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Nathan Goodyear

Depression and risk of sudden cardiac death and co... [J Am Coll Cardiol. 2009] - PubMe... - 0 views

  • Although antidepressant use might be a marker of worse depression, its specific association with SCD merits further study.
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    antidepressants increase sudden cardiac death and are marker for worse depression
Nathan Goodyear

Aerobic fitness in late adolescence and the risk of early death: a prospective cohort s... - 0 views

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    study finds death rates of obese, physically active individuals exceeds that of normal weight individuals that don't exercise.
Nathan Goodyear

Artesunate induces oncosis-like cell death in vitro and has antitumor activity against ... - 0 views

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    Study finds that Artesunate induces cell death of pancreatic cancer cells in in vitro and in vivo studies via a non-apoptosis effect-oncosis.
Nathan Goodyear

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stre... - 0 views

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    Describes the mechanism by which THC induces autophagy cell death of glioma cells.
Nathan Goodyear

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

  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
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  • 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
       
      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
       
      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
       
      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
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    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

The current state and future perspectives of cannabinoids in cancer biology - 0 views

  • The activation of each of them leads to an inhibition of adenylyl cyclase via G proteins (Gi/o), which in turn activates many metabolic pathways such as mitogen‐activated protein kinase pathway (MAPK), phosphoinositide 3‐kinase pathway (PI3K), cyclooxygenase‐2 pathway (COX‐2), accumulation of ceramide, modulation of protein kinase B (Akt), and ion channels
  • phytocannabinoids, endocannabinoids, and synthetic cannabinoids
  • Action of THC in human organism relies on mimicking endogenous agonists of CB receptors—endocannabinoids
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  • The upregulated expression of CB receptors and the elevated levels of endocannabinoids have been observed in a variety of cancer cells (skin, prostate, and colon cancer, hepatocellular carcinoma, endometrial sarcoma, glioblastoma multiforme, meningioma and pituitary adenoma, Hodgkin lymphoma, chemically induced hepatocarcinoma, mantel cell lymphoma)
  • concentration of endocannabinoids, expression level of their receptors, and the enzymes involved in their metabolism frequently are associated with an aggressiveness of cancer
  • CB2 receptor contributes to human epidermal growth factor receptor (HER2) pro‐oncogenic signaling and an overexpression of CB2 increases susceptibility for leukemia development after leukemia viral infection
  • endocannabinoid‐degrading enzymes are upregulated in cancer cell lines and in human tumors
  • Many cannabinoids, ranging from phytocannabinoids (THC, CBD), endocannabinoids (2‐arachidonoylglycerol, anandamide), to synthetic cannabinoids (JWH‐133, WIN‐55,212‐2), have shown ability to inhibit proliferation, metastasis, and angiogenesis in a variety of models of cancer
  • Despite some inconsistent data, the main effect of cannabinoids in a tumor is the inhibition of cancer cells’ proliferation and induction of cancer cell death by apoptosis
  • CB1 and CB2 receptor agonists stimulate apoptotic cell death in glioma cells by induction of de novo synthesis of ceramide, sphingolipid with proapoptotic activity
  • process of autophagy is upstream of apoptosis in mechanism of cell death induced by cannabinoids
Nathan Goodyear

Blood Levels of Long-Chain n-3 Fatty Acids and the Risk of Sudden Death - NEJM - 0 views

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    Higher omega 3 fatty acids associated with 81% lower risk of sudden cardiac death.
Nathan Goodyear

Searching For an Old New Cure: Ivermectin Deficiency Syndrome? « The Healthy ... - 0 views

  • Ivermectin can inactivate the protein kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines
  • PAK proteins encoded by the PAK1 gene are critical for cytoskeleton reorganization and nuclear signaling.
  • PAK-1 kinase is required for the growth of more than 70% of human cancers such as pancreatic, colon, breast and prostate cancers, and neurofibromatosis
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  • The p21 activated Kinase PAK1 is implicated in tumor genesis.
  • Inhibiting PAK1 signals induce tumor cell apoptosis (cell death)
  • PAK1 has also been implicated for maintenance of glucose homeostasis in pancreatic beta cells and skeletal muscle
  • Ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells (Blood, November 4, 2010, vol.115). The paper states Ivermectin synergizes with chemo agents cytarabine and daunorubicin to induce cell death in leukemia cells.
  • Praziquantel , my other favorite parasite medication for liver flukes, synergistically enhances Paclitaxel (Taxol) efficacy to inhibit cancer cell growth
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    Just a commentary but with important information on ivermectin in its inhibitory activity against another oncogene PAK1.
Nathan Goodyear

Thirty-Day Mortality Underestimates the Risk of Early Death after Major Resections for ... - 0 views

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    Increased cause of death outside of 30 days from surgery is surgery.
Nathan Goodyear

Chemotherapy induces tumor immune evasion by upregulation of programmed cell ... - 0 views

  • upregulation of glycolysis in cancer cells, with subsequent exhaustion of glucose in the microenvironment, leading to the death of T cells from starvation
  • PD‐L1 expression promotes the production of interleukin 10, a cytokine involved in the death of activated T cells
  • PD‐L1 expression in tumor tissue might lead to T‐cell exhaustion and unresponsiveness
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  • PD‐L1 on cancer cells could induce T‐cell apoptosis through
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    Chemotherapy found to increase PD-L1 expression in vitro and in vivo studies.
Nathan Goodyear

