a predictor of lethal cancer metabolism
  • tumor microenvironment is intimately involved in tumor development and progression
  • mitochondrial dysregulation is likely the “root cause” of several human disease(s), and especially epithelial cancers
  • Both in vitro and in vivo studies have now provided convincing evidence that “activated” stromal fibroblasts, a.k.a., myofibroblasts, may play a critical role in initiating tumor recurrence, via paracrine interactions with adjacent tumor epithelial cells
  • A new hypothesis is that cancer is not a cell autonomous disease, but rather a disease of the tumor microenvironment
  • cancer cells behave as metabolic parasites, by inducing oxidative stress in adjacent normal fibroblasts
  • recent experimental evidence indicates that cancer-associated fibroblasts have a catabolic phenotype, and undergo autophagy and mitophagy, resulting in the onset of glycolytic metabolism, driving L-lactate production, and its release into the tumor microenvironment
  • oncogenic mutations in cancer cells lead to ROS production and the “secretion” of hydrogen peroxide species
  • Nathan Goodyear on 11 Nov 14
     
    A good discussion of what is proposed the Reverse Warburg effect.  A process by which the local environment dictates tumor progression.  The cancer cells release ROS primarily in the form of H2O2 and this leads to Cancer Associated Fibroblasts (CAFs) in the stroma.  The altered stromal environment increases ROS further and promotes ocogenic metabolites through the classic Warburg effect.  This high lactate production from the CAFs then is used by the cancer cells via classic oxidative phosphorylation.  Complex, beautiful and still an the understanding is a work in progress.   This study/article points to the importance of oxidative stress in some cancer development through CAFs.
Nathan Goodyear

Role of Oxidative Stress and the Microenvironment in Breast Cancer Development and Prog... - 0 views

www.ncbi.nlm.nih.gov/...PMC3950899

cancer oxidative stress warburg effect reverse warburg effect ROS

shared by Nathan Goodyear on 11 Nov 14 - No Cached
  • oxidative stress leads to HIF-1α accumulation
  • increased levels of hydrogen peroxide in exhaled breath condensate from patients with localized breast malignancy, associated with increased clinical severity
  • Oxidative stress generated by breast cancer cells activates HIF-1α and NFκB in fibroblasts, leading to autophagy and lysosomal degradation of Cav-1
  • ...18 more annotations...
  • Comparing mitochondrial metabolic activity revealed a difference between stroma and epithelial cells
  • metalloproteinases (MMP) such as MMP-2, MMP-3, and MMP-9 increase extracellular matrix turnover and are themselves activated by oxidative stress
  • Overexpression of NOX4 in normal breast epithelial cells results in cellular senescence, resistance to apoptosis, and tumorigenic transformation, as well as increased aggressiveness of breast cancer cells
  • Lowered expression of Cav-1 not only leads to myofibroblast conversion and inflammation but also seems to impact aerobic glycolysis, leading to secretion of high energy metabolites such as pyruvate and lactate that drive mitochondrial oxidative phosphorylation in cancer cells
  • Reverse Warburg Effect
  • secreted transforming growth factor β (TGFβ), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor 2, and stromal-derived factor 1 (SDF1) are able to activate fibroblasts and increase cancer cell proliferation
  • oxidative stress has an important role in the initiation and preservation of breast cancer progression
  • cancer preventive role of healthy mitochondria
  • the cancer cells produce hydrogen peroxide and by driving the “Reverse Warburg Effect” initiate oxidative stress in fibroblasts. As a result of this process, fibroblasts exhibited reduced mitochondrial activity, increased glucose uptake, ROS, and metabolite production.
  • Oxidative stress results from an imbalance between unstable reactive species lacking one or more unpaired electrons (superoxide anion, hydrogen peroxide, hydroxyl radical, reactive nitrogen species) and antioxidants
  • cancer cells are able to induce drivers of oxidative stress, autophagy and mitophagy: HIF-1α and NFκB in surrounding stroma fibro-blasts
  • Studies show that loss of Cav-1 in adjacent breast cancer stroma fibroblasts can be prevented by treatment with N-acetyl cysteine, quercetin, or metformin
  • However, diets rich in antioxidants have fallen short in sufficiently preventing cancer
  • obstructing oxidative stress in the tumor microenvironment can lead to mitophagy and promote breast cancer shutdown is a promising discovery for the development of future therapeutic interventions.
  • It is widely held that HIF-1α function is dependent upon its location within the tumor microenvironment. It acts as a tumor promoter in CAFs and as a tumor suppressor in cancer cells
  • It was reported that overexpression of recombinant (SOD2) (Trimmer et al., 2011) or injection of SOD, catalase, or their pegylated counterparts can block recurrence and metastasis in mice
  • hydrogen peroxide is one of the main factors that can push fibroblasts and cancer cells into senescence
  • Recent studies show that in the breast cancer microenvironment, oxidative stress causes mitochondrial dysfunction
  • Nathan Goodyear on 11 Nov 14
     
