very nice of how glucocorticoids and progesterone interact with the immune system. This review article discusses the current understanding of how hormones can contribute to autoimmune disease states through inflammation.
Low cortisol found in those with PTSD. This study suggest the high ACTH/cortisol ratio is not due to enhanced peripheral sensitization to glucocorticoids.
Progesterone must be considered a potential physiological inhibitor of glucocorticoid-dependent aromatase induction in adipose tissue. It is proposed that it is a suppressor of aromatase induction in adipose tissue in premenopausal women.
Study proposes that 11beta-HSD type 1 is the key to linking glucocorticoids and metabolic dysfunction. The key point of this study is that it is the adipose tissue expression of 11beta-HSD type 1 that is the key.
Nice article describing solid tumors with high GC receptor expression. The authors point to GC antagonistic activity as an option for adjuvant therapy.
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
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
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.
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
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
Morning salivary cortisol is as good as serum as screening test for patients with Addison's disease and nighttime salivary cortisol is more adequate than serum in the screening of Cushing's syndrome.