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Nathan Goodyear

Tumor regionalization after surgery: Roles of the tumor microenvironment and neutrophil extracellular traps | Experimental & Molecular Medicine - 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

An Overview of Melatonin and Breast Cancer | Natural Medicine Journal - 0 views

www.naturalmedicinejournal.com/...ew-melatonin-and-breast-cancer

melatonin cancer

shared by Nathan Goodyear on 31 May 18 - No Cached
  • Overall its effect on cancer cells is oncostatic at physiological levels, or cytotoxic at higher concentrations
  • direct antioxidant, antimitotic, antiestrogenic, prodifferentiating and antimetastatic effects have been well characterized
  • hypothalamic-pituitary axis (HPA) and immune system
  • ...2 more annotations...
  • On a cellular level, melatonin acts as a selective estrogen receptor modulator (SERM) through decreased expression of estrogen receptor alpha and reduction in the ability of estrogen-estrogen receptor alpha (ERα) complex to bind to the estrogen response element (ERE) on DNA
  • Melatonin also acts as a selective estrogen enzyme modulator (SEEM), reducing the activity of aromatase in cells
  • Nathan Goodyear on 31 May 18
     
    review of melatonins activity in cancer battle.
Nathan Goodyear

Overtraining Syndrome - 0 views

www.ncbi.nlm.nih.gov/...PMC3435910

overtraining syndrome OTS exercise athletes cortisol adrenals Testosterone Testosterone:Cortisol hormones

shared by Nathan Goodyear on 29 Jan 16 - No Cached
  • Alterations in the HPA and hypothalamic-pituitary-gonadal axes with a resultant decrease in testosterone:cortisol ratios have been implicated in OTS. Proinflammatory cytokines are potent activators of the HPA system, which cause release of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol. These cytokines suppress testosterone through central inhibition
  • Some have suggested that a decreased testosterone:cortisol ratio can be diagnostic of NFO and/or OTS. However, the ratio represents the physiologic strain of training rather than the athlete’s maladaption to that stress
  • Cortisol (catabolic and anti-inflammatory) is converted to inactive cortisone by 11β-HSD2
  • ...2 more annotations...
  • A prospective study found a clinically significant increase in overnight urinary cortisol:cortisone ratio during a high training load period in triathletes, who subsequently underperformed and reported fatigue
  • It is proposed that cytokines may inhibit 11β-HSD2 activity and result in relative increases in cortisol and, hence, catabolism
  • Nathan Goodyear on 29 Jan 16
     
    Overtraining syndrome described.
Nathan Goodyear

Sex hormone synthesis, regulation, and function | McMaster Pathophysiology Review - 0 views

www.pathophys.org/sexhormones

hormones HPA Testosterone DHEA estradiol LH FSH Progesterone androgens estrogen

shared by Nathan Goodyear on 02 Oct 17 - No Cached
  • Nathan Goodyear on 02 Oct 17
     
    Good review of the HPA-sex hormone pathways, called the Hypothalamic-Pituitary-Gondal axis, including HP feedback.  This is not a study but has nice diagrams. This is based on 14 referenced articles and 1 book chapter.
Nathan Goodyear

Secondary Adrenal Insufficiency: An Overlooked Cause of Hyponatremia - 0 views

www.ncbi.nlm.nih.gov/...PMC4330026

adrenal insufficiency hyponatraemia sodium ADH cortisol CRH ACTH

shared by Nathan Goodyear on 25 Sep 17 - No Cached
  • Nathan Goodyear on 25 Sep 17
     
    Good case review of secondary adrenal insufficiency.  A common cause of low sodium and needs to be considered in elderly patients.  Also, low cortisol is associated with increased ADH.  In the case of adrenal insufficiency, the negative feed back of cortisol to the HPA is lost and recreation of CRH, which is an ADH secretagogue, will increase ADH secretion.
Nathan Goodyear

Amygdala - Scholarpedia - 0 views

www.scholarpedia.org/...Amygdala

amygdala stress HPA axis stress response brain

shared by Nathan Goodyear on 03 Sep 17 - No Cached
  • Nathan Goodyear on 03 Sep 17
     