Glutathione in Cancer Cell Death - PMC - 0 views

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    Glutathione depletion leads to cancer cell death.
Nathan Goodyear

Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumo... - 0 views

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    Boswellia shown to stimulate human breast cancer cell death.
Nathan Goodyear

JAMA Network | JAMA | Pharmaceutical Overdose Deaths, United States, 2010 - 1 views

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    2010 pharmaceutical overdose #'s.  Over 38.000.
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    i will be doing a lot of research on your articles. thank u. rita johnston
Nathan Goodyear

Diagnostic Pathology | Full text | Estrogen receptor beta expression in prostate adenoc... - 0 views

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    ER beta and prostate cancer.  More aggressive prostate cancer is found to be associated with lower ER beta expression in the prostate.  this makes sense, as other studies have shown that ER beta in the prostate can induce apoptosis (cell death), which is a powerful mechanism to regulate uncontrolled growth as found in cancer.
Nathan Goodyear

Persistent Subclinical Hypothyroidism and Cardiovascular Risk in the Elderly: The Cardi... - 0 views

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    study finds no increased risk of CHD, HF, or CV death in subclinical hypothyroidism in older adults.  No insight is gained from this article, due to the use of TSH as the only tool for thyroid assessment.  TSH has been shown to become unreliable as a sole thyroid assessment tool an aging population.
Nathan Goodyear

The telomerase activator TA-65 elongates short telomeres and increases health span of a... - 0 views

  • studies have demonstrated that the shortest telomeres are causal of reduced cell viability
  • a stable and enforced expression of telomerase leads to an improved health-span, accompanied by an extension of lifespan
  • TA-65 influences the percentage of cellular short telomeres through the activation of telomerase
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  • TA-65 administration during 4 months significantly improved the capacity to uptake glucose after a glucose pulse
  • liver protective action of TA-65
  • A disadvantage of mTERT potentiation could be associated to its capacity to favor proliferation of cancerous cells in murine models
  • TA-65 treated mice presented a similar incidence of malignant cancers at time of death, with a tendency to show decreased sarcomas and slightly increased lymphomas
  • We demonstrate here that TA-65 leads to a significant rescue of short telomeres through telomerase activation
  • TA-65 treatment increases proliferation and mobilization potential of mouse keratinocytes in vitro, a situation mimicking telomerase overexpression
  • TAT2, a similar molecule, have beneficial effects in the activation of CD8+ T lymphocytes from HIV-infected patients where they observe an increase of the proliferative potential and enhancement of cytokine/chemokine production
  • TA-65 resulted in a similar rescue of short telomeres in leukocytes post-treatment as observed with humans, most likely through an activation of telomerase
  • we observe that TA-65 lead to 10 fold increase of telomerase RNA levels in the liver of treated mice comparing to the non-treated same-age cohorts
  • TA-65 regulates telomerase at the transcription level, probably through the regulation of the MAPK pathway
  • TA-65 dependent telomerase activation results in a better organ fitness as demonstrated by the improved scores at the glucose tolerance test and insulin levels at fasting
  • TA-65 supplemented mice also present modest enhancement of the subcutaneous and epidermal thickness, as well as higher bone density, representative of an overall fitness status improvemen
  • TA-65 treated mice present higher levels of RBC and hemoglobin comparing to the control cohorts
  • improved health-span of TA-65 treated mice is not accompanied by increased cancer incidence, which may be related to the fact that TERT levels are very modestly increased in all tissues tested except for the liver
  • systemic telomerase overexpression from the germline leads to protection from aging associated pathologies
  • similar situation could be mimicked expressing telomerase late in life in a telomerase deficient background
  • we observed a higher proliferation rate and a partial protection from cell death in some tissues of TA65 treated mice
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    TA-65 shown to increase telomerase activity, and thus telomere length of short telomeres, in mouse study.  
arunaraayala

Brazil Gang Kills 31, Many Killed to Death as Incarceration Violence | Locality News - 0 views

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    Members of the most powerful drug gang in Brazil killed 31 inmates in a penitentiary on Friday, decapitating and cutting off the hearts of most of them, to take revenge for a separate massacre that left 56 dead this week.
Nathan Goodyear

Testosterone Making an Entry Into the Cardiometabolic World - 0 views

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    low Testosterone associated with increased CVD and death.
Nathan Goodyear

Apigenin Induces Apoptosis and Blocks Growth of Medroxyprogesterone Acetate-Dependent B... - 0 views

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    Finally, something that lowers the risk associated with synthetic progestins. Progestins are progesterone pretenders that increase breast cancer. Apigenin, a component of bioflavonoid, was shown to inhibit growth and intact cause cell death.
Nathan Goodyear

Acute Effects of Triiodothyronine (T3) Replacement Therapy in Patients with Chronic Hea... - 0 views

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    IV T3 was given to patients with chronic heart failure.  What the study found may surprise you: improved heart function (ventricular), improved BNP, decrease heart rate, no side effects.  T3 has been shown to be more predictive of cardiac death in those with cardiac disease, than elevated lipids or decreased ejection fraction.
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