    Really fascinating article on tumor signaling. The article points to a complex signaling between cancer cells and stromal fibroblasts that results in myofibroblast transformation that increases the microenvironment favorability of cancer. This article points to oxidative stress as the primary driving force.  
Nathan Goodyear

Stuck at the bench: Potential natural neuroprotective compounds for concussion - 0 views

www.ncbi.nlm.nih.gov/...PMC3205506

concussions concussion natural therapies brain curcumin omega 3 resveratrol green tea EGCG EPA DHA vitamin E vitamin c vitamin D

shared by Nathan Goodyear on 20 Feb 16 - No Cached
  • Long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are highly enriched in neuronal synaptosomal plasma membranes and vesicles
  • The predominant CNS polyunsaturated fatty acid is DHA
  • effective supplementation and/or increased ingestion of dietary sources rich in EPA and DHA, such as cold-water fish species and fish oil, may help improve a multitude of neuronal functions, including long-term potentiation and cognition.
  • ...45 more annotations...
  • multiple preclinical studies have suggested that DHA and/or EPA supplementation may have potential benefit through a multitude of diverse, but complementary mechanisms
  • pre-injury dietary supplementation with fish oil effectively reduces post-traumatic elevations in protein oxidation
  • The benefits of pre-traumatic DHA supplementation have not only been independently confirmed,[150] but DHA supplementation has been shown to significantly reduce the number of swollen, disconnected and injured axons when administered following traumatic brain injury.
  • DHA has provided neuroprotection in experimental models of both focal and diffuse traumatic brain injury
  • potential mechanisms of neuroprotection, in addition to DHA and EPA's well-established anti-oxidant and anti-inflammatory properties
  • Despite abundant laboratory evidence supporting its neuroprotective effects in experimental models, the role of dietary DHA and/or EPA supplementation in human neurological diseases remains uncertain
  • Several population-based, observational studies have suggested that increased dietary fish and/or omega-3 polyunsaturated fatty acid consumption may reduce risk for ischemic stroke in several populations
  • Randomized control trials have also demonstrated significant reductions in ischemic stroke recurrence,[217] relative risk for ischemic stroke,[2] and reduced incidence of both symptomatic vasospasm and mortality following subarachnoid hemorrhage
  • Clinical trials in Alzheimer's disease have also been largely ineffective
  • The clinical evidence thus far appears equivocal
  • curcumin has gained much attention from Western researchers for its potential therapeutic benefits in large part due to its potent anti-oxidant[128,194,236] and anti-inflammatory properties
  • Curcumin is highly lipophilic and crosses the blood-brain barrier enabling it to exert a multitude of different established neuroprotective effects
  • in the context of TBI, a series of preclinical studies have suggested that pre-traumatic and post-traumatic curcumin supplementation may bolster the brain's resilience to injury and serve as a valuable therapeutic option
  • Curcumin may confer significant neuroprotection because of its ability to act on multiple deleterious post-traumatic, molecular cascades
  • studies demonstrated that both pre- and post-traumatic curcumin administration resulted in a significant reduction of neuroinflammation via inhibition of the pro-inflammatory molecules interleukin 1β and nuclear factor kappa B (NFκB)
  • no human studies have been conducted with respect to the effects of curcumin administration on the treatment of TBI, subarachnoid or intracranial hemorrhage, epilepsy or stroke
  • studies have demonstrated that resveratrol treatment reduces brain edema and lesion volume, as well as improves neurobehavioral functional performance following TBI
  • green tea consumption or supplementation with its derivatives may bolster cognitive function acutely and may slow cognitive decline
  • At least one population based study, though, did demonstrate that increased green tea consumption was associated with a reduced risk for Parkinson's disease independent of total caffeine intake
  • a randomized, placebo-controlled trial demonstrated that administration of green tea extract and L-theanine, over 16 weeks of treatment, improved indices of memory and brain theta wave activity on electroencephalography, suggesting greater cognitive alertness
  • Other animal studies have also demonstrated that theanine, another important component of green tea extract, exerts a multitude of neuroprotective benefits in experimental models of ischemic stroke,[63,97] Alzheimer's disease,[109] and Parkinson's disease
  • Theanine, like EGCG, contains multiple mechanisms of neuroprotective action including protection from excitotoxic injury[97] and inhibition of inflammation
  • potent anti-oxidant EGCG which is capable of crossing the blood-nerve and blood-brain barrier,
  • Epigallocatechin-3-gallate also displays neuroprotective properties
  • More recent research has suggested that vitamin D supplementation and the prevention of vitamin D deficiency may serve valuable roles in the treatment of TBI and may represents an important and necessary neuroprotective adjuvant for post-TBI progesterone therapy
  • Progesterone is one of the few agents to demonstrate significant reductions in mortality following TBI in human patients in preliminary trials
  • in vitro and in vivo studies have suggested that vitamin D supplementation with progesterone administration may significantly enhance neuroprotection
  • Vitamin D deficiency may increase inflammatory damage and behavioral impairment following experimental injury and attenuate the protective effects of post-traumatic progesterone treatment.[37]
  • emerging evidence has suggested that daily intravenous administration of vitamin E following TBI significantly decreases mortality and improves patient outcomes
  • high dose vitamin C administration following injury stabilized or reduced peri-lesional edema and infarction in the majority of patients receiving post-injury treatment
  • it has been speculated that combined vitamin C and E therapy may potentiate CNS anti-oxidation and act synergistically with regards to neuroprotection
  • one prospective human study has found that combined intake of vitamin C and E displays significant treatment interaction and reduces the risk of stroke
  • Pycnogenol has demonstrated the ability to slow or reduce the pathological processes associated with Alzheimer's disease
  • Pcynogenol administration, in a clinical study of elderly patients, led to improved cognition and reductions in markers of lipid peroxidase
  • One other point of consideration is that in neurodegenerative disease states like Alzheimer's disease and Parkinson's disease, where there are high levels of reactive oxygen species generation, vitamin E can tend to become oxidized itself. For maximal effectiveness and to maintain its anti-oxidant capacity, vitamin E must be given in conjunction with other anti-oxidants like vitamin C or flavonoids
  • These various factors might account for the null effects of alpha-tocopherol supplementation in patients with MCI and Alzheimer's disease
  • preliminary results obtained in a pediatric population have suggested that post-traumatic oral creatine administration (0.4 g/kg) given within four hours of traumatic brain injury and then daily thereafter, may improve both acute and long-term outcomes
  • Acutely, post-traumatic creatine administration seemed to reduce duration of post-traumatic amnesia, length of time spent in the intensive care unit, and duration of intubation
  • At three and six months post-injury, subjects in the creatine treatment group demonstrated improvement on indices of self care, communication abilities, locomotion, sociability, personality or behavior and cognitive function when compared to untreated controls
  • patients in the creatine-treatment group were less likely to experience headaches, dizziness and fatigue over six months of follow-up
  • CNS creatine is derived from both its local biosynthesis from the essential amino acids methionine, glycine and arginine
  • Studies of patients with CNS creatine deficiency and/or murine models with genetic ablation of creatine kinase have consistently demonstrated significant neurological impairment in the absence of proper creatine, phosphocreatine, or creatine kinase function; thus highlighting its functional importance
  • chronic dosing may partially reverse neurological impairments in human CNS creatine deficiency syndromes
  • Several studies have suggested that creatine supplementation may also reduce oxidative DNA damage and brain glutamate levels in Huntington disease patients
  • Another study highlighted that creatine supplementation marginally improved indices of mood and reduced the need for increased dopaminergic therapy in patients with Parkinson's disease
  • Nathan Goodyear on 20 Feb 16
     