    Great article on the amygdala and its processing of the stress response.
Nathan Goodyear

Corticosteroids: way upstream - 0 views

www.ncbi.nlm.nih.gov/...PMC2841592

HPA axis cortisol stress ACTH corticosteroids

shared by Nathan Goodyear on 03 Sep 17 - No Cached
  • Nathan Goodyear on 03 Sep 17
     
    Great read on the hypothalmo-pituitary-adrenal axis.  
Nathan Goodyear

http://www.nature.com/ijo/journal/v24/n2s/pdf/0801281a.pdf?origin=publication_detail - 0 views

www.nature.com/...0801281a.pdf

SHBG IR insulin resistance insulin Estrogen Estradiol obesity hormone hormones

shared by Nathan Goodyear on 02 Mar 15 - No Cached
  • Nathan Goodyear on 02 Mar 15
     
    Elevated insulin levels in men is associated with decreased liver production of SHBG and thus reduced SHBG levels.  Obesity is associated with decreased urinary cortisol in this study.  The authors found the low cortisol also contributed to the low SHBG as well. Low SHBG is associated with puberty, obesity, IR, hypothyroidism, and during androgen therapy.  SHBG is increased as a result of aging, short-term fasting, Estrogen, hyperthyroid, and liver disease.
Nathan Goodyear

Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity - 0 views

www.ncbi.nlm.nih.gov/...PMC3991026

stress HPA cortisol adaptogens alternative medicine

shared by Nathan Goodyear on 04 Feb 17 - No Cached
  • Nathan Goodyear on 04 Feb 17
     
    Great review of the mechanisms of adaptogens on stress management
Nathan Goodyear

Inflammation and cortisol response in coronary artery disease: Annals of Medicine: Vol 41, No 3 - 0 views

www.tandfonline.com/...07853890802508934

HPA axis HPA inflammation hormones stress cortisol CAD coronary artery disease

shared by Nathan Goodyear on 12 Oct 16 - No Cached
  • Nathan Goodyear on 12 Oct 16
     
    Inflammation disrupts HPA axis.  This is no surprise as we Know that inflammation can disrupt Testosterone in men and progesterone production in women.  This study suggests that this HPA axis disruption contributes to CAD.
Nathan Goodyear

The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-Diol Inhibit the Hypothalamo-Pituitary-Adrenal Response to Stress by Acting through Estrogen Receptor β-Expressing Neurons in the Hypothalamus - 0 views

www.jneurosci.org/...1448.full

DHT 3 beta androstanediol androgens Hypothalamus HPA hormones stress

shared by Nathan Goodyear on 15 Jul 15 - No Cached
  • Sex steroid hormones are primarily responsible for sex difference in adult HPA function; androgens inhibit whereas estrogens enhance HPA axis activation after a stressor
  • the PVN contains relatively high levels of AR (Bingaman et al., 1994; Zhou et al., 1994) and ERβ (Alves et al., 1998; Hrabovszky et al., 1998; Somponpun and Sladek, 2003) but is essentially devoid of ERα
  • the nonaromatizable androgen DHT and the nonselective ER ligand E2 influence HPA reactivity by acting on neurons within or surrounding the PVN
  • ...9 more annotations...
  • inhibitory action of DHT is detectable at both the level of hormone secretion as well as PVN c-fos mRNA expression
  • the inhibition can be mimicked by the DHT metabolite 3β-diol and by the subtype selective ERβ agonist DPN
  • E2 acts to enhance HPA reactivity
  • the ability of the ER antagonist tamoxifen, but not the AR antagonist flutamide, to block the inhibitory actions of DHT, speaks to the intracellular mechanism by which this inhibitory signal might be transduced.
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      that is because the interaction with the DHT metabolite is not with the AR, but with the ER-beta.
  • the DHT metabolite 3β-diol and the ERβ-subtype-selective agonist DPN suppressed ACTH, corticosterone, and c-fos mRNA responses to restraint stress in a manner similar to DHT
  • metabolism of DHT to 3β-diol and subsequent binding to ERβ can be inhibitory to HPA reactivity, and this is one possible mechanism for the action of DHT.
  • Our data also suggest that E2 enhances the reactivity of the HPA axis to stress by acting on or near neurons of the PVN
  • the actions of E2 appear to be through an ERα-dependent mechanism
  • these studies suggest that ERβ, within the male hypothalamus, acts to inhibit the HPA axis and that the inhibitory effects of DHT may be, at least in part, via its intracellular conversion to 3β-diol and subsequent binding to ERβ
  • Nathan Goodyear on 15 Jul 15
     