    great review of natural therapies in the treatment of concussions
Nathan Goodyear

18FDG-PET/CT for predicting the outcome in ER+/HER2- breast cancer patients: comparison... - 0 views

breast-cancer-research.biomedcentral.com/...s13058-016-0793-2

PET scan cancer breast cancer

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • our study confirms that baseline PET parameters measured before neoadjuvant treatment have prognostic values in ER+/HER2- locally advanced breast cancer patients
  • It has been suggested that high baseline 18F-fluorodeoxyglucose (18FDG) uptake assessed by high standardized uptake value (SUV) could be associated with poor prognostic factors such as the high histological grade [2] as well as worse survival
  • several teams observed that the change in SUV values early during neoadjuvant treatment could be a good indicator of pathological response and potentially outcome
  • ...5 more annotations...
  • others studies suggested that baseline 18FDG uptake, which would avoid performing a second examination, could also be of interest to predict patient outcome, especially in ER+/HER2- BC
  • ER+/HER2- BC has less intense 18FDG uptake than some other phenotypes such as TN carcinoma
  • Patients with high baseline 18FDG tumor uptake are at higher risk of early recurrence
  • The 3-year EFS was 78.4% in patients with baseline tumor SUVmax > 8.3 (vs. 94.0% in those with SUVmax ≤ 8.3)
  • event-free survival (EFS)
  • Nathan Goodyear on 19 Mar 18
     
    Study finds benefit of PET scan in prognosis in ER+/HER2- breast cancers.
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