    DHT metabolites: particularly 3beta-androstanediol inhibit HPA axis through ER-beta.
Nathan Goodyear

Testosterone Suppression of CRH-stimulated Cortisol in Men - 0 views

www.ncbi.nlm.nih.gov/...PMC1470424

Testosterone cortisol HPA hormone hormones men male

shared by Nathan Goodyear on 19 Jun 15 - No Cached
  • Nathan Goodyear on 19 Jun 15
     
    Testosterone inhibits CRH and thus cortisol production in men.  This has implications in men with low T and low Cortisol.
Nathan Goodyear

Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses : Nature Communications : Nature Publishing Group - 0 views

www.nature.com/...ncomms7266.html

Leptin HPA hormone hormones

shared by Nathan Goodyear on 19 Jun 15 - No Cached
  • Nathan Goodyear on 19 Jun 15
     
    Leptin does have inhibitory activity at the level at the HPA; in addition to the inhibition at the gonadal level.
Nathan Goodyear

Age-related testosterone decline is due to waning of both testicular and hypothalamic-pituitary function, The Aging Male, Informa Healthcare - 0 views

informahealthcare.com/...13685538.2015.1052392

low T low Testosterone Testosterone men male hormone hormones

shared by Nathan Goodyear on 17 Jun 15 - No Cached
  • Nathan Goodyear on 17 Jun 15
     
    Only abstract available here, but low T is the result of primary (testicular failure) and/or secondary (HPA failure). 
Nathan Goodyear

Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...9275075

leptin CRH HPA axis HPA hormone hormones

shared by Nathan Goodyear on 17 Jun 15 - No Cached
  • Nathan Goodyear on 17 Jun 15
     
    Leptin inhibits CRH, thus decreasing the HPA axis.
Nathan Goodyear

Leptin and the regulation of the hypothalamic-pituitary-adrenal axis. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17725965

Leptin adrenal HPA hormone hormones

shared by Nathan Goodyear on 17 Jun 15 - No Cached
  • Nathan Goodyear on 17 Jun 15
     
    Leptin inhibits hormone production from the adrenal cortex, but increases catecholamine release from the adrenal medulla.
Nathan Goodyear

Acute effects of interferon-alpha administration on testosterone concentrations in healthy men - 0 views

www.eje-online.org/...371.short

interferon hepatitis Hepatitis C low T low Testosterone Testosterone FAI free Androgen Index men male hormone hormones

shared by Nathan Goodyear on 22 Apr 15 - No Cached
  • Nathan Goodyear on 22 Apr 15
     
    Interferon therapy in men with hepatitis C was found to decrease total Testosterone and Free Androgen index at the level of the gonads; this was independent of the HPA in this study.
Nathan Goodyear

Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional androgen deficiency or depression? - 0 views

joe.endocrinology-journals.org/...345.long

hepatitis Hepatitis C HCV interferon low T low testosterone deficiency men male hormone hormones depression

shared by Nathan Goodyear on 22 Apr 15 - No Cached
  • Nathan Goodyear on 22 Apr 15
     
    Study of men with hepatitis C and interferon therapy found decrease in free and total Testosterone levels in men.  The study results suggest a non-HPA effect, which suggests more of a peripheral effect at the level of the TEsticles.
Nathan Goodyear

Low testosterone in a young combat veteran with dual diagnosis and ... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...25528760

combat low T low Testosterone PTSD

shared by Nathan Goodyear on 02 Feb 15 - No Cached
  • Nathan Goodyear on 02 Feb 15
     
    Low T found in young combat veteran with PTSD and SI.  This is no surpass as there is significant HPA dysfunction in these men/women.  The overwhelming cortisol response and resultant PTSD will shut down endogenous Testosterone production.  I have seen this in several combat veterans.